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Sample records for acid asa aspirin

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

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

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

  2. Does acetyl salicylic acid (ASA) have a role in the prevention of venous thromboembolism?

    PubMed

    Karthikeyan, Ganesan; Eikelboom, John W; Turpie, Alexander G G; Hirsh, Jack

    2009-07-01

    Guidelines differ on whether acetyl salicylic acid (ASA, aspirin) should be used for prophylaxis in patients at high-risk of venous thromboembolism (VTE), principally because of differences in perceptions of its efficacy. ASA is an attractive therapeutic option because it is inexpensive, easy to administer and does not require monitoring. We critically reappraised the evidence from randomized controlled trials for the efficacy of ASA in VTE prevention. ASA is clearly efficacious in preventing VTE compared to placebo or no treatment, but appears to be less efficacious than the low molecular weight heparins in small trials. There is little data for ASA in comparison with unfractionated heparin and warfarin. A large randomized controlled trial is required to clarify the role of ASA compared to contemporary anticoagulant strategies for the prevention of VTE.

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

    PubMed

    Viganò, G; Garagiola, U; Gaspari, F

    1991-01-01

    A single-blind, randomized, crossover pharmacokinetic study was carried out to investigate the bioavailability of a new oral buffered 325 mg acetylsalicylic acid (ASA) formulation (ASPIRINA 03) in comparison with a 325 mg plain tablet. Twelve healthy volunteers of both sexes, aged between 20 and 37 years, received buffered or plain ASA on two separate occasions with a wash-out interval of at least two weeks. ASA and salicylic acid (SA) plasma levels were determined by a chromatographic method. The results showed no difference between the area under concentration time curve (AUC0-infinity) ASA values of both formulations (p = 0.19), and buffered ASA relative bioavailability was 102.49% (= bioequivalence). A significant difference was found between the AUC0-30 min ASA values: 90.5 micrograms. min/ml with buffered and 67.7 micrograms. min/ml with the plain tablet (p less than 0.05). The buffered ASA time of maximum concentration was shorter (28 +/- 8 min) than the plain one (38 +/- 19 min, p less than 0.05). The plasma concentrations and pharmacokinetic parameters of SA were not significantly different after the administration of the two ASA formulations. The plain ASA tablet had a significantly lower (p less than 0.05) dissolution rate than buffered ASA tablet. Moreover, the buffered ASA tablet significantly (p less than 0.01) increased the pH by 0.5 units. In conclusion, the bioavailability of the new oral buffered ASA was equivalent to that of plain ASA, but the plasma concentration peak was reached in a shorter time. PMID:1809699

  4. Water-soluble nitric-oxide-releasing acetylsalicylic acid (ASA) prodrugs.

    PubMed

    Rolando, Barbara; Lazzarato, Loretta; Donnola, Monica; Marini, Elisabetta; Joseph, Sony; Morini, Giuseppina; Pozzoli, Cristina; Fruttero, Roberta; Gasco, Alberto

    2013-07-01

    A series of water-soluble (benzoyloxy)methyl esters of acetylsalicylic acid (ASA), commonly known as aspirin, are described. The new derivatives each have alkyl chains containing a nitric oxide (NO)-releasing nitrooxy group and a solubilizing moiety bonded to the benzoyl ring. The compounds were synthesized and evaluated as ASA prodrugs. After conversion to the appropriate salt, most of the derivatives are solid at room temperature and all possess good water solubility. They are quite stable in acid solution (pH 1) and less stable at physiological pH. In human serum, these compounds are immediately metabolized by esterases, producing a mixture of ASA, salicylic acid (SA), and of the related NO-donor benzoic acids, along with other minor products. Due to ASA release, the prodrugs are capable of inhibiting collagen-induced platelet aggregation of human platelet-rich plasma. Simple NO-donor benzoic acids 3-hydroxy-4-(3-nitrooxypropoxy)benzoic acid (28) and 3-(morpholin-4-ylmethyl)-4-[3-(nitrooxy)propoxy]benzoic acid (48) were also studied as representative models of the whole class of benzoic acids formed following metabolism of the prodrugs in serum. These simplified derivatives did not trigger antiaggregatory activity when tested at 300 μM. Only 28 displays quite potent NO-dependent vasodilatatory action. Further in vivo evaluation of two selected prodrugs, {[2-(acetyloxy)benzoyl]oxy}methyl-3-[(3-[aminopropanoyl)oxy]-4-[3-(nitrooxy)propoxy]benzoate⋅HCl (38) and {[2-(acetyloxy)benzoyl]oxy}methyl 3-(morpholin-4-ylmethyl)-4-[3-(nitrooxy)propoxy]benzoate oxalate (49), revealed that their anti-inflammatory activities are similar to that of ASA when tested in the carrageenan-induced paw edema assay in rats. The gastrotoxicity of the two prodrugs was also determined to be lower than that of ASA in a lesion model in rats. Taken together, these results indicated that these NO-donor ASA prodrugs warrant further investigation for clinical application.

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

    PubMed

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

    2011-01-01

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

  6. Ticlopidine, Alka-Seltzer, or a combination of citric acid with aspirin: effects on platelet aggregation in individuals with an insufficient response to aspirin alone.

    PubMed

    Kaplan, S; Kaplan, A; Marcoe, K; Sauvage, L R

    2000-10-01

    Aspirin (ASA) does not effectively lower platelet aggregation in all people. The platelet aggregation (PA) score is an easily used clinical method for measuring the effect in individuals of antiplatelet medications. Fifteen apparently healthy subjects (2 men and 13 women), selected for their resistance to ASA's antiaggregation effect, completed a sequential trial of ticlopidine, Alka-Seltzer, and ASA + citric acid (CTA). Ticlopidine was the strongest aggregation inhibitor and the ASA + CTA combination was more inhibitory than Alka-Seltzer. It was determined that measuring antiaggregation effects of a particular agent in an individual prior to usage would optimize treatment. The PA score methodology provides a means for testing patients prior to antiplatelet therapy for prevention and treatment of the thrombotic complications of vascular disease. PMID:11030528

  7. 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

  8. DNA immobilization on a polypyrrole nanofiber modified electrode and its interaction with salicylic acid/aspirin.

    PubMed

    Yousef Elahi, M; Bathaie, S Z; Kazemi, S H; Mousavi, M F

    2011-04-15

    A double-stranded calf thymus DNA (dsDNA) was physisorbed onto a polypyrrole (PPy) nanofiber film that had been electrochemically deposited onto a Pt electrode. The surface morphology of the polymeric film was characterized using scanning electron microscopy (SEM). The electrochemical characteristics of the PPy film and the DNA deposited onto the PPy modified electrode were investigated by cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS). Then the interaction of DNA with salicylic acid (SA) and acetylsalicylic acid (ASA), or aspirin, was studied on the electrode surface with DPV. An increase in the DPV current was observed due to the oxidation of guanine, which decreased with the increasing concentrations of the ligands. The interactions of SA and ASA with the DNA follow the saturation isotherm behavior. The binding constants of these interactions were 1.15×10(4)M for SA and 7.46×10(5)M for ASA. The numbers of binding sites of SA and ASA on DNA were approximately 0.8 and 0.6, respectively. The linear dynamic ranges of the sensors were 0.1-2μM (r(2)=0.996) and 0.05-1mM (r(2)=0.996) with limits of detection of 8.62×10(-1) and 5.24×10(-6)μM for SA and ASA, respectively.

  9. Effects of acetylsalicylic acid (ASA), ASA plus L-glutamine and L-glutamine on healing of chronic gastric ulcer in the rat.

    PubMed

    Okabe, S; Takeuchi, K; Honda, K; Takagi, K

    1976-01-01

    A chronic gastric ulcer model was produced in rats by the subserosal injection of 20% acetic acid solution (0.015 ml) in order to examine whether (1) acetylsalicylic acid (ASA) irritates the chronic gastric ulcer in active or healed or diminished stage, (2) L-glutamine, given together with ASA, inhibits the adverse effect of ASA. Oral ASA 200 mg/kg/day, given in two divided doses for 10 consecutive days, apparently delayed the healing of the gastric ulcer and irritated the healed ulcer to reulcerate. L-Glutamine, 1,500 mg/kg/day, which was given together with ASA in two divided doses, markedly protected the gastric ulcer both in active and healed stages from the deleterious activity of ASA. PMID:955326

  10. Semi-micro column high-performance liquid chromatography with UV detection for quantification of aspirin and salicylic acid and its application to patients' sera administered with low-dose enteric-coated aspirin.

    PubMed

    Ohwaki, Yuichi; Yamane, Tomoko; Ishimatsu, Takashi; Wada, Mitsuhiro; Nakashima, Kenichiro

    2007-03-01

    A simultaneous determination of aspirin (ASA) and its metabolite, salicylic acid (SA), in human serum by a semi-micro column HPLC-UV was developed. A relatively small size of serum sample (100 microL) containing ASA and SA was cleaned up by a simple solid phase extraction. A good separation of ASA and SA could be achieved within 25 min using a semi-micro ODS column with an eluent of MeOH/0.7 mm phosphoric acid solution (pH 2.5) = 50:50 (v/v). The calibration curves for ASA and SA showed good linearity (r = 0.999) with the detection limits 114 and 38 ng/mL at a signal-to-noise ratio of 3, respectively. ASA and SA in patients' sera administered with low-dose enteric-coated aspirin were determined, and the concentration ranges obtained for ASA and SA were 1.2-2.2 and 0.5-57.3 microg/mL, respectively. PMID:17221906

  11. Semi-micro column high-performance liquid chromatography with UV detection for quantification of aspirin and salicylic acid and its application to patients' sera administered with low-dose enteric-coated aspirin.

    PubMed

    Ohwaki, Yuichi; Yamane, Tomoko; Ishimatsu, Takashi; Wada, Mitsuhiro; Nakashima, Kenichiro

    2007-03-01

    A simultaneous determination of aspirin (ASA) and its metabolite, salicylic acid (SA), in human serum by a semi-micro column HPLC-UV was developed. A relatively small size of serum sample (100 microL) containing ASA and SA was cleaned up by a simple solid phase extraction. A good separation of ASA and SA could be achieved within 25 min using a semi-micro ODS column with an eluent of MeOH/0.7 mm phosphoric acid solution (pH 2.5) = 50:50 (v/v). The calibration curves for ASA and SA showed good linearity (r = 0.999) with the detection limits 114 and 38 ng/mL at a signal-to-noise ratio of 3, respectively. ASA and SA in patients' sera administered with low-dose enteric-coated aspirin were determined, and the concentration ranges obtained for ASA and SA were 1.2-2.2 and 0.5-57.3 microg/mL, respectively.

  12. Aspirin

    MedlinePlus

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

  13. Efficacy of acetylsalicylic acid (aspirin) in skin B16-F0 melanoma tumor-bearing C57BL/6 mice.

    PubMed

    Vad, Nikhil M; Kudugunti, Shashi K; Wang, Hezhen; Bhat, G Jayarama; Moridani, Majid Y

    2014-05-01

    Several epidemiological studies show that aspirin can act as a chemopreventive agent and decrease the incidences of various cancers including melanoma. In this work, we investigated the in vitro and in vivo efficacy of acetylsalicylic acid (ASA) as an antimelanoma agent in B16-F0 cells and skin B16-F0 melanoma tumor mouse model. Our findings indicate that the IC50 (48 h) for ASA in B16-F0 melanoma cells was 100 μM and that ASA caused a dose- and time-dependent GSH depletion and increase in reactive oxygen species (ROS) formation in B16-F0 melanoma cells. Male C57BL/6 mice were inoculated s.c. with 1 × 10(6) B16-F0 melanoma cells. ASA (80, 100, and 150 mg/kg) was initiated on day 1 or day 7, or day 9 after cell inoculation and continued daily for 13, 7, and 5 days, respectively. Animals were weighed daily and sacrificed on day 13. The tumors were excised and weighed. The animals receiving 13 days of ASA therapy at 80, 100, and 150 mg/kg demonstrated tumor growth inhibition by 1 ± 12%, 19 ± 22%, and 50 ± 29%, respectively. Animals receiving 7 days of therapy at 80, 100, and 150 mg/kg demonstrated tumor growth inhibition by 12 ± 14%, 27 ± 14%, and 40 ± 14%, respectively. No significant tumor growth inhibition was observed with 5 days of therapy. ASA at 100 and 150 mg/kg caused significant tumor growth inhibition in C57BL/6 mice when administered for 13 and 7 days, respectively. The results obtained in this study are consistent with the recent epidemiologically based report that aspirin is associated with lower melanoma risk in humans.

  14. Searching for new NO-donor aspirin-like molecules: Furoxanylacyl derivatives of salicylic acid and related furazans.

    PubMed

    Lazzarato, Loretta; Cena, Clara; Rolando, Barbara; Marini, Elisabetta; Lolli, Marco Lucio; Guglielmo, Stefano; Guaita, Elena; Morini, Giuseppina; Coruzzi, Gabriella; Fruttero, Roberta; Gasco, Alberto

    2011-10-01

    A new group of derivatives of salicylic acid containing NO-donor furoxans, and the related des-NO-furazans, were synthesized and evaluated as new aspirin-like molecules. Their stability was assessed in acid (pH 1) and physiological solutions (pH 7.4), and in human serum. No compound exhibited COX-inhibitory activity against COX-1 and COX-2 isoforms, when tested up to 100μM, respectively, on isolated platelets and on monocytes. Phenylsulfonyl- and cyano-substituted furoxans inhibited platelet aggregation induced by collagen in human platelet-rich plasma, through a cGMP dependent mechanism. Furoxan derivatives displayed cGMP-dependent vasodilator activities, tested on rat aorta strips precontracted with phenylephrine. All products showed anti-inflammatory activity similar to that of ASA, tested on rats by the carrageenan-induced paw edema assay. Unlike ASA, all products showed markedly reduced gastrotoxicity in a rat lesion model.

  15. Strong and Long-Lasting Antinociceptive and Anti-inflammatory Conjugate of Naturally Occurring Oleanolic Acid and Aspirin

    PubMed Central

    Bednarczyk-Cwynar, Barbara; Wachowiak, Natalia; Szulc, Michal; Kamińska, Ewa; Bogacz, Anna; Bartkowiak-Wieczorek, Joanna; Zaprutko, Lucjusz; Mikolajczak, Przemyslaw L.

    2016-01-01

    The conjugate 8 was obtained as a result of condensation of 3-hydroxyiminooleanolic acid morfolide (7) and aspirin in dioxane. Analgesic effect of OAO-ASA (8) for the range of doses 0.3–300.0 mg/kg (p.o.) was performed in mice using a hot-plate test. Anti-inflammatory activity was assessed on carrageenan-induced paw edema in rats for the same range of doses. The conjugate OAO-ASA (8) did not significantly change locomotor activity of mice, therefore sedative properties of the compound should be excluded. The compound 8 proved a simple, proportional, dose-dependent analgesic action and expressed strong anti-inflammatory activity showing a reversed U-shaped, dose-dependent relation with its maximum at 30.0 mg/kg. After its combined administration with morphine (MF, 5.0 mg/kg, s.c.) the lowering of antinociceptive activity was found; however, the interaction with naloxone (NL, 3.0 mg/kg, s.c.) did not affect the antinociceptive effect of OAO-ASA (8), therefore its opioid mechanism of action should be rather excluded. After combined administration with acetylsalicylic acid (ASA, 300.0 mg/kg, p.o.) in hot-plate test, the examined compound 8 enhanced the antinociceptive activity in significant way. It also shows that rather the whole molecule is responsible for the antinociceptive and anti-inflammatory effect of the tested compound 8, however, it cannot be excluded that the summarizing effect is produced by ASA released from the compound 8 and the rest of triterpene derivative. The occurrence of tolerance for triterpenic derivative 8 was not observed, since the analgesic and anti-inflammatory effects after chronic administration of the conjugate OAO-ASA (8) was on the same level as after its single treatment. It seemed that the anti-inflammatory mechanism of action of OAO-ASA (8) is not simple, even its chronic administration lowered both blood concentration of IL-6 and mRNA IL-6 expression. However, the effects of the conjugate OAO-ASA (8) on TNF-α level and m

  16. Hypersensitivity to acetylsalicylic acid (ASA) and tartrazine in patients with asthma.

    PubMed

    Stenius, B S; Lemola, M

    1976-03-01

    One-hundred and forty asthmatics were tested perorally with acetylsalicylic acid (ASA), and/or with the azo-colour tartrazine; a fall in PEF of more than 20% was accepted as a positive result. About one quarter of the patients displayed a positive reaction to one of the two tested agents. No significant correlation was found between the reactions of these, and the presence of atopy, nasal polyposis, sinusitis, rhinitis, sensitivity to cold air, the age at onset, duration of asthma, or history of sensitivity to alcoholic drinks. The history suggested sensitivity to ingested, possibly coloured, food and drink, in only about one third of the tartrazine-positive cases. The ASA provocation tests were mainly applied to patients with doubtful or negative histories of sensitivity to ASA-containing drugs. The frequency of cross-reactivity between the two tested agents was statistically significant; patients reacting to tartrazine were for the most part, also sensitive to ASA. Tests for sensitivity to analgesics and food additives should be conducted as a routine measure in asthmatics, and sensitive patients should be given information on suitable medication and dietary control. PMID:1277437

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

    PubMed

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

    2015-09-01

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

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

    PubMed

    Voelker, M; Hammer, M

    2012-08-01

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

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

    PubMed

    Voelker, M; Hammer, M

    2012-08-01

    Aspirin (acetylsalicylic acid, ASA) has been used as an analgesic, antipyretic and antiinflammatory drug for many years. A new 500 mg aspirin tablet formulation containing micronized active ingredient and an effervescent component has been developed for potential improvement in the onset of action for acute pain treatment. This paper describes the dissolution and the pharmacokinetics of the new formulation in comparison with regular aspirin tablets, aspirin granules and aspirin effervescent tablets. Micronized aspirin tablets dissolve significantly faster over a pH range from 1.2 to 6.8 compared to regular 500 mg aspirin tablets. Plasma concentration time curve comparison to regular 500 mg aspirin tablets showed a substantial improvement in the time to maximum plasma concentrations (T(max)) (ASA 17.5 min vs. 45 min) and an increase in maximum plasma concentration (C(max)) (ASA 13.8 μg/ml vs. 4.4 μg/ml) while the overall extent of exposure (AUC) remains almost unchanged. The data suggest a potential improvement for onset of action in treating acute pain with the new micronized aspirin formulation. PMID:22057729

  20. Acetylsalicylic acid (ASA) - How much, how often, and when? A clinical-pharmacological perspective.

    PubMed

    Loew, Dieter; Belz, Gustav G

    2016-08-01

    The dose of acetylsalicylic acid (ASA) commonly used in the prevention and treatment of arteriosclerotic angiopathies is equal to or less than 100 mg daily. This choice of dose is predominantly based on molecular-pharmacological findings showing an inhibition in synthesis of the prothrombotic thromboxane (TXB2) and an irreversible inhibition in blood platelet aggregation. However, an analysis of ASA dose-effect relationships for doses of 50 - 500 mg (PO and IV) shows that doses of ASA up to 100 mg daily produce only a small or moderate inhibition in collagen/epinephrine-induced platelet aggregation and have no significant effect on the important platelet factors, PF3 and PF4. Doses of ASA 300 - 500 mg, on the other hand, inhibit platelet aggregation almost completely and, in addition, produce a 50 - 70% inhibition in PF3 and PF4 lasting at least 24 hours. There is also evidence that doses of ASA above 100 mg daily markedly inhibit thromboxane synthesis for up to 24 hours and that doses of 500 mg daily produce a clinically relevant inhibition in platelet adhesion to vessel walls for up 72 hours and prevent procoagulatory shape changes for up to 12 hours. These findings suggest that a dose of ≥ 300 mg at intervals of 2 - 3 days would be more appropriate for primary and secondary prophylaxis of arteriosclerotic angiopathies and that the benefit-risk ratio would be greater because of the increased availability of mucoprotective prostaglandins, PGI2 (prostacyclin) and the gastroprotective, PGE2. Our viewpoint, predominantly based on findings with biomarkers, could serve as a basis for further randomized controlled studies.

  1. 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.

  2. Effect of 5-aminosalicylic acid (5-ASA) and other salicylates on short-chain fat metabolism in the colonic mucosa. Pharmacological implications for ulcerative colitis.

    PubMed

    Roediger, W; Schapel, G; Lawson, M; Radcliffe, B; Nance, S

    1986-01-15

    5-Aminosalicylic acid (5-ASA) suppressed nitrite-stimulated oxidation of the fatty acid n-butyrate in a dose-dependent manner in isolated human and rat colonic epithelial cells. 4-ASA had one-sixth of the capacity of 5-ASA and sulphapyridine (SP) little of the capacity of 5-ASA to suppress fatty acid oxidation in human colonic epithelial cells. Sulphasalazine (SASP), azodisalicylic acid (ADS), acetyl-5-ASA and acetyl salicylic acid (ASA) did not suppress fatty acid oxidation in rat colonocytes. The suppression index of fatty acid oxidation (SIFO) of respective salicylic acids correlated with the reported clinical effectiveness of each drug against ulcerative colitis (UC). The capacity of 5-ASA to affect nitrite-stimulated oxidation of fat in the colonic mucosa suggests that nitrite ions and control of fatty acid oxidation play a central role in the development and therapy of active UC. PMID:2867767

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

    PubMed

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

    2016-10-01

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

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

    NASA Astrophysics Data System (ADS)

    El-Shahawy, Anwar S.

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

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

    PubMed

    Bazzi, Mohammad D

    2002-04-26

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

  6. 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.

  7. 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

  8. 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.

  9. Salicylic acid sans aspirin in animals and man: persistence in fasting and biosynthesis from benzoic acid.

    PubMed

    Paterson, John R; Baxter, Gwendoline; Dreyer, Jacob S; Halket, John M; Flynn, Robert; Lawrence, James R

    2008-12-24

    Salicylic acid (SA), which is central to defense mechanisms in plants and the principal metabolite of aspirin, occurs naturally in man with higher levels of SA and its urinary metabolite salicyluric acid (SU) in vegetarians overlapping with levels in patients on low-dose aspirin regimens. SA is widely distributed in animal blood. Fasting for major colorectal surgery did not cause disappearance of SA from plasma, even in patients following total proctocolectomy. A (13)C(6) benzoic acid load ingested by six volunteers led, between 8 and 16 h, to a median 33.9% labeling of urinary salicyluric acid. The overall contribution of benzoic acid (and its salts) to the turnover of circulating SA thus requires further assessment. However, that SA appears to be, at least partially, an endogenous compound should lead to reassessment of its role in human (and animal) pathophysiology. PMID:19053387

  10. Salicylic acid sans aspirin in animals and man: persistence in fasting and biosynthesis from benzoic acid.

    PubMed

    Paterson, John R; Baxter, Gwendoline; Dreyer, Jacob S; Halket, John M; Flynn, Robert; Lawrence, James R

    2008-12-24

    Salicylic acid (SA), which is central to defense mechanisms in plants and the principal metabolite of aspirin, occurs naturally in man with higher levels of SA and its urinary metabolite salicyluric acid (SU) in vegetarians overlapping with levels in patients on low-dose aspirin regimens. SA is widely distributed in animal blood. Fasting for major colorectal surgery did not cause disappearance of SA from plasma, even in patients following total proctocolectomy. A (13)C(6) benzoic acid load ingested by six volunteers led, between 8 and 16 h, to a median 33.9% labeling of urinary salicyluric acid. The overall contribution of benzoic acid (and its salts) to the turnover of circulating SA thus requires further assessment. However, that SA appears to be, at least partially, an endogenous compound should lead to reassessment of its role in human (and animal) pathophysiology.

  11. Salicylic Acid sans Aspirin in Animals and Man: Persistence in Fasting and Biosynthesis from Benzoic Acid

    PubMed Central

    2008-01-01

    Salicylic acid (SA), which is central to defense mechanisms in plants and the principal metabolite of aspirin, occurs naturally in man with higher levels of SA and its urinary metabolite salicyluric acid (SU) in vegetarians overlapping with levels in patients on low-dose aspirin regimens. SA is widely distributed in animal blood. Fasting for major colorectal surgery did not cause disappearance of SA from plasma, even in patients following total proctocolectomy. A 13C6 benzoic acid load ingested by six volunteers led, between 8 and 16 h, to a median 33.9% labeling of urinary salicyluric acid. The overall contribution of benzoic acid (and its salts) to the turnover of circulating SA thus requires further assessment. However, that SA appears to be, at least partially, an endogenous compound should lead to reassessment of its role in human (and animal) pathophysiology. PMID:19053387

  12. Positional isomerism markedly affects the growth inhibition of colon cancer cells by NOSH-aspirin: COX inhibition and modeling☆

    PubMed Central

    Vannini, Federica; Chattopadhyay, Mitali; Kodela, Ravinder; Rao, Praveen P.N.; Kashfi, Khosrow

    2015-01-01

    We recently reported the synthesis of NOSH-aspirin, a novel hybrid that releases both nitric oxide (NO) and hydrogen sulfide (H2S). In NOSH-aspirin, the two moieties that release NO and H2S are covalently linked at the 1, 2 positions of acetyl salicylic acid, i.e. ortho-NOSH-aspirin (o-NOSH-aspirin). In the present study, we compared the effects of the positional isomers of NOSH-ASA (o-NOSH-aspirin, m-NOSH-aspirin and p-NOSH-aspirin) to that of aspirin on growth of HT-29 and HCT 15 colon cancer cells, belonging to the same histological subtype, but with different expression of cyclooxygenase (COX) enzymes; HT-29 express both COX-1 and COX-2, whereas HCT 15 is COX-null. We also analyzed the effect of these compounds on proliferation and apoptosis in HT-29 cells. Since the parent compound aspirin, inhibits both COX-1 and COX-2, we also evaluated the effects of these compounds on COX-1 and COX-2 enzyme activities and also performed modeling of the interactions between the positional isomers of NOSH-aspirin and COX-1 and COX-2 enzymes. We observed that the three positional isomers of NOSH aspirin inhibited the growth of both colon cancer cell lines with IC50s in the nano-molar range. In particular in HT-29 cells the IC50s for growth inhibition were: o-NOSH-ASA, 0.04±0.011 µM; m-NOSH-ASA, 0.24±0.11 µM; p-NOSH-ASA, 0.46±0.17 µM; and in HCT 15 cells the IC50s for o-NOSH-ASA, m-NOSH-ASA, and p-NOSH-ASA were 0.062 ±0.006 µM, 0.092±0.004 µM, and 0.37±0.04 µM, respectively. The IC50 for aspirin in both cell lines was >5 mM at 24 h. The reduction of cell growth appeared to be mediated through inhibition of proliferation, and induction of apoptosis. All 3 positional isomers of NOSH-aspirin preferentially inhibited COX-1 over COX-2. These results suggest that the three positional isomers of NOSH-aspirin have the same biological actions, but that o-NOSH-ASA displayed the strongest anti-neoplastic potential. PMID:26319435

  13. Positional isomerism markedly affects the growth inhibition of colon cancer cells by NOSH-aspirin: COX inhibition and modeling.

    PubMed

    Vannini, Federica; Chattopadhyay, Mitali; Kodela, Ravinder; Rao, Praveen P N; Kashfi, Khosrow

    2015-12-01

    We recently reported the synthesis of NOSH-aspirin, a novel hybrid that releases both nitric oxide (NO) and hydrogen sulfide (H2S). In NOSH-aspirin, the two moieties that release NO and H2S are covalently linked at the 1, 2 positions of acetyl salicylic acid, i.e. ortho-NOSH-aspirin (o-NOSH-aspirin). In the present study, we compared the effects of the positional isomers of NOSH-ASA (o-NOSH-aspirin, m-NOSH-aspirin and p-NOSH-aspirin) to that of aspirin on growth of HT-29 and HCT 15 colon cancer cells, belonging to the same histological subtype, but with different expression of cyclooxygenase (COX) enzymes; HT-29 express both COX-1 and COX-2, whereas HCT 15 is COX-null. We also analyzed the effect of these compounds on proliferation and apoptosis in HT-29 cells. Since the parent compound aspirin, inhibits both COX-1 and COX-2, we also evaluated the effects of these compounds on COX-1 and COX-2 enzyme activities and also performed modeling of the interactions between the positional isomers of NOSH-aspirin and COX-1 and COX-2 enzymes. We observed that the three positional isomers of NOSH aspirin inhibited the growth of both colon cancer cell lines with IC50s in the nano-molar range. In particular in HT-29 cells the IC50s for growth inhibition were: o-NOSH-ASA, 0.04±0.011 µM; m-NOSH-ASA, 0.24±0.11 µM; p-NOSH-ASA, 0.46±0.17 µM; and in HCT 15 cells the IC50s for o-NOSH-ASA, m-NOSH-ASA, and p-NOSH-ASA were 0.062 ±0.006 µM, 0.092±0.004 µM, and 0.37±0.04 µM, respectively. The IC50 for aspirin in both cell lines was >5mM at 24h. The reduction of cell growth appeared to be mediated through inhibition of proliferation, and induction of apoptosis. All 3 positional isomers of NOSH-aspirin preferentially inhibited COX-1 over COX-2. These results suggest that the three positional isomers of NOSH-aspirin have the same biological actions, but that o-NOSH-ASA displayed the strongest anti-neoplastic potential.

  14. Effects of paracetamol and propacetamol on gastric mucosal damage and gastric lipid peroxidation caused by acetylsalicylic acid (ASA) in rats.

    PubMed

    Galunska, B; Marazova, K; Tankova, T; Popov, A; Frangov, P; Krushkov, I; Di Massa, A

    2002-08-01

    We have studied the effect of paracetamol and its pro-drug propacetamol on gastric mucosal damage induced by acetylsalicylic acid (ASA) and its possible relation to changes in gastric lipid peroxidation status in rats. Paracetamol or propacetamol were administered intragastrically 1h before ASA (300 mg kg(-1)) in the following equivalent doses: 62.5, 125.0 and 250.0 mg kg(-1) or 125.0, 250.0 and 500.0 mg kg(-1), respectively. The effects of the tested agents were compared to that of prostaglandin E2 (PGE2) 15, 30 and 60 mg kg(-1). Gastric ulcer formation was estimated morphometrically 4h after ASA administration. Malondialdehyde (MDA), glutathione (reduced, GSH, and oxidized, GSSG) and uric acid (UA) were determined in gastric mucosa and blood plasma and used as biochemical markers of the oxidative status. The results showed that paracetamol (250, 125, 62.5 mg kg(-1)) and propacetamol (500, 250, 125 mg kg(-1)) diminished the area of ASA-induced gastric lesions. The effect of propacetamol was more pronounced than that of paracetamol and similar to that of PGE2. Gastric MDA increased 3-fold in the ASA-group. The tested agents reduced it by a range of 30-70%. In all pretreated groups gastric glutathione and UA levels were found higher than that of control group and lower than that of ASA-group. Paracetamol and propacetamol, as well as PGE2, diminished the lipid peroxidation in plasma to a lesser extent than in gastric mucosa, but maintained elevated levels of the selective plasma antioxidant UA. These results show that the ASA-induced gastric mucosal damage is accompanied by the development of oxidative stress, evidenced by the accumulation of MDA, and concomitant initial activation of cell antioxidant defences. As paracetamol and propacetamol tend to decrease gastric lesions caused by ASA and alter gastric mucosal MDA, glutathione and UA values in a favorable manner, it could be suggested that their effects on the gastric mucosa could be related to interference with

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

    PubMed

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

    1989-01-01

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

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

    PubMed

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

    1989-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2002-05-01

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

  20. 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

  1. Solid-state 17O NMR of pharmaceutical compounds: salicylic acid and aspirin.

    PubMed

    Kong, Xianqi; Shan, Melissa; Terskikh, Victor; Hung, Ivan; Gan, Zhehong; Wu, Gang

    2013-08-22

    We report solid-state NMR characterization of the (17)O quadrupole coupling (QC) and chemical shift (CS) tensors in five site-specifically (17)O-labeled samples of salicylic acid and o-acetylsalicylic acid (Aspirin). High-quality (17)O NMR spectra were obtained for these important pharmaceutical compounds under both static and magic angle spinning (MAS) conditions at two magnetic fields, 14.0 and 21.1 T. A total of 14 (17)O QC and CS tensors were experimentally determined for the seven oxygen sites in salicylic acid and Aspirin. Although both salicylic acid and Aspirin form hydrogen bonded cyclic dimers in the solid state, we found that the potential curves for the concerted double proton transfer in these two compounds are significantly different. In particular, while the double-well potential curve in Aspirin is nearly symmetrical, it is highly asymmetrical in salicylic acid. This difference results in quite different temperature dependencies in (17)O MAS spectra of the two compounds. A careful analysis of variable-temperature (17)O MAS NMR spectra of Aspirin allowed us to obtain the energy asymmetry (ΔE) of the double-well potential, ΔE = 3.0 ± 0.5 kJ/mol. We were also able to determine a lower limit of ΔE for salicylic acid, ΔE > 10 kJ/mol. These asymmetrical features in potential energy curves were confirmed by plane-wave DFT computations, which yielded ΔE = 3.7 and 17.8 kJ/mol for Aspirin and salicylic acid, respectively. To complement the solid-state (17)O NMR data, we also obtained solid-state (1)H and (13)C NMR spectra for salicylic acid and Aspirin. Using experimental NMR parameters obtained for all magnetic nuclei present in salicylic acid and Aspirin, we found that plane-wave DFT computations can produce highly accurate NMR parameters in well-defined crystalline organic compounds.

  2. Teratogenic effects of the interaction acetylsalicylic acid (ASA) and ethanol: morphologic and morphometric evaluation of the lingual epithelium in rat fetuses.

    PubMed

    Marinho, S A; Sala, M A; Lopes, R A; de Moraes Grisi, M F; Novaes, A B; de Souza, S L S; Taba, M

    2007-02-01

    The objective of the present work was to evaluate the teratogenic effects of the interaction between acetylsalicylic acid (ASA) and ethanol on the epithelium of the lingual mucosa in rat fetuses. On the 10th pregnancy day, a single intraperitoneal ethanol dose (2.96 g/kg body weight) (Group I), ASA (200 mg/kg body weight) (Group II) and ASA plus ethanol, in the same doses (Group III), or saline (Group IV - control), were administrated. The epithelial alterations were assessed by means of histological and morphometric methods, on posterior dorsal, anterior dorsal and ventral regions of the tongue. ASA reduced, in rat fetuses, the ethanol deleterious effects on nuclear size in the epithelial prickle cell of the lingual mucosa. On the other hand, ASA did not influence the effects of ethanol in both epithelial layers of the lingual mucosa, when the nuclear shape, cell volume or epithelial layers thickness were evaluated.

  3. Aromatic hydroxylation of salicylic acid and aspirin by human cytochromes P450.

    PubMed

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

    2015-06-20

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

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

    PubMed

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

    2010-02-28

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

  5. Nitrooxyacyl derivatives of salicylic acid: aspirin-like molecules that covalently inactivate cyclooxygenase-1.

    PubMed

    Cena, Clara; Tosco, Paolo; Marini, Elisabetta; Lazzarato, Loretta; Piccinini, Marco; Ramondetti, Cristina; Lupino, Elisa; Fruttero, Roberta; Gasco, Alberto

    2011-03-01

    A recently described series of nitrooxyacyl derivatives of salicylic acid, displaying aspirin-like anti-inflammatory and platelet anti-aggregatory properties, were evaluated for their abilities to inhibit cyclooxygenase (COX). A number of these compounds irreversibly inhibited both COX-1 and COX-2 isoforms when tested in isolated human platelets and monocytes. Further studies using COX-1 expressed in human HEK293T cells showed that this inhibition mechanism is similar to that of aspirin; namely, the products are able to covalently bind to the Ser 530 residue present in the active cleft of the enzyme. Molecular modeling enabled us to rationalize this behavior. Because these products were previously found to display NO-dependent properties in rat animal models, particularly as they decreased in vivo gastrotoxicity and induced in vitro vasodilation, they represent a new and interesting class of potential aspirin-like antithrombotic agents worthy of further study.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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…

  11. 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

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

    PubMed

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

    2015-06-18

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

  13. Epithelial MUC1 promotes cell migration, reduces apoptosis and affects levels of mucosal modulators during acetylsalicylic acid (aspirin)-induced gastropathy.

    PubMed

    Banerjee, Debashish; Fernandez, Harvey Robert; Patil, Pradeep Bhatu; Premaratne, Pushpa; Quiding-Järbrink, Marianne; Lindén, Sara Katarina

    2015-02-01

    MUC1 is a transmembrane mucin highly expressed in the stomach. Although extensive research has uncovered many of its roles in cancer, knowledge about the functions of MUC1 in normal tissues is limited. In the present study, we showed that acetylsalicylic acid (ASA; aspirin) up-regulated MUC1/Muc1 expression in the gastric mucosa of humans and wild-type (WT) mice. ASA induced mucosal injury in all mice to a similar extent; however, WT animals and those chimaeras with Muc1 on the epithelia recovered faster than Muc1-knockout (KO) mice and chimaeras carrying Muc1 on haemopoietic but not epithelial cells. MUC1 enhanced proliferation and migration of the human gastric cell line MKN-7 and increased resistance to apoptosis. The repeated treatment regime used caused a reduction in cyclo-oxygenase-1 (Cox-1) expression, though WT animals returned faster towards pre-treatment levels and had increased Cox-2 and vascular endothelial growth factor levels during recovery. Thus we found that epithelial Muc1 is more important for the healing process than haemopoietic Muc1 and Muc1/MUC1 facilitates wound healing by enhancing cell migration and proliferation, protecting against apoptosis and mediating expression of mucosal modulators. Thus MUC1 plays essential roles during wound healing and development of treatment modalities targeting enhanced expression of MUC1 may be beneficial to treat mucosal wounds.

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

    PubMed

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

    1988-03-01

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

  15. 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

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2003-01-31

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

  18. Pharmacokinetic and pharmacodynamic study of NO-donating aspirin in F344 rats.

    PubMed

    Rao, Chinthalapally V; Joseph, Stancy; Gao, Li; Patlolla, Jagan M R; Choi, Chang-In; Kopelovich, Levy; Steele, Vernon E; Rigas, Basil

    2008-10-01

    Nitric oxide-donating aspirin (NO-ASA) represents class of promising chemopreventive NO-NSAIDs. NO-ASA combines the beneficial effects of ASA and the gut-sparing effect of the NO moiety. There is, however, limited information on its pharmacokinetic and pharmacodynamic effects in vivo. Herein, experiments were designed to identify the optimal dose, the effective route of administration, and targeted markers in plasma and colonic tissues of male F344 rats. Seven weeks old male F344 rats were randomized into 9 groups (16/group) and fed the control diet. At eight weeks of age, groups 2-5 were each administered one of four different doses of NO-ASA by gavage (33, 66, 132 and 264 mg/kg) and each of groups 6-9 were fed diets containing NO-ASA (35, 700, 1,400 and 2,800 ppm) for two weeks. Rats were sacrificed 2 and 10 h after completion of the two weeks of treatment with NO-ASA and plasma and colonic mucosa were collected and analyzed for NO-ASA, its metabolites, and PGE2 and TXB2 levels. Our results indicate that NO-ASA is rapidly metabolized, predominantly to salicylic acid; no intact NO-ASA was detected in plasma. Compared to diet-fed NO-ASA, gavaging generated much higher salicylic acid levels over a wide range of doses and a relatively broad time period (10 h). Regardless of its route of administration, NO-ASA lowered the levels of PGE2 in colonic tissues and plasma, as well as TxB2 in plasma in a dose- and time-dependent manner. These findings may have practical utility for the administration of NO-ASA to humans. PMID:18813794

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

    SciTech Connect

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

    2012-03-15

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

  20. 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

  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.

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

    PubMed

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

    2006-02-01

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

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

    PubMed

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

    2006-02-01

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

  4. Prandial and diurnal effects on the absorption of orally administered enteric coated 5-aminosalicylic acid (5-ASA).

    PubMed

    De Mey, C; Meineke, I

    1992-02-01

    Plasma and urine concentrations of 5-ASA and its N-acetyl metabolite 5-AcASA were measured over 48 h in 12 young healthy male subjects, who received three doses of three times enteric coated 500 mg 5-ASA tablets at 7 h interval, on two occasions 14 days apart. On one occasion the doses were given after standard meals; on the other occasion, they were given 1 h before meals. Administration of the tablets after meals delayed systemic drug absorption but did not affect the extent of absorption. There was a sharp rise in the plasma concentrations of 5-ASA and 5-AcASA in the early morning (i.e. circa 24 h after administration of the 1st dose) independent of when the tablets were taken with respect to the meals. This suggests that tablets or tablet fragments remained in the stomach until the later part of the night. Thus, diurnal effects may be more important than prandial effects in the evaluation of the kinetics of 5-ASA and its metabolites after peroral administration of enteric coated tablets.

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

    PubMed

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

    2010-06-10

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

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

    PubMed

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

    2016-08-15

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

  7. In vitro release of arachidonic acid metabolites, glutathione peroxidase, and oxygen-free radicals from platelets of asthmatic patients with and without aspirin intolerance.

    PubMed Central

    Plaza, V.; Prat, J.; Rosellò, J.; Ballester, E.; Ramis, I.; Mullol, J.; Gelpí, E.; Vives-Corrons, J. L.; Picado, C.

    1995-01-01

    BACKGROUND--An abnormal platelet release of oxygen-free radicals has been described in acetylsalicylic acid (aspirin)-induced asthma, a finding which might suggest the existence of an intrinsic, specific platelet abnormality of arachidonic acid metabolism in these patients. The objective of this study was to evaluate platelet arachidonic acid metabolism in asthmatic patients with or without intolerance to aspirin. METHODS--Thirty subjects distributed into three groups were studied: group 1, 10 healthy subjects; group 2, 10 asthmatic patients with aspirin tolerance; and group 3, 10 aspirin-intolerant asthmatics. Platelets were isolated from blood, preincubated with 3H-arachidonic acid for 30 minutes and then incubated for 10 minutes with platelet activating factor (PAF) and aspirin. Cyclo-oxygenase (thromboxane, PGE2, PGF2 alpha, and HHT) and lipoxygenase (12-HETE) arachidonic acid metabolites were measured by high pressure liquid chromatography. Release of oxygen free radicals after incubation with PAF and aspirin was measured by chemiluminescence. Platelet levels of glutathione peroxidase (GSH-Px) were also measured using spectrophotometry. RESULTS--Platelets from aspirin-intolerant asthmatic patients produced higher quantities of arachidonic acid metabolites than the control group at baseline conditions. This increase was significant only for lipoxygenase products. No differences were found amongst the three groups in the response of arachidonic acid metabolism to PAF and aspirin. Incubation with aspirin but not with PAF caused an increase in oxygen-free radical production in aspirin-intolerant patients whereas in aspirin-tolerant patients PAF, rather than aspirin, was the more potent stimulus for oxygen-free radical production. No differences in GSH-Px levels were found amongst the three groups. CONCLUSIONS--These results suggest that the platelet lipoxygenase pathway is activated in aspirin-intolerant patients and that the production of oxygen-free radicals may

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  10. Acetyl salicylic acid (aspirin) improves synthesis of maspin and lowers incidence of metastasis in breast cancer patients [corrected].

    PubMed

    Bhattacharyya, Mau; Girish, Gannareddy V; Ghosh, Rajeshwary; Chakraborty, Somashree; Sinha, Asru K

    2010-10-01

    Maspin, a 42 kDa protein produced in normal breast cells, has been shown to inhibit the invasion and metastasis of breast cancer in an animal model. Ingestion of acetylsalicylic acid (aspirin) by breast cancer patients has been reported to restore the systemic synthesis of maspin through the stimulation of systemic nitric oxide production. Studies were carried out to determine the effect of aspirin on the incidence of breast cancer metastasis, which is reported to occur in 50% of patients who have previously received chemotherapy, radiation, and/or surgery. Thirty-five female patients (aged 41-65 years) with breast cancer who had previously received these therapies took one 75 mg/70 kg body weight enteric-coated aspirin tablet every 24 h, after an adequate meal, for 3 years. Their plasma nitric oxide and maspin levels were measured. The occurrence of metastasis was ascertained monthly by a qualified oncologist, and confirmed, if necessary, by biopsy. Daily ingestion of aspirin by participants resulted in an increase in maspin levels from 0.95 ± 0.04 to 4.63 ± 0.05 nM after 24 h. These levels were maintained for 3 years. These studies suggest that daily ingestion of aspirin might significantly reduce the incidence of breast cancer metastasis in patients who have previously received anticancer therapies.

  11. Aspirin Increases the Solubility of Cholesterol in Lipid Membranes

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

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

    PubMed Central

    Block, Robert C; Abdolahi, Amir; Tu, Xin; Georas, Steve N; Brenna, J. Thomas; Phipps, Richard P; Lawrence, Peter; Mousa, Shaker A

    2015-01-01

    Aspirin’s prevention of cardiovascular disease (CVD) events in individuals with type 2 diabetes mellitus is controversial. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and aspirin all affect the cyclooxygenase enzyme. The relationship between plasma EPA and DHA and aspirin’s effects has not been determined. Thirty adults with type 2 diabetes mellitus ingested aspirin (81 mg/day) for 7 days, then EPA+DHA (2.6 g/day) for 28 days, then both for another 7 days. Lysophosphatidic acid (LPA) species and more classic platelet function outcomes were determined. Plasma concentrations of total EPA+DHA were associated with 7-day aspirin reduction effects on these outcomes in a “V”-shaped manner for all 11 LPA species and ADP-induced platelet aggregation. This EPA+DHA concentration was quite consistent for each of the LPA species and ADP. These results support aspirin effects on lysolipid metabolism and platelet aggregation depending on plasma EPA+DHA concentrations in individuals with a disturbed lipid milieu. PMID:25555354

  13. Newly Identified Targets of Aspirin and Its Primary Metabolite, Salicylic Acid.

    PubMed

    Klessig, Daniel F

    2016-04-01

    Salicylic acid (SA) is a plant hormone, which influences several physiological processes, and is a critical modulator of multiple levels of immunity in plants. Several high-throughput screens, which were developed to identify SA-binding proteins through which SA mediates its many physiological effects in plants, uncovered several novel targets of aspirin and its primary metabolite, SA, in humans. These include glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and high mobility group box 1 (HMGB1), two proteins associated with some of the most prevalent and devastating human diseases. In addition, natural and synthetic SA derivatives were discovered, which are much more potent than SA at inhibiting the disease-associated activities of these targets. PMID:26954428

  14. Newly Identified Targets of Aspirin and Its Primary Metabolite, Salicylic Acid.

    PubMed

    Klessig, Daniel F

    2016-04-01

    Salicylic acid (SA) is a plant hormone, which influences several physiological processes, and is a critical modulator of multiple levels of immunity in plants. Several high-throughput screens, which were developed to identify SA-binding proteins through which SA mediates its many physiological effects in plants, uncovered several novel targets of aspirin and its primary metabolite, SA, in humans. These include glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and high mobility group box 1 (HMGB1), two proteins associated with some of the most prevalent and devastating human diseases. In addition, natural and synthetic SA derivatives were discovered, which are much more potent than SA at inhibiting the disease-associated activities of these targets.

  15. Determinants of Aspirin Metabolism in Healthy Men and Women: Effects of Dietary Inducers of UDP-Glucuronosyltransferases

    PubMed Central

    Navarro, Sandi L.; Saracino, Misty R.; Makar, Karen W.; Thomas, Sushma S.; Li, Lin; Zheng, Yingye; Levy, Lisa; Schwarz, Yvonne; Bigler, Jeannette; Potter, John D.; Lampe, Johanna W.

    2011-01-01

    Background/Aims Interindividual variation in aspirin (ASA) metabolism is attributed to concomitant use of drugs or alcohol, urine pH, ethnicity, sex, and genetic variants in UDP-glucuronosyltransferases (UGT). Little is known about the effects of diet. Methods We evaluated cross-sectionally whether urinary excretion of ASA and its metabolites [salicylic acid (SA), salicyluric acid (SUA) phenolic glucuronide (SUAPG), salicylic acid acyl glucuronide (SAAG) and salicylic acid phenolic glucuronide (SAPG)] differed by UGT1A6 genotype and dietary factors shown to induce UGT. Following oral treatment with 650 mg ASA, urine was collected over 8 h in 264 men and 264 women (21–45 years old). Results There were statistically significant differences in metabolites excreted between sexes and ethnicities. Men excreted more SUA; women more ASA (p = 0.03), SA, SAAG and SAPG (p ≤ 0.001 for all). Compared to Caucasians, Asians excreted more ASA, SA and SAAG, and less SUA and SUAPG (p ≤ 0.03 for all); African-Americans excreted more SAAG and SAPG and less SUA (p ≤ 0.04). There was no effect of UGT1A6 genotypes. Increased ASA and decreased SUAPG excretion was observed with increased servings of vegetables (p = 0.008), specifically crucifers (p = 0.05). Conclusion Diet may influence the pharmacokinetics of ASA, but effects may be through modulation of glycine conjugation rather than glucuronidation. PMID:21625173

  16. 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

  17. [Autopsy case of aspirin intoxication: distribution of salicylic acid and salicyluric acid in body fluid and organs].

    PubMed

    Ihama, Yoko; Ageda, Saori; Fuke, Chiaki; Miyazaki, Tetsuji

    2007-10-01

    A 52 year-old woman ingested approximately 300 tablets (325 mg) of aspirin in a suicide attempt. We analyzed the concentrations of salicylic acid (SA) and salicyluric acid (SUA) in body fluids and organs using a modified previous high-performance liquid chromatographic method. The concentrations of SA in heart and femoral blood were 1.1 mg/mL and 1.3 mg/mL, respectively; the results were far higher than the lethal level. The concentration of SA was 0.3-0.4 mg/g in brain, 0.9-1.4 mg/g in lung, 0.6-0.8 mg/g in liver and 0.9 mg/mL in kidney.

  18. 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 ...

  19. 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.

  20. 5-ASA Dose-Response

    PubMed Central

    Katz, Seymour; Lichtenstein, Gary R; Safdi, Michael A

    2010-01-01

    Mesalamine (5-aminosalicylic acid; 5-ASA) represents the cornerstone of first-line therapy for mild-to-moderate ulcerative colitis (UC). Current guidelines suggest that the combination of oral and rectal therapies provide optimal symptom resolution and effectively maintain remission in the majority of these patients. Although effective, most oral 5-ASA formulations have a high pill burden and rectal therapies are associated with low adherence. Recent research has examined patterns of compliance, as well as the efficacy of different dose levels of 5-ASA in terms of symptom resolution, the maintenance of remission, and improvements in quality of life. The ASCEND I, II, and III trials found that doses of 4.8 g/day are more effective than 2.4 g/day doses in patients with moderate disease, those with previous steroid use, and those with a history of multiple medications. The benefits of effective long-term 5-ASA therapy include the avoidance of more costly and potentially toxic drugs (such as corticosteroids and biologic therapies), as well as improvements in quality of life, reductions in the need for future colectomy, and a lower risk of developing colorectal cancer. PMID:20567558

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

    PubMed

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

    2010-08-01

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

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

    PubMed

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

    2010-08-01

    The electrochemical behavior of triflusal (TRF) and aspirin (ASA), before and after hydrolysis in water and in alkaline medium using two different electrode surfaces, glassy carbon and boron doped diamond, was study by differential pulse voltammetry over a wide pH range. The hydrolysis products are 2-(hydroxyl)-4-(trifluoromethyl)-benzoic acid (HTB) for triflusal and salicylic acid (SA) for aspirin, which in vivo represent their main metabolites. The hydrolysis processes were also followed by spectrophotometry. The UV results showed complete hydrolysis after one hour for TRF and after two hours for ASA in alkaline solution. The glassy carbon electrode enables only indirect determination of TRF and ASA through the electrochemical detection of their hydrolysis products HTB and SA, respectively. The oxidation processes of HTB and SA are pH dependent and involve different numbers of electrons and protons. Moreover, the difference between the oxidation peak potential of SA and HTB was equal to 100 mV in the studied pH range from 1 to 8 due to the CF3 of the aromatic ring of HTB molecule. Due to its wider oxidation potential range, the boron doped diamond electrode was used to study the direct oxidation of TRF and ASA, as well as of their respective metabolites HTB and SA. PMID:20402644

  3. Sensitive determination of aspirin and its metabolites in plasma by LC-UV using on-line solid-phase extraction with methylcellulose-immobilized anion-exchange restricted access media.

    PubMed

    Yamamoto, Eiichi; Takakuwa, Susumu; Kato, Takashi; Asakawa, Naoki

    2007-02-01

    We describe a sensitive determination of aspirin (ASA) and its three metabolites (salicylic acid [SA], 2,3-dihydroxybenzoic acid [2,3-DHBA], and 2,5-dihydroxybenzoic acid [gentisic acid (GA)]) in rat plasma. Analysis was carried out by on-line solid-phase extraction (SPE) using a methylcellulose-immobilized-strong anion-exchanger (MC-SAX), followed by liquid chromatography (LC) coupled with UV detection. The lower limits of quantitation for ASA and SA were 60 ng/mL in 100 microL of plasma, respectively. This method was validated with respect to intra- and inter-day precision, accuracy, and linearity up to concentrations of 20,000 ng/mL for ASA, SA, 2,3-DHBA and gentisic acid, respectively. The method was successfully applied to an analysis of the pharmacokinetics of ASA and SA in rats. PMID:16959551

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

    PubMed

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

    2015-01-01

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

  5. ASA24-Canada-2014

    Cancer.gov

    A Canadian adaptation of the Automated Self-Administered 24-hour (ASA24-Canada-2014) Recall has been developed by the Food Directorate at Health Canada in collaboration with the National Cancer Institute (NCI).

  6. Role of TGF-β1 and MAP Kinases in the Antiproliferative Effect of Aspirin in Human Vascular Smooth Muscle Cells

    PubMed Central

    Redondo, Santiago; Ruiz, Emilio; Gordillo-Moscoso, Antonio; Navarro-Dorado, Jorge; Ramajo, Marta; Carnero, Manuel; Reguillo, Fernando; Rodriguez, Enrique; Tejerina, Teresa

    2010-01-01

    Background We aimed to test the antiproliferative effect of acetylsalicylic acid (ASA) on vascular smooth muscle cells (VSMC) from bypass surgery patients and the role of transforming growth factor beta 1 (TGF-β1). Methodology/Principal Findings VSMC were isolated from remaining internal mammary artery from patients who underwent bypass surgery. Cell proliferation and DNA fragmentation were assessed by ELISA. Protein expression was assessed by Western blot. ASA inhibited BrdU incorporation at 2 mM. Anti-TGF-β1 was able to reverse this effect. ASA (2 mM) induced TGF-β1 secretion; however it was unable to induce Smad activation. ASA increased p38MAPK phosphorylation in a TGF-β1-independent manner. Anti-CD105 (endoglin) was unable to reverse the antiproliferative effect of ASA. Pre-surgical serum levels of TGF-β1 in patients who took at antiplatelet doses ASA were assessed by ELISA and remained unchanged. Conclusions/Significance In vitro antiproliferative effects of aspirin (at antiinflammatory concentration) on human VSMC obtained from bypass patients are mediated by TGF-β1 and p38MAPK. Pre-surgical serum levels of TGF- β1 from bypass patients who took aspirin at antiplatelet doses did not change. PMID:20339548

  7. A rapid high-performance liquid chromatographic method for the simultaneous quantitation of aspirin, salicylic acid, and caffeine in effervescent tablets.

    PubMed

    Sawyer, MaryJean; Kumar, Vimal

    2003-09-01

    A rapid reversed-phase high-performance liquid chromatographic procedure is developed and validated for the simultaneous quantitation of aspirin, salicylic acid, and caffeine extracted from an effervescent tablet. The method uses a Hypersil C18 column (5 micro m, 15 cm x 4.6 mm) for an isocratic elution in a water-methanol-acetic acid mobile phase at a wavelength of 275 nm. The tablets' buffering effects and acid neutralizing capacity require an extraction solvent of methanol-formic acid. The range of linearity for aspirin is 0.5-1.25 mg/mL, caffeine 0.065-0.195 mg/mL, and salicylic acid 0.4-6.0% of aspirin. The overall recovery is 100.2%, 100.7%, and 99.2% for aspirin, caffeine, and salicylic acid, respectively. Under the conditions of the method, aspirin, caffeine, and salicylic acid are adequately resolved with proper peak symmetry in less than 7 min.

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

    PubMed

    Shaw, Lee-Hsin; Tsai, Tung-Hu

    2012-05-01

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

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

    PubMed

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

    2015-01-01

    The plant hormone salicylic acid (SA) controls several physiological processes and is a key regulator of multiple levels of plant immunity. To decipher the mechanisms through which SA's multiple physiological effects are mediated, particularly in immunity, two high-throughput screens were developed to identify SA-binding proteins (SABPs). Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH) from plants (Arabidopsis thaliana) was identified in these screens. Similar screens and subsequent analyses using SA analogs, in conjunction with either a photoaffinity labeling technique or surface plasmon resonance-based technology, established that human GAPDH (HsGAPDH) also binds SA. In addition to its central role in glycolysis, HsGAPDH participates in several pathological processes, including viral replication and neuronal cell death. The anti-Parkinson's drug deprenyl has been shown to suppress nuclear translocation of HsGAPDH, an early step in cell death and the resulting cell death induced by the DNA alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine. Here, we demonstrate that SA, which is the primary metabolite of aspirin (acetyl SA) and is likely responsible for many of its pharmacological effects, also suppresses nuclear translocation of HsGAPDH and cell death. Analysis of two synthetic SA derivatives and two classes of compounds from the Chinese medicinal herb Glycyrrhiza foetida (licorice), glycyrrhizin and the SA-derivatives amorfrutins, revealed that they not only appear to bind HsGAPDH more tightly than SA, but also exhibit a greater ability to suppress translocation of HsGAPDH to the nucleus and cell death. PMID:26606248

  10. ASA education outreach

    NASA Astrophysics Data System (ADS)

    Hansen, Uwe J.; Everbach, E. Carr

    2003-04-01

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

  11. Derivative-ratio spectrophotometric method for the determination of ternary mixture of aspirin, paracetamol and salicylic acid.

    PubMed

    El-Yazbi, Fawzi A; Hammud, Hassan H; Assi, Sulaf A

    2007-10-01

    A derivative spectrophotometric method was developed for the assay of a ternary mixture of aspirin (ASP), paracetamol (PAR) and salicylic acid (SAL). The method is based on the use of the first and second derivatives of the ratio spectra and measurement at zero-crossing wavelengths. The ratio spectra were obtained by dividing the absorption spectrum of the mixture by that of one of the components. The concentration of the other components are then determined from their respective calibration curves treated similarly. The described method was applied for the determination of these combinations in synthetic mixtures and dosage forms. The results obtained were accurate and precise.

  12. Derivative-ratio spectrophotometric method for the determination of ternary mixture of aspirin, paracetamol and salicylic acid

    NASA Astrophysics Data System (ADS)

    El-Yazbi, Fawzi A.; Hammud, Hassan H.; Assi, Sulaf A.

    2007-10-01

    A derivative spectrophotometric method was developed for the assay of a ternary mixture of aspirin (ASP), paracetamol (PAR) and salicylic acid (SAL). The method is based on the use of the first and second derivatives of the ratio spectra and measurement at zero-crossing wavelengths. The ratio spectra were obtained by dividing the absorption spectrum of the mixture by that of one of the components. The concentration of the other components are then determined from their respective calibration curves treated similarly. The described method was applied for the determination of these combinations in synthetic mixtures and dosage forms. The results obtained were accurate and precise.

  13. Aspirin allergy.

    PubMed

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

    1981-03-01

    This paper represents a 17-year prospective study of the clinical characteristics of patients with a history of having had allergic reactions to aspirin. The following points are especially important. (1) The most common manifestation is urticarica/angioedema; the second most common, asthma. (2) Women of child-bearing age are especially prone to develop aspirin sensitivity, otherwise the age of onset is approximately equal in the two sexes, varying from one year to 60 years. (3) Although an immunologic basis of aspirin sensitivity has not been demonstrated, 90% of its victims are also sensitive to inhalants (76%), foods (74%) or drugs (43%). (4) The authors could not confirm the widely held view that aspirin cross-reacts with tartrazine. (5) They were also unable to confirm another widely held view that asthmatic patients who are sensitive to aspirin have a strong tendency to develop nasal polyps. (6) The prognosis of asthma in patients sensitive to aspirin does not differ from that of patients who are not. These findings underline the importance of giving every aspirin-sensitive patient the benefit of a complete allergic work-up. PMID:7469139

  14. 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.

  15. 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.

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

    SciTech Connect

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

    1989-03-01

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

  17. 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

  18. [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

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

    PubMed

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

    2008-03-27

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

  20. The effects of aspirin and fish oil consumption on lysophosphatidylcholines and lysophosphatidic acids and their correlates with platelet aggregation in adults with diabetes mellitus.

    PubMed

    Abdolahi, Amir; Georas, Steve N; Brenna, J Thomas; Cai, Xueya; Thevenet-Morrison, Kelly; Phipps, Richard P; Lawrence, Peter; Mousa, Shaker A; Block, Robert C

    2014-01-01

    Many diabetics are insensitive to aspirin's platelet anti-aggregation effects. The influence of co-administration of aspirin and fish oil (FO) on plasma lysophospholipids in subjects with diabetes is poorly characterized. Thirty adults with type 2 diabetes mellitus were treated with aspirin (81mg/day) for seven days, then with FO (4g/day) for 28 days, then in combination for another seven days. Lysophospholipids and platelet measures were determined after acute (4h) and chronic (7 days) ingestion of aspirin, FO, or both in combination. FO ingestion reduced all lysophosphatidic acid (LPA) concentrations, while EPA (20:5n-3) and DHA (22:6n-3) lysophosphatidylcholine (LPC) concentrations significantly increased after FO alone and in combination with aspirin. In vitro arachidonic acid-induced platelet aggregation was most strongly correlated with palmitoleic (16:1) and oleic (18:1) LPA and LPC concentrations at all time points. The ingestion of these agents may reduce cardiovascular disease risk in diabetic adults, with a disrupted lipid milieu, via lysolipid mediated mechanisms.

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

    PubMed

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

    2013-11-01

    Despite the well-documented information, there are insufficient reports concerning the effects of salicylate compounds on the structure and functions of cell membranes, particularly those of human erythrocytes. With the aim to better understand the molecular mechanisms of the interaction of acetylsalicylic acid (ASA) and salicylic acid (SA) with cell membranes, human erythrocyte membranes and molecular models were utilized. These consisted of bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. The capacity of ASA and SA to perturb the multibilayer structures of DMPC and DMPE was evaluated by X-ray diffraction while DMPC unilamellar vesicles (LUV) were studied by fluorescence spectroscopy. Moreover, we took advantage of the capability of differential scanning calorimetry (DSC) to detect the changes in the thermotropic phase behavior of lipid bilayers resulting from ASA and SA interaction with PC and PE molecules. In an attempt to further elucidate their effects on cell membranes, the present work also examined their influence on the morphology of intact human erythrocytes by means of defocusing and scanning electron microscopy, while isolated unsealed human erythrocyte membranes (IUM) were studied by fluorescence spectroscopy. Results indicated that both salicylates interact with human erythrocytes and their molecular models in a concentration-dependent manner perturbing their bilayer structures. PMID:24055635

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

    PubMed

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

    2013-11-01

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

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

    PubMed

    Rahmani, M A

    1998-04-27

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

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

    PubMed

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

    2014-11-01

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

  5. Aspirin blocks growth of breast tumor cells and tumor-initiating cells and induces reprogramming factors of mesenchymal to epithelial transition.

    PubMed

    Maity, Gargi; De, Archana; Das, Amlan; Banerjee, Snigdha; Sarkar, Sandipto; Banerjee, Sushanta K

    2015-07-01

    Acetylsalicylic acid (ASA), also known as aspirin, a classic, nonsteroidal, anti-inflammatory drug (NSAID), is widely used to relieve minor aches and pains and to reduce fever. Epidemiological studies and other experimental studies suggest that ASA use reduces the risk of different cancers including breast cancer (BC) and may be used as a chemopreventive agent against BC and other cancers. These studies have raised the tempting possibility that ASA could serve as a preventive medicine for BC. However, lack of in-depth knowledge of the mechanism of action of ASA reshapes the debate of risk and benefit of using ASA in prevention of BC. Our studies, using in vitro and in vivo tumor xenograft models, show a strong beneficial effect of ASA in the prevention of breast carcinogenesis. We find that ASA not only prevents breast tumor cell growth in vitro and tumor growth in nude mice xenograft model through the induction of apoptosis, but also significantly reduces the self-renewal capacity and growth of breast tumor-initiating cells (BTICs)/breast cancer stem cells (BCSCs) and delays the formation of a palpable tumor. Moreover, ASA regulates other pathophysiological events in breast carcinogenesis, such as reprogramming the mesenchymal to epithelial transition (MET) and delaying in vitro migration in BC cells. The tumor growth-inhibitory and reprogramming roles of ASA could be mediated through inhibition of TGF-β/SMAD4 signaling pathway that is associated with growth, motility, invasion, and metastasis in advanced BCs. Collectively, ASA has a therapeutic or preventive potential by attacking possible target such as TGF-β in breast carcinogenesis. PMID:25867761

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

    PubMed

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

    2011-04-01

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

  7. 3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets.

    PubMed

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

    2015-01-01

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

  8. 3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets.

    PubMed

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

    2015-01-01

    The aim of this study was to explore the potential of fused-deposition 3-dimensional printing (FDM 3DP) to produce modified-release drug loaded tablets. Two aminosalicylate isomers used in the treatment of inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA, mesalazine) and 4-aminosalicylic acid (4-ASA), were selected as model drugs. Commercially produced polyvinyl alcohol (PVA) filaments were loaded with the drugs in an ethanolic drug solution. A final drug-loading of 0.06% w/w and 0.25% w/w was achieved for the 5-ASA and 4-ASA strands, respectively. 10.5mm diameter tablets of both PVA/4-ASA and PVA/5-ASA were subsequently printed using an FDM 3D printer, and varying the weight and densities of the printed tablets was achieved by selecting the infill percentage in the printer software. The tablets were mechanically strong, and the FDM 3D printing was shown to be an effective process for the manufacture of the drug, 5-ASA. Significant thermal degradation of the active 4-ASA (50%) occurred during printing, however, indicating that the method may not be appropriate for drugs when printing at high temperatures exceeding those of the degradation point. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) of the formulated blends confirmed these findings while highlighting the potential of thermal analytical techniques to anticipate drug degradation issues in the 3D printing process. The results of the dissolution tests conducted in modified Hank's bicarbonate buffer showed that release profiles for both drugs were dependent on both the drug itself and on the infill percentage of the tablet. Our work here demonstrates the potential role of FDM 3DP as an efficient and low-cost alternative method of manufacturing individually tailored oral drug dosage, and also for production of modified-release formulations. PMID:25497178

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

    PubMed Central

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

    2015-01-01

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

  10. ASA24-Kids-2014 and ASA24-Kids-2012

    Cancer.gov

    >ASA24-Kids-2014 was released in February 2014 and researchers can still register new studies in this version of the ASA24® system. A mobile accessible version is in development and is expected to be open to new studies later in 2016.

  11. Canadian Drug Products Containing ASA

    PubMed Central

    Parker, William A.; Shearer, Cameron A.; Kirkpatrick, Susan L.

    1977-01-01

    A list of nearly 200 Canadian ASA-containing drug products is presented. Information was supplied by the major pharmaceutical companies and data were also obtained from various Canadian reference sources. This information should aid the physician and other health-related personnel in identifying ASA-containing products and counselling the salicylate-endangered patient. PMID:21304856

  12. Development and validation of a high-performance liquid chromatography method for the simultaneous determination of aspirin and folic acid from nano-particulate systems.

    PubMed

    Chaudhary, Abhishek; Wang, Jeffrey; Prabhu, Sunil

    2010-09-01

    Attention has shifted from the treatment of colorectal cancer (CRC) to chemoprevention using aspirin and folic acid as agents capable of preventing the onset of colon cancer. However, no sensitive analytical method exists to simultaneously quantify the two drugs when released from polymer-based nanoparticles. Thus, a rapid, highly sensitive method of high-performance liquid chromatography analysis to simultaneously detect low quantities of aspirin (hydrolyzed to salicylic acid, the active moiety) and folic acid released from biodegradable polylactide-co-glycolide (PLGA) copolymer nanoparticles was developed. Analysis was done on a reversed-phase C(18) column using a photodiode array detector at wavelengths of 233 nm (salicylic acid) and 277 nm (folic acid). The mobile phase consisted of acetonitrile-0.1% trifluoroacetic acid mixture programmed for a 30 min gradient elution analysis. In the range of 0.1-100 microg/mL, the assay showed good linearity for salicylic acid (R(2) = 0.9996) and folic acid (R(2) = 0.9998). The method demonstrated good reproducibility, intra- and inter-day precision and accuracy (99.67, 100.1%) and low values of detection (0.03, 0.01 microg/mL) and quantitation (0.1 and 0.05 microg/mL) for salicylic acid and folic acid, respectively. The suitability of the method was demonstrated by simultaneously determining salicylic acid and folic acid released from PLGA nanoparticles.

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

    PubMed

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

    2016-07-15

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

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

    PubMed

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

    2016-07-15

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

  15. Aspirin resistance as cardiovascular risk after kidney transplantation

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

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

    PubMed

    Zhang, Ren-gang; Zhang, Jun-ping

    2007-05-01

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

  17. Identification and absolute configuration of dihydroxy-arachidonic acids formed by oxygenation of 5S-HETE by native and aspirin-acetylated COX-2.

    PubMed

    Mulugeta, Surafel; Suzuki, Takashi; Hernandez, Noemi Tejera; Griesser, Markus; Boeglin, William E; Schneider, Claus

    2010-03-01

    Biosynthesis of the prostaglandin endoperoxide by the cyclooxygenase (COX) enzymes is accompanied by formation of a small amount of 11R-hydroxyeicosatetraenoic acid (HETE), 15R-HETE, and 15S-HETE as by-products. Acetylation of COX-2 by aspirin abrogates prostaglandin synthesis and triggers formation of 15R-HETE as the sole product of oxygenation of arachidonic acid. Here, we investigated the formation of by-products of the transformation of 5S-HETE by native COX-2 and by aspirin-acetylated COX-2 using HPLC-ultraviolet, GC-MS, and LC-MS analysis. 5S,15S- dihydroxy (di)HETE, 5S,15R-diHETE, and 5S,11R-diHETE were identified as by-products of native COX-2, in addition to the previously described di-endoperoxide (5S,15S-dihydroxy-9S,11R,8S,12S-diperoxy-6E,13E-eicosadienoic acid) as the major oxygenation product. 5S,15R-diHETE was the only product formed by aspirin-acetylated COX-2. Both 5,15-diHETE and 5,11-diHETE were detected in CT26 mouse colon carcinoma cells as well as in lipopolysaccharide-activated RAW264.7 cells incubated with 5S-HETE, and their formation was attenuated in the presence of the COX-2 specific inhibitor, NS-398. Aspirin-treated CT26 cells gave 5,15-diHETE as the most prominent product formed from 5S-HETE. 5S,15S-diHETE has been described as a product of the cross-over of 5-lipoxygenase (5-LOX) and 15-LOX activities in elicited rat mononuclear cells and human leukocytes, and our studies implicate cross-over of the 5-LOX and COX-2 pathways as an additional biosynthetic route.

  18. 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

  19. Increases in ambient particulate matter air pollution, acute changes in platelet function, and effect modification by aspirin and omega-3 fatty acids: A panel study.

    PubMed

    Becerra, Adan Z; Georas, Steve; Brenna, J Thomas; Hopke, Philip K; Kane, Cathleen; Chalupa, David; Frampton, Mark W; Block, Robert; Rich, David Q

    2016-01-01

    Increased particulate matter (PM) air pollutant concentrations have been associated with platelet activation. It was postulated that elevated air pollutant concentrations would be associated with increases in measures of platelet function and that responses would be blunted when taking aspirin and/or fish oil. Data from a sequential therapy trial (30 subjects with type 2 diabetes mellitus), with 4 clinic visits (first: no supplements, second: aspirin, third: omega-3 fatty acid supplements, fourth: aspirin and omega-3 fatty acids) per subject, were utilized. Using linear mixed models, adjusted for relative humidity, temperature, visit number, and season, changes in three platelet function measures including (1) aggregation induced by adenosine diphosphate (ADP), (2) aggregation induced by collagen, and (3) thromboxane B2 production were associated with interquartile range (IQR) increases in mean concentrations of ambient PM2.5, black carbon, ultrafine particles (UFP; 10-100 nm), and accumulation mode particles (AMP; 100-500 nm) in the previous 1-96 h. IQR increases in mean UFP and AMP concentrations were associated with significant decreases in platelet response, with the largest being a -0.43 log(pg/ml) decrease in log(thromboxane B2) (95% CI = -0.8, -0.1) associated with each 582-particles/cm(3) increase in AMP, and a -1.7 ohm reduction in collagen-induced aggregation (95% CI = -3.1, -0.3) associated with each 2097-particles/cm(3) increase in UFP in the previous 72 h. This UFP effect on thromboxane B2 was significantly muted in diabetic subjects taking aspirin (-0.01 log[pg/ml]; 95% CI = -0.4, 0.3). The reason for this finding remains unknown, and needs to be investigated in future studies. PMID:27029326

  20. Increases in ambient particulate matter air pollution, acute changes in platelet function, and effect modification by aspirin and omega-3 fatty acids: A panel study.

    PubMed

    Becerra, Adan Z; Georas, Steve; Brenna, J Thomas; Hopke, Philip K; Kane, Cathleen; Chalupa, David; Frampton, Mark W; Block, Robert; Rich, David Q

    2016-01-01

    Increased particulate matter (PM) air pollutant concentrations have been associated with platelet activation. It was postulated that elevated air pollutant concentrations would be associated with increases in measures of platelet function and that responses would be blunted when taking aspirin and/or fish oil. Data from a sequential therapy trial (30 subjects with type 2 diabetes mellitus), with 4 clinic visits (first: no supplements, second: aspirin, third: omega-3 fatty acid supplements, fourth: aspirin and omega-3 fatty acids) per subject, were utilized. Using linear mixed models, adjusted for relative humidity, temperature, visit number, and season, changes in three platelet function measures including (1) aggregation induced by adenosine diphosphate (ADP), (2) aggregation induced by collagen, and (3) thromboxane B2 production were associated with interquartile range (IQR) increases in mean concentrations of ambient PM2.5, black carbon, ultrafine particles (UFP; 10-100 nm), and accumulation mode particles (AMP; 100-500 nm) in the previous 1-96 h. IQR increases in mean UFP and AMP concentrations were associated with significant decreases in platelet response, with the largest being a -0.43 log(pg/ml) decrease in log(thromboxane B2) (95% CI = -0.8, -0.1) associated with each 582-particles/cm(3) increase in AMP, and a -1.7 ohm reduction in collagen-induced aggregation (95% CI = -3.1, -0.3) associated with each 2097-particles/cm(3) increase in UFP in the previous 72 h. This UFP effect on thromboxane B2 was significantly muted in diabetic subjects taking aspirin (-0.01 log[pg/ml]; 95% CI = -0.4, 0.3). The reason for this finding remains unknown, and needs to be investigated in future studies.

  1. Determination of acetylsalicylic acid and its major metabolite, salicylic acid, in human plasma using liquid chromatography-tandem mass spectrometry: application to pharmacokinetic study of Astrix in Korean healthy volunteers.

    PubMed

    Bae, Soo Kyung; Seo, Kyung Ah; Jung, Eun Ji; Kim, Ho-Sook; Yeo, Chang-Woo; Shon, Ji-Hong; Park, Kyung-Mi; Liu, Kwang-Hyeon; Shin, Jae-Gook

    2008-06-01

    The first liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for determination of acetylsalicylic acid (aspirin, ASA) and one of its major metabolites, salicylic acid (SA), in human plasma using simvastatin as an internal standard has been developed and validated. For ASA analysis, a plasma sample containing potassium fluoride was extracted using a mixture of ethyl acetate and diethyl ether in the presence of 0.5% formic acid. SA, a major metabolite of ASA, was extracted from plasma using protein precipitation with acetonitrile. The compounds were separated on a reversed-phase column with an isocratic mobile phase consisting of acetonitrile and water containing 0.1% formic acid (8:2, v/v). The ion transitions recorded in multiple reaction monitoring mode were m/z 179 --> 137, 137 --> 93 and 435 --> 319 for ASA, SA and IS, respectively. The coefficient of variation of the assay precision was less than 9.3%, and the accuracy exceeded 86.5%. The lower limits of quantification for ASA and SA were 5 and 50 ng/mL, respectively. The developed assay method was successfully applied for the evaluation of pharmacokinetics of ASA and SA after single oral administration of Astrix (entero-coated pellet, 100 mg of aspirin) to 10 Korean healthy male volunteers.

  2. Determination of acetylsalicylic acid and its major metabolite, salicylic acid, in human plasma using liquid chromatography-tandem mass spectrometry: application to pharmacokinetic study of Astrix in Korean healthy volunteers.

    PubMed

    Bae, Soo Kyung; Seo, Kyung Ah; Jung, Eun Ji; Kim, Ho-Sook; Yeo, Chang-Woo; Shon, Ji-Hong; Park, Kyung-Mi; Liu, Kwang-Hyeon; Shin, Jae-Gook

    2008-06-01

    The first liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for determination of acetylsalicylic acid (aspirin, ASA) and one of its major metabolites, salicylic acid (SA), in human plasma using simvastatin as an internal standard has been developed and validated. For ASA analysis, a plasma sample containing potassium fluoride was extracted using a mixture of ethyl acetate and diethyl ether in the presence of 0.5% formic acid. SA, a major metabolite of ASA, was extracted from plasma using protein precipitation with acetonitrile. The compounds were separated on a reversed-phase column with an isocratic mobile phase consisting of acetonitrile and water containing 0.1% formic acid (8:2, v/v). The ion transitions recorded in multiple reaction monitoring mode were m/z 179 --> 137, 137 --> 93 and 435 --> 319 for ASA, SA and IS, respectively. The coefficient of variation of the assay precision was less than 9.3%, and the accuracy exceeded 86.5%. The lower limits of quantification for ASA and SA were 5 and 50 ng/mL, respectively. The developed assay method was successfully applied for the evaluation of pharmacokinetics of ASA and SA after single oral administration of Astrix (entero-coated pellet, 100 mg of aspirin) to 10 Korean healthy male volunteers. PMID:18254152

  3. The influence of aspirin on exercise-induced changes in adrenocorticotrophic hormone (ACTH), cortisol and aldosterone (ALD) concentrations.

    PubMed

    Przybyłowski, Jan; Obodyński, Kazimierz; Lewicki, Czesław; Kuźniar, Jerzy; Zaborniak, Stanisław; Drozd, Sławomir; Czarny, Wojciech; Garmulewicz, Maciej

    2003-04-01

    The influence of aspirin (ASA) on the endocrinology system and prostaglandin (PGs) synthesis is not completely clear. The aim of the study was to estimate the influence of ASA on the changes in the concentration of ACTH, cortisol and aldosterone (ALD) induced by physical exercise. This study was conducted on 19 healthy students (age 21-23 years). They were subjected to intensive physical exercise on a cycle ergometer. On the day prior to the experiment, 12 subjects took two 0.5-g doses of ASA in a wafer, and another 0.5 g 3-4 h before the test on the day of the investigation (ASA group). The remaining seven subjects (control group) received placebo. Hematocrit, lactate concentration and concentrations of ACTH, cortisol and ALD were determined before exercise, after exercise, and after 30 min of recovery, in a blood sample taken from a cubital vein. Before exercise, the degree of platelet aggregation in response to arachidonic acid was estimated, in order to confirm the correct allocation to the two groups. Aggregation should only occur in the ASA group. ASA and control groups exercised for 30.3 (3.1) min and 30.2 (1.6) min, respectively. Maximal heart rate and lactate concentration were similar in both groups, as were the basal concentrations of ACTH and cortisol; the ALD concentration seemed lower in the ASA group, but the difference was not significant (p<0.1). In both groups after exercise ACTH, cortisol and ALD concentrations were significantly increased, however when compared to the control group, the increase of ACTH in the ASA group was significantly higher, and ALD increase significantly lower. After recovery there was a significant decrease in ACTH concentration, whereas the concentrations of ALD and cortisol did not change. The concentrations of cortisol in both groups after exercise and recovery were similar. That is most likely because the ACTH concentrations in the ASA and control groups were sufficient for almost maximal cortisol secretion. It is

  4. Aspirin Exacerbated Respiratory Disease.

    PubMed

    Fruth, Kai; Gosepath, Jan

    2016-01-01

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

  5. Low-dose aspirin (acetylsalicylate) prevents increases in brain PGE2, 15-epi-lipoxin A4 and 8-isoprostane concentrations in 9 month-old HIV-1 transgenic rats, a model for HIV-1 associated neurocognitive disorders

    PubMed Central

    Blanchard, Helene C.; Taha, Ameer Y.; Rapoport, Stanley I; Yuan, Zhi-Xin

    2015-01-01

    Background Older human immunodeficiency virus (HIV)-1 transgenic rats are a model for HIV-1 associated neurocognitive disorders (HAND). They show behavioral changes, neuroinflammation, neuronal loss, and increased brain arachidonic acid (AA) enzymes. Aspirin (acetylsalicylate, ASA) inhibits AA oxidation by cyclooxygenase (COX)-1 and COX-2. Hypothesis Chronic low-dose ASA will downregulate brain AA metabolism in HIV-1 transgenic rats. Methods Nine month-old HIV-1 transgenic and wildtype rats were given 42 days of 10 mg/kg/day ASA or nothing in drinking water; eicosanoids were measured using ELISAs on microwaved brain extracts. Results Brain 15-epi-lipoxin A4 and 8-isoprostane concentrations were significantly higher in HIV-1 transgenic than wildtype rats; these differences were prevented by ASA. ASA reduced prostaglandin E2 and leukotriene B4 concentrations in HIV-1 Tg but not wildtype rats. Thromboxane B2, 15-HETE, lipoxin A4 and resolvin D1 concentrations were unaffected by genotype or treatment. Conclusion Chronic low-dose ASA reduces AA-metabolite markers of neuroinflammation and oxidative stress in a rat model for HAND. PMID:25638779

  6. Addition of aspirin to a fish oil-rich diet decreases inflammation and atherosclerosis in ApoE-null mice.

    PubMed

    Sorokin, Alexander V; Yang, Zhi-Hong; Vaisman, Boris L; Thacker, Seth; Yu, Zu-Xi; Sampson, Maureen; Serhan, Charles N; Remaley, Alan T

    2016-09-01

    Aspirin (ASA) is known to alter the production of potent inflammatory lipid mediators, but whether it interacts with omega-3 fatty acids (FAs) from fish oil to affect atherosclerosis has not been determined. The goal was to investigate the impact of a fish oil-enriched diet alone and in combination with ASA on the production of lipid mediators and atherosclerosis. ApoE(-/-) female mice were fed for 13weeks one of the four following diets: omega-3 FA deficient (OD), omega-3 FA rich (OR) (1.8g omega-3 FAs/kg·diet per day), omega-3 FA rich plus ASA (ORA) (0.1g ASA/kg·diet per day) or an omega-3 FA deficient plus ASA (ODA) with supplement levels equivalent to human doses. Plasma lipids, atherosclerosis, markers of inflammation, hepatic gene expression and aortic lipid mediators were determined. Hepatic omega-3 FAs were markedly higher in OR (9.9-fold) and ORA (7-fold) groups. Mice in both OR and ORA groups had 40% less plasma cholesterol in very low-density lipoprotein-cholesterol and low-density lipoprotein fractions, but aortic plaque area formation was only significantly lower in the ORA group (5.5%) compared to the OD group (2.5%). Plasma PCSK9 protein levels were approximately 70% lower in the OR and ORA groups. Proinflammatory aortic lipid mediators were 50%-70% lower in the ODA group than in the OD group and more than 50% lower in the ORA group. In summary, less aortic plaque lesions and aortic proinflammatory lipid mediators were observed in mice on the fish oil diet plus ASA vs. just the fish oil diet. PMID:27394692

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

    PubMed

    Romero-Castro, Aurelio; Gutiérrez-Sánchez, Mara; Correa-Basurto, José; Rosales Hernández, Martha Cecilia; Padilla Martínez, Itzia Irene; Mendieta-Wejebe, Jessica Elena

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Romero-Castro, Aurelio; Gutiérrez-Sánchez, Mara; Correa-Basurto, José; Rosales Hernández, Martha Cecilia; Padilla Martínez, Itzia Irene; Mendieta-Wejebe, Jessica Elena

    2016-01-01

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

  10. (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

  11. Aspirin, Butalbital, and Caffeine

    MedlinePlus

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

  12. 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

  13. 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

  14. 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

  15. 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

  16. The epigenetic effects of aspirin: the modification of histone H3 lysine 27 acetylation in the prevention of colon carcinogenesis in azoxymethane- and dextran sulfate sodium-treated CF-1 mice.

    PubMed

    Guo, Yue; Liu, Yue; Zhang, Chengyue; Su, Zheng-Yuan; Li, Wenji; Huang, Mou-Tuan; Kong, Ah-Ng

    2016-06-01

    Colorectal cancer (CRC) is the third most common cancer worldwide. Chronic inflammation appears to enhance the risk of CRC. Emerging evidence has suggested that epigenetic mechanisms play an important role in CRC. Aspirin [acetylsalicylic acid (ASA)] has been shown to prevent CRC; however, the epigenetic mechanisms of its action remain unknown. This study investigated the protective role of ASA in azoxymethane (AOM)-initiated and dextran sulfate sodium (DSS)-promoted colitis-associated colon cancer (CAC) and examined the epigenetic effects, particularly on histone 3 lysine 27 acetylation (H3K27ac), underlying the preventive effect of ASA. CF-1 mice were fed with AIN-93M diet with or without 0.02% ASA from 1 week prior to AOM initiation until the mice were killed 20 weeks after AOM injection. Our results showed that AOM/DSS + ASA significantly suppressed inflammatory colitis symptoms and tumor multiplicity. AOM/DSS + ASA reduced AOM/DSS-induced protein expression and the activity of histone deacetylases (HDACs) and globally restored H3K27ac. Furthermore, AOM/DSS + ASA inhibited AOM/DSS-induced enrichment of H3K27ac in the promoters of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) that corresponded to the dramatic suppression of the messenger RNA (mRNA) and protein levels. Surprisingly, no significant changes in the H3K27ac abundance in the prostaglandin-endoperoxide synthase 2 (Cox-2) promoters or in the Cox-2 mRNA and protein expression were observed. Collectively, our results suggest that a potential novel epigenetic mechanism underlies the chemopreventive effects of ASA, and this mechanism attenuates CAC in AOM/DSS-induced CF-1 mice via the inhibition of HDACs and the modification of H3K27ac marks that suppress iNOS, TNF-α and IL-6. PMID:27207670

  17. 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.

  18. A molecular dynamics approach to ligand-receptor interaction in the aspirin-human serum albumin complex.

    PubMed

    Alvarez, H Ariel; McCarthy, Andrés N; Grigera, J Raúl

    2012-01-01

    In this work, we present a study of the interaction between human serum albumin (HSA) and acetylsalicylic acid (ASA, C(9)H(8)O(4)) by molecular dynamics simulations (MD). Starting from an experimentally resolved structure of the complex, we performed the extraction of the ligand by means of the application of an external force. After stabilization of the system, we quantified the force used to remove the ASA from its specific site of binding to HSA and calculated the mechanical nonequilibrium external work done during this process. We obtain a reasonable value for the upper boundary of the Gibbs free energy difference (an equilibrium thermodynamic potential) between the complexed and noncomplexed states. To achieve this goal, we used the finite sampling estimator of the average work, calculated from the Jarzynski Equality. To evaluate the effect of the solvent, we calculated the so-called "viscous work," that is, the work done to move the aspirin in the same trajectory through the solvent in absence of the protein, so as to assess the relevance of its contribution to the total work. The results are in good agreement with the available experimental data for the albumin affinity constant for aspirin, obtained through quenching fluorescence methods.

  19. A Molecular Dynamics Approach to Ligand-Receptor Interaction in the Aspirin-Human Serum Albumin Complex

    PubMed Central

    Alvarez, H. Ariel; McCarthy, Andrés N.; Grigera, J. Raúl

    2012-01-01

    In this work, we present a study of the interaction between human serum albumin (HSA) and acetylsalicylic acid (ASA, C9H8O4) by molecular dynamics simulations (MD). Starting from an experimentally resolved structure of the complex, we performed the extraction of the ligand by means of the application of an external force. After stabilization of the system, we quantified the force used to remove the ASA from its specific site of binding to HSA and calculated the mechanical nonequilibrium external work done during this process. We obtain a reasonable value for the upper boundary of the Gibbs free energy difference (an equilibrium thermodynamic potential) between the complexed and noncomplexed states. To achieve this goal, we used the finite sampling estimator of the average work, calculated from the Jarzynski Equality. To evaluate the effect of the solvent, we calculated the so-called “viscous work,” that is, the work done to move the aspirin in the same trajectory through the solvent in absence of the protein, so as to assess the relevance of its contribution to the total work. The results are in good agreement with the available experimental data for the albumin affinity constant for aspirin, obtained through quenching fluorescence methods. PMID:23251150

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

    PubMed Central

    2014-01-01

    Cost-effective strategies to maintain healthy active lifestyle in aging populations are required to address the global burden of age-related diseases. ASPREE will examine whether the potential primary prevention benefits of low dose aspirin outweigh the risks in older healthy individuals. Our primary hypothesis is that daily oral 100 mg enteric-coated aspirin will extend a composite primary endpoint termed ‘disability-free life’ including onset of dementia, total mortality, or persistent disability in at least one of the Katz Activities of Daily Living in 19,000 healthy participants aged 65 years and above (‘US minorities’) and 70 years and above (non ‘US minorities’). ASPREE is a double-blind, randomized, placebo-controlled trial of oral 100 mg enteric-coated acetyl salicylic acid (ASA) or matching placebo being conducted in Australian and US community settings on individuals free of dementia, disability and cardiovascular disease (CVD) events. Secondary endpoints are all-cause and cause specific mortality, fatal and non-fatal cardiovascular events, fatal and non-fatal cancer (excluding non-melanoma skin cancer), dementia, mild cognitive impairment, depression, physical disability, and clinically significant bleeding. To 20 September 2013 14383 participants have been recruited. Recruitment and study completion is anticipated in July 2014 and December 2018 respectively. In contrast to other aspirin trials that have largely focused on cardiovascular endpoints, ASPREE has a unique composite primary endpoint to better capture the overall risk and benefit of aspirin to extend healthy independent lifespan in older adults in the US and Australia. PMID:24113028

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

    PubMed

    2013-11-01

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

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

    PubMed

    2013-11-01

    Cost-effective strategies to maintain healthy active lifestyle in aging populations are required to address the global burden of age-related diseases. ASPREE will examine whether the potential primary prevention benefits of low dose aspirin outweigh the risks in older healthy individuals. Our primary hypothesis is that daily oral 100 mg enteric-coated aspirin will extend a composite primary endpoint termed 'disability-free life' including onset of dementia, total mortality, or persistent disability in at least one of the Katz Activities of Daily Living in 19,000 healthy participants aged 65 years and above ('US minorities') and 70 years and above (non-'US minorities'). ASPREE is a double-blind, randomized, placebo-controlled trial of oral 100mg enteric-coated acetyl salicylic acid (ASA) or matching placebo being conducted in Australian and US community settings on individuals free of dementia, disability and cardiovascular disease (CVD) events. Secondary endpoints are all-cause and cause specific mortality, fatal and non-fatal cardiovascular events, fatal and non-fatal cancer (excluding non-melanoma skin cancer), dementia, mild cognitive impairment, depression, physical disability, and clinically significant bleeding. To 20 September 2013 14,383 participants have been recruited. Recruitment and study completion are anticipated in July 2014 and December 2018 respectively. In contrast to other aspirin trials that have largely focused on cardiovascular endpoints, ASPREE has a unique composite primary endpoint to better capture the overall risk and benefit of aspirin to extend healthy independent lifespan in older adults in the US and Australia. PMID:24113028

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

    NASA Astrophysics Data System (ADS)

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

    2014-01-01

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

  4. Plasma levels of acetylsalicylic acid and salicylic acid after oral ingestion of plain and buffered acetylsalicylic acid in relation to bleeding time and thrombocyte function.

    PubMed

    Proost, J H; Van Imhoff, G W; Wesseling, H

    1983-02-25

    Buffered acetylsalicylic acid (Alka Seltzer, B-ASA) and plain aspirin (P-ASA) tablets were compared as to their effects on bleeding time and platelet function in eight healthy male volunteers. Two doses (500 and 1000 mg) of each preparation were investigated in a cross-over design, each volunteer being his own control in each dose group (n=4). Both preparations disturbed platelet aggregation to the same extent. Bleeding time increased after both preparations, though significantly more after the buffered preparation than after plain acetylsalicylic acid, irrespective of the dosage. The 1000 mg dose prolonged bleeding time significantly more than the 500 mg dose, irrespective of the preparation. Kinetic analysis showed that B-ASA gave higher peak plasma levels of acetylsalicylic acid (ASA) and accordingly salicylic acid peak levels were also higher after the buffered preparation. It is concluded that B-ASA in equi-analgesic doses prolongs bleeding time more than the plain preparation. Since it is less agressive on the gastro-intestinal mucosa, its use may be advantageous in situations where acetylsalicylic acid induced loss of platelet aggregation is desired. However, the risk of prolonged bleeding--e.g. after tooth extractions--is probably higher after the buffered preparation. PMID:6844122

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

    PubMed

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

    2015-08-27

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

  6. Role of acetyl salicylic acid and sodium metabisulfite in chronic childhood asthma.

    PubMed

    Towns, S J; Mellis, C M

    1984-05-01

    The role of a commonly ingested food additive, the preservative sodium metabisulfite (MBS), and aspirin (ASA), in chronic asthma has been studied in 29 children. After 1 week on a strict elimination diet, all 29 children were challenged, in a single-blind fashion, in the pulmonary function laboratory on three consecutive days with placebo, MBS (capsule form and solution), and ASA. Children with a positive response to MBS were prescribed a diet that excluded foods containing MBS. Patients with a positive response to ASA were prescribed a diet excluding medications containing aspirin and natural salicylates. After 3 months on these restricted diets, the children were reassessed to determine whether there had been any therapeutic response. There was a 66% (19/29) incidence of positive challenge (greater than 20% decrease in forced expiratory volume in one second) with MBS and a 21% (6/29) incidence of positive challenge with ASA. None of the children reacted to MBS in capsule form (maximum dose = 100 mg), but 19/29 reacted to MBS in solution with 30 mL of 0.5% citric acid. After 3 months on the restricted diet, four of 19 children on the MBS-free diet and one of six on the salicylate-free diet had objective signs of improvement, namely, reduction in asthma medications and/or improvement in lung function. Unfortunately, compliance with the restrictive diet during this 3-month period was poor, particularly with the ASA-sensitive children.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. 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

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

    NASA Astrophysics Data System (ADS)

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

    2013-05-01

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

  9. Synthesis of Aspirin: A General Chemistry Experiment

    NASA Astrophysics Data System (ADS)

    Olmsted, John A., III

    1998-10-01

    An experiment is described that is suitable for the early portion of the laboratory in a general chemistry course and integrates organic examples. It is the two-step synthesis of aspirin starting from oil of wintergreen. The mechanism for this synthesis provides examples of three major classes of chemical reactions: hydrolysis, condensation, and proton transfer. To understand the chemistry, the student must be able to recognize the common molecular framework shared by oil of wintergreen, salicylic acid, and aspirin and to identify the -OH and -CO2 sites where chemical changes occur. The experiment differs in three ways from traditional aspirin synthesis experiments for general chemistry. It is designed to be performed early rather than late; it starts from a naturally occurring material and requires two steps rather than one; and it utilizes FTIR spectroscopy to distinguish among oil of wintergreen starting material, salicylic acid intermediate, and aspirin product. The use of FTIR spectroscopy introduces students to a modern analytical technique that is currently used in research involving aspirin.

  10. 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

  11. Influence of aspirin on development and treatment of experimental Staphylococcus aureus endocarditis.

    PubMed Central

    Nicolau, D P; Marangos, M N; Nightingale, C H; Quintiliani, R

    1995-01-01

    Previously, we have shown that a 5-mg/kg of body weight daily dose of aspirin (ASA) caused reductions in the bacterial densities and weights of aortic vegetations in a rabbit model of Staphylococcus aureus endocarditis. We sought to determine (i) whether ASA dosage influences the development of vegetations and (ii) whether ASA given with antimicrobial therapy improves the treatment outcome of infective endocarditis. To study the influence of ASA dosage, animals received either no ASA (control) or oral doses of 2.5, 10, 20, and 50 mg/kg daily. The 2.5- and 10-mg/kg groups had statistically significant reductions in vegetation weight compared with untreated controls. The 10-mg/kg dose also resulted in a significant decrease in bacterial densities compared with those of the controls. Although reductions in weight and bacterial density were observed in other ASA-treated groups, these did not achieve statistical significance. To study the influence of ASA and antimicrobial therapy, the animals received either vancomycin alone or vancomycin with ASA. When ASA was given prior to and during antimicrobial therapy, a significant reduction in vegetation weight was observed. Additionally, the rate of sterilization was directly proportional to this observed reduction in weight. ASA's impact on the reduction of both the bacterial density and the weight of aortic vegetations is a dose-dependent phenomenon. When given with antimicrobial therapy, ASA not only reduces vegetation weight but also improves the rate of sterilization. This study provides additional data regarding the role of ASA in the treatment of endocarditis. PMID:7486913

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

    NASA Astrophysics Data System (ADS)

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

    2011-11-01

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

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

    PubMed

    Schwartz, Kenneth A

    2011-04-01

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

  14. [ASA - from cardiovascular to cancer prevention].

    PubMed

    Sanin, Veronika; Pfetsch, Vanessa; Koenig, Wolfgang

    2016-03-01

    Cardiovascular disease and cancer are the leading causes of morbidity and mortality worldwide. Low-dose ASA has been shown to effectively prevent about one fifth of atherothrombotic vascular complications in patients with previous myocardial infarction, peripheral arterial occlusive disease (PAOD), or stroke 2. In secondary prevention, the benefits of antiplatelet therapy substantially exceed its risk 2. By contrast, recommendations for the use of ASA in primary prevention are still a matter of controversy. The aim of this article is to review the current evidence for the efficacy of low-dose ASA in primary and secondary prevention of cardiovascular diseases as well as to discuss its potential additional chemopreventive action. PMID:26939106

  15. Rapid and sensitive determination of acetylsalicylic acid and salicylic acid in plasma using liquid chromatography-tandem mass spectrometry: application to pharmacokinetic study.

    PubMed

    Xu, Xiangrong; Koetzner, Lee; Boulet, Jamie; Maselli, Harry; Beyenhof, Jessica; Grover, Gary

    2009-09-01

    A simple and sensitive analytical method using liquid chromatography-tandem mass spectrometry (LC/MS/MS) for determination of acetylsalicylic acid (aspirin, ASA) and its major metabolite, salicylic acid (SA), in animal plasma has been developed and validated. Both ASA and SA in plasma samples containing potassium fluoride were extracted using acetonitrile (protein precipitation) with 0.1% formic acid in it. 6-Methoxysalicylic acid was used as the internal standard (IS). The compounds were separated on a reversed-phase column. The multiple reaction monitoring mode was used with ion transitions of m/z 178.9 --> 136.8, 137.0 --> 93.0 and 167.0 --> 123.0 for ASA, SA and IS, respectively. The lower limits of quantification for ASA and SA were 3 and 30 ng/mL, respectively. The developed method was successfully applied for the evaluation of pharmacokinetics of ASA and SA after p.o. and i.v. administration of 1 mg/kg to rats.

  16. LC-MS/MS for the simultaneous analysis of arachidonic acid and 32 related metabolites in human plasma: Basal plasma concentrations and aspirin-induced changes of eicosanoids.

    PubMed

    Shinde, Dhananjay D; Kim, Kwon-Bok; Oh, Kyung-Suk; Abdalla, Nagi; Liu, Kwang-Hyeon; Bae, Soo Kyung; Shon, Ji-Hong; Kim, Ho-Sook; Kim, Dong-Hyun; Shin, Jae Gook

    2012-12-12

    Eicosanoids play an important role in various biological responses and can be used as biomarkers for specific diseases. Therefore, we developed a highly selective, sensitive, and robust liquid chromatography-tandem mass spectrometric method to measure arachidonic acid and its 32 metabolites in human plasma. Sample preparation involved solid phase extraction, which efficiently removed sources of interference present in human plasma. Chromatographic separation was performed using a Luna C(8)-column with 0.5mM ammonium formate buffer and acetonitrile as the mobile phase under gradient conditions. Detection was performed using tandem mass spectrometry equipped with an electrospray ionization interface in negative ion mode. The matrix did not affect the reproducibility and reliability of the assay. All analytes showed good linearity over the investigated concentration range (r>0.997). The validated lower limit of quantitation for the analytes ranged from 10 to 400pg/mL. Intra- and inter-day precision (RDS%) over the concentration ranges for all eicosanoids were within 16.8%, and accuracy ranged between 88.1 and 108.2%. This assay was suitable for the determination of basal plasma levels of eicosanoids and the evaluation of effect of aspirin on eicosanoid plasma levels in healthy subjects. PMID:23217314

  17. 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 ...

  18. ASA24-Australian Version (Under Development)

    Cancer.gov

    In collaboration with the National Cancer Institute (NCI), a consortium of Australian Researchers is adapting the ASA24 system to the Australian context to account for variations in food consumed, portion sizes, and nutrient composition.

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

    SciTech Connect

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

    1984-07-01

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

  20. Standards 101: The ASA Standards program

    NASA Astrophysics Data System (ADS)

    Schomer, Paul

    2001-05-01

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

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

    SciTech Connect

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

    1985-02-01

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

  2. Aspirin and lipid mediators in the cardiovascular system.

    PubMed

    Schrör, Karsten; Rauch, Bernhard H

    2015-09-01

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

  3. Aspirin and lipid mediators in the cardiovascular system.

    PubMed

    Schrör, Karsten; Rauch, Bernhard H

    2015-09-01

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

  4. Novel mixed metal Ag(I)-Sb(III)-metallotherapeutics of the NSAIDs, aspirin and salicylic acid: Enhancement of their solubility and bioactivity by using the surfactant CTAB.

    PubMed

    Gkaniatsou, E I; Banti, C N; Kourkoumelis, N; Skoulika, S; Manoli, M; Tasiopoulos, A J; Hadjikakou, S K

    2015-09-01

    The already known Ag(I)-Sb(III) compound of the formula {Ag(Ph3Sb)3(NO3)} (1) and two novel mixed metal Ag(I)-Sb(III) metallotherapeutics of the formulae {Ag(Ph3Sb)3(SalH)}(2) and {Ag(Ph3Sb)3(Asp)}(3) (SalH2=salicylic acid, AspH=aspirin or 2-acetylsalicylic acid and Ph3Sb=triphenyl antimony(III)) have been synthesised and characterised by m.p., vibrational spectroscopy (mid-FT-IR), (13)C-,(1)H-NMR, UV-visible (UV-vis) spectroscopic techniques, high resolution mass spectroscopy (HRMS) and X-ray crystallography. Compounds 1,-3 were treated with the surfactant cetyltrimethylammonium bromide (CTAB) in order to enhance their solubility and as a consequence their bioactivity. The resulting micelles a-c were characterised with X-ray powder diffraction (XRPD) analysis, X-ray fluorescence (XRF) spectroscopy, Energy-dispersive X-ray spectroscopy (EDX), conductivity, Thermal gravimetry-differential thermal analysis (TG-DTA), and atomic absorption. Compounds 1-3 and the relevant micelles a-c were evaluated for their in vitro cytotoxic activity against human cancer cell lines: MCF-7 (breast, estrogen receptor (ER) positive), MDA-MB-231 (breast, ER negative) and MRC-5 (normal human fetal lung fibroblast cells) with sulforhodamine B (SRB) colorimetric assay. The results show significant increase in the activity of micelles compared to that of the initial compounds. Moreover, micelles exhibited lower activity against normal cells than tumor cells. The binding affinity of a-c towards the calf thymus (CT)-DNA, lipoxygenase (LOX) and glutathione (GSH) was studied by the fluorescent emission light and UV-vis spectroscopy.

  5. Polysaccharide arabinogalactan from larch Larix sibirica as carrier for molecules of salicylic and acetylsalicylic acid: preparation, physicochemical and pharmacological study.

    PubMed

    Chistyachenko, Yulia S; Dushkin, Alexandr V; Polyakov, Nikolay E; Khvostov, Mikhail V; Tolstikova, Tatyana G; Tolstikov, Genrikh A; Lyakhov, Nikolay Z

    2015-05-01

    Inclusion complexes of salicylic acid (SA) and acetylsalicylic acid (aspirin, ASA) with polysaccharide arabinogalactan (AG) from larch wood Larix sibirica and Larix gmelinii were synthesized using mechanochemical technology. In the present study, we have investigated physicochemical properties of the synthesized complexes in solid state and in aqueous solutions as well as their anti-aggregation and ulcerogenic activity. The evidence of the complexes formation was obtained by nuclear magnetic resonance (NMR) relaxation technique. It was shown that in aqueous solution the molecules of SA and ASA are in fast exchange between the complex with AG macromolecules and solution. The stability constant of aspirin complex was calculated. It was shown that mechanochemically synthesized complexes are more stable when compared to the complex obtained by mixing solutions of the components. Complexes of ASA show two-fold increase of anti-platelet effect. It allows to reduce the dose of the antithrombotic drug and its ulcerogenic activity. These results substantiate the possibility to design new preparations on the basis of ASA with increased activity and safety.

  6. Polysaccharide arabinogalactan from larch Larix sibirica as carrier for molecules of salicylic and acetylsalicylic acid: preparation, physicochemical and pharmacological study.

    PubMed

    Chistyachenko, Yulia S; Dushkin, Alexandr V; Polyakov, Nikolay E; Khvostov, Mikhail V; Tolstikova, Tatyana G; Tolstikov, Genrikh A; Lyakhov, Nikolay Z

    2015-05-01

    Inclusion complexes of salicylic acid (SA) and acetylsalicylic acid (aspirin, ASA) with polysaccharide arabinogalactan (AG) from larch wood Larix sibirica and Larix gmelinii were synthesized using mechanochemical technology. In the present study, we have investigated physicochemical properties of the synthesized complexes in solid state and in aqueous solutions as well as their anti-aggregation and ulcerogenic activity. The evidence of the complexes formation was obtained by nuclear magnetic resonance (NMR) relaxation technique. It was shown that in aqueous solution the molecules of SA and ASA are in fast exchange between the complex with AG macromolecules and solution. The stability constant of aspirin complex was calculated. It was shown that mechanochemically synthesized complexes are more stable when compared to the complex obtained by mixing solutions of the components. Complexes of ASA show two-fold increase of anti-platelet effect. It allows to reduce the dose of the antithrombotic drug and its ulcerogenic activity. These results substantiate the possibility to design new preparations on the basis of ASA with increased activity and safety. PMID:24517849

  7. Aspirin resistance and other aspirin-related concerns.

    PubMed

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

    2016-02-01

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

  8. 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

  9. Standards 101; the ASA standards program

    NASA Astrophysics Data System (ADS)

    Schomer, Paul D.

    2002-11-01

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

  10. 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

  11. Effects of ebrotidine on aspirin-induced gastric mucosal damage and blood flow in humans.

    PubMed

    Konturek, S J; Kwiecien, N; Sito, E; Obtulowicz, W; Kaminski, K; Oleksy, J

    1993-12-01

    Nonsteroidal anti-inflammatory agents (NSAIDs) such as aspirin (ASA) damage the gastric mucosa both in normal subjects and in arthritic patients. The aim of this study was to investigate the protective action of a new H2-receptor antagonist, ebrotidine, in the prevention of ASA-induced acute mucosal injury in the stomach of healthy volunteers. In a double-blind randomized crossover study 10 male volunteers received treatment with either placebo plus ASA (500 mg) or ebrotidine (800 mg) plus ASA twice daily for 3 days with 10 days' washout period between treatments. The mean number of gastric erosions seen at endoscopy after treatment with ebrotidine plus ASA (2.0 +/- 0.3) was significantly lower than that after placebo plus ASA (3.7 +/- 0.2). This reduction in lesion core by ebrotidine was accompanied by a significant increase in gastric blood flow (by 15% in corpus and 26% in antrum), by a rise in transmucosal potential difference (by 12%), and by a decrease of mucosal microbleeding. Ebrotidine afforded substantial protection from ASA-induced injury to the gastric mucosa, and this was accompanied by increase of the mucosal blood flow. We conclude that ebrotidine provides mucosal protection for patients taking NSAIDs.

  12. Aspirin Treatment of Mice Infected with Trypanosoma cruzi and Implications for the Pathogenesis of Chagas Disease

    PubMed Central

    Mukherjee, Shankar; Machado, Fabiana S.; Huang, Huang; Oz, Helieh S.; Jelicks, Linda A.; Prado, Cibele M.; Koba, Wade; Fine, Eugene J.; Zhao, Dazhi; Factor, Stephen M.; Collado, J. Elias; Weiss, Louis M.

    2011-01-01

    Chagas disease, caused by infection with Trypanosoma cruzi, is an important cause of cardiovascular disease. It is increasingly clear that parasite-derived prostaglandins potently modulate host response and disease progression. Here, we report that treatment of experimental T. cruzi infection (Brazil strain) beginning 5 days post infection (dpi) with aspirin (ASA) increased mortality (2-fold) and parasitemia (12-fold). However, there were no differences regarding histopathology or cardiac structure or function. Delayed treatment with ASA (20 mg/kg) beginning 60 dpi did not increase parasitemia or mortality but improved ejection fraction. ASA treatment diminished the profile of parasite- and host-derived circulating prostaglandins in infected mice. To distinguish the effects of ASA on the parasite and host bio-synthetic pathways we infected cyclooxygenase-1 (COX-1) null mice with the Brazil-strain of T. cruzi. Infected COX-1 null mice displayed a reduction in circulating levels of thromboxane (TX)A2 and prostaglandin (PG)F2α. Parasitemia was increased in COX-1 null mice compared with parasitemia and mortality in ASA-treated infected mice indicating the effects of ASA on mortality potentially had little to do with inhibition of prostaglandin metabolism. Expression of SOCS-2 was enhanced, and TRAF6 and TNFα reduced, in the spleens of infected ASA-treated mice. Ablation of the initial innate response to infection may cause the increased mortality in ASA-treated mice as the host likely succumbs more quickly without the initiation of the “cytokine storm” during acute infection. We conclude that ASA, through both COX inhibition and other “off-target” effects, modulates the progression of acute and chronic Chagas disease. Thus, eicosanoids present during acute infection may act as immunomodulators aiding the transition to and maintenance of the chronic phase of the disease. A deeper understanding of the mechanism of ASA action may provide clues to the differences

  13. [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

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

    PubMed

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

    2015-05-01

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

  15. Cyclooxygenase product inhibition with acetylsalicylic acid slows disease progression in the Han:SPRD-Cy rat model of polycystic kidney disease.

    PubMed

    Ibrahim, Naser H M; Gregoire, Melanie; Devassy, Jessay G; Wu, Yinhong; Yoshihara, Daisuke; Yamaguchi, Tamio; Nagao, Shizuko; Aukema, Harold M

    2015-01-01

    Renal cyclooxygenase (COX) derived eicosanoids are elevated and lipoxygenase (LOX) products are reduced in the Han:SPRD-Cy rat model of polycystic kidney disease (PKD). Selective COX2 inhibition reduces kidney disease progression, but COX1 levels also are elevated in this model. Since the effect of reducing the products of both COX isoforms and the role of LOX products is not known, weanling normal and diseased Han:SPRD-cy littermates were given either low dose acetylsalicylic acid (ASA), nordihydroguaiaretic (NDGA) or no treatment for eight weeks. Renal eicosanoids were altered in the diseased compared to normal cortex, with COX products being higher and LOX products being lower. ASA reduced COX products, cyst growth and kidney water content, while NDGA reduced LOX products without altering disease progression or kidney function. Hence, a human equivalent ASA dose equal to less than one regular strength aspirin per day slowed disease progression, while further reduction of LOX products did not worsen disease progression.

  16. An Efficient Microscale Procedure for the Synthesis of Aspirin

    NASA Astrophysics Data System (ADS)

    Pandita, Sangeeta; Goyal, Samta

    1998-06-01

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

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

    PubMed

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

    1991-01-01

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

  18. Asa Wright Nature Center, Like Another World.

    ERIC Educational Resources Information Center

    Trimm, Wayne

    1983-01-01

    The Asa Wright Nature Center, on the Caribbean island of Trinidad, offers a diversity of wildlife species: 108 mammals, 400 birds, 55 reptiles, 25 amphibians, and over 600 butterflies. Learning opportunities include art and photography instruction, lectures, interpretive nature walks, annual resident seminars, and a two-day trip to Tobago. (MH)

  19. Asa Grant Hilliard III: Scholar Supreme

    ERIC Educational Resources Information Center

    Watkins, William H.

    2008-01-01

    This integrative review uses two of Asa Grant Hilliard's books, "SBA: The Reawakening of the African Mind" and "The Maroon Within Us: Selected Essays on African American Community Socialization", to discuss aspects of his scholarly legacy in teaching, history, and psychology. His scholarship is provocative. Hilliard rejected the supremacy of the…

  20. ASA24® Respondent Website Features

    Cancer.gov

    The ASA24 Respondent Website guides the participant through the completion of either a 24-hour recall for the previous day (from midnight-to-midnight or for the past 24-hours) or for a single or multiple day food record.

  1. Dielectric study of equimolar acetaminophen-aspirin, acetaminophen-quinidine, and benzoic acid-progesterone molecular alloys in the glass and ultraviscous states and their relevance to solubility and stability.

    PubMed

    Johari, G P; Kim, S; Shanker, Ravi M

    2010-03-01

    Equimolar mixtures of acetaminophen-aspirin, acetaminophen-quinidine, and benzoic acid-progesterone have been vitrified and dielectric properties of their glassy and ultraviscous alloys have been studied. For 20 K/min heating rate, their T(g)s are 266, 330, and 263 K, respectively. The relaxation has an asymmetric distribution of times, and the distribution parameter increases with increase in temperature. The dielectric relaxation time varies with T according to the Vogel-Fulcher-Tammann equation, log(10)(tau(0)) = A(VFT) + [B(VFT)/(T - T(0))], where A(VFT), B(VFT), and T(0) are empirical constants. The equilibrium permittivity is highest for the aspirin-acetaminophen and lowest for the benzoic acid-progesterone alloy, indicating a substantial interpharmaceutical hydrogen bonding that makes the alloy more stable against crystallization than the pure components. The benzoic acid-progesterone alloy is thermodynamically the most nonideal. It showed cold crystallization on heating, which is attributed to its relatively greater magnitude of the JG relaxation in relation to its alpha-relaxation. It is argued that the difference between the free energy of an alloy and the pure components would have an effect on the solubility. Studies of solution thermodynamics of a glassy molecular alloy may be useful for optimizing choice of components and composition to form molecular alloys and to impact drug delivery. PMID:19780138

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

    PubMed

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

    2006-04-01

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

  3. Acetylsalicylic acid-induced oxidative stress, cell cycle arrest, apoptosis and mitochondrial dysfunction in human hepatoma HepG2 cells.

    PubMed

    Raza, Haider; John, Annie; Benedict, Sheela

    2011-10-01

    It is widely accepted that non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, reduce the risk of cancer. The anti-cancer and anti-inflammatory effects of NSAIDs are associated with the inhibition of prostaglandin synthesis and cyclooxygenase-2 activity. Several other mechanisms which contribute to the anti-cancer effect of these drugs in different cancer models both in vivo and in vitro are also presumed to be involved. The precise molecular mechanism, however, is still not clear. We investigated, therefore, the effects of acetylsalicylic acid (ASA, aspirin) on multiple cellular and functional targets, including mitochondrial bioenergetics, using human hepatoma HepG2 cancer cells in culture. Our results demonstrate that ASA induced G0/G1 cell cycle arrest and apoptosis in HepG2 cells. ASA increased the production of reactive oxygen species, reduced the cellular glutathione (GSH) pool and inhibited the activities of the mitochondrial respiratory enzyme complexes, NADH-ubiquinone oxidoreductase (complex I), cytochrome c oxidase (complex IV) and the mitochondrial matrix enzyme, aconitase. Apoptosis was triggered by alteration in mitochondrial permeability transition, inhibition of ATP synthesis, decreased expression of the anti-apoptotic protein Bcl-2, release of cytochrome c and activation of pro-apoptotic caspase-3 and the DNA repairing enzyme, poly (-ADP-ribose) polymerase (PARP). These findings strongly suggest that ASA-induced toxicity in human hepatoma HepG2 cells is mediated by increased metabolic and oxidative stress, accompanied by mitochondrial dysfunction which result in apoptosis.

  4. Acetylsalicylic acid-induced oxidative stress, cell cycle arrest, apoptosis and mitochondrial dysfunction in human hepatoma HepG2 cells.

    PubMed

    Raza, Haider; John, Annie; Benedict, Sheela

    2011-10-01

    It is widely accepted that non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, reduce the risk of cancer. The anti-cancer and anti-inflammatory effects of NSAIDs are associated with the inhibition of prostaglandin synthesis and cyclooxygenase-2 activity. Several other mechanisms which contribute to the anti-cancer effect of these drugs in different cancer models both in vivo and in vitro are also presumed to be involved. The precise molecular mechanism, however, is still not clear. We investigated, therefore, the effects of acetylsalicylic acid (ASA, aspirin) on multiple cellular and functional targets, including mitochondrial bioenergetics, using human hepatoma HepG2 cancer cells in culture. Our results demonstrate that ASA induced G0/G1 cell cycle arrest and apoptosis in HepG2 cells. ASA increased the production of reactive oxygen species, reduced the cellular glutathione (GSH) pool and inhibited the activities of the mitochondrial respiratory enzyme complexes, NADH-ubiquinone oxidoreductase (complex I), cytochrome c oxidase (complex IV) and the mitochondrial matrix enzyme, aconitase. Apoptosis was triggered by alteration in mitochondrial permeability transition, inhibition of ATP synthesis, decreased expression of the anti-apoptotic protein Bcl-2, release of cytochrome c and activation of pro-apoptotic caspase-3 and the DNA repairing enzyme, poly (-ADP-ribose) polymerase (PARP). These findings strongly suggest that ASA-induced toxicity in human hepatoma HepG2 cells is mediated by increased metabolic and oxidative stress, accompanied by mitochondrial dysfunction which result in apoptosis. PMID:21722632

  5. Deciphering glycomics and neuroproteomic alterations in experimental traumatic brain injury: Comparative analysis of aspirin and clopidogrel treatment.

    PubMed

    Abou-Abbass, Hussein; Bahmad, Hisham; Abou-El-Hassan, Hadi; Zhu, Rui; Zhou, Shiyue; Dong, Xue; Hamade, Eva; Mallah, Khalil; Zebian, Abir; Ramadan, Naify; Mondello, Stefania; Fares, Jawad; Comair, Youssef; Atweh, Samir; Darwish, Hala; Zibara, Kazem; Mechref, Yehia; Kobeissy, Firas

    2016-06-01

    As populations age, the number of patients sustaining traumatic brain injury (TBI) and concomitantly receiving preinjury antiplatelet therapy such as aspirin (ASA) and clopidogrel (CLOP) is rising. These drugs have been linked with unfavorable clinical outcomes following TBI, where the exact mechanism(s) involved are still unknown. In this novel work, we aimed to identify and compare the altered proteome profile imposed by ASA and CLOP when administered alone or in combination, prior to experimental TBI. Furthermore, we assessed differential glycosylation PTM patterns following experimental controlled cortical impact model of TBI, ASA, CLOP, and ASA + CLOP. Ipsilateral cortical brain tissues were harvested 48 h postinjury and were analyzed using an advanced neuroproteomics LC-MS/MS platform to assess proteomic and glycoproteins alterations. Of interest, differential proteins pertaining to each group (22 in TBI, 41 in TBI + ASA, 44 in TBI + CLOP, and 34 in TBI + ASA + CLOP) were revealed. Advanced bioinformatics/systems biology and clustering analyses were performed to evaluate biological networks and protein interaction maps illustrating molecular pathways involved in the experimental conditions. Results have indicated that proteins involved in neuroprotective cellular pathways were upregulated in the ASA and CLOP groups when given separately. However, ASA + CLOP administration revealed enrichment in biological pathways relevant to inflammation and proinjury mechanisms. Moreover, results showed differential upregulation of glycoproteins levels in the sialylated N-glycans PTMs that can be implicated in pathological changes. Omics data obtained have provided molecular insights of the underlying mechanisms that can be translated into clinical bedside settings. PMID:27249377

  6. Analgesic and Decongestant Efficacy of the Combination of Aspirin with Pseudoephedrine in Patients With Symptoms of Upper Respiratory Tract Infection

    PubMed Central

    Eccles, Ronald; Voelker, Michael

    2014-01-01

    The study investigated the efficacy and safety of a combination therapy of 1,000 mg aspirin (ASA) and 60 mg pseudoephedrine (PSE) on the symptoms of pain (combined score for headache and sore throat) and nasal congestion in 833 patients with acute upper respiratory tract viral infection (URTI), over 4 hours after a single dose in the clinic and over 3 days with multiple doses at home. The study demonstrated that over 4 hours in the clinic the combination ASA plus PSE was superior to PSE or placebo for relief of pain symptoms measured subjectively with pain scores, and was superior to ASA or placebo for relief of nasal congestion as measured objectively with rhinomanometry and subjectively with congestion scores. After 3 days of treatment, ASA plus PSE was superior to PSE but not to placebo or ASA for global pain assessments, and ASA plus PSE was superior to ASA and placebo but not to PSE for congestion assessments. No unexpected adverse events occurred and no serious adverse events were attributed to study medicines. This study demonstrates that a combination therapy of ASA plus PSE provides safe and effective relief of both common cold pain related symptoms and nasal congestion. PMID:26097788

  7. 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

  8. 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 ...

  9. Citing ASA24® Dietary Assessment Tool in Publications & Presentations

    Cancer.gov

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

  10. 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

  11. The effect of chitosan as internal or external coating on the 5-ASA release from calcium alginate microparticles.

    PubMed

    Tapia, Cristián; Molina, Sergio; Diaz, Alvaro; Abugoch, Lilian; Diaz-Dosque, Mario; Valenzuela, Fernando; Yazdani-Pedram, Mehrdad

    2010-09-01

    The effect of chitosan as internal or external coating on the mesalamine (5-ASA) release from calcium alginate microparticles (CaAl) was studied, and a delayed release of 5-ASA system intended for colonic drug delivery was developed. The external chitosan coating was developed by immersion of wetted CaAl in chitosan solution and the internal coating by mixing 5-ASA with chitosan solution and drying before the preparation of CaAl. Both systems were coated with Acryl-EZE® using combined fluid bed coating and immersion procedure. The results showed that in phosphate medium (pH 7.5), chitosan as 5-ASA coating promotes a quick erosion process accelerating drug release, but chitosan as external coating (CaAlCS) does not increase the T (50) value compared with the microparticles without chitosan (CaAl). Chitosan as internal or external coating was not effective to avoid the quick 5-ASA release in acidic medium (pH 1.2). The presence of β-glucosidase enzymes increases significantly the 5-ASA release for CaAl, while no effect was observed with chitosan as internal or external coating. Fourier transform infrared spectroscopy, thermogravimetric analysis, and X-ray data revealed that 5-ASA did not form a solid solution but was dispersed in the microparticles. The Acryl-EZE® coating of microparticles was effective because all the formulations showed a low release, less than 15%, of 5-ASA in acid medium at pH 1.2. Significant differences in the percentage of 5-ASA released between formulations were observed in phosphate buffer at pH 6.0. In phosphate buffer at pH 7.2, all the formulations released 100% of 5-ASA.

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

    PubMed Central

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

    2015-01-01

    The development of nitric oxide (NO)- and hydrogen sulfide (H2S)-releasing nonsteroidal anti-inflammatory drugs (NSAIDs) has generated more potent anti-inflammatory drugs with increased safety profiles. A new hybrid molecule incorporating both NO and H2S donors into aspirin (NOSH-aspirin) was recently developed. In the present study, the antinociceptive activity of this novel molecule was compared with aspirin in different models of inflammatory pain. It was found that NOSH-aspirin inhibits acetic acid-induced writhing response and carrageenan (Cg)-induced inflammatory hyperalgesia in a dose-dependent (5–150 μmol/kg, v.o.) manner, which was superior to the effect of the same doses of aspirin. NOSH-aspirin’s antinociceptive effect was also greater and longer compared to aspirin upon complete Freund’s adjuvant (CFA)-induced inflammatory hyperalgesia. Mechanistically, NOSH-aspirin, but not aspirin, was able to reduce the production/release of interleukin-1 beta (IL-1β) during Cg-induced paw inflammation. Furthermore, NOSH-aspirin, but not aspirin, reduced prostaglandin E2-induced hyperalgesia, which was prevented by treatment with a ATP-sensitive potassium channel (KATP) blocker (glibenclamide; glib.). Noteworthy, the antinociceptive effect of NOSH-aspirin was not associated with motor impairment. The present results indicate that NOSH-aspirin seems to present greater potency than aspirin to reduce inflammatory pain in several models. The enhanced effects of NOSH-aspirin seems to be due to its ability to reduce the production of pronociceptive cytokines such as IL-1 β and directly block hyperalgesia caused by a directly acting hyperalgesic mediator in a mechanism dependent on modulation of KATP channels. In conclusion, we would like to suggest that NOSH-aspirin represents a prototype of a new class of analgesic drugs with more potent effects than the traditional NSAID, aspirin. PMID:26236481

  13. Nitric Oxide-Releasing Aspirin Suppresses NF-κB Signaling in Estrogen Receptor Negative Breast Cancer Cells in Vitro and in Vivo.

    PubMed

    Nath, Niharika; Chattopadhyay, Mitali; Rodes, Deborah B; Nazarenko, Anna; Kodela, Ravinder; Kashfi, Khosrow

    2015-01-01

    Estrogen receptor negative (ER(-)) breast cancer is aggressive, responds poorly to current treatments and has a poor prognosis. The NF-κB signaling pathway is implicated in ER(-) tumorigenesis. Aspirin (ASA) is chemopreventive against ER(+) but not for ER(-) breast cancers. Nitric oxide-releasing aspirin (NO-ASA) is a safer ASA where ASA is linked to an NO-releasing moiety through a spacer. In vitro, we investigated anti-proliferation effects of NO-ASA (para- and meta-isomers) against ER(-) breast cancer cells MDA-MB-231 and SK-BR-23, effects on NF-κB signaling, and reactive oxygen species by standard techniques. In vivo, effects of NO-ASA were evaluated in a mouse xenograft model using MDA-MB-231 cells. p-NO-ASA inhibited the growth of MDA-MB-231 and SK-BR-3 cells at 24 h, the respective IC50s were 13 ± 2 and 17 ± 2 μM; ASA had an IC50 of >3000 μM in both cell lines. The IC50s for m-NO-ASA in MDA-MB-231 and SK-BR-3 were 173 ± 15 and 185 ± 12 μM, respectively, therefore, implying p-NO-ASA as a stronger inhibitor of growth p-NO-ASA reduced cell growth by inhibiting proliferation, inducing apoptosis and causing G0/G1 cell cycle block. Activation of NF-κB was inhibited by both isomers as demonstrated by decreases in NF-κB-DNA binding and luciferase activity at 24 h, However, m-NO-ASA produced transient effects at 3 h such as increased NF-κB-DNA-binding, increased levels of nuclear p50, even though both isomers inhibited IκB degradation. Increase in nuclear p50 by m-NO-ASA was associated with translocation of p50 in to the nucleus as observed by immunoflouresence at 3 h. NO-ASA induced reactive oxygen species (ROS) as evidenced by overall increases in both H2DCFDA (2',7'-dichlorodihydrofluorescein) and DHE (dihydroethidium)-derived fluorescence. Inhibition of ROS by N-acetyl-cysteine reversed the m-NO-ASA-mediated translocation of p50 in to the nucleus. In xenografts, p-NO-ASA inhibited tumor growth by inhibiting proliferation (PCNA and tumor volume

  14. Extrusion-spheronisation of highly loaded 5-ASA multiparticulate dosage forms.

    PubMed

    Di Pretoro, G; Zema, L; Gazzaniga, A; Rough, S L; Wilson, D I

    2010-12-15

    The aim of the current work was to develop an extrusion-spheronisation (E-S) route to manufacture pellets with a high loading (≥90wt%) of 5-aminosalicylic acid (5-ASA). Ram extrusion studies, supported by centrifuge testing, were employed to investigate the effect of the chemical (acidity) and physical (particle size and shape) characteristics of 5-ASA on the ability of microcrystalline cellulose (MCC)-based pastes to retain water when subjected to pressure. Liquid phase migration (LPM) within the paste during the extrusion, and hence variation in water content of extrudates and reproducibility of the final E-S product, was generally observed. The extent of LPM was found to be related to both the drug loading and its physical properties, most notably the particle shape (needle-like). A reduction in particle size, combined with a change in the shape of the 5-ASA particles, allowed LPM to be reduced considerably or eliminated. The performance of colloidal grades of MCC (Avicel RC591 and CL611) as alternative extrusion aids to the standard Avicel PH101 was also investigated: these proved to be superior aids for the highly loaded 5-ASA pastes as their greater water retention capacity mitigated LPM. Combining these results yielded a route for manufacturing pellets with 5-ASA loading ≥90wt%. PMID:20934502

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

    PubMed

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

    2014-12-01

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

  16. A double blind comparison of piroxicam and enteric coated ASA in rheumatoid arthritis. A Cooperative Multicenter Canadian trial.

    PubMed

    1985-02-01

    A double blind study compared piroxicam, 20 mg OD to enteric coated acetylsalicylic acid (EC ASA), 3.9-5.2 g daily in divided doses, in 145 patients with rheumatoid arthritis (RA). Both drugs improved the signs and symptoms of RA. Patients showed significantly better compliance with a once daily dosage regimen. Gastrointestinal side effect profiles were similar. The EC ASA group showed a higher frequency of tinnitis and more dropouts, while there were more skin reactions in the piroxicam group. Decreased hemoglobin and hematocrit values were more prevalent in the piroxicam group. Piroxicam proved to be an effective alternative therapy to EC ASA. PMID:3884806

  17. [Aspirin suppresses microsatellite instability].

    PubMed

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

    1999-01-01

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

  18. The effect of a platelet cholesterol modulation on the acetylsalicylic acid-mediated blood platelet inhibition in hypercholesterolemic patients.

    PubMed

    Luzak, Boguslawa; Boncler, Magdalena; Rywaniak, Joanna; Wilk, Radoslaw; Stanczyk, Lidia; Czyz, Malgorzata; Rysz, Jacek; Watala, Cezary

    2011-05-11

    Aspirin (acetylsalicylic acid, ASA) is widely used in the prevention of cardiovascular disease, but its beneficial effects may be restrained in some individuals, where the reduced ability of ASA to protect against arterial thrombotic events is observed. We analyzed the influence of the treatment with atorvastatin (10mg/day) on the platelet sensitivity to ASA monitored under in vitro conditions in hypercholesterolemic patients. The associations between plasma or platelet cholesterol parameters and the ASA-mediated inhibition of platelet reactivity or the extent of platelet protein acetylation by ASA were estimated in the patients treated with atorvastatin for 1, 3, or 6 months. Out of 27 patients, in 17 individuals platelets appeared significantly more sensitive to 50 μM ASA in arachidonic acid- or collagen-induced whole blood aggregation following 1 month atorvastatin therapy (inhibition by 60.9 ± 5.6% vs. 48.8 ± 5.4%, P<0.05 for 0.5mM arachidonic acid, 40.8 ± 2.9% vs. 27.0 ± 4.1%, P<0.05 for 1 μg/ml collagen), and this effect lasted for 3 and 6 months, remaining in a weak, although significant, relation to the reduction of platelet cholesterol content (R(S)=-0.277, P<0.002 for arachidonic acid, R(S)=-0.197, P<0.02 for collagen). It was, however, not dependent upon either antiplatelet action or plasma lipid-lowering activity of atorvastatin. In addition, in about 50% of patients, we noticed that ASA (50 μM) significantly and time-dependently diminished thromboxane B(2) concentration in atorvastatin-treated patients. The ASA-induced acetylation of platelet proteins significantly increased in the course of atorvastatin therapy and was associated with reduced platelet cholesterol (R(S)=-0.598, P<0.0001). In conclusion, statin therapy may improve platelet sensitivity to ASA in some hypercholesterolemic patients. This effect may extend beyond the action of atorvastatin as merely a lipid-lowering agent. The mechanisms of resistance of some patients to such a

  19. Photometric solutions of some contact ASAS binaries

    NASA Astrophysics Data System (ADS)

    Gezer, İ.; Bozkurt, Z.

    2016-04-01

    We present the first light curve solution of 6 contact binary systems which are chosen from the ASAS catalog. The photometric elements and the estimated absolute parameters of all systems are obtained with the light curve analyses. We calculated the values of degree of contact for the systems. The location of the targets on the Hertzsprung-Russell diagram and the mass-radius plane is compared to the other well-known contact binaries and the evolutionary status of the systems are also discussed.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  2. 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

  3. In Vivo Evaluation of 5-ASA Colon-Specific Tablets Using Experimental-Induced Colitis Rat Animal Model.

    PubMed

    Sawarkar, Sujata P; Deshpande, S G; Bajaj, A N; Nikam, V S

    2015-12-01

    Colonic drug delivery is intended not only for local treatment in inflammatory bowel disease (IBD) but also for systemic delivery of therapeutics. Intestinal myeloperoxidase (MPO) determination could be used to estimate the average level of inflammation in colon as well as to determine the efficacy of drugs to be used in the treatment of inflammatory bowel diseases or study the specificity of dosage forms to be used for colonic targeting of anti-inflammatory drugs. Colonic prodrug sulfasalazine (SASP) gets metabolized to give 5-aminosalicylic acid (5-ASA), which is the active portion of SASP. However, when given orally, 5-ASA is absorbed in upper part of gastrointestinal tract (GIT) and not made available in colon. In the present study, colon-targeted delivery of 5-ASA was achieved by formulating tablets with two natural polymers namely guar gum and pectin using compression coating method. Colonic specificity of 5-ASA tablets (prepared using guar gum and pectin as polymers) was evaluated in vitro using simulated fluids mimicking in vivo environment as well as in vivo method using chemically (2,4,6-trinitrobenzenesulfonic acid and acetic acid)-induced colitis rat model. Both colon-specific formulations of 5-ASA (guar gum and pectin) were observed to be more effective in reducing inflammation in chemically induced colitis rat models when compared to colon-specific prodrug sulfasalazine as well as conventional 5-ASA administered orally. PMID:26017284

  4. In Vivo Evaluation of 5-ASA Colon-Specific Tablets Using Experimental-Induced Colitis Rat Animal Model.

    PubMed

    Sawarkar, Sujata P; Deshpande, S G; Bajaj, A N; Nikam, V S

    2015-12-01

    Colonic drug delivery is intended not only for local treatment in inflammatory bowel disease (IBD) but also for systemic delivery of therapeutics. Intestinal myeloperoxidase (MPO) determination could be used to estimate the average level of inflammation in colon as well as to determine the efficacy of drugs to be used in the treatment of inflammatory bowel diseases or study the specificity of dosage forms to be used for colonic targeting of anti-inflammatory drugs. Colonic prodrug sulfasalazine (SASP) gets metabolized to give 5-aminosalicylic acid (5-ASA), which is the active portion of SASP. However, when given orally, 5-ASA is absorbed in upper part of gastrointestinal tract (GIT) and not made available in colon. In the present study, colon-targeted delivery of 5-ASA was achieved by formulating tablets with two natural polymers namely guar gum and pectin using compression coating method. Colonic specificity of 5-ASA tablets (prepared using guar gum and pectin as polymers) was evaluated in vitro using simulated fluids mimicking in vivo environment as well as in vivo method using chemically (2,4,6-trinitrobenzenesulfonic acid and acetic acid)-induced colitis rat model. Both colon-specific formulations of 5-ASA (guar gum and pectin) were observed to be more effective in reducing inflammation in chemically induced colitis rat models when compared to colon-specific prodrug sulfasalazine as well as conventional 5-ASA administered orally.

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

    PubMed Central

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

    2002-01-01

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

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

    PubMed

    Bell, David S H

    2016-01-01

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

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

    PubMed

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

    2008-05-01

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

  8. 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

  9. Neutrophils influx and proinflammatory cytokines inhibition by sodium salicylate, unlike aspirin, in Candida albicans-induced peritonitis model.

    PubMed

    Pereira, Priscilla Aparecida Tártari; Bini, Daniel; Bovo, Fernanda; Faccioli, Lucia Helena; Monteiro, Marta Chagas

    2016-07-01

    Sodium salicylate (NaS) and aspirin (ASA) are known to have a variety of effects on microorganisms, such as fungus (C. albicans and C. neoformans), moreover, it have effects in leukocyte adhesion and migration in vitro. In this report, we investigated the effect of ASA and NaS in neutrophil migration and cytokine production in C. albicans-induced peritonitis murine model. For this, mice were treated intraperitoneally (i.p) or orally (po) with NaS or ASA; after they were stimulated i.p. with C. albicans, the cellular migration was evaluated 24 h after stimulation. NaS, in mice treated i.p., unlike ASA, was able to inhibit the neutrophil migration and proinflammatory cytokine production induced by C. albicans, such as TNF-α, IL-1, IFN-γ, IL-12, and IL-10, but did not alter the IL-4 levels in these animals. However, the po treatment with same the dose of NaS or ASA did not affect the influx of this cell for inflammatory site. These results suggest that the NaS inhibits cellular migration and proinflammatory cytokine by different anti-inflammatory mechanism compared to ASA.

  10. 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

  11. Aspirin resistant patients with recent ischemic stroke.

    PubMed

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

    2014-04-01

    Some patients with a recent ischemic stroke who are being treated with aspirin as an antiaggregant suffer a new ischemic stroke. These patients (15-25%) have been called unresponsive to aspirin or aspirin resistant. The aspirin-resistant patients have a four-time greater risk of suffering a stroke. Furthermore, these strokes are generally more severe, with increased infarct volume and greater risk of recurrence. There is currently no ideal laboratory test to detect the resistance to the antiaggregant effect of aspirin. The study of resistance to aspirin would only be indicated in selected cases. In these patients, one should first rule out any "pseudo-resistance" to aspirin (lack of compliance, concomitant treatments that interfere with the action of the aspirin). PMID:24211052

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

    PubMed

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

    2013-01-01

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

  13. Studies on the hydrolysis of biocompatible acrylic polymers having aspirin-moieties.

    PubMed

    Gu, Z W; Li, F M; Feng, X D; Voong, S T

    1983-01-01

    Both the homogeneous and heterogeneous hydrolysis of five new acrylic polymers having aspirin-moieties, i.e. polymers of beta-(acetylsalicylyloxy)ethyl methacrylate, beta-(acetylsalicylyloxy) propyl methacrylate,beta-(acetylsalicylyloxy) ethyl acrylate, beta-hydroxy-gamma-(acetylsalicylyloxy) propyl methacrylate, beta-hydroxy-gamma-(acetylsalicylyloxy) propyl acrylate were investigated in acidic or alkaline medium at 30 degrees C or 60 degrees C, respectively. It was observed that the chief hydrolyzed product is always aspirin with minor amount of salicylic acid.

  14. Isolation, Characterization of a Potential Degradation Product of Aspirin and an HPLC Method for Quantitative Estimation of Its Impurities.

    PubMed

    Acharya, Subasranjan; Daniel, Alex; Gyadangi, Bharath; Ramsamy, Sriramulu

    2015-10-01

    In this work, a new degradation product of Aspirin was isolated, characterized and analyzed along with other impurities. New unknown degradation product referred as UP was observed exceeding the limit of ICH Q3B identification thresholds in the stability study of Aspirin and Dipyridamole capsule. The UP isolated from the thermal degradation sample was further studied by IR, Mass and (1)H NMR spectrometry, revealing structural similarities with the parent molecule. Finally, UP was identified as a new compound generated from the interaction of Aspirin and Salicylic acid to form a dehydrated product. A specific HPLC method was developed and validated for the analysis of UP and other Aspirin impurities (A, B, C, E and other unknown degradation products). The proposed method was successfully employed for estimation of Aspirin impurities in a pharmaceutical preparation of Aspirin (Immediate Release) and Dipyridamole (Extended Release) Capsules.

  15. 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

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

    SciTech Connect

    Williams, Jennie L.; Ji, Ping; Ouyang, Nengtai; Kopelovich, Levy; Rigas, Basil

    2011-06-10

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

  17. Comparative effects of immediate-release and extended-release aspirin on basal and bradykinin-stimulated excretion of thromboxane and prostacyclin metabolites.

    PubMed

    Gamboa, Jorge L; Devin, Jessica K; Ramirez, Claudia E; Yu, Chang; Nian, Hui; Lee, Rhonda H; Brown, Nancy J

    2016-04-01

    A goal of aspirin therapy is to inhibit thromboxane production and platelet aggregation without inhibiting endothelial production of the vasodilator and anti-thrombotic prostacyclin. This study tested the hypothesis that extended-release aspirin (NHP-554C) would have increased selectivity for inhibition of basal and simulated thromboxane formation compared to immediate-release aspirin (ASA). Thirty-six healthy subjects were randomized to NHP-554C or ASA groups. Within each group, subjects were randomized to 5-day treatment with 81 mg/d, 162.5 mg/d and placebo in a crossover design in which treatment periods were separated by 2-week washout. On the fifth day of treatment, 81 mg/d and 162.5 mg/d ASA reduced basal urinary excretion of the stable thromboxane metabolite 11-dehydro-thromboxane B2 62.3% and 66.2% and basal excretion of the stable prostacyclin metabolite 2,3-dinor-6-keto-PGF1α 22.8% and 26.5%, respectively, compared to placebo. NHP-554C 81 mg/d and 162.5 mg/d reduced 11-dehydro-thromboxane B2 53% (P = 0.03 vs. ASA 81 mg/d) and 67.9% and 2,3-dinor-6-keto-PGF1α 13.4% and 18.5%, respectively. NHP-554C 81 mg/d did not significantly reduce basal excretion of the prostacyclin metabolite. Both doses of ASA and NHP significantly reduced excretion of both thromboxane and prostacyclin metabolites following intravenous bradykinin. During NHP-554C 162.5 mg/d, but not during ASA, bradykinin significantly increased urinary 2,3-dinor-6-keto-PGF1α. Nevertheless, 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-PGF1α responses to bradykinin were statistically similar during ASA and NHP-554C. In conclusion, at doses of 81 and 162.5 mg/d immediate- and extended-release aspirin selectively decrease basal thromboxane production. Both forms of aspirin decrease bradykinin-stimulated thromboxane and prostacyclin production, but some stimulated prostacyclin production remains during treatment with NHP-554C. PMID:27069632

  18. Hydrogen sulfide-releasing aspirin modulates xenobiotic metabolizing enzymes in vitro and in vivo.

    PubMed

    Chattopadhyay, Mitali; Kodela, Ravinder; Nath, Niharika; Street, Cherease R; Velázquez-Martínez, Carlos A; Boring, Daniel; Kashfi, Khosrow

    2012-03-15

    The balance between phase-I carcinogen-activating and phase-II detoxifying xenobiotic metabolizing enzymes is critical to determining an individual's risk for cancer. We evaluated the effect of Hydrogen sulfide-releasing aspirin (HS-ASA) on xenobiotic metabolizing enzymes in HT-29 human colon and Hepa 1c1c7 mouse liver adenocarcinoma cells and in Wistar rats. HS-ASA inhibited the growth of HT-29 and Hepa 1c1c7 cells, with an IC(50) of 3.2 ± 0.3 μM and 4.2 ± 0.4 μM, respectively. The IC(50) for ASA in both cell lines was greater than 5000 μM at 24h. In these cell lines, HS-ASA caused a dose-dependent increase in activity and expression of the phase-II enzymes glutathione S-transferase (GST) and NAD(P)H:quinoneoxireductase (NQO1). It also caused an increase in UDP-glucuronosyltransferase (UGT) expression. The levels of CYP 1A1 a phase-I enzyme was increased by HS-ASA in both cell lines. Pretreatment of cells with NaF, an esterase inhibitor, abrogated the HS-ASA-mediated increases in NQO1 enzyme activity. HS-ASA increased the protein levels of the transcription factor Nrf2, which is a regulator of the phase-II enzymes. In vivo, HS-ASA at 100mg/kg/day had no effect on rat's weights; it induced a 3.4-fold and 1.4-fold increase in hepatic GST and NQO1 enzyme activities, respectively. GST and NQO1 protein levels were also increased. In contrast to that in cultured cells, CYP 1A1 protein levels were not altered in vivo. Therefore, HS-ASA induces phase-II enzymes, at least in part, through the action of H(2)S and by modulating Nrf2; these effects may be part of its mechanism of action against carcinogenesis.

  19. Aspirin and Clopidogrel Alter Core Temperature and Skin Blood Flow during Heat Stress

    PubMed Central

    Bruning, Rebecca S.; Dahmus, Jessica D.; Kenney, W. Larry; Holowatz, Lacy A.

    2012-01-01

    Antithrombotic therapy with oral aspirin or clopidogrel (PlavixR) is associated with an attenuated skin vasodilator response and a greater rate of rise in core temperature in healthy, middle-aged individuals during passive heating in a water perfused suit. Purpose The present double-blind, crossover study examined the functional consequences of 7 days of low-dose aspirin (ASA, 81 mg/day) vs. clopidogrel (CLO, 75 mg/day) treatment in 14 healthy, middle-aged (50–65 yrs) men and women during passive heating in air (40 min at 30°C, 40% rh) followed by exercise (60% V̇O2peak). Methods Oral temperature (Tor) was measured in the antechamber (23.0 ± 0.1°C) before entering a warm environmental chamber. After 40 minutes of rest subjects cycled on a recumbent cycle ergometer for up to 120 minutes. Esophageal temperature (Tes) and laser Doppler flux were measured continuously, and the latter was normalized to maximal cutaneous vascular conductance (%CVCmax). Results Prior to entry into the environmental chamber there were no differences in Tor among treatments; however, after 40 minutes of rest in the heat, Tes was significantly higher for ASA and CLO vs. placebo (37.2±0.1°C, 37.3±0.1°C, vs. 37.0±0.1°C, both P<0.001), a difference that persisted throughout exercise (P<0.001 vs. placebo). The mean body temperature thresholds for the onset of cutaneous vasodilation were shifted to the right for both ASA and CLO during exercise (P<0.05). Conclusion ASA and CLO resulted in elevated core temperatures during passive heat stress and shifted the onset of peripheral thermoeffector mechanisms toward higher body temperatures during exercise heat stress. PMID:23135368

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

    PubMed

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

    2010-03-01

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

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

    PubMed

    Cook, Kevin A; White, Andrew A

    2016-02-01

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

  2. Use of aspirin combinations with caffeine and increasing headache frequency: a prospective population-based study.

    PubMed

    Schramm, Sara H; Moebus, Susanne; Özyurt Kugumcu, Melek; Geisel, Marie H; Obermann, Mark; Yoon, Min-Suk; Diener, Hans-Christoph; Jöckel, Karl-Heinz; Katsarava, Zaza

    2015-09-01

    Combinations of analgesics with caffeine have been discussed as bearing a risk for headache chronicity. We investigated whether aspirin with caffeine (ASA+) increases headache frequency compared with aspirin alone in migraine, tension-type headache (TTH), and migraine + TTH (MigTTH). The population-based German Headache Consortium Study, which included participants aged 18 to 65 years, collected information about headache and analgesics at baseline (2003-2007, t0, response rate: 55.2%), first follow-up after 1.87 ± 0.39 years (t1, 37.2%), and second follow-up after 3.26 ± 0.60 years (t2, 38.8%). We included participants with headache at t0, aspirin intake, ASA+ or no analgesics at t0 and t2, and known headache frequency. Linear regression was used to estimate changes of headache frequency (Δt2-t0) and 95% confidence intervals depending on analgesic intake, stratified by headache subtypes, adjusting for sex, age, analgesics at t1, changes of headache frequency at t1, drinking, smoking, body mass index, education, headache frequency at t0. Of 509 participants (56.0% women, 42.0 ± 11.8 years [mean ± SD]), 45.2% reported aspirin intake (41.3 ± 10.9 years, 59.6% women, headache days at t0: 2.8 ± 3.1 d/mo, t2: 3.6 ± 4.1 d/mo), 11.8% ASA+ intake (46.0 ± 9.8 years, 73.3%, t0: 4.8 ± 6.1 d/mo, t2: 5.3 ± 5.1 d/mo), and 43.0% no analgesics (41.6 ± 13.1 years, 47.5%, t0: 3.8 ± 6.2 d/mo, t2: 5.3 ± 6.6 d/mo). There was no increase in headache frequency in participants with ASA+ intake compared with aspirin (adjusted, all headache: -0.34 d/mo [95% confidence intervals: -2.50 to 1.82], migraine: -1.36 d/mo [-4.76 to 2.03], TTH: -0.57 d/mo [-4.97 to 3.84], MigTTH: 2.46 d/mo [-5.19 to 10.10]) or no analgesics (all headache: -2.24 d/mo [-4.54 to 0.07], migraine: -3.77 d/mo [-9.22 to 1.68], TTH: -4.68 d/mo [-9.62 to 0.27]; MigTTH: -3.22 d/mo [-10.16 to 3.71]). In our study, ASA+ intake did not increase headache frequency compared with aspirin or no analgesics. PMID

  3. Considerations for Using the ASA24® Dietary Assessment Tool

    Cancer.gov

    ASA24 has been used by thousands of Researchers conducting studies in multiple settings. Through our support of Researchers, NCI has gained insights into best practices for implementation, as well as common issues encountered by study Respondents.

  4. Overview of the ASA24® Researcher Website

    Cancer.gov

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

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

    PubMed

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

    2004-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  8. 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

  9. Platelet thromboxane (11-dehydro-Thromboxane B2) and aspirin response in patients with diabetes and coronary artery disease.

    PubMed

    Lopez, Luis R; Guyer, Kirk E; Torre, Ignacio Garcia De La; Pitts, Kelly R; Matsuura, Eiji; Ames, Paul Rj

    2014-04-15

    Aspirin (ASA) irreversibly inhibits platelet cyclooxygenase-1 (COX-1) leading to decreased thromboxane-mediated platelet activation. The effect of ASA ingestion on thromboxane generation was evaluated in patients with diabetes (DM) and cardiovascular disease. Thromboxane inhibition was assessed by measuring the urinary excretion of 11-dehydro-thromboxane B2 (11dhTxB2), a stable metabolite of thromboxane A2. The mean baseline urinary 11dhTxB2 of DM was 69.6% higher than healthy controls (P = 0.024): female subjects (DM and controls) had 50.9% higher baseline 11dhTxB2 than males (P = 0.0004), while age or disease duration had no influence. Daily ASA ingestion inhibited urinary 11dhTxB2 in both DM (71.7%) and controls (75.1%, P < 0.0001). Using a pre-established cut-off of 1500 pg/mg of urinary 11dhTxB2, there were twice as many ASA poor responders (ASA "resistant") in DM than in controls (14.8% and 8.4%, respectively). The rate of ASA poor responders in two populations of acute coronary syndrome (ACS) patients was 28.6 and 28.7%, in spite of a significant (81.6%) inhibition of urinary 11dhTxB2 (P < 0.0001). Both baseline 11dhTxB2 levels and rate of poor ASA responders were significantly higher in DM and ACS compared to controls. Underlying systemic oxidative inflammation may maintain platelet function in atherosclerotic cardiovascular disease irrespective of COX-1 pathway inhibition and/or increase systemic generation of thromboxane from non-platelet sources. PMID:24748925

  10. Nitric oxide-donating aspirin inhibits the growth of pancreatic cancer cells through redox-dependent signaling

    PubMed Central

    Zhou, Hui; Huang, Liqun; Sun, Yu; Rigas, Basil

    2009-01-01

    The novel chemopreventive nitric oxide-donating aspirin (NO-ASA) prevents nearly 90% of ductal adenocarcinomas in a animal tumor model. To decipher the mechanism of this effect, we studied in BxPC-3 human pancreatic cancer cells the sequence of signaling events leading from NO-ASA treatment to cell growth inhibition. NO-ASA inhibited the growth of BxPC-3 cells (IC50 = 13 μM), by inhibiting proliferation modestly and inducing apoptosis, necrosis and G1/S cell cycle block. At 15 min of treatment with NO-ASA, the intracellular levels of reactive oxygen species (ROS) began increasing (peak at 8 h, baseline levels by 24 h). ROS activated almost immediately in a time- and concentration-dependent manner the MAPK pathways p38, ERK, and JNK (their activation was abrogated by the antioxidant N-acetylcysteine). MAPK activation induced p21cip-1, which suppressed the levels of cyclin D1 that controls G1/S cell cycle transition. NO-ASA induced COX-2 expression starting 90 min after p21cip-1 was induced. When COX-2 expression was knocked-down using siRNA against cox-2, the expression of p21cip-1 was induced by NO-ASA, regardless of the level of expression of COX-2, suggesting a marginal, if any, role for COX-2 in the growth inhibitory effect of NO-ASA. These findings along with the temporal sequence of individual changes indicate a signaling sequence that involves ROS → MAPKs → p21cip-1 → cyclin D1 → cell death. Our findings establish the critical role of ROS as proximal signaling molecules in the action of anticancer compounds and may be useful in designing mechanism-driven approaches to cancer control. PMID:18805632

  11. 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' ...

  12. Effect of cotreatment of aspirin metabolites on mitomycin C-induced genotoxicity using the somatic mutation and recombination test in Drosophila melanogaster.

    PubMed

    Niikawa, Miki; Nakamura, Takeshi; Nagase, Hisamitsu

    2006-01-01

    In our previous reports, aspirin, an antipyretic analgesic, suppressed the genotoxicity of mitomycin C (MMC) in a somatic mutation and recombination test (SMART) in Drosophila melanogaster. In order to reveal the mechanism of the anti-genotoxicity of aspirin, we evaluated the suppressing ability of each aspirin metabolite, such as salicylic acid (SA), salicyluric acid (SUA), gentisic acid (GA), gentisuric acid (GUA), and 2,3-dihydroxybenzoic acid (DHBA), in SMART in Drosophila melanogaster using the cotreatment protocol in this report. SUA, GA, GUA, and DHBA reduced the number of the three types of spot induced by MMC without decrease of survival. These aspirin metabolites decreased the genotoxicity frequency of MMC for total spots in a dose-dependent manner. Furthermore, each metabolite decreased the genotoxicity frequency of MMC by approximately 80% at a dose of 40 mg/bottle, respectively. It is suggested that these metabolites are the main substances of anti-genotoxicity in the aspirin metabolic pathway. PMID:16931440

  13. 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

  14. Aspirin promotes TFF2 gene activation in human gastric cancer cell lines.

    PubMed

    Azarschab, P; Al-Azzeh, E; Kornberger, W; Gött, P

    2001-01-19

    Trefoil factor family (TFF) peptides promote cell migration, heal the mucosa and may suppress tumor growth. In reporter gene assays we show that aspirin (1-12 mM) evokes a six-fold up-regulation of TFF2, but not TFF1 and TFF3 transcription in human gastrointestinal cell lines. 6 h after application up-regulation of endogenous TFF2 mRNA was observed. TFF2 transcription was enhanced by indomethacin and arachidonic acid but repressed by staurosporine, suggesting mediation via protein kinase C. We mapped an aspirin responding element -546 to -758 bp upstream of TFF2. Up-regulation of TFF2 by aspirin may partially explain the chemopreventive potential of low dose aspirin in gastrointestinal carcinogenesis.

  15. Aspirin inhibits hepatitis C virus entry by downregulating claudin-1.

    PubMed

    Yin, P; Zhang, L

    2016-01-01

    Aspirin has previously been reported to inhibit hepatitis C virus (HCV) replication. The aim of this study was to investigate whether aspirin is involved in blocking HCV entry. We found that aspirin inhibits the entry of HCVpp and infectious HCV. The level of claudin-1, an HCV receptor, is reduced by aspirin. Our results extend the anti-HCV effect of aspirin to the HCV entry step and further reinforce the anti-HCV role of aspirin.

  16. VizieR Online Data Catalog: ASAS low-mass eclipsing binaries light curves (Helminiak+, 2011)

    NASA Astrophysics Data System (ADS)

    Helminiak, K. G.; Konacki, M.

    2010-09-01

    Photometric observations of two newly-discovered low-mass eclipsing binaries: ASAS J045304-0700.4 (ASAS-04) and ASAS J082552-1622.8 (ASAS-08). V and I band curves were obtained in January 2008 with the 1.0-m Elizabeth telescope and its STE4 camera at the South African Astronomical Observatory (SAAO). (4 data files).

  17. Clinical pharmacology of cyclooxygenase inhibition and pharmacodynamic interaction with aspirin by floctafenine in Thai healthy subjects.

    PubMed

    Maenthaisong, R; Tacconelli, S; Sritara, P; Del Boccio, P; Di Francesco, L; Sacchetta, P; Archararit, N; Aryurachai, K; Patrignani, P; Suthisisang, C

    2013-01-01

    Floctafenine, a hydroxyquinoline derivative with analgesic properties, is widely used in Thailand and many other countries. The objectives of this study were to evaluate in Thai healthy volunteers: i) the inhibition of whole blood cyclooxygenase(COX)-2 and COX-1 activity by floctafenine and its metabolite floctafenic acid in vitro and ex vivo after dosing with floctafenine; ii) the possible interference of floctafenine administration with aspirin antiplatelet effects. We performed an open-label, cross-over, 3-period study, on 11 healthy Thai volunteers, who received consecutively floctafenine(200mg/TID), low-dose aspirin(81mg/daily) or their combination for 4 days, separated by washout periods. Floctafenine and floctafenic acid resulted potent inhibitors of COX-1 and COX-2 in vitro (floctafenic acid was more potent than floctafenine) showing a slight preference for COX-1. After dosing with floctafenine alone, whole blood COX-1 and COX-2 activities were inhibited ex vivo in a time-dependent fashion which paralleled floctafenic acid plasma concentrations. Aspirin alone inhibited profoundly and persistently platelet COX-1 activity and AA-induced platelet aggregation throughout 24-h dosing interval which was affected by the co-administration of floctafenine. At 24 h after dosing with aspirin and floctafenine, the inhibition of platelet thromboxane(TX)B2 generation and aggregation were significantly(P less than 0.05) lower than that caused by aspirin alone. Therapeutic dosing with floctafenine profoundly inhibited prostanoid biosynthesis through the rapid conversion to floctafenic acid. Floctafenine interfered with the antiplatelet effect of aspirin. Our results suggest that floctafenine should be avoided in patients with cardiovascular disease under treatment with low-dose aspirin. PMID:23755755

  18. Enteric coating can lead to reduced antiplatelet effect of low-dose acetylsalicylic acid.

    PubMed

    Haastrup, Peter Fentz; Grønlykke, Thor; Jarbøl, Dorte Ejg

    2015-03-01

    Low-dose acetylsalicylic acid (ASA) is widely used as antithrombotic prophylaxis. Enteric-coated ASA has been developed to decrease the risk of gastrointestinal side effects. The consequences of enteric coating on pharmacokinetics and antiplatelet effect of ASA have not systematically been assessed. This MiniReview demonstrates that data from clinical trials indicate that enteric coating can reduce the antiplatelet effect of ASA compared to plain ASA. This is possibly due to decreased bioavailability of ASA caused by prolonged solvation and absorption of the enteric-coated formulations. Therefore, low-dose enteric-coated ASA might not be bioequivalent to plain ASA, entailing the risk of insufficient cardiovascular prophylaxis.

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

    PubMed Central

    Sandborn, William J.; Rubin, David T.; Harper, Joseph R.

    2016-01-01

    Background: Rectal budesonide foam is a second-generation corticosteroid efficacious for active mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis. This subgroup analysis examined the impact of baseline oral 5-aminosalicylic acid (5-ASA) on the efficacy and safety of budesonide foam in patients with mild to moderate ulcerative proctitis or ulcerative proctosigmoiditis. Methods: Patients received budesonide foam 2 mg/25 mL twice daily for 2 weeks, then once daily for 4 weeks, or placebo, with or without continued stable dosing of baseline oral 5-ASAs, for remission induction at week 6 (primary endpoint) in 2 identically designed, randomized, double-blind, phase 3 studies. Results: Of the 267 and 279 patients randomized to treatment with budesonide foam or placebo (pooled population), 55.1% and 55.2%, respectively, reported baseline 5-ASA use. A significantly greater percentage of patients achieved remission with budesonide foam versus placebo, either with (42.2% versus 31.8%, respectively; P = 0.03) or without (40.0% versus 14.4%; P < 0.0001) baseline 5-ASA use at week 6. A significantly greater percentage of patients achieved a Modified Mayo Disease Activity Index rectal bleeding subscale score of 0 at week 6, regardless of baseline 5-ASA use (5-ASA, 50.3% versus 35.7%; P = 0.003: no 5-ASA, 45.8% versus 19.2%; P < 0.0001). The frequency of adverse events was comparable between groups, regardless of baseline 5-ASA use. Conclusions: Budesonide foam was efficacious and safe for induction of remission of mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis in patients receiving oral 5-ASA at baseline and those who were not (Clinicaltrials.gov: NCT01008410 and NCT01008423). PMID:27416045

  20. Aspirin resistance or variable response or both?

    PubMed

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

    2006-11-20

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

  1. 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

  2. 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 ...

  3. Biochemical pathogenesis of aspirin exacerbated respiratory disease (AERD).

    PubMed

    Narayanankutty, Arun; Reséndiz-Hernández, Juan Manuel; Falfán-Valencia, Ramcés; Teran, Luis M

    2013-05-01

    Aspirin exacerbated respiratory disease (AERD) is a distinct clinical entity characterized by eosinophilic rhinosinusitis, asthma and often nasal polyposis. Exposure to aspirin or other nonsteroid anti-inflammatory drugs (NSAIDs) exacerbates bronchospasms with asthma and rhinitis. Disease progression suggests a skewing towards TH2 type cellular response along with moderate to severe eosinophil and mast cell infiltration. Alterations in upper and lower airway cellular milieu with abnormalities in eicosanoid metabolism and altered eicosanoid receptor expression are the key features underlying AERD pathogenesis. Dysregulation of arachidonic acid (AA) metabolism, notably reduced prostaglandin E2 (PGE2) synthesis compared to their aspirin tolerant counterpart and relatively increased PGD2 production, a TH2/eosinophil chemoattractant are reported in AERD. Underproduced PGE2 is metabolized by overexpression of 15 prostaglandin dehydrogenase (15-PGDH) to inactive products further reducing PGE2 at real time. This relives the inhibitory effect of PGE2 on 5-lipoxygenase (5-LOX) resulting in overproduction of cysteinyl leukotrienes (CysLTs). Diminished formation of CysLT antagonists called lipoxins (LXs) also augments CysLTs responsiveness. Occasional intake of NSAIDs favors even more 5-LOX product formation, further narrowing the bronchoconstrictive bottle neck, resulting in acute asthmatic exacerbations along with increased mucus production. This review focuses on abnormalities in biochemical and molecular mechanisms in eicosanoid biosynthesis, eicosanoid receptor dysregulation and associated polymorphisms with special reference to arachidonic acid metabolism in AERD. PMID:23246457

  4. Low dose aspirin estimation: an application to a human pharmacokinetic study.

    PubMed

    Vijaya Bharathi, D; Hotha, Kishore Kumar; Kolagatla, Pandu Ranga Reddy; Venkateswarlu, V

    2013-05-01

    Low dose to very high dose aspirin is used to prevent heart attack. We have developed and validated a sensitive and robust method that could detect low levels of aspirin and salicylic acid in plasma and also a novel sample collection procedure to carry out sample preparation at room temperature. The total run time was 3.00 min; the developed method was validated in human plasma with a lower limit of quantitation of 0.99 ng/mL for aspirin and 2.01 ng/mL for salicylic acid. A linear response function was established for the range of concentrations 0.99-756.20 ng/mL (r > 0.998) for aspirin and 2.01-2486.86 ng/mL for salicylic acid. The intra- and inter-day precision values for aspirin and salicylic acid met the acceptance as per FDA guidelines. The developed assay method was applied to an oral pharmacokinetic study in humans.

  5. 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

  6. Pharmacogenetics of the antiplatelet effect of aspirin.

    PubMed

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

    2012-01-01

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

  7. Breaking action of ascorbic acid on nucleic acids.

    PubMed

    Omura, H; Iiyama, S; Tomita, Y; Narazaki, Y; Shinohara, K

    1975-01-01

    The lowering of the viscosity of DNA solution was caused by the action of AsA or EA and facilitated in the presence of CU2+. However, the action of AsA-3-P was very weak. By sucrose density gradient centrifugation, it was observed that single- and double-strand scissions of DNA were provoked by AsA or EA and enhanced with Cu2+, while only a single-strand scission was caused by AsA-3-P and Cu2+. Similar action of AsA or AsA-3-P was also observed for RNA. Thus, the result indicates that the enediol group of AsA takes an essential part in the breakage of nucleic acids, and Cu2+ enhances the action. It was shown that Apu was mainly decomposed by AsA, whereas Apy not, suggesting that some pyrimidine cluster may be one of the regions attacked by AsA. During the reaction with DNA, the reducing activity of AsA decreased first to some extent and then increased, whereas the reducing activity of AsA-3-P was much lower than that of AsA and decreased steadily. The priming activity of DNA for DNA polymerase was changed after treatment with AsA according to the condition. It was enhanced when DNA was treated under mild conditions but decreased with severer action.

  8. ASAS classification criteria for axial spondyloarthritis: time to modify.

    PubMed

    Akkoc, Nurullah; Khan, Muhammad A

    2016-06-01

    The relationship between ankylosing spondylitis and the recently proposed entity called axial spondyloarthritis with its radiographic and non-radiographic forms that have been defined by the Assessment of Spondyloarthritis International Society (ASAS) criteria for axial spondyloarthritis (axSpA), is currently being debated. The Food and Drug Agency (FDA) had criticized the ASAS criteria and the studies which used these criteria to enroll patients in a clinical trial of certolizumab and adalimumab for the treatment of non-radiographic axial spondyloarthritis. The primary aim of classification criteria is to create homogenous patient populations for basic and clinical research. But the multi-arm construct of the ASAS criteria is a potential source of heterogeneity reducing their utility. Criteria sets should be regarded as dynamic concepts open to modifications or updates as our knowledge advances. We provide evidence to conclude that it is time to modify the ASAS Criteria for axSpA, and we propose some of the steps that can be taken to start moving forward in improving the validity of these criteria. PMID:27094940

  9. Interaction of acupuncture and electroacupuncture on the pharmacokinetics of aspirin and the effect of brain blood flow in rats.

    PubMed

    Wu, Ming-Tsang; Shaw, Lee-Hsin; Wu, Yu-Tse; Tsai, Tung-Hu

    2013-01-01

    Acupuncture and electroacupuncture have been used to improve the brain and motor functions of poststroke patients, and aspirin is used for the prevention of stroke recurrence. Our hypothesis is that acupuncture and electroacupuncture treatments may interact with aspirin in terms of pharmacokinetics via affecting the brain blood flow. The aim of this study is to investigate the potential interactions of acupuncture and electroacupuncture on the pharmacokinetics of aspirin. The effects of acupuncture treatments on brain blood flow were measured by the laser Doppler blood flow imager. The parallel pharmacokinetic study design included three groups: control, acupuncture, and electroacupuncture groups. Two acupoints, namely, Quchi (LI 11) and Zusanli (ST 36), were needled and stimulated electronically in anaesthetized rats. The concentrations of aspirin and its metabolite, salicylic acid were determined by microdialysis and HPLC analysis after aspirin administration (30 mg/kg, i.v.). The brain blood flow responded to electroacupuncture treatments, but the pharmacokinetic parameters of aspirin and salicylic acid in blood and brain were not significantly changed by acupuncture and electroacupuncture treatments. This study may, in part, offer some evidence to support the contention that there is no significant interaction for the combination of aspirin with acupuncture or electroacupuncture. PMID:24371465

  10. Chemopreventive effects of aspirin at a glance.

    PubMed

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

    2015-04-01

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

  11. 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

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

    PubMed

    Pasero, G; Marson, P

    2010-01-01

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

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

    SciTech Connect

    Sung, Jin Young; Choi, Hyoung Chul

    2011-05-06

    Highlights: {yields} Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. {yields} Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. {yields} Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. {yields} Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. {yields} Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effects via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.

  14. Enhanced expression of cyclo-oxygenase isoenzyme 2 (COX-2) in asthmatic airways and its cellular distribution in aspirin-sensitive asthma

    PubMed Central

    Sousa, A.; Pfister, R.; Christie, P. E.; Lane, S. J.; Nasser, S. M.; Schmitz-Schumann, M.; Lee, T. H.

    1997-01-01

    BACKGROUND: There are two isoforms of cyclo-oxygenase (COX), namely COX- 1 and COX-2. COX-1 is constitutively expressed in most tissues and in blood platelets. The metabolites derived from COX-1 are probably involved in cellular housekeeping functions. COX-2 is expressed only following cellular activation by inflammatory stimuli and is thought to be involved in inflammation. METHODS: The expression of COX-1 and COX-2 isoenzymes has been studied in the bronchial mucosa of 10 normal and 18 asthmatic subjects, 11 of whom had aspirin-sensitive asthma (ASA) and seven had non-aspirin-sensitive asthma (NASA) RESULTS: There was a significant fourfold and 14-fold increase, respectively, in the epithelial and submucosal cellular expression of COX-2, but not of COX- 1, in asthmatic patients. There was no significant difference in the total number of cells staining for either COX-1 or COX-2 between subjects with ASA and NASA, but the number and percentage of mast cells that expressed COX-2 was significantly increased sixfold and twofold, respectively, in individuals with ASA. There was a mean fourfold increase in the percentage of COX-2 expressing cells that were mast cells in subjects with ASA and the number of eosinophils expressing COX- 2 was increased 2.5-fold in these subjects. CONCLUSION: COX-2-derived metabolites may play an essential part in the inflammatory processes present in asthmatic airways and development of drugs targeted at this isoenzyme may have therapeutic potential in the treatment of asthma. Mast cells and eosinophils may also have a central role in the pathology of aspirin-sensitive asthma. 


 PMID:9487340

  15. Aspirin

    MedlinePlus

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

  16. 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. Spectroscopic Survey of Detached Eclipsing Binaries from the ASAS Catalog

    NASA Astrophysics Data System (ADS)

    Helminiak, Krzysztof; Konacki, M.; Kaluzny, J.; Rozyczka, M.; Zloczewski, K.; Ratajczak, M.; Muterspaugh, M. W.; Reichart, D. E.; Ivarsen, K. M.; Haislip, J. B.; Crain, A.; Foster, A. C.; Nysewander, M. C.; LaCluyze, A. P.

    2010-05-01

    We present the most interesting results from our survey of eclipsing binaries from the All-Sky Automated Survey (ASAS) catalog. Radial velocities were calculated from high-resolution spectra obtained with Keck I/HIRES, Radcliffe/GIRAFFE and AAT/UCLES telescopes/spectrographs. A novel iodine cell technique for double-lined binaries was also involved. Photometry was taken directly from the ASAS or from dedicated observations at the Elizabeth telescope (SAAO) and fully-automated PROMPT facility. For a sample of systems we derived very precise absolute values of fundamental parameters. In our sample we found 6 new low-mass systems, 4 pre-main-sequence candidates, and several other binaries interesting from the evolutionary point of view.

  18. Du Pont Classifications of 2 ASAS-SN Supernovae

    NASA Astrophysics Data System (ADS)

    Shappee, Benjamin J.; Prieto, J. L.; Rich, J.; Madore, B.; Poetrodjojo, Henry; D'Agostino, Joshua

    2016-09-01

    We report optical spectroscopy (range 370-910 nm) of two supernovae discovered by the All-Sky Automated Survey for Supernovae (ASAS-SN; Shappee et al. 2014, ApJ, 788, 48) using the du Pont 2.5-m telescope (+ WFCCD) at Las Campanas Observatory on Aug. 30 and Sep. 1 2016 UT. We performed a cross-correlation with a library of supernova spectra using the "Supernova Identification" code (SNID; Blondin and Tonry 2007, Ap.J.

  19. Du Pont Classifications of 4 ASAS-SN Supernovae

    NASA Astrophysics Data System (ADS)

    Morrell, N.; Shappee, Benjamin J.

    2016-08-01

    We report optical spectroscopy (range 370-910 nm) of four supernovae discovered by the All-Sky Automated Survey for Supernovae (ASAS-SN; Shappee et al. 2014, ApJ, 788, 48) using the du Pont 2.5-m telescope (+ WFCCD) at Las Campanas Observatory on July 31 and Aug. 01 2016 UT. We performed a cross-correlation with a library of supernova spectra using the "Supernova Identification" code (SNID; Blondin and Tonry 2007, Ap.J.

  20. Multiples Among Detached Eclipsing Binaries from the ASAS Catalog

    NASA Astrophysics Data System (ADS)

    Hełminiak, K. G.; Konacki, M.; Ratajczak, M.; Jordán, A.; Espinoza, N.; Brahm, R.; Kambe, E.; Ukita, N.

    2015-07-01

    We have been conducting a spectroscopic survey of detached eclipsing binaries (DEBs) from the All-Sky Automated Survey (ASAS) database for more than three years. Thousands of high-resolution spectra of >300 systems have been secured, and used for radial velocity measurements and spectral analysis. We have found a zoo of multiple systems in our sample, such as spectroscopic triples and quadruples, visual binaries with eclipsing components, and circumbinary low-mass companions, including sub-stellar-mass candidates.

  1. 78 FR 32477 - ASA Gold and Precious Metals Limited; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-30

    ... COMMISSION ASA Gold and Precious Metals Limited; Notice of Application May 22, 2013. AGENCY: Securities and... Company Act of 1940 (the ``Act''). ] SUMMARY: Summary of Application: Applicant, ASA Gold and Precious... gold and other precious minerals. To this end, ASA's management is seeking to take advantage...

  2. 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.

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

    PubMed

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

    2014-05-01

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

  4. Adverse Effects of Subchronic Dose of Aspirin on Reproductive Profile of Male Rats

    PubMed Central

    Vyas, Archana; Ram, Heera; Purohit, Ashok; Jatwa, Rameshwar

    2016-01-01

    Aspirin (acetylsalicylic acid) is widely used for cardiovascular prophylaxis and as anti-inflammatory pharmaceutical. An investigation was carried out to evaluate the influence of subchronic dose of aspirin on reproductive profile of male rats, if any. Experimental animals were divided into three groups: control and aspirin subchronic dose of 12.5 mg/kg for 30 days and 60 days, respectively, while alterations in sperm dynamics, testicular histopathological and planimetric investigations, body and organs weights, lipid profiles, and hematology were performed as per aimed objectives. Subchronic dose of aspirin reduced sperm density, count, and mobility in cauda epididymis and testis; histopathology and developing primary spermatogonial cells (primary spermatogonia, secondary spermatogonia, and mature spermatocyte) count were also significantly decreased in rats. Hematological investigations revealed hemopoietic abnormalities in 60-day-treated animals along with dysfunctions in hepatic and renal functions. The findings of the present study revealed that administration with subchronic dose of aspirin to male rats resulted in altered reproductive profiles and serum biochemistry. PMID:27190691

  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. 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

  7. 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

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

    PubMed

    Ghislain, P D; Ghislain, E

    2000-05-01

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

  9. Preparation of Oil of Wintergreen from Commercial Aspirin Tablets: A Microscale Experiment Highlighting Acyl Substitutions

    ERIC Educational Resources Information Center

    Hartel, Aaron M.; Hanna, James M., Jr.

    2009-01-01

    A single-pot procedure for the preparation of methyl salicylate (oil of wintergreen) from commercial aspirin tablets has been developed. The synthesis proceeds via a tandem transesterification-Fischer esterification using acidic methanol and can be carried out using either conventional or microwave heating. The experiment helps demonstrate acyl…

  10. Lack of effect of multiple doses of vortioxetine on the pharmacokinetics and pharmacodynamics of aspirin and warfarin.

    PubMed

    Chen, Grace; Zhang, Wencan; Serenko, Michael

    2015-06-01

    Vortioxetine is an antidepressant with multimodal activity approved for the treatment of major depressive disorder. Two separate randomized, placebo-controlled trials evaluated the effects of multiple doses of vortioxetine (10 mg/day) on the pharmacokinetics and pharmacodynamics of aspirin and warfarin in healthy volunteers. In the aspirin study, subjects received vortioxetine 10 mg or placebo once daily for 14 days, followed by coadministration with aspirin 150 mg once daily for 6 days, in 2 periods with a crossover design. In the warfarin study, subjects were randomized after reaching target international normalized ratio (INR) values on warfarin to receive vortioxetine 10 mg or matching placebo once daily for 14 days, with all subjects receiving a maintenance dose of warfarin (1-10 mg). Vortioxetine had no effect on the steady-state pharmacokinetic parameters of aspirin or its metabolite salicylic acid, and no statistically significant effect on the inhibition of arachidonic acid-, adenosine-5'-diphosphate-, or collagen-induced platelet aggregation at any time points. Coadministration of vortioxetine did not alter the pharmacokinetics of (R)- and (S)-warfarin enantiomers, or the mean coagulation parameters of warfarin treatment alone. Coadministration of vortioxetine doses in healthy volunteers had no effect on aspirin or warfarin pharmacokinetics or pharmacodynamics. Vortioxetine was well tolerated when coadministered with aspirin or warfarin. PMID:25641606

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

    PubMed

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

    2015-10-15

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

  12. 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

  13. 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

  14. 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

  15. Aspirin, cyclooxygenase inhibition and colorectal cancer

    PubMed Central

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

    2014-01-01

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

  16. Aspirin, cyclooxygenase inhibition and colorectal cancer.

    PubMed

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

    2014-02-01

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

  17. First photometric analyses of five contact ASAS binaries

    NASA Astrophysics Data System (ADS)

    Saygan, S.

    2016-07-01

    We present the first light curve solutions of five binary systems selected from All Sky Automated Survey (ASAS) Catalog of Variable Stars. The light curves of the systems are analyzed and the light parameters are derived. The estimated absolute parameters of the components and the degree of contact values for all targets are also calculated. We compared our results to other known contact binaries by emphasizing the locations of the components on the mass-radius and the H-R diagram. The evolutionary statuses of the systems are also discussed. Results of our analyses confirm that the systems are contact binaries.

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

    PubMed

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

    2016-08-01

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

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

    PubMed

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

    2016-08-01

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

  20. New formulation of old aspirin for better delivery.

    PubMed

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

    2016-01-01

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

  1. 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)...

  2. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  3. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c)...

  4. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  5. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  6. The cyclooxygenase-2 selective inhibitor, etodolac, but not aspirin reduces neovascularization in a murine ischemic hind limb model.

    PubMed

    Tanaka, Kohei; Yamamoto, Yasutaka; Tsujimoto, Shunsuke; Uozumi, Naonori; Kita, Yoshihiro; Yoshida, Akio; Shimizu, Takao; Hisatome, Ichiro

    2010-02-10

    Cyclooxygenase inhibitors are often prescribed to relieve severe ischemic leg pain in critical ischemic limb patients. Prescription of high doses of aspirin and selective cyclooxygenase-2 inhibitors is reported to increase cardiovascular events through suppression of the vasodilative prostanoid prostaglandin I(2) in endothelium. Here, we evaluated the influence of aspirin and etodolac, a selective cyclooxygenase-2 inhibitor, on neovascularization using a murine ischemia hind limb model. C57BL/6J mice were treated with aspirin or etodolac for twenty-eight days after induction of ischemia. We exploited a concentration of the agents that suppressed cyclooxygenase activity efficiently, especially in prostaglandin I(2) production. Recovery of limb blood perfusion and capillary density in ischemic limbs was significantly suppressed by etodolac treatment when compared to the aspirin treated group and untreated group. Production of 6-keto prostaglandin F(1alpha) and prostaglandin E(2) was lower in the aspirin treated group when compared with the etodolac-treated group. Also, these concentrations were lower in both treatment groups compared with the untreated group. Immunohistochemical analysis suggested cyclooxygenase-2 was expressed in endothelium but not in inflammatory cells in ischemic tissue from the acute to chronic phase. Cyclooxygenase-1 was expressed strongly in inflammatory cells in the acute phase. Furthermore, bone marrow-derived mononuclear cell transplantation improved neovascularization, whereas aspirin and etodolac did not inhibit these effects. Production of arachidonic acid metabolites by transplanted cells was independent of the improvement of neovascularization. In conclusion, cyclooxygenase-2 inhibition reduces ischemia-induced neovascularization. PMID:19879866

  7. Impact of aspirin dose on adenosine diphosphate-mediated platelet activities. Results of an in vitro pilot investigation.

    PubMed

    Tello-Montoliu, Antonio; Thano, Estela; Rollini, Fabiana; Patel, Ronakkumar; Wilson, Ryan E; Muñiz-Lozano, Ana; Franchi, Francesco; Darlington, Andrew; Desai, Bhaloo; Guzman, Luis A; Bass, Theodore A; Angiolillo, Dominick J

    2013-10-01

    Different aspirin dosing regimens have been suggested to impact outcomes when used in combination with adenosine diphosphate (ADP) P2Y12 receptor antagonists. Prior investigations have shown that not only aspirin, but also potent ADP P2Y12 receptor blockade can inhibit thromboxane A2-mediated platelet activation. The impact of aspirin dosing on ADP mediated platelet activities is unknown and represents the aim of this in vitro pilot pharmacodynamic (PD) investigation. Twenty-six patients with stable coronary artery disease on aspirin 81 mg/day and P2Y12 naïve were enrolled. PD assessments were performed at baseline, while patients were on 81 mg/day aspirin and after switching to 325 mg/day for 7 ± 2 days with and without escalating concentrations (vehicle, 1, 3, and 10 μM) of prasugrel's active metabolite (P-AM). PD assays included flow cytometric assessment of VASP to define the platelet reactivity index (PRI) and the Multiplate Analyzer (MEA) using multiple agonists [ADP, ADP + prostaglandin (PGE1), arachidonic acid (AA), and collagen]. Escalating P-AM concentrations showed incremental platelet P2Y12 inhibition measured by VASP-PRI (p<0.001). However, there were no differences according to aspirin dosing regimen at any P-AM concentration (vehicle: p=0.899; 1 μM: p=0.888; 3 μM: p=0.524; 10 μM: p=0.548). Similar findings were observed in purinergic markers assessed by MEA (ADP and ADP+PGE1). P-AM addition significantly reduced AA and collagen induced platelet aggregation (p<0.001 for all measures), irrespective of aspirin dose. In conclusion, aspirin dosing does not appear to affect PD measures of ADP-mediated platelet reactivity irrespective of the degree of P2Y12 receptor blockade. P2Y12 receptor blockade modulates platelet reactivity mediated by alternative activators. PMID:23884248

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

    NASA Astrophysics Data System (ADS)

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

    2010-12-01

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

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

    SciTech Connect

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

    1985-07-01

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

  11. 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

  12. The effect of aspirin on atherogenic diet-induced diabetes mellitus.

    PubMed

    Sethi, Apoorva; Parmar, Hamendra S; Kumar, Anil

    2011-06-01

    Exploration of atherogenic diet-induced diabetes mellitus and the evaluation of antidiabetic potential of aspirin were carried out in this study. Male albino Wistar rats were divided into three groups of seven each (1, 2 and 3). Animals of groups 2 and 3 received CCT diet (normal rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5%, 2-thiouracil), whereas the animals of group 1 received normal feed and served as control. In addition to CCT, animals of group 3 (CCT + Asp) also received aspirin (8 gm/kg), commencing from day 8 till the end of study (day 15). In another experiment (exp. 2), aspirin-supplemented normal rat chow (Asp) was fed to the animals for 7 days and compared with the normal rat chow-fed control group. In experiment 3, an in vitro nitric oxide radical-scavenging potential of aspirin at three different doses (25, 50 and 100 μg/ml) was evaluated. In response to CCT diet, a decrease in serum insulin, α-amylase activity, hepatic glycogen, pancreatic calcium with a concomitant increase in serum glucose, lipid profile (except high-density lipoprotein cholesterol (HDL-C)), pancreatic nitrite and lipid peroxidation and the size of adipocytes along with macrophages infiltration were observed. Aspirin administration to CCT diet-fed animals (CCT + Asp) reverted all the studied biochemical and histological changes towards normality. In experiment 2, aspirin administration decreased the serum glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and VLDL-C with concomitantly increased HDL-C and insulin; however, it increased hepatic glycogen and pancreatic calcium concentration with a decrease in pancreatic and adipose lipid peroxidation. In vitro assay revealed the nitric oxide radical-scavenging potential of aspirin in all the studied doses. It is concluded that CCT diet-induced diabetes mellitus might be the outcome of nitric oxide radical-induced oxidative stress in pancreatic tissue, as well as diminished

  13. Comparison of intraoperative and postoperative complications based on ASA risks in patients who underwent percutaneous nephrolithotomy

    PubMed Central

    Karakaş, Hüseyin Buğra; Çiçekbilek, İzzet; Tok, Adem; Alışkan, Tamer; Akduman, Bülent

    2016-01-01

    Objective In this study we aimed to evaluate intraoperative and postoperative complications which developed according to pre-operative American Society of Anesthesiologists (ASA) risk criteria in patients who had undergone percutaneous nephrolithotomy (PNL). Material and methods Five hundred and sixty patients who had undergone PNL between 2002 and 2014 were included in the study. Patients operated on the ipsilateral kidney, those with solitary kidney or the cases who had previously undergone more than one access were excluded from this study. Preoperative anesthesia risks were determined according to preoperative classification developed by ASA. Postoperative complications were evaluated using Clavien Complication Grading Scale. Results The mean age of the cases was 47±14 years. The 57% (n=319) of the cases were male, 241 (43%) of them were female. The average indwell time of nephrostomy catheter was 2.88±1.00 (1–8), and length of hospital stay was 4.91±1.54 (2–17) days. When the cases were assessed according to ASA risk groups, intraoperative complications were observed in 9 (5.5%) ASA I, 27 (8.6%) ASA II, and 18 (22%) ASA III patients and and distribution of the patients was statistically significant (p<0.001). When intraoperative complications were evaluated one by one, intraoperative hypotension developed in ASA I (n=3; 1.8%), ASA II (n=20; 6.4%) and ASA III (n=11; 13.4%) risk groups and this distribution (p=0.002) of patients was statistically significant. When assessed according to Clavien Postoperative Scale, postoperative complications developed (p=0.053) in ASAI (n=24; 14.7%), ASA II (n=27, 8.6%) and ASA III (n=13; 15.9%) risk groups, and this distribution of the patients was not statistically significant. In postoperative complications, Grade 3a complications developed in ASA I (n=12; 7.4%), ASA II (n=19; 6%) and ASA III (n=8; 9.8%) risk groups and this distribution was not seen to be statistically significant (p=0.485). Conclusion A statistically

  14. Comparison of intraoperative and postoperative complications based on ASA risks in patients who underwent percutaneous nephrolithotomy

    PubMed Central

    Karakaş, Hüseyin Buğra; Çiçekbilek, İzzet; Tok, Adem; Alışkan, Tamer; Akduman, Bülent

    2016-01-01

    Objective In this study we aimed to evaluate intraoperative and postoperative complications which developed according to pre-operative American Society of Anesthesiologists (ASA) risk criteria in patients who had undergone percutaneous nephrolithotomy (PNL). Material and methods Five hundred and sixty patients who had undergone PNL between 2002 and 2014 were included in the study. Patients operated on the ipsilateral kidney, those with solitary kidney or the cases who had previously undergone more than one access were excluded from this study. Preoperative anesthesia risks were determined according to preoperative classification developed by ASA. Postoperative complications were evaluated using Clavien Complication Grading Scale. Results The mean age of the cases was 47±14 years. The 57% (n=319) of the cases were male, 241 (43%) of them were female. The average indwell time of nephrostomy catheter was 2.88±1.00 (1–8), and length of hospital stay was 4.91±1.54 (2–17) days. When the cases were assessed according to ASA risk groups, intraoperative complications were observed in 9 (5.5%) ASA I, 27 (8.6%) ASA II, and 18 (22%) ASA III patients and and distribution of the patients was statistically significant (p<0.001). When intraoperative complications were evaluated one by one, intraoperative hypotension developed in ASA I (n=3; 1.8%), ASA II (n=20; 6.4%) and ASA III (n=11; 13.4%) risk groups and this distribution (p=0.002) of patients was statistically significant. When assessed according to Clavien Postoperative Scale, postoperative complications developed (p=0.053) in ASAI (n=24; 14.7%), ASA II (n=27, 8.6%) and ASA III (n=13; 15.9%) risk groups, and this distribution of the patients was not statistically significant. In postoperative complications, Grade 3a complications developed in ASA I (n=12; 7.4%), ASA II (n=19; 6%) and ASA III (n=8; 9.8%) risk groups and this distribution was not seen to be statistically significant (p=0.485). Conclusion A statistically

  15. 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.

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  18. Non-enzymatic modifications of prostaglandin H synthase 1 affect bifunctional enzyme activity - Implications for the sensitivity of blood platelets to acetylsalicylic acid.

    PubMed

    Kassassir, Hassan; Siewiera, Karolina; Talar, Marcin; Stec-Martyna, Emilia; Pawlowska, Zofia; Watala, Cezary

    2016-06-25

    Due to its ability to inhibit the blood platelet PGHS-1, acetylsalicylic acid (ASA, Aspirin(®)) is widely used as a preventive agent in atherothrombotic diseases. However, its beneficial effects seem to be lower in diabetic patients, suggesting that protein glycation may impair effective ASA-mediated acetylation process. On the other hand, it is proposed that ASA can prevent some of the late complications of diabetes by lowering the extent of glycation at protein free amino groups. The aim of this work was to evaluate the extents of non-enzymatic N-glycosylation (glycation) and acetylation of blood platelet PGHS-1 (COX-1) and the competition between glycation and acetylation was investigated in order to demonstrate how these two reactions may compete against platelet PGHS-1. When PGHS-1 was incubated with glycating/acetylating agents (glucose, Glu; 1,6-bisphosphofructose, 1,6-BPF; methylglyoxal, MGO, acetylsalicylic acid, ASA), the enzyme was modified in 13.4 ± 1.6, 5.3 ± 0.5, 10.7 ± 1.2 and 6.4 ± 1.1 mol/mol protein, respectively, and its activity was significantly reduced. The prior glycation/carbonylation of PGHS-1 with Glu, 1,6-BPF or MGO decreased the extent of acetylation from 6.4 ± 1.1 down to 2.5 ± 0.2, 3.6 ± 0.3 and 5.2 ± 0.2 mol/mol protein, respectively, but the enzyme still remained susceptible to the subsequent inhibition of its activity with ASA. When PGHS-1 was first acetylated with ASA and then incubated with glycating/carbonylating agents, we observed the following reductions in the enzyme modifications: from 13.4 ± 1.6 to 8.7 ± 0.6 mol/mol protein for Glu, from 5.3 ± 0.5 to 3.9 ± 0.3 mol/mol protein for 1,6-BPF and from 10.7 ± 1.2 to 7.5 ± 0.5 mol/mol protein for MGO, however subsequent glycation/carbonylation did not significantly affect PGHS-1 function. Overall, our outcomes allow to better understand the structural aspects of the chemical competition between glycation and acetylation of PGHS-1

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

    PubMed

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

    2016-08-01

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

  20. 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

  1. Effect of stress and aspirin on extrahepatic portal hypertension in rats.

    PubMed

    Grosfeld, J L; Phelps, T O; Jesseph, J M

    1975-10-01

    Extrahepatic portal hypertension was induced in rats by portal venous constriction. Portal pressures on the fourth postconstriction day were significantly elevated in PVC rats when compared to control rats. Splenoportograms showed decreased hepatic flow and venous collaterals. Histologic sections showed gastric mucosal congestion in PVC rats. Gastric acid production and H+ ion equilibration were similar in PVC and control rats. Rats with portal hypertension had a significant increase (p less than 0.001) in mucosal erosions when subjected to a 7-hr restraint stress. Erosion formation was significantly augmented by aspirin administration. Although the exact relationship between the stress of a respiratory infection and variceal bleeding is unknown, these data demonstrate an increased susceptibility of PVC rats to nonhemorrhagic stress. This response is clearly augmented by aspirin treatment. Gastric congestion and the known effect of aspirin on gastric mucosal permeability and the gastric mucosal barrier are implicated in these observations. These findings correlated with clinical observations and strongly suggest avoidance of aspirin therapy in children with extrahepatic portal hypertension.

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

    PubMed

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

    2015-03-01

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

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

    PubMed Central

    Chen, Jiandong; Zhang, Haowen; Chen, Xiaohu

    2016-01-01

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

  4. Subunit Asa1 spans all the peripheral stalk of the mitochondrial ATP synthase of the chlorophycean alga Polytomella sp.

    PubMed

    Colina-Tenorio, Lilia; Miranda-Astudillo, Héctor; Cano-Estrada, Araceli; Vázquez-Acevedo, Miriam; Cardol, Pierre; Remacle, Claire; González-Halphen, Diego

    2016-04-01

    Mitochondrial F1FO-ATP synthase of chlorophycean algae is dimeric. It contains eight orthodox subunits (alpha, beta, gamma, delta, epsilon, OSCP, a and c) and nine atypical subunits (Asa1 to 9). These subunits build the peripheral stalk of the enzyme and stabilize its dimeric structure. The location of the 66.1kDa subunit Asa1 has been debated. On one hand, it was found in a transient subcomplex that contained membrane-bound subunits Asa1/Asa3/Asa5/Asa8/a (Atp6)/c (Atp9). On the other hand, Asa1 was proposed to form the bulky structure of the peripheral stalk that contacts the OSCP subunit in the F1 sector. Here, we overexpressed and purified the recombinant proteins Asa1 and OSCP and explored their interactions in vitro, using immunochemical techniques and affinity chromatography. Asa1 and OSCP interact strongly, and the carboxy-terminal half of OSCP seems to be instrumental for this association. In addition, the algal ATP synthase was partially dissociated at relatively high detergent concentrations, and an Asa1/Asa3/Asa5/Asa8/a/c10 subcomplex was identified. Furthermore, Far-Western analysis suggests an Asa1-Asa8 interaction. Based on these results, a model is proposed in which Asa1 spans the whole peripheral arm of the enzyme, from a region close to the matrix-exposed side of the mitochondrial inner membrane to the F1 region where OSCP is located. 3D models show elongated, helix-rich structures for chlorophycean Asa1 subunits. Asa1 subunit probably plays a scaffolding role in the peripheral stalk analogous to the one of subunit b in orthodox mitochondrial enzymes. PMID:26657474

  5. ASAS-SN Confirmation of a Bright, Fast-Rising Supernova in NGC 613

    NASA Astrophysics Data System (ADS)

    Nicholls, B.; Brown, J. S.; Dong, Subo; Stanek, K. Z.; Holoien, T. W.-S.; Kochanek, C. S.; Shields, J.; Shappee, B. J.; Prieto, J. L.; Bersier, D.; Bose, S.; Chen, Ping; Brimacombe, J.

    2016-09-01

    During the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN or "Assassin"), using data from the quadruple 14-cm "Cassius" telescope in Cerro Tololo, Chile, we confirmed a bright supernova candidate in NGC 613. The transient is present in ASAS-SN "Cassius" data on UT 2016-09-21.29 (V~15.0).

  6. A Photometric Study of ASAS J184708-3340.2: an Eclipsing Binary with Total Eclipses

    NASA Astrophysics Data System (ADS)

    Berrington, R. C.; Tuhey, E. M.

    2015-06-01

    We present new multi-band differential aperture photometry of the eclipsing variable star ASAS J184708-3340.2. The light curves are analyzed with the Wilson-Devinney model to determine best-fit stellar models. Our models show that ASAS J184708-3340.2 is consistent with an overcontact eclipsing binary (W Ursae Majoris) system with total eclipses.

  7. 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.

  8. 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.

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

    PubMed

    Hamada, Hiromichi

    2014-09-01

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

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

    MedlinePlus

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

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

    MedlinePlus

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

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

    Cancer.gov

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

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

    PubMed

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

    2016-01-01

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

  14. 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.

  15. Aconitine-induced writhing as a method for assessing aspirin-like analgesic activity.

    PubMed

    Bhalla, T N; Bhargava, K P

    1980-01-01

    A painful writhing syndrome is produced by aconitine when given intraperitoneally. It is similar to that induced by other chemical agent viz. phenylquinone, acetic acid, and bradykinin. Aconitine writhing is quick to appear, shows greater frequency and longer duration than that induced by other agents. The nonnarcotic analgesics more selectively antagonize the aconitine writhing than orally-administered narcotic analgesics. Thus the aconitine writhing method is a very suitable method for the selective screening of the aspirin type of analgesic agent.

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

    SciTech Connect

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

    1987-12-01

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

  17. Suppressive effect of post- or pre-treatment of aspirin metabolite on mitomycin C-induced genotoxicity using the somatic mutation and recombination test in Drosophila melanogaster.

    PubMed

    Niikawa, Miki; Shin, Seizai; Nagase, Hisamitsu

    2007-01-01

    In our previous paper, we found that aspirin suppressed in a somatic mutation and recombination test (SMART) of mitomycin C (MMC) in Drosophila melanogaster. In order to reveal the mechanism of bio-antimutagenicity and/or preventive effect of aspirin, we evaluated the suppressive ability of each aspirin metabolite, such as salicylic acid (SA), salicyluric acid (SUA), gentisic acid (GA), gentisuric acid (GUA) and 2,3-dihydroxybenzoic acid (DHBA), in SMART in D. melanogaster using post- and pre-treatments. As for the post-treatment, SA reduced the numbers of large single and twin spots. GA reduced the small single and large single spots, and GUA reduced the single spots, large single and twin spots. The inhibition of GUA is slightly stronger than that of any other metabolites; the inhibition percentage is 49 at the dose of 5 mg/bottle. On the other hand, as for the pre-treatment, aspirin, SUA, GA and DHBA reduced the numbers of small single spots. SUA, GE and DHBA reduced the number of large single spots. Aspirin and its metabolites did not reduce the number of twin spots. The results of the present study suggest that SA, GA and GUA repair or replicate DNA-damage by MMC and SUA, GA, GUA and DHBA prevent DNA-damage by MMC. It is suggested that secondary cancer is prevented by aspirin post-treatment without losing the medicinal effectiveness (anti-tumor activity). Therefore, we consider there are effective doses and/or administration timing of aspirin and MMC to prevent secondary cancer. PMID:17275250

  18. The Best and the Brightest: Tidal Disruption Events Discovered by ASAS-SN

    NASA Astrophysics Data System (ADS)

    Warren-Son Holoien, Thomas; ASAS-SN

    2016-01-01

    Even today only human eyes scan the entire optical sky for the violent, variable, and transient events that shape our universe. The All-Sky Automated Survey for SuperNovae (ASAS-SN or "Assassin") is changing this by monitoring the visible sky to 17th magnitude every 2-3 days using multiple telescopes in the northern and southern hemispheres. Having been in operation for two years, ASAS-SN is discovering new transient objects daily, and while the primary goal of ASAS-SN is a complete survey of bright, nearby supernovae, ASAS-SN also discovers many other interesting nearby transients. Notably, ASAS-SN has discovered three bright tidal disruption events (TDEs), the three closest such events ever discovered at optical wavelengths, providing the opportunity to obtain detailed follow-up data at many wavelengths. ASAS-SN is discovering roughly 1 TDE for every 60 Type Ia supernovae, a rate that is significantly higher than other surveys. By virtue of their brightness, TDEs discovered by ASAS-SN can also be studied in unprecedented detail for many months, allowing deeper insight into their physics.

  19. The ASAS-SN Bright Supernova Catalog I: 2013-2014

    NASA Astrophysics Data System (ADS)

    Holoien, T. W.-S.; Stanek, K. Z.; Kochanek, C. S.; Shappee, B. J.; Prieto, J. L.; Brimacombe, J.; Bersier, D.; Bishop, D. W.; Dong, Subo; Brown, J. S.; Danilet, A. B.; Simonian, G. V.; Basu, U.; Beacom, J. F.; Falco, E.; Pojmanski, G.; Skowron, D. M.; Woźniak, P. R.; Ávila, C. G.; Conseil, E.; Contreras, C.; Cruz, I.; Fernández, J. M.; Koff, R. A.; Guo, Zhen; Herczeg, G. J.; Hissong, J.; Hsiao, E. Y.; Jose, J.; Kiyota, S.; Long, Feng; Monard, L. A. G.; Nicholls, B.; Nicolas, J.; Wiethoff, W. S.

    2016-09-01

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

  20. Aspirin-induced inhibition of adipogenesis was p53-dependent and associated with inactivation of pentose phosphate pathway.

    PubMed

    Su, Ying-Fang; Yang, Shih-Huang; Lee, Yu-Hsien; Wu, Buor-Chang; Huang, Shu-Ching; Liu, Chia-Ming; Chen, Shiow-Ling; Pan, Ya-Fang; Chou, Shih-Shen; Chou, Ming-Yung; Yang, Hui-Wen

    2014-09-01

    Obesity has become a major public health problem of global significance. Today, aspirin remains the most commonly used medication for the treatment of pyrexia, pain, inflammation and antiplatelet. The present study aims at evaluating the possible existence of a putative p53-dependent pathway underlying the aspirin-induced inhibition of adipogenesis. Cell migration assay was identified by the ability to migrate through Transwell insert. Oil Red O staining was employed to quantify adipose accumulation. The concentration of glucose and triglyceride were measured by using assay kits. The expression levels of several master regulatory molecules controlling various signal pathways were monitored using the immunoblotting techniques. Aspirin significantly inhibited preadipocyte migration and adipose accumulation. The p53-p21 signaling and the expression of differentiation marker glycerol-3-phosphate dehydrogenase were increased in a dose-dependent manner. It indicated that aspirin induced adipocyte differentiation through p53-p21 pathway. The oncogenic ERK 1/2 MAPK signaling was induced, whereas, the expression of adipogenic markers peroxisome proliferator-activated receptor γ (PPARγ), adipocyte fatty acid-binding protein (A-FABP) and inflammatory factors cyclooxygenase-2 (Cox-2), tumor necrosis factor α (TNFα) and inducible nitric oxide synthase (iNOS) were inhibited. Aspirin negatively regulated the pentose phosphate pathway (PPP) by inhibiting the expression of rate-limiting enzyme glucose-6-phosphate dehydrogenase. Knockdown the expression of oncogenic ERK 1/2 MAPK by using 10 μM PD98059 significantly increased triglyceride synthesis, adipose accumulation and activated PPP, however, decreased glucose uptake. Diverted the glucose flux to PPP, rather than increased glucose uptake, was associated with adipogenesis. Down-regulated the expression of tumor suppressor p53 by 10 μM pifithrin-α (PFTα) alone had no effect on adipose accumulation. However, administration

  1. 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.

  2. Validation of canopy bidirectional reflectance models with asas imagery of a spruce forest in Maine

    SciTech Connect

    Schaaf, C.B.; Li, X.; Strahler, A.H.

    1994-08-12

    Advanced Solid-state Array Spectroradiometer (ASAS) directional imagery of a spruce forest are used in an initial validation of the Li-Strahler geometric-optical model and the Li-Strahler hybrid geometric-optical radiative-transfer model. Although the magnitudes of the modeled principal plane bidirectional reflectances generally correspond to the ASAS measurements. the geometric-optical model results reproduce the trends of the ASAS reflectances more closely. Both models tend to overestimate the impact of mutual shadowing at large view zenith angles. reflectances.

  3. [Acetylsalicylic acid desensitization in the new era of percutaneous coronary intervention].

    PubMed

    Fuertes Ferre, Georgina; Ferrer Gracia, Maria Cruz; Calvo Cebollero, Isabel

    2015-09-21

    Dual antiplatelet therapy is essential in patients undergoing percutaneous coronary intervention with stent implantation. Hypersensitivity to acetylsalicylic acid (ASA) limits treatment options. Desensitization to ASA has classically been studied in patients with respiratory tract disease. Over the last years, many protocols have been described about ASA desensitization in patients with ischemic heart disease, including acute coronary syndrome and the need for coronary stent implantation. It is important to know the efficacy and safety of ASA desensitization in these patients. PMID:25577589

  4. [Acetylsalicylic acid desensitization in the new era of percutaneous coronary intervention].

    PubMed

    Fuertes Ferre, Georgina; Ferrer Gracia, Maria Cruz; Calvo Cebollero, Isabel

    2015-09-21

    Dual antiplatelet therapy is essential in patients undergoing percutaneous coronary intervention with stent implantation. Hypersensitivity to acetylsalicylic acid (ASA) limits treatment options. Desensitization to ASA has classically been studied in patients with respiratory tract disease. Over the last years, many protocols have been described about ASA desensitization in patients with ischemic heart disease, including acute coronary syndrome and the need for coronary stent implantation. It is important to know the efficacy and safety of ASA desensitization in these patients.

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

    PubMed

    Feldman, M; Cryer, B

    1999-08-15

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

  6. 1,2Aspirin-exacerbated respiratory disease involves a cysteinyl leukotriene-driven IL-33-mediated mast cell activation pathway

    PubMed Central

    Liu, Tao; Kanaoka, Yoshihide; Barrett, Nora A.; Feng, Chunli; Garofalo, Denise; Lai, Juying; Buchheit, Kathleen; Bhattacharya, Neil; Laidlaw, Tanya M.; Katz, Howard R.; Boyce, Joshua A.

    2015-01-01

    Aspirin exacerbated respiratory disease (AERD), a severe eosinophilic inflammatory disorder of the airways, involves overproduction of cysteinyl leukotrienes (cysLTs), activation of airway mast cells (MCs), and bronchoconstriction in response to nonselective cyclooxygenase inhibitors that deplete homeostatic prostaglandin (PG)E2. The mechanistic basis for MC activation in this disorder is unknown. We now demonstrate that patients with AERD have markedly increased epithelial expression of the alarmin-like cytokine IL-33 in nasal polyps, as compared to polyps from aspirin tolerant (AT) controls. The murine model of AERD, generated by dust mite priming of mice lacking microsomal PGE2 synthase (ptges−/− mice), shows a similar upregulation of IL-33 protein in the airway epithelium, along with marked eosinophilic bronchovascular inflammation. Deletion of LTC4 synthase (LTC4S), the terminal enzyme needed to generate cysLTs, eliminates the increased IL-33 content of the ptges−/− lungs and sharply reduces pulmonary eosinophilia and basal secretion of MC products. Challenges of dust mite-primed ptges−/− mice with lysine aspirin (Lys-ASA) induce IL-33-dependent MC activation and bronchoconstriction. Thus, IL-33 is a component of a cysLT-driven innate type 2 immune response that drives pathogenic MC activation and contributes substantially to AERD pathogenesis. PMID:26342029

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

    PubMed Central

    Hammond, E C; Garfinkel, L

    1975-01-01

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

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

    ERIC Educational Resources Information Center

    Morgan, Gareth

    2014-01-01

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

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

    PubMed

    Vela Vásquez, R S; Peláez Romero, R

    2015-11-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-07-28

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

  12. Association of aspirin dose and vorapaxar safety and efficacy in patients with non-ST-segment elevation acute coronary syndrome (from the TRACER Trial).

    PubMed

    Mahaffey, Kenneth W; Huang, Zhen; Wallentin, Lars; Storey, Robert F; Jennings, Lisa K; Tricoci, Pierluigi; White, Harvey D; Armstrong, Paul W; Aylward, Philip E; Moliterno, David J; Van de Werf, Frans; Chen, Edmond; Leonardi, Sergio; Rorick, Tyrus; Held, Claes; Strony, John; Harrington, Robert A

    2014-03-15

    Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial compared vorapaxar and placebo in 12,944 high-risk patients with non-ST-segment elevation acute coronary syndrome. We explored aspirin (ASA) use and its association with outcomes. Kaplan-Meier event rates were compared in groups defined by ASA dose (low, medium, and high). Landmark analyses with covariate adjustment were performed for 0 to 30, 31 to 180, and 181 to 365 days. Of 12,515 participants, 7,523, 1,049, and 3,943 participants were treated with low-, medium-, and high-dose ASA at baseline, respectively. Participants enrolled in North America versus elsewhere were more often treated with a high dose at baseline (66% vs 19%) and discharge (60% vs 3%). Unadjusted cardiovascular death, myocardial infarction, stroke, hospitalization for ischemia, or urgent revascularization event rates tended to be higher with higher baseline ASA (18.45% low, 19.13% medium, and 20.27% high; p for trend = 0.15573). Unadjusted and adjusted hazard ratios (95% confidence intervals) for effect of vorapaxar on cardiovascular (unadjusted p for interaction = 0.065; adjusted p for interaction = 0.140) and bleeding (unadjusted p for interaction = 0.915; adjusted p for interaction = 0.954) outcomes were similar across groups. Landmark analyses showed similar safety and efficacy outcomes with vorapaxar and placebo by ASA dose at each time point except for 0 to 30 days, when vorapaxar tended to be worse for efficacy (hazard ratio 1.13, 95% confidence interval 0.89 to 1.44, p for interaction = 0.0157). In conclusion, most TRACER participants were treated with low-dose ASA, although a high dose was common in North America. High-dose participants tended to have higher rates of ischemic and bleeding outcomes. Although formal statistical testing did not reveal heterogeneity in vorapaxar's effect across dose subgroups, consistent trends support use of low-dose ASA with other antiplatelet therapies

  13. ASASSN-16bh: A Very Bright CV Candidate Discovered By ASAS-SN

    NASA Astrophysics Data System (ADS)

    Simonian, G.; Stanek, K. Z.; Kochanek, C. S.; Brown, J. S.; Holoien, T. W.-S.; Godoy-Rivera, D.; Basu, U.; Shappee, B. J.; Prieto, J. L.; Bersier, D.; Dong, Subo; Chen, Ping; Brimacombe, J.

    2016-02-01

    During the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN or "Assassin"), using data from the quadruple 14-cm "Cassius" telescope in Cerro Tololo, Chile, we discovered a new transient source.

  14. Acceptance of the Theory of Evolution in America: Louis Agassiz vs. Asa Gray

    ERIC Educational Resources Information Center

    Wolfe, Elaine Claire Daughetee

    1975-01-01

    Provides some background information on the contributions of Louis Agassiz and Asa Gray to the history of American science as these two men disagreed concerning the ideas in Darwin's "The Orgin of Species." (PB)

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

    PubMed

    Kacprzak, Dorota; Pawliczak, Rafał

    2015-06-19

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

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

    PubMed

    Ganjehei, Leila; Becker, Richard C

    2015-11-01

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

  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. Predictors of thromboxane levels in patients with non-ST-elevation acute coronary syndromes on chronic aspirin therapy.

    PubMed

    Niccoli, Giampaolo; Giubilato, Simona; Leo, Andrea; Cosentino, Nicola; Fracassi, Francesco; Cataneo, Leonardo; Porto, Italo; Leone, Antonio Maria; Burzotta, Francesco; Trani, Carlo; Biasucci, Luigi Marzio; Narducci, Maria Lucia; Pulcinelli, Fabio Maria; Crea, Filippo

    2012-07-01

    High levels of thromboxane A2 (TxA2), a key mediator of platelet activation and aggregation, are associated with an increased risk of cardiovascular events. We aimed at assessing the predictors of higher plasma levels of TxB2, the stable metabolite of TxA2, in consecutive patients presenting with non-ST-elevation acute coronary syndrome (NSTE-ACS) on previous aspirin (ASA) treatment undergoing coronary angiography. Ninety-eight consecutive patients (age 61 ± 11, 75% males) with NSTE-ACS, on previous chronic ASA treatment, were prospectively enrolled in this study. Coronary disease extent was assessed by angiography according to the Bogaty score. In all patients, admission plasma levels of TxB2 (pg/ml) were measured by enzyme-linked immunosorbent assay, and patients showing TxB2 levels in the fourth quartile were compared to patients showing TxB2 levels in the lower quartiles. Multivariable logistic regression analysis showed that platelet count (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.02-1.63, p=0.04), multivessel coronary disease (OR 1.37, 95% CI 1.13-3.67, p=0.03), and coronary atherosclerosis extent index (OR 1.91, 95% CI 1.45-6.79, p=0.001) were independent predictors of TxB2 level upper quartile. Of note, C-reactive protein serum levels were similar in patients with TxB2 levels in the upper quartile as compared to those in the lower quartiles (p=0.49). In conclusion, NSTE-ACS patients with severe coronary atherosclerosis may have incomplete suppression of TxA2 production despite chronic ASA therapy. This finding suggests that additional efforts should be made to lower TxA2 levels in patients with widespread coronary artery disease. PMID:22535468

  19. Preventive effects of lansoprazole and famotidine on gastric mucosal injury induced by low-dose aspirin in Helicobacter pylori-negative healthy volunteers.

    PubMed

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

    2011-07-01

    The preventive effects of lansoprazole and famotidine on low-dose aspirin-induced gastric mucosal injury in relation to gastric acidity were compared in healthy Japanese volunteers. Fifteen Helicobacter pylori-negative volunteers with different CYP2C19 genotypes were randomly administered aspirin 100 mg, aspirin plus famotidine 20 mg twice daily, or aspirin plus lansoprazole 15 mg once daily for 7 days each in a crossover fashion. Gastroscopy for the evaluation of mucosal injury based on modified Lanza score (MLS) and 24-hour intragastric pH monitoring were performed on day 7 of each regimen. Aspirin induced gastric mucosal injury (median MLS = 3). Lansoprazole significantly decreased MLS to 0, which was significantly lower than that by famotidine (MLS = 1) (P < .05). Medians of pH 3 holding time and mean 24-hour pH values with the lansoprazole regimen were significantly higher than those with famotidine (P < .05). No significant differences in MLS were observed among the different CYP2C19 genotype groups in any of the treatment regimens. In this 7-day study, lansoprazole appeared to be more protective than famotidine against low-dose aspirin-induced mucosal injury but a larger well-controlled study is necessary to establish a definitive clinical benefit. PMID:20663999

  20. BOREAS RSS-2 Level-1B ASAS Image Data: At-Sensor Radiance in BSQ Format

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

    The BOREAS RSS-2 team used the ASAS instrument, mounted on the NASA C-130 aircraft, to create at-sensor radiance images of various sites as a function of spectral wavelength, view geometry (combinations of view zenith angle, view azimuth angle, solar zenith angle, and solar azimuth angle), and altitude. The level-1b ASAS images of the BOREAS study areas were collected from April to September 1994 and March to July 1996.

  1. Twice daily dosing of aspirin improves platelet inhibition in whole blood in patients with type 2 diabetes mellitus and micro- or macrovascular complications.

    PubMed

    Spectre, Galia; Arnetz, Lisa; Östenson, Claes-Göran; Brismar, Kerstin; Li, Nailin; Hjemdahl, Paul

    2011-09-01

    The efficacy of low-dose aspirin in type 2 diabetes mellitus (T2DM) has been questioned. We tested if twice daily dosing of aspirin would be more effective in T2DM, possibly due to increased platelet turnover. A randomised cross-over study compared 75 mg aspirin OD, 75 mg BID and 320 mg OD (≥ 2 week treatment periods) in 25 patients with T2DM and micro- or macrovascular complications. Platelet responses were examined by impedance aggregometry (WBA) and the IMPACT-R aspirin test in whole blood, light transmittance aggregometry in platelet-rich plasma (LTA), and urinary 11-dehydro-thromboxane B2 (TxM). Aspirin 75 mg BID decreased arachidonic acid (AA)-induced WBA compared to 75 mg OD (9.7 ± 4.5 vs. 12.6 ± 3.5 ohm; p = 0.003) or to 320 mg OD (11.5 ± 4.2 Ohms; p = 0.049). WBA responses to collagen were similarly attenuated by BID or high dosing (by 12-14%; p = 0.02 for both). The IMPACT-R showed a better response to 75 mg BID compared to 75 mg OD (p = 0.049), but not to 320 mg OD. AA-induced aggregation by LTA was <6.5% on all occasions, with no differences between aspirin dosages. TxM was reduced after 320 mg OD (p = 0.002), but not 75 mg BID (p = 0.07). Reticulated platelets were highly correlated with mean platelet volume (MPV; r2 = 0.74, p<0.0001). Both markers for platelet turnover were correlated with AA-induced WBA, but neither identified patients who benefited from BID dosing dependably. In conclusion, twice daily dosing improved laboratory responses to aspirin in high risk T2DM patients. Studies of whether BID dosing of aspirin can improve clinical outcomes in such patients are of interest. PMID:21800009

  2. A comparison of platelet function tests and thromboxane metabolites to evaluate aspirin response in healthy individuals and patients with coronary artery disease.

    PubMed

    Grove, Erik Lerkevang; Hvas, Anne-Mette; Johnsen, Helle Ladefoged; Hedegaard, Sofie Sommer; Pedersen, Susanne Bendesgaard; Mortensen, Jette; Kristensen, Steen Dalby

    2010-06-01

    Individualised antiplatelet therapy and platelet function testing have attracted considerable clinical interest, but several aspects of test performance have not been thoroughly evaluated. We investigated repeatability and concordance of light transmission aggregometry (LTA) induced with arachidonic acid (AA) 1.0 mM, PFA-100 induced with collagen/epinephrine, multiple electrode aggregometry (MEA) induced with AA 0.5 or 0.75 mM and VerifyNow Aspirin. Patients with stable coronary artery disease (n=43) and healthy individuals (n=21) were included. All tests were performed in duplicate at baseline in healthy individuals and in duplicate for four days in all study participants during aspirin treatment. Serum and urinary thromboxane metabolites were measured several times to evaluate cyclooxygenase-1 inhibition by aspirin. MEA was most sensitive for aspirin as treatment induced a 12-fold difference in AA-induced platelet aggregation. Coefficients of variation for duplicate measurements at baseline (0.4-12%), during aspirin treatment (3-46%) and for day-to-day variability (3-37%) differed markedly between tests and were lowest for VerifyNow. The prevalence of aspirin low-responsiveness also differed between tests (0-9%) and the agreement was low: kappaAspirin (r=0.41, p=0.001). Overall, repeatability was moderate and the correlation between tests was low. VerifyNow Aspirin proved most reproducible, and this was the only assay showing a significant positive correlation with serum thromboxane. This study demonstrated that conclusions based on platelet function testing strongly depend on the assay used. PMID:20352155

  3. Comparison of Three Aspirin Formulations in Human Volunteers

    PubMed Central

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

    2011-01-01

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

  4. 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…

  5. Do NSAIDs and ASA Cause More Upper Gastrointestinal Bleeding in Elderly than Adults?

    PubMed Central

    Kocoglu, Hakan; Oguz, Basak; Dogan, Hakan; Okuturlar, Yildiz; Hursitoglu, Mehmet; Harmankaya, Ozlem; Altuntas, Yuksel; Kumbasar, Abdulbaki

    2016-01-01

    Purpose. NSAIDs and ASA may cause upper gastrointestinal bleeding (UGIB) both in adults and in elderly. There is no study that compares this increased bleeding risk between adult and elderly subjects. Methods. A total of 524 patients with UGIB were included in this study. The data of patients were, respectively, analyzed. Results. NSAIDs and ASA-associated UGIB rates were similar between <65 years (345 patients) (group 1) and ≥65 years (179 patients) (group 2) (28.4% versus 23.5%, p = 0.225 and 13% versus 19%, p = 0.071, resp.). Warfarin-associated UGIB was found significantly higher in group 2 than group 1. Elderly patients with NSAID-associated UGIB had significantly higher length of stay (LoS) and CoH than adult patients with NSAID-associated UGIB (p = 0.002 and 0.001, resp.). Elderly patients with ASA-associated UGIB had significantly higher CoH than adult patients with NSAID-associated UGIB. Conclusions. Using NSAIDs without gastroprotective drugs or using ASA with gastroprotective drugs in elderly patients is as safe as in adult patients. Not only should adding gastroprotective drugs to ASA or NSAID be based on their risk of UGIB, but the cost of hospitalization of ASA or NSAID-associated UGIB should be considered. PMID:26880898

  6. ASA grade and disease-free mortality in head and neck cancer patients: a prospective study.

    PubMed

    Kanatas, Anastasios; Gorton, Heather; Smith, Adam B; Mannion, Christopher; Ong, Thian K; Mitchell, David

    2010-12-01

    Complex surgery with curative intent as part of the care of patients with head and neck cancer, who also have serious coexisting conditions is sometimes viewed critically as being unduly, optimistic. We have used American Society of Anesthesiologists' (ASA) grading by a single anaesthetist prospectively as a baseline to investigate a possible link between coexisiting conditions and disease-free survival in 114 patients with head and neck cancer patients treated by the same anaesthetist and surgical team, and found that the ASA grade is not a reliable predictor of disease-free survival. There was no significant association between ASA grade and overall mortality, but there was a significant association between ASA grade and mortality associated with metastatic disease. However, the test for trend was not significant, which suggested that deaths from metastatic disease did not increase in line with ASA grading. All patients in ASA grades II and III were alive 2 years after their initial operation and the risk of mortality after 2 years may increase by up to 10%.

  7. The mosaic architecture of Aeromonas salmonicida subsp. salmonicida pAsa4 plasmid and its consequences on antibiotic resistance

    PubMed Central

    Tanaka, Katherine H.; Vincent, Antony T.; Trudel, Mélanie V.; Paquet, Valérie E.; Frenette, Michel

    2016-01-01

    Aeromonas salmonicida subsp. salmonicida, the causative agent of furunculosis in salmonids, is an issue especially because many isolates of this bacterium display antibiotic resistances, which limit treatments against the disease. Recent results suggested the possible existence of alternative forms of pAsa4, a large plasmid found in A. salmonicida subsp. salmonicida and bearing multiple antibiotic resistance genes. The present study reveals the existence of two newly detected pAsa4 variants, pAsa4b and pAsa4c. We present the extensive characterization of the genomic architecture, the mobile genetic elements and the antimicrobial resistance genes of these plasmids in addition to the reference pAsa4 from the strain A449. The analysis showed differences between the three architectures with consequences on the content of resistance genes. The genomic plasticity of the three pAsa4 variants could be partially explained by the action of mobile genetic elements like insertion sequences. Eight additional isolates from Canada and Europe that bore similar antibiotic resistance patterns as pAsa4-bearing strains were genotyped and specific pAsa4 variants could be attributed to phenotypic profiles. pAsa4 and pAsa4c were found in Europe, while pAsa4b was found in Canada. In accordance with their content in conjugative transfer genes, only pAsa4b and pAsa4c can be transferred by conjugation in Escherichia coli. The plasticity of pAsa4 variants related to the acquisition of antibiotic resistance indicates that these plasmids may pose a threat in terms of the dissemination of antimicrobial-resistant A. salmonicida subsp. salmonicida bacteria. PMID:27812409

  8. Long-distance transport of L-ascorbic acid in potato

    PubMed Central

    Tedone, Luigi; Hancock, Robert D; Alberino, Salvatore; Haupt, Sophie; Viola, Roberto

    2004-01-01

    Background Following on from recent advances in plant AsA biosynthesis there is increasing interest in elucidating the factors contributing to the L-ascorbic acid (AsA) content of edible crops. One main objective is to establish whether in sink organs such as fruits and tubers, AsA is synthesised in situ from imported photoassimilates or synthesised in source tissues and translocated via the phloem. In the current work we test the hypothesis that long-distance transport is involved in AsA accumulation within the potato tuber, the most significant source of AsA in the European diet. Results Using the EDTA exudation technique we confirm the presence of AsA in the phloem of potato plants and demonstrate a correlation between changes in the AsA content of source leaves and that of phloem exudates. Comparison of carboxyflourescein and AgNO3 staining is suggestive of symplastic unloading of AsA in developing tubers. This hypothesis was further supported by the changes in AsA distribution during tuber development which closely resembled those of imported photoassimilates. Manipulation of leaf AsA content by supply of precursors to source leaves resulted in increased AsA content of developing tubers. Conclusion Our data provide strong support to the hypothesis that long-distance transport of AsA occurs in potato. We also show that phloem AsA content and AsA accumulation in sink organs can be directly increased via manipulation of AsA content in the foliage. We are now attempting to establish the quantitative contribution of imported AsA to overall AsA accumulation in developing potato tubers via transgenic approaches. PMID:15377389

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

    PubMed

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

    2007-01-01

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

  10. Aspirin-mediated acetylation induces structural alteration and aggregation of bovine pancreatic insulin.

    PubMed

    Yousefi, Reza; Taheri, Behnaz; Alavi, Parnian; Shahsavani, Mohammad Bagher; Asadi, Zahra; Ghahramani, Maryam; Niazi, Ali; Alavianmehr, Mohammad Mehdi; Moosavi-Movahedi, Ali Akbar

    2016-01-01

    The simple aggregation of insulin under various chemical and physical stresses is still an important challenge for both pharmaceutical production and clinical formulation. In the storage form, this protein is subjected to various chemical modifications which alter its physicochemical and aggregation properties. Aspirin (acetylsalicylic acid) which is the most widely used medicine worldwide has been indicated to acetylate a large number of proteins both in vitro and in vivo. In this study, as insulin treated with aspirin at 37°C, a significant level of acetylation was observed by flourescamine and o-phthalaldehyde assay. Also, different spectroscopic techniques, gel electrophoresis, and microscopic assessment were applied to compare the structural variation and aggregation/fibrillation propensity among acetylated and non-acetylated insulin samples. The results of spectroscopic assessments elucidate that acetylation induces insulin unfolding which is accompanied with the exposure of protein hydrophobic patches, a transition from alpha-helix to beta-sheet and increased propensity of the protein for aggregation. The kinetic studies propose that acetylation increases aggregation rate of insulin under both thermal and chemical stresses. Also, gel electrophoresis and dynamic light scattering experiments suggest that acetylation induces insulin oligomerization. Additionally, the results of Thioflavin T fluorescence study, Congo red absorption assessment, and microscopic analysis suggest that acetylation with aspirin enhances the process of insulin fibrillation. Overall, the increased susceptibility of acetylated insulin for aggregation may reflect the fact that this type of modification has significant structural destabilizing effect which finally makes the protein more vulnerable for pathogenic aggregation/fibrillation.

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

    NASA Astrophysics Data System (ADS)

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

    2011-06-01

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

  12. Impairment of aminopyrine clearance in aspirin-damaged canine gastric mucosa

    SciTech Connect

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

    1983-09-01

    Using an in vivo canine chambered stomach preparation, the clearance of (/sup 14/C)aminopyrine across mucosa when intravenously infused and the back-diffusion of this substance from gastric lumen to mucosa when topically applied to gastric epithelium were evaluated in aspirin-damaged gastric epithelium. In mucosa damaged by either 20 mM or 40 mM aspirin, the recovery of (/sup 14/C)aminopyrine, when topically mixed with acid (pH . 1.1) perfusate solution, was not significantly different from nondamaged control mucosa. In addition, the degree of ''trapping'' of this substance from back-diffusion was not different in damaged mucosa from that observed in nondamaged epithelium. In contrast, when (/sup 14/C)aminopyrine was intravenously infused, its clearance was significantly impaired in aspirin-damaged mucosa when compared with control studies, as evidenced by the increased ''trapping'' of this substance in injured epithelium. These findings indicate that movement of aminopyrine from plasma to gastric lumen is impaired in damaged epithelium, making the aminopyrine clearance technique an unreliable method to accurately measure absolute gastric blood flow in this experimental setting.

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

    PubMed

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

    2016-05-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  16. Individual dosing of ASA prophylaxis by controlling platelet aggregation.

    PubMed

    Syrbe, G; Redlich, H; Weidlich, B; Ludwig, J; Kopitzsch, S; Göckefitz, A; Herzog, T

    2001-07-01

    Acetylsalicylic acid is widely used in the primary and secondary prevention of cardiovascular diseases. In the current study, we used platelet aggregation ex vivo in platelet-rich plasma induced with arachidonic acid as a routine method for the determination of the individual dose of acetylsalicylic acid necessary to inhibit platelet aggregation in 108 patients with cardiovascular diseases. In 40% of all patients studied, a dose of 30 mg/day was sufficient to block the arachidonic acid-induced platelet aggregation nearly completely. In 50% of all patients, a dose of 100 mg/day was necessary. In 10% of all patients, the dose had to be further increased to 300 mg/day or even to 500 mg/day to inhibit platelet aggregation nearly completely. These results demonstrate that platelet aggregation can be used as a simple routine laboratory method to control acetylsalicylic acid treatment in patients with cardiovascular diseases and to determine individual doses of acetylsalicylic acid for a nearly complete inhibition of platelet aggregation. With a standard dose of 100 mg/day, 10% of the patients were nonresponders. PMID:11441981

  17. Association analysis of formyl peptide receptor 2 (FPR2) polymorphisms and aspirin exacerbated respiratory diseases.

    PubMed

    Kim, Hee-Jeong; Cho, Sung-Hwan; Park, Jong-Sook; Lee, Tae-Hyeong; Lee, Eun-Ju; Kim, Yong-Hoon; Uh, Soo-Taek; Chung, Il Yup; Kim, Mi-Kyeong; Choi, Inseon S; Park, Byung-Lae; Shin, Hyoung-Doo; Park, Choon-Sik

    2012-04-01

    Aspirin-exacerbated respiratory diseases (AERD) are associated with the metabolism of arachidonic acid. FPR2 (formyl peptide receptor2) is a high-affinity ligand receptor for potent anti-inflammatory lipid metabolites: lipoxins. Thus, functional alterations of the FPR2 may contribute to AERD. We investigated the relationship between single-nucleotide polymorphisms (SNPs) in the FPR2 and AERD. Asthmatics were categorized into AERD <15% decreases in forced expiratory volume in one second (FEV(1)), and/or naso-ocular reactions after oral aspirin challenge (n=170) and aspirin-tolerant asthma (ATA, n=268). In all, 11 SNPs were genotyped. FPR2 protein expressions on CD14-positive monocytes in peripheral blood were measured using flow cytometric analysis. We performed RT-PCR of the FPR2 mRNA expressed by peripheral blood mononuclear cells. Logistic regression analysis showed that the minor allele frequency of FPR2 -4209T>G (rs1769490) in intron 2 was significantly lower in the AERD group (n=170) than in the ATA group (n=268) (P=0.006, P(corr)=0.04, recessive model). The decline of FEV(1) after aspirin challenge was significantly lower in the subjects with GG homozygotes of FPR2 -4209T>G than those with the other genotypes (P=0.0002). Asthmatic homozygotes for FPR2 -4209T>G minor allele exhibited significantly higher FPR2 protein expression in CD14-positive monocytes than did those with the common allele of FPR2 -4209T>G allele (P=0.01). There was no difference in the expression of the wild form and the exon 2 deleted variant form of FPR2 gene according to the genotypes of FPR2 -4209T>G. The minor allele at FPR2 -4209T>G may have a protective role against the development of AERD, via increase of FPR2 protein expression in inflammatory cells. PMID:22377711

  18. Effects of L-glutamine on acetylsalycylic acid induced gastric lesions and acid back diffusion in dogs.

    PubMed

    Hung, C R; Takeuchi, K; Okabe, S; Murata, T; Takagi, K

    1976-12-01

    Effects of L-glutamine on acetylsalicylic acid (ASA)-induced gastric mucosal lesions were studied in mongrel dogs. It was confirmed that when oral ASA at 1.0 or 2.0 g per dog is given in two divided doses, there is severe and consistent dose-dependent mucosal damage in the glandular portion of the stomach in fasted dogs. However, when L-glutamine 2.0 or 4.0 g per dog in two divided doses is given concomitantly with ASA 2.0 g per dog orally, the gastric irritation is significantly inhibited. Instillation of 20 mM of ASA in 100 mM HCl solution into the Heidenhain pouch of Beagle dogs produced a significant loss of H+ from the pouch and a gain of Na+ in the lumen compared with ASA-free controls. When L-glutamine (100 mM) was given concomitantly with ASA (20 mM) into the pouch, changes of electrolyte fluxes in response to ASA alone were significantly suppressed. However, 50 mM of L-glutamine had no appreciable effect on acid back diffusion caused by ASA 20 mM. The amino acid itself had little effect on the ionic movement in the pouch. Gross bleeding from the pouch treated with ASA was never observed with the concomitant dosing of ASA and L-glutamine 50 or 100 mM. PMID:15154

  19. 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

  20. 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.

  1. Effect of Tamarindus indica L. on the bioavailability of aspirin in healthy human volunteers.

    PubMed

    Mustapha, A; Yakasai, I A; Aguye, I A

    1996-01-01

    The influence of Tamarindus indica L. fruit extract incorporated in a traditional meal on the bioavailability of aspirin tablets 600 mg dose was studied in 6 healthy volunteers. There was a statistically significant increase in the plasma levels of aspirin and salicylic acid, respectively, when the meal containing Tamarindus indica fruit extract was administered with the aspirin tablets than when taken under fasting state or with the meal without the fruit extract. The Cmax, AUC0-6h and t1/2 for aspirin increased from 10.04 +/- 0.1 mg/ml to 28.62 +/- 0.21 mg/ml (P < 0.05); 14.03 +/- 0.11 mg/ml.h to 86.51 +/- 0.21 mg/ml.h (P < 0.085) and 1.04 +/- 0.12 h to 1.50 +/- 0.44 h (P < 0.05) respectively. There was no change in the tmax (0.50 +/- 0.17 h) but there was a decrease in the kel from 0.633 +/- 0.22 to 0.463 +/- 0.29 (P < 0.05). Similarly, the Cmax, AUC0-6h and kel for salicylic acid rose from 43.84 +/- 0.21 mg/ml to 68.19 +/- 0.71 mg/ml (P < 0.05); 171.59 +/- 0.07 mg/ml.h to 266.22 +/- 0.21 mg/ml/.h (P < 0.05) and 7.37 +/- 0.29 to 19.30 +/- 0.21 (P < 0.05), respectively. The tmax decreased from 2.0 +/- 0.18 h to 1.0 +/- 0.08 h (P < 0.05) and t1/2 from 0.25 +/- 0.21 h to 0.184 +/- 0.11 h (P < 0.05). The study has indicated that Tamarindus indica L. fruit extract significantly increased the bioavailability of aspirin.

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

    PubMed

    Salah Khalil, Mahmoud

    2015-07-01

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

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

    PubMed

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

    1987-01-01

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

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

    SciTech Connect

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

    2012-03-16

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

  5. Reduced mucosal side-effects of acetylsalicylic acid after conjugation with tris-hydroxymethyl-aminomethane. Synthesis and biological evaluation of a new anti-inflammatory compound.

    PubMed

    Varga, Gabriella; Lajkó, Norbert; Ugocsai, Melinda; Érces, Dániel; Horváth, Gyöngyi; Tóth, Gábor; Boros, Mihály; Ghyczy, Miklós

    2016-06-15

    Acetylsalicylic acid (ASA) causes adverse haemorrhagic reactions in the upper gastrointestinal (GI) tract, and previous results have suggested that combination therapy with 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) could provide protection in this scenario. Based on this hypothesis, our aim was to develop a new compound from ASA and Tris precursors and to characterize the biological effects of ASA-Tris and the derivatives ASA-bis- and mono-hydroxymethyl-aminomethane (ASA-Bis, ASA-Mono, respectively) using in vivo and in vitro test systems. ASA or ASA conjugates (0.55mmol/kg, each) were administered intragastrically to Sprague-Dawley rats. Changes in the mucosal structure and in the serosal microcirculation were detected by in vivo imaging techniques, the plasma TNF-alpha, tissue xanthine oxidoreductase and myeloperoxidase activities, and liver cytochrome c changes were also determined. In two separate series, platelet aggregation and carrageenan arthritis-induced inflammatory pain were measured in control, ASA and ASA-Tris-treated groups. Severe mucosal injury and a significant decrease in serosal red blood cell velocity developed in the ASA-treated group and an ~2-fold elevation in proinflammatory mediator levels evolved. ASA-Tris did not cause bleeding, microcirculatory dysfunction, mucosal injury or an elevation in proinflammatory markers. The ASA-Mono and ASA-Bis conjugates did not cause macroscopic bleeding, but the inflammatory activation was apparent. ASA-Tris did not influence the cyclooxygenase-induced platelet aggregation significantly, but the inflammatory pain was reduced as effectively as in the case of equimolar ASA doses. ASA-Tris conjugation is an effective approach through which the GI side-effects of ASA are controlled by decreasing the cytokine-mediated progression of pro-inflammatory events.

  6. Reduced mucosal side-effects of acetylsalicylic acid after conjugation with tris-hydroxymethyl-aminomethane. Synthesis and biological evaluation of a new anti-inflammatory compound.

    PubMed

    Varga, Gabriella; Lajkó, Norbert; Ugocsai, Melinda; Érces, Dániel; Horváth, Gyöngyi; Tóth, Gábor; Boros, Mihály; Ghyczy, Miklós

    2016-06-15

    Acetylsalicylic acid (ASA) causes adverse haemorrhagic reactions in the upper gastrointestinal (GI) tract, and previous results have suggested that combination therapy with 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) could provide protection in this scenario. Based on this hypothesis, our aim was to develop a new compound from ASA and Tris precursors and to characterize the biological effects of ASA-Tris and the derivatives ASA-bis- and mono-hydroxymethyl-aminomethane (ASA-Bis, ASA-Mono, respectively) using in vivo and in vitro test systems. ASA or ASA conjugates (0.55mmol/kg, each) were administered intragastrically to Sprague-Dawley rats. Changes in the mucosal structure and in the serosal microcirculation were detected by in vivo imaging techniques, the plasma TNF-alpha, tissue xanthine oxidoreductase and myeloperoxidase activities, and liver cytochrome c changes were also determined. In two separate series, platelet aggregation and carrageenan arthritis-induced inflammatory pain were measured in control, ASA and ASA-Tris-treated groups. Severe mucosal injury and a significant decrease in serosal red blood cell velocity developed in the ASA-treated group and an ~2-fold elevation in proinflammatory mediator levels evolved. ASA-Tris did not cause bleeding, microcirculatory dysfunction, mucosal injury or an elevation in proinflammatory markers. The ASA-Mono and ASA-Bis conjugates did not cause macroscopic bleeding, but the inflammatory activation was apparent. ASA-Tris did not influence the cyclooxygenase-induced platelet aggregation significantly, but the inflammatory pain was reduced as effectively as in the case of equimolar ASA doses. ASA-Tris conjugation is an effective approach through which the GI side-effects of ASA are controlled by decreasing the cytokine-mediated progression of pro-inflammatory events. PMID:27079640

  7. 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

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

    PubMed

    Kraus, Sarah; Sion, Daniel; Arber, Nadir

    2015-01-01

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

  9. 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

  10. All Source Analysis System (ASAS): Migration from VAX to Alpha AXP computer systems

    NASA Technical Reports Server (NTRS)

    Sjoholm-Sierchio, Michael J.; Friedman, Steven Z. (Editor)

    1994-01-01

    The Jet Propulsion Laboratory's (JPL's) experience migrating existing VAX applications to Digital Equipment Corporation's new Alpha AXP processor is covered. The rapid development approach used during the 10-month period required to migrate the All Source Analysis System (ASAS), 1.5 million lines of FORTRAN, C, and Ada code, is also covered. ASAS, an automated tactical intelligence system, was developed by the Jet Propulsion Laboratory for the U. S. Army. Other benefits achieved as a result of the significant performance improvements provided by Alpha AXP platform are also described.

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2001-02-15

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

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

    PubMed

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

    2015-08-01

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

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

    MedlinePlus

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

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

    PubMed

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

    2012-08-01

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

  16. 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

  17. Simultaneous Determination of Atorvastatin and Aspirin in Human Plasma by LC-MS/MS: Its Pharmacokinetic Application.

    PubMed

    Gajula, Ramakrishna; Pilli, Nageswara Rao; Ravi, Vasu Babu; Maddela, Rambabu; Inamadugu, Jaswanth Kumar; Polagani, Srinivasa Rao; Busa, Sobha

    2012-12-01

    A simple, rapid, and sensitive liquid chromatography tandem mass spectro-metric (LC-MS/MS) assay method has been developed and fully validated for the simultaneous quantification of atorvastatin and aspirin in human plasma using a polarity switch. Proguanil and furosemide were used as the internal standards for the quantification of atorvastatin and aspirin, respectively. The analytes were extracted from human plasma by the liquid-liquid extraction technique using methyl tert-butyl ether. The reconstituted samples were chromatographed on a Zorbax XDB Phenyl column by using a mixture of 0.2% acetic acid buffer, methanol, and acetonitrile (20:16:64, v/v) as the mobile phase at a flow rate of 0.8 mL/min. Prior to detection, atorvastatin and aspirin were ionized using an ESI source in the multiple reaction monitoring (MRM) mode. The ions were monitored at the positive m/z 559.2→440.0 transition for atorvastatin and the negative m/z 179.0→136.6 transition for aspirin. The calibration curve obtained was linear (r(2) ≥ 0.99) over the concentration range of 0.20-151 ng/mL for atorvastatin and 15.0-3000 ng/mL for aspirin. The method validation was performed as per FDA guidelines and the results met the acceptance criteria. A run time of 3.0 min for each sample made it possible to analyze more than 300 human plasma samples per day. The proposed method was found to be applicable to clinical studies.

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

    PubMed Central

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

    2012-01-01

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

  19. Comparison between urinary 11-dehydrothromboxane B2 detection and platelet Light Transmission Aggregometry (LTA) assays for evaluating aspirin response in elderly patients with coronary artery disease.

    PubMed

    Liu, Tengfei; Zhang, Jingwei; Chen, Xiahuan; Feng, Xueru; Fu, Sidney W; McCaffrey, Timothy A; Liu, Meilin

    2015-10-15

    Aspirin is widely used in the primary and secondary prevention of cardiovascular diseases. The aim of our study was to compare between two established methods of aspirin response, urinary 11-dehydrothromboxane B2 (11dhTXB2) and platelet Light Transmission Aggregometry (LTA) assays in elderly Chinese patients with coronary artery disease (CAD), and to investigate the clinical significance of both methods in predicting cardiovascular events. Urinary 11dhTxB2 assay and arachidonic acid-induced (AA, 0.5mg/ml) platelet aggregation by Light Transmission Aggregometry (LTAAA) assay were measured to evaluate aspirin responses. High-on aspirin platelet reactivity (HAPR) was defined as urinary 11dhTxB2>1500pg/mg or AA-induced platelet aggregation≥15.22%-the upper quartile of our enrolled population. The two tests showed a poor correlation for aspirin inhibition (r=0.063) and a poor agreement in classifying HAPR (kappa=0.053). With a mean follow-up time of 12months, cardiovascular events occurred more frequently in HAPR patients who were diagnosed by LTA assay as compared with no-HAPR patients (22.5% versus 10.6%, P=0.039, OR=2.45, 95% CI=1.06-5.63). However, the HAPR status, as determined by urinary 11dTXB2 measurement, did not show a significant correlation with outcomes. PMID:26095809

  20. Comparison between urinary 11-dehydrothromboxane B2 detection and platelet Light Transmission Aggregometry (LTA) assays for evaluating aspirin response in elderly patients with coronary artery disease.

    PubMed

    Liu, Tengfei; Zhang, Jingwei; Chen, Xiahuan; Feng, Xueru; Fu, Sidney W; McCaffrey, Timothy A; Liu, Meilin

    2015-10-15

    Aspirin is widely used in the primary and secondary prevention of cardiovascular diseases. The aim of our study was to compare between two established methods of aspirin response, urinary 11-dehydrothromboxane B2 (11dhTXB2) and platelet Light Transmission Aggregometry (LTA) assays in elderly Chinese patients with coronary artery disease (CAD), and to investigate the clinical significance of both methods in predicting cardiovascular events. Urinary 11dhTxB2 assay and arachidonic acid-induced (AA, 0.5mg/ml) platelet aggregation by Light Transmission Aggregometry (LTAAA) assay were measured to evaluate aspirin responses. High-on aspirin platelet reactivity (HAPR) was defined as urinary 11dhTxB2>1500pg/mg or AA-induced platelet aggregation≥15.22%-the upper quartile of our enrolled population. The two tests showed a poor correlation for aspirin inhibition (r=0.063) and a poor agreement in classifying HAPR (kappa=0.053). With a mean follow-up time of 12months, cardiovascular events occurred more frequently in HAPR patients who were diagnosed by LTA assay as compared with no-HAPR patients (22.5% versus 10.6%, P=0.039, OR=2.45, 95% CI=1.06-5.63). However, the HAPR status, as determined by urinary 11dTXB2 measurement, did not show a significant correlation with outcomes.

  1. Stereocontrolled total synthesis of the potent anti-inflammatory and pro-resolving lipid mediator resolvin D3 and its aspirin-triggered 17R-epimer.

    PubMed

    Winkler, Jeremy W; Uddin, Jasim; Serhan, Charles N; Petasis, Nicos A

    2013-04-01

    The first total synthesis of stereochemically pure resolvin D3 and aspirin-triggered resolvin D3 is reported. These enzymatic metabolites of docosahexaenoic acid (DHA) have potent anti-inflammatory and pro-resolving actions. The convergent synthetic strategy is based on enantiomerically pure starting materials, and it is highly stereocontrolled. PMID:23510485

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

    PubMed

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

    1989-08-01

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

  3. The in vitro effect of aspirin on increased whole blood platelet aggregation in oral contraceptive users.

    PubMed

    Norris, L A; Bonnar, J

    1994-05-01

    The effects of triphasic oral contraceptives on whole blood platelet aggregation in 36 Italian women are reported here. Aspirin's effects on platelet aggregation were also studied. 18 women took a triphasic oral contraceptive; 10 women took Trinordiol, while 8 took Trinovum for at least 90 days. The remaining 18 women took nothing and served as controls. The study was aligned with each woman's birth control pill cycle. Blood was taken daily on days 15-21 of their cycle. Either saline solution or acetylsalicylic acid was added to the blood samples and compared. All data was statistically analyzed using unpaired student's t-test. Effects of 3 aggregating agents, ADP, PAF, and EDTA, on platelet aggregation were studied. Arachidonic acid and adrenalin bitartrate were also studied in this manner. An increase in platelet aggregation was observed in women taking oral contraceptives. No difference was found between patients taking Trinordiol and those taking Trinovum. The results of this study indicate an increase in whole blood platelet sensitivity to collagen, adrenalin, and arachidonic acid when using oral contraceptives. Aspirin, at low doses, may have a role in preventing early thrombus formation in women taking oral contraceptives. PMID:8042198

  4. Terbium-macrocycle complexes as chemical sensors: detection of an aspirin metabolite in urine using a salicylurate-specific receptor site.

    PubMed

    Esplin, Taran L; Cable, Morgan L; Gray, Harry B; Ponce, Adrian

    2010-05-17

    Salicylurate (SU) is the major metabolite in urine of acetylsalicylic acid (aspirin) and can be used as a metric to monitor aspirin pharmacokinetics and as an indicator of appendicitis, anemia, and liver disease. Detection in urine and plasma currently requires solvent extraction or other sample handling prior to analysis. We present a simple method to quantify SU in urine via chelation to a terbium binary complex with the macrocycle 1,4,7,10-tetraazacyclododecane-1,7-bisacetate (DO2A). Binding of SU to form the [Tb(DO2A)(SU)](-) ternary complex triggers intense luminescence under UV excitation due to an absorbance-energy transfer-emission mechanism. Here we report characterization of the [Tb(DO2A)(SU)](-) ternary complex and application of this sensitized lanthanide luminescence method to quantify SU in urine samples following a low-dose aspirin regimen.

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

    PubMed

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

    1994-04-01

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

  6. Making a Theist out of Darwin: Asa Gray's Post-Darwinian Natural Theology

    ERIC Educational Resources Information Center

    Hunter, T. Russell

    2012-01-01

    In March of 1860 the eminent Harvard Botanist and orthodox Christian Asa Gray began promoting the Origin of Species in hopes of securing a fair examination of Darwin's evolutionary theory among theistic naturalists. To this end, Gray sought to demonstrate that Darwin had not written atheistically and that his theory of evolution by natural…

  7. ASAS-SN Discovery of A Likely Galactic Nova ASASSN-16ma on the Rise

    NASA Astrophysics Data System (ADS)

    Stanek, K. Z.; Kochanek, C. S.; Brown, J. S.; Holoien, T. W.-S.; Shields, J.; Shappee, B. J.; Prieto, J. L.; Bersier, D.; Dong, Subo; Bose, S.; Chen, Ping; Chomiuk, L.; Strader, J.; Brimacombe, J.

    2016-10-01

    During the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN or "Assassin"), using data from the quadruple 14-cm "Cassius" telescope in CTIO, Chile, we detect a new transient source, most likely a classical nova, near the Galactic center Object RA (J2000) DEC (J2000) Gal l (deg) Gal b (deg) Disc.

  8. ASASSN-16bl and ASASSN-16bm: ASAS-SN Discovery of Two Probable Supernovae

    NASA Astrophysics Data System (ADS)

    Brimacombe, J.; Kiyota, S.; Brown, J. S.; Holoien, T. W.-S.; Stanek, K. Z.; Kochanek, C. S.; Godoy-Rivera, D.; Basu, U.; Shappee, B. J.; Prieto, J. L.; Bersier, D.; Dong, Subo; Chen, Ping; Bock, G.; Cruz, I.; Fernandez, J. M.

    2016-02-01

    During the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN or "Assassin"), using data from the quadruple 14-cm "Cassius" telescope in Cerro Tololo, Chile, we discovered two new transient sources, most likely supernovae, in the galaxies 2MASX J11422674-3654256 and GALEXASC J115155.68-132459.3.

  9. ASAS-SN Discovery of A Likely Galactic Nova ASASSN-16kd

    NASA Astrophysics Data System (ADS)

    Stanek, K. Z.; Kochanek, C. S.; Brown, J. S.; Holoien, T. W.-S.; Shields, J.; Shappee, G. Simonian B. J.; Prieto, J. L.; Bersier, D.; Dong, Subo; Bose, S.; Chen, Ping; Chomiuk, L.; Strader, J.; Brimacombe, J.

    2016-09-01

    During the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN or "Assassin"), using data from the quadruple 14-cm "Cassius" telescope in Cerro Tololo, Chile, we detect a new transient source, most likely a classical nova, near the Galactic center.

  10. Per Aa Asa Hilliard: The Great House of Black Light for Educational Excellence

    ERIC Educational Resources Information Center

    Nobles, Wade W.

    2008-01-01

    This interpretive review draws on a number of Asa G. Hilliard's Kemetic (ancient Egyptian) writings to examine his conception of educational excellence in ancient Kemet and for African American education today. The review offers an interpretation of Hilliard's lifelong quest for excellence in education, which is especially revealed in his analysis…

  11. Spectroscopic classification of Gaia, ASAS-SN and TOCP transients with the WHT+ISIS

    NASA Astrophysics Data System (ADS)

    Campbell, H.; Wevers, T.; Fraser, M.; Jonker, P. G.; Wyrzykowski, L.; Hodgkin, S.; Blagorodnova, N.

    2015-06-01

    We report spectroscopic confirmation and classifications for reported Gaia Photometric Science Alerts (http://gaia.ac.uk/selected-gaia-science-alerts), together with targets from the All-Sky Automated Survey for Supernovae (ASAS-SN; Shappee et al. 2014) and the TOCP list.

  12. ASAS-SN Discovery of A Likely, Heavily-Obscured Galactic Nova ASASSN-16ig

    NASA Astrophysics Data System (ADS)

    Stanek, K. Z.; Kiyota, S.; Kochanek, C. S.; Brown, J. S.; Holoien, T. W.-S.; Shields, J.; Shappee, G. Simonian B. J.; Prieto, J. L.; Bersier, D.; Dong, Subo; Bose, S.; Chen, Ping; Chomiuk, L.; Strader, J.; Brimacombe, J.

    2016-08-01

    During the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN or "Assassin"), using data from the quadruple 14-cm "Cassius" telescope in CTIO, Chile, we detect a new transient source, most likely a classical nova, near the Galactic center.

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

    PubMed Central

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

    2015-01-01

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

  14. Acetylsalicylic acid protects erectile function in diabetic rats.

    PubMed

    Hafez, G; Gonulalan, U; Kosan, M; Arioglu, E; Ozturk, B; Cetinkaya, M; Gur, S

    2014-01-01

    We aimed to evaluate the effect of acetylsalicylic acid (ASA) treatment on diabetes-induced erectile dysfunction. Adult male Sprague-Dawley rats were divided into four groups as follows: (i) control (C), (ii) diabetic (D), (iii) ASA-treated control (C+ASA) and (iv) ASA-treated diabetic (D+ASA) groups. In groups 2 and 4, diabetes was induced by injection of 35 mg kg(-1) streptozotocin. ASA (100 mg kg(-1) day(-1) , orally) was administrated to rats in groups 3 and 4 for 8 weeks. Both intracavernosal pressure (ICP) and mean arterial blood pressure (MAP) were measured in in vivo studies. In organ bath, the relaxation responses to acetylcholine (ACh), electrical field stimulation (EFS) and sodium nitroprusside were tested in corpus cavernosum (CC) strips. The mRNA expression for neuronal nitric oxide synthase (nNOS) was calculated using reverse transcription polymerase chain reaction technique. In in vivo experiments, diabetic rats displayed reduced ICP/MAP values, which were normalised with ASA treatment. The relaxant response to high-dose ACh and EFS at low frequencies (1-8 Hz) in CC strips from the D+ASA group were significantly higher when compared to the D group. Treatment with ASA normalised the raised mRNA expressions of nNOS in diabetic penile tissues. ASA may be involved in mRNA of protein synthesis of NO released from nonadrenergic and noncholinergic cavernosal nerve in diabetes.

  15. ExSPO: A Discovery Class Apodized Square Aperture (ASA) Expo-Planet Imaging Space Telescope Concept

    NASA Technical Reports Server (NTRS)

    Gezari, D.; Harwit, M.; Lyon, R.; Melnick, G.; Papaliolos, G.; Ridgeway, S.; Woodruff, R.; Nisenson, P.; Oegerle, William (Technical Monitor)

    2002-01-01

    ExSPO is a Discovery Class (approx. 4 meter) apodized square aperture (ASA) space telescope mission designed for direct imaging of extrasolar Earth-like planets, as a precursor to TPF. The ASA telescope concept, instrument design, capabilities, mission plan and science goals are described.

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

    MedlinePlus

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

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

    PubMed

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

    2013-10-01

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

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

    PubMed

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

    1999-12-01

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

  19. 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

  20. 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.

  1. Simultaneous determination of acetylsalicylic and salicylic acids by first derivative spectrometry in pharmaceutical preparations

    NASA Astrophysics Data System (ADS)

    Rogić, Dunja

    1993-03-01

    A multicomponent first derivative UV spectrometric procedure for determination of acetylsalicylic acid (aspirin) and salicylic acid in the solution containing 1 % (w/v) of citric acid in some pharmaceutical preparations is presented. The method is based on the use of the first derivative minimum spectrometric measurements at 286 nm for aspirin and at 318 nm for salicylic acid. Four kinds of cmmercial Aspirin tablets were assayed without a long pretreatment of the pharmaceuticals from the tablet additives. Beer's law is obeyed from 13.62-68.1 μg ml -1 of aspirin and from 2.723-13.616 μg ml -1 of salicylic acid. Detection limits at the 0.05 level of significance were calculated to be 1.24 and 0.25 μg ml -1 with relative standard deviations of 1.09 % and 1.2 % of aspirin and salicylic acid, respectively.

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

    PubMed

    Whitworth, C W; Asker, A F

    1975-12-01

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

  3. Acetylsalicylic acid and ascorbic acid combination improves cognition; via antioxidant effect or increased expression of NMDARs and nAChRs?

    PubMed

    Kara, Yusuf; Doguc, Duygu Kumbul; Kulac, Esin; Gultekin, Fatih

    2014-05-01

    Chronic inflammation occurs systematically in the central nervous system during ageing, it has been shown that neuroinflammation plays an important role in the pathogenesis of many neurodegenerative disorders. Aspirin, a nonselective COX inhibitor, as well as ascorbic acid, has been purported to protect cerebral tissue. We investigated the effects of subchronic aspirin and ascorbic acid usage on spatial learning, oxidative stress and expressions of NR2A, NR2B, nAChRα7, α4 and β2. Forty male rats (16-18 months) were divided into 4 groups, namely, control, aspirin-treated, ascorbic acid-treated, aspirin+ascorbic acid-treated groups. Following 10-weeks administration period, rats were trained and tested in the Morris water maze. 8-Hydroxy-2-deoxyguanosine and malondialdehyde were evaluated by ELISA and HPLC, respectively. Receptor expressions were assessed by western blotting of hippocampi. Spatial learning performance improved partially in the aspirin group, but significant improvement was seen in the aspirin+ascorbic acid group (p < 0.05). While 8-hydroxy-2-deoxyguanosine and malondialdehyde levels were significantly decreased, NR2B and nAChRα7 expressions were significantly increased in the aspirin+ascorbic acid group as compared to the control group (p < 0.05). Subchronic treatment with aspirin+ascorbic acid in aged rats was shown to enhance cognitive performance and increase the expressions of several receptors related to learning and memory process.

  4. Graphene modified glassy carbon sensor for the determination of aspirin metabolites in human biological samples.

    PubMed

    Purushotham, Meruva; Gupta, Pankaj; Goyal, Rajendra N

    2015-10-01

    A graphene modified glassy carbon (GR/GCE) sensor has been developed for the determination of aspirin metabolites 2,3- and 2,5-dihydroxybenzoic acids (2,3- and 2,5-DHB). The modified sensor was characterized by Field Emission Scanning Electron Microscopy and Electrochemical Impedance Spectroscopy. The electrochemical behavior of 2,3- and 2,5-DHB was investigated by cyclic and square wave voltammetry. The modified sensor exhibited excellent electrocatalytic activity for the oxidation of 2,3- and 2,5-DHB, leading to a remarkable enhancement in the peak current as compared to the bare sensor. The results were attributed to the enhanced surface area and high conductivity of GR. The anodic peak currents of 2,3- and 2,5-DHB were found to be linear in the concentration range of 1-150 µM and 1-200 µM with the detection limits of 47 nM and 51 nM, respectively. The sensor was capable to determine 2,5-DHB effectively without any interference from the uric acid and other metabolites present in the urine samples. The practical utility of GR/GCE has been successfully demonstrated for the determination of 2,5-DHB in the urine samples of persons undergoing treatment with aspirin. PMID:26078167

  5. Characterization of total plasma glycosaminoglycan levels in healthy volunteers following oral administration of a novel antithrombotic odiparcil with aspirin or enoxaparin.

    PubMed

    Myers, Alan L; Upreti, Vijay V; Khurana, Manoj; Eddington, Natalie D

    2008-10-01

    Odiparcil is a novel, orally active beta-d-thioxyloside analog with antithrombotic activity associated with a reduced risk of adverse bleeding events. Its unique mechanism of action is postulated by means of an elevation in circulating endogenous chondroitin sulfate-related glycosaminoglycans (GAGs) levels. The purpose of these 2 separate clinical studies was to evaluate plasma GAG levels in healthy subjects administered odiparcil with either aspirin (ASA) or enoxaparin. Clinical plasma samples were processed and analyzed using validated HPLC bioassays that indirectly estimate GAG levels based on the simultaneous detection of the chondroitin disaccharide derivatives. The concomitant administration of odiparcil with or without ASA resulted in a significant elevation in GAG levels over baseline for both treatment groups. In the other clinical study, the concomitant administration of odiparcil with or without enoxaparin displayed significant increases in plasma DeltaDi-OS, DeltaDi-4S, and total disaccharide levels versus control group. Neither plasma GAG levels nor odiparcil plasma levels were correlated with a rise in hepatic transaminases, an adverse drug event observed in several subjects; and plasma odiparcil levels were indirectly correlated with plasma GAG levels. These clinical studies were proof of concept of preclinical rat studies indicating that chronic odiparcil treatment elevates endogenous GAG levels in human subjects. PMID:18757783

  6. Effects of acetylsalicylic acid on germination, growth and chlorophyll amounts of cucumber (Cucumis sativus L.) seeds.

    PubMed

    Canakci, Songül; Munzuroğlu, Omer

    2007-09-01

    Germination activities, various growth parameters (primary root length, hypocotyl length, primary leaf length, plant length and increase in fresh weight) and chlorophyll (a+b) amounts of cucumber seeds exposed to 0, 10(-5), 10(-4), 10(-3) and 0.5x 10(-2) M aqueous solutions of acetylsalicylic acid (ASA) for 48 h were established. While 0.5x 10(-2) M ASA significantly prevented germination activity of the seeds, other concentrations did not produce any effect, either positive or negative. Meanwhile, 0.5x 10(-2) M ASA inhibited radicle growth of the germinated seeds, while 10(-5) M ASA increased radicle growth. Other concentrations of ASA did not affect radicle growth. The following findings were obtained from the one-week seedlings exposed to ASA for 48 h: 0.5x10(-2) M ASA prevented growth (lengthening) of root, hypocotyl, leaf and plant and increased chlorophyll (a+b) amount with an increase in fresh weight. Contrary to 0.5x 10(-2) M ASA application, these features of the seedlings (except for the leaf length) were encouraged by 10(-5) M ASA. 10(-3)) M ASA only prevented root growth and reduced chlorophyll (a+b) amount. Other concentrations of ASA did not bring about any positive or negative effect on the features studied.

  7. 76 FR 53907 - Determination That TALWIN COMPOUND (Aspirin; Pentazocine Hydrochloride) Tablets, 325 Milligrams...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-30

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

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

    PubMed

    Tfelt-Hansen, P; Olesen, J

    1984-06-01

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

  9. Stability of aspirin in propoxyphene compound dosage forms.

    PubMed

    Goldberg, R; Nightingale, C H

    1977-03-01

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

  10. 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.

  11. All Sky Automated Survey for SuperNovae (ASAS-SN or "Assassin")

    NASA Astrophysics Data System (ADS)

    Shappee, Benjamin; Prieto, J.; Stanek, K. Z.; Kochanek, C. S.; Holoien, T.; Jencson, J.; Basu, U.; Beacom, J. F.; Szczygiel, D.; Pojmanski, G.; Brimacombe, J.; Dubberley, M.; Elphick, M.; Foale, S.; Hawkins, E.; Mullins, D.; Rosing, W.; Ross, R.; Walker, Z.

    2014-01-01

    Even in the modern era, only human eyes scan the entire optical sky for the violent, variable, and transient events that shape our universe. The "All Sky Automated Survey for Supernovae" (ASAS-SN or "Assassin") is changing this by surveying the extragalactic sky roughly once a week, and within a year ASAS-SN will triple in size. We began running our real-time search for variable sources in late April 2013 with our first unit, "Brutus". Brutus presently consists of two telescopes on a common mount hosted by Las Cumbres Observatory Global Telescope Network in the Faulkes Telescope North enclosure on Mount Haleakala, Hawaii. Each telescope consists of a 14-cm Nikon telephoto lens and has a 4.47 by 4.47 degree field-of-view. On a typical clear night, it can survey 5000+ square degrees. The data are reduced in real-time, and we can search for transient candidates about an hour after the data are taken using an automated difference imaging pipeline. We are now meeting, and frequently exceeding, our current depth goal of 16 mag, corresponding to the apparent brightness at maximum light of core-collapse SNe within ~30 Mpc and SNe Ia out to ~100 Mpc. Brutus will shortly expand to have four cameras instead of two, and a second unit, "Cassius", with two cameras, should commence operations in early 2014 on Cerro Tololo, Chile. With these expansions, ASAS-SN will be able to observe the entire extragalactic sky every 2-3 nights. ASAS-SN has already discovered 10+ nearby SNe, 100+ outbursts from CVs and novae, 15+ M-dwarf and other stellar flares, and AGN outbursts which have resulted in 35+ ATel and CBET telegrams and 3 publications. In particular, ASAS-SN discovered one of the most extreme M-dwarf Flares ever detected (delta 9 mag). Furthermore, after triggering on an outburst in NGC 2617 we found that the AGN had changed from a Type 1.8 into a Type 1 Seyfert. After monitoring the transient with Swift and ground-based telescopes for 70 days, we clearly determined that the X

  12. Aspirin insensitive thrombophilia: Transcript profiling of blood identifies platelet abnormalities and HLA restriction

    PubMed Central

    Fallahi, Payam; Katz, Richard; Toma, Ian; Li, Ranyang; Reiner, Jonathan; VanHouten, Kiersten; Carpio, Larry; Marshall, Lorraine; Lian, Yi; Bupp, Sujata; Fu, Sidney W.; Rickles, Frederick; Leitenberg, David; Lai, Yinglei; Weksler, Babette B.; Rebling, Frederik; Yang, Zhaoqing; McCaffrey, Timothy A.

    2016-01-01

    Aspirin is the most widely used antiplatelet agent because it is safe, efficient, and inexpensive. However, a significant subset of patients does not exhibit a full inhibition of platelet aggregation, termed ‘aspirin resistance’ (AR). Several major studies have observed that AR patients have a 4-fold increased risk of myocardial infarction (MI), stroke, and other thrombotic events. Arachidonic acid-stimulated whole blood aggregation was tested in 132 adults at risk for ischemic events, and identified an inadequate response to aspirin therapy in 9 patients (6.8%). Expression profiling of blood RNA by microarray was used to generate new hypotheses about the etiology of AR. Among the differentially expressed genes, there were decreases in several known platelet transcripts, including clusterin (CLU), glycoproteins IIb/IIIa (ITGA2B/3), lipocalin (LCN2), lactoferrin (LTF), and the thrombopoetin receptor (MPL), but with increased mRNA for the T-cell Th1 chemokine CXCL10. There was a strong association of AR with expression of HLA-DRB4 and HLA-DQA1. Similar HLA changes have been linked to autoimmune disorders, particularly antiphospholipid syndrome (APS), in which autoantibodies to phospholipid/protein complexes can trigger platelet activation. Consistent with APS, AR patients exhibited a 30% reduction in platelet counts. Follow-up testing for autoimmune antibodies observed only borderline titers in AR patients. Overall, these results suggest that AR may be related to changes in platelet gene expression creating a hyperreactive platelet, despite antiplatelet therapy. Future studies will focus on determining the protein levels of these differential transcripts in platelets, and the possible involvement of HLA restriction as a contributing factor. PMID:23454623

  13. Theoretical modeling of infrared spectra of the hydrogen and deuterium bond in aspirin crystal

    NASA Astrophysics Data System (ADS)

    Ghalla, Houcine; Rekik, Najeh; Michta, Anna; Oujia, Brahim; Flakus, Henryk T.

    2010-01-01

    An extended quantum theoretical approach of the ν IR lineshape of cyclic dimers of weakly H-bonded species is proposed. We have extended a previous approach [M.E.-A. Benmalti, P. Blaise, H.T. Flakus, O. Henri-Rousseau, Chem. Phys. 320 (2006) 267] by accounting for the anharmonicity of the slow mode which is described by a "Morse" potential in order to reproduce the polarized infrared spectra of the hydrogen and deuterium bond in acetylsalicylic acid (aspirin) crystals. From comparison of polarized IR spectra of isotopically neat and isotopically diluted aspirin crystals it resulted that centrosymmetric aspirin dimer was the bearer of the crystal main spectral properties. In this approach, the adiabatic approximation is performed for each separate H-bond bridge of the dimer and a strong non-adiabatic correction is introduced into the model via the resonant exchange between the fast mode excited states of the two moieties. Within the strong anharmonic coupling theory, according to which the X-H→⋯Y high-frequency mode is anharmonically coupled to the H-bond bridge, this model incorporated the Davydov coupling between the excited states of the two moieties, the quantum direct and indirect dampings and the anharmonicity for the H-bond bridge. The spectral density is obtained within the linear response theory by Fourier transform of the damped autocorrelation functions. The evaluated spectra are in fairly good agreement with the experimental ones by using a minimum number of independent parameters. The effect of deuteration has been well reproduced by reducing simply the angular frequency of the fast mode and the anharmonic coupling parameter.

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

    PubMed Central

    Larson, Robin J; Fisher, Elliott S

    2004-01-01

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

  15. Acetylsalicylic acid induces programmed cell death in Arabidopsis cell cultures.

    PubMed

    García-Heredia, José M; Hervás, Manuel; De la Rosa, Miguel A; Navarro, José A

    2008-06-01

    Acetylsalicylic acid (ASA), a derivative from the plant hormone salicylic acid (SA), is a commonly used drug that has a dual role in animal organisms as an anti-inflammatory and anticancer agent. It acts as an inhibitor of cyclooxygenases (COXs), which catalyze prostaglandins production. It is known that ASA serves as an apoptotic agent on cancer cells through the inhibition of the COX-2 enzyme. Here, we provide evidences that ASA also behaves as an agent inducing programmed cell death (PCD) in cell cultures of the model plant Arabidopsis thaliana, in a similar way than the well-established PCD-inducing agent H(2)O(2), although the induction of PCD by ASA requires much lower inducer concentrations. Moreover, ASA is herein shown to be a more efficient PCD-inducing agent than salicylic acid. ASA treatment of Arabidopsis cells induces typical PCD-linked morphological and biochemical changes, namely cell shrinkage, nuclear DNA degradation, loss of mitochondrial membrane potential, cytochrome c release from mitochondria and induction of caspase-like activity. However, the ASA effect can be partially reverted by jasmonic acid. Taking together, these results reveal the existence of common features in ASA-induced animal apoptosis and plant PCD, and also suggest that there are similarities between the pathways of synthesis and function of prostanoid-like lipid mediators in animal and plant organisms.

  16. 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

  17. Spectroscopic survey of ASAS eclipsing variables: search for chromospherically active eclipsing binary stars - I

    NASA Astrophysics Data System (ADS)

    Parihar, Padmakar; Messina, S.; Bama, P.; Medhi, B. J.; Muneer, S.; Velu, C.; Ahmad, A.

    2009-05-01

    We have started a spectroscopic survey to identify new chromospherically active components and low-mass pre-main sequence (PMS) stars in recently discovered All Sky Automated Survey (ASAS) eclipsing binaries. In this paper, we briefly describe our scientific motivation, the observing tools and the results obtained from the first phase of this survey. Using the available observing facilities in India, the spectroscopic observations of a sample of 180 candidate eclipsing binary stars selected from ASAS-I&II releases were carried out during 2004-2006. The strength of Hα emission was used to characterize the level of chromospheric activity. Our spectroscopic survey reveals that out of 180 stars about 36 binary systems show excess Hα emission. One of the objects in our sample, ASAS 081700-4243.8, displays very strong Hα emission. Follow-up high-resolution spectroscopic observations reveal that this object is indeed very interesting and most likely a classical Be-type system with K0III companion.

  18. The Curious Case of ASAS J174600-2321.3: an Eclipsing Symbiotic Nova in Outburst?

    NASA Astrophysics Data System (ADS)

    Hümmerich, S.; Otero, S.; Tisserand, P.; Bernhard, K.

    2015-06-01

    The star ASAS J174600-2321.3 was found to exhibit peculiar photometric variability (conspicuous brightening of ~4 magnitudes (V), fast luminosity declines, intrinsic pulsations). It was rejected as an RCB candidate in recent investigations on spectroscopic grounds. We have collected and present all available data from public sky surveys, photometric catalogues, and the literature. From an analysis of these data, we have identified ASAS J174600-2321.3 as a long-period eclipsing binary (Porb = 1,011.5 days). The primary star, which is probably a white dwarf, is currently in outburst and exhibits the spectral characteristics of a reddened, early F-type supergiant; the secondary star is a giant of spectral type late M. We discuss the possible origin of the observed brightening, which is related to the primary component. ASAS J174600-2321.3 is most certainly an eclipsing symbiotic binary—probably a symbiotic nova of GCVS type NC—that is currently in outburst. However, further photometric and spectroscopic data are needed to confirm this.

  19. Human brucellosis mimicking axial spondyloarthritis: a challenge for rheumatologists when applying the 2009 ASAS criteria.

    PubMed

    Ye, Cong; Shen, Gui-Fen; Li, Shou-Xin; Dong, Ling-Li; Yu, Yi-Kai; Tu, Wei; Zhu, Ying-Zi; Hu, Shao-Xian

    2016-06-01

    Although the development of the 2009 SpA classification criteria by Assessment of SpondyloArthritis international Society (ASAS) represents an important step towards a better definition of the early disease stage particularly in axial spondyloarthritis (axSpA), the specificity of the criteria has been criticized these days. As the commonest zoonotic infection worldwide, human brucellosis can mimic a large number of diseases, including SpA. This study was performed to determine the frequency of rheumatologic manifestations in patients with brucellosis and the chance of misdiagnosing them as having axSpA in central China. The results showed that clinical manifestations of axSpA could be observed in brucellosis. Over half of patients had back pain, and one fifth of the patients with back pain were less than 45 years old at onset and had the symptom for more than 3 months. Two young males were falsely classified as suffering from axSpA according to the ASAS criteria, and one with MRI proved sacroiliitis was once given Etanercept for treatment. Therefore, differential diagnosis including human brucellosis should always be kept in mind when applying the ASAS criteria, even in traditionally non-endemic areas. PMID:27376805

  20. Analysis of variability of TW Hya as observed by MOST and ASAS in 2009

    NASA Astrophysics Data System (ADS)

    Siwak, Michal; Rucinski, Slavek M.; Matthews, Jaymie M.; Pojmański, Grzegorz; Kuschnig, Rainer; Guenther, David B.; Moffat, Anthony F. J.; Sasselov, Dimitar; Weiss, Werner W.

    2011-02-01

    As a continuation of our previous studies in 2007 and 2008, new photometric observations of the T Tauri star TW Hya obtained by the MOST satellite and the All Sky Automated Survey (ASAS) project over 40 d in 2009 with temporal resolution of 0.2 d are presented. A wavelet analysis of the combined MOST-ASAS data provides a rich picture of coherent, intermittent, variable-period oscillations, similarly as discovered in the 2008 data. The periods (1.3-10 d) and systematic period shortening on time-scales of weeks can be interpreted within the model of magnetorotationally controlled accretion processes in the inner accretion disc around the star. Within this model and depending on the assumed visibility of plasma parcels causing the oscillations, the observed shortest oscillation period may indicate the stellar rotation period of 1.3 or 2.6 d, synchronized with the disc at 4.5 or 7.1 R⊙, respectively. Based on data from the MOST satellite, a Canadian Space Agency mission, jointly operated by Dynacon Inc., the University of Toronto Institute of Aerospace Studies, and the University of British Columbia, with the assistance of the University of Vienna, and from the All Sky Automated Survey (ASAS) (conducted by the Warsaw University Observatory, Poland) at the Las Campanas Observatory.

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

    PubMed

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

    2014-07-01

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

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

    PubMed

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

    2015-01-01

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

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. Ascorbic Acid Metabolism in Pea Seedlings. A Comparison of d-Glucosone, l-Sorbosone, and l-Galactono-1,4-Lactone as Ascorbate Precursors1

    PubMed Central

    Pallanca, Jane E.; Smirnoff, Nicholas

    1999-01-01

    l-Ascorbic acid (AsA) accumulates in pea (Pisum sativum L.) seedlings during germination, with the most rapid phase of accumulation coinciding with radicle emergence. Monodehydroascorbate reductase and dehydroascorbic acid reductase were active in the embryonic axes before AsA accumulation started, whereas AsA oxidase and AsA peroxidase activities increased in parallel with AsA. Excised embryonic axes were used to investigate the osone pathway of AsA biosynthesis, in which d-glucosone and l-sorbosone are the proposed intermediates. [U-14C]Glucosone was incorporated into AsA and inhibited the incorporation of [U-14C]glucose (Glc) into AsA. A higher d-glucosone concentration (5 mm) inhibited AsA accumulation. l-Sorbosone did not affect AsA pool size but caused a small inhibition in the incorporation of [U-14C]Glc into AsA. Oxidase and dehydrogenase activities capable of converting Glc or Glc-6-phosphate to glucosone were not detected in embryonic axis extracts. The osones are therefore unlikely to be physiological intermediates of AsA biosynthesis. l-Galactono-1,4-lactone, recently proposed as the AsA precursor (G.L. Wheeler, M.A. Jones, N. Smirnoff [1998] Nature 393: 365–369), was readily converted to AsA by pea embryonic axes. Although l-galactono-1,4-lactone did not inhibit [14C]Glc incorporation into AsA, this does not mean that it is not a precursor, because competition between endogenous and exogenous pools was minimized by its very small pool size and rapid metabolism. PMID:10364396

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

    PubMed

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

    2014-06-01

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

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

    PubMed

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

    2014-06-01

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

  10. Aspirin use for primary prevention in elderly patients.

    PubMed

    Terrosu, Pierfranco

    2016-01-01

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

  11. The role of aspirin in colorectal cancer chemoprevention.

    PubMed

    Singh Ranger, Gurpreet

    2016-08-01

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

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

    ERIC Educational Resources Information Center

    Marrs, Peter S.

    2004-01-01

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

  13. Distribution of prostaglandins in gastric and duodenal mucosa of healthy subjects and duodenal ulcer patients: effects of aspirin and paracetamol.

    PubMed

    Konturek, S J; Obtulowicz, W; Sito, E; Oleksy, J; Wilkon, S; Kiec-Dembinska, A

    1981-04-01

    The distribution of mucosal PGE2-like activity was determined by bioassay technique in the body and antrum of the stomach and in the duodenum of healthy subjects and duodenal ulcer patients before and after administration of aspirin, paracetamol, or histamine. In healthy subjects, the oxyntic, antral and duodenal mucosa was found to be capable of generating large amounts of PGE2, which were not significantly different from those found in duodenal ulcer patients. No correlation was found between the generation of PGE2 and gastric acid secretory status or serum gastrin level. Aspirin-and to a much lesser extent, paracetamol-caused a dramatic reduction in the ability of the gastric mucosa to biosynthesis PGE2 and this was accompanied by marked side-effects and injury to the gastric mucosa. Administration of histamine caused small but significant reduction in the biosynthesis of PGE2 but it was accompanied by marked mucosal damage. This study indicates that the gastric and duodenal mucosa is capable of generating PGE2-like activity which may be involved in the mechanism that protects the mucosa against the damage caused by aspirin.

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2016-03-01

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

  16. First light curve analyses of binary systems AO Aqr, CW Aqr and ASAS 012206-4924.7

    NASA Astrophysics Data System (ADS)

    Ulaş, B.; Ulusoy, C.

    2015-11-01

    Using the data from the public database of the All Sky Automated Survey (ASAS) we performed the very first light curve analyses of the three eclipsing binary systems AO Aqr, CW Aqr and ASAS 012206-4924.7. The physical parameters of the systems were determined by the PHOEBE (Prša and Zwitter, 2005) software. From an analysis of the ASAS data it was concluded that AO Aqr was found to be a contact binary system while CW Aqr and ASAS 012206-4924.7 were found to be near-contact and detached binaries, respectively. Finally, the locations of the components, corresponding to the estimated physical parameters, in the HR diagram were also discussed.

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    1982-12-01

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

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

    PubMed

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

    2015-10-01

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

  20. Prolonged acetylsalicylic-acid-supplementation-induced gastritis affects the chemical coding of the stomach innervating vagal efferent neurons in the porcine dorsal motor vagal nucleus (DMX).

    PubMed

    Gańko, Marta; Całka, Jarosław

    2014-01-01

    The main goal of our research was to study the possible alterations of the chemical coding of the dorsal motor vagal nucleus (DMX) neurons projecting to the porcine stomach prepyloric region following prolonged acetylsalicylic acid supplementation. Fast Blue (FB) was injected into the studied area of the stomach. Since the seventh day following the FB injection, acetylsalicylic acid (ASA) was given orally to the experimental gilts. All animals were euthanized on the 28th day after FB injection. Medulla oblongata sections were then processed for double-labeling immunofluorescence for choline acetyltransferase (ChAT), pituitary adenylate cyclase-activating peptide (PACAP), vasoactive intestinal polypeptide (VIP), nitric oxide synthase (NOS), galanin (GAL), substance P (SP), leu enkephalin (LENK), and cocaine- and amphetamine-regulated transcript (CART). In the control DMX, only PACAP was observed in 30.08 ± 1.97 % of the FB-positive neurons, while VIP, NOS, GAL, SP, LENK, and CART were found exclusively in neuronal processes running between FB-labeled perikarya. In the ASA DMX, PACAP was revealed in 49.53 ± 5.73 % of traced vagal perikarya. Moreover, we found de novo expression of VIP in 40.32 ± 7.84 %, NOS in 25.02 ± 6.08 %, and GAL in 3.37 ± 0.85 % of the FB-labeled neurons. Our results suggest that neuronal PACAP, VIP, NOS, and GAL are mediators of neural response to aspirin-induced stomach inflammatory state.

  1. A Nanometer Aerosol Size Analyzer (nASA) for Rapid Measurement of High-Concentration Size Distributions

    NASA Technical Reports Server (NTRS)

    Han, Hee-Siew; Chen, Da-Ren; Pui, David Y. H.; Anderson, Bruce E.

    2001-01-01

    We have developed a fast-response Nanometer Aerosol Size Analyzer (nASA) that is capable of scanning 30 size channels between 3 and 100 nm in a total time of 3 seconds. The analyzer includes a bipolar charger (P0210), an extended-length Nanometer Differential Mobility Analyzer (Nano-DMA), and an electrometer (TSI 3068). This combination of components provides particle size spectra at a scan rate of 0.1 second per channel free of uncertainties caused by response-time-induced smearing. The nASA thus offers a fast response for aerosol size distribution measurements in high-concentration conditions and also eliminates the need for applying a de-smearing algorithm to resulting data. In addition, because of its thermodynamically stable means of particle detection, the nASA is useful for applications requiring measurements over a broad range of sample pressures and temperatures. Indeed, experimental transfer functions determined for the extended-length Nano-DMA using the Tandem Differential Mobility Analyzer (TDMA) technique indicate the nASA provides good size resolution at pressures as low as 200 Torr. Also, as was demonstrated in tests to characterize the soot emissions from the J85-GE engine of a T38 aircraft, the broad dynamic concentration range of the nASA makes it particularly suitable for studies of combustion or particle formation processes. Further details of the nASA performance as well as results from calibrations, laboratory tests and field applications are presented.

  2. Mechanism of action of 5-arninosalicylic acid

    PubMed Central

    Greenfield, S. M.; Thompson, R. P. H.

    1992-01-01

    5-Aminosalicylic Acid (5-ASA) has been used for over 50 years in the treatment of inflammatory bowel disease in the pro-drug form sulphasalazine (SASP). SASP is also used to treat rheumatoid arthritis. However whether the therapeutic properties of SASP are due to the intact molecule, the 5-ASA or sulphapyridine components is unknown. Several mechanisms of action have been proposed for 5-ASA and SASP including interference in the metabolism of arachidonic acid to prostaglandins and leukotrienes, scavenging,of reactive oxygen species, effects on leucocyte function and production of cytokines. However, it is unlikely that the anti-inflammatory properties of SASP and 5-ASA are due to several different properties but more likely that a single property of 5-ASA explains the theraapeutic effects of 5-ASA and SASP. Reactive oxygen species (ROS) are involved in the metabolism of prostaglandins and leukotrienes and can act as second messengers, and so the scavenging of ROS may be the single mechanism of action of 5-ASA that gives rise to its antiinflammatory effects in both inflammatory bowel disease and rheumatoid arthritis. PMID:18475455

  3. Tissue-specific patterns of gene expression in the epithelium and stroma of normal colon in healthy individuals in an aspirin intervention trial.

    PubMed

    Thomas, Sushma S; Makar, Karen W; Li, Lin; Zheng, Yingye; Yang, Peiying; Levy, Lisa; Rudolph, Rebecca Y; Lampe, Paul D; Yan, Min; Markowitz, Sanford D; Bigler, Jeannette; Lampe, Johanna W; Potter, John D

    2015-12-01

    Regular aspirin use reduces colon adenoma and carcinoma incidence. UDP-glucuronosyltransferases (UGT) are involved in aspirin metabolism and clearance, and variant alleles in UGT1A6 have been shown to alter salicylic acid metabolism and risk of colon neoplasia. In a randomized, cross-over, placebo-controlled trial of 44 healthy men and women, homozygous for UGT1A6*1 or UGT1A6*2, we explored differences between global epithelial and stromal expression, using Affymetrix U133 + 2.0 microarrays and tested effects of 60-day aspirin supplementation (325 mg/d) on epithelial and stromal gene expression and colon prostaglandin E2 (PGE2) levels. We conducted a comprehensive study of differential gene expression between normal human colonic epithelium and stroma from healthy individuals. Although no statistically significant differences in gene expression were observed in response to aspirin or UGT1A6 genotype, we have identified the genes uniquely and reproducibly expressed in each tissue type and have analyzed the biologic processes they represent. Here we describe in detail how the data, deposited in the Gene Expression Omnibus (GEO) - accession number GSE71571 - was generated including the basic analysis as contained in the manuscript published in BMC Medical Genetics with the PMID 25927723 (Thomas et al., 2015 [9]).

  4. Tissue-specific patterns of gene expression in the epithelium and stroma of normal colon in healthy individuals in an aspirin intervention trial

    PubMed Central

    Thomas, Sushma S.; Makar, Karen W.; Li, Lin; Zheng, Yingye; Yang, Peiying; Levy, Lisa; Rudolph, Rebecca Y.; Lampe, Paul D.; Yan, Min; Markowitz, Sanford D.; Bigler, Jeannette; Lampe, Johanna W.; Potter, John D.

    2015-01-01

    Regular aspirin use reduces colon adenoma and carcinoma incidence. UDP-glucuronosyltransferases (UGT) are involved in aspirin metabolism and clearance, and variant alleles in UGT1A6 have been shown to alter salicylic acid metabolism and risk of colon neoplasia. In a randomized, cross-over, placebo-controlled trial of 44 healthy men and women, homozygous for UGT1A6*1 or UGT1A6*2, we explored differences between global epithelial and stromal expression, using Affymetrix U133 + 2.0 microarrays and tested effects of 60-day aspirin supplementation (325 mg/d) on epithelial and stromal gene expression and colon prostaglandin E2 (PGE2) levels. We conducted a comprehensive study of differential gene expression between normal human colonic epithelium and stroma from healthy individuals. Although no statistically significant differences in gene expression were observed in response to aspirin or UGT1A6 genotype, we have identified the genes uniquely and reproducibly expressed in each tissue type and have analyzed the biologic processes they represent. Here we describe in detail how the data, deposited in the Gene Expression Omnibus (GEO) – accession number GSE71571 – was generated including the basic analysis as contained in the manuscript published in BMC Medical Genetics with the PMID 25927723 (Thomas et al., 2015 [9]). PMID:26697360

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

    SciTech Connect

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

    1986-07-01

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

  6. Low-dose acetylsalicylic acid and bleeding risks with ventriculoperitoneal shunt placement.

    PubMed

    Kamenova, Maria; Croci, Davide; Guzman, Raphael; Mariani, Luigi; Soleman, Jehuda

    2016-09-01

    OBJECTIVE Ventriculoperitoneal (VP) shunt placement is a common procedure for the treatment of hydrocephalus following diverse neurosurgical conditions. Most of the patients present with other comorbidities and receive antiplatelet therapy, usually acetylsalicylic acid (ASA). Despite its clinical relevance, the perioperative management of these patients has not been sufficiently investigated. The aim of this study was to compare the peri- and postoperative bleeding complication rates associated with ASA intake in patients undergoing VP shunt placement. METHODS Of 172 consecutive patients undergoing VP shunt placement between June 2009 and December 2015, 40 (23.3%) patients were receiving low-dose ASA treatment. The primary outcome measure was bleeding events in ASA users versus nonusers, whereas secondary outcome measures were postoperative cardiovascular events, hematological findings, morbidity, and mortality. A subgroup analysis was conducted in patients who discontinued ASA treatment for < 7 days (n = 4, ASA Group 1) and for ≥ 7 days (n = 36, ASA Group 2). RESULTS No statistically significant difference for bleeding events was observed between ASA users and nonusers (p = 0.30). Cardiovascular complications, surgical morbidity, and mortality did not differ significantly between the groups either. Moreover, there was no association between ASA discontinuation regimens (< 7 days and ≥ 7 days) and hemorrhagic events. CONCLUSIONS Given the lack of guidelines regarding perioperative management of neurosurgical patients with antiplatelet therapy, these findings elucidate one issue, showing comparable bleeding rates in ASA users and nonusers undergoing VP shunt placement. PMID:27581316

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

    PubMed Central

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

    2016-01-01

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

  8. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  11. ASAS J083241+2332.4: A New Extreme Low Mass Ratio Overcontact Binary System

    NASA Astrophysics Data System (ADS)

    Sriram, K.; Malu, S.; Choi, C. S.; Vivekananda Rao, P.

    2016-03-01

    We present the R- and V-band CCD photometry and Hα line studies of an overcontact binary ASAS J083241+2332.4. The light curves exhibit totality along with a trace of the O’Connell effect. The photometric solution indicates that this system falls into the category of extreme low-mass ratio overcontact binaries with a mass ratio, q ˜ 0.06. Although a trace of the O’ Connell effect is observed, constancy of the Hα line along various phases suggest that a relatively higher magnetic activity is needed for it to show a prominent fill-in effect. The study of O-C variations reveals that the period of the binary shows a secular increase at the rate of dP/dt ˜ 0.0765 s years-1, which is superimposed by a low, but significant, sinusoidal modulation with a period of ˜8.25 years. Assuming that the sinusoidal variation is due to the presence of a third body, orbital elements have been derived. There exist three other similar systems, SX Crv, V857 Her, and E53, which have extremely low mass ratios and we conclude that ASAS J083241+2332.4 resembles SX Crv in many respects. Theoretical studies indicate that at a critical mass ratio range, qcritical = 0.07-0.09, overcontact binaries should merge and form a fast rotating star, but it has been suggested that qcritical can continue to fall up to 0.05 depending on the primary's mass and structure. Moreover, the obtained fill-out factors (50%-70%) indicate that mass loss is considerable and hydrodynamical simulations advocate that mass loss from L2 is mandatory for a successful merging process. Comprehensively, the results indicate that ASAS J083241+2332.4 is at a stage of merger. The pivotal role played by the subtle nature of the derived mass ratio in forming a rapidly rotating star has been discussed.

  12. L-Ascorbic acid metabolism during fruit development in an ascorbate-rich fruit crop chestnut rose (Rosa roxburghii Tratt).

    PubMed

    Huang, Ming; Xu, Qiang; Deng, Xiu-Xin

    2014-09-01

    Chestnut rose (Rosa roxburghii Tratt) is a fruit crop that contains unusually high levels of l-ascorbic acid (AsA; ∼1300 mg 100g(-1) FW). To explore the mechanisms underlying AsA metabolism, we investigated the distribution and abundance of AsA during fruit development. We also analyzed gene expression patterns, enzyme activities, and content of metabolites related to AsA biosynthesis and recycling. AsA first accumulated during late fruit development and continued to accumulate during ripening, with the highest accumulation rate near fruit maturity. The redox state of AsA in fruit was also enhanced during late fruit development, while leaf and other tissues had much lower levels of AsA and the redox state of AsA was lower. In mature fruit, AsA was mainly distributed in the cytoplasm of the mesocarp. Correlation analysis suggested that the gene expression patterns, enzyme activities, and related metabolite concentrations involved in the l-galactose pathway showed relatively high correlations with the accumulation rate of AsA. The gene expression pattern and activity of dehydroascorbate reductase (DHAR, EC 1.8.5.1) correlated strongly with AsA concentration, possibly indicating the crucial role of DHAR in the accumulation of high levels of AsA in chestnut rose fruit. Over expression of DHAR in Arabidopsis significantly increased the reduced AsA content and redox state. This was more effective than over expression of the l-galactose pathway gene GDP-d-mannose-3,5-epimerase (EC 5.1.3.18). These findings will enhance understanding of the molecular mechanisms regulating accumulation of AsA in chestnut rose.

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2009-04-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-06-01

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

  17. 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.

  18. Effects of volumetric expansion in molecular crystals: A quantum mechanical investigation on aspirin and paracetamol most stable polymorphs

    NASA Astrophysics Data System (ADS)

    Adhikari, Kapil; Flurchick, Kenneth M.; Valenzano, Loredana

    2015-02-01

    This work reports a study performed at hybrid semi-empirical density functional level (B3LYP-D2*) of the physico-chemical properties of aspirin (acetylsalicylic acid) and paracetamol (acetaminophen) in their most stable crystalline forms. It is shown how effects arising from volumetric expansions influence the properties of the materials. Structural, energetic, and vibrational properties are in good agreement with experimental values reported at temperatures far from 0 K. Results show that the proposed approach is reliable enough to reproduce effects of volumetric expansion on lattice energies and other measurable physico-chemical observables related to inter-molecular forces.

  19. 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.

  20. Aspirin treatment exacerbates oral infections by Trypanosoma cruzi.

    PubMed

    Cossentini, Luana Aparecida; Da Silva, Rosiane Valeriano; Yamada-Ogatta, Sueli Fumie; Yamauchi, Lucy Megumi; De Almeida Araújo, Eduardo José; Pinge-Filho, Phileno

    2016-05-01

    Oral transmission of the protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas disease, has been documented in Latin American countries. The reported cases of infection were due to the ingestion of contaminated fresh fruit, juices, or sugar cane juice. There have been few studies on the physiopathology of the disease in oral transmission cases. Gastritis is a common ailment that can be caused by poor dietary habits, intake of alcohol or other gastric irritants, bacterial infection, or by the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs). This study investigated in a mouse model whether gastric mucosal injury, induced by aspirin, would affect the course of disease in animals infected with T. cruzi by the oral route. The CL14 and G strains of T. cruzi, both of low infectivity, were used. To this end, groups of BALB/c mice were treated during 5 days with aspirin (100 mg kg(-1)) before oral infection with T. cruzi metacyclic forms (4 × 10(5) or 5 × 10(7) parasites/mouse). Histological analysis and determination of nitric oxide and TNF-α were performed in gastric samples obtained 5 days after infection. Parasitemia was monitored from the thirteenth day after infection. The results indicate that aspirin treatment of mice injured their gastric mucosa and facilitated invasion by both CL14 and G strains of T. cruzi. Strain CL14 caused more severe infection compared to the G strain, as larger numbers of amastigote nests were found in the stomach and parasitemia levels were higher. Our study is novel in that it shows that gastric mucosal damage caused by aspirin, a commonly used NSAID, facilitates T. cruzi infection by the oral route. PMID:26826555

  1. Aspirin Prevention of Cholesterol Gallstone Formation in Prairie Dogs

    NASA Astrophysics Data System (ADS)

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

    1981-03-01

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

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

    PubMed Central

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

    2014-01-01

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

  3. Regulation of L-ascorbic acid content in strawberry fruits

    PubMed Central

    Cruz-Rus, Eduardo; Amaya, Iraida; Sánchez-Sevilla, José F.; Botella, Miguel A.; Valpuesta, Victoriano

    2011-01-01

    Plants have several L-ascorbic acid (AsA) biosynthetic pathways, but the contribution of each one to the synthesis of AsA varyies between different species, organs, and developmental stages. Strawberry (Fragaria×ananassa) fruits are rich in AsA. The pathway that uses D-galacturonate as the initial substrate is functional in ripe fruits, but the contribution of other pathways to AsA biosynthesis has not been studied. The transcription of genes encoding biosynthetic enzymes such as D-galacturonate reductase (FaGalUR) and myo-inositol oxygenase (FaMIOX), and the AsA recycling enzyme monodehydroascorbate reductase (FaMDHAR) were positively correlated with the increase in AsA during fruit ripening. Fruit storage for 72 h in a cold room reduced the AsA content by 30%. Under an ozone atmosphere, this reduction was 15%. Ozone treatment increased the expression of the FaGalUR, FaMIOX, and L-galactose-1-phosphate phosphatase (FaGIPP) genes, and transcription of the L-galactono-1,4-lactone dehydrogenase (FaGLDH) and FAMDHAR genes was higher in the ozone-stored than in the air-stored fruits. Analysis of AsA content in a segregating population from two strawberry cultivars showed high variability, which did not correlate with the transcription of any of the genes studied. Study of GalUR protein in diverse cultivars of strawberry and different Fragaria species showed that a correlation between GalUR and AsA content was apparent in most cases, but it was not general. Three alleles were identified in strawberry, but any sequence effect on the AsA variability was eliminated by analysis of the allele-specific expression. Taken together, these results indicate that FaGalUR shares the control of AsA levels with other enzymes and regulatory elements in strawberry fruit. PMID:21561953

  4. Synthesis of L-ascorbic acid in the phloem

    PubMed Central

    Hancock, Robert D; McRae, Diane; Haupt, Sophie; Viola, Roberto

    2003-01-01

    Background Although plants are the main source of vitamin C in the human diet, we still have a limited understanding of how plants synthesise L-ascorbic acid (AsA) and what regulates its concentration in different plant tissues. In particular, the enormous variability in the vitamin C content of storage organs from different plants remains unexplained. Possible sources of AsA in plant storage organs include in situ synthesis and long-distance transport of AsA synthesised in other tissues via the phloem. In this paper we examine a third possibility, that of synthesis within the phloem. Results We provide evidence for the presence of AsA in the phloem sap of a wide range of crop species using aphid stylectomy and histochemical approaches. The activity of almost all the enzymes of the primary AsA biosynthetic pathway were detected in phloem-rich vascular exudates from Cucurbita pepo fruits and AsA biosynthesis was demonstrated in isolated phloem strands from Apium graveolens petioles incubated with a range of precursors (D-glucose, D-mannose, L-galactose and L-galactono-1,4-lactone). Phloem uptake of D-[U-14C]mannose and L-[1-14C]galactose (intermediates of the AsA biosynthetic pathway) as well as L-[1-14C]AsA and L-[1-14C]DHA, was observed in Nicotiana benthamiana leaf discs. Conclusions We present the novel finding that active AsA biosynthesis occurs in the phloem. This process must now be considered in the context of mechanisms implicated in whole plant AsA distribution. This work should provoke studies aimed at elucidation of the in vivo substrates for phloem AsA biosynthesis and its contribution to AsA accumulation in plant storage organs. PMID:14633288

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

    SciTech Connect

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

    1984-05-01

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

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

    PubMed

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

    2015-06-01

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

  7. [Effects of exogenous AsA and GSH on the growth of Dianthus chinensis seedlings exposed to Cd].

    PubMed

    Ding, Ji-Jun; Liu, Shi-Liang; Pan, Yuan-Zhi; Li, Li

    2014-02-01

    A pot experiment was carried out under greenhouse condition to investigate the effects of different concentrations (0, 20, 40, 60, 80 and 100 mg x L(-1)) of exogenous AsA, GSH on Dianthus chinensis seedlings which were stressed by 50 mg x kg(-1) Cd in the soil. The results indicated that 50 mg x kg(-1) of Cd significantly inhibited the growth of D. chinensis seedlings. An appropriate concentration of exogenous AsA significantly improved the biomass, plant height, tiller number, GAT and APX activities, and AsA and GSH contents. However, with the increase of exogenous AsA concentration, the ameliorating effect decreased and prooxidant effect occurred. Exogenous GSH could replenish the non-enzymatic antioxidants of D. chinensis seedlings, but the changes of antioxidant enzyme activities were relatively slight. The main mechanisms of GSH to alleviate Cd toxicity might be promoting root PCs synthesis, thereby reducing the Cd concentration in the seedlings. Both 35-45 mg x L(-1) exogenous AsA and 55-65 mg x L(-1) exogenous GSH could alleviate the Cd toxicity on D. chinensis seedlings, and the former was superior to the latter.

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

    PubMed

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

    2010-08-01

    Alcohol and nonsteroidal anti-inflammatory drugs are noxious agents that can disrupt the integrity of the gastroduodenal mucosal and damage the epithelial barrier and lead to increased gastroduodenal permeability. Moreover, it is not uncommon that patients are exposed to these two barrier stressors at the same time. It is thus important to know how simultaneous exposure affects the gastroduodenal barrier, and acquiring that knowledge was the goal of this study. We used a method that has been widely used for the assessment of injury to the gastroduodenal barrier induced by these noxious agents-measurement of gastroduodenal permeability as indicated by urinary excretion of ingested sucrose. We used gas chromatography to measure the amount of sucrose excreted in the urine over the 5-12h after ingestion of a bolus of sucrose. The 148 participants in the study included 92 alcoholics and 56 healthy controls. All study subjects had a baseline permeability test. To determine whether addition of a second noxious agent, in addition to chronic alcohol, further decreases gastroduodenal barrier integrity, a subset of 118 study subjects participated in another permeability test in which they were exposed to aspirin. For this test, participants ingested 1,300 mg aspirin twice, 12 and 1h before the final permeability test. The baseline permeability test showed that alcoholics have significantly higher gastroduodenal permeability than controls. Aspirin caused a significant within-group absolute increase in gastroduodenal permeability in both alcoholics and controls (+7.72%, P=.003 and +2.25%, P=.011, respectively), but the magnitude of these increases was not significantly different from each other. Baseline permeability did vary by gender, self-reported illegal drug use, and employment type. The extent of the permeability increase after aspirin ingestion varied with illegal drug use and recruitment site (a surrogate marker of socioeconomic status). Our data show that alcoholics

  9. Effects of Aspirin on Gastroduodenal Permeability in Alcoholics and Controls

    PubMed Central

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

    2010-01-01

    Alcohol and non-steroidal anti-inflammatory drugs (NSAIDS) are noxious agents that can disrupt the integrity of the gastroduodenal mucosal and damage the epithelial barrier, and lead to increased gastroduodenal permeability. Moreover, it is not uncommon that patients are exposed to these two barrier stressors at the same time. It is thus important to know how simultaneous exposure affects the gastroduodenal barrier, and acquiring that knowledge was the goal of this study. We used a method that has been widely used for the assessment of injury to the gastroduodenal barrier induced by these noxious agents – measurement of gastroduodenal permeability as indicated by urinary excretion of ingested sucrose. We used gas chromatography to measure the amount of sucrose excreted in the urine over the 5–12 h following ingestion of a bolus of sucrose. The 148 participants in the study included 92 alcoholics and 56 healthy controls. All study subjects had a baseline permeability test. To determine whether addition of a second noxious agent, in addition to chronic alcohol, further decreases gastroduodenal barrier integrity, a subset of 118 study subjects participated in another permeability test in which they were exposed to aspirin. For this test, participants ingested 1300 mg aspirin twice, 12 hours and 1 hour before the final permeability test. The baseline permeability test showed that alcoholics have significantly higher gastroduodenal permeability than controls. Aspirin caused a significant within group absolute increase in gastroduodenal permeability in both alcoholics and controls (+7.72%, p=0.003 and +2.25%, p = 0.011, respectively) but the magnitude of these increases were not significantly different from each other. Baseline permeability did vary by gender, self-reported illegal drug use, and employment type. The extent of the permeability increase after aspirin ingestion varied with illegal drug use and recruitment site (a surrogate marker of socioeconomic status

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

    PubMed

    Amico, Frank; Schlesinger, Alex; Mazzoni, Jennifer

    2016-01-01

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

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

    PubMed

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

    2014-07-18

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

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

    PubMed

    Amico, Frank; Schlesinger, Alex; Mazzoni, Jennifer

    2016-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  14. Ascorbic acid mitigation of water stress-inhibition of root growth in association with oxidative defense in tall fescue (Festuca arundinacea Schreb.)

    PubMed Central

    Xu, Yi; Xu, Qian; Huang, Bingru

    2015-01-01

    Root growth inhibition by water stress may be related to oxidative damages. The objectives of this study were to determine whether exogenous application of ascorbic acid (ASA) could mitigate root growth decline due to water stress and whether ASA effects on root growth could be regulated through activating non-enzymatic or enzymatic antioxidant systems in perennial grass species. Tall fescue (Festuca arundinacea Schreb. cv. “K-31”) plants were grown in nutrient solution, and polyethylene glycol (PEG)-8000 was added into the solution to induce water stress. For exogenous ASA treatment, ASA (5 mM) was added into the solution with or without PEG-8000. Plants treated with ASA under water stress showed significantly increased root growth rate, and those roots had significantly lower content of reactive oxygen species (ROS) (H2O2 and O2− content) than those without ASA treatment. Malondialdehyde content in root tips treated with ASA under water stress was also significantly reduced compared with those under water stress alone. In addition, free ascorbate and total ascorbate content were significantly higher in roots treated with ASA under water stress than those without ASA treatment. The enzymatic activities for ROS scavenging-related genes were not significantly altered by ASA treatment under water stress, while transcript abundances of genes encoding superoxide dismutase, catalase, ascorbate peroxidase, glutathione reductase, dehydroascorbate reductase, and monohydroascorbate reductase showed significant decreases in the root elongation zone and significant increases in the root maturation zone treated with ASA under water stress. Transcripts of genes for expansins and xyloglucan endotransglycosylases showed increased abundances in ASA-treated root maturation zone under water stress, indicating that ASA could accelerated cell wall loosening and cell expansion. The results suggested that exogenous treatment of roots with ASA enhanced root elongation under water

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

    PubMed

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

    2016-08-01

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

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

    PubMed Central

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

    1999-01-01

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

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

    SciTech Connect

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

    1986-03-01

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

  18. New Photometrically Variable Magnetic Chemically Peculiar Stars in the ASAS-3 Archive

    NASA Astrophysics Data System (ADS)

    Hümmerich, Stefan; Paunzen, Ernst; Bernhard, Klaus

    2016-10-01

    The magnetic Ap or CP2 stars are natural atomic and magnetic laboratories. Strictly periodic changes are observed in the spectra and brightness of these stars, which allow the derivation of rotational periods. Related to this group of objects are the He-weak (CP4) and He-rich stars, some of which also undergo brightness changes due to rotational modulation. Increasing the sample size of known rotational periods among CP2/4 stars is important and will contribute to our understanding of these objects and their evolution in time. We have compiled an extensive target list of CP2/4 stars from the General Catalog of Ap, HgMn, and Am stars, including several early-type (spectral types B/A) variables of undetermined type from the International Variable Star Index. We investigated our sample stars using publicly available observations from the ASAS-3 archive. Our previous efforts in this respect led to the discovery of 323 variable stars. Using a refined analysis approach, we were able to identify another 360 stars exhibiting photometric variability in ASAS-3 data. Summary data, folded light curves and, if available, information from the literature are presented for our final sample, which is composed of 334 bona-fide {α }2 Canum Venaticorum (ACV) variables, 23 ACV candidates, and 3 eclipsing binary systems. Interesting and unusual objects are discussed in detail. In particular, we call attention to HD 66051 (V414 Pup), which is an eclipsing binary system showing obvious rotational modulation of the light curve due to the presence of an ACV variable in the system.

  19. Transcriptomic Analysis Reveals the Metabolic Mechanism of L-Ascorbic Acid in Ziziphus jujuba Mill.

    PubMed Central

    Zhang, Chunmei; Huang, Jian; Li, Xingang

    2016-01-01

    Chinese jujube (Ziziphus jujuba Mill.) is the most economically important member of the Rhamnaceae family and contains a high concentration of ascorbic acid (AsA). To explore the metabolic mechanism of AsA accumulation, we investigated the abundance of AsA in the fruit development stages, the leaf and flower of Z. jujuba cv Junzao, and the mature fruit of one type of wild jujube (Z. jujuba var. spinosa Hu, Yanchuan sour jujube). And the expression patterns of genes involved in AsA biosynthesis, degradation, and recycling were analyzed. The result showed that AsA biosynthesis during early fruit development (the enlargement stage) is the main reason for jujube high accumulation. The L-galactose pathway plays a predominant role in the biosynthesis of AsA during jujube fruit development, and the genes GMP1, GME1, GGP, and GaLDH involved in the determination of AsA concentration during fruit development and in different genotypes; the myo-inositol pathway along with the genes GME2 and GMP2 in the L-galactose pathway play a compensatory role in maintaining AsA accumulation during the ripening stage. These findings enhance our understanding of the molecular mechanism in regulating AsA accumulation for jujube. PMID:26913041

  20. Dual effects of acetylsalicylic acid on ERK signaling and Mitf transcription lead to inhibition of melanogenesis.

    PubMed

    Nishio, Takashi; Usami, Mai; Awaji, Mizuki; Shinohara, Sumire; Sato, Kazuomi

    2016-01-01

    Acetylsalicylic acid (ASA) is widely used as an analgesic/antipyretic drug. It exhibits a wide range of biological effects, including preventative effects against heart attack and stroke, and the induction of apoptosis in various cancer cells. We previously found that ASA inhibits melanogenesis in B16 melanoma cells. However, the mechanisms of how ASA down-regulates melanin synthesis remain unclear. Here, we investigated the effect of ASA on melanogenic pathways, such as extracellular signal-regulated kinase (ERK) and microphthalmia-associated transcription factor (Mitf) transcription. ASA significantly inhibited melanin synthesis in a dose-dependent manner without oxidative stress and cell death. Semi-quantitative reverse transcription-polymerase chain reaction analysis showed that the inhibitory effect of ASA might be due to the inhibition of Mitf gene transcription. Interestingly, ASA also induced ERK phosphorylation. Additionally, treatment with PD98059, a specific ERK phosphorylation inhibitor, abolished the anti-melanogenic effect of ASA. These results suggest that the depigmenting effect of ASA results from down-regulation of Mitf, which is induced by both the induction of ERK phosphorylation and the inhibition of Mitf transcription.

  1. Dual effects of acetylsalicylic acid on ERK signaling and Mitf transcription lead to inhibition of melanogenesis.

    PubMed

    Nishio, Takashi; Usami, Mai; Awaji, Mizuki; Shinohara, Sumire; Sato, Kazuomi

    2016-01-01

    Acetylsalicylic acid (ASA) is widely used as an analgesic/antipyretic drug. It exhibits a wide range of biological effects, including preventative effects against heart attack and stroke, and the induction of apoptosis in various cancer cells. We previously found that ASA inhibits melanogenesis in B16 melanoma cells. However, the mechanisms of how ASA down-regulates melanin synthesis remain unclear. Here, we investigated the effect of ASA on melanogenic pathways, such as extracellular signal-regulated kinase (ERK) and microphthalmia-associated transcription factor (Mitf) transcription. ASA significantly inhibited melanin synthesis in a dose-dependent manner without oxidative stress and cell death. Semi-quantitative reverse transcription-polymerase chain reaction analysis showed that the inhibitory effect of ASA might be due to the inhibition of Mitf gene transcription. Interestingly, ASA also induced ERK phosphorylation. Additionally, treatment with PD98059, a specific ERK phosphorylation inhibitor, abolished the anti-melanogenic effect of ASA. These results suggest that the depigmenting effect of ASA results from down-regulation of Mitf, which is induced by both the induction of ERK phosphorylation and the inhibition of Mitf transcription. PMID:26699907

  2. Effect of controlled local acetylsalicylic acid release on in vitro platelet adhesion to vascular grafts.

    PubMed

    Hall, J D; Rittgers, S E; Schmidt, S P

    1994-04-01

    Thrombosis is the most serious acute problem for small diameter arterial bypass grafts. In this research, small diameter expanded polytetrafluoroethylene (e-PTFE) vascular grafts were coated with acetylsalicylic acid (ASA) loaded poly (d,l-lactide) (PLA) by a solvent casting method. The feasibility and efficacy of this approach were evaluated by ASA release studies and platelet adhesion tests. First, the ASA release kinetics were evaluated from the ASA/PLA coated vascular grafts in an in vitro steady flow loop model. ASA release was measured by a spectrophotometric technique. Finally, the efficacy of local ASA release to reduce in vitro canine platelet adhesion to grafts was determined with epifluorescent video microscopy and quantitative image analysis. The steady state release rates from the 5%, 10%, and 15% ASA/PLA coated grafts were 13.2 x 10(-5), 32.0 x 10(-5), and 41.5 x 10(-5) micrograms/cm2.sec, respectively. Platelet adhesion to 10% and 15% ASA/PLA coated grafts was reduced with respect to the control and 5% grafts for 10 days. Platelet adhesion to 5% ASA/PLA coated grafts was reduced with respect to controls at 2 and 10 days, but not initially. PMID:8064590

  3. 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.

  4. 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

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

    PubMed

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

    1985-01-01

    Several types of reactions to drugs and chemicals may precipitate or perpetuate asthmatic relapse. This review focuses on reactions to aspirin and sulfites. Approximately 40 percent of patients with rhinosinusitis, nasal polyps, and asthma and 5 to 10 percent of all asthmatic patients are sensitive to aspirin and aspirin-like nonsteroidal anti-inflammatory drugs at some time in their course. A prudent recommendation to all asthmatics is to substitute acetaminophen for aspirin. When aspirin/aspirin-like drug is essential for treatment of cardiovascular or musculoskeletal disorder, desensitization by cautious oral challenges with graded doses of aspirin can be accomplished. Treatment of the respiratory disorder per se by desensitization followed by daily therapeutic aspirin remains investigational. Sulfur dioxide and sulfites, commonly used as sanitizers and preservatives of foods and pharmaceuticals, may precipitate acute asthma in 5 percent or more of asthmatic patients. When the history suggests sulfite sensitivity, challenges can be used to confirm sensitivity and the patient counseled in avoidance of these chemicals. PMID:3880531

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

    PubMed Central

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

    1993-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    Cancer.gov

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

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

    PubMed

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

    1990-01-01

    Indications for aspirin following percutaneous transluminal angioplasty are not well defined. Although aspirin's early antithrombotic effect is believed to be beneficial, the long-term influence of aspirin on myointimal proliferative response following balloon-catheter