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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. Aspirin increases mitochondrial fatty acid oxidation.

    PubMed

    Uppala, Radha; Dudiak, Brianne; Beck, Megan E; Bharathi, Sivakama S; Zhang, Yuxun; Stolz, Donna B; Goetzman, Eric S

    2017-01-08

    The metabolic effects of salicylates are poorly understood. This study investigated the effects of aspirin on fatty acid oxidation. Aspirin increased mitochondrial long-chain fatty acid oxidation, but inhibited peroxisomal fatty acid oxidation, in two different cell lines. Aspirin increased mitochondrial protein acetylation and was found to be a stronger acetylating agent in vitro than acetyl-CoA. However, aspirin-induced acetylation did not alter the activity of fatty acid oxidation proteins, and knocking out the mitochondrial deacetylase SIRT3 did not affect the induction of long-chain fatty acid oxidation by aspirin. Aspirin did not change oxidation of medium-chain fatty acids, which can freely traverse the mitochondrial membrane. Together, these data indicate that aspirin does not directly alter mitochondrial matrix fatty acid oxidation enzymes, but most likely exerts its effects at the level of long-chain fatty acid transport into mitochondria. The drive on mitochondrial fatty acid oxidation may be a compensatory response to altered mitochondrial morphology and inhibited electron transport chain function, both of which were observed after 24 h incubation of cells with aspirin. These studies provide insight into the pathophysiology of Reye Syndrome, which is known to be triggered by aspirin ingestion in patients with fatty acid oxidation disorders.

  3. 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.

  4. 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.

  5. Application of gas-liquid chromatography and high-performance liquid chromatography to the analysis of trace amounts of salicylic acid, acetylsalicylic anhydride and acetylsalicylsalicylic acid in aspirin samples and aspirin formulations.

    PubMed

    Ali, S L

    1976-11-03

    The gas-liquid chromatographic (GLC) determination of salicylic acid (SA) in 12 commercial acetylsalicylic acid (aspirin, ASA) samples and 12 ASA formulations is reported. The GLC determination of SA as an impurity in ASA, utilising methylation with methyl iodide in the presence of potassium carbonate, requires a column chromatographic separation of SA prior to derivatization. Trace amounts of SA in ASA have also been determined by high-performance liquid chromatography (HPLC) on a Sil-X-I adsorption column using light petroleum-ethyl acetate-acetic acid as the mobile phase. Acetylsalicylic anhydride (ASN) and acetylsalicylsalicylic acid (ASSA) were determined by HPLC on a reversed-phase C18 column with water-methanol mixtures as the mobile phase. GLC was also applied to the determination of ASN as an impurity in ASA formulations.

  6. 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.

  7. Rationale and design of a Phase II clinical trial of aspirin and simvastatin for the treatment of pulmonary arterial hypertension: ASA-STAT

    PubMed Central

    Kawut, Steven M.; Bagiella, Emilia; Shimbo, Daichi; Lederer, David J.; Al-Naamani, Nadine; Roberts, Kari E.; Barr, R. Graham; Post, Wendy; Horn, Evelyn; Tracy, Russell; Hassoun, Paul; Girgis, Reda

    2011-01-01

    Background Pulmonary arterial hypertension (PAH) is a progressive disease which causes exercise limitation, heart failure, and death. Aspirin and simvastatin are highly effective and safe therapies for other cardiovascular diseases characterized by platelet activation and endothelial dysfunction, but have not been formally studied in PAH. Methods ASA-STAT is a Phase II, randomized, double-blind, placebo-controlled 2 × 2 factorial clinical trial of aspirin and simvastatin in patients with PAH. A total of 92 subjects were to be randomized to aspirin or aspirin placebo and simvastatin or simvastatin placebo. The primary outcome is the distance walked in six minutes at six months after randomization. Secondary measures include brachial artery flow-mediated dilation, circulating biomarkers of platelet and endothelial function, functional class, quality-of-life, and time to clinical end points. The incidence of adverse events will be compared between treatment groups. Screening and Enrollment We screened a total of 712 individuals with PAH. Sixty-five subjects were enrolled when the trial was terminated for futility in reaching the primary end point for simvastatin. Conclusions This study aims to determine whether aspirin or simvastatin have beneficial biologic or clinical effects in patients with PAH. The safety and side effects of these commonly prescribed cardiovascular drugs will also be assessed. PMID:21146637

  8. Aspirin resistance: truth or dare.

    PubMed

    Lordkipanidzé, Marie; Pharand, Chantal; Palisaitis, Donald A; Diodati, Jean G

    2006-12-01

    Acetylsalicylic acid, or aspirin (ASA), is widely used in patients with cardiovascular disease to prevent acute ischemic events. However, platelet response to ASA is not equal in all individuals, and a high variability in the prevalence of ASA resistance is reported in the literature (0.4-83%). Actually, ASA resistance is poorly understood; this stems from the fact that its definition is unclear, its presence can be evaluated by a number of assays that are not equivalent, and its prevalence may vary widely based on the population studied. This article (1) exposes the difficulties in defining ASA resistance; (2) discusses the mechanisms by which ASA resistance may occur; (3) presents the characteristics that may put patients at greater risk of exhibiting ASA resistance; and (4) discusses the clinical impact of ASA resistance in patients requiring chronic therapy.

  9. Aspirin

    MedlinePlus

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

  10. Aspirin

    MedlinePlus

    ... risk of developing blood clots in the legs (deep vein thrombosis) or lungs (pulmonary embolism) by ≈30% ( ... enoxaparin, fondaparinux, rivaroxaban) over aspirin for prevention of deep vein thrombosis and pulmonary embolism in patients undergoing ...

  11. Gastroprotective [6]-Gingerol Aspirinate as a Novel Chemopreventive Prodrug of Aspirin for Colon Cancer

    PubMed Central

    Zhu, Yingdong; Wang, Fang; Zhao, Yantao; Wang, Pei; Sang, Shengmin

    2017-01-01

    A growing body of research suggests daily low-dose aspirin (ASA) reduces heart diseases and colorectal cancers. However, the major limitation to the use of aspirin is its side effect to cause ulceration and bleeding in the gastrointestinal tract. Preclinical studies have shown that ginger constituents ameliorate ASA-induced gastric ulceration. We here report the design and synthesis of a novel prodrug of aspirin, [6]-gingerol aspirinate (GAS). Our data show that GAS exerts enhanced anti-cancer properties in vitro and superior gastroprotective effects in mice. GAS was also able to survive stomach acid and decomposed in intestinal linings or after absorption to simultaneously release ASA and [6]-gingerol. We further present that GAS inactivates both COX-1 and COX-2 equally. Our results demonstrate the enhanced anticancer properties along with gastroprotective effects of GAS, suggesting that GAS can be a therapeutic equivalent for ASA in inflammatory and proliferative diseases without the deleterious effects on stomach mucosa. PMID:28067282

  12. [ASA and clopidogrel for urological operations. Perioperative management].

    PubMed

    Fischer, C; Lümmen, G

    2013-11-01

    In a systematic overview and meta-analysis among more than 50,000 patients at risk for coronary artery disease, not adhering to or discontinuing aspirin (acetylsalicylic acid, ASA) was associated with a significantly increased risk of non-fatal myocardial infarction or death. Withdrawal of low dose aspirin was correlated with a threefold increase in the risk of adverse cardiovascular events. This risk is present irrespective of the length of time patients had been taking low dose aspirin. Therefore, in patients on chronic low dose aspirin for secondary prevention of cardiovascular disease, aspirin should never be discontinued. In the few available studies in urological surgery the increase in bleeding does not translate into a significant increase in specific morbidity. This seems to be also true for the additional administration of clopidogrel to aspirin. Nevertheless, in patients with drug-eluting stents and dual antiplatelet therapy, urologists should ensure a multidisciplinary management of the perioperative course.

  13. Salicylic acid retention impairs aspirin reactivity in type 2 diabetes.

    PubMed

    Zhang, Haowen; Xie, Hao; Zheng, Xiao; Chai, Yingying; Tang, Zhiyuan; Chen, Hanyu; Li, Feiyan; Christoph, Heier; Chen, Jiandong; Sun, Weixin; Ye, Hui; Wang, Shiguang; Hao, Haiping; Chen, Xiaohu

    2017-01-05

    High on-aspirin platelet reactivity (HAPR) has been associated with compromised aspirin efficacy in patients with diabetes suffering from acute cardiovascular events, but the key mechanisms remain elusive. The objective of this study was to uncover the potential link between pathogenic accumulation of salicylic acid (SA), the major metabolite of aspirin, and HAPR in diabetic state. Aspirin failed to inhibit platelet CD62P expression and thromboxane (TX) B2/6-keto-prostaglandin(PG)F1α ratio in a type 2 diabetes mellitus (T2DM) mice model, particularly in the female, which were unanimously accompanied by significantly higher plasma SA concentrations. Pre-administration with SA increased both platelet CD62P expression and TXB2/6-keto-PGF1α ratio in female T2DM mice, while pretreatment with NaHCO3 caused the opposite effect. On the in vitro human umbilical vein endothelial cells (HUVECs)-platelet interaction assay, SA suppressed inflammation-induced cyclooxygenase-2 upregulation on HUVECs and attenuated their inhibitory effect on platelet aggregation in a dose-dependent manner. The prolonged retention of SA in diabetes may be partially explained by the downregulation of various SA efflux transporters in the kidney and the decreased urine pH. Importantly, in female aspirin non-responsive patients, the trough plasma concentration of SA are markedly increased with T2DM treated with long-term aspirin, and TXB2/6-keto-PGF1α ratio and uric acid level in plasma are positively correlated with SA concentration. Our findings support that the accumulation of SA represents an important factor in causing HAPR in diabetes, and that targeting impaired SA excretion may become a novel intervention strategy to diabetes-associated HAPR.

  14. 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

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

    PubMed

    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. Acid-NSAID/aspirin interaction in peptic ulcer disease.

    PubMed

    Hunt, Richard H; Yuan, Yuhong

    2011-01-01

    The presence of gastric acid plays a critical role in the mechanisms of NSAIDs/aspirin-associated gastric and duodenal mucosal injury and ulceration. The role of gastric acid and its relationship to NSAIDs/aspirin in mucosal damage, ulcer and ulcer complications continues to be an important concern because of the increasing worldwide use of NSAIDs and aspirin. Acid suppression continues to be an important prevention strategy for NSAID-associated gastric and duodenal ulcer and ulcer complications. While a coxib or an NSAID and PPI in combination are considered to have comparable safety profiles, the evidence from direct comparisons in high-risk patients is limited, and the cardiovascular safety of coxibs and NSAIDs remains a concern especially in patients with a high risk of cardiovascular disease. An evaluation of individual gastrointestinal and cardiovascular risks and benefits, selection of the most appropriate NSAID and dose for each particular patient should always be emphasized. Twice daily PPI is more appropriate to protect a patient who is taking NSAIDs twice daily. PPI co-therapy is still recommended in patients receiving dual antiplatelet treatment, although conflicting results have been reported about adverse drug interactions between PPIs and clopidogrel.

  17. 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.

  18. EFFECTS OF ASPIRIN& SIMVASTATIN AND ASPIRIN, SIMVASTATIN & LIPOIC ACID ON HEME OXYGENASE-1 IN HEALTHY HUMAN SUBJECTS

    PubMed Central

    Bharucha, Adil E.; Choi, Kyoung Moo; Saw, Jessica; Gibbons, Simon J.; Farrugia, Gianrico; Carlson, David; Zinsmeister, Alan R

    2014-01-01

    SUMMARY Background Heme-oxygenase 1 (HO-1) degrades heme and protects against oxidative stress. In vitro and animal models suggest that HO-1 is beneficial in several diseases (e.g., post-operative ileus, gastroparesis, acute pancreatitis, and colitis). However the only drugs (i.e., hemin and heme arginate) which pharmacologically up-regulate HO-1 in humans are expensive and can only be administered intravenously. Our aims were to compare the effects of placebo, aspirin and simvastatin alone, and with α-lipoic acid, on HO-1 protein concentration and activity in humans. Methods This randomized, double-blind, placebo-controlled study compared the effects of 3 oral regimens administered for 7 days, ie, placebo; aspirin (325 mg twice daily) and simvastatin (40 mg twice daily); aspirin, simvastatin, and the sodium salt of R-α-lipoic acid (NaRLA, 600 mg three times daily) on markers of HO-1 activation (i.e., plasma HO-1 protein concentration and venous monocyte HO-1 protein activity) in 18 healthy subjects (14 females). Markers of HO-1 activation were evaluated at baseline, days 2 and 7. Key Results Baseline HO-1 protein concentrations and activity were similar amongst the three groups. Compared to placebo, aspirin and simvastatin combined, or together with NaRLA did not affect HO-1 protein concentration or activity at 2 or 7 days. HO-1 protein concentrations and activity were correlated on day 7 (r = 0.75, p = 0.0004) but not at baseline and on day 2. Conclusions At therapeutic doses, aspirin, simvastatin, and α-lipoic acid do not increase plasma HO-1 protein concentration or venous monocyte HO-1 activity in healthy humans. PMID:25093998

  19. 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.

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

    PubMed

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

    2015-07-01

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

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

    PubMed

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

    1993-08-01

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

  2. 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.

  3. 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.

  4. 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

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

    PubMed

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

    2015-08-03

    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.

  6. Adjunct therapy of n-3 fatty acids to 5-ASA ameliorates inflammatory score and decreases NF-κB in rats with TNBS-induced colitis.

    PubMed

    Mbodji, Khaly; Charpentier, Cloé; Guérin, Charlène; Querec, Coraline; Bole-Feysot, Christine; Aziz, Moutaz; Savoye, Guillaume; Déchelotte, Pierre; Marion-Letellier, Rachel

    2013-04-01

    5-aminosalicylic acid (5-ASA) is widely used for the treatment of inflammatory bowel disease (IBD). Recent studies have evaluated the potential of nutritional intervention as adjunct therapy to 5-ASA in IBD. N-3 polyunsaturated fatty acids (PUFA) have shown potent anti-inflammatory properties in gut inflammation. Therefore, we aimed to evaluate the efficacy of the dual therapy (n-3 PUFA plus 5-ASA) in rats with 2, 4, 6-trinitrobenzen sulfonic acid (TNBS)-induced colitis. Colitis was induced by intrarectal injection of TNBS while control rats received the vehicle. Rats received by gavage a fish oil-rich formula (n-3 groups) or an isocaloric and isolipidic oil formula supplemented with 5-ASA for 14 days. A dose response of 5-ASA (5-75 mg. suppression mg kg(-1) d(-1)) was tested. Colitis was evaluated and several inflammatory markers were quantified in the colon. COX-2 expression (P<.05) and pro-inflammatory eicosanoids production of prostaglandin E2 (P<.001) and leukotriene B4 (P<.001) were significantly inhibited by n-3 PUFA or 5-ASA therapy. 5-ASA also reduces mRNA levels of tumor necrosis factor α (P<.05). n-3 PUFA or 5-ASA significantly inhibits nuclear factor κB (NF-κB) activation (P<.01 and P<.05, respectively). The dual therapy n-3 PUFA plus 5-ASA also inhibited inflammatory response by lowering NF-κB activation (P<.01) or inducing peroxisome proliferator-activated receptor-γ (PPARγ) expression (P<.05). These results indicate that 5-ASA plus n-3 PUFAs are more effective than a higher dose of 5-ASA alone to reduce NF-κB activation and to induce PPARγ. By contrast, the dual therapy did not improve the effects of individual treatments on eicosanoids or cytokine production. Use of n-3 PUFA in addition to 5-ASA may reduce dose of standard therapy.

  7. 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.

  8. 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.

  9. Experiments with Aspirin.

    ERIC Educational Resources Information Center

    Borer, Londa L.; Barry, Edward

    2000-01-01

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

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

    PubMed

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

    2015-05-01

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

  11. 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.

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

    PubMed Central

    RAO, CHINTHALAPALLY V.; JOSEPH, STANCY; GAO, LI; PATLOLLA, JAGAN M.R.; CHOI, CHANG-IN; KOPELOVICH, LEVY; STEELE, VERNON E.; RIGAS, BASIL

    2008-01-01

    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

  13. 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

  14. ASA24-2016

    Cancer.gov

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

  15. The infrared spectra and structure of acetylsalicylic acid (aspirin) and its oxyanion: an ab initio force field treatment

    NASA Astrophysics Data System (ADS)

    Binev, I. G.; Stamboliyska, B. A.; Binev, Y. I.

    1996-05-01

    The structures of acetylsalicylic acid (aspirin) (I) and its oxyanion (II) have been studied by means of infrared spectra and ab initio 3-21 G force field calculations. The 3100-1100 cm -1 region bands of both the aspirin molecule and its oxyanion have been assigned. The theoretical infrared data for the free aspirin anion are in good agreement with the experimental data for aspirin alkali-metal salts in dimethyl sulfoxide- d6. The theoretical geometrical parameters for the isolated aspirin molecule are close to the literature X-ray diffraction data for its dimer in the solid state, except for those of the carboxy group, which participates directly in hydrogen bond formation. The changes in both the spectral and geometrical parameters, caused by the conversion of the aspirin molecule into the anion, are essential, but they are localized mainly within the carboxy group and the adjacent C-Ph bond. This is also true for the changes in the corresponding bond indices and electronic charges.

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

    PubMed

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

    2017-05-10

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

  17. Aspirin-sensitive asthma due to diffuse neuroendocrine system pathology.

    PubMed

    Evsyukova, Helen V

    2002-08-01

    Available clinical data on aspirin-sensitive asthma (ASA) indicate that ASA patients have certain disturbances in the nervous, endocrine, immune and other body systems. It has been found that such patients have a lower melatonin (MT) production in daytime, a pathology of the platelet membrane-receptor complex, and a pathological response to exogenic MT and acetylsalicylic acid. A hypothesis has been suggested in which ASA is considered as apudopathy caused by dysfunction of MT-producing cells. The decreased MT production and the disturbed cell sensitivity to MT lead to pathological changes in individual organs and functional systems. As a result, there is an enhanced lipid peroxidation, an excessive production of reactive oxygen radicals, and a reduced inhibitory action of MT on the 5-lipoxygenase and NO-synthase activities. The lower MT content also results in an intense aggregation of platelets, activating these cells and increasing the production of leukotrienes and nitric oxide. These changes disturb the pulmonary microcirculation, causing the bronchial obturation syndrome even in patient who do not take aspirin or other nonsteroidal anti-inflammatory drugs. The lower basic production of MT is also responsible for a lower content of its metabolite-endogenic acetylsalicylic acid, thereby increasing the sensitivity of melatonin-producing cells, in particular of platelets, to this acid. So, even minimal aspirin doses inhibit the activity of COX-1, which shunts the already abnormal metabolism of arachidonic acid. This, in turn, leads to a greater production of leukotrienes and, hence, to a severe course of the disease. This hypothesis has become the basis for a new pathogenetic approach to the treatment of ASA patients by correcting the melatonin content with peptide bioregulators--the epiphysis extracts--Epithalamin and Epiphamin.

  18. The abnormal in vitro response to aspirin of platelets from aspirin-sensitive asthmatics is inhibited after inhalation of nedocromil sodium but not of sodium cromoglycate.

    PubMed Central

    Marquette, C H; Joseph, M; Tonnel, A B; Vorng, H; Lassalle, P; Tsicopoulos, A; Capron, A

    1990-01-01

    1. Blood platelets from patients with aspirin-sensitive asthma (ASA) generated cytotoxic mediators in the presence of aspirin. This abnormal in vitro response to aspirin was abolished within 1 h after nedocromil sodium inhalation but not after sodium cromoglycate inhalation. 2. Platelets recovered this reactivity to aspirin by 12 hours after nedocromil sodium treatment of ASA-patients. 3. The in vitro reactivity to aspirin of ASA platelets isolated before inhalation was inhibited in the presence of serum isolated 15 and 60 min after nedocromil sodium inhalation. PMID:2161678

  19. Drug delivery and therapeutic impact of extended-release acetylsalicylic acid.

    PubMed

    Bliden, Kevin P; Patrick, Jeff; Pennell, Andrew T; Tantry, Udaya S; Gurbel, Paul A

    2016-01-01

    Current treatment guidelines recommend once-daily, low-dose acetylsalicylic acid (ASA; aspirin) for secondary prevention of cardiovascular events. However, the anti-thrombotic benefits of traditional ASA formulations may not extend over a 24-h period, especially in patients at high risk for a recurrent cardiovascular event. A next-generation, extended-release ASA formulation (ER-ASA) has been developed to provide 24-h anti-thrombotic coverage with once-daily dosing. The pharmacokinetics of ER-ASA indicates slower absorption and prolonged ASA release versus immediate-release ASA, with a favorable safety profile. ER-ASA minimizes systemic ASA absorption and provides sustained antiplatelet effects over a 24-h period.

  20. 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.

  1. 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

  2. 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

  3. ASA24-Kids

    Cancer.gov

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

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

    PubMed

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

    1987-10-01

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

  5. 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

  6. 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.

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

    MedlinePlus

    ... Some medication labels may use the words acetylsalicylate, acetylsalicylic acid, salicylic, salicylamide, phenyl salicylate, etc., instead of the word aspirin. There is not data as to other forms ...

  8. 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 ...

  9. Aspirin revealed

    NASA Astrophysics Data System (ADS)

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

    2007-03-01

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

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

    PubMed Central

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

    2013-01-01

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

  11. 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.

  12. Effect of Panax notoginseng saponins on the pharmacokinetics of aspirin in rats.

    PubMed

    Tian, Zhihao; Pang, Huanhuan; Du, Shouying; Lu, Yang; Zhang, Lin; Wu, Huichao; Guo, Shuang; Wang, Min; Zhang, Qiang

    2017-01-01

    Aspirin (ASA) is widely used to treat fever, pain, inflammation and cerebral infarction in clinic. Panax Notoginseng Saponins (PNS) is the extracts of Panax Notoginseng (PN)-a traditional Chinese medicine extensively used in cardiovascular diseases. Panax notoginseng saponins and ASA are both widely used to treat cerebral infarction in China. Good results in clinical practice have been achieved when the two drugs were taken together. To investigate the effect of PNS on ASA in vivo, the concentrations of salicylic acid (SA) in blood were measured after oral administration of ASA or ASA combined with PNS by UPLC-MS/MS. Sample preparation was carried out by the protein precipitation technique with an internal Saikosaponin A standard. The separation of two components was achieved by using an ACQUITY UPLC (®)BEH C18 Column (1.7μm 2.1×100mm) by gradient elution using water (containing 0.2% formic acid) and acetonitrile (containing 0.2% formic acid) as the mobile phase at a flow rate of 0.2mL/min. The pharmacokinetic parameters were determined by using non-compartmental analysis. The results suggested that drug-drug interaction in vivo existed between PNS and ASA. The concentration of the SA was increasing when the two drugs were administered together. The transport of ASA and SA in MDCK -MDR1 cell monolayer was used to verify this conclusion. The values of apparent permeability coefficients (Papp) were significantly increased when the two drugs were used together. This result suggested PNS could increase the gastrointestinal tract absorption of ASA and SA. These findings provide more insight for wise use of two drugs to treat or prevent cardiovascular diseases.

  13. Topical diclofenac does not affect the antiplatelet properties of aspirin as compared to the intermediate effects of oral diclofenac: A prospective, randomized, complete crossover study.

    PubMed

    Rowcliffe, M; Nezami, B; Westphal, E S; Rainka, M; Janda, M; Bates, V; Gengo, F

    2016-04-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) adversely interact with aspirin, diminishing its antiplatelet effect and potentially placing patients at an increased risk for recurrent thrombotic events. This crossover study aimed to determine whether the topical NSAID diclofenac epolamine 1.3% patch or oral diclofenac 50 mg interfered with the antiplatelet effects of aspirin 325 mg. Twelve healthy men and women aged 18-50 were included. Participants were randomized into 5 treatment arms: aspirin, diclofenac potassium 50 mg, diclofenac patch, diclofenac potassium plus ASA 325 mg, and diclofenac patch plus aspirin. Platelet responsiveness was determined using whole-blood impedance aggregation (WBA) to collagen 1 μg/mL and arachidonic acid (AA) 0.5 mM and was sampled every 2 hours. No significant difference in platelet function was observed following the diclofenac patch and aspirin vs aspirin alone. Oral diclofenac produced a mixed effect with significant reduction in platelet inhibition at hour 2 and hour 8 following aspirin administration. Topical diclofenac does not significantly interfere with the antiplatelet effects of aspirin and may be a safer alternative to the oral formulation.

  14. 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.

  15. ASA24-Canada

    Cancer.gov

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

  16. Arachidonic acid metabolism and inhibition of cyclooxygenase in platelets from asthmatic subjects with aspirin intolerance.

    PubMed

    Bonne, C; Moneret-Vautrin, D A; Wayoff, M; Descharmes, A; Gazel, P; Legrand, A; Kalt, C

    1985-02-01

    Exaggerated inhibition of cyclooxygenase has been proposed as a mechanism of drug-induced bronchospasm in aspirin-intolerant patients. This study, using platelets, shows that inhibition of prostaglandin biosynthesis by aspirin is unmodified in patients when compared with healthy subjects. The ratio of cyclooxygenase:lipoxygenase products is similar in platelets from patients and control subjects. We conclude that the cyclooxygenase alteration observed in cells from the respiratory tract is not generalised to other cells such as platelets. We also propose that the major abnormality in NSAID-intolerant patients would affect receptivity to lipoxygenase products more than their biosynthesis.

  17. Increased blood plasma hydrolysis of acetylsalicylic acid in type 2 diabetic patients: a role of plasma esterases.

    PubMed

    Gresner, Peter; Dolník, Martin; Waczulíková, Iveta; Bryszewska, Maria; Sikurová, Libusa; Watala, Cezary

    2006-02-01

    Hydrolysis of acetylsalicylic acid (ASA, aspirin), an antiplatelet drug commonly used in the prevention of stroke and myocardial infarction, seems to play a crucial role in its pharmacological action. Thirty-eight healthy volunteers and 38 type 2 diabetic patients were enrolled to test the hypothesis that the enhanced plasma degradation and lowered bioavailability of ASA in diabetic patients is associated with the attenuation of platelet response. Aspirin esterase activities were tested at pH 7.4 and 5.5. A significantly higher overall aspirin esterase activity was noted at pH 7.4 in the diabetic patients (P<0.003), corresponding to faster ASA hydrolysis (P<0.006). This increased activity was attributable to butyrylcholinesterase and probably to albumin, because it was effectively inhibited by eserine and 4-bis-nitrophenyl phosphate (P<0.01). No significant differences between control and diabetic subjects were found at pH 5.5 in either enzymatic activities or ASA hydrolysis rates. The enhanced plasma ASA degradation in diabetic subjects was significantly associated with the refractoriness of blood platelets to ASA (P<0.05) and modulated by plasma cholesterol (P<0.01). No direct effects of plasma pH or albumin were observed. In conclusion, higher aspirin esterase activity contributes to the lowered response of diabetic platelets to ASA-mediated antiplatelet therapy.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Aspirin overdose

    MedlinePlus

    ... it is only used as a very last resort. Outlook (Prognosis) A toxic dose of aspirin is ... evidence-based consensus guideline for out-of-hospital management. Clinical Toxicology . 2007:Vol. 45; pp 95-131. ...

  3. 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).

  4. 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 Central

    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 (81 mg/day) for seven days, then with FO (4 g/day) for 28 days, then in combination for another seven days. Lysophospholipids and platelet measures were determined after acute (4 hours) 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. PMID:24373610

  5. 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.

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

    PubMed Central

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

    2016-01-01

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

  7. Effectiveness of combined salmon calcitonin and aspirin therapy for osteoporosis in ovariectomized rats.

    PubMed

    Wei, Jinsong; Wang, Jian; Gong, Yan; Zeng, Rong

    2015-08-01

    The objective of the present study was to assess the effectiveness of combined salmon calcitonin (sCT) and aspirin [acetylsalicylic acid (ASA)] treatment in an ovariectomized (OVX) rat model of postmenopausal osteoporosis. Following 12 weeks of treatment, therapeutic efficacy was assessed by evaluating changes in the biochemical and biophysical properties of bone (n=8 rats per group). Serological markers of bone metabolism were measured by ELISA; bone mineral densities (BMD) by dual energy X-ray absorptiometry; bone biomechanics of the femur and lumbar vertebrae by three-point stress test; trabecular bone morphology of lumbar vertebrae by hematoxylin and eosin staining; messenger RNA expression levels of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in bone marrow cells by reverse transcription-quantitative polymerase chain reaction and OPG and RANKL protein expression levels in the proximal tibia were analyzed by immunohistochemistry. Compared with treatment by sCT or ASA alone, combined treatment (sCT+ASA) increased BMD, improved femur bone strength, normalized trabecular network architecture and morphology, and increased mRNA and protein expression of OPG, while reducing the expression of RANKL. Collectively, these results demonstrated that combined treatment (sCT+ASA) of osteoporotic symptoms in OVX rats was more effective than treatment with sCT or ASA alone. Furthermore, these two drugs appeared to alter the expression of two distinct factors in the OPG/RANKL/RANK system, suggesting that their effects may be synergistic. Since sCT and ASA are currently approved for use in humans, the results of the present study suggest that the safety and efficacy of sCT+ASA combined therapy for post-menopausal osteoporosis should be assessed in clinical trials.

  8. THE EFFECT OF ACETYLSALICYLIC ACID ON PLATELET FUNCTION

    PubMed Central

    Evans, Geoffrey; Packham, Marian A.; Nishizawa, Edward E.; Mustard, James F.; Murphy, Edmund A.

    1968-01-01

    Acetylsalicylic acid (ASA, aspirin) and sodium salicylate inhibit platelet aggregation induced by collagen, antigen-antibody complexes, gamma globulin-coated particles or thrombin. These compounds suppress the release of platelet constituents, such as adenosine diphosphate (ADP) and serotonin, induced by such stimuli. Since ASA and sodium salicylate do not inhibit ADP-induced platelet aggregation, it appears that their effect on the action of the other stimuli is due to a decrease in the amount of ADP released. The administration of ASA to rabbits (in doses which inhibited collagen-induced platelet aggregation) impaired hemostasis, prolonged platelet survival, and diminished the amount of deposit formed in an extracorporeal shunt. PMID:4176225

  9. Paracetamol (acetaminophen), aspirin (acetylsalicylic acid) and indomethacin are anti-androgenic in the rat foetal testis.

    PubMed

    Kristensen, D M; Lesné, L; Le Fol, V; Desdoits-Lethimonier, C; Dejucq-Rainsford, N; Leffers, H; Jégou, B

    2012-06-01

    More than half the pregnant women in the Western world report taking mild analgesics. These pharmaceutical compounds have been associated with congenital cryptorchidism in humans, the best-known risk factor for low semen quality and testicular germ cell cancer. Furthermore, some of these mild analgesics exert potent anti-androgenic effects in the male rat and several endocrine-disrupting compounds, known to alter masculinization, have also been shown to be potent inhibitors of prostaglandin (PG) synthesis similar to mild analgesics. Using a 3-day ex vivo organotypic model system based on gestational day 14.5 rat testes, we herein show that testosterone production was inhibited by paracetamol, at doses of 0.1 μm to 100 μm. Similar results were obtained for aspirin (1-100 μm) and indomethacin (10 μm). The production of the other Leydig cell hormone, Insl3, was not disrupted by exposure to paracetamol. Investigations of the gross anatomy of the testis as well as Leydig cells number and rate of gonocyte apoptosis after the 3 days of ex vivo differentiation showed no significant effect of the analgesics tested compared with controls. These data indicate therefore that mild analgesics specifically inhibit testosterone production in rat foetal testes in vitro and that these compounds had no effect on gonocyte survival. Parallel determinations of prostaglandin D2 (PGD2) production indicated that the effects of paracetamol and aspirin on PGD2 and testosterone were not connected, whereas the effects of indomethacin were correlated. We conclude that mild analgesics exert direct and specific anti-androgenic effects in rat foetal testis in our experimental setup and that the mechanism of action is probably uncoupled from the inhibition of PG synthesis.

  10. The Active Component of Aspirin, Salicylic Acid, Promotes Staphylococcus aureus Biofilm Formation in a PIA-dependent Manner.

    PubMed

    Dotto, Cristian; Lombarte Serrat, Andrea; Cattelan, Natalia; Barbagelata, María S; Yantorno, Osvaldo M; Sordelli, Daniel O; Ehling-Schulz, Monika; Grunert, Tom; Buzzola, Fernanda R

    2017-01-01

    Aspirin has provided clear benefits to human health. But salicylic acid (SAL) -the main aspirin biometabolite- exerts several effects on eukaryote and prokaryote cells. SAL can affect, for instance, the expression of Staphylococcus aureus virulence factors. SAL can also form complexes with iron cations and it has been shown that different iron chelating molecules diminished the formation of S. aureus biofilm. The aim of this study was to elucidate whether the iron content limitation caused by SAL can modify the S. aureus metabolism and/or metabolic regulators thus changing the expression of the main polysaccharides involved in biofilm formation. The exposure of biofilm to 2 mM SAL induced a 27% reduction in the intracellular free Fe(2+) concentration compared with the controls. In addition, SAL depleted 23% of the available free Fe(2+) cation in culture media. These moderate iron-limited conditions promoted an intensification of biofilms formed by strain Newman and by S. aureus clinical isolates related to the USA300 and USA100 clones. The slight decrease in iron bioavailability generated by SAL was enough to induce the increase of PIA expression in biofilms formed by methicillin-resistant as well as methicillin-sensitive S. aureus strains. S. aureus did not produce capsular polysaccharide (CP) when it was forming biofilms under any of the experimental conditions tested. Furthermore, SAL diminished aconitase activity and stimulated the lactic fermentation pathway in bacteria forming biofilms. The polysaccharide composition of S. aureus biofilms was examined and FTIR spectroscopic analysis revealed a clear impact of SAL in a codY-dependent manner. Moreover, SAL negatively affected codY transcription in mature biofilms thus relieving the CodY repression of the ica operon. Treatment of mice with SAL induced a significant increase of S aureus colonization. It is suggested that the elevated PIA expression induced by SAL might be responsible for the high nasal

  11. The Active Component of Aspirin, Salicylic Acid, Promotes Staphylococcus aureus Biofilm Formation in a PIA-dependent Manner

    PubMed Central

    Dotto, Cristian; Lombarte Serrat, Andrea; Cattelan, Natalia; Barbagelata, María S.; Yantorno, Osvaldo M.; Sordelli, Daniel O.; Ehling-Schulz, Monika; Grunert, Tom; Buzzola, Fernanda R.

    2017-01-01

    Aspirin has provided clear benefits to human health. But salicylic acid (SAL) -the main aspirin biometabolite- exerts several effects on eukaryote and prokaryote cells. SAL can affect, for instance, the expression of Staphylococcus aureus virulence factors. SAL can also form complexes with iron cations and it has been shown that different iron chelating molecules diminished the formation of S. aureus biofilm. The aim of this study was to elucidate whether the iron content limitation caused by SAL can modify the S. aureus metabolism and/or metabolic regulators thus changing the expression of the main polysaccharides involved in biofilm formation. The exposure of biofilm to 2 mM SAL induced a 27% reduction in the intracellular free Fe2+ concentration compared with the controls. In addition, SAL depleted 23% of the available free Fe2+ cation in culture media. These moderate iron-limited conditions promoted an intensification of biofilms formed by strain Newman and by S. aureus clinical isolates related to the USA300 and USA100 clones. The slight decrease in iron bioavailability generated by SAL was enough to induce the increase of PIA expression in biofilms formed by methicillin-resistant as well as methicillin-sensitive S. aureus strains. S. aureus did not produce capsular polysaccharide (CP) when it was forming biofilms under any of the experimental conditions tested. Furthermore, SAL diminished aconitase activity and stimulated the lactic fermentation pathway in bacteria forming biofilms. The polysaccharide composition of S. aureus biofilms was examined and FTIR spectroscopic analysis revealed a clear impact of SAL in a codY-dependent manner. Moreover, SAL negatively affected codY transcription in mature biofilms thus relieving the CodY repression of the ica operon. Treatment of mice with SAL induced a significant increase of S aureus colonization. It is suggested that the elevated PIA expression induced by SAL might be responsible for the high nasal colonization

  12. Immunological mechanisms in aspirin hypersensitivity. Studies on the immunogenicity of free aspirin.

    PubMed

    Cîrstea, M; Suhaciu, G; Cîrje, M; Ciontescu, L

    1976-10-01

    Anti-aspiryl antibodies were produced in rabbits and guinea pigs by inoculation of aspirin incorporated in complete or incomplete Freund's adjuvant. These antibodies were readily detected by passive haemagglutination using rabbit erythrocytes incubated with aspirin at alkaline pH. Aspiryl conjugates with ovalbumin, human gamma-globulin, bovine gamma-globulin and rabbit serum were also prepared by incubating the proteins with aspirin at alkaline pH. Aspiryl conjugates prepared by this technique behaved, immunologically, identically with the conjugates prepared from aspirin chloride. By contrast, the molar absorbance at 305 nm of the conjugates prepared from aspirin was about 25 times lower than the molar absorbance of the conjugates prepared from aspirin chloride. Since the absorbance of salicylic acid is about eight times greater than that of aspirin, the conclusion is drawn that the aspiryl/salicylyl ratio is significantly higher in the conjugates prepared by incubating proteins with aspirin at alkaline pH than in the conjugates prepared from aspirin chloride. In parallel experiments, salicylic acid did not induce formation of specific antibodies capable of reacting with aspirin- or salicylic acid-treated red cells. Sera giving positive passive haemagglutination with aspirin-treated erythrocytes did not react with erythrocytes treated with salicylic acid or acetic anhydride.

  13. 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.

  14. 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.

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

    PubMed

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

    2005-01-01

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

  16. 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

  17. Hydrogen atoms in acetylsalicylic acid (Aspirin): the librating methyl group and probing the potential well in the hydrogen-bonded dimer

    NASA Astrophysics Data System (ADS)

    Wilson, Chick C.

    2001-02-01

    The structure of acetylsalicylic acid (2-(acetoyloxy)benzoic acid; Aspirin) has been studied by variable temperature single crystal neutron diffraction. The usual large torsional librational motion of the terminal methyl group is observed and its temperature dependence analysed using a simple model for the potential, yielding the force constant and barrier height for this motion. In addition, asymmetry of the scattering density of the proton involved in the hydrogen bond forming the carboxylic acid dimer motif is observed at temperatures above 200 K. This asymmetry is discussed in terms of its possible implications for the shape of the hydrogen bonding potential well.

  18. Swelling and aspirin release study: cross-linked pH-sensitive vinyl acetate-co-acrylic acid (VAC-co-AA) hydrogels.

    PubMed

    Ranjha, Nazar Mohammad; Mudassir, Jahanzeb

    2008-05-01

    The objective of this work was to develop new pH-sensitive hydrogels to deliver gastric mucosal irritating drugs to the lower part of the gastrointestinal tract. For this purpose, cross-linked vinyl acetate-co-acrylic acid (VAC-co-AA) hydrogels were synthesized by using N, N, methylene bisacrylamide (MBAAm) as a cross-linking agent. Different ratios of 90:10, 70:30, 50:50, 30:70, and 10:90 of VAC-co-AA were synthesized. All of the compositions were cross-linked using 0.15, 0.30, 0.45, and 0.60 mol percent MBAAm. Swelling and aspirin release were studied for 8 hour period. The drug release data were fitted into various kinetic models like the zero-order, first-order, Higuchi, and Peppas. Hydrogels were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. In addition to the above, these hydrogels were loaded with 2%, 8% and 14% w/v aspirin solutions, keeping the monomeric composition and degree of cross-linking constant. In conclusion, it can be said that aspirin can be successfully incorporated into cross-linked VAC/AA hydrogels and its swelling and drug release can be modulated by changing the mole fraction of the acid component in the gels.

  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.

  20. ASA24® Researcher Instructions

    Cancer.gov

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

  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. (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.

  3. Acetylation of prostaglandin synthase by aspirin.

    PubMed Central

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

    1975-01-01

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

  4. 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

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

    PubMed

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

    2014-07-01

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

  6. 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

  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).

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

    PubMed Central

    Dai, Shao-Xing; Li, Wen-Xing

    2016-01-01

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

  10. New insights on the possible role of mast cells in aspirin-induced asthma.

    PubMed

    Mortaz, Esmaeil; Engels, Ferdi; Nijkamp, Frans P; Redegeld, Frank A

    2009-06-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are major drugs used in the treatment of inflammation and pain in a wide variety of disorders. The best-known mechanism of action of NSAIDs is the inhibition of prostaglandin synthesis as a result of their action on cyclooxygenase (COX) enzymes. However, data have been accumulating through the years indicating that NSAIDs also act on other targets in cell signaling. It has been established that NSAIDs induce anti-inflammatory effects independent of COX. Acetylsalicylic acid (ASA) and other inhibitors of COX induce severe bronchospasms and asthmatic attacks in a significant population of asthmatic patients. The etiology of ASA induced asthma is complex and not fully understood, but most evidence points towards an abnormality of arachidonic acid (AA) metabolism. Since doses of ASA necessary to treat chronic inflammatory diseases appeared much higher than those required to inhibit PG synthesis, COX-independent mechanisms of NSAIDs were postulated. Recently, we have shown that NSAIDs induced expression of heat shock proteins specially HSP70. Heat shock proteins (HSPs) are normal intracellular proteins that are produced in greater amounts when cells are subjected to stress or injury. Interestingly, a potential pathogenic role for heat shock proteins in diseases such as autoimmune disease, vascular disease has been reported. Because mast cells have been reported to play a role in the pathogenesis of ASA induced asthma, a link between heat shock proteins and this disease could postulated. In this review, an overview is given on aspirin-induced asthma and the cells and mediators that may play a role therein. Mast cell signaling with regard to interaction with NSAIDs and heat shock proteins (HSPs) and toll-like receptors (TLRs) is further highlighted.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. Interaction between the LMWH reviparin and aspirin in healthy volunteers

    PubMed Central

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

    2000-01-01

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

  18. Comparison between 3-Nitrooxyphenyl acetylsalicylate (NO-ASA) and O2-(acetylsalicyloxymethyl)-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (NONO-ASA) as safe anti-inflammatory, analgesic, antipyretic, antioxidant prodrugs.

    PubMed

    Chattopadhyay, Mitali; Velazquez, Carlos A; Pruski, April; Nia, Kamran V; Abdellatif, Khaled R; Keefer, Larry K; Kashfi, Khosrow

    2010-11-01

    Chronic inflammation is an underlying etiological factor in carcinogenesis; nonsteroidal anti-inflammatory drugs (NSAIDs) and their chemically modified NO-releasing prodrugs (NO-NSAIDs) are promising chemopreventive agents. The aim of this study was to conduct a head-to-head comparison between two NO-ASAs possessing different NO donor groups, an organic nitrate [3-nitrooxyphenyl acetylsalicylate (NO-ASA; NCX-4016)] and an N-diazeniumdiolate [NONO-ASA, O(2)- (acetylsalicyloxymethyl)-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (NONO-ASA; CVM-01)], as antiulcerogenic, analgesic, anti-inflammatory, and antipyretic agents. All drugs were administered orally at equimolar doses. For antiulcerogenic study, 6 h after administration, the number and size of hemorrhagic lesions in stomachs from euthanized animals were counted. Tissue samples were frozen for prostaglandin E(2) (PGE(2)), superoxide dismutase (SOD), and malondialdehyde determination. For anti-inflammatory study, 1 h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 6 h. For antipyretic study, 1 h after dosing, fever was induced by intraperitoneal LPS, and body core temperatures measured for 5 h. For analgesic study, time-dependent analgesic effect of prodrugs was evaluated by carrageenan-induced hyperalgesia. Drugs were administered 30 min after carrageenan. NO-ASA and NONO-ASA were equipotent as analgesic and anti-inflammatory agents but were better than aspirin. Despite a drastic reduction of PGE(2) in stomach tissue, both prodrugs were devoid of gastric side effects. Lipid peroxidation induced by aspirin was higher than that observed by prodrugs. SOD activity induced by both prodrugs was similar, but approximately 2-fold higher than that induced by aspirin. CVM-01 is as effective as NCX-4016 in anti-inflammatory, analgesic, and antipyretic assays in vivo, and it showed an equivalent safety profile in the stomach. These results underscore the use of N

  19. Aspirin and (or) omega-3 polyunsaturated fatty acids protect against corticohippocampal neurodegeneration and downregulate lipoxin A4 production and formyl peptide receptor-like 1 expression in pentylenetetrazole-kindled rats.

    PubMed

    Abd-Elghafour, Basma A; El-Sayed, Norhan M; Ahmed, Amal A M; Zaitone, Sawsan A; Moustafa, Yasser M

    2016-11-10

    There is evidence for a relationship between inflammation and seizures because epilepsy can be caused by or result in inflammation. This study aimed to investigate the effect of aspirin and (or) omega-3 polyunsaturated fatty acids (PUFAs) on seizure activity and neurodegeneration in pentylenetetrazole (PTZ)-kindled rats focusing on their effect on corticohippocampal production of lipoxin A4 (LXA4) and expression of formyl peptide receptor-like 1 (FPRL1) receptors. Male rats were injected with PTZ (35 mg/kg, i.p.) 3 times per week for a total of 15 doses. Rats were treated daily with aspirin (20 mg/kg, i.p.), omega-3 PUFAs (85 mg/kg, p.o.), or a combination of them for 35 days. Both LXA4 level and expression of FPRL1 receptor in the cortices and hippocampi of rats' brains were greater in PTZ-kindled rats compared to a saline control group. Cotreatment with aspirin and (or) omega-3 PUFAs reduced convulsive behaviour; reduced levels of LXA4, interleukin-1β, and nuclear factor-κB; and showed a lower percentage of corticohippocampal degenerative cells compared to PTZ-kindled rats. The combination of the 2 therapeutic agents did not provide significant improvement in comparison with the monotherapies. These findings suggest the use of aspirin or omega-3 PUFAs may delay the development of seizures and provide neuroprotection in a clinical setting.

  20. Aspirin for vascular dementia

    PubMed Central

    Rands, Gianetta; Orrell, Martin

    2014-01-01

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

  1. Evaluation the effect of low-dose aspirin on endothelial dysfunction in preeclamptic patients

    PubMed Central

    Hashemi, Mohammad; Baktash, Forouz; Heshmat-Ghahdarijani, Kiyan; Zarean, Elahe; Bahrani, Saeide

    2016-01-01

    Background: Preeclampsia complicates up to 3% of pregnancies in developing countries. Endothelial dysfunction plays an important role in pathogenesis of preeclampsia. In this study, we aim to evaluate the effect of low-dose aspirin on endothelial dysfunction in preeclamptic patients. Materials and Methods: in this triple-blind randomized clinical trial, enrolled patients were divided randomly into two groups. Acetylsalicylic acid (ASA) 80 mg or placebo will be taken daily by oral administration from the initiation of diagnosis until 2 months after delivery. Every patient's flow-mediated dilation (FMD) were evaluated at the beginning of study and 2 months after delivery with the same experienced operator at a same period of the time (3–5 pm) by high-resolution B-mode ultrasonographic. T-test or Mann–Whitney test was used in the comparison of means between the intervention and placebo groups. To compare FMD in each group, before and after the intervention, paired t-test was used. Results: Mean value of FMD in intervention (9.61 ± 5.58) and control group (9.40 ± 4.33) have no significant differences before drug consumption (P = 0.089). FMD in intervention group significantly increased after ASA consumption ([9.61 ± 5.58 vs. 13.65 ± 7.91] [P = 0.044]). Conclusion: Increase mean of FMD in intervention group shows that this supplement can improve endothelial function. PMID:28331517

  2. 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.

    PubMed

    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 (r(2)>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.

  3. 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.

  4. The Effects of EPA+DHA and Aspirin on Inflammatory Cytokines and Angiogenesis Factors.

    PubMed

    Block, Robert C; Dier, Usawadee; Calderonartero, Pedro; Shearer, Gregory C; Kakinami, Lisa; Larson, Mark K; Harris, William S; Georas, Steve; Mousa, Shaker A

    2012-01-01

    OBJECTIVE: In a recent study, we showed that the combination of aspirin plus the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) synergistically inhibited platelet function. As aspirin, EPA, and DHA have demonstrated anti-inflammatory properties, we hypothesized that the ingestion of EPA and DHA, with and without aspirin, would reduce plasma levels of inflammatory cytokines and angiogenesis factors more than aspirin alone and before aspirin was ingested. METHODS: Using multiplex technology, we investigated the effects of aspirin (single-dose 650 mg on day 1), EPA+DHA (3.4 g/d for days 2-29), and aspirin with EPA+DHA (day 30) on plasma levels of inflammatory cytokines and angiogenesis factors in healthy adults. RESULTS: Aspirin alone had no effect on any factor versus baseline, but EPA+DHA, with and without aspirin, significantly reduced concentrations of 8 of 9 factors. Although EPA+DHA plus aspirin reduced concentrations of a subset of the factors compared to baseline, neither aspirin alone nor the combination significantly reduced the level of any analyte more robustly than EPA+DHA alone. CONCLUSIONS: These data suggest that EPA+DHA has more pronounced down-regulatory effects on inflammation and angiogenesis than aspirin. The implications of these findings for the use of combined therapy for cardiovascular disease remain to be clarified.

  5. Synthesis of Aspirin: A General Chemistry Experiment

    NASA Astrophysics Data System (ADS)

    Olmsted, John A., III

    1998-10-01

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

  6. Gentisic Acid, a Compound Associated with Plant Defense and a Metabolite of Aspirin, Heads a New Class of in Vivo Fibroblast Growth Factor Inhibitors*

    PubMed Central

    Fernández, Israel S.; Cuevas, Pedro; Angulo, Javier; López-Navajas, Pilar; Canales-Mayordomo, Ángeles; González-Corrochano, Rocío; Lozano, Rosa M.; Valverde, Serafín; Jiménez-Barbero, Jesús; Romero, Antonio; Giménez-Gallego, Guillermo

    2010-01-01

    Fibroblast growth factors are key proteins in many intercellular signaling networks. They normally remain attached to the extracellular matrix, which confers on them a considerable stability. The unrestrained accumulation of fibroblast growth factors in the extracellular milieu, either due to uncontrolled synthesis or enzymatic release, contributes to the pathology of many diseases. Consequently, the neutralization of improperly mobilized fibroblast growth factors is of clear therapeutic interest. In pursuing described rules to identify potential inhibitors of these proteins, gentisic acid, a plant pest-controlling compound, an aspirin and vegetarian diet common catabolite, and a component of many traditional liquors and herbal remedies, was singled out as a powerful inhibitor of fibroblast growth factors. Gentisic acid was used as a lead to identify additional compounds with better inhibitory characteristics generating a new chemical class of fibroblast growth factor inhibitors that includes the agent responsible for alkaptonuria. Through low and high resolution approaches, using representative members of the fibroblast growth factor family and their cell receptors, it was shown that this class of inhibitors may employ two different mechanisms to interfere with the assembly of the signaling complexes that trigger fibroblast growth factor-driven mitogenesis. In addition, we obtained evidence from in vivo disease models that this group of inhibitors may be of interest to treat cancer and angiogenesis-dependent diseases. PMID:20145243

  7. Aspirin treatment reduces platelet resistance to deformation.

    PubMed

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

    1987-01-01

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

  8. New nitric oxide or hydrogen sulfide releasing aspirins.

    PubMed

    Lazzarato, Loretta; Chegaev, Konstantin; Marini, Elisabetta; Rolando, Barbara; Borretto, Emily; Guglielmo, Stefano; Joseph, Sony; Di Stilo, Antonella; Fruttero, Roberta; Gasco, Alberto

    2011-08-11

    A new series of (((R-oxy)carbonyl)oxy)methyl esters of aspirin (ASA), bearing nitric oxide (NO) or hydrogen sulfide (H(2)S) releasing groups, was synthesized, and the compounds were evaluated as new ASA co-drugs. All the products were quite stable in buffered solution at pH 1 and 7.4. Conversely, they were all rapidly metabolized, producing ASA and the NO/H(2)S releasing moiety used for their preparation. Consequent on ASA release, the compounds were capable of inhibiting collagen-induced platelet aggregation of human platelet-rich plasma (PRP). The simple NO/H(2)S donor substructures were able to relax contracted rat aorta strips, with a NO- and H(2)S-dependent mechanism, respectively, but they either did not trigger antiaggregatory activity or displayed antiplatelet potency markedly below that of the related co-drug. The new products might provide a safer and improved alternative to the use of ASA principally in its anti-inflammatory and antithrombotic applications.

  9. 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.

  10. 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

  11. 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.

  12. The mechanism of aspirin reactions in the human body

    NASA Astrophysics Data System (ADS)

    Graves, Alan; di Ventra, Massimiliano; Sohlberg, Karl; Pantelides, Sokrates T.

    2001-03-01

    We report first-principles (density functional theory) calculations of possible reaction pathways for the break-up of aspirin that leads to pain relief in the human body. An aspirin molecule consists of an acetyl group attached to a salicylate. Upon entering a membrane protein known as COX, the aspirin molecule is pulled apart. The acetyl group of the aspirin molecule attaches to SER-530, a serine residue that is located near the entrance of the COX protein channel. The resulting acetyl-serine residue effectively forms a gate within the COX channel blocking certain fatty acids from reaching the protein active site where they are converted into prostaglandins, the molecules that are responsible for the sensation of pain. An important new finding is that the aspirin molecule undergoes a transformation prior to breaking up.

  13. 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.

  14. 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.

  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. 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.

  17. Vitamins B2, B6 and B12 and Risk of New Colorectal Adenomas in a Randomized Trial of Aspirin Use and Folic Acid Supplementation

    PubMed Central

    Figueiredo, Jane C.; Levine, A. Joan; Grau, Maria V.; Midttun, Øivind; Ueland, Per M.; Ahnen, Dennis J.; Barry, Elizabeth L.; Tsang, Shirley; Munroe, David; Ali, Iqbal; Haile, Robert W.; Sandler, Robert S.; Baron, John A.

    2008-01-01

    Background Folate, other vitamin B cofactors, and genes involved in folate-mediated one-carbon metabolism (FOCM) all may play important roles in colorectal neoplasia. In this study, we examined the associations between dietary and circulating plasma levels of vitamins B2, B6 and B12 and risk colorectal adenomas. Methods The Aspirin/Folate Polyp Prevention Study is a randomized clinical trial of folic acid supplementation and incidence of new colorectal adenomas in individuals with a history of adenomas (n=1,084). Diet and supplement use were ascertained through a food-frequency questionnaire administered at baseline. Blood collected at baseline was used to determine plasma B-vitamin levels. We used generalized linear regression to estimate risk ratios (RR) and 95% confidence limits (CI) as measures of association. Results We found a borderline significant inverse association with plasma B6 (pyridoxal 5′phosphate, PLP) and adenoma risk (adjusted RR Q4 vs. Q1=0.78, 95% CI=0.61-1.00, p-trend=0.08). This association was not modified by folic acid supplementation or plasma folate. However, the protective association of PLP with adenoma risk was observed only among subjects who did not drink alcohol (p-interaction=0.03). Plasma B2 (riboflavin) was inversely associated with risk of advanced lesions (adjusted RR Q4 vs. Q1=0.51; 95% CI=0.26-0.99, p-trend=0.12). No significant associations were observed between adenoma risk and plasma vitamin B12 or dietary intake of vitamin B2 and B6. When we examined specific gene-B-vitamin interactions, we observed a possible interaction between MTHFR-C677T and plasma B2 on risk of all adenomas. Conclusion Our results suggest that high levels of PLP and B2 may protect against colorectal adenomas. PMID:18708408

  18. 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.

  19. An aspirin a day.

    PubMed

    Majerus, Philip W

    2014-01-01

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

  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. Standards 101: The ASA Standards program

    NASA Astrophysics Data System (ADS)

    Schomer, Paul

    2004-05-01

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

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

    PubMed Central

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

    2013-01-01

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

  3. Healing of aspirin-associated peptic ulcer disease despite continued salicylate ingestion.

    PubMed

    O'Laughlin, J C; Silvoso, G R; Ivey, K J

    1981-05-01

    Patients who have rheumatic disease and who are undergoing long-term aspirin therapy have a high incidence of peptic ulcer disease. Whether it is possible to heal long-term aspirin-related peptic ulcer disease if aspirin intake is continued is unknown. Nine patients with rheumatic disease who were receiving long-term aspirin therapy and who had 15 endoscopically verified gastric and/or duodenal ulcers were studied. Patients were treated daily with 1,200 mg of cimetidine plus at least 120 mL of antacid (Mylanta II), while continuing aspirin therapy at the same dose and type. By eight weeks, 14 ulcers had healed. This study shows that some aspirin-associated peptic ulcers can be healed, despite continued aspirin intake, by intensive medical therapy aimed at lowering intragastric acidity.

  4. Aspirin enhances the cytotoxic activity of bortezomib against myeloma cells via suppression of Bcl-2, survivin and phosphorylation of AKT

    PubMed Central

    Ding, Jiang-Hua; Yuan, Li-Ya; Chen, Guo-An

    2017-01-01

    In our previous study, it was found that aspirin (ASA) exerted antimyeloma actions in vivo and in vitro. The resistance to bortezomib (BTZ) in multiple myeloma (MM) is partly due to AKT activation and the upregulation of survivin induced by BTZ, which are the targets of ASA in gastric and ovarian cancer, respectively. Thus, the present study investigated the interaction between ASA and BTZ in MM and further clarified the underlying mechanisms. MM1.S and RPMI-8226 cell lines harboring the N- and K-Ras mutations, respectively, were treated with 2.5 mM ASA, 10 nM BTZ and ASA+BTZ for different durations. The proliferation and apoptosis of the cells were determined, and the underlying mechanisms governing the interaction of ASA and BTZ were examined in the MM cells. Treatment with ASA+BTZ caused higher rates of proliferative inhibition and apoptosis in the MM1.S and RPMI-8226 cells in time-dependent manner, compared with either agent alone. A drug interaction assay revealed the additive effect of ASA and BTZ on the myeloma cells. ASA alone inhibited the levels of phosphorylated AKT (p-AKT) and survivin, whereas BTZ alone augmented the levels of p-AKT and survivin. Of note, ASA markedly decreased the upregulation of p-AKT and survivin induced by BTZ. Treatment with ASA+BTZ significantly suppressed the level of Bcl-2, compared with either agent alone. ASA may potentiate the antimyeloma activity of BTZ against myeloma cells via suppression of AKT phosphorylation, survivin and Bcl-2, indicating the potential of ASA+BTZ in treating MM, particularly for cases of BTZ-refractory/relapsed MM. PMID:28356941

  5. Calculations of aspirin reaction mechanisms in the human body

    NASA Astrophysics Data System (ADS)

    Graves, Alan; Sohlberg, Karl; Pantelides, Sokrates T.

    1999-11-01

    We report quantum mechanical calculations of possible reaction pathways for the breakup of aspirin that lead to pain relief in the human body. Animations of the reactions will be shown. An aspirin molecule consists of an acetyl group attached to a salicylate. Upon entering a membrane protein known as COX, the aspirin molecule is pulled apart. The acetyl group of the aspirin molecule attaches to SER-530, a serine residue that is located near the entrance of the COX protein channel. The resulting acetyl-serine residue effectively forms a gate within the COX channel blocking certain fatty acids from reaching the protein active site where the fatty acids are converted into prostaglandins, the molecules that are responsible for inflammation and the sensation of pain.

  6. ASA24-2014, 2012, and 2011, all versions

    Cancer.gov

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

  7. 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.

  8. Recovery Time of Platelet Function After Aspirin Withdrawal

    PubMed Central

    Lee, Jeonghun; Kim, Jeong Kyung; Kim, Jeong Hee; Dunuu, Tsagaan; Park, Sang-Ho; Park, Sang Joon; Kang, Ji Yeon; Choi, Rak Kyeong; Hyon, Min Su

    2014-01-01

    Introduction Inappropriate antiplatelet therapy discontinuation increases the risk of thrombotic complications and bleeding after dental procedures. To determine the platelet reactivity recovery time after aspirin withdrawal in vivo, our study was conducted in patients with low-risk cardiovascular disease who can stop aspirin administration following the guidelines stipulated by the American College of Chest Physicians. The time it takes for platelet activity to normalize and the diagnostic accuracy of testing methods were assessed for a residual antiplatelet activity with multiple electrode aggregometry. Our study included patients with clinically indicated hypertension preparing for a dental extraction procedure. Materials and methods A total of 212 patients not taking aspirin (control group) and 248 patients with hypertension receiving long-time aspirin treatment at a 100-mg daily dose were prospectively included in the study, which involved stopping aspirin intake before dental extraction. The residual platelet activity and dental bleeding in patients who stopped aspirin intake were analyzed and compared with those of the control group. In addition, platelet reactivity recovery time and bleeding risk in patients who stopped taking aspirin every 24 hours for 0 to 5 days (0–143 hours) before dental extraction was also assessed. Results Platelet reactivity normalized 96 hours after aspirin withdrawal. The cut-off value of 49 arbitrary units in the arachidonic acid platelet aggregation test excluded the effect of aspirin with 91% sensitivity and 66% specificity. AUC showed 0.86 (P < 0.001) diagnostic accuracy. The immediate bleeding complications in all treatment groups were similar to those seen in the control group and were successfully managed with local hemostatic measures. Conclusions The antiplatelet effects of aspirin disappeared 96 hours after aspirin withdrawal in our study, and dental extractions may be safely performed in this period when appropriate

  9. 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).

  10. 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.

  11. Intracellular Erythrocyte Platelet-activating Factor Acetylhydrolase I Inactivates Aspirin in Blood*

    PubMed Central

    Zhou, Gang; Marathe, Gopal K.; Willard, Belinda; McIntyre, Thomas M.

    2011-01-01

    Aspirin (acetylsalicylic acid) prophylaxis suppresses major adverse cardiovascular events, but its rapid turnover limits inhibition of platelet cyclooxygenase activity and thrombosis. Despite its importance, the identity of the enzyme(s) that hydrolyzes the acetyl residue of circulating aspirin, which must be an existing enzyme, remains unknown. We find that circulating aspirin was extensively hydrolyzed within erythrocytes, and chromatography indicated these cells contained a single hydrolytic activity. Purification by over 1400-fold and sequencing identified the PAFAH1B2 and PAFAH1B3 subunits of type I platelet-activating factor (PAF) acetylhydrolase, a phospholipase A2 with selectivity for acetyl residues of PAF, as a candidate for aspirin acetylhydrolase. Western blotting showed that catalytic PAFAH1B2 and PAFAH1B3 subunits of the type I enzyme co-migrated with purified erythrocyte aspirin hydrolytic activity. Recombinant PAFAH1B2, but not its family member plasma PAF acetylhydrolase, hydrolyzed aspirin, and PAF competitively inhibited aspirin hydrolysis by purified or recombinant erythrocyte enzymes. Aspirin was hydrolyzed by HEK cells transfected with PAFAH1B2 or PAFAH1B3, and the competitive type I PAF acetylhydrolase inhibitor NaF reduced erythrocyte hydrolysis of aspirin. Exposing aspirin to erythrocytes blocked its ability to inhibit thromboxane A2 synthesis and platelet aggregation. Not all individuals or populations are equally protected by aspirin prophylaxis, the phenomenon of aspirin resistance, and erythrocyte hydrolysis of aspirin varied 3-fold among individuals, which correlated with PAFAH1B2 and not PAFAH1B3. We conclude that intracellular type I PAF acetylhydrolase is the major aspirin hydrolase of human blood. PMID:21844189

  12. Aspirin Allergy: What Are the Symptoms?

    MedlinePlus

    ... allergy I think I may have an aspirin allergy. What are the symptoms and what can I do? Answers from James ... aspirin are common. If you have an aspirin allergy or sensitivity, you may also have a reaction ...

  13. Quinone Induced Activation of Keap1/Nrf2 Signaling by Aspirin Prodrugs Masquerading as Nitric Oxide

    PubMed Central

    Dunlap, Tareisha; Piyankarage, Sujeewa C.; Wijewickrama, Gihani T.; Abdul-Hay, Samer; Vanni, Michael; Litosh, Vladislav; Luo, Jia; Thatcher, Gregory R. J.

    2013-01-01

    The promising therapeutic potential of the NO-donating hybrid aspirin prodrugs (NO-ASA), includes induction of chemopreventive mechanisms, and has been reported in almost 100 publications. One example, NCX-4040 (pNO-ASA), is bioactivated by esterase to a quinone methide (QM) electrophile. In cell cultures, pNO-ASA and QM-donating X-ASA prodrugs that cannot release NO rapidly depleted intracellular GSH and caused DNA damage; however, induction of Nrf2 signaling elicited cellular defense mechanisms including upregulation of NAD(P)H:quinone oxidoreductase-1 (NQO1) and glutamate-cysteine ligase (GCL). In HepG2 cells, the “NO-specific” 4,5-diaminofluorescein reporter, DAF-DA, responded to NO-ASA and X-ASA, with QM-induced oxidative stress masquerading as NO. LC-MS/MS analysis demonstrated efficient alkylation of Cys residues of proteins including glutathione-S-transferase-P1 (GST-P1) and Kelch-like ECH-associated protein 1 (Keap1). Evidence was obtained for alkylation of Keap1 Cys residues associated with Nrf2 translocation to the nucleus, nuclear translocation of Nrf2, activation of antioxidant response element (ARE), and upregulation of cytoprotective target genes. At least in cell culture, pNO-ASA acts as a QM-donor, bioactivated by cellular esterase activity to release salicylates, NO3−, and an electrophilic QM. Finally, two novel aspirin prodrugs were synthesized, both potent activators of ARE, designed to release only the QM and salicylates on bioactivation. Current interest in electrophilic drugs acting via Nrf2 signaling suggests that QM-donating hybrid drugs can be designed as informative chemical probes in drug discovery. PMID:23035985

  14. 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.

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

    PubMed

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

    2016-10-01

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

  16. 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…

  17. 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)

  18. Interactions of m-xylene and aspirin metabolism in man.

    PubMed Central

    Campbell, L; Wilson, H K; Samuel, A M; Gompertz, D

    1988-01-01

    In a series of experiments to investigate interactions between industrial solvents and common medications the interaction between m-xylene and aspirin was studied. As both these substances are metabolised and excreted as glycine conjugates there would possibly be competition for this conjugation pathway. Five male volunteers were exposed on separate occasions to m-xylene by inhalation (100 ppm), aspirin (1500 mg) by mouth, and m-xylene and aspirin together under controlled conditions in an exposure chamber. Urine and blood samples were collected and analysed for m-xylene, aspirin, and their metabolites. The amounts of the major glycine conjugates produced from m-xylene (m-methylhippuric acid) and aspirin (salicyluric acid) were significantly reduced by about 50% when m-xylene and aspirin were coadministered. There appears to be a mutual inhibition on the formation of the respective glycine conjugates. It is suggested that the inhibition is due to competition for either the enzymes, acyl-CoA synthetase, or glycine N-acylase. These findings have implications in the biological monitoring of workers exposed to m-xylene. Images PMID:3342195

  19. Impact of Acetylsalicylic Acid on the Clinicopathological Characteristics and Prognosis of Patients with Invasive Breast Cancer

    PubMed Central

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

    2014-01-01

    Summary Background The impact of acetylsalicylic acid (ASA) on the clinicopathological characteristics of breast cancer has not yet been elucidated in detail; we therefore aimed to investigate the effects of ASA on the clinicopathological characteristics of patients with breast cancer. Patients and Methods Patients diagnosed with breast cancer were retrospectively analyzed. Breast cancer patients who were taking ASA at the time of breast cancer diagnosis were enrolled as ASA users (n = 84); matching patients with the same age who were not taking ASA were included as control group (n = 890). Results The median age was 56 (range 34–82) years in both groups. ASA users had a significantly lower incidence of grade II–III tumors compared to non-users (P = 0.02). The other clinicopathological characteristics and treatment histories were similar in both groups. In patients using ASA, the disease-free survival (DFS) rate was 97.3%, 89.4%, and 79.9% and in non-users it was 94.1%, 81.8%, and 70.9% in the 1rst, 3rd, and 5th year, respectively (P = 0.01). In aspirin users, the overall survival rate was 95.0%, 90.6%, and 87.6% and in non-users it was 98.1%, 91.2%, and 85.5% in the 1rst, 3rd, and 5th year, respectively (P = 0.50). Conclusion Using ASA at the time of breast cancer diagnosis was associated with significantly improved DFS in breast cancer patients. PMID:25404885

  20. Homocysteine is a novel risk factor for suboptimal response of blood platelets to acetylsalicylic acid in coronary artery disease: a randomized multicenter study.

    PubMed

    Karolczak, Kamil; Kamysz, Wojciech; Karafova, Anna; Drzewoski, Jozef; Watala, Cezary

    2013-08-01

    The incomplete inhibition of platelet function by acetylsalicylic acid (ASA), despite the patients are receiving therapeutic doses of the drug ('aspirin-resistance'), is caused by numbers of risk factors. In this study we verified the idea that plasma homocysteine (Hcy) contributes to 'aspirin-resistance' in patients with coronary artery disease (CAD) and with or without type 2 diabetes mellitus (T2DM). A cross-designed randomized controlled intervention study has been performed (126 CAD pts incl. 26 with T2DM) to determine whether increasing ASA dose from 75mg to 150mg daily may result in the increased antiplatelet effect, in the course of four-week treatment. Platelet response to collagen (coll) or arachidonic acid (AA) was monitored with whole blood aggregometry, plasma thromboxane (Tx), and Hcy levels were determined immunochemically. The ASA-mediated reductions in platelet response to coll (by 12±3%) or AA (by 10±3%) and in plasma Tx (by 20±9%; p<0.02 or less) were significantly greater for higher ASA dose and significantly correlated with plasma Hcy, which was significantly lower in "good" ASA responders compared to "poor" responders (p<0.001). Higher plasma Hcy appeared a significant risk factor for blood platelet refractoriness to low ASA dose (OR=1.11; ±95%CI: 1.02-1.20, p<0.02, adjusted to age, sex and CAD risk factors). Hcy diminished in vitro antiplatelet effect of low ASA concentration and augmented platelet aggregation (by up to 62% (p<0.005) for coll and up to 15% (p<0.005) for AA), whereas its acetyl derivative acted oppositely. Otherwise, Hcy intensified antiplatelet action of high ASA. Hyperhomocysteinaemia may be a novel risk factor for the suppressed blood platelet response to ASA, and homocysteine may act as a specific sensitizer of blood platelets to some agonists. While homocysteine per se acts as a proaggregatory agent to blood platelets, its acetylated form is able to reverse this effect. Thus, these findings reveal a possibly new

  1. The effectiveness of antioxidant therapy in aspirin resistance, diabetes population for prevention of thrombosis.

    PubMed

    Aboonabi, Anahita; Singh, Indu

    2016-10-01

    Thrombosis as the main complication of coronary heart disease (CHD) represents the primary cause of morbidity and mortality in patients with diabetes mellitus (DM). In the course of diabetes mellitus some coagulation abnormalities occur, that may result in a thrombogenic propensity. Aspirin (ASA) as a platelet-inhibiting agent through inactivation of Cyclooxygenase-1 (COX-1) is mostly used for the prevention and treatment of atherothrombotic disorders. ASA inhibits the COX-1 enzyme and therefore blocks platelet thromboxane A2 (TXA2) synthesis. However, some of the serious vascular events in high-risk vascular patients are attributable to a failure of ASA to suppress platelet aggregation. The consumption of antioxidant or antioxidant rich foods such as vitamin C, E, and polyphenols might impart anti-thrombotic and cardiovascular protective effects via their inhibition of platelet hyper-activation or aggregation similar to the action of aspirin. This review will discuss the risk of thrombosis in diabetes, what aspirin resistance means, and the effectiveness of antioxidant therapy in the prevention and possible treatment of atherothrombotic disorders.

  2. A preliminary study: aspirin discontinuation before elective operations; when is the optimal timing?

    PubMed Central

    Ozdemir, Suleyman; Ozis, Erpulat; Sahli, Zafer; Demirtas, Selda; Korkmaz, Atilla

    2013-01-01

    Purpose To evaluate the optimum timing of aspirin cessation before noncardiac surgeries. We have conducted a pilot study to minimize the aspirin cessation time before various surgeries. Methods Eighty patients who were taking regular aspirin for secondary prevention undergoing elective surgical operations were enrolled in the study. We separated the patients into two groups. The control group had 35 patients who stopped aspirin intake 10 days before surgery. The study group had 45 patients who stopped their aspirin intake and underwent surgery one day after arachidonic acid aggregation tests were within normal limits. Bleeding, blood loss, and transfusion requirements were assessed perioperatively. Results The mean time between aspirin cessation and aspirin nonresponsiveness were found to be 4.2 days with a median value of 4 days. In addition, the mean time between aspirin cessation and operation day were found to be 5.5 days with a median value of 5 days. No perioperative bleeding, thromboembolic or cardiovascular complications were encountered. Conclusion Reducing time of aspirin cessation from 7-10 days to 4-5 days is a possibility for patients using aspirin for secondary prevention without increased perioperative complications. PMID:24106686

  3. Effect of aspirin dose, preparation, and withdrawal on platelet response in normal volunteers.

    PubMed

    Coleman, Jacqueline L; Alberts, Mark J

    2006-09-15

    A significant difference in individual response to aspirin therapy has been described, and studies have shown that a minimal response to aspirin may be associated with increased risk for some cardiovascular events. However, it remains unclear if aspirin dose, coating, or termination alters the antiplatelet effects of aspirin. Normal volunteers were randomly assigned to enteric-coated or uncoated aspirin 81 or 325 mg and monitored over 12 days with a point-of-care aspirin assay that incorporates the platelet agonist arachidonic acid. The antiplatelet response was greater with a 325-mg dose than with an 81-mg dose. A coating slowed the antiplatelet response to the 81-mg dose only. There were no differences among the groups after maximum response was achieved between days 4 and 7. There was significant recovery of platelet aggregation <48 hours after the cessation of aspirin, with a return to baseline values by the fifth day. A significant interpatient variation in response to the 4 dosing regimes was observed. In conclusion, the antiplatelet response was more rapid to a 325-mg/day dose of aspirin compared with an 81-mg/day dose. An enteric-coated preparation delayed the time of response to an 81-mg/day dose. These results suggest that aspirin dose and preparation may be important mediators of the antiplatelet effects of aspirin in some patients.

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

    PubMed Central

    Roth, G J; Majerus, P W

    1975-01-01

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

  5. Rhinosinusitis and aspirin-exacerbated respiratory disease.

    PubMed

    Garcia Cruz, Maria L; Jimenez-Chobillon, M Alejandro; Teran, Luis M

    2012-01-01

    Rhinosinusitis is a feature of aspirin-exacerbated respiratory disease (AERD), which in the initial phase is manifested as nasal congestion, mostly affecting females at the age of around 30 years on average. Subsequently, nasal inflammation progresses to chronic eosinophilic rhinosinusitis, asthma, nasal polyposis, and intolerance to aspirin and to other NSAIDs. While it has been long established that NSAIDs cause inhibition of cyclooxygenase-1 (COX-1), leading to excessive metabolism of arachidonic acid (AA) to cysteinyl-leukotrienes (cys-LTs), there is now evidence that both cytokines and staphylococcus superantigens amplify the inflammatory process exacerbating the disease. This paper gives a brief overview of the development of chronic rhinosinusitis (CRS) in sensitive patients, and we share our experience in the diagnosis and management of CRS in AERD.

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

    PubMed Central

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

    2017-01-01

    Aspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. Important to this function is its ability to irreversibly acetylate cyclooxygenases at active site serines. Aspirin has the potential to acetylate other amino acid side-chains, leading to the possibility that aspirin-mediated lysine acetylation could explain some of its as-yet unexplained drug actions or side-effects. Using isotopically labeled aspirin-d3, in combination with acetylated lysine purification and LC-MS/MS, we identified over 12000 sites of lysine acetylation from cultured human cells. Although aspirin amplifies endogenous acetylation signals at the majority of detectable endogenous sites, cells tolerate aspirin mediated acetylation very well unless cellular deacetylases are inhibited. Although most endogenous acetylations are amplified by orders of magnitude, lysine acetylation site occupancies remain very low even after high doses of aspirin. This work shows that while aspirin has enormous potential to alter protein function, in the majority of cases aspirin-mediated acetylations do not accumulate to levels likely to elicit biological effects. These findings are consistent with an emerging model for cellular acetylation whereby stoichiometry correlates with biological relevance, and deacetylases act to minimize the biological consequences of nonspecific chemical acetylations. PMID:27913581

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

    PubMed

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

    2017-02-01

    Aspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. Important to this function is its ability to irreversibly acetylate cyclooxygenases at active site serines. Aspirin has the potential to acetylate other amino acid side-chains, leading to the possibility that aspirin-mediated lysine acetylation could explain some of its as-yet unexplained drug actions or side-effects. Using isotopically labeled aspirin-d3, in combination with acetylated lysine purification and LC-MS/MS, we identified over 12000 sites of lysine acetylation from cultured human cells. Although aspirin amplifies endogenous acetylation signals at the majority of detectable endogenous sites, cells tolerate aspirin mediated acetylation very well unless cellular deacetylases are inhibited. Although most endogenous acetylations are amplified by orders of magnitude, lysine acetylation site occupancies remain very low even after high doses of aspirin. This work shows that while aspirin has enormous potential to alter protein function, in the majority of cases aspirin-mediated acetylations do not accumulate to levels likely to elicit biological effects. These findings are consistent with an emerging model for cellular acetylation whereby stoichiometry correlates with biological relevance, and deacetylases act to minimize the biological consequences of nonspecific chemical acetylations.

  8. Overview of the ASA24® Researcher Website

    Cancer.gov

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

  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. 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.

  11. Taking Aspirin to Protect Your Heart

    MedlinePlus

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

  12. Comparison of intravenous acetylsalicylic acid and dipyrone in postoperative pain

    PubMed Central

    Blendinger, I.; Eberlein, H. J.

    1980-01-01

    1 In 17 gynaecological patients with postoperative pain the analgesic efficacy of intravenous lysine salicylate 1.8 g (corresponding to acetylsalicyclic acid (ASA) 1.0 g) and dipyrone 1.0 g were compared in a double-blind randomized study. 2 In the ASA group, mean pain relief and pain intensity difference scores reached a maximum 30 min after drug administration and remained at this level for the next 90 minutes. 3 In the dipyrone group, these scores reached their peak 60 min after drug administration and seemed to fall off during the next hour. 4 The mean pain relief and intensity difference scores were greater following aspirin than dipyrone. However, firm conclusions cannot be drawn from the results of this small study. PMID:7437274

  13. 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%.

  14. Comparison of aspirin and indobufen in healthy volunteers.

    PubMed

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

    2016-01-01

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

  15. The acetylation of hemoglobin by aspirin. In vitro and in vivo.

    PubMed Central

    Bridges, K R; Schmidt, G J; Jensen, M; Cerami, A; Bunn, H F

    1975-01-01

    The chemical modification of hemoglobin by aspirin (ASA) has been studied, both in intact human red cells and in purified hemoglobin solutions. After incubation of red cells with 20 mM [acetyl-1minus14C]ASA, incorporation of radioactivity into hemoglobin was observed in agreement with the results of Klotz and Tam (1973. Proc. Natl. Acad. Sci. U. S. A. 70: 1313-1315). In contrast, no labeling of hemoglobin was seen when [carbosyl-14-C]ASA was used. These results indicate that ASA acetylates hemoglobin. The acetylated hemoglobin was readily separated from unmodified hemoglobin by both gel electrofocusing and by column chromatography. Quantitation of the extent of acetylation by densitometric scanning of gels agreed very well with estimates obtained from radioactivity measurements. Hemolysates prepared from red cells incubated with ASA showed normal oxygen affinity and heme-heme interaction. Purified acetylated hemoglobin had a slightly increased oxygen affinity and decreased heme-heme interaction. There was no difference in the rate of acetylation of oxy- and deoxyhemoglobin. ASA acetylated column-purified hemoglobin A more readily than hemoglobin in crude hemolysate, but less rapidly than purified human serum albumin. The rate of acetylation of hemoglobulin increased with pH up to approximately pH 8,5. Structural studies were done on hemoglobin incubated with 2.0 mM and 20 mM [acetyl-1-14-C]ASA. Alpha- and beta-chains were acetylated almost equally. Tryptic digests of purified acetylated subunits were fingerprinted on cellulose thin layer plates and autoradiographed. Both alpha- and beta-chains showed a number of radioactive spots that were either ninhydrin negative or weakly ninhydrin positive. These results indicate that hemoglobin is acetylated at a number of sites, probably at the epislon-amino group of lysine residues. To determine whether ASA acetylates hemoglobin in vivo, hemolysates of 14 patients on long-term high-dose ASA therapy were analyzed by gel

  16. Aspirin-induced peptic ulcer and genetic polymorphisms.

    PubMed

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

    2010-05-01

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

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

    PubMed Central

    Yamashita, Masamichi

    2016-01-01

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

  18. 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.

  19. Quinone-induced activation of Keap1/Nrf2 signaling by aspirin prodrugs masquerading as nitric oxide.

    PubMed

    Dunlap, Tareisha; Piyankarage, Sujeewa C; Wijewickrama, Gihani T; Abdul-Hay, Samer; Vanni, Michael; Litosh, Vladislav; Luo, Jia; Thatcher, Gregory R J

    2012-12-17

    The promising therapeutic potential of the NO-donating hybrid aspirin prodrugs (NO-ASA) includes induction of chemopreventive mechanisms and has been reported in almost 100 publications. One example, NCX-4040 (pNO-ASA), is bioactivated by esterase to a quinone methide (QM) electrophile. In cell cultures, pNO-ASA and QM-donating X-ASA prodrugs that cannot release NO rapidly depleted intracellular GSH and caused DNA damage; however, induction of Nrf2 signaling elicited cellular defense mechanisms including upregulation of NAD(P)H:quinone oxidoreductase-1 (NQO1) and glutamate-cysteine ligase (GCL). In HepG2 cells, the "NO-specific" 4,5-diaminofluorescein reporter, DAF-DA, responded to NO-ASA and X-ASA, with QM-induced oxidative stress masquerading as NO. LC-MS/MS analysis demonstrated efficient alkylation of Cys residues of proteins including glutathione-S-transferase-P1 (GST-P1) and Kelch-like ECH-associated protein 1 (Keap1). Evidence was obtained for alkylation of Keap1 Cys residues associated with Nrf2 translocation to the nucleus, nuclear translocation of Nrf2, activation of antioxidant response element (ARE), and upregulation of cytoprotective target genes. At least in cell culture, pNO-ASA acts as a QM donor, bioactivated by cellular esterase activity to release salicylates, NO(3)(-), and an electrophilic QM. Finally, two novel aspirin prodrugs were synthesized, both potent activators of ARE, designed to release only the QM and salicylates on bioactivation. Current interest in electrophilic drugs acting via Nrf2 signaling suggests that QM-donating hybrid drugs can be designed as informative chemical probes in drug discovery.

  20. Variability and Persistence of Poor Response to Aspirin by Aggregometry and PFA-100 over Twelve-Months in Peripheral Arterial Disease from the Effect of Lipid Modification on Peripheral Arterial Disease after Endovascular Intervention Trial (ELIMIT)

    PubMed Central

    Saunders, Justin; Nambi, Vijay; Kimball, Kay T.; Virani, Salim S.; Morrisett, Joel D.; Lumsden, Alan B.; Ballantyne, Christie M.; Dong, Jing-Fei

    2011-01-01

    Objective To determine the prevalence of poor response to aspirin (ASA) therapy over 12-month follow-up in patients with lower extremity peripheral arterial disease (PAD), and to compare the classification agreement among different ASA response assays. Subjects Patients with PAD on ASA therapy at baseline were included from the ongoing Effect of Lipid Modification on Peripheral Arterial Disease after Endovascular Intervention Trial (ELIMIT), which is a randomized trial testing whether combination treatment with ezetimibe, niacin, and a statin will halt/regress atherosclerosis compared to statin monotherapy. Main Outcome Measures Patients who had baseline platelet testing and repeat testing at 6-month or 12-month follow-up were included. ASA responsiveness was tested using three different assays: Optical aggregation with 0.5-mg/mL of arachidonic acid (AA), optical aggregation with 10-μM of adenosine diphosphate (ADP), and platelet function analyzer-100 (PFA-100) testing with collagen/Epinephrine (Epi) loaded cartridges. ASA response was defined as AA aggregation <30%, ADP aggregation <70%, or PFA-100 Epi> 164 sec. Patients who showed response to ASA at baseline were classified as Responders. Poor response to ASA was defined as AA aggregation ≥30%, ADP aggregation ≥70%, or PFA-100 Epi ≤164 sec. Patients who showed poor response (PR) to an assay at baseline, but then were responsive at follow-up visits were classified as Initial PRs. Patients who showed poor response at baseline and all follow-up visits were classified as Persistent PRs. The classification agreement between assays was tested using the kappa statistic. Results Of 102 patients randomized in ELIMIT, 80 patients satisfied inclusion criteria. There were no significant baseline demographic differences between Responders, Initial PRs, and Persistent PRs. The prevalence of persistent poor response varied by the assay used; 5% of subjects (4/80) were Persistent PRs by AA aggregation, compared to 27

  1. Aspirin to Zoloft: Ways Medicines Work

    MedlinePlus

    ... Inside Life Science > Aspirin to Zoloft: Ways Medicines Work Inside Life Science View All Articles | Inside Life Science Home Page Aspirin to Zoloft: Ways Medicines Work By Emily Carlson Posted August 8, 2013 Most ...

  2. Aspirin resistant patients with recent ischemic stroke.

    PubMed

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

    2014-04-01

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

  3. Aspirin during Pregnancy: Is It Safe?

    MedlinePlus

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

  4. 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.

  5. 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.

  6. Aspirin attenuates monocrotaline-induced pulmonary arterial hypertension in rats by suppressing the ERK/MAPK pathway.

    PubMed

    Gao, Hua; Cheng, Yuqing; Zong, Liguo; Huang, Linian; Qiao, Chenchen; Li, Wei; Gong, Beilei; Hu, Junfeng; Liu, Haitao; Wang, Xiaojing; Zhao, Chengling

    2017-01-01

    This study aimed to investigate the therapeutic effects of aspirin (ASA) and its potential mechanisms of action in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. PAH was induced in a rat model by a single intraperitoneal (IP) injection of MCT. Saline was injected in a control group. Two weeks following MCT injection, right ventricular systolic pressure (RVSP) and systolic blood pressure (SBP) were measured in six rats from each group to confirm establishment of a PAH model. The remaining MCT-treated rats were randomly allocated to receive IP injection of saline, ASA, or ERK1/2 inhibitor PD98059. Four weeks following treatment, RVSP was measured and all rats were sacrificed for histological study. There was no significant difference in SBP in any group two weeks following MCT administration. Nonetheless RVSP was significantly increased in the MCT group compared with the control group. At 6 weeks, ASA treatment remarkably attenuated MCT-induced increased RVSP, RV hypertrophy, and pulmonary artery remodeling compared with the MCT group. The density of pulmonary capillaries in ASA-treated rats was also dramatically increased. Treatment with ASA significantly inhibited the increased p-ERK1/2 and restored the impaired endothelial nitric oxide synthase (eNOS) in MCT-treated rats. This study demonstrated that ASA distinctively attenuates MCT-induced PAH by inhibition of the ERK1/2 signaling pathway.

  7. Dietary garlic (Allium sativum) lectins, ASA I and ASA II, are highly stable and immunogenic.

    PubMed

    Clement, Fatima; Venkatesh, Yeldur P

    2010-10-01

    The immunomodulatory proteins present in garlic have recently been shown to be identical to the garlic lectins ASA I and ASA II [Clement F, Pramod SN, Venkatesh YP. Int. Immunopharmacol. 2010; 10: 316-324]. In this study, the stability of garlic lectins as a function of pH, temperature and denaturants has been examined in relation to biological activity (hemagglutination and hagocytosis). Stability of garlic lectins in simulated gastric fluid (SGF) was assessed by their hemagglutination activity, immunoreactivity, and intactness by SDS-PAGE. Garlic lectins were moderately stable in SGF for up to 30 min; while they retained hemagglutination activities, immunoreactivity with the respective rabbit antiserum decreased immediately (0.5 min) to 10-30%. ASA I retained ~80% hemagglutination activity in the pH range 2-12; however, ASA II retained only 40% in the pH ranges 2-4 and 10-12. Garlic lectins exposed to 60 °C (30 min) and pepsin (1 and 2 min) retained hemagglutination and phagocytic activities. Urea (4M) and Gdn.HCl (2M) did not affect hemagglutination. The immunogenicity of garlic lectins upon oral feeding in BALB/c mice was examined. A lectin-specific serum IgG response was seen in mice comparable to the oral immunogen, phytohemagglutinin. The recovered lectin in feces of mice administered with garlic lectins showed antigenicity identical to that of the administered proteins. The stabilities of the garlic lectins, their ability to withstand the gastrointestinal passage, and their recognition by the immune system upon oral feeding reinforce the reported presence of natural antibodies to garlic proteins in normal human sera.

  8. Aspirin sensitivity: acetylsalicylate or excipients.

    PubMed

    Hebron, B S; Hebron, H J

    2009-08-01

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

  9. Aspirin for the next generation

    PubMed Central

    Henderson, Nick; Smith, Tom

    2013-01-01

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

  10. BOREAS RSS-2 Extracted Reflectance Factors Derived from ASAS Imagery

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  11. The effect of different doses and different routes of acetylsalicylic acid administration on platelet aggregation in healthy volunteers and ischemic stroke patients.

    PubMed

    Chýlová, Miroslava; Moťovská, Zuzana; Osmančík, Pavel; Procházka, Bohumír; Kalvach, Pavel

    2015-04-01

    The purpose was to assess the effect of different doses and different routes of acetylsalicylic acid (ASA) administration on platelet aggregation and the comparison between platelet aggregation after the single and the repetitive administration of ASA in healthy individuals and in patients after ischemic stroke. The study group consists of 22 healthy individuals and 30 patients with documented ischemic stroke. Platelet aggregation was measured in healthy individuals: (a) twice before ASA and (b) 2 h after different single doses and different routes of ASA administration-(b1) 500 mg orally, (b2) 500 mg intravenously, and (b3) 100 mg orally. We measured aggregability in healthy individuals after five consecutive days of 100 mg of ASA q.d. and in patients on chronic ASA 100 mg q.d. The VerifyNow was used with results expressed in aspirin reaction units (ARU). In healthy individuals, the dose-(b1) 500 mg orally-reduced the aggregability to mean (SD) 392 (36) ARU (p < 0.001), (b2) 500 mg intravenously to 428 (46) (p < 0.001) and (b3) 100 mg orally to 460 (76) (p < 0.001). The suppression of aggregation after 500 mg was (p = 0.029) higher after the oral compared to intravenous administration, and the same is true for the suppression after single dose of 500 mg orally and 100 mg orally (p = 0.011). Oral dose 100 mg for 5 days in healthy individuals reduced aggregation to 405 (37) and in post-stroke patients to 433 (54). All doses of ASA, both orally and intravenously, have produced a significant reduction of platelet aggregation. Preference of the parenteral to oral application has not been established.

  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. Effect of dietary aspirin on ascites in broilers raised in a hypobaric chamber.

    PubMed

    Balog, J M; Huff, G R; Rath, N C; Huff, W E

    2000-08-01

    During the course of ascites development in broilers, many factors can interact to cause hypoxia. To counteract hypoxia, birds with ascites develop greatly increased hematocrit and red cell counts. Increasing hematocrits result in more viscous blood. Prostaglandins are involved in the regulation of constriction and dilation of pulmonary blood vessels and in the formation of blood clots. Dietary aspirin, a prostaglandin inhibitor, was used in an attempt to promote vasodilation and inhibit blood clotting in broilers, with the objective of determining the effect of aspirin on ascites progression. The experimental design consisted of two trials with a total of 1,360, 1-d-old male broiler chicks, which were placed at either local altitude (390 m above sea level) or in a hypobaric chamber that simulated an altitude of 2,900 m above sea level. At each elevation, five dietary treatments were employed: [control, 0.025% crystalline acetylsalicylic acid (aspirin), 0.05% aspirin, 0.10% aspirin, and 0.20% aspirin]. Bird and feed weights were recorded weekly. At the end of 5 wk, blood samples and organ weights were collected, and all birds were examined for signs of ascites. In both trials, birds raised at high altitudes were significantly lighter, had a higher incidence of ascites, and had differences in hematology, compared with birds raised at local elevation. Only in Trial 2, however, did dietary aspirin appear to have any effect on ascites incidence. At the 0.20% aspirin level, a reduction in ascites incidence approached significance compared with controls (34% vs. 56%, P < or = 0.06). Unfortunately, birds fed 0.20% aspirin also were significantly (P < or = 0.01) lighter than controls. Because slowing growth rate is known to reduce ascites, this decrease in BW may have been partially responsible for any beneficial effect on ascites development and progression obtained through feeding aspirin.

  14. 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.

  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. Aspirin Has Limited Ability to Modulate Shear-Mediated Platelet Activation Associated with Elevated Shear Stress of Ventricular Assist Devices

    PubMed Central

    Valerio, Lorenzo; Tran, Phat L.; Sheriff, Jawaad; Brengle, William; Ghosh, Ram; Chiu, Wei-Che; Redaelli, Alberto; Fiore, Gianfranco B.; Pappalardo, Federico; Bluestein, Danny; Slepian, Marvin J.

    2016-01-01

    Continuous flow ventricular assist devices (cfVADs) while effective in advanced heart failure, remain plagued by thrombosis related to abnormal flows and elevated shear stress. To limit cfVAD thrombosis, patients utilize complex anti-thrombotic regimens built upon a foundation of aspirin (ASA). While much data exists on ASA as a modulator of biochemically-mediated platelet activation, limited data exists as to the efficacy of ASA as a means of limiting shear-mediated platelet activation, particularly under elevated shear stress common within cfVADs. We investigated the ability of ASA (20, 25 and 125 μM) to limit shear-mediated platelet activation under conditions of: 1) constant shear stress (30 dyne/cm2 and 70 dyne/cm2); 2) dynamic shear stress, and 3) initial high shear exposure (70 dyne/cm2) followed by low shear exposure – i.e. a platelet sensitization protocol, utilizing a hemodynamic shearing device providing uniform shear stress in vitro. The efficacy of ASA to limit platelet activation mediated via passage through a clinical cfVAD system (DeBakey Micromed) in vitro was also studied. ASA reduced platelet activation only under conditions of low shear stress (38% reduction compared to control, n = 10, p < 0.004), with minimal protection at higher shear stress and under dynamic conditions (n = 10, p > 0.5) with no limitation of platelet sensitization. ASA had limited ability (25.6% reduction in platelet activation rate) to modulate shear-mediated platelet activation induced via cfVAD passage. These findings, while performed under “deconstructed” non-clinical conditions by utilizing purified platelets alone in vitro, provide a potential contributory mechanistic explanation for the persistent thrombosis rates experienced clinically in cfVAD patients despite ASA therapy. An opportunity exists to develop enhanced pharmacologic strategies to limit shear-mediated platelet activation at elevated shear levels associated with mechanical circulatory support

  17. NOSH-aspirin (NBS-1120), a novel nitric oxide and hydrogen sulfide releasing hybrid, attenuates neuroinflammation induced by microglial and astrocytic activation: a new candidate for treatment of neurodegenerative disorders.

    PubMed

    Lee, Moonhee; McGeer, Edith; Kodela, Ravinder; Kashfi, Khosrow; McGeer, Patrick L

    2013-10-01

    Hydrogen sulfide (H2 S) and nitric oxide (NO) have been described as gasotransmitters. Anti-inflammatory activity in the central and peripheral nervous systems may be one of their functions. Previously we demonstrated that several SH(-) donors including H2 S-releasing aspirin (S-ASA) exhibited anti-inflammatory and neuroprotective activity in vitro against toxins released by activated microglia and astrocytes. Here we report that NOSH-ASA, an NO- and H2 S-releasing hybrid of aspirin, has a significantly greater anti-inflammatory and neuroprotective effect than S-ASA or NO-ASA. When activated by LPS/IFNγ, human microglia and THP-1 cells release materials that are toxic to differentiated SH-SY5Y cells. These phenomena also occur with IFNγ-stimulated human astroglia and U373 cells. When the cells were treated with the S-ASA or NO-ASA, there was a significant enhancement of neuroprotection. However, NOSH-ASA had significantly more potent protection properties than NO-ASA or S-ASA. The effect was concentration-dependent, as well as incubation time-dependent. Such treatment not only reduced the release of the TNFα and IL-6, but also attenuated activation of P38 MAPK and NFκB proteins. All the compounds tested were not harmful when applied directly to SH-SY5Y cells. These data suggest that NOSH-ASA has significant anti-inflammatory properties and may be a new candidate for treating neurodegenerative disorders that have a prominent neuroinflammatory component such as Alzheimer disease and Parkinson disease.

  18. 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.

  19. Systems Pharmacogenomics Finds RUNX1 Is an Aspirin-Responsive Transcription Factor Linked to Cardiovascular Disease and Colon Cancer.

    PubMed

    Voora, Deepak; Rao, A Koneti; Jalagadugula, Gauthami S; Myers, Rachel; Harris, Emily; Ortel, Thomas L; Ginsburg, Geoffrey S

    2016-09-01

    Aspirin prevents cardiovascular disease and colon cancer; however aspirin's inhibition of platelet COX-1 only partially explains its diverse effects. We previously identified an aspirin response signature (ARS) in blood consisting of 62 co-expressed transcripts that correlated with aspirin's effects on platelets and myocardial infarction (MI). Here we report that 60% of ARS transcripts are regulated by RUNX1 - a hematopoietic transcription factor - and 48% of ARS gene promoters contain a RUNX1 binding site. Megakaryocytic cells exposed to aspirin and its metabolite (salicylic acid, a weak COX-1 inhibitor) showed up regulation in the RUNX1 P1 isoform and MYL9, which is transcriptionally regulated by RUNX1. In human subjects, RUNX1 P1 expression in blood and RUNX1-regulated platelet proteins, including MYL9, were aspirin-responsive and associated with platelet function. In cardiovascular disease patients RUNX1 P1 expression was associated with death or MI. RUNX1 acts as a tumor suppressor gene in gastrointestinal malignancies. We show that RUNX1 P1 expression is associated with colon cancer free survival suggesting a role for RUNX1 in aspirin's protective effect in colon cancer. Our studies reveal an effect of aspirin on RUNX1 and gene expression that may additionally explain aspirin's effects in cardiovascular disease and cancer.

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

    PubMed Central

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

    2003-01-01

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

  1. 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.

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

    PubMed Central

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

    2014-01-01

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

  3. Potentiation by caffeine of the analgesic effect of aspirin in the pain-induced functional impairment model in the rat.

    PubMed

    Castañeda-Hernández, G; Castillo-Méndez, M S; López-Muñoz, F J; Granados-Soto, V; Flores-Murrieta, F J

    1994-10-01

    The ability of caffeine to potentiate the analgesic effect of aspirin was studied in the pain-induced functional impairment model in the rat. Female Wistar rats received an intra-articular injection of 30% uric acid in the right hind limb, inducing its dysfunction. Once the dysfunction was complete, animals received aspirin oral doses of 0, 0.55, 0.98, and 1.74 mmol/kg with and without 0.17 mmol/kg of caffeine, and the recovery of functionality over time was considered as an expression of analgesia. Blood samples were drawn simultaneously with hind limb functionality determinations, and plasma concentrations of aspirin, salicylic acid, and gentisic acid were measured by high-performance liquid chromatography. Aspirin induced a dose-dependent analgesic effect. Caffeine alone was ineffective. However, caffeine significantly increased the analgesic effect of aspirin at all doses, without modifying aspirin, salicylic acid, or gentisic acid plasma levels. It is concluded that caffeine potentiates the analgesic effect of aspirin by a pharmacodynamic, but not by a pharmacokinetic mechanism.

  4. 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

  5. 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' ...

  6. Aspirin to Prevent a First Heart Attack or Stroke

    MedlinePlus

    ... NHLBI on Twitter. Aspirin to Prevent a First Heart Attack or Stroke Also known as aspirin primary prevention. ... if I’m taking aspirin to prevent another heart attack or stroke? The information discussed in Who may ...

  7. 5-ASA-loaded SiO2 nanoparticles-a novel drug delivery system targeting therapy on ulcerative colitis in mice

    PubMed Central

    Tang, Haiying; Xiang, Dan; Wang, Feng; Mao, Jingwei; Tan, Xiaoyan; Wang, Yingde

    2017-01-01

    The targeting of 5-aminosalicylic acid (5-ASA), a first-line therapeutic agent for mild to moderate active ulcerative colitis (UC), to the site of inflammation has remained a challenge and an unmet requirement in the treatment of UC. However, nanoscale carriers for targeted drug delivery are promising for pharmacotherapy, and nanoparticles improve the pharmacokinetics of the loaded therapeutics based on their physical properties. To design and prepare 5-ASA-loaded silicon dioxide nanoparticles (5-ASA-SiO2 NPs), a micro-emulsion method was conducted, and their respective therapeutic effects were validated in a mouse model of UC. Cytotoxicity of 5-ASA-SiO2 NPs was detected in vitro using the Cell Counting Kit-8 method. The therapeutic effect of 5-ASA-SiO2 NPs was assessed based on their disease activity index (DAI), colon histopathology, myeloperoxidase (MPO) and levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). SiO2 NPs were successfully prepared, and cytotoxicity of 5-ASA-SiO2 NPs was identified as being similar to 5-ASA and SiO2 NPs. DAI and colonic histopathology scores in the normal dosage, high dosage and the 5-ASA-SiO2 NP groups demonstrated a significant improvement when compared with the model group. DAI in the high dosage and 5-ASA-SiO2 NP groups also demonstrated a significant improvement when compared with the normal dosage group. However, MPO, serum IL-6 and TNF-α levels in normal dosage, high dosage and 5-ASA-SiO2 NPs groups were significantly lower than in the model group, and these indexes in the high dosage group and 5-ASA-SiO2 NP group were significantly lower than that in the normal dosage group. Expression of IL-6 and TNF-α mRNA in colonic mucosa in the normal dosage, high dosage and 5-ASA-SiO2 NP group was significantly lower than that in the model group. Colonic mucosal IL-6 and TNF-α mRNA expression in the high dosage and 5-ASA-SiO2 NP groups was significantly lower than that in the normal dosage group (P<0.05). In

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

    PubMed

    Yin, P; Zhang, L

    2016-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed Central

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

    2016-01-01

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

  13. 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.

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

    PubMed

    Lee, Yongju; Kwon, Dae-Gyeon; Kim, Gunn; Kwon, Young-Kyun

    2017-03-15

    Using density functional theory, we investigate the adsorption properties of acetylsalicylic acid (aspirin) on the outer surfaces of a (10,0) carbon nanotube (CNT) and a (8,0) triazine-based graphitic carbon nitride nanotube (CNNT). The adsorption energies for the CNNT and CNT are 0.67 and 0.51 eV, respectively, and hence, the aspirin molecule binds more strongly to the CNNT. The stronger adsorption energy for the binding to the CNNT is ascribed to the high reactivity of its nitrogen atoms with high electron affinity. The CNNT exhibits local electric dipole moments that cause strong charge redistribution in the adsorbed aspirin molecule. The influence of an external electric field on the adsorption of aspirin on the nanotubes is explored by examining modifications in their electronic band structures, partial densities of states, and charge distributions. An electric field applied along a particular direction is found to induce molecular states of aspirin that lie within the in-gap region of the CNNT. This implies that the CNNT can be potentially utilized for the detection of aspirin.

  15. Gastroduodenal mucosal damage with salsalate versus aspirin: results of experimental models and endoscopic studies in humans.

    PubMed

    Scheiman, J M; Elta, G H

    1990-10-01

    Animal models have identified multiple mechanisms of aspirin toxicity. Aspirin inhibits cyclooxygenase in the gastroduodenal mucosa leading to a decrease in endogenous prostaglandins. Prostaglandin mediated mucus and bicarbonate secretion, epithelial hydrophobicity, blood flow, and cellular proliferation are all decreased. Salicylates may cause direct cellular toxicity via inhibition of energy metabolism and membrane transport properties. Salicylate preparations have been designed to decrease gastroduodenal absorption. Endoscopic studies in humans have confirmed that buffering of aspirin does not ameliorate damage, but enteric coating does. Salicylsalicylic acid (salsalate) is an effective antirheumatic drug that bypasses gastric absorption and also avoids cyclooxygenase inhibition. In a randomized, single-blind, endoscopic comparison of salsalate versus enteric-coated aspirin, significantly less gastroduodenal damage was observed in volunteers after salsalate administration compared to enteric-coated aspirin. An endoscopic study in rheumatoid arthritics also confirmed the ability of salsalate to spare gastroduodenal mucosa when compared to naproxen administration. Salsalate may cause less gastroduodenal damage than enteric-coated aspirin based on the results of animal models and endoscopic studies in humans.

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

    PubMed

    Lui, C Y; Oberle, R; Fleisher, D; Amidon, G L

    1986-05-01

    The bioavailability of enteric coated and plain aspirin tablets was studied in four beagle dogs. Blood sampling for enteric coated tablets was planned with the aid of a radiotelemetric system. The release of aspirin from its dosage form was detected by monitoring the change in intestinal pH. Aspirin and salicylic acid levels in plasma obtained from the enteric coated dosage form exhibited familiar concentration versus time absorption profiles. Variation in the plasma concentrations of these two compounds within each dog studied (four runs each) was relatively small when time zero was adjusted to the commencement of tablet dissolution. The plasma levels obtained from plain aspirin (three runs each), however, show atypical absorption. The estimated absolute bioavailability was 0.432 +/- 0.0213 and 0.527 +/- 0.0260 for enteric coated and plain aspirin, respectively. Other pharmacokinetic parameters for these two dosage forms such as the highest observed plasma concentration (Cmax) (10.9 +/- 0.535 microgram/mL versus 13.6 +/- 1.88 micrograms/mL) and the time to reach Cmax (tmax) (26.6 +/- 1.94 min versus 31.0 +/- 7.04 min) agree well. The mean values for gastric emptying time, in vivo coating dissolution time, and in vivo disintegration/dissolution time of the tablet core for enteric coated aspirin are 48.7 +/- 7.23 min, 44.3 +/- 3.80 min, and 34.7 +/- 2.04 min, respectively.

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

    PubMed Central

    Cadavid, Angela P.

    2017-01-01

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

  18. The ASAS-SN Bright Supernova Catalog - II. 2015

    NASA Astrophysics Data System (ADS)

    Holoien, T. W.-S.; Brown, J. S.; Stanek, K. Z.; Kochanek, C. S.; Shappee, B. J.; Prieto, J. L.; Dong, Subo; Brimacombe, J.; Bishop, D. W.; Basu, U.; Beacom, J. F.; Bersier, D.; Chen, Ping; Danilet, A. B.; Falco, E.; Godoy-Rivera, D.; Goss, N.; Pojmanski, G.; Simonian, G. V.; Skowron, D. M.; Thompson, Todd A.; Woźniak, P. R.; Ávila, C. G.; Bock, G.; Carballo, J.-L. G.; Conseil, E.; Contreras, C.; Cruz, I.; Andújar, J. M. F.; Guo, Zhen; Hsiao, E. Y.; Kiyota, S.; Koff, R. A.; Krannich, G.; Madore, B. F.; Marples, P.; Masi, G.; Morrell, N.; Monard, L. A. G.; Munoz-Mateos, J. C.; Nicholls, B.; Nicolas, J.; Wagner, R. M.; Wiethoff, W. S.

    2017-01-01

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

  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. Studies on the release of leukotrienes and histamine by human lung parenchymal and bronchial fragments upon immunologic and nonimmunologic stimulation. Effects of nordihydroguaiaretic acid, aspirin, and sodium cromoglycate

    PubMed Central

    1985-01-01

    Fragments of human lung parenchyma or bronchi were studied by high performance liquid chromatography, gas chromatography-mass spectrometry, and bioassay for the biosynthesis of 5-lipoxygenase metabolites of arachidonic acid, and by radioenzymatic assay for the release of histamine, upon immunologic and nonimmunologic stimulation. Human lung parenchyma were passively sensitized with serum from timothy- positive allergic patients (radioallergosorbent test, 30-40%) and challenged with 0.5 microgram/ml of timothy allergen. Analysis of the incubation media showed the presence of LTB4, LTC4, LTD4, LTE4, and histamine. Maximum release of LTB4 and LTD4 was observed after 15 min of challenge (92.8 +/- 21, and 67.8 +/- 14 pmol/g tissue wet weight, respectively; mean +/- SEM) whereas maximum release of LTC4 was observed after 5 min of challenge (25 +/- 7.1 pmol). In parallel to leukotriene formation, histamine was released rapidly and reached a maximum after approximately 15 min of challenge (2.85 +/- 0.76 nmol/g tissue). When fragments of human lung parenchyma were stimulated with ionophore A23187 (4 microM), we observed a profile of leukotriene and histamine release similar to that seen in response to the allergen. Ionophore A23187 stimulated the release of two- to fivefold greater amounts of leukotrienes and histamine than did the allergen. Release of LTC4 and histamine was maximal after 5 min of stimulation (83 +/- 22.2 and 5.2 +/- 0.95 nmol/g tissue, respectively), whereas LTB4 and LTD4 release reached a maximum after 15 min (438 +/- 66.6 and 205 +/- 68 nmol/g tissue, respectively). In addition, human lung parenchyma metabolized LTB4 into omega-OH-LTB4 and omega-COOH-LTB4. This tissue also released 5-hydroxy-eicosatetraenoic acid (5-Hete), 12-Hete, and 15- Hete. Fragments of human lung bronchi also released a similar profile of leukotrienes (except LTC4) and histamine when challenged with the allergen or ionophore A23187. Maximum release of LTB4 and LTD4 by allergen or

  1. 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.

  2. 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.

  3. 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.

  4. Ibuprofen or aspirin in rheumatoid arthritis therapy.

    PubMed

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

    1975-07-28

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

  5. 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)

  6. Narrow-line waveguide terahertz time-domain spectroscopy of aspirin and aspirin precursors.

    PubMed

    Laman, N; Harsha, S Sree; Grischkowsky, D

    2008-03-01

    Low frequency vibrational modes of pharmaceutical molecules are dependent on the molecule as a whole and can be used for identification purposes. However, conventional Fourier transform far-infrared spectroscopy (FT-IR) and terahertz time-domain spectroscopy (THz-TDS) often result in broad, overlapping features that are difficult to distinguish. The technique of waveguide THz-TDS has been recently developed, resulting in sharper spectral features. Waveguide THz-TDS consists of forming an ordered polycrystalline film on a metal plate and incorporating that plate in a parallel-plate waveguide, where the film is probed by THz radiation. The planar order of the film on the metal surface strongly reduces the inhomogeneous broadening, while cooling the waveguide to 77 K reduces the homogeneous broadening. This combination results in sharper absorption lines associated with the vibrational modes of the molecule. Here, this technique has been demonstrated with aspirin and its precursors, benzoic acid and salicylic acid, as well as the salicylic acid isomers 3- and 4-hydroxybenzoic acid. Linewidths as narrow as 20 GHz have been observed, rivaling single crystal measurements.

  7. Effect of diltiazem and low-dose aspirin on platelet aggregation and ATP release induced by paired agonists.

    PubMed

    Zucker, M L; Budd, S E; Dollar, L E; Chernoff, S B; Altman, R

    1993-08-02

    The authors studied the effects of diltiazem, administered alone and together with low-dose aspirin, on the platelet response to paired agonists. After a baseline period, 25 healthy volunteers were given oral diltiazem for 1 week (120, 240, or 360 mg/day), and then crossed over randomly between 1 week on diltiazem plus aspirin (81 mg/day), and 1 week on aspirin (81 mg/day) alone. Platelet function was tested on 2 consecutive days in each period. Synergistic platelet aggregation and ATP release were obtained at baseline using a subthreshold concentration of arachidonic acid combined with platelet activating factor, ADP, or epinephrine. Diltiazem resulted in significant decrease from baseline in platelet aggregation and ATP release using the arachidonic acid-epinephrine combination (35% and 40% decrease, respectively, p < 0.01) and a significant decrease in aggregation using the arachidonic acid-ADP combination (22% decrease, p < 0.01). The effects were neither dose-related, nor accompanied by any significant change in serum thromboxane B2 levels or bleeding times. There was no significant difference between the effects of aspirin alone and aspirin plus diltiazem on the synergistic platelet aggregation and ATP release induced by the paired agonists, or on thromboxane B2 levels or bleeding times. Diltiazem administered in vivo partially inhibits the synergistic platelet aggregation and ATP release induced by paired agonists; however, in contrast to a previous in vitro study it does not potentiate the platelet-inhibitory effect of aspirin.

  8. 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.

  9. Determinants of Reduced Antiplatelet Effect of Aspirin in Patients with Stable Coronary Artery Disease

    PubMed Central

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

    2015-01-01

    Background Aspirin is a cornerstone in management of coronary artery disease (CAD). However, considerable variability in the antiplatelet effect of aspirin has been reported. Aim To investigate independent determinants of reduced antiplatelet effect of aspirin in stable CAD patients. Methods We performed a cross-sectional study including 900 stable, high-risk CAD patients. Among these, 795 (88%) had prior myocardial infarction, 250 (28%) had type 2 diabetes, and 170 (19%) had both. All patients received 75 mg aspirin daily as mono antiplatelet therapy. The antiplatelet effect of aspirin was assessed by measurement of platelet aggregation employing 1) multiple electrode aggregometry (MEA, Multiplate Analyzer) in whole blood anticoagulated with citrate or hirudin using arachidonic acid (AA) or collagen as agonists, and 2) VerifyNow Aspirin Assay. Compliance was assessed by measurement of serum thromboxane B2. Results Platelet count, prior myocardial infarction, type 2 diabetes and body mass index were independent determinants of increased AA-induced MEA platelet aggregation in citrate and hirudin anticoagulated blood (p-values ≤ 0.045). Similar results were found with VerifyNow. Prior coronary artery bypass grafting, age, smoking (MEA, AA/citrate) and female gender (MEA, AA/hirudin) were also independent determinants of increased platelet aggregation (p-values ≤ 0.038). Compliance was confirmed by low serum thromboxane B2 levels in all patients (median [25%;75%]: 0.97 [0.52;1.97], range 0.02-26.44 ng/ml). Conclusion Platelet count, prior myocardial infarction, type 2 diabetes and body mass index were independent determinants of increased platelet aggregation, indicating that these characteristics may be key factors in reduced antiplatelet effect of aspirin in stable CAD patients. PMID:25993271

  10. Effect of carnosine, aminoguanidine, and aspirin drops on the prevention of cataracts in diabetic rats

    PubMed Central

    Guo, Yong; Zhang, Jie; Ding, Zhenghua; Ha, Wenjing; Harding, J.J.

    2008-01-01

    Purpose To investigate the effect of carnosine (CA), aminoguanidine (AG), and aspirin (ASA) drops, all inhibitors of glycation, on the development of diabetic cataract in rat. Methods Rats were made diabetic with streptozotocin, and based on the level of plasma glucose, they were assigned as non-diabetic rats (<14 mmol/l plasma glucose) and diabetic rats (>14 mmol/l plasma glucose). Animals in the treated groups received CA, AG, and ASA as drops to the left eyes starting from the day of streptozotocin injection. Progression of lens opacification was recorded using the slit lamp at regular time intervals. All the rats were killed after the week 13, and the levels of advanced glycation end products (AGE), glutathione reductase (GR), catalase (CAT), and glutathione (GSH) were determined. Results Lens opacification progressed in a biphasic manner in the diabetic rats, an initial slow increase during the first eight weeks of diabetes followed by a steep increase in the next five weeks. Carnosine treatment delayed the progression of cataracts in diabetic rats, and the delay was statistically significant on the fourth week of diabetes (p<0.05, when compared with untreated moderately diabetic rats). A decrease in the antioxidant enzymes of CAT and the level of GSH was found in the lens of the untreated diabetic rats at 13 weeks after injection. Some protection was provided in the treated eyes. The level of glycation in the untreated diabetic rats was significantly higher than that in the normal rats (p<0.001). After treatment with CA, AG, and ASA, those diabetic rats had a lower level of glycated lens protein compared to the untreated diabetic rats (p<0.001). Conclusions These results thus suggest that the effect of CA, AG, and ASA is indeed inhibition of the formation of AGEs. However, the effect of CA, AG, and ASA is overwhelmed by the excessive accumulation of AGEs in the severely diabetic rats. CA compared with AG and ASA treatment can delay the progression of lens

  11. The relationship between relative solvent accessible surface area (rASA) and irregular structures in protean segments (ProSs)

    PubMed Central

    Shaji, Divya

    2016-01-01

    Intrinsically Disordered Proteins (IDPs) lack a stable, three-dimensional structure under physiological conditions, yet they exhibit numerous biological activities. Protean segments (ProSs) are the functional regions of intrinsically disordered proteins that undergo disorder-to-order transitions upon binding to their partners. Example ProSs collected from the intrinsically disordered proteins with extensive annotations and literature (IDEAL) database. The interface of protean segments (ProSs) is classified into core, rim, and support, and analyzed their secondary structure elements (SSEs) based on the relative accessible surface area (rASA). The amino acid compositions and the relative solvent accessible surface areas (rASAs) of ProS secondary structural elements (SSEs) at the interface, core and rim were compared to those of heterodimers. The average number of contacts of alpha helices and irregular residues was calculated for each ProS and heterodimer. Furthermore, the ProSs were classified into high and low efficient based on their average number of contacts at the interface. The results indicate that the irregular structures of ProSs and heterodimers are significantly different. The rASA of irregular structures in the monomeric state (rASAm) is large, leads to the formation of larger ΔrASA and many contacts in ProSs. PMID:28250616

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

    PubMed

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

    2016-05-20

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

  13. Lipid Mediators in Aspirin-Exacerbated Respiratory Disease.

    PubMed

    Parker, Andrew R; Ayars, Andrew G; Altman, Matthew C; Henderson, William R

    2016-11-01

    Aspirin-exacerbated respiratory disease (AERD) is a syndrome of severe asthma and rhinosinusitis with nasal polyposis with exacerbations of baseline eosinophil-driven and mast cell-driven inflammation after nonsteroidal antiinflammatory drug ingestion. Although the underlying pathophysiology is poorly understood, dysregulation of the cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism is thought to be key. Central features of AERD pathogenesis are overproduction of proinflammatory and bronchoconstrictor cysteinyl leukotrienes and prostaglandin (PG) D2 and inhibition of bronchoprotective and antiinflammatory PGE2. Imbalance in the ratio of these lipid mediators likely leads to the increased eosinophilic and mast cell inflammatory responses in the respiratory tract.

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

    PubMed

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

    2017-03-03

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

  15. Assessing the Photometric Calibration of the ASAS Survey

    NASA Astrophysics Data System (ADS)

    Berdnikov, L. N.; Dambis, A. K.

    2016-05-01

    We compare bona fide calibrated mean VIC magnitudes of several hundred stars found in the CCD frames taken in 2012 during our photometric observations of 109 Cepheids and RR Lyrae type stars made at the South African Astronomical Observatory to the corresponding mean VIC magnitudes measured in the course of the ASAS survey to assess the quality of ASAS photometry and derive the appropriate transformation equations. We conclude that as far as the only serious caveat due to photometric errors, which range from ˜ 0.05m for relatively bright stars to about ˜ 0.15m for ˜ 14m stars and translates into extra fractional distance error of 0.025-0.07.

  16. 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

  17. 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

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

    PubMed

    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.

  19. 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.

  20. 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.

  1. Analysis of Kepler Observations of ASAS Variable Stars

    NASA Astrophysics Data System (ADS)

    Pezzato, Jacklyn M.; Mighell, Kenneth J.

    2016-01-01

    We present preliminary results of a study that compares the performance of period-finding algorithms when using data gathered by ground-based telescopes to their performance when using data gathered by space-based telescopes. In order to make this comparison, the periods reported by the All Sky Automated Survey (ASAS) Catalog for Variable Stars in the Kepler Field of View, a study that identified targets for the Kepler Mission before its launch, were compared to periods determined by this study. Only targets that were identified in the ASAS Catalog and later observed by the Kepler Mission were selected for analysis, for a total of 599 targets. The observations gathered by the Kepler Mission were analyzed using three period-finding algorithms: the Lafler-Kinman algorithm, the Analysis of Variance algorithm, and the Conditional Entropy algorithm. These three algorithms analyzed the light curves of each target, and one of the periods produced was selected to be compared to the period found by the ASAS Catalog. The analysis of the two data sets highlights issues with the performance of period finding algorithms with ground-based data, leading to crude period estimates for all targets with periods longer than 10 days. Since the Large Synoptic Scanning Telescope (LSST), due for first light in 2020, will have a similar observation schedule to that of the ASAS survey, similar issues can be expected with the analysis of LSST data for some types of long period variables, like semiregulars), that have periods longer than 10 days. Pezzato was supported by the NOAO/KPNO Research Experiences for Undergraduates (REU) Program which is funded by the National Science Foundation Research Experiences for Undergraduates Program (AST-1262829).

  2. Comparison of the pharmacokinetic profiles of soluble aspirin and solid paracetamol tablets in fed and fasted volunteers.

    PubMed

    Stillings, M; Havlik, I; Chetty, M; Clinton, C; Schall, R; Moodley, I; Muir, N; Little, S

    2000-01-01

    The aim of this study was to investigate the absorption of popular preparations of two common analgesics--soluble aspirin and solid paracetamol tablets. An open, randomised, crossover study design was used to compare the pharmacokinetic parameters of soluble aspirin and solid paracetamol tablets in 16 healthy, male volunteers from the University of the Witwatersrand, South Africa, in both fed and fasted states. Plasma concentrations of paracetamol, aspirin and salicylic acid were measured. It was found that the rate of absorption was significantly faster for soluble aspirin than for solid paracetamol, regardless of fed or fasting state, considering time to maximum concentration (p < 0.01), time to first quantifiable concentrations (p < 0.05) and absorption rate (p < 0.01). Absorption rate was significantly affected by food for both soluble aspirin (p = 0.028) and for solid paracetamol (p = 0.0003). Time to maximum concentration was not significantly affected by food for soluble aspirin (p = 0.17) but significantly lengthened for solid paracetamol (p = 0.0003). The extent of absorption was affected by food in terms of maximum concentration for both drugs (p = 0.0001), with a reduction of 49% in the fed state for solid paracetamol compared to 18% for soluble aspirin, the difference between the drugs being statistically significant (p = 0.0024). The overall bioavailability of soluble aspirin was unaffected by food and the bioavailability of salicylic acid was increased in the fed state, whereas that of solid paracetamol was lowered in the fed state. Greater inter-individual variation was seen in paracetamol concentrations compared with aspirin or salicylic acid levels. In conclusion, these results show that the absorption of soluble aspirin is largely unaffected by food, whereas, in the same volunteers, the absorption of solid paracetamol tablets is greatly affected. In some volunteers, maximum plasma concentrations of paracetamol following food did not reach levels

  3. 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…

  4. Identifying SRD Variables Among "Miscellaneous" ASAS Stars (Poster abstract)

    NASA Astrophysics Data System (ADS)

    Quinonez, M.; Larsen, K.

    2016-06-01

    (Abstract only) The International Variable Star Index (VSX) contains a large number of stars observed and analyzed by the All Sky Automated Survey (ASAS). While ASAS is a powerful tool in terms of the sheer volume of data it collects, its automated light curve analysis is not always robust enough to reliably identify stars that are not strictly regular in their magnitude variations. As a consequence, it was suspected that potentially many variable stars of the semiregular type were instead added to the VSX under a miscellaneous (MISC) classification. A subset of these semiregular stars, known as SRD variables, has a well-defined set of parameters regarding their classification - they are of the F, G, or K spectral type, their amplitudes of light variation are between 0.1 and 4 magnitudes, and their periods of variation can span 30 to 1,100 days. Furthermore, SRD variables are giants or supergiants, and therefore typically distant with small proper motions. A search was made through stars listed as MISC in the VSX using the above parameters, as well detailed light curve analyses via the AAVSO's VStar program, in order to find ASAS SRDs that were misclassified as MISC. This study of 90 stars has yielded five new SRDs to date. In addition, some data pertaining to several stars that were not confirmed to be of the SRD type were found to contain errors, and have since been revised accordingly in VSX.

  5. On the period determination of ASAS eclipsing binaries

    NASA Astrophysics Data System (ADS)

    Mayangsari, L.; Priyatikanto, R.; Putra, M.

    2014-03-01

    Variable stars, or particularly eclipsing binaries, are very essential astronomical occurrence. Surveys are the backbone of astronomy, and many discoveries of variable stars are the results of surveys. All-Sky Automated Survey (ASAS) is one of the observing projects whose ultimate goal is photometric monitoring of variable stars. Since its first light in 1997, ASAS has collected 50,099 variable stars, with 11,076 eclipsing binaries among them. In the present work we focus on the period determination of the eclipsing binaries. Since the number of data points in each ASAS eclipsing binary light curve is sparse, period determination of any system is a not straightforward process. For 30 samples of such systems we compare the implementation of Lomb-Scargle algorithm which is an Fast Fourier Transform (FFT) basis and Phase Dispersion Minimization (PDM) method which is non-FFT basis to determine their period. It is demonstrated that PDM gives better performance at handling eclipsing detached (ED) systems whose variability are non-sinusoidal. More over, using semi-automatic recipes, we get better period solution and satisfactorily improve 53% of the selected object's light curves, but failed against another 7% of selected objects. In addition, we also highlight 4 interesting objects for further investigation.

  6. Synthesis of 1-O-(2'-acetoxy)benzoyl-alpha-D-2-deoxyglucopyranose, a novel aspirin prodrug.

    PubMed

    Truelove, J E; Hussain, A A; Kostenbauder, H B

    1980-02-01

    The synthesis and characterization of 1-O-(2'-acetoxy)benzoyl-alpha-D-2-deoxyglucopyranose, a novel aspirin prodrug, are described. 3,4,6-Tri-O-benzyl-alpha-D-2-deoxyglucopyranose was synthesized by methylating the anomeric hydroxyl group of 2-deoxyglucose, benzylating the 3-, 4-, and 6-hydroxy functional grups, and cleaving hydrolytically the anomeric methyl group. Reaction of the tribenzylated sugar with the acid chloride of aspirin and subsequent hydrogenolysis of the benzyl groups resulted in the prodrug, mp 128 degrees. The compound was further characterized by elemental analysis and PMR and 13C-NMR spectroscopy. In vitro, the compound cleaved to aspirin with a half-life of 7 min at 37 degrees. Prodrug cleavage was independent of pH over the pH 3--9 range.

  7. 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.

  8. 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.

  9. A comparison of the anti-inflammatory and anti-nociceptive activity of nitroaspirin and aspirin

    PubMed Central

    al-Swayeh, O A; Clifford, R H; del Soldato, P; Moore, P K

    2000-01-01

    Nitroaspirin (2.5–50 mg kg−1, i.p. or 2.5–100 mg kg−1, p.o.) and aspirin (2.5–100 mg kg−1, i.p. or p.o.) exhibit anti-inflammatory activity in the carrageenan-induced hindpaw oedema model in the rat. When administered i.p., nitroaspirin was a more effective anti-oedema agent than aspirin particularly in the ‘early' phase (i.e. up to 60 min) of the response. The ED50 values for nitroaspirin and aspirin as inhibitors of the ‘late' phase response (measured at 180 min) were 64.3 μmol kg−1 and >555 μmol kg−1, respectively. When administered p.o., neither nitroaspirin nor aspirin exhibited significant anti-inflammatory activity in the ‘early' phase and were of similar potency in the ‘late' phase. Thus, at the highest dose used (100 mg kg−1, 360 min) orally administered nitroaspirin (aspirin in parenthesis) inhibited oedema formation by 46.9±1.6% (47.2±3.8%, both n=6, P<0.05). Nitroaspirin and aspirin (25–200 mg kg−1, p.o.) caused dose-related inhibition of the hyperalgesia to mechanical stimulation following intraplantar injection of carrageenan in the rat. ED50 values were 365 μmol kg−1 and 784 μmol kg−1, respectively. Neither drug influenced the threshold for mechanical stimulation in the contralateral (i.e. untreated) hindpaw. Nitroaspirin and aspirin (2.5–100 mg kg−1, p.o.) caused dose-related inhibition of acetic acid induced abdominal constrictions in the mouse (ED50 values of 154.7 μmol kg−1 and 242.8 μmol kg−1, respectively). Nitroaspirin and aspirin (>200 mg kg−1, p.o.) reduced the ‘late' phase (but not the ‘early' phase) of the formalin-induced hindpaw licking assay in the mouse. Similarly, nitroaspirin and aspirin (>50 mg kg−1, p.o.) prolonged tail withdrawal latency following application of a noxious heat stimulus in the mouse. PMID:10694241

  10. Daily Aspirin May Help Prevent Some Recurrent Miscarriages

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_163515.html Daily Aspirin May Help Prevent Some Recurrent Miscarriages Approach seemed ... as simple as taking a daily low-dose aspirin could help prevent a recurrence. The intervention appears ...

  11. Daily Aspirin Therapy: Understand the Benefits and Risks

    MedlinePlus

    ... made for or against aspirin use to prevent cardiovascular disease and colorectal cancer for these age groups. Although ... of aspirin in secondary and primary prevention of cardiovascular disease. http://www.uptodate.com/home. Accessed Feb. 3, ...

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

    PubMed Central

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

    2016-01-01

    Background Simultaneous prescription of clopidogrel and low-dose aspirin is recommended for the treatment of acute coronary syndrome because of improvements in efficacy and patient compliance. In this study, the pharmacokinetics of a fixed-dose combination (FDC) of clopidogrel and aspirin was compared with coadministration of individual formulations to clarify the equivalence of the FDC. Methods This was a randomized, open-label, two-period, two-treatment, crossover study in healthy Korean men aged 20–55 years. Subjects received two FDC capsules of clopidogrel/aspirin 75/100 mg (test) or two tablets of clopidogrel 75 mg and two capsules of aspirin 100 mg (reference) with a 14-day washout period. Plasma concentrations of clopidogrel, aspirin, and salicylic acid were measured using validated ultraperformance liquid chromatography–tandem mass spectrometry. Bioequivalence was assessed by analysis of variance and calculation of the 90% confidence intervals (CIs) of the ratios of the geometric means (GMRs) for AUClast and Cmax for clopidogrel and aspirin. Results Sixty healthy subjects were enrolled, and 53 completed the study. Clopidogrel, aspirin, and salicylic acid showed similar absorption profiles and no significant differences in Cmax, AUClast, and Tmax between FDC administration and coadministration of individual formulations. The GMRs (90% CI) for the Cmax and AUClast of clopidogrel were 1.08 (0.95, 1.23) and 0.93 (0.84, 1.03), respectively. The GMRs (90% CI) for the Cmax and AUClast of aspirin were 0.98 (0.84, 1.13) and 0.98 (0.93, 1.04), respectively. Both treatments were well tolerated in the study subjects. Conclusion The FDC of clopidogrel and aspirin was bioequivalent to coadministration of each individual formulation. The FDC capsule exhibited similar safety and tolerability profiles to the individual formulations. Therefore, clopidogrel/aspirin 75 mg/100 mg FDC capsules can be prescribed to improve patient compliance. PMID:27822013

  13. Aspirin-induced post-gingivectomy haemorrhage: a timely reminder.

    PubMed

    Thomason, J M; Seymour, R A; Murphy, P; Brigham, K M; Jones, P

    1997-02-01

    A case report is described of significant aspirin-induced haemorrhage following a gingivectory procedure in an organ transplant patient. Aspirin-induced platelet impairment secondary to low-dose aspirin was implicated as the cause of the haemorrhage. Haemostasis was eventually achieved after platelet transfusion. The case illustrates the problems that can arise when carrying out gingival surgery on patients medicated with low-dose aspirin.

  14. Analysis of the mechanism for the development of allergic skin inflammation and the application for its treatment: aspirin modulation of IgE-dependent mast cell activation: role of aspirin-induced exacerbation of immediate allergy.

    PubMed

    Suzuki, Yoshihiro; Ra, Chisei

    2009-07-01

    Aspirin (acetylsalicylic acid) is a well-known nonsteroidal anti-inflammatory drug that can potentiate some acute allergies and causes adverse immunological reactions collectively referred to as aspirin intolerance, a disorder that induces urticaria, asthma, and anaphylaxis in response to oral administration of the drug. Aspirin also potentiates some acute allergies such as food-dependent exercise-induced anaphylaxis (FDEIA), a food allergy induced by physical exercise. The anti-inflammatory actions as well as the adverse immunological effects have been thought to be primarily due to inhibition of cyclooxygenase activity. However, a growing body of evidence suggests that mechanisms unrelated to inhibition of prostaglandin synthesis are involved. One key feature of aspirin intolerance is the overproductions of cysteinyl leukotrienes (LTs), in which mast cells have been implicated to play a role. In this review, we provide an overview of our current knowledge about the regulatory mechanisms of LTC(4) secretion in mast cells and its modulation by aspirin, with a special emphasis on the role of Ca(2+) signals. We also introduced our recent findings that mast cells express dihydropyridine-sensitive L-type Ca(2+) channels (LTCCs) and that Ca(2+) channels of this kind mediate aspirin modulation of LTC(4) secretion in mast cells.

  15. Evaluation of an enteric coated aspirin preparation.

    PubMed

    Day, R O; Paull, P D; Champion, G D; Graham, G G

    1976-02-01

    The bioavailability and gastrointestinal site of release of enteric coated aspirin tablets ("Rhusal", G.P. Laboratories) were investigated following dosage with single tablets. A delay of one to more than eight hours was observed between dosage and the appearance of salicylate in plasma or saliva. This delay was decreased by pretreatment with metoclopramide. No aspirin or salicylate was detected in gastric aspirates. The mean urinary recovery of salicylate was equivalent to 92% of the administered dose. All these tests were consistent with the designed function of the enteric coating. The time course of concentrations of salicylate in saliva rather than in plasma was confirmed as a useful technique for the evaluation of different formulations of aspirin. The acceleration of gastric emptying by metoclopramide is a useful technique for the evaluation of enteric coated tablets.

  16. [ASA classification : Transition in the course of time and depiction in the literature].

    PubMed

    Irlbeck, T; Zwißler, B; Bauer, A

    2017-01-01

    The American Society of Anesthesiologists classification of physical status (ASA PS) is a widely used system for categorizing the preoperative status of patients. The ASA class is a good independent predictor of perioperative morbidity and mortality. The definitions of the ASA classes have been amended several times since 1941, resulting in inconsistent and confusing usage in the current literature. Conflicting definitions of ASA PS exist, particularly for classes III, IV and V. The high variability of individual classifications by different anesthesiologist, however, can be explained by the previous lack of examples for diagnoses. In 2014, the ASA has added a catalogue of examples for a simplified definition for classification of the ASA PS. This has so far received limited attention in German-speaking countries. This article describes the transition of the ASA classification over the past 75 years und summarizes the currently valid definitions.

  17. Detoxifying emulsion for overdosed aspirin intoxication.

    PubMed

    Zhang, Wenjun; Stambouli, Moncef; Pareau, Dominique

    2013-01-30

    Aspirin overdose could lead to intoxication, with the clinical manifestations of vomit, pulmonary edema and severe dyspnea. Stomach washing, emetics and activated charcoal are the common treatments with a limited efficiency for the intoxication. In this study, an active emulsion for aspirin intoxication was prepared with the detoxifying efficiency of 100% in less than 15 min, with the conditions of dodecane used as the oil phase, 8% Abil EM90 as the surfactant and 0.1 mol/L sodium hydroxide as the inner aqueous phase in a volume ratio of 2 between internal aqueous phase and the oil phase.

  18. Mechanisms underlying aspirin-mediated growth inhibition and apoptosis induction of cyclooxygenase-2 negative colon cancer cell line SW480

    PubMed Central

    Lai, Ming-Yu; Huang, Jie-An; Liang, Zhi-Hai; Jiang, Hai-Xing; Tang, Guo-Du

    2008-01-01

    AIM: To investigate the effects of aspirin (acetylsalicylic acid) on proliferation and apoptosis of colorectal cancer cell line SW480 and its mechanism. METHODS: Cyclooxygenase (COX)-2 negative colorectal cancer cell line SW480 was treated with aspirin at concentrations of 2.5 mmol/L, 5.0 mmol/L, 10.0 mmol/L for different periods in vitro. Anti-proliferation effect of aspirin on SW480 was detected by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle and apoptosis were observed by flow cytometry (FCM). Transmission electron microscope (TEM) was used for morphological study. Apoptosis-associated genes were detected by immunohistochemical staining and Western blotting. RESULTS: Aspirin inhibited SW480 proliferation and induced apoptosis in a dose- and time-dependent manner. Treatment with different concentrations of aspirin significantly increased the proportions of cells at the G0/G1 phase and decreased the proportions of cells at the S- and G2/M phases in a concentration-dependent manner. Aspirin not only induced apoptosis but also caused cell necrosis at a high concentration as well. After treatment with aspirin, SW480 cells displayed typically morphological features of apoptosis and necrosis under TEM, and increased the Bcl-2 expression in cells, but the expression of Bax was down regulated. CONCLUSION: Aspirin inhibits proliferation and induces apoptosis of SW480 cells. Its anti-tumor mechanism may arrest cell cycle and shift Bax/Bcl-2 balance in cells. PMID:18636671

  19. 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.

  20. Aspirin inhibits the production of proangiogenic 15(S)-HETE by platelet cyclooxygenase-1

    PubMed Central

    Rauzi, Francesca; Kirkby, Nicholas S.; Edin, Matthew L.; Whiteford, James; Zeldin, Darryl C.; Mitchell, Jane A.; Warner, Timothy D.

    2016-01-01

    Regular consumption of low-dose aspirin reduces the occurrence of colorectal, esophageal, stomach, and gastrointestinal cancers. The underlying mechanism is unknown but may be linked to inhibition of angiogenesis. Because the effective doses of aspirin are consistent with the inhibition of cyclooxygenase-1 in platelets, we used liquid chromatography with tandem mass spectrometry analyses and immunoassays of human platelet releasates coupled with angiogenesis assays to search for the mediators of these effects. Blood or platelet-rich plasma from healthy volunteers stimulated with platelet activators produced a broad range of eicosanoids. Notably, preincubation of platelets with aspirin, but not with a P2Y12 receptor antagonist, caused a marked reduction in the production of 11-hydroxyeicosatetraenoic acid (HETE) and 15(S)-HETE, in addition to prostanoids such as thromboxane A2. Releasates from activated platelets caused cell migration and tube formation in cultured human endothelial cells and stimulated the sprouting of rat aortic rings in culture. These proangiogenic effects were absent when platelets were treated with aspirin but returned by coincubation with exogenous 15(S)-HETE. These results reveal 15(S)-HETE as a major platelet cyclooxygenase-1 product with strong proangiogenic effects. Thus, 15(S)-HETE represents a potential target for the development of novel antiangiogenic therapeutics, and blockade of its production may provide a mechanism for the anticancer effects of aspirin.—Rauzi, F., Kirkby, N. S., Edin, M. L., Whiteford, J. Zeldin, D. C., Mitchell, J. A., Warner, T. D. Aspirin inhibits the production of proangiogenic 15(S)-HETE by platelet cyclooxygenase-1. PMID:27633788

  1. Measurement of platelet P-selectin for remote testing of platelet function during treatment with clopidogrel and/or aspirin.

    PubMed

    Fox, S C; May, J A; Shah, A; Neubert, U; Heptinstall, S

    2009-06-01

    There is great interest in assessing the efficacy of treatment with clopidogrel and aspirin in patients with cardiovascular disease using procedures that can be used in a remote setting. Here we have established methods to assess the effects of clopidogrel and aspirin on platelets based on measurements of platelet P-selectin. Platelets were stimulated in whole blood by adding the combination of adenosine diphosphate and the TXA(2) mimetic U46619 (ADP/U4, designed to assess P2Y(12) inhibition) or the combination of arachidonic acid and epinephrine (AA/Epi, designed to assess COX-1 inhibition). The stimulated samples were then fixed using a fixative solution that provides stability for at least 9 days, and sent to a central laboratory for analysis of P-selectin by flow cytometry. Measurements were performed in blood from healthy volunteers and patients with cardiovascular disease. The inhibitory effects of clopidogrel and aspirin were assessed ex vivo and the effects of the direct acting P2Y(12) antagonist cangrelor and aspirin were assessed in vitro. Measurements of platelet aggregation were also performed for comparison. In healthy volunteers clopidogrel ex vivo and cangrelor in vitro markedly inhibited P-selectin expression induced by ADP/U4. Aspirin did not inhibit and did not interfere with the effects of clopidogrel or cangrelor using this test. There was very little overlap of results obtained in the absence and presence of clopidogrel or cangrelor. In contrast, over half of 42 patients with cardiovascular disease did not respond well to clopidogrel treatment, although cangrelor was still effective. Aspirin markedly inhibited P-selectin expression induced by AA/Epi. Clopidogrel had much less effect and did not interfere with the effects of aspirin. There was no overlap of results obtained in the absence and presence of aspirin. Aspirin provided near-complete inhibition in 29 of 30 patients with cardiovascular disease. Aggregometry measurements agreed well with

  2. 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.

  3. Effect of S-aspirin, a novel hydrogen-sulfide-releasing aspirin (ACS14), on atherosclerosis in apoE-deficient mice.

    PubMed

    Zhang, Huili; Guo, Changfa; Zhang, Alian; Fan, Yuqi; Gu, Ting; Wu, Duojiao; Sparatore, Anna; Wang, Changqian

    2012-12-15

    Hydrogen sulfide (H(2)S) is a novel gaseous mediator that plays important roles in atherosclerosis. The present study investigated the effect of a novel H(2)S-releasing aspirin, ACS14 (2-acetyloxybenzoic acid 4-(3-thioxo-3H-1,2-dithiol-5-yl)phenyl ester), on atherosclerotic plaques in fat-fed apoE(-/-) mice and the underlying mechanism with respect to CX3C chemokine receptor 1 (CX3CR1) in macrophages. Mouse macrophage cell line RAW264.7 or mouse peritoneal macrophages were preincubated with aspirin (50, 100 or 200μM), ACS14 (50, 100 or 200μM) or vehicle for 6h, and then stimulated with interferon (IFN)-γ (500U/ml) or lipopolysaccharide (LPS; 10μg/ml) for 12h. ACS14, but not aspirin, dose-dependently inhibited IFN-γ or LPS-induced CX3CR1 expression and CX3CR1-mediated chemotaxis in macrophages. The inhibitory effect of ACS14 on CX3CR1 expression was abolished by pretreatment with GW9662, a selective peroxisome proliferator-activated receptor (PPAR)-γ antagonist, suggesting that suppression of macrophage CX3CR1 expression by ACS14 is PPAR-γ dependent. Eight-week-old male apoE(-/-) mice received intraperitoneal ACS14 (15 or 30μmol/kg/day) or aspirin (15 or 30μmol/kg/day) 4 weeks after fat feeding. Twelve weeks after ACS14 or aspirin treatment, mice were sacrificed to evaluate the extent of atherosclerosis and CX3CR1 expression in brachiocephalic artery (BCA). We found that ACS14, but not aspirin, significantly downregulated CX3CR1 expression in atherosclerotic plaques. ACS14 considerably impeded the formation and development of atherosclerosis as compared to a molar equivalent dose of aspirin. These data indicate that ACS14 may prevent the progression of atherosclerosis by downregulating macrophage CX3CR1 expression via a PPAR-γ-dependent mechanism.

  4. 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.

  5. 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.

  6. Acetylation of prostaglandin synthetase by aspirin. Purification and properties of the acetylated protein from sheep vesicular gland.

    PubMed

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

    1977-09-20

    We previously presented evidence that aspirin (acetylsalicylic acid) inhibits prostaglandin synthetase by acetylating and active site of the enzyme. In the current work, we have labeled the enzyme from an aceton-pentane powder of sheep vesicular gland using [acetyl-3H]aspirin and purified the [3H]acetyl-protein to near homogeneity. The final preparation contains protein of a single molecular weight (85 000) and an amino-terminal sequence of Asp-Ala-Gly-Arg-Ala. The [3H]acetyl-protein contained 0.5 mol of acetyl residues per mol of protein based on amino acid composition but only a single sequence was found.

  7. Identification of Misclassified Rotational Variables in the ASAS Catalog

    NASA Astrophysics Data System (ADS)

    Larsen, Kristine; Johnson, Jessica M.; Hoover, Corwin

    2017-01-01

    Rotating variables are a subset of extrinsic variable stars in which variations in the apparent brightness of a star are tied to its rotation. Among these are BY Draconis stars, K or M dwarfs that feature transient spots. The light curves of these stars have similarities to those of pulsating variables, leading to misclassification by automated programs. Likewise, the transient and unpredictable nature of the spots can lead automated programs to miss the period of the star’s rotation and lead to both misclassification of these stars as “miscellaneous” as well as erroneous period determinations. A survey by P. Wils of a random sample of stars classified as either Cepheids or Beta Cepheid pulsating variables in the ASAS (All Sky Automated Survey) catalog demonstrated that BY Draconis stars were an important polluter of this data set. Work by J. Johnson and K. Larsen on this data set analyzed light curves using the AAVSO’s VStar program as well as used proper motion and color indices to find additional BY Draconis stars that had been classified as either Cepheids or Beta Cepheids, as well as a number of Ellipsoidal variables. These are non-eclipsing binaries in which the shape of each star is distorted by their mutual gravitational pull. As the stars orbit each other, the elongated stars rotate, yielding two maximum and two minimum magnitudes per cycle with a period equal to the orbital period. Thus these stars can be misclassified as “miscellaneous” type and with periods that are only half of the true period. C. Hoover and K. Larsen investigated stars from the ASAS catalogue with periods up to 15 days that were included in the Variable Star Index (VSX) under the classification “miscellaneous.” Light curve analysis using VStar, as well as color indices and other physical properties, were used to identify both Ellipsoidal variables and spotted stars of the RS Canum Venaticorum type (binary systems that include a spotted star) in this data set. Taken

  8. 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.

  9. 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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

    Ogundeji, Adepemi O.; Pohl, Carolina H.

    2016-01-01

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

  12. 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.

  13. A Review on the Relationship between Aspirin and Bone Health

    PubMed Central

    2017-01-01

    Aspirin is a cyclooxygenase inhibitor commonly used in primary prevention of cardiovascular diseases and cancers. Its users are elderly population susceptible to osteoporosis. It also inhibits the synthesis of prostaglandin E2 essential in bone remodeling. This prompts the question whether it can influence bone health among users. This review aimed to summarize the current literature on the use of aspirin on bone health. A literature search on experimental and clinical evidence on the effects of aspirin on bone health was performed using major scientific databases. In vitro studies showed that aspirin could enhance the survival of bone marrow mesenchymal stem cells, the progenitors of osteoblasts, and stimulate the differentiation of preosteoblasts. Aspirin also inhibited the nuclear factor kappa-B (NFκB) pathway and decreased the expression of receptor activator of NFκB ligand, thus suppressing the formation of osteoclast. Aspirin could prevent bone loss in animal models of osteoporosis. Despite a positive effect on bone mineral density, the limited human epidemiological studies revealed that aspirin could not reduce fracture risk. A study even suggested that the use of aspirin increased fracture risk. As a conclusion, aspirin may increase bone mineral density but its effect on fracture prevention is inconclusive. More data are needed to determine the effects of aspirin and bone health in human. PMID:28163951

  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. Identification of Cepheid Variables in ASAS Data (Poster abstract)

    NASA Astrophysics Data System (ADS)

    Swenton, V.; Larsen, K.

    2014-06-01

    (Abstract only) Through studying the characteristics of Cepheid variables, we can further understand the nature and evolution of stars, as well as the scale of the Universe (through the famous period-luminosity relationship). Classical Cepheid stars, or Type I Cepheids, are radially-pulsating supergiants. Type II Cepheids are older and have lower mass than Type I Cepheids. They are rarer and existing classifications of these stars have been shown to be erroneous at unusual high rates. Computerized automatic classification programs sift through the data of large photometric surveys to produce a list of (what the program recognizes as) Cepheid star candidates. Unfortunately, this automatic classification of light curves has demonstrated to be ambiguous. Therefore, it takes a human to further sift through the list in order to come up with a more accurate (and, as a result, a more useful) list of probable Cepheids. This study was based on a list of 3,548 Cepheid candidates in the ASAS data provided by Patrick Wils (through Doug Welch). Patrick Wils had previously examined eighty-four stars on the spreadsheet and positively identified only five of these stars as Cepheids. The methodology of the current study was to use known properties of Cepheids including available infrared photometry (2MASS), proper motion (PPMXL), and X-Ray emission (ROTSE) data (for which we received helpful guidance from Sebastian Otero) to cull the list down to the most likely Cepheids. The ASAS light curves of these candidates were investigated to determine whether the shapes were truly consistent with those of Cepheids. This poster will summarize the methodology used and give examples of how individual Cepheid candidates were evaluated. Candidates of interest are currently being crosschecked for any updated information on VSX, and the light curves more closely analyzed using VStar. Results concerning the misidentification of candidate Cepheids will be reported to VSX and summarized in JAAVSO.

  16. 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

  17. A randomized, controlled study on the influence of acetaminophen, diclofenac, or naproxen on aspirin-induced inhibition of platelet aggregation.

    PubMed

    Galliard-Grigioni, Katja S; Reinhart, Walter H

    2009-05-01

    Nonsteroidal anti-inflammatory drugs (NSAID) may interfere with aspirin (acetylsalicylic acid) and increase the risk for cardiovascular events. The clinical relevance is uncertain. The aim of this study was to analyse the influence of a co-administration of aspirin and NSAID on platelet aggregation. In a randomized, placebo controlled trial, eleven healthy volunteers were studied during 4 separate study periods of 4 days each. Individuals were treated on each occasion with 100 mg aspirin daily in combination with either 3 x 1 g acetaminophen, 3 x 50 mg diclofenac, 3 x 250 mg naproxen, or 3 x 1 placebo. Primary hemostasis was assessed with a platelet function analyser (PFA-100), which measures the closure time (CT) of a collagen- and epinephrine-coated pore by aggregating platelets in flowing blood. Naproxen enhanced the anti-aggregatory action of aspirin after 24 h (CT rising from 104+/-16 s at baseline to 212+/-69 s at 24 h, P<0.001), which was not seen with any other drug combination. Diclofenac reduced the anti-aggregatory action of aspirin in the first two days, since the CT did not rise significantly (109+/-19 s, 148+/-56 s, and 168+/-66 s at 0 h, 24 h, 48 h, respectively, P>0.05). Acetaminophen had no effect compared with placebo. After 4 days of treatment platelet aggregation was similarly inhibited by all combinations. We conclude that a co-administration of NSAID and aspirin may interfere with platelet inhibition at the beginning of a treatment with an increase of naproxen and a decrease of diclofenac. This effect is lost after 4 days, suggesting that a regular daily co-administration of NSAID does not have an influence on platelet inhibition by aspirin.

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

    PubMed

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

    2005-12-01

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

  19. 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.

  20. 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.

  1. Aspirin dosing frequency in the primary and secondary prevention of cardiovascular events.

    PubMed

    Kim, Joonseok; Becker, Richard C

    2016-04-01

    Aspirin has been a cornerstone of cardiovascular disease prevention since the late 1980s. Despite the popularity of aspirin and its wide use, the proper dosing and frequency of aspirin has yet to be determined. Early aspirin trials focused on its utility in broad target populations, but this strategy did not magnify the benefit of aspirin, and rather increased the complication rate. We have learned from previous studies that laboratory and clinical response to aspirin therapy in patients with different conditions and settings are diverse. This difference in aspirin response necessitates a personalized, tailored aspirin therapy. We aim to perform a comprehensive review of the current evidence surrounding aspirin responsiveness in several distinct patient populations and the rationale of different aspirin frequency and dosing strategies. Our conclusions call for future studies to determine individualized aspirin strategies to maximize the benefit and minimize the risk of aspirin.

  2. 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 ...

  3. [Nasosinusal polyposis and aspirin intolerance. Fernand Widal-Lermoyez syndrome].

    PubMed

    Wayoff, M; Moneret-Vautrin, D; Gazel, P

    1979-01-01

    The authors describe the clinical picture of the aspirin idiosyncrasy and propose to call this peculiar entity: syndrom of Widal and Lermoyez. They compare 25 cases of aspirin nasal polyposis with 26 other cases of various etiologies. Other substances than aspirin seem to be charged. The complications are regular with severe asthma and infection. The pathogenesis is discussed, excluding an allergic mechanism; it remain not quite clear. Essentially prophylactic, the treatment is poor and difficult.

  4. 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. |

  5. 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.

  6. 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.

  7. Aspirin in episodic tension-type headache: placebo-controlled dose-ranging comparison with paracetamol.

    PubMed

    Steiner, T J; Lange, R; Voelker, M

    2003-02-01

    Most people with episodic tension-type headache (TTH) treat themselves with over-the-counter analgesics. In the absence of clear evidence of dose-related efficacy of the two most commonly used analgesics, aspirin (acetylsalicylic acid) and paracetamol (acetaminophen), this study compared two doses of each with placebo. In a double-blind, double-dummy, randomized parallel-groups comparative trial, 638 consenting subjects aged 16-65 years with episodic TTH (but not migraine) by IHS criteria were recruited from the UK general population by advertisement. They treated one episode of moderate or severe TTH with a single dose of 500 or 1000 mg aspirin, 500 or 1000 mg paracetamol or placebo. The primary objective was to compare aspirin 1000 mg with placebo, and the primary end-point was subjective pain relief (total or worthwhile) 2 h after treatment ('response'). Additionally, pain intensity on a 100-mm visual analogue scale and functional impairment were monitored regularly for 4 h and at 24 h, although rescue medication was allowed after 2 h. The analysis was of the intention-to-treat population of 542 who took treatment (all providing outcome data). Treatment groups were matched at baseline. Aspirin 1000 mg (75.7% response rate; P = 0.0009) and to a lesser extent aspirin 500 mg (70.3%; P = 0.011) and paracetamol 1000 mg (71.2%; P = 0.007), but not paracetamol 500 mg (63.8%; P = 0.104), were statistically more effective than placebo despite a high placebo-response rate (54.5%). Outcome was not affected by headache intensity at baseline. Secondary end-points including functional recovery (by median times of 4.0-13.5 h) were consistent with these findings, although a minority of subjects recorded long-duration functional impairment (37-54 h). Adverse events reported by 13.4-18.9% of subjects were mild or moderate, and transient. No safety concerns arose.

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

    PubMed

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

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

  9. A Copper (II) Aspirinate Project for the General Chemistry Laboratory

    ERIC Educational Resources Information Center

    Dudek, Emily

    1977-01-01

    Describes an experiment that involves the synthesis of copper (II) aspirinate and the analysis of copper content in the product using electrogravimetric, spectrophotometric, and titrimetric methods. (MLH)

  10. [Analgesics; the use of aspirin in dogs; effects of tablet type and food intake on plasma salicylate level].

    PubMed

    Nap, R C; Breen, D J; Lam, T J; Peters, I O; Willemsen, A; De Bruyne, J J

    1993-07-15

    Administration of acetylsalicylic acid (aspirin) in the dog may cause gastric mucosal damage. Enteric-coated tablets protect the canine stomach during oral aspirin medication. A therapeutic plasma salicylate concentration can be attained using enteric-coated aspirin tablets at a dosage of 25 mg/kg TID. In a series 4 of experiments using adult beagle and large mixed breed dogs and two types enteric-coated tablets, the influence of food intake on the plasma salicylate concentration was studied. Tablets were administered with 8h intervals and food intake was either once daily or three time daily with 8h intervals. Plasma salicylate concentrations were also studied during fasting. It is concluded that, when using enteric-coated tablets, the plasma salicylate concentration in the dog after oral medication is strongly influenced by the aspirin dosage, the tablet type and the feeding pattern. Large enteric-coated tablets may accumulate in the stomach over several days and are not suitable for use in the dog. The gastric accumulation is caused by the enteric-coating of the large tablets and not by the aspirin medication.

  11. Nutrient and Food Group Analysis in the 2016 ASA24® System

    Cancer.gov

    Researchers, clinicians, and educators can use the ASA24 system to analyze 65 nutrients and 37 food groups (U.S. and Canadian versions) from food recall or record data. Analyses for ASA24-Australia-2016 provide 41 nutrients and no food groups.

  12. 78 FR 32477 - ASA Gold and Precious Metals Limited; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-30

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION ASA Gold and Precious Metals Limited; Notice of Application May 22, 2013. AGENCY: Securities and... Metals Limited (``ASA''), a Bermuda closed-end management investment company registered under section...

  13. Reversal of IL-13-induced inflammation and Ca(2+) sensitivity by resolvin and MAG-DHA in association with ASA in human bronchi.

    PubMed

    Khaddaj-Mallat, Rayan; Sirois, Chantal; Sirois, Marco; Rizcallah, Edmond; Morin, Caroline; Rousseau, Éric

    2015-09-01

    The aim of this study was to investigate the effects of resolvin D1 (RvD1), as well as the combined treatment of docosahexaenoic acid monoglyceride (MAG-DHA) and acetylsalicylic acid (ASA), on the resolution of inflammation markers and Ca(2+) sensitivity in IL-13-pretreated human bronchi (HB). Tension measurements performed with 300 nM RvD1 largely abolished (50%) the over-reactivity triggered by 10 ng/ml IL-13 pretreatment and reversed hyper Ca(2+) sensitivity. Addition of 300 nM 17(S)-HpDoHE, the metabolic intermediate between DHA and RvD1, displayed similar effects. In the presence of 100 μM ASA (a COX inhibitor), the inhibitory effect of 1 μM MAG-DHA on muscarinic tone was further amplified, but not in the presence of Ibuprofen. Western blot analysis revealed that the combined treatment of MAG-DHA and ASA upregulated GPR-32 expression and downregulated cytosolic TNFα detection, hence preventing IκBα degradation and p65-NFκB phosphorylation. The Ca(2+) sensitivity of HB was also quantified on β-escin permeabilized preparations. The presence of ASA potentiated the inhibitory effects of MAG-DHA in reducing the Ca(2+) hypersensitivity triggered by IL-13 by decreasing the phosphorylation levels of the PKC-potentiated inhibitor protein-17 regulatory protein (CPI-17). In summary, MAG-DHA combined with ASA, as well as exogenously added RvD1, may represent valuable assets against critical AHR disorder.

  14. 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.

  15. Label-Free LSPR Detection of Trace Lead(II) Ions in Drinking Water by Synthetic Poly(mPD-co-ASA) Nanoparticles on Gold Nanoislands.

    PubMed

    Qiu, Guangyu; Ng, Siu Pang; Liang, Xiongyi; Ding, Ning; Chen, Xiangfeng; Wu, Chi-Man Lawrence

    2017-02-07

    Using self-assembly gold nanoislands (SAM-AuNIs) functionalized by poly(m-phenylenediamine-co-aniline-2-sulfonic acid) (poly(mPD-co-ASA)) copolymer nanoparticles as specific receptors, a highly sensitive localized surface plasmon resonance (LSPR) optochemical sensor is demonstrated for detection of trace lead cation (Pb(II)) in drinking water. The copolymer receptor is optimized in three aspects: (1) mole ratio of mPD:ASA monomers, (2) size of copolymer nanoparticles, and (3) surface density of the copolymer. It is shown that the 95:5 (mPD:ASA mole ratio) copolymer with size less than 100 nm exhibits the best Pb(II)-sensing performance, and the 200 times diluted standard copolymer solution contributes to the most effective functionalization protocol. The resulting poly(mPD-co-ASA)-functionalized LSPR sensor attains the detection limit to 0.011 ppb toward Pb(II) in drinking water, and the linear dynamic range covers 0.011 to 5000 ppb (i.e., 6 orders of magnitude). In addition, the sensing system exhibits robust selectivity to Pb(II) in the presence of other metallic cations as well as common anions. The proposed functional copolymer functionalized on AuNIs is found to provide excellent Pb(II)-sensing performance using simple LSPR instrumentation for rapid drinking-water inspection.

  16. 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…

  17. 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.

  18. Theoretical modeling of infrared spectra of aspirin and its deuterated derivative

    NASA Astrophysics Data System (ADS)

    Boczar, Marek; Wójcik, Marek J.; Szczeponek, Krzysztof; Jamróz, Dorota; Zi e̡ba, Adam; Kawałek, Bożena

    2003-01-01

    Theoretical simulation of the νs stretching band is presented for aspirin (acetylsalicylic acid) and its OD derivative at 300 and 77 K. The simulation takes into account an adiabatic coupling between the high-frequency O-H(D) stretching and the low-frequency intermolecular O⋯O stretching modes, linear and quadratic distortions of the potential energy for the low-frequency vibrations in the excited state of the O-H(D) stretching vibration, resonance interaction between two hydrogen bonds in the dimer, and Fermi resonance between the O-H(D) stretching and the overtone of the O-H(D) bending vibrations. The effect of deuteration and the temperature has been successfully reproduced by our model calculations. Infrared, far-infrared, Raman and low-frequency Raman spectra of the polycrystalline aspirin have been measured. The geometry and experimental frequencies are compared with the results of our B3LYP/6-31++G** calculations.

  19. Late-Time Follow-up of ASAS-SN Tidal Disruption Events

    NASA Astrophysics Data System (ADS)

    Warren-Son Holoien, Thomas; ASAS-SN Team

    2017-01-01

    Humanity should have a continuous record of the sky, and for the past 3.5 years, the All-Sky Automated Survey for SuperNovae (ASAS-SN or "Assassin") has been working to provide that record. ASAS-SN is a long-term project to monitor the entire sky with a rapid cadence using a global array of small telescopes in both hemispheres, searching for new bright transients that can be studied in detail by the world's astronomers. By focusing only on the brightest objects, ASAS-SN limits its discoveries to only those that can be studied in the greatest detail, and it is unique among professional surveys in this respect. While the primary goal of ASAS-SN is a complete survey of bright, nearby supernovae, ASAS-SN also finds many other interesting transients. ASAS-SN has discovered 3 of the brightest tidal disruption events (TDEs) ever found at optical wavelengths, and we have performed extensive follow-up studies of these objects since discovery. I will present the results of late-time follow-up studies of the ASAS-SN TDEs and discuss the deeper insight into TDE physics that can be gained from this work.

  20. The ASAS-SN bright supernova catalogue - 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.

    2017-01-01

    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 catalogue of bright supernovae and their hosts from multiple professional and amateur sources, allowing for population studies that were not previously possible because the all-sky emphasis of ASAS-SN redresses many previously existing biases. In particular, ASAS-SN systematically finds bright supernovae closer to the centres of host galaxies than either other professional surveys or amateurs, a remarkable result given ASAS-SN's poorer angular resolution. 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.

  1. 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

  2. Aspirin use and post-operative bleeding from dental extractions.

    PubMed

    Brennan, M T; Valerin, M A; Noll, J L; Napeñas, J J; Kent, M L; Fox, P C; Sasser, H C; Lockhart, P B

    2008-08-01

    Aspirin is a common, chronically administered preventive treatment for cardiovascular disease, but is often discontinued prior to invasive dental procedures because of concern for bleeding complications. We hypothesized that aspirin does not cause increased bleeding following a single tooth extraction. Thirty-six healthy persons requiring a tooth extraction were randomized to receive 325 mg/day aspirin or placebo for 4 days. Cutaneous bleeding time (BT) and platelet aggregation tests were obtained prior to extraction. The primary outcome measure, oral BT, and secondary bleeding outcomes were evaluated during and following extraction. No significant baseline differences, except for diastolic blood pressure, were found between groups. There were no differences in oral BT, cutaneous BT, secondary outcome measures, or compliance. Whole-blood aggregation results were significantly different between the aspirin and placebo groups. These findings suggest that there is no indication to discontinue aspirin for persons requiring single-tooth extraction.

  3. Inhibition of aspirin-induced bronchoconstriction by sodium cromoglycate inhalation.

    PubMed Central

    Martelli, N A; Usandivaras, G

    1977-01-01

    Five patients with asthma and severe aspirin hypersensitivity were challenged on separate days with increasing doses of aspirin given by mouth, starting with 5 mg, until a reduction in FEV1 greater than 15% was obtained. Sodium cromoglycate in doses of 20-40 mg inhibited the bronchoconstrictive reaction not only when inhaled before the challenge but also after it, at a time when progressive reduction in FEV1 values was taking place. According to these results, it seems reasonable to postulate sequential mast cell degranulation and liberation of mediators of anaphylaxis as the mechanism through which aspirin induces bronchoconstriction in aspirin-sensitive asthmatics. The differences between bronchial provocation tests and oral challenge with aspirin are stressed. PMID:414371

  4. 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.

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

    PubMed Central

    Kacprzak, Dorota

    2015-01-01

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

  6. ASA conference on radiation and health, Coolfont VI: Final report

    SciTech Connect

    Not Available

    1988-05-01

    The 1986 ASA Conference on Radiation and Health (Coolfont VI) continued the procedure established in 1981 of holding forenoon and evening sessions, leaving afternoons free for discussion and relaxation. One exception was made this year in that Michael and Marie Stoline were invited to discuss the Chernobyl Disaster on Monday afternoon. The program consisted of the following topics: a general overview of radiation and health problems; cytogenetics and radiation (human and animal studies and statistical analysis of dose-response curves); uranium and health effects, including continuing emphasis on radon, which has attracted considerable national interest lately; epidemiologic studies of workers at nuclear power plants and an uranium processing plant; the latest assessment of atomic bomb dosimetry. These Coolfont Conferences provide an excellent environment for an interchange of ideas and information in an assemblage of scientists from a variety of disciplines. Unfortunately there is one important factor which limits this interchange: language. In order to overcome the difficulty of statisticians understanding nuclear scientists and nuclear scientists understanding statisticians, I suggested one of two procedures: each group prepare a set of commonly used terms with definitions which would be understood by the other group(s); have an introductory session in which each group attempts to explain its language to the other group(s). This problem of communication is even more serious when scientists attempt to explain their research efforts to the general public. The Coolfont Conferences on Radiation and Health should be ideal forums for development of a language which could be understood by the general public as well as different scientific groups. This document contains the abstracts of 12 presented papers.

  7. ASA conference on radiation and health: Coolfont 7: Final report

    SciTech Connect

    Not Available

    1987-01-01

    These proceedings provide a summary of papers presented at the seventh annual ASA Conference on Radiation and Health, held at the Coolfont Conference Center in Berkeley Springs, West Virginia. More than forty scientists, including statisticians, epidemiologists, biologists, and physicists, participated in the conference. The 1987 conference focused on lung cancer risks, especially lung cancer risks due to radon. The BEIR IV report, which addresses health risks of radon and other internally deposited alpha-emitters, was summarized early in the conference. Results of analyses of data on miners in Colorado and in New Mexico were presented, as well as analyses of combined data from several studies, which were used as the basis of estimates in the BEIR IV report. Statistical issues related to appropriate analysis of chronic exposure and of smoking data received considerable attention and discussion. Papers describing models for lung cancer risks based on exposure to cigarette smoke, radiation, and other substances provided insights into general understanding of lung cancer mechanisms. Carcinogenic models were also the subject of a presentation on radiation-induced skin cancer in humans and animals. In addition, relevant data on animal experiments involving radon exposure were summarized. Understanding risks requires relating them to dose, and thus the presentation on dosimetry, both for miner populations and for residents of US homes, made an important contribution to the conference. Presentations on current efforts at the state and national level to assess radon levels in US homes were also of considerable interest to the participants. Individual papers were processed separately for the data base.

  8. Oral anticoagulant treatment with and without aspirin.

    PubMed

    Altman, R; Rouvier, J; Gurfinkel, E

    1995-07-01

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

  9. 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.

  10. Aspirin in the Chemoprevention of Colorectal Neoplasia: An Overview

    PubMed Central

    Chan, Andrew T.; Arber, Nadir; Burn, John; Chia, John Whay-Kuang; Elwood, Peter; Hull, Mark A.; Logan, Richard F.; Rothwell, Peter M.; Schrör, Karsten; Baron, John A.

    2011-01-01

    Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal cancer (CRC) in addition to its well-established benefits in the prevention of vascular disease. Epidemiologic studies have consistently observed an inverse association between aspirin use and risk of CRC. A recent pooled analysis of a long-term post-trial follow-up of nearly 14,000 patients from 4 randomized, cardiovascular disease prevention trials showed that daily aspirin treatment for about 5 years was associated with a 34% reduction in 20-year CRC mortality. A separate meta-analysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in 4 randomized adenoma prevention trials demonstrated that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%. Aspirin has also been shown to be beneficial in a clinical trial of patients with Lynch syndrome, a hereditary CRC syndrome; in those treated with aspirin for at least 2 years, there was a ≥ 50% reduction in the risk of CRC commencing 5 years after randomization and after aspirin had been discontinued. A few observational studies have shown an increase in survival among patients with CRC who use aspirin. Taken together, these findings strengthen the case for consideration of long-term aspirin use in CRC prevention. Despite these compelling data, there is a lack of consensus about the balance of risks and benefits associated with long-term aspirin use, particularly in low-risk populations. The optimal dose to use for cancer prevention and the precise mechanism underlying aspirin’s anticancer effect require further investigation. PMID:22084361

  11. 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…

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

    PubMed

    Tang, Yu; Singh, Jagdish

    2008-06-05

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

  13. 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.

  14. Amino Acid Metabolism Disorders

    MedlinePlus

    ... acidemia? In ASA, the body can’t remove ammonia or a substance called argininosuccinic acid from the ... and children include: Breathing problems High levels of ammonia in the bloodIntense headache, especially after a high- ...

  15. Associations of MDR1, TBXA2R, PLA2G7, and PEAR1 genetic polymorphisms with the platelet activity in Chinese ischemic stroke patients receiving aspirin therapy

    PubMed Central

    Peng, Ling-ling; Zhao, Yuan-qi; Zhou, Zi-yi; Jin, Jing; Zhao, Min; Chen, Xin-meng; Chen, Ling-yan; Cai, Ye-feng; Li, Jia-li; Huang, Min

    2016-01-01

    Aim: Aspirin resistance has an incidence of 5%–65% in patients with ischemic stroke, who receive the standard dose of aspirin, but the platelet function is inadequately inhibited, thereby leading to thrombotic events. Numerous evidence shows that thromboxane A2 receptor (TXA2 receptor, encoded by TBXA2R), lipoprotein-associated phospholipase A2 (Lp-PLA2, encoded by PLA2G7) and platelet endothelial aggregation receptor-1 (PEAR1, encoded by PEAR1) are crucial in regulating platelet activation, and P-glycoprotein (P-gp, encoded by MDR1) influences the absorption of aspirin in the intestine. In this study we examined the correlation between MDR1, TBXA2R, PLA2G7, PEAR1 genetic polymorphisms and platelet activity in Chinese ischemic stroke patients receiving aspirin therapy. Methods: A total of 283 ischemic stroke patients receiving 100 mg aspirin for 7 d were genotyped for polymorphisms in MDR1 C3435T, TBXA2R (rs1131882), PLA2G7 (rs1051931, rs7756935), and PEAR1 (rs12566888, rs12041331). The platelet aggregation response was measured using an automatic platelet aggregation analyzer and a commercially available TXB2 ELISA kit. Results: Thirty-three patients (11.66%) were insensitive to aspirin treatment. MDR1 3435TT genotype carriers, whose arachidonic acid (AA) or adenosine diphosphate (ADP)-induced platelet aggregation was lower than that of CC+CT genotype carriers, were less likely to suffer from aspirin resistance (odds ratio=0.421, 95% CI: 0.233–0.759). The TBXA2R rs1131882 CC genotype, which was found more frequently in the aspirin-insensitive group (81.8% vs 62.4%) than in the sensitive group, was identified as a risk factor for aspirin resistance (odds ratio=2.712, 95% CI: 1.080–6.810) with a higher level of AA-induced platelet aggregation. Due to the combined effects of PLA2G7 rs1051931 and rs7756935, carriers of the AA-CC haplotype had a higher level of ADP-induced platelet aggregation, and were at considerably higher risk of aspirin resistance than

  16. Biological properties of citral and its potential protective effects against cytotoxicity caused by aspirin in the IEC-6 cells.

    PubMed

    Bouzenna, Hafsia; Hfaiedh, Najla; Giroux-Metges, Marie-Agnès; Elfeki, Abdelfattah; Talarmin, Hélène

    2017-03-01

    Citral, 3,7-dimethyl-2,6-octadienal, is a key component of several essential oils extracted from lemon-scented herbal plants. The present study was designed to investigate the antioxidant activities of citral and assess its possible protective effects against aspirin-induced toxicity in vitro. We used IEC-6 cells (rat small intestine epithelial cells). The antioxidant activities were determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH), β-carotene/linoleic acid and Ferric reducing antioxidant power (FRAP). Cytotoxicity was evaluated by cell viability, anti-oxidant enzyme activities, malondialdehyde (MDA) production and by the expression of MAPKs (Mitogen-Activated Protein Kinases) pathways. According to results, citral showed an important antioxidant activity. It inhibited the oxidation of linoleic acid, a moderate DPPH was found and it showed a Ferric reducing antioxidant potential with an EC50 value of 125±28.86μg/mL. Then, the co-treatment of aspirin with citral significantly decreased the aspirin-induced cell death, and the MDA level. It modulated the superoxide dismutase (SOD) and glutathione (GSH) activities. Also, the activation of MAPKs was attenuated by citral. These findings suggest that citral can protect IEC-6 cells against aspirin-induced oxidative stress that may help to discover new chemicals out of natural antioxidant substances.

  17. [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.

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

    PubMed

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

    2013-01-01

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

  19. 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)

  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. 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.

  2. 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

  3. Synthesis of aspirin-loaded polymer-silica composites and their release characteristics.

    PubMed

    Kierys, Agnieszka

    2014-08-27

    This study describes a novel approach to the synthesis of polymer-drug-silica nanocomposites via encapsulation/isolation of drug molecules, introduced into the polymer matrix by the silica gel. For the first time, tetraethoxysilane (TEOS) gelation in the vapor phase of the acidic catalyst is presented as an efficient method to enter the silica gel nanoparticles into the polymer-aspirin conjugate. The conducted studies reveal that the internal structure of the polymer carrier is significantly reorganized after the embedding of aspirin molecules and the silica gel. The total porosity of the polymer-drug-silica nanocomposites and the molecular structure of the silica gel embedded in the system strongly depend on the conditions of the silica source transformation. Additionally, the release of the drug was fine-tuned by adapting the conditions of hydrolysis and condensation of the silica gel precursor. Finally, to prove the usefulness of the proposed synthesis, the controlled release of aspirin from the polymer-drug-silica nanocomposites is demonstrated.

  4. Antiplatelet therapies: aspirin at the heart of new directions.

    PubMed

    Bunimov, Natalia; Laneuville, Odette

    2013-12-01

    When introduced over 100 years ago, aspirin was prescribed as an analgesic drug to arthritic patients for pain relief. The prevalence of users grew quite rapidly and to this day, aspirin remains widely used in clinical practice. The popularity of aspirin resulted not only from its analgesic properties but also from a second benefit recognized later as an anti-platelet effect. It was this important activity of aspirin that made it one of the most recommended drugs for the treatment and prevention of cardiovascular diseases. The anti-platelet effect of aspirin emerged from the first few case reports published in the early 1900s and was described as a mild bleeding. The molecular mechanisms involved were described in 1971 and constituted the irreversible inhibition of cyclooxygenase-1 enzyme and prevention of platelet aggregation. Today, the contribution of aspirin to our understanding of cardiovascular health persists and remains considerable. Observations from large cohorts of aspirin users generate massive amount of valuable information used in the identification of factors influencing the potential risk for cardiovascular diseases, including sex, age and genetic predisposition. Aspirin and the path of discovery leading to its anti-platelet activity has taken a hundred years was based on manifestations of effects observed in its users, and it remains a successful strategy for the identification of new avenues to treat cardiovascular diseases associated with hyper-platelet activity. The contribution of aspirin to the understanding of cardiovascular diseases and to the design of effective treatment and prevention strategies, remains of high importance in our society.

  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. 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

  7. 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.

  8. 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

  9. Role of endogenous gastric mucosal prostaglandins in the formation of acute gastric mucosal lesions induced by aspirin, ethanol, HCl and CH3COOH.

    PubMed

    Amioka, I; Arima, T; Nagashima, H

    1987-06-01

    The role of endogenous mucosal prostaglandins (PGs) in the production of acute gastric mucosal lesions (AGML) was examined in rats. Aspirin, ethanol or 0.6 N-HCl was given intragastrically and 20% acetic acid was injected into the gastric wall. Endogenous gastric mucosal PG (A + B), PGE and PGF were determined by radioimmunoassay. Their gastric contents were markedly reduced by aspirin administration (p less than 0.001). The level of gastric mucosal PGs still remained low (p less than 0.001) after the aspirin-induced AGML began to heal. Furthermore, rats with AGML induced by ethanol, HCl or acetic acid, showed no decrease in endogenous gastric mucosal PGs compared with the controls. These findings indicated that endogenous PGs are not necessary for either the induction or healing of experimental AGML.

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

    PubMed

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

    2017-04-15

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

  11. 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.

  12. Defining functioning categories in axial Spondyloarthritis: the role of the ASAS Health Index.

    PubMed

    Di Carlo, Marco; Lato, Valentina; Di Matteo, Andrea; Carotti, Marina; Salaffi, Fausto

    2017-01-06

    The Assessment of SpondyloArthritis international Society Health Index (ASAS HI) is an inclusive questionnaire, able to describe the total impairments and restrictions due to axial spondyloarthritis (axSpA). Considering the relationship between ASAS HI and the Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP, the aim of this study is to establish the ASAS HI cut-off values for functioning categories employing the ASDAS-CRP disease activity states in axSpA patients. ASAS HI and ASDAS-CPR were obtained from 140 consecutive axSpA patients, divided in the four ASDAS-CRP disease activity categories. High and very high disease activity were considered together. The ASAS HI cut-offs were obtained from the arithmetic mean, rounded off to the closest whole number, of the 75th percentile mean value of a lower rank and the 25th percentile mean value of the adjacent higher rank. This approach was applied in the transition from inactive disease and moderate disease activity, and in the transition from moderate disease activity and high/very high disease activity. Twenty-three patients were classified as having inactive disease, 36 were classified as having moderate disease activity, and 81 were in a high/very high disease activity state. Using the approach of the 75th-25th percentile mean values of adjacent disease activity states, the ASAS HI cut-offs resulted: ≤4 to dinstinguish a normal functioning, >4 and ≤8 to distinguish a moderate impairment of functioning, and >8 to distinguish a severe impairment of functioning. ASAS HI seems a reliable tool to define functioning categories in patients with axSpA.

  13. Functional testing methods for the antiplatelet effects of aspirin.

    PubMed

    Schrör, Karsten; Huber, Kurt; Hohlfeld, Thomas

    2011-02-01

    At antiplatelet doses of 75-325 mg/day, aspirin irreversibly inhibits the platelet cyclooxygenase (COX)-1-dependent thromboxane A(2) (TXA(2)) formation. This is the pharmacological mode of action of aspirin, and it can be predicted that if aspirin does not inhibit COX-1 sufficiently, patients will not benefit from its antiplatelet effects. A pharmacodynamic failure of aspirin occurs in 1-2% of patients. The vast majority of atherothrombotic events in patients treated with aspirin result from mechanisms that are dependent on residual (non-COX-1-dependent) platelet reactivity. Global tests of platelet activation in vitro may identify patients with high residual platelet reactivity but are not sufficiently specific to test the pharmacological effect of aspirin. A further problem is the absence of standardized normal ranges for many assays and the fact that different equipment measures different signals, which are also influenced by the agonist and the anticoagulant used. Similar considerations apply for the determination of platelet-derived biomarkers such as circulating P-selectin, soluble CD40 ligand and others. The direct measurement of inhibition of thromboxane-forming capacity is the most specific pharmacological assay for aspirin. However, there is no linear correlation between inhibition of TXA(2) formation and inhibition of platelet function. Measurement of urinary levels of the TXB(2) metabolite, 11-dehydro-thromboxane B(2), represents an index of TXA(2) biosynthesis in vivo, but is also sensitive to other cellular sources of TXA(2). One general problem of all assays is the relationship with clinical outcome, which is still unclear. Monitoring aspirin treatment by testing platelet function or measuring biomarkers in clinical practice should not be recommended until a clear relationship for the predictive value of these assays for clinical outcome has been established.

  14. Effect of aspirin dosage and enteric coating on platelet reactivity.

    PubMed

    Feng, D; McKenna, C; Murillo, J; Mittleman, M A; Gebara, O C; Lipinska, I; Muller, J E; Tofler, G H

    1997-07-15

    Although aspirin is effective in the prevention and treatment of cardiovascular diseases, the optimal dose remains uncertain. The purpose of this study was to compare the platelet inhibitory and prostacyclin-sparing effects of 2 doses (81 and 325 mg) and forms (enteric-coated and regular) of aspirin. Since platelet reactivity has been reported to increase after strenuous exercise, a known trigger of myocardial infarction, subjects were studied following maximal treadmill exercise as well as at rest. Forty male healthy subjects were evaluated using a randomized, double-blind, parallel study design. Blood samples were obtained before and after maximal treadmill exercise at baseline and after 7 days on aspirin therapy. Both enteric and regular aspirin in 81- and 325-mg dosages markedly inhibited adenosine diphosphate and epinephrine-induced aggregation at rest and after exercise. Aspirin also inhibited the platelet response to collagen as assessed by a longer lag time to aggregation. The prolongation of lag time was greater for 325 mg than for 81 mg (100 +/- 7 vs 91 +/- 7; p = 0.04, after exercise). There were no significant dose-related differences in plasma 6-keto-prostaglandin F1alpha level; however, enteric-coated aspirin inhibited the exercise-induced increase in 6-keto-prostaglandin F1alpha to a lesser extent than regular aspirin. Although both doses (81 and 325 mg) and types (regular and enteric-coated) of aspirin inhibited adenosine diphosphate and epinephrine-induced aggregation equally, the 325-mg dose inhibited collagen-induced aggregation to a greater extent than 81 mg. The greater platelet inhibition observed with 325 mg may be clinically relevant in acute coronary syndromes characterized by plaque rupture with extensive collagen exposure and platelet activation.

  15. Diltiazem potentiates the inhibitory effect of aspirin on platelet aggregation.

    PubMed

    Altman, R; Scazziota, A; Dujovne, C

    1988-09-01

    Platelet aggregation in vivo occurs through the combined effects of many agonists. Aspirin inhibits platelet aggregation but its antiaggregate effects can be overcome by the synergistic action of sodium arachidonate (AA) plus platelet activating factor (PAF). We tested the effect of a calcium entry-blocking agent, diltiazem, on AA-PAF-induced platelet aggregation in platelet-rich plasma from seven healthy volunteers. The studies were done before and after aspirin (100 mg/day) administration for 7 to 10 days. Stimulation of platelet was done in vitro by AA, PAF, or both. Before aspirin treatment, diltiazem (2 micrograms/ml) added in vitro to the platelet-rich plasma inhibited platelet aggregation induced by AA (0.75 mmol/L) by 50%. When PAF was used the inhibition of aggregation was obtained at a lower concentration of diltiazem (0.4 to 1 microgram/ml). After aspirin treatment, AA-induced aggregation was inhibited, and PAF alone (30 nmol/L) produced a first-wave aggregation followed by complete disaggregation. When AA and PAF were added together a full aggregation of postaspirin treatment platelets was obtained. Diltiazem added in vitro at the clinically attainable concentration of 0.1 microgram/ml produced a complete inhibition of this AA-PAF synergism on platelet aggregation. These results suggest that administration of a combination of low-dose aspirin and diltiazem may be of greater benefit than aspirin alone for prophylaxis of cardiovascular diseases where platelets are involved in the pathogenesis.

  16. Mechanistic and Pharmacological Issues of Aspirin as an Anticancer Agent

    PubMed Central

    Dovizio, Melania; Tacconelli, Stefania; Sostres, Carlos; Ricciotti, Emanuela; Patrignani, Paola

    2012-01-01

    Recent findings have shown that aspirin, taken for several years, reduces the long-term risk of some cancers, particularly colorectal cancer. The result that aspirin benefit is detectable at daily low-doses (at least 75mg), the same used for the prevention of cardiovascular disease, positions the antiplatelet action of aspirin at the center of its antitumor efficacy. At low-doses given every 24 h, aspirin is acting by a complete and persistent inhibition of cyclooxygenase (COX)-1 in platelets (in the 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 (approximately 20 min); nucleated cells have the ability to resynthesize the acetylated COX-isozymes within a few hours, while platelets do not. COX-independent mechanisms of aspirin, such as the inhibition of Wnt/ β-catenin and NF-kB signaling and the acetylation of extra-COX proteins, have been suggested to play a role in its chemo-preventive effects, but their relevance remains to be demonstrated in vivo at clinical doses. In conclusion, the results of clinical pharmacology and the analysis of randomized and epidemiological studies suggest that colorectal cancer and atherothrombosis share a common mechanism of disease, i.e. enhanced platelet activation in response to injury at distinct sites. PMID:24281340

  17. 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

  18. 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.

  19. Cooperative antiproliferative signaling by aspirin and indole-3-carbinol targets microphthalmia-associated transcription factor gene expression and promoter activity in human melanoma cells.

    PubMed

    Poindexter, Kevin M; Matthew, Susanne; Aronchik, Ida; Firestone, Gary L

    2016-04-01

    Antiproliferative signaling of combinations of the nonsteroidal anti-inflammatory drug acetylsalicylic acid (aspirin) and indole-3-carbinol (I3C), a natural indolecarbinol compound derived from cruciferous vegetables, was investigated in human melanoma cells. Melanoma cell lines with distinct mutational profiles were sensitive to different extents to the antiproliferative response of aspirin, with oncogenic BRAF-expressing G361 cells and wild-type BRAF-expressing SK-MEL-30 cells being the most responsive. I3C triggered a strong proliferative arrest of G361 melanoma cells and caused only a modest decrease in the proliferation of SK-MEL-30 cells. In both cell lines, combinations of aspirin and I3C cooperatively arrested cell proliferation and induced a G1 cell cycle arrest, and nearly ablated protein and transcript levels of the melanocyte master regulator microphthalmia-associated transcription factor isoform M (MITF-M). In melanoma cells transfected with a -333/+120-bp MITF-M promoter-luciferase reporter plasmid, treatment with aspirin and I3C cooperatively disrupted MITF-M promoter activity, which accounted for the loss of MITF-M gene products. Mutational analysis revealed that the aspirin required the LEF1 binding site, whereas I3C required the BRN2 binding site to mediate their combined and individual effects on MITF-M promoter activity. Consistent with LEF1 being a downstream effector of Wnt signaling, aspirin, but not I3C, downregulated protein levels of the Wnt co-receptor LDL receptor-related protein-6 and β-catenin and upregulated the β-catenin destruction complex component Axin. Taken together, our results demonstrate that aspirin-regulated Wnt signaling and I3C-targeted signaling pathways converge at distinct DNA elements in the MITF-M promoter to cooperatively disrupt MITF-M expression and melanoma cell proliferation.

  20. Assessment of Water Quality in Asa River (Nigeria) and Its Indigenous Clarias gariepinus Fish

    PubMed Central

    Kolawole, Olatunji M.; Ajayi, Kolawole T.; Olayemi, Albert B.; Okoh, Anthony I.

    2011-01-01

    Water is a valued natural resource for the existence of all living organisms. Management of the quality of this precious resource is, therefore, of special importance. In this study river water samples were collected and analysed for physicochemical and bacteriological evaluation of pollution in the Unity Road stream segment of Asa River in Ilorin, Nigeria. Juvenile samples of Clarias gariepinus fish were also collected from the experimental Asa River and from the control Asa Dam water and were analysed for comparative histological investigations and bacterial density in the liver and intestine in order to evaluate the impact of pollution on the aquatic biota. The water pH was found to range from 6.32 to 6.43 with a mean temperature range of 24.3 to 25.8 °C. Other physicochemical parameters monitored including total suspended solids, total dissolved solids, biochemical oxygen demand and chemical oxygen demand values exceeded the recommended level for surface water quality. Results of bacteriological analyses including total heterotrophic count, total coliform and thermotolerant coliform counts revealed a high level of faecal pollution of the river. Histological investigations revealed no significant alterations in tissue structure, but a notable comparative distinction of higher bacterial density in the intestine and liver tissues of Clarias gariepinus from Asa River than in those collected from the control. It was inferred that the downstream Asa River is polluted and its aquatic biota is bacteriologically contaminated and unsafe for human and animal consumption. PMID:22163210

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

    NASA Astrophysics Data System (ADS)

    Pigulski, A.

    2005-06-01

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

  2. Assessment of water quality in Asa River (Nigeria) and its indigenous Clarias gariepinus fish.

    PubMed

    Kolawole, Olatunji M; Ajayi, Kolawole T; Olayemi, Albert B; Okoh, Anthony I

    2011-11-01

    Water is a valued natural resource for the existence of all living organisms. Management of the quality of this precious resource is, therefore, of special importance. In this study river water samples were collected and analysed for physicochemical and bacteriological evaluation of pollution in the Unity Road stream segment of Asa River in Ilorin, Nigeria. Juvenile samples of Clarias gariepinus fish were also collected from the experimental Asa River and from the control Asa Dam water and were analysed for comparative histological investigations and bacterial density in the liver and intestine in order to evaluate the impact of pollution on the aquatic biota. The water pH was found to range from 6.32 to 6.43 with a mean temperature range of 24.3 to 25.8 °C. Other physicochemical parameters monitored including total suspended solids, total dissolved solids, biochemical oxygen demand and chemical oxygen demand values exceeded the recommended level for surface water quality. Results of bacteriological analyses including total heterotrophic count, total coliform and thermotolerant coliform counts revealed a high level of faecal pollution of the river. Histological investigations revealed no significant alterations in tissue structure, but a notable comparative distinction of higher bacterial density in the intestine and liver tissues of Clarias gariepinus from Asa River than in those collected from the control. It was inferred that the downstream Asa River is polluted and its aquatic biota is bacteriologically contaminated and unsafe for human and animal consumption.

  3. 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 ...

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

    PubMed

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

    2016-04-01

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

  5. Does enteric-coated aspirin result in a lower incidence of gastrointestinal complications compared to normal aspirin?

    PubMed

    Walker, Jay; Robinson, James; Stewart, Jamie; Jacob, Samuel

    2007-08-01

    A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether enteric-coated aspirin results in a lower incidence of gastrointestinal complications compared to normal aspirin in CABG surgery. Using the reported search, 340 papers were identified. Nine papers represented the best evidence on the subject. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, weaknesses, results and study comments were tabulated. Five randomised controlled trials of healthy volunteers undergoing endoscopy after a period of either enteric-coated aspirin or plain aspirin administration all demonstrated a clear reduction of gastric mucosal injury. However, these trials on healthy volunteers taking short-term aspirin have not been supported by clinical studies in older age-group adults taking lower doses of aspirin for long periods. No clinical benefits in terms of reduction of gastrointestinal bleeding or ulceration with enteric coating have, therefore, been successfully demonstrated, although the endoscopic studies show that potentially these benefits could exist.

  6. 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

  7. 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.

  8. Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder.

    PubMed

    Gris, Jean-Christophe; Mercier, Eric; Quéré, Isabelle; Lavigne-Lissalde, Géraldine; Cochery-Nouvellon, Eva; Hoffet, Médéric; Ripart-Neveu, Sylvie; Tailland, Marie-Laure; Dauzat, Michel; Marès, Pierre

    2004-05-15

    The prospective evaluation of the effect of thromboprophylaxis in women with one unexplained pregnancy loss from the 10th week of amenorrhea was performed. A total of 160 patients with heterozygous factor V Leiden mutation, prothrombin G20210A mutation, or protein S deficiency were given 5 mg folic acid daily before conception, to be continued during pregnancy, and low-dose aspirin 100 mg daily or low-molecular-weight heparin enoxaparin 40 mg was taken from the 8th week. Twenty-three of the 80 patients treated with low-dose aspirin and 69 of the 80 patients treated with enoxaparin had a healthy live birth (odds ratio [OR], 15.5; 95% confidence interval [CI], 7-34, P <.0001). Enoxaparin was superior to low-dose aspirin in each subgroup defined according to the underlying constitutional thrombophilic disorder. An associated protein Z deficiency and/or positive antiprotein Z antibodies were associated with poorer outcomes. The neonate weight was higher in the women successfully treated with enoxaparin, and neonates small for gestational age were more frequent in patients treated with low-dose aspirin. No significant side effects of the treatments could be evidenced in patients or newborns. As there is no argument to prove that low-dose aspirin may have been deleterious, these results support enoxaparin use during such at-risk pregnancies.

  9. Double blind controlled study on the effect of sucralfate on gastric prostaglandin formation and microbleeding in normal and aspirin treated man.

    PubMed Central

    Konturek, S J; Kwiecień, N; Obtułowicz, W; Kopp, B; Oleksy, J

    1986-01-01

    Two groups A and B each comprising 12 healthy young male subjects were used in a double blind, placebo controlled trial to assess the effects of 1.0 g sucralfate qid on prostaglandin (PG) generation and mucosal integrity in the intact and aspirin-treated stomach. Mucosal formation and luminal release of PGE2, 6-keto-PGE1 alpha and thromboxane B2, gastric microbleeding and DNA loss (integrity indicators) and basal and pentagastrin induced acid secretion were measured after placebo and sucralfate treatment in subjects without (group A) and with administration of 2.5 g aspirin (group B). Sucralfate significantly reduced spontaneous gastric microbleeding and DNA loss in group A and prevented blood loss but not DNA loss caused by aspirin in group B. The protective effects of sucralfate on spontaneous gastric microbleeding were accompanied by increased mucosal biosynthesis and luminal release of PGE2 and 6-keto-PGF1 alpha with a reduction in release of thromboxane B2. In aspirin treated subjects both mucosal generation and luminal release of prostaglandins and thromboxane B2 were greatly suppressed although sucralfate treatment did not influence these prostaglandins in spite of the reduction in mucosal damage. It is concluded that sucralfate has a potent protective action on spontaneous and aspirin treated gastric microbleeding in man and that this protection may be partly because of the increased mucosal biosynthesis of prostaglandins. PMID:3492413

  10. Effects of ticlopidine or ticlopidine plus aspirin on platelet aggregation and ATP release in normal volunteers: why aspirin improves ticlopidine antiplatelet activity.

    PubMed

    Altman, R; Scazziota, A; Rouvier, J; Gonzalez, C

    1999-10-01

    Aspirin and ticlopidine are used to prevent arterial thrombosis. In some clinical settings ticlopidine is administered with aspirin for improving antithrombotic effect. We administered aspirin (100 mg/day), ticlopidine (500 mg/day), or ticlopidine and aspirin for 7 days to healthy volunteers. Platelet aggregation and ATP release induced by sodium arachidonate, ADP, or a combination of both were measured. Sodium arachidonate (0.25 mmol/L), which produces no platelet aggregation, combined with adenosine diphosphate (1 mumol/L), which produced a reversible platelet aggregation of 20% after ticlopidine, resulted in a synergistic platelet aggregation response in normal (74.6 +/- 9.2%) and in ticlopidine platelet-rich plasma (59.1% +/- 14.9%, p < 0.0001). Synergism after sodium arachidonate (0.75 mmol/L) plus adenosine diphosphate (4 mumol/L) fell from 75.8% +/- 11.0% and 59.1% +/- 15.6% after ticlopidine or aspirin, respectively, to 14.8% +/- 18.0% (p < 0.0001) after ticlopidine plus aspirin. Aspirin and ticlopidine alone did not inhibit adenosine triphosphate release as thoroughly as did aspirin plus ticlopidine. Aspirin or ticlopidine does not adequately prevent platelet activity as ticlopidine plus aspirin do. Addition of aspirin to treatment with ticlopidine improves their antiplatelet activity and better results could be obtained in arterial thrombotic prevention strategies.

  11. Stereocontrolled Total Synthesis of the Potent Anti-inflammatory and Pro-resolving Lipid Mediator Resolvin D3 and its Aspirin-Triggered 17R-Epimer

    PubMed Central

    Winkler, Jeremy W.; Uddin, Jasim; Serhan, Charles N.

    2013-01-01

    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

  12. 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

  13. 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.

  14. Aspirin induces cell death by directly modulating mitochondrial voltage-dependent anion channel (VDAC)

    PubMed Central

    Tewari, Debanjan; Majumdar, Dhriti; Vallabhaneni, Sirisha; Bera, Amal Kanti

    2017-01-01

    Aspirin induces apoptotic cell death in various cancer cell lines. Here we showed that silencing of VDAC1 protected HeLa cells from aspirin-induced cell death. Compared to the wild type cells, VDAC1 knocked down cells showed lesser change of mitochondrial membrane potential (Δψm), upon aspirin treatment. Aspirin augmented ATP and ionomycin-induced mitochondrial Ca2+ uptake which was abolished in VDAC1 knocked down cells. Aspirin dissociated bound hexokinase II (HK-II) from mitochondria. Further, aspirin promoted the closure of recombinant human VDAC1, reconstituted in planar lipid bilayer. Taken together, these results imply that VDAC1 serves as a novel target for aspirin. Modulation of VDAC1 is possibly associated with the cell death and anticancer effects of aspirin. PMID:28327594

  15. 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 ...

  16. Aspirin can stimulate luminol-enhanced chemiluminescence of activated platelets.

    PubMed

    Gabbasov, Zufar; Ivanova, Oksana; Kogan-Yasny, Victor; Vasilieva, Elena

    2010-01-01

    A preliminary investigation was conducted into the influence of aspirin on the luminol-enhanced chemiluminescence of platelets stimulated with platelet-activating factor (PAF). Ten coronary artery disease patients and six volunteers without coronary artery disease were included in the study. All the patients received aspirin (daily dose, 100 mg) for at least 10 days before in vitro experiments. Luminol-enhanced luminescence of platelet-rich plasma samples mixed with a PAF solution was measured. After stimulation of platelets with PAF, we did not find a luminol-enhanced chemiluminescent response either in the non-coronary artery disease volunteers or in eight out of the 10 coronary artery disease patients examined. However, in samples from two patients where platelets were stimulated with PAF reactive oxygen species were formed. This ability was expressed as an intensive luminol-enhanced luminescence of activated platelets. Such a reaction was observed against the background of the administration of aspirin. The addition of aspirin to a test tube considerably enhanced the intensity of chemiluminescence. In one case, the cancellation of aspirin was accompanied by diminution of the intensity of luminol-enhanced chemiluminescence of platelets. The clinical significance of this phenomenon is unknown.

  17. 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.

  18. The effect of concurrent aspirin upon plasma concentrations of tenoxicam.

    PubMed Central

    Day, R O; Paull, P D; Lam, S; Swanson, B R; Williams, K M; Wade, D N

    1988-01-01

    1. The effect of chronic, high-dose aspirin therapy upon the disposition of a single dose and multiple doses of tenoxicam was examined in normal volunteers. 2. Aspirin caused a 24% drop in the t1/2 (P less than 0.005), a 49% rise in the volume of distribution (P less than 0.0003) and a 98% increase in the clearance (P less than 0.0001) of tenoxicam after a single dose of the tenoxicam. 3. Steady-state concentrations of tenoxicam decreased significantly from 10.4 +/- 1.5 to 4.5 +/- 1.6 micrograms ml-1 in the presence of chronic, high-dose aspirin treatment. 4. Tenoxicam percentage free measured in plasma from a normal volunteer was 0.56 +/- 0.05% over the tenoxicam concentration range 1-20 micrograms ml-1 and rose to 1.24 +/- 0.07% in the presence of aspirin 150 micrograms ml-1. 5. The effect of aspirin upon the disposition of tenoxicam was consistent with a competitive protein binding interaction. PMID:3190995

  19. Non-compliance is the predominant cause of aspirin resistance in chronic coronary arterial disease patients

    PubMed Central

    Schwartz, Kenneth A; Schwartz, Dianne E; Barber, Kimberly; Reeves, Mathew; De Franco, Anthony C

    2008-01-01

    Background Our previous publication showed that 9% of patients with a history of myocardial infarction MI. could be labeled as aspirin resistant; all of these patients were aspirin resistant because of non-compliance. This report compares the relative frequency of aspirin resistance between known compliant and non-compliance subjects to demonstrate that non-compliance is the predominant cause of aspirin resistance. Methods The difference in the slopes of the platelet prostaglandin agonist (PPA) light aggregation curves off aspirin and 2 hours after observed aspirin ingestion was defined as net aspirin inhibition. Results After supposedly refraining from aspirin for 7 days, 46 subjects were judged non-compliant with the protocol. Of the remaining 184 compliant subjects 39 were normals and 145 had a past history of MI. In known compliant subjects there was no difference in net aspirin inhibition between normal and MI subjects. Net aspirin inhibition in known compliant patients was statistically normally distributed. Only 3% of compliant subjects (2 normals and 5 MI) had a net aspirin inhibitory response of less than one standard deviation which could qualify as a conservative designation of aspirin resistance. A maximum of 35% of the 191 post MI subjects could be classified as aspirin resistant and/or non-compliant: 9% aspirin resistant because of non-compliance, 23% non-compliant with the protocol and possibly 3% because of a decreased net aspirin inhibitory response in known compliant patients. Conclusion Our data supports the thesis that the predominant cause of aspirin resistance is noncompliance. PMID:18759978

  20. 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…

  1. 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.

  2. Drei neue gamma-Doradus-Sterne aus der ASAS-3 Datenbank

    NASA Astrophysics Data System (ADS)

    Bernhard, Klaus; Huemmerich, Stefan

    2016-02-01

    By analysis of data from the ASAS-3 archive, the stars HD 18011, NSV 16873 and NSV 3272 were identified as multiperiodic gamma Doradus variables. Essential information on these variables is presented, along with unwhitened frequency spectra and statistically significant frequencies, as derived with Period 04.

  3. The ASAS Criteria for Axial Spondyloarthritis: Strengths, Weaknesses, and Proposals for a Way Forward.

    PubMed

    van der Linden, Sjef; Akkoc, Nurullah; Brown, Matthew A; Robinson, Philip C; Khan, Muhammad A

    2015-09-01

    Classification criteria should facilitate selection of similar patients for clinical and epidemiologic studies, therapeutic trials, and research on etiopathogenesis to enable comparison of results across studies from different centers. We critically appraise the validity and performance of the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (axSpA). It is still debatable whether all patients fulfilling these criteria should be considered as having true axSpA. Patients with radiographically evident disease by the ASAS criteria are not necessarily identical with ankylosing spondylitis (AS) as classified by the modified New York criteria. The complex multi-arm selection design of the ASAS criteria induces considerable heterogeneity among patients so classified, and applying them in settings with a low prevalence of axial spondyloarthritis (SpA) greatly increases the proportion of subjects falsely classified as suffering from axial SpA. One of the unmet needs in non-radiographic form of axial SpA is to have reliable markers that can identify individuals at risk for progression to AS and thereby facilitate early intervention trials designed to prevent such progression. We suggest needed improvements of the ASAS criteria for axSpA, as all criteria sets should be regarded as dynamic concepts open to modifications or updates as our knowledge advances.

  4. 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…

  5. 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.

  6. 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.

  7. 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.

  8. Aspirin insensitive thrombophilia: transcript profiling of blood identifies platelet abnormalities and HLA restriction.

    PubMed

    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

    2013-05-15

    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.

  9. 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.

  10. Association analysis of FABP1 gene polymorphisms with aspirin-exacerbated respiratory disease in asthma.

    PubMed

    Chang, Hun Soo; Park, Jong Sook; Shin, Hye-Rim; Park, Byung Lae; Shin, Hyoung Doo; Park, Choon-Sik

    2014-12-01

    Previously, we used a proteomic approach to demonstrate that the protein level of fatty acid-binding protein 1 (FABP1) is increased in nasal polyps in patients with aspirin-exacerbated respiratory disease (AERD). To reveal the genetic effect of FABP1 variants, we evaluated the association of FABP1 polymorphisms with the risk of AERD in 207 asthmatics with AERD and 1019 aspirin-tolerant asthmatics (ATA). Seven polymorphisms of FABP1 were selected from the National Center for Biotechnology Information (build 36) using minor allele frequency and linkage disequilibrium criteria. The genotype and haplotype distributions were not significantly different between the AERD and ATA groups in all of the genetic models. The percent decline of forced expiratory volume in 1 second (FEV1) after the oral aspirin challenge (OAC) test did not differ according to single-nucleotide polymorphism (SNP) genotypes. In haplotype analysis, asthmatic patients who were BL2ht2 homozygotes showed a greater decline in FEV1 after the OAC test than subjects who possessed 1 or no copy of BL2ht2 (P = 0.035). However, these observations were not significant after correction for multiple comparisons (corrected P value = 1.00). Neither genotype nor haplotype was associated with the presence of nasal polyposis in the study subjects. Although we did not find a significant association between the FABP1 polymorphisms and AERD, our data suggest that the 7 SNPs are not associated with the increased expression of FABP1 in asthmatic patients with AERD. Further studies of epigenetic factors that may contribute to the increased expression of FABP1 in AERD should be performed.

  11. 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.

  12. l-Ascorbic Acid Is Accumulated in Source Leaf Phloem and Transported to Sink Tissues in Plants1

    PubMed Central

    Franceschi, Vincent R.; Tarlyn, Nathan M.

    2002-01-01

    l-Ascorbic acid (AsA) was found to be loaded into phloem of source leaves and transported to sink tissues. When l-[14C]AsA was applied to leaves of intact plants of three different species, autoradiographs and HPLC analysis demonstrated that AsA was accumulated into phloem and transported to root tips, shoots, and floral organs, but not to mature leaves. AsA was also directly detected in Arabidopsis sieve tube sap collected from an English green aphid (Sitobion avenae) stylet. Feeding a single leaf of intact Arabidopsis or Medicago sativa with 10 or 20 mm l-galactono-1,4-lactone (GAL-l), the immediate precursor of AsA, lead to a 7- to 8-fold increase in AsA in the treated leaf and a 2- to 3-fold increase of AsA in untreated sink tissues of the same plant. The amount of AsA produced in treated leaves and accumulated in sink tissues was proportional to the amount of GAL-l applied. Studies of the ability of organs to produce AsA from GAL-l showed mature leaves have a 3- to 10-fold higher biosynthetic capacity and much lower AsA turnover rate than sink tissues. The results indicate AsA transporters reside in the phloem, and that AsA translocation is likely required to meet AsA demands of rapidly growing non-photosynthetic tissues. This study also demonstrates that source leaf AsA biosynthesis is limited by substrate availability rather than biosynthetic capacity, and sink AsA levels may be limited to some extent by source production. Phloem translocation of AsA may be one factor regulating sink development because AsA is critical to cell division/growth. PMID:12376632

  13. [Enteric-coated aspirin does not reduce the risk of gastrointestinal side effects].

    PubMed

    Haastrup, Peter; Jarbøl, Dorte Ejg

    2014-04-28

    Enteric-coated aspirin has been developed in order to decrease the risk of gastrointestinal side effects. When reviewing the existing literature on the effects of the coating on the incidence of gastrointestinal side effects we find that enteric-coated aspirin causes significantly less minor gastrointestinal lesions compared to plain aspirin evaluated by endoscopy after short-term treatment, but there seems to be no effect of enteric-coating on the incidence of dyspepsia or gastrointestinal bleeding of clinical relevance. In conclusion enteric-coated aspirin is not superior to plain aspirin.

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

    PubMed

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

    2015-07-26

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

  15. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

    The cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs) may be influenced by interactions with antiplatelet doses of aspirin. We sought to quantitate precisely the propensity of commonly consumed NSAIDs—ibuprofen, naproxen, and celecoxib—to cause a drug–drug interaction with aspirin in vivo by measuring the target engagement of aspirin directly by MS. We developed a novel assay of cyclooxygenase-1 (COX-1) acetylation in platelets isolated from volunteers who were administered aspirin and used conventional and microfluidic assays to evaluate platelet function. Although ibuprofen, naproxen, and celecoxib all had the potential to compete with the access of aspirin to the substrate binding channel of COX-1 in vitro, exposure of volunteers to a single therapeutic dose of each NSAID followed by 325 mg aspirin revealed a potent drug–drug interaction between ibuprofen and aspirin and between naproxen and aspirin but not between celecoxib and aspirin. The imprecision of estimates of aspirin consumption and the differential impact on the ability of aspirin to inactivate platelet COX-1 will confound head-to-head comparisons of distinct NSAIDs in ongoing clinical studies designed to measure their cardiovascular risk. PMID:25385584

  18. Aspirin acetylates wild type and mutant p53 in colon cancer cells: identification of aspirin acetylated sites on recombinant p53.

    PubMed

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

    2016-05-01

    Aspirin's ability to inhibit cell proliferation and induce apoptosis in cancer cell lines is considered to be an important mechanism for its anti-cancer effects. We previously demonstrated that aspirin acetylated the tumor suppressor protein p53 at lysine 382 in MDA-MB-231 human breast cancer cells. Here, we extended these observations to human colon cancer cells, HCT 116 harboring wild type p53, and HT-29 containing mutant p53. We demonstrate that aspirin induced acetylation of p53 in both cell lines in a concentration-dependent manner. Aspirin-acetylated p53 was localized to the nucleus. In both cell lines, aspirin induced p21(CIP1). Aspirin also acetylated recombinant p53 (rp53) in vitro suggesting that it occurs through a non-enzymatic chemical reaction. Mass spectrometry analysis and immunoblotting identified 10 acetylated lysines on rp53, and molecular modeling showed that all lysines targeted by aspirin are surface exposed. Five of these lysines are localized to the DNA-binding domain, four to the nuclear localization signal domain, and one to the C-terminal regulatory domain. Our results suggest that aspirin's anti-cancer effect may involve acetylation and activation of wild type and mutant p53 and induction of target gene expression. This is the first report attempting to characterize p53 acetylation sites targeted by aspirin.

  19. 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.

  20. Aspirin and clopidogrel response variability: review of the published literature.

    PubMed

    Ferguson, Angela D; Dokainish, Hisham; Lakkis, Nasser

    2008-01-01

    Antiplatelet resistance has been proposed as a possible mechanism to explain recurrent cardiovascular events in patients who have coronary artery disease and who are undergoing dual antiplatelet therapy. A comprehensive search on PubMed was conducted for literature that was printed in the English language between January 1996 and November 2007 on aspirin and clopidogrel resistance. Significant traits for aspirin hyporesponsiveness were female sex, older age, and lower levels of hemoglobin. Diabetes mellitus and elevated body mass index showed trends toward a higher incidence of resistance in some aspirin trials but did not reach statistical significance. Clopidogrel studies suggested that patients with type-2 diabetes mellitus are more likely to manifest inadequate response to the medication. Although 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors were initially suspected to decrease response to clopidogrel, later studies refuted this possibility. Patients with a suboptimal response to aspirin or clopidogrel seem to be at increased risk of recurrent cardiovascular events. Large clinical trials with standardized laboratory methods and well-defined protocols are needed to determine whether common features exist in patients with suspected hyporesponsiveness to antiplatelet therapy, and to validate the clinical relevance of response variability. A concise nonarbitrary definition of physiologic "resistance" is needed, and investigators should identify patients as having a variable response to antiplatelet therapy.

  1. 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.

  2. 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.

  3. Effects of a fish oil enriched diet on aspirin intolerant asthmatic patients: a pilot study.

    PubMed

    Picado, C; Castillo, J A; Schinca, N; Pujades, M; Ordinas, A; Coronas, A; Agusti-Vidal, A

    1988-02-01

    The effect of a fish oil enriched diet containing about 3 g of eicosapentaenoic acid was studied in 10 patients with aspirin intolerant asthma. Subjects were studied during six weeks on a control diet followed by six weeks on the fish oil diet in a single blind study design. They were asked to record their peak expiratory flow (PEF) twice daily, bronchodilator and steroid doses, and subjective ratings of pulmonary symptoms on diary cards. There were no significant changes in symptom scores over the six weeks of either the control diet or the fish oil diet. PEF values, however, were significantly lower during the fifth and sixth week of the fish oil diet than during the control diet (308 v 262 l/min week 5 and 306 v 256 l/min week 6). Bronchodilator usage was also greater during the fifth and sixth week of the fish oil diet than during the control period (12.0 v 7.4 and 13.0 v 7.4 puffs a day in weeks 5 and 6). This pilot study suggests that fish diets may have a deleterious effect on patients with aspirin intolerant asthma.

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

    PubMed

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

    2015-01-01

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

  5. 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.

  6. THE CRYSTAL STRUCTURE OF ASPIRIN ACETYLATED HUMAN CYCLOOXYGENASE-2: INSIGHT INTO THE FORMATION OF PRODUCTS WITH REVERSED STEREOCHEMISTRY

    PubMed Central

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

    2016-01-01

    Aspirin and other nonsterroidal 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 mono-oxygenated product 15(R)-hydroxyeicosatetraenoic acid (15R-HETE). Ser-530 has also been shown to influence the stereochemistry for oxygen addition into 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 1.9Å, 2.0Å, and 2.4Å, 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. Based on 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. PMID:26859324

  7. Combined aspirin and anticoagulant therapy in patients with atrial fibrillation.

    PubMed

    So, Charlotte H; Eckman, Mark H

    2017-01-01

    The combined use of aspirin and oral anticoagulant therapy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) has been questioned due to an increased risk of major bleeding with little to no benefit in preventing ischemic events. (1) To better understand patterns and indications for combined antiplatelet and anticoagulant therapy and identify patients who might reasonably be treated with oral anticoagulant (OAC) therapy alone. (2) To perform an updated literature review regarding the use of combined antiplatelet and OAC therapy in patients with AF and stable CAD. Retrospective review. Patients within the University of Cincinnati Health System with a diagnosis of non-valvular AF, excluding those with acute coronary syndrome or revascularization within the last 12 months. Numbers and indications for combined antiplatelet and anticoagulant therapy and sequence of events leading to the initiation of each. Of 948 patients receiving OAC, 430 (45 %) were receiving concomitant OAC and aspirin. Among patients receiving combined antiplatelet and anticoagulant therapy, 49 and 42 % of patients respectively, had CAD or DM. In a more detailed analysis including chart review of 219 patients receiving combined OAC and aspirin, 27 % had a diagnosis of CAD and 14 % had a diagnosis of DM prior to the development of AF. These patients were initially treated with aspirin. Warfarin was added when they subsequently developed AF but aspirin wasn't discontinued. A surprisingly large proportion of patients (22.8 %) had no obvious indication for dual therapy. Prior myocardial infarction, CAD, vascular disease and DM (among others) increase the likelihood of receiving combined antiplatelet and anticoagulant therapy among patients with AF. A literature review suggests this may lead to increased major bleeding with little benefit in decreasing either AF-related stroke or cardiovascular events.

  8. 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.

  9. Nutritional risk screening 2002 and ASA score predict mortality after elective liver resection for malignancy

    PubMed Central

    Ferreira, Nelio

    2017-01-01

    Introduction The aim of the study was to evaluate whether Nutritional risk screening 2002 (NRS 2002) at hospital admission may predict postoperative mortality and complications within 90 days after elective liver resection for malignancy. Material and methods A retrospective cohort study of a prospective database was performed. Two-hundred and three patients with elective liver resection for malignancy between 9 November 2007 and 27 May 2014 were included. Clinical data, NRS 2002, surgical procedures and histology were recorded. The primary endpoint was 90-day mortality. Complications were registered within 90 days postoperatively according to the Clavien-Dindo classification. Results The 90-day mortality was 5.9% and the overall complication rate was 59.1%. Multivariate analysis identified NRS 2002 score ≥ 4 (odds ratio (OR) = 9.24; p = 0.005) and American Society of Anesthesiologists (ASA) score ≥ 3 (OR = 6.20; p = 0.009) as predictors of 90-day mortality. The 90-day mortality was 27.6% (8/29) for patients with both risk factors (NRS 2002 score ≥ 4 and ASA score ≥ 3) vs. 2.3% (4/174) for patients without or with only one risk factor (p < 0.001). Conclusions In the present study NRS 2002 score ≥ 4 and ASA score ≥ 3 were predictors of 90-day mortality after elective liver resection for malignancy. PMID:28261289

  10. Identification of ASAS Ellipsoidal Variables Misclassified as Miscellaneous in VSX (Poster abstract)

    NASA Astrophysics Data System (ADS)

    Larsen, K.; Hoover, C.

    2016-12-01

    (Abstract only) Over 25,000 variable stars found in VSX were classified as miscellaneous by the automated analysis program for ASAS (All Sky Automated Survey) light curve data. As has been demonstrated by other authors, many of these stars can be classified as one of a number of standard variable classes through human analysis. Among the types of variable stars mislabeled as miscellaneous are ellipsoidal variable stars (ELL's). These are close binary systems in which the stars do not eclipse; the changes in brightness are due to the nonspherical shape of the stars. This project identified and then analyzed ELL candidates in the spreadsheet of ASAS "miscellaneous stars," specifically concentrating on early spectral class variables with periods of less than 15 days. ASAS data of the candidates was analyzed using vstar in order to generate phase plots and determine periods. The goal of this project has been to identify ELL's from this sample in order to update the VSX (Variable Star Index). This poster will describe the process used to identify and analyze 540 candidates as well as preliminary results.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. Development and Validation of a Reversed-phase HPLC Method for Simultaneous Determination of Aspirin, Atorvastatin Calcium and Clopidogrel Bisulphate in Capsules.

    PubMed

    Londhe, S V; Deshmukh, R S; Mulgund, S V; Jain, K S

    2011-01-01

    A simple, accurate, rapid and precise isocratic reversed-phase high-performance liquid chromatographic method has been developed and validated for simultaneous determination of aspirin, atorvastatin calcium and clopidogrel bisulphate in capsules. The chromatographic separation was carried out on an Inertsil ODS analytical column (150×4.6 mm; 5 μm) with a mixture of acetonitrile:phosphate buffer pH 3.0 adjusted with o-phosphoric acid (50:50, v/v) as mobile phase; at a flow rate of 1.2 ml/min. UV detection was performed at 235 nm. The retention times were 1.89, 6.6 and 19.8 min. for aspirin, atorvastatin calcium and clopidogrel bisulphate, respectively. Calibration plots were linear (r(2)>0.998) over the concentration range 5-30 μg/ml for atorvastatin calcium and 30-105 μg/ml for aspirin and clopidogrel bisulphate. The method was validated for accuracy, precision, specificity, linearity, and sensitivity. The proposed method was successfully used for quantitative analysis of capsules. No interference from any component of pharmaceutical dosage form was observed. Validation studies revealed that method is specific, rapid, reliable, and reproducible. The high recovery and low relative standard deviation confirm the suitability of the method for routine determination of aspirin, atorvastatin calcium and clopidogrel bisulphate in bulk drug and capsule dosage form.

  16. 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]).

  17. 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

  18. Aspirin Protects against Acinar Cells Necrosis in Severe Acute Pancreatitis in Mice

    PubMed Central

    Lu, Guotao; Tong, Zhihui; Ding, Yanbing; Liu, Jinjiao; Pan, Yiyuan; Gao, Lin; Tu, Jianfeng; Liu, George

    2016-01-01

    Aspirin has a clear anti-inflammatory effect and is used as an anti-inflammatory agent for both acute and long-term inflammation. Previous study has indicated that aspirin alleviated acute pancreatitis induced by caerulein in rat. However, the role of aspirin on severe acute pancreatitis (SAP) and the necrosis of pancreatic acinar cell are not yet clear. The aim of this study was to determine the effects of aspirin treatment on a SAP model induced by caerulein combined with Lipopolysaccharide. We found that aspirin reduced serum amylase and lipase levels, decreased the MPO activity, and alleviated the histopathological manifestations of pancreas and pancreatitis-associated lung injury. Proinflammatory cytokines were decreased and the expression of NF-κB p65 in acinar cell nuclei was suppressed after aspirin treatment. Furthermore, aspirin induced the apoptosis of acinar cells by TUNEL assay, and the expression of Bax and caspase 3 was increased and the expression of Bcl-2 was decreased. Intriguingly, the downregulation of critical necrosis associated proteins RIP1, RIP3, and p-MLKL was observed; what is more, we additionally found that aspirin reduced the COX level of pancreatic tissue. In conclusion, our data showed that aspirin could protect pancreatic acinar cell against necrosis and reduce the severity of SAP. Clinically, aspirin may potentially be a therapeutic intervention for SAP. PMID:28119929

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

    PubMed

    Bretagne, Jean-François

    2008-09-15

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

  20. Aspirin-induced gastric mucosal damage: prevention by enteric-coating and relation to prostaglandin synthesis.

    PubMed

    Hawthorne, A B; Mahida, Y R; Cole, A T; Hawkey, C J

    1991-07-01

    1. Gastric damage induced by low-dose aspirin and the protective effect of enteric-coating was assessed in healthy volunteers in a double-blind placebo-controlled cross-over trial using Latin square design. Each was administered placebo, plain aspirin 300 mg daily, plain aspirin 600 mg four times daily, enteric-coated aspirin 300 mg daily, or enteric-coated aspirin 600 mg four times daily for 5 days. Gastric damage was assessed endoscopically, and gastric mucosal bleeding measured. 2. Aspirin 300 mg daily and 600 mg four times daily caused significant increases in gastric injury compared with placebo. Gastric mucosal bleeding was significantly more with the high dose, with a trend towards increased gastric erosions, compared with the low dose. 3. Enteric-coating of aspirin eliminated the injury caused by low dose aspirin and substantially reduced that caused by the higher dose. 4. All dosages and formulations caused similar inhibition of gastric mucosal prostaglandin E2 synthesis. 5. Serum thromboxane levels were suppressed equally with plain and enteric-coated aspirin. 6. In this short-term study in healthy volunteers, gastric toxicity from aspirin was largely topical, independent of inhibition of prostaglandin synthesis, and could be virtually eliminated by the use of an enteric-coated preparation.

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

    PubMed

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

    2015-03-01

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

  2. Prevalence of Aspirin Resistance in Diabetic Patients and its Associated Factors

    PubMed Central

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

    2015-01-01

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

  3. 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

  4. 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.

  5. All Source Analysis System (ASAS). Block 1. Abbreviated HARDMAN Analysis (Tradeoff Analysis). Volume 1. Technical Report. Volume 3. Executive Summary

    DTIC Science & Technology

    1992-04-01

    1-2 1.3.1 TSE Hardware ........................................ 1-2 1.3.2 ASAS TCAE Hardware ................................. 1-3...Software ........................... 1-5 3 1.4.2 ASAS TCAE System Software ......................... 1-5 1.5 CONFIGURATIONS...Operators .................................. 1-8 1.6.3 CCS Operators ..................................... 1-8 1.6.4 TCAE W/S Operators

  6. Ascorbic acid does not reduce the anticancer effect of radiotherapy

    PubMed Central

    Hosokawa, Yoichiro; Saga, Ryo; Monzen, Satoru; Terashima, Shingo; Tsuruga, Eichi

    2017-01-01

    The present study hypothesized that the therapeutic use of ascorbic acid (AsA) in combination with radiation may reduce therapy-related side effects and increase the antitumor effects. The aim of the study was to examine the association between the scavenged activity of AsA and the biological anticancer effect of hydroxyl (OH) radicals generated by X-ray irradiation. Cell survival, DNA fragmentation of human leukemia HL60 cells and the amount of OH radicals were investigated following X-ray irradiation and AsA treatment. The number of living cells decreased, and DNA fragmentation increased at AsA concentrations >1 mM. Electron spin resonance spectra revealed that X-ray irradiation generated OH radicals, which were scavenged by AsA at concentrations >75 µM. The AsA concentration inside the cell was 75 µM when cells underwent extracellular treatment with 5 mM AsA, which significantly induced HL60 cell death even without irradiation. No increase in the number of viable HL60 cells was observed following AsA treatment with irradiation when compared to irradiation alone. In conclusion, the disappearance of the radiation anticancer effects with AsA treatment in combination with radiotherapy for cancer treatment is not a cause for concern. PMID:28123717

  7. The effects of acetylsalicylic acid on the pituitary prolactin of the lizard, Uromastix hardwickii.

    PubMed

    Ahmad, Mahmood; Hasan, Ruqaiya; Ahmad, Mansoor; Qureshi, Anila; Masroor, Shama

    2005-07-01

    This study deals with the intravenous administration of 7 mg acetylsalicylic acid (ASA) solution to Uromastix hardwickii for 4 days. It enhances the activity of anterior pituitary lactotrophs, when 0.1 ml of pituitary homogenate of ASA treated was injected hypodermically to crop-sac showed a greater diametric response and increased activity with milk like secretion than that of the injections of 0.1 ml homogenate of control pituitary. The present study indicated that ASA induces hyperprolactinemia.

  8. Stereocontrolled total synthesis of neuroprotectin D1 / protectin D1 and its aspirin-triggered stereoisomer

    PubMed Central

    Petasis, Nicos A.; Yang, Rong; Winkler, Jeremy W.; Zhu, Min; Uddin, Jasim; Bazan, Nicolas G.; Serhan, Charles N.

    2012-01-01

    Neuroprotectin D1 / protectin D1, a potent anti-inflammatory, proresolving, and neuroprotective lipid mediator derived biosynthetically from docosahexaenoic acid, was prepared in enantiomerically pure form via total organic synthesis. The synthetic strategy is highly stereocontrolled and convergent, featuring epoxide opening of glycidol starting materials for the introduction of the 10(R) and 17(S) hydroxyl groups. The desired alkene Z geometry was secured via the cis-reduction of alkyne precursors, while the conjugated E,E,Z triene was introduced at the end, in order to minimize Z/E isomerization. The same strategy, was also employed for the total synthesis of aspirin-triggered neuroprotectin D1 / protectin D1 having the 17(R)-stereochemistry. Synthetic compounds obtained with the reported method were matched with endogenously derived materials, and helped establish their complete stereochemistry. PMID:22690022

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

    PubMed

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

    1996-02-01

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

  10. A Nanometer Aerosol Size Analyzer (nASA) for Rapid Measurement of High-concentration Size Distributions

    NASA Astrophysics Data System (ADS)

    Han, Hee-Siew; Chen, Da-Ren; Pui, David Y. H.; Anderson, Bruce E.

    2000-03-01

    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 s. The analyzer includes a bipolar charger (Po210), 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 s 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 T-38 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 below.

  11. Tissue culture specificity of the tobacco ASA2 promoter driving hpt as a selectable marker for soybean transformation selection.

    PubMed

    Zernova, Olga; Zhong, Wei; Zhang, Xing-Hai; Widholm, Jack

    2008-11-01

    This study was carried out to determine if the tobacco anthranilate synthase ASA2 2.3 kb promoter drives tissue culture specific expression and if it is strong enough to drive hpt (hygromycin phosphotransferase) gene expression at a level sufficient to allow selection of transformed soybean embryogenic culture lines. A number of transformed cell lines were selected showing that the promoter was strong enough. Northern blot analysis of plant tissues did not detect hpt mRNA in the untransformed control or in the ASA2-hpt plants except in developing seeds while hpt mRNA was detected in all tissues of the CaMV35S-hpt positive control line plants. However, when the more sensitive RT-PCR assay was used all tissues of the ASA2-hpt plants except roots and mature seeds were found to contain detectable hpt mRNA. Embryogenic tissue cultures initiated from the ASA2-hpt plants contained hpt mRNA detectable by both northern and RT-PCR analysis and the cultures were hygromycin resistant. Friable callus initiated from leaves of ASA2-hpt plants did in some cases contain hpt mRNA that was only barely detectable by northern hybridization even though the callus was very hygromycin resistant. Thus the ASA2 promoter is strong enough to drive sufficient hpt expression in soybean embryogenic cultures for hygromycin selection and only very low levels of expression were found in most plant tissues with none in mature seeds.

  12. 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.

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

    PubMed

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

    2014-09-01

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

  14. 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.

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

    PubMed

    Brune, Kay; Hinz, Burkhard; Otterness, Ivan

    2009-02-01

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

  16. Novel NaCS-CS-PPS microcapsules as a potential enzyme-triggered release carrier for highly-loading 5-ASA.

    PubMed

    Wu, Qing-Xi; Yao, Shan-Jing

    2013-09-01

    In order to develop novel spherical micro-drug-carriers, an orifice-polymerization method was used to prepare spherical microcapsules which were composed of chemically crosslinked chitosan (CS) with sodium cellulose sulfate (NaCS) and sodium polyphosphate (PPS). 5-Aminosalicylic acid (5-ASA) was chosen as a model drug. The microcapsules prepared had an average diameter of 1.90 mm with loading efficiency of 60.77% and encapsulation efficiency of 90.03%. SEM results showed that the microcapsules had a double-walled capsule structure with an outer wall thickness of approximately 4.40 μm and inner wall (shell) thickness of approximately 187.14 μm. SEM transection images of the microcapsules showed that 5-ASA entrapped in the microcapsule was in a crystal form. The results of in vitro swelling/erosion and release analysis showed that the drug was preferentially and completely released in simulated colonic fluid (SCF, pH 6.4) under the mechanism of Anomalous transport. All these results indicate that the microcapsules could be a good candidate as an enzyme-triggered controlled release drug carrier.

  17. 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.

  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 and paracetamol removal using a commercial micro-sized TiO2 catalyst in deionized and tap water.

    PubMed

    Bianchi, Claudia L; Sacchi, Benedetta; Pirola, Carlo; Demartin, Francesco; Cerrato, Giuseppina; Morandi, Sara; Capucci, Valentino

    2016-10-21

    Micro-sized TiO2 catalyst was employed to degrade pharmaceutical compounds, i.e. aspirin and paracetamol, two of the most widely used drugs, purchasable without prescription. Their active agents, acetylsalicylic acid and acetaminophen, are characterized by different substituent groups, linked to the aromatic ring, which affect both the photodegradation and mineralization processes. The experimental conditions highlight the relationship between the nature of the pristine molecules, their degradation mechanisms, their mutual interference and the water's role. The research started from model systems with a single pollutant to the mixture of them and finally by moving from deionized water to tap water.

  20. Pharmacodynamic effects of EV-077 in patients with diabetes mellitus and coronary artery disease on aspirin or clopidogrel monotherapy: results of an in vitro pilot investigation.

    PubMed

    Rollini, Fabiana; Tello-Montoliu, Antonio; Patel, Ronakkumar; Darlington, Andrew; Wilson, Ryan E; Franchi, Francesco; Muñiz-Lozano, Ana; Desai, Bhaloo; Bender, Norbert; Sakariassen, Kjell S; Angiolillo, Dominick J

    2014-01-01

    Patients with diabetes mellitus (DM) have increased propensity to generate thromboxane A2 (TXA2) and other eicosanoids which can contribute to their heightened platelet reactivity. EV-077 is a potent thromboxane receptor antagonist and thromboxane synthase inhibitor and thus represents an attractive therapy in patients with DM. However, the effects of EV-077 on pharmacodynamic (PD) profiles in patients with DM and coronary artery disease (CAD) while on antiplatelet therapy is poorly explored and represented the aim of this in vitro pilot investigation. Patients with DM and stable CAD (n = 10) on low-dose aspirin (81 mg/day) were enrolled and then switched to clopidogrel (75 mg/day) monotherapy for 7-10 days. PD assessments were conducted while on aspirin and on clopidogrel using light transmittance aggregometry following stimuli with U-46619 [TXA2 stable analogue (7 μM)], arachidonic acid [AA (1 mM)], collagen (3 μg/mL) and adenosine diphosphate [ADP (5 μM and 20 μM)] with and without in vitro EV-077. EV-077 completely inhibited U-46619-stimulated platelet aggregation (p = 0.005 for both aspirin and clopidogrel) and also showed a significant reduction of collagen-induced aggregation (aspirin p = 0.008; clopidogrel p = 0.005). EV-077 significantly reduced AA-induced platelet aggregation in clopidogrel (p = 0.009), but not aspirin (p = 0.667) treated patients. Ultimately, EV-077 significantly reduced ADP-mediated platelet aggregation in both aspirin (ADP 5 μM p = 0.012; ADP 20 μM p = 0.032) and clopidogrel (ADP 5 μM p = 0.007; ADP 20 μM p = 0.008) treated patients. In conclusion, in DM patients with CAD on aspirin or clopidogrel monotherapy, in vitro EV-077 exerts potent platelet inhibitory effects on multiple platelet signaling pathways. These data support that EV-077 has only additive platelet inhibiting effects on top of standard antiplatelet therapies. These findings warrant further investigation in ex vivo settings.

  1. ASA-FTL: An adaptive separation aware flash translation layer for solid state drives

    DOE PAGES

    Xie, Wei; Chen, Yong; Roth, Philip C.

    2016-11-03

    Here, the flash-memory based Solid State Drive (SSD) presents a promising storage solution for increasingly critical data-intensive applications due to its low latency (high throughput), high bandwidth, and low power consumption. Within an SSD, its Flash Translation Layer (FTL) is responsible for exposing the SSD’s flash memory storage to the computer system as a simple block device. The FTL design is one of the dominant factors determining an SSD’s lifespan and performance. To reduce the garbage collection overhead and deliver better performance, we propose a new, low-cost, adaptive separation-aware flash translation layer (ASA-FTL) that combines sampling, data clustering and selectivemore » caching of recency information to accurately identify and separate hot/cold data while incurring minimal overhead. We use sampling for light-weight identification of separation criteria, and our dedicated selective caching mechanism is designed to save the limited RAM resource in contemporary SSDs. Using simulations of ASA-FTL with both real-world and synthetic workloads, we have shown that our proposed approach reduces the garbage collection overhead by up to 28% and the overall response time by 15% compared to one of the most advanced existing FTLs. We find that the data clustering using a small sample size provides significant performance benefit while only incurring a very small computation and memory cost. In addition, our evaluation shows that ASA-FTL is able to adapt to the changes in the access pattern of workloads, which is a major advantage comparing to existing fixed data separation methods.« less

  2. ASA-FTL: An adaptive separation aware flash translation layer for solid state drives

    SciTech Connect

    Xie, Wei; Chen, Yong; Roth, Philip C.

    2016-11-03

    Here, the flash-memory based Solid State Drive (SSD) presents a promising storage solution for increasingly critical data-intensive applications due to its low latency (high throughput), high bandwidth, and low power consumption. Within an SSD, its Flash Translation Layer (FTL) is responsible for exposing the SSD’s flash memory storage to the computer system as a simple block device. The FTL design is one of the dominant factors determining an SSD’s lifespan and performance. To reduce the garbage collection overhead and deliver better performance, we propose a new, low-cost, adaptive separation-aware flash translation layer (ASA-FTL) that combines sampling, data clustering and selective caching of recency information to accurately identify and separate hot/cold data while incurring minimal overhead. We use sampling for light-weight identification of separation criteria, and our dedicated selective caching mechanism is designed to save the limited RAM resource in contemporary SSDs. Using simulations of ASA-FTL with both real-world and synthetic workloads, we have shown that our proposed approach reduces the garbage collection overhead by up to 28% and the overall response time by 15% compared to one of the most advanced existing FTLs. We find that the data clustering using a small sample size provides significant performance benefit while only incurring a very small computation and memory cost. In addition, our evaluation shows that ASA-FTL is able to adapt to the changes in the access pattern of workloads, which is a major advantage comparing to existing fixed data separation methods.

  3. Bidirectional reflectance effects derived from ASAS imagery of a pecan orchard

    NASA Astrophysics Data System (ADS)

    Staenz, Karl; Gauthier, Robert P.; Teillet, Phil M.; Williams, Daniel J.

    1993-09-01

    Bidirectional reflectance factors (BRF) for a pecan orchard have been studied using Advanced Solid-State Array Spectrometer (ASAS) data acquired in the solar principal plane at altitudes of 2300 m and 5300 m above ground. In particular, the angular dependency of the BRF of different targets such as sunlit and shaded portions of the pecan tree, orchard floor, and soil (road) have been studied for viewing directions between -45 degrees and +45 degrees. The results indicate in general an increasing reflectance from the forward scattering direction to the backscattering direction. In addition, an increase in pixel size has significant effects on the surface BRFs.

  4. 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.

  5. Aspirin therapy and primary prevention of cardiovascular disease in diabetes mellitus.

    PubMed

    Younis, Naveed; Williams, Steve; Soran, Handrean

    2009-11-01

    The benefits of aspirin therapy in reducing the subsequent risk of myocardial infarction, stroke and death is well documented in individuals with cardiovascular disease including those with diabetes mellitus (DM). The evidence for aspirin use in primary prevention of cardiovascular events in DM is debatable and meta-analyses do not suggest a proven benefit. Despite the lack of evidence, low-dose aspirin therapy has been recommended by many current diabetes guidelines. This article reviews the results of two recently published large randomized clinical trials that have looked at primary prevention of cardiovascular events using aspirin in patients with DM.

  6. Aspirin-induced recurrent urticaria and recurrent angioedema in non-atopic children.

    PubMed

    Botey, J; Ibero, M; Malet, A; Marin, A; Eseverri, J L

    1984-09-01

    Recurrent urticaria and recurrent angioedema are frequent adverse reactions in non-atopic patients who do not tolerate aspirin. Of 1,632 infants and children who visited our allergy department for the first time, nine children (0.55%), five males and four females, presented recurrent urticaria or recurrent angioedema after taking aspirin. No evidence of atopy was disclosed either by clinical history (personal and family), skin testing, eosinophil levels or total IgE. Aspirin intolerance was established by oral challenge. Only three of the nine patients reported aspirin intolerance in their histories.

  7. Dental Extraction Can Be Performed Safely in Patients on Aspirin Therapy: A Timely Reminder

    PubMed Central

    2014-01-01

    Cardiac patients on aspirin therapy may require extractions for their diseased teeth. It is a common practice among physicians and treating surgeons to stop aspirin prior to tooth extraction because of fear of bleeding complications. This practice often predisposes the patient to adverse thromboembolic events. This practice is based on theoretical risk of bleeding and on isolated case reports of excessive bleeding with aspirin therapy. The current consensus and recommendations are in favor of continuing aspirin therapy during simple tooth extraction as the bleeding complication incidence is very less and if it occurs can be controlled efficiently with local hemostasis measures. PMID:25093121

  8. Report: frequency of aspirin resistance in patients with coronory artery disease in Pakistan.

    PubMed

    Akhtar, Naveed; Junaid, Ayesha; Khalid, Ayesha; Ahmed, Waqas; Shah, Mumtaz Ali; Rahman, Habibur

    2009-04-01

    Aspirin resistance is an emerging clinical entity. However the data available on aspirin resistance in Asian population is scarce. This study was initiated to prospectively evaluate the frequency of aspirin resistance in patients with stable coronary artery disease (CAD) in Pakistan. A cross sectional prospective study was conducted in cardiology and hematology departments at Shifa International Hospital, Islamabad from January to December 2007. Two hundred and fifty patients were enrolled from cardiology out patient department having met the specific inclusion criteria. Details were entered on a pre-designed questionnaire and aspirin response assay was performed on IMPACT-R (Dia Med AG 1785 Cressier Morat, Switzerland). Data was analyzed using SPSS V12. Aspirin resistance was observed in 12% of patients. 73.2% of study population were male and 26.8% were female, with a mean age of 57.2 years. There was no significant correlation of aspirin resistance with traditional risk factors like diabetes mellitus (DM), hypertension or dyslipidemia. 84% of aspirin non responders were taking 75 mg per day and 16% were on 150 mg per day. A positive trend was noted between aspirin resistance and cigarette smoking. Aspirin resistance is a real phenomenon in Pakistani population with an estimated frequency of 12%. Large scale prospective randomized trials with long term follow up are needed to assess the impact of different doses and the clinical significance of this biochemical entity.

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

    PubMed

    Czernichow, Pierre; Merle, Véronique

    2004-04-01

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

  10. 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.

  11. Transcriptional profiling of genes involved in ascorbic acid biosynthesis, recycling, and degradation during three leaf developmental stages in celery.

    PubMed

    Huang, Wei; Wang, Guang-Long; Li, Hui; Wang, Feng; Xu, Zhi-Sheng; Xiong, Ai-Sheng

    2016-12-01

    Ascorbic acid (AsA) is an important nutrient in the human body and performs various healthy functions. With considerable medicinal properties, celery (Apium graveolens L.) could be a good source of AsA for human health. However, the biosynthetic, recycling, and degradation pathways of AsA in celery have yet to be characterized. To study the metabolic pathways involved in AsA, the genes involved in AsA biosynthesis, recycling, and degradation were isolated from celery, and their expression profiles and AsA levels were analyzed in the leaf blades and petioles of two celery varieties at three different growth stages. AsA levels were higher in 'Ventura' compared with 'Liuhehuangxinqin' in both tissues possibly because of different transcription levels of genes, such as L-galactose dehydrogenase (GalDH), L-galactono-1,4-lactone dehydrogenase (GalLDH), and glutathione reductase (GR). Results revealed that the D-mannose/L-galactose pathway may be the predominant pathway in celery, and the D-galacturonic acid pathway appeared to contribute largely to AsA accumulation in petioles than in leaf blades in 'Liuhehuangxinqin.' AsA contents are regulated by complex regulatory mechanisms and vary at different growth stages, tissues, and varieties in celery. The results provide novel insights into AsA metabolic pathways in leaf during celery growth and development.

  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. 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.

  14. Recent ASA Presidents and 'Top' Journals: Observed Publication Patterns, Alleged Cartels and Varying Careers.

    PubMed

    Platt, Jennifer

    2016-01-01

    It has been common for studies presented as about American sociology as a whole to rely on data compiled from leading journals (American Sociological Review [ASR] and American Journal of Sociology [AJS]), or about presidents of the American Sociological Association [ASA], to represent it. Clearly those are important, but neither can be regarded as providing a representative sample of American sociology. Recently, Stephen Turner has suggested that dominance in the ASA rests with a 'cartel' initially formed in graduate school, and that it favors work in a style associated with the leading journals. The adequacy of these ideas is examined in the light of available data on the last 20 years, which show that very few of the presidents were in the same graduate schools at the same time. All presidents have had distinguished academic records, but it is shown that their publication strategies have varied considerably. Some have had no ASR publications except their presidential addresses, while books and large numbers of other journals not normally mentioned in this context have figured in their contributions, as well as being more prominent in citations. It seems clear that articles in the leading journals have not been as closely tied to prestigious careers as has sometimes been suggested, and that if there is a cartel it has not included all the presidents.

  15. Aspirin Resistance Predicts Adverse Cardiovascular Events in Patients with Symptomatic Peripheral Artery Disease

    PubMed Central

    Pasala, Tilak; Hoo, Jennifer Soo; Lockhart, Mary Kate; Waheed, Rehan; Sengodan, Prasanna; Alexander, Jeffrey

    2016-01-01

    Antiplatelet therapy reduces the risk of myocardial infarction, stroke, and vascular death in patients who have symptomatic peripheral artery disease. However, a subset of patients who take aspirin continues to have recurrent cardiovascular events. There are few data on cardiovascular outcomes in patients with peripheral artery disease who manifest aspirin resistance. Patients with peripheral artery disease on long-term aspirin therapy (≥4 wk) were tested for aspirin responsiveness by means of the VerifyNow Aspirin Assay. The mean follow-up duration was 22.6 ± 8.3 months. The primary endpoint was a composite of death, myocardial infarction, or ischemic stroke. Secondary endpoints were the incidence of vascular interventions (surgical or percutaneous), or of amputation or gangrene caused by vascular disease. Of the 120 patients enrolled in the study, 31 (25.8%) were aspirin-resistant and 89 (74.2%) were aspirin-responsive. The primary endpoint occurred in 10 (32.3%) patients in the aspirin-resistant group and in 13 (14.6%) patients in the aspirin-responsive group (hazard ratio=2.48; 95% confidence interval, 1.08–5.66; P=0.03). There was no significant difference in the secondary outcome of revascularization or tissue loss. By multivariate analysis, aspirin resistance and history of chronic kidney disease were the only independent predictors of long-term adverse cardiovascular events. Aspirin resistance is highly prevalent in patients with symptomatic peripheral artery disease and is an independent predictor of adverse cardiovascular risk. Whether intervening in these patients with additional antiplatelet therapies would improve outcomes needs to be explored. PMID:28100965

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

    PubMed

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

    1991-10-01

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

  17. Case-control Study of Aspirin Use and Risk of Pancreatic Cancer

    PubMed Central

    Streicher, Samantha A.; Yu, Herbert; Lu, Lingeng; Kidd, Mark S.; Risch, Harvey A.

    2014-01-01

    Background Pancreas-cancer prognosis is dismal, with 5-year survival less than 5%. Significant relationships between aspirin use and decreased pancreas-cancer incidence and mortality have been shown in four of 13 studies. Methods To evaluate further a possible association between aspirin use and risk of pancreatic cancer, we used data from a population-based Connecticut study conducted from January 2005-August 2009, of 362 pancreas-cancer cases frequency matched to 690 randomly sampled controls. Results Overall, regular use of aspirin was associated with reduced risk of pancreatic cancer (odds ratio [OR], 0.52; 95% CI, 0.39–0.69). Increments of decreasing risk of pancreatic cancer were observed for each year of low-dose or regular-dose aspirin use (OR, 0.94; 95% CI, 0.91–0.98 and OR, 0.98; 95% CI, 0.96–1.01, respectively) and for increasing years in the past that low-dose or regular-dose aspirin use had started (OR, 0.95; 95% CI, 0.92–0.99 and OR, 0.98; 95% CI, 0.96–1.00, respectively). Reduced risk of pancreatic cancer was seen in most categories of calendar time period of aspirin use, for both low-dose aspirin and regular-dose aspirin use. Relative to continuing use at the time of interview, termination of aspirin use within 2 years of interview was associated with increased risk of pancreatic cancer (OR, 3.24; 95% CI, 1.58–6.65). Conclusions Our results provide some support that a daily aspirin regimen may reduce risk of developing pancreatic cancer. Impact Long-term aspirin use has benefits for both cardiovascular disease and cancer, but appreciable bleeding complications that necessitate risk-benefit analysis for individual applications. PMID:24969230

  18. 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

  19. Evaluation of platelet function using PFA-100® in patients treated with Acetylsalicylic acid and qualified for Trauma and Orthopedic surgery procedures.

    PubMed

    Kurak, J; Zając, P; Czyżewski, D; Kucharski, R; Grzanka, R; Kasperska-Zajac, A; Koczy, B

    2016-11-01

    The phenomenon of high on-acetylsalicylic acid (ASA) treatment platelet (PLT) reactivity - HATPR - and its clinical implications have not been fully understood. Little data is available on assessing PLT activity based on the severity of intra- and postoperative bleeding in a population of orthopedic patients with normal closure time (CT) measured by a PLT function analyzer PFA-100®, despite being given long-term ASA therapy. The aim is to assess PLT function using PFA-100® in patients with ASA therapy and qualified for trauma and orthopedic surgery procedures. The retrospective analysis covered 384 patients whose PLT reactivity was assessed using PFA-100®. Out of those, 198 had been taking ASA with a 75 mg dose until hospital admission. In addition, a group of 70 patients with a proximal femoral fracture surgically treated using the dynamic hip screw (DHS) was selected, in whom severity of bleeding was assessed by HIP ASA (+). The reference group comprised 52 patients (without ASA therapy) who were operated on due to the same indications. Normal CT was found in 37% of ASA-receiving patients. Patients with normal CT, despite ASA therapy, exhibited significantly more intense bleeding after DHS surgery. A similar number of patients required red blood cells (RBCs) transfusion in HIP ASA (+) and HIP ASA (-). Increased risk of complications in HIP ASA (+) group was not found.

  20. 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.

  1. [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.

  2. 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

  3. European Stroke Prevention Study 2: A study of low-dose acetylsalicylic acid and of high dose dipyridamole in secondary prevention of cerebro-vascular accidents.

    PubMed

    1995-11-01

    In spite of some data being added to our knowledge of the effect of antiplatelets in secondary prevention of brain ischemic lesion in recent years, the main reasons to perform a second European Stroke Prevention Study (ESPS 2), which started in 1987-1988, were: (a) clarify the relative roles of aspirin (ASA) and dipyridamole (DP) alone or in combination; (b) confirm the efficacy of small doses of ASA and, so doing, decrease the number of drop-outs due to ASA side effects; (c) join information to the effect of antiplatelets in complete stroke. General characteristics of the sample of 6602 patients are presented and compared with other major trials and series. The patients in the four treatment arms (aspirin, dipyridamole, aspirin + dipyridamole and placebo) are compared. The more relevant features and risk factors known to influence long term prognosis are described and discussed. The small proportion of patients included with TIA (23.7%) and the comparability among treatment groups are stressed. No relevant differences have been found, among groups, on the sex or age distribution, prevalence of hypertension, diabetes, previous vascular events or atrial fibrillation, nor in the characteristics of the accident leading to the inclusion in trial.

  4. Activation of activator protein 2 alpha by aspirin alleviates atherosclerotic plaque growth and instability in vivo

    PubMed Central

    Yang, Jing-Jing; Li, Peng; Wang, Fu; Liang, Wen-Jing; Ma, Hui; Chen, Yuan; Ma, Zhi-Min; Li, Quan-Zhong; Peng, Qi-Sheng; Zhang, Yun; Wang, Shuang-Xi

    2016-01-01

    Aims Aspirin has been used for the secondary prevention and treatment of cardiovascular disease for several decades. We investigated the roles of transcriptional factor activator protein 2α (AP-2α) in the beneficial effects of aspirin in the growth and vulnerability of atherosclerotic plaque. Methods and Results In mice deficient of apolipoprotein E (Apoe-/-), aspirin (20, 50 mg/kg/day) suppressed the progression of atherosclerosis in aortic roots and increased the plaque stability in carotid atherosclerotic plaques induced by collar-placement. In vivo lentivirus-mediated RNA interference of AP-2α reversed the inhibitory effects of aspirin on atherosclerosis in Apoe-/- mice. Mechanically, aspirin increased AP-2α phosphorylation and its activity, upregulated IkBα mRNA and protein levels, and reduced oxidative stress in cultured vascular smooth muscle cells. Furthermore, deficiency of AP-2α completely abolished aspirin-induced upregulation of IkBα levels and inhibition of oxidative stress in Apoe-/- mice. Clinically, conventional doses of aspirin increased AP-2α phosphorylation and IkBα protein expression in humans subjects. Conclusion Aspirin activates AP-2α to upregulate IkBα gene expression, resulting in attenuations of plaque development and instability in atherosclerosis. PMID:27391154

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

    PubMed

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

    2016-07-01

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

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

    PubMed

    Velazquez, Juan R; Teran, Luis M

    2013-08-01

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

  7. 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. Aspirin and zileuton may interfere with genes related to tobacco use and may be useful in preventing lung cancer in current smokers. |

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

    ERIC Educational Resources Information Center

    Morgan, Gareth

    2008-01-01

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

  9. Aspirin use and risk of type 2 diabetes in apparently healthy men

    PubMed Central

    Hayashino, Yasuaki; Hennekens, Charles H.; Kurth, Tobias

    2008-01-01

    Background Epidemiological data on aspirin use and the risk of diabetes are limited. The Physician’s Health Study has accumulated 22 years of follow-up data, including 5 years of randomized data, from 22,071 apparently healthy men. Methods and results At baseline and in yearly follow-up questionnaires, participants self-reported a history of diabetes, aspirin use and various lifestyle factors. To evaluate the association between aspirin use and risk of subsequent diabetes, we used a Cox-proportional hazards model with time-varying regression coefficients. During the 22 follow-up years, 1719 cases of diabetes were reported. The multivariable-adjusted hazard ratio (HR) of developing diabetes was 0.86 (95% confidence interval [CI], 0.77–0.97) for those who self-selected any aspirin. During the 5 years of randomized treatment, 318 cases of diabetes were observed, with an HR of 0.91 (95%CI, 0.73–1.14) for those randomized to aspirin. Conclusions Our data suggest a small but not significant decrease in the risk of diabetes during 5 years of randomized comparison of 325 mg of aspirin every other day. This trend was continued during 22 years of follow-up, indicating that self-selection of any use of aspirin is associated with a significant, approximately 14% decrease in the risk of diabetes. Decreased risk of type 2 diabetes may be added to the list of the clinical benefits of aspirin. PMID:19233341

  10. 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

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

    PubMed Central

    Rocca, Bianca; Petrucci, Giovanna

    2012-01-01

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

  12. The effects of enteric coating of aspirin tablets on occult gastrointestinal blood loss.

    PubMed

    Howe, G B; Champion, G D; Corrigan, A B; Hewson, J; Haski, A; Day, R O; Paull, P D; Graham, G G

    1977-12-01

    The effect of enteric coating of aspirin tablets on the gastrointestinal blood loss associated with high dose aspirin therapy was investigated in 12 patients with rheumatoid arthritis. Occult blood loss was measured after labelling the patients' red blood cells with Cr51. Three salicylate preparations were used: enteric coated tablets of aspirin ("Rhusal", G.P. Laboratories, 7 x 650 mg per day), uncoated tablet cores of aspirin from the same batch (7 x 650 mg per day) and enteric coated tablets of sodium salicylate (7 x 600 mg and 1 x 300 mg per day). Daily blood loss during a salicylate-free period was (0.7 +/- 0.15 ml, mean +/- SE). Blood loss was significantly increased during dosage with all three salicylate preparations. Daily blood loss during dosage with the uncoated tablets of aspirin (5.3 +/- 0.3 ml) was significantly greater than during dosage with the enteric coated tablets of aspirin (2.3 +/- 0.3 ml) and enteric coated tablets of sodium salicylate (2.1 +/- 0.4 ml). The bioavailability of the salicylate preparations was studied in seven of the 12 patients. Mean plasma salicylate concentration two hours after the second daily dose during dosage with the enteric coated tablets of aspirin was 118 +/- 15 microgram/ml compared to 131 +/- 16 microgram/ml during dosage with the uncoated tablets. Urinary recoveries of the daily dosage of aspirin in the two formulations were also similar.

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

    PubMed Central

    Cryer, Byron; Mahaffey, Kenneth W

    2014-01-01

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

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

    PubMed

    Hennekens, Charles H; Dalen, James E

    2014-11-01

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

  15. 76 FR 53907 - Determination That TALWIN COMPOUND (Aspirin; Pentazocine Hydrochloride) Tablets, 325 Milligrams...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-30

    ... hydrochloride (HCl)) tablets, 325 milligrams (mg); equivalent to (EQ) 12.5 mg base, were not withdrawn from sale... drug applications (ANDAs) for aspirin; pentazocine HCl tablets, 325 mg; EQ 12.5 mg base, if all other... ANDA that does not refer to a listed drug. TALWIN COMPOUND (aspirin; pentazocine HCl) tablets, 325...

  16. 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.

  17. Aspirin and clopidogrel: a sweeping combination in cardiology.

    PubMed

    Manolis, Antonis S; Tzeis, Stylianos; Andrikopoulos, George; Koulouris, Spyros; Melita, Helen

    2005-07-01

    Platelets play a pivotal role in the pathogenesis of atherothrombosis, believed to be integrally involved in both the development and progression of atherosclerotic heart disease, as well as in its acute thrombotic complications. Antiplatelet therapy constitutes the cornerstone in the management of patients with acute coronary syndromes and generally high-risk patients with atherothrombosis. Until recently, long-term antiplatelet therapy for the treatment and prevention of the complications of atherothrombotic disease was traditionally limited to aspirin. The availability of the thienopyridines, in particular clopidogrel, represents an important addition to the physician's armamentarium. Clopidogrel is currently one of the most widely prescribed drugs for the treatment of symptomatic coronary artery disease. Aspirin and clopidogrel interfere with platelet activation in complementary, but separate pathways. Aspirin irreversibly inhibits cyclooxygenase, thus preventing the production of thromboxane A(2), which is a prothrombotic and vasoconstrictive substance. Clopidogrel, a newer thienopyridine which has largely supplanted ticlopidine due to a more favorable safety profile, irreversibly prevents platelet activation by blocking one of the three known adenosine 5'-diphosphate (ADP) receptors (the P2Y(12) receptor) on the platelet surface, thus interfering with platelet activation, degranulation and aggregation. Both these antiplatelet agents have a potent protective effect against adverse vascular events, but the combination of these two agents has an even stronger antiplatelet effect translating into superior antithrombotic protection in coronary, cerebral or peripheral arterial disease, without an inordinate increase in bleeding complications. A number of seminal clinical trials have demonstrated and confirmed the incremental benefit and efficacy of the combination of clopidogrel and aspirin therapy above and beyond that of aspirin alone, with multiple other

  18. Inhibition of glycation of albumin and hemoglobin by acetylation in vitro and in vivo.

    PubMed

    Rendell, M; Nierenberg, J; Brannan, C; Valentine, J L; Stephen, P M; Dodds, S; Mercer, P; Smith, P K; Walder, J

    1986-10-01

    Aspirin (acetylsalicylic acid or ASA) is known to inhibit glycosylation (glycation) of albumin in vitro. The mechanism has been presumed to be acetylation, but this has never been validated. The new affinity aminophenylboronic acid procedure for determination of glycosylated albumin was used to demonstrate inhibition of glycosylation by aspirin. ASA, but not salicylic acid, inhibited glycation. The inhibition of glycation by equimolar acetic anhydride was greater than that by ASA. Pretreatment of albumin with ASA in the absence of glucose demonstrated that inhibition was extremely rapid, occurring in a matter of minutes. However, the inhibition by ASA could not be prevented by massive acceleration of glycation induced by borohydride reduction. Glycation of hemoglobin was also inhibited by ASA, but the dose requirement was considerably higher. Various analogues of ASA were evaluated for inhibition of glycation. Only acetyl-5-ethylsalicylic acid was more effective than ASA in inhibiting albumin glycation. None of these agents was more potent than ASA in inhibiting glycation of hemoglobin. ASA was fed to diabetic rats in a long-term experiment. Glycohemoglobin and glycoalbumin levels were decreased by ASA administration. We conclude that ASA inhibits glycation by a very rapid acetylation process. This process is apparently quite selective in terms of the protein involved, presumably because of the local environment of affected lysine groups. The phenomenon can be produced in vivo by administration of ASA.

  19. ASAS J083241+2332.4: A NEW EXTREME LOW MASS RATIO OVERCONTACT BINARY SYSTEM

    SciTech Connect

    Sriram, K.; Malu, S.; Vivekananda Rao, P.; Choi, C. S.

    2016-03-15

    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{sup −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, q{sub critical} = 0.07–0.09, overcontact binaries should merge and form a fast rotating star, but it has been suggested that q{sub critical} 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 L{sub 2} 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.

  20. VizieR Online Data Catalog: LCs re-analysis of Mira variables in ASAS (Vogt+, 2016)

    NASA Astrophysics Data System (ADS)

    Vogt, N.; Contreras-Quijada, A.; Fuentes-Morales, I.; Vogt-Geisse, S.; Arcos, C.; Abarca, C.; Agurto-Gangas, C.; Caviedes, M.; Dasilva, H.; Flores, J.; Gotta, V.; Penaloza, F.; Rojas, K.; Villasenor, J. I.

    2017-01-01

    The ASAS database (All Sky Automated Survey, Pojmanski 2002, II/264) is the outcome of a sky patrol program with CCD photometry, conducted at the Las Campanas Observatory, Chile, between 2000 and 2009 (-90<=DEC<=+28°). The visual limiting magnitude is about 14.5m and a total of up to 500 measurements per star are available. An automatic procedure identified 50122 ASAS variable stars and classified part of them according to their type of variability. A total of 2895 variables are listed as Mira stars in this database. The aim of this paper is to re-analyze the light curves of all stars classified as Mira in ASAS. (2 data files).

  1. Molecular Pathways: Aspirin and Wnt Signaling—A Molecularly Targeted Approach to Cancer Prevention and Treatment

    PubMed Central

    Gala, Manish K.; Chan, Andrew T.

    2014-01-01

    The anti-inflammatory properties of aspirin have resulted in its widespread use as an analgesic, anti-pyretic, and cardioprotective agent. Beyond these applications, multiple observational studies and randomized controlled trials have demonstrated a chemopreventative role for aspirin, particularly in the development of colorectal neoplasia. Given the critical importance of Wnt dysregulation in colorectal carcinogenesis, the interplay between aspirin and canonical Wnt signaling has become a focus of investigation. These studies have illuminated our understanding of the anti-cancer mechanisms of aspirin, yielding the identification of potential biomarkers for which aspirin's chemopreventative efficacy can be safely optimized into routine clinical practice and providing leads into the discovery of novel preventive and therapeutic targets. In this review, we summarize key experimental and clinical studies of this interaction, as well as highlight future strategies to advance their clinical translation. PMID:25501125

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

    PubMed

    1997-05-01

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

  3. Evaluation of the stability of aspirin in solid state by the programmed humidifying and non-isothermal experiments.

    PubMed

    Li, Lin-Li; Zhan, Xian-Cheng; Tao, Jian-Lin

    2008-03-01

    The influence of both moisture and heat on the stability of aspirin was investigated by a single pair of experiments, one with programmed humidity control and the other non-isothermal, rather than many standard isothermal studies, each at constant relative humidity. In experiments, we adopted the acid-base back titration method to measure the content of aspirin in the presence of its degradation products. It was found that the degradation of aspirin could be expressed as ln[(c0-c)/c]=kt+D, where D was a lag time item not related to humidity and temperature. The relationship between the degradation rate constant k and humidity Hr) and temperature T could be described as Arrhenius equation multiplied by an exponential item of relative humidity: k = A . exp(mHr) . exp(-(Ea/RT)), where A, Ea and m were the pre-exponential factor, observed activation energy, and a parameter related to humidity, respectively. The results obtained from the programmed humidifying and non-isothermal experiments, A=(1.09+/-2.04)x10(12) h(-1), Ea=(93.5+/-2.2) kJ . mol(-1) and m=1.18+/-0.19, were comparable to those from isothermal studies at constant humidity, A=(1.71+/-0.35)x10(12) h(-1), Ea=(94.9+/-0.7) kJ . mol(-1) and m=1.20+/-0.02. Since the programmed humidifying and non-isothermal experiments save time, labor and materials, it is suggested that the new experimental method can be used to investigate the stability of drugs unstable to both moisture and heat, instead of many classical isothermal experiments at constant humidity.

  4. [Ability to Overcome the Thrombocyte Resistance to Acetylsalicylic Acid in Patients With Coronary Artery Disease After Myocardial Revascularization With Coronary Stenting].

    PubMed

    Pershukov, I V; Ostaschenko, S L; Kuznetsova, T N; Scherbo, S N; Karben, Z A; Sokryukina, E V; Omarov, A A; Ramazanov, D M; Bosak, N V; Shulzhenko, L V; Kalmatov, R K; Batyraliev, T A; Sidorenko, B A

    2016-07-01

    Resistance to acetylsalicylic acid (ASA) in patients with coronary artery disease is a poor predictor for the development of atherothrombotic complications. In 277 patients with coronary artery disease suffered uncomplicated coronary angioplasty with stent implantation, we was estimated arachidon-induced platelet aggregation during treatment with acetylsalicylic acid by bedside VerifyNow Assay test at 28-90 days after the intervention. It was found that 18.9% of the 144 patients receiving a combination of ASA 75 mg with 15.2 mg of magnesium hydroxide had true (laboratory) resistance to ASA. At the same time on the original enteric coated ASA 100 mg, we can found only 0.8% resistance to ASA among 129 patients. We made switch from combination of ASA 75 mg with 15.2 mg of magnesium hydroxide to original enteric coated ASA 100 mg and repeat VerifyNow Assay test at 2-4 days and found lost of resistance in 92% of 28 patients. Thus, resistance to the ASA is not constant, it depends on the form and the applied dose of ASA, and eliminating more than 92% when ASA changes from ineffective to effective form.

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

    PubMed Central

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

    2016-01-01

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

  6. [New ASAS criteria for the diagnosis of spondyloarthritis: diagnosing sacroiliitis by magnetic resonance imaging].

    PubMed

    Banegas Illescas, M E; López Menéndez, C; Rozas Rodríguez, M L; Fernández Quintero, R M

    2014-01-01

    Radiographic sacroiliitis has been included in the diagnostic criteria for spondyloarthropathies since the Rome criteria were defined in 1961. However, in the last ten years, magnetic resonance imaging (MRI) has proven more sensitive in the evaluation of the sacroiliac joints in patients with suspected spondyloarthritis and symptoms of sacroiliitis; MRI has proven its usefulness not only for diagnosis of this disease, but also for the follow-up of the disease and response to treatment in these patients. In 2009, The Assessment of SpondyloArthritis international Society (ASAS) developed a new set of criteria for classifying and diagnosing patients with spondyloarthritis; one important development with respect to previous classifications is the inclusion of MRI positive for sacroiliitis as a major diagnostic criterion. This article focuses on the radiologic part of the new classification. We describe and illustrate the different alterations that can be seen on MRI in patients with sacroiliitis, pointing out the limitations of the technique and diagnostic pitfalls.

  7. An acetylsalicylic acid-sensitive aggregation phenomenon in Dipodascopsis uninucleata.

    PubMed

    Kock, J L; van Wyk, P W; Venter, P; Coetzee, D J; Smith, D P; Viljoen, B C; Nigam, S

    1999-04-01

    Aggregation of ascospores has been discovered in the yeast Dipodascopsis uninucleata. When this yeast is cultivated to reach the sexual reproductive stage, small ascospores are individually released from the tip of a sac-like ascus which then aggregate in orderly clusters. Acetylsalicylic acid (ASA) inhibited ascospore release and subsequent ordered aggregation process. We suggest that novel ASA-sensitive oxidised fatty acids (3R-hydroxy-oxylipins) and small hooks located on the surface of these ascospores, are involved.

  8. 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.

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-01-01

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

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

    PubMed

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

    2007-05-17

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

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

    PubMed

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

    2014-02-25

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

  13. Total organic carbon method for aspirin cleaning validation.

    PubMed

    Holmes, A J; Vanderwielen, A J

    1997-01-01

    Cleaning validation is the process of assuring that cleaning procedures effectively remove the residue from manufacturing equipment/facilities below a predetermined level. This is necessary to assure the quality of future products using the equipment, to prevent cross-contamination, and as a World Health Organization Good Manufacturing Practices requirement. We have applied the Total Organic Carbon (TOC) analysis method to a number of pharmaceutical products. In this article we discuss the TOC method that we developed for measuring residual aspirin on aluminum, stainless steel, painted carbon steel, and plexiglass. These are all surfaces that are commonly found as part of pharmaceutical production equipment. The method offers low detection capability (parts per million levels) and rapid sample analysis time. The recovery values ranged from 25% for aluminum to about 75% for plexiglass with a precision of 13% or less. The results for the plexiglass tended to vary with the age of the surface making the determination of an accurate recovery value difficult for this type of surface. We found that the TOC method is applicable for determining residual aspirin on pharmaceutical surfaces and will be useful for cleaning validation.

  14. Can Aspirin and Cancer Prevention be Ageless Companions?

    PubMed

    Farag, Mohamed

    2015-01-01

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

  15. A validated HPLC method with electrochemical detection for simultaneous assay of 5-aminosalicylic acid and its metabolite in human plasma.

    PubMed

    Palumbo, Giancarlo; Bacchi, Simona; Primavera, Luisa; Palumbo, Paola; Carlucci, Giuseppe

    2005-06-01

    A high-performance liquid chromatographic method was developed, validated and applied to the simultaneous determination of 5-aminosalicylic acid (5-ASA) and its acetylated metabolite (acetyl-5-ASA) in human plasma. The method involves liquid-liquid extraction with methanol followed by isocratic reversed-phase chromatography on a Kromasil KR100 C(18) column with electrochemical detection. The recovery, selectivity, linearity, precision and accuracy of the method were evaluated from spiked human plasma samples. The effects of mobile phase composition, buffer concentration, mobile phase pH and concentration of organic modifiers on retention of 5-ASA, acetyl 5-ASA and internal standard were investigated. Limits' of detection were 5 ng/mL for 5-ASA and 10 ng/mL for acetyl-5-ASA, respectively. The method can be used for supporting therapeutical drug monitoring and pharmacokinetic studies.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  18. Light avoidance reduces ascorbic acid accumulation in the peel of Citrus fruit.

    PubMed

    Lado, Joanna; Alós, Enriqueta; Rodrigo, María Jesús; Zacarías, Lorenzo

    2015-02-01

    Citrus fruits are highly consumed worldwide and represent one of the most important sources of ascorbic acid (AsA). However, information about the molecular mechanisms regulating AsA accumulation in Citrus fruit and the effects of environmental factors is scarce. In this study we have investigated the effect of fruit shading on AsA content and the expression of AsA biosynthetic, degrading and recycling genes in fruits of different Citrus species. Immature-green fruits were covered at the end of the cell enlargement phase and AsA concentration in the flavedo declined and remained at low levels as compared with light-exposed fruits. Fruit shading marginally altered the expression of genes from the l-galactose pathway and this effect was variable in the four Citrus species. However, specific isoforms (GalUR8 or GalUR12) from the l-galacturonic acid pathway were significantly repressed paralleling the reduction in AsA concentration. No significant effect of shading was detected in transcription of genes of the myo-inositol and l-gulose pathways as well as recycling and degradation. Collectively, results indicate that light avoidance inhibited accumulation of AsA in the flavedo of Citrus fruits and suggest that the l-galacturonic acid pathway has a relevant contribution to AsA content in this tissue.

  19. 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.

  20. 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

  1. Aspirin resistance is more common in lacunar strokes than embolic strokes and is related to stroke severity.

    PubMed

    Englyst, Nicola A; Horsfield, Gill; Kwan, Joseph; Byrne, Christopher D

    2008-06-01

    The aim of this study was to investigate the relationship between aspirin resistance, ischaemic stroke subtype, stroke severity, and inflammatory cytokines. Aspirin resistance was assessed by thrombelastography in 45 people with ischaemic stroke and 25 controls. Plasma interleukin (IL)-6 was measured. Stroke severity was assessed using the modified Rankin scale and National Institute of Health Stroke Score within 72 h of stroke. Aspirin resistance was more common in the stroke than the control group (67% versus 40%, P=0.028), and within the stroke group the aspirin-resistant group had a higher Rankin score (4.0 versus 2.0, P=0.013). Aspirin resistance was greater in lacunar than embolic strokes (platelet activation 79% versus 59%, P=0.020). The stroke aspirin-resistant group had higher levels of IL-6 than the stroke aspirin-sensitive group (2.4+/-1 versus 1.8+/-0.9 ng/mL, P=0.037). Using multivariate analysis, we examined the interrelationships between aspirin resistance, IL-6, and stroke severity. These analyses showed that IL-6 was independently associated with stroke severity as the outcome (B=3.738, P=0.036), and aspirin resistance was independently associated with IL-6 (B=0.765, P=0.005) as the outcome. In conclusion, aspirin resistance is related to stroke severity and aspirin resistance is more common in lacunar strokes than embolic strokes.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Crook, D; Collins, A J

    1977-01-01

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

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

    PubMed

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

    2016-02-01

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

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

    PubMed Central

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

    2016-01-01

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

  6. Luteolin supplementation adjacent to aspirin treatment reduced dimethylhydrazine-induced experimental colon carcinogenesis in rats.

    PubMed

    Osman, Neamt H A; Said, Usama Z; El-Waseef, Ahmed M; Ahmed, Esraa S A

    2015-02-01

    Previous studies have shown that aspirin is used in colon cancer treatment. However, long-term of Aspirin usage is limited to gastric and renal toxicity. Luteolin (LUT) has cancer prevention and anti-inflammatory effects. The present study was designed to investigate the effect of LUT supplementation and Aspirin treatment in dimethylhydrazine (DMH)-induced carcinogenesis in rats. DMH (20 mg/kg BW/week) treated rats received gavages with Aspirin (50 mg/kg BW/week) and LUT (0.2 mg/kg BW/day) for 15 weeks. DMH injections induce colon polyps and renal bleeding, significantly increasing carcinoembryonic antigen (CEA), cyclooxygenase-2 (COX-2), oxidative stress, and kidney function tests and reducing antioxidant markers. Either Aspirin or LUT gavages alone or combined produce a significant decrease in colon polyp number and size, significantly decreasing CEA, COX-2, and oxidative stress and increasing antioxidant markers. In conclusion, the supplementations of LUT adjacent to Aspirin in the treatment of DMH-induced carcinogenesis in rats reflect a better effect than the use of Aspirin alone.

  7. Aspirin for primary prevention of cardiovascular events in the elderly: current status and future directions.

    PubMed

    Ward, Stephanie A; Demos, Lisa; Workman, Barbara; McNeil, John J

    2012-04-01

    The role of aspirin in the secondary prevention of occlusive cardiovascular events has now been well established. Given this, aspirin in primary prevention has been the focus of several large trials and subsequent meta-analyses over the past 3 decades, and yet the issue remains controversial. Recent studies in populations with high baseline risk - such as diabetics and those with asymptomatic peripheral arterial disease - have not found the expected benefits of aspirin on cardiovascular endpoints, which contrasts with earlier studies that reported a reduced relative risk for outcomes such as myocardial infarction and ischaemic stroke, but not for mortality. Furthermore, in healthy populations, the absolute risk reduction conferred by aspirin is small and needs to be balanced against the risk of a major haemorrhage. Older adults have a higher risk for cardiovascular events and therefore might represent the group in which aspirin for primary prevention could deliver the greatest absolute benefit, yet at the same time, the elderly bear an increased vulnerability to major haemorrhage, including haemorrhagic stroke. It is also not known whether older adults experience the same risk reduction from aspirin as middle-aged individuals. The current evidence base does not sufficiently clarify whether aspirin for primary prevention confers a meaningful net benefit in the elderly.

  8. The Overarm-Throwing Pattern among U-14 ASA Female Softball Players: A Comparative Study of Gender, Culture, and Experience

    ERIC Educational Resources Information Center

    Petranek, Laura Jones; Barton, Gina V.

    2011-01-01

    A developmental description of overarm-throwing characteristics of U-14 female ASA softball players is presented here. Comparisons were made between these athletes and teens of similar age in the United States (Runion, Roberton, & Langendorfer, 2003) and in Germany (Ehl, Roberton, & Langendorfer, 2005). A majority of the softball players…

  9. Pac-Man in Space? ASAS-SN Discovery of A Probable Supernova in Galaxy Pair CGCG 314-006

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

    During the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN or "Assassin"), using data from the quadruple 14-cm "Brutus" telescope in Haleakala, Hawaii, we discovered a new transient source, most likely a supernova, in the middle of the Pac-Man-shaped galaxy pair CGCG 314-006.

  10. ASA conference on radiation and health: Health effects of electric and magnetic fields: Statistical support for research strategies. Final report

    SciTech Connect

    Not Available

    1990-05-01

    This report is a collection of papers documenting presentations made at the VIII ASA (American Statistical Association) Conference on Radiation and Health entitled Health Effects of Electric and Magnetic Fields: Statistical Support for Research Strategies. Individual papers are abstracted and indexed for the database.

  11. The IL1B-511 Polymorphism (rs16944 AA Genotype) Is Increased in Aspirin-Exacerbated Respiratory Disease in Mexican Population.

    PubMed

    Falfán-Valencia, Ramcés; Pavón-Romero, Gandhi F; Camarena, Angel; García, María de la Luz; Galicia-Negrete, Gustavo; Negrete-García, María Cristina; Teran, Luis Manuel

    2012-01-01

    Aspirin exacerbated respiratory disease (AERD) is characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity. The mechanisms which produce these manifestations of intolerance are not fully defined, current research focuses on cyclooxygenase 1 (COX-1) inhibition, metabolism of arachidonic acid, and the COX pathway to the lipoxygenase (LO) route, inducing increased synthesis of leukotrienes (LT). The biological plausibility of this model has led to the search for polymorphisms in genes responsible for proinflammatory cytokines synthesis, such as IL1B and IL8. We performed a genetic association study between IL8-251 (rs4073) and IL1B-511 (rs16944) polymorphisms in AERD, aspirin-tolerant asthma (ATA), and healthy control subjects. Using allelic discrimination by real-time PCR, we found statistically nonsignificant associations between AERD, ATA, and healthy control subjects for the GG and GA genotypes of IL1B (rs16944). Interestingly, the AA genotype showed an increased frequency in the AERD patients versus the ATA group (GF = 0.19 versus 0.07, p = 0.018, OR 2.98, and 95% CI 1.17-7.82). This is the first observation that IL1B polymorphisms are involved in AERD. Thus, future studies must investigate whether interleukin-1β is released in the airways of AERD patients and whether it relates to genetic polymorphisms in the IL1B gene.

  12. No Effect of Aspirin on Mammographic Density in a Randomized Controlled Clinical Trial

    PubMed Central

    McTiernan, Anne; Wang, CY; Sorensen, Bess; Xiao, Liren; Buist, Diana S. M.; Bowles, Erin J. Aiello; White, Emily; Rossing, Mary Anne; Potter, John; Urban, Nicole

    2009-01-01

    Background: Epidemiologic studies suggest a reduced risk of breast cancer among women who regularly use aspirin; a plausible mechanism is through aspirin effect on mammographic breast density, a breast cancer risk factor, possibly mediated through aspirin interference with estrogen synthesis. Methods: In a 2-arm randomized placebo-controlled clinical trial, we evaluated the effects of 6-months administration of 325 mg/day aspirin on total mammographic breast dense area and percent of the mammographic breast image occupied by dense areas (% density) in 143 postmenopausal women. Eligible women, recruited 2005-7, were healthy, not taking hormone therapy, with elevated mammographic breast density (American College of Radiology Breast Imaging Reporting and Data System (BI-RADS®) density category 2, 3 or 4) within 6 months prior to enrollment. Results: Women were a mean (s.d.) 59.5 (5.5) years. Geometric mean baseline percent density was 17.6% (95% CI 14.8, 20.9) in women randomized to aspirin and 19.2% (95% CI 16.3, 22.7) in women randomized to placebo. Percent density decreased in women randomized to aspirin by an absolute 0.8% vs. an absolute decrease of 1.2% in controls (p = 0.84). Total breast area and dense area decreased to a similar degree in women assigned to aspirin and in those assigned to placebo, with no differences statistically significantly different between trial arms. Conclusions: A single daily administration of adult-dose aspirin for 6 months had no effect on mammographic density in postmenopausal women. If aspirin affects breast cancer risk in postmenopausal women, it may do so through alternative pathways than mammographic breast density. PMID:19423529

  13. Aspirin Use and Lung Cancer Risk: A Possible Relationship? Evidence from an Updated Meta-Analysis

    PubMed Central

    Xu, Lei; Yu, Jing; Wu, Yan; Geng, Jiang; Yao, Xu-dong

    2015-01-01

    Background and Purpose Growing evidence has emerged and controversial results reported on possible relationship between aspirin use and lung cancer risk. We, therefore, conducted this updated and comprehensive meta-analysis to evaluate this issue, with focus on dose-risk and duration-risk relationships. Methods We searched electronic databases including PUBMED, EMBASE and Cochrane library to identify eligible studies. Relative risk (RR) and its 95% confidence interval (CI) were used for cohort studies, while odds ratio (OR) were employed for case-control studies. The random effects and fixed effects models were used for analyses. Results 18 studies were identified including 19835 lung cancer cases, which were eligible for inclusion in the present meta-analysis. Pooled data from case-control studies showed a significant inverse association between regular aspirin use and lung cancer risk. But for cohort studies, insignificant association was detected with little evidence of heterogeneity (RR: 1.05, 95%CI: 0.95 – 1.16; I2: 10.3%, p value: 0.351). In case-control studies, standard aspirin use (>325mg) was related to lower lung cancer incidence, compared with low-dose aspirin use (75–100mg). A similar trend was observed in cohort studies. Besides, when analysis was restricted to long time regular aspirin use (>5 years), insignificant results were reported in both cohort and case-control studies. Finally, regular aspirin use might result in higher reduction of non-small cell lung cancer incidence among men. Conclusions Our findings do not support the protective effect of regular aspirin use on lung cancer risk. Long time aspirin use, sex, dose and type of lung cancer might alter the effect of aspirin use on lung cancer risk. More well-designed studies are needed to further clarify these associations. PMID:25849465

  14. AspiriN To Inhibit SEPSIS (ANTISEPSIS) randomised controlled trial protocol

    PubMed Central

    Eisen, Damon P; Moore, Elizabeth M; Leder, Karin; Lockery, Jessica; McBryde, Emma S; McNeil, John J; Pilcher, David; Wolfe, Rory; Woods, Robyn L

    2017-01-01

    Introduction Sepsis is a leading global cause of morbidity and mortality, and is more common at the extremes of age. Moreover, the cost of in-hospital care for elderly patients with sepsis is significant. There are indications from experimental and observational studies that aspirin may reduce inflammation associated with infection. This paper describes the rationale and design of the AspiriN To Inhibit SEPSIS (ANTISEPSIS) trial, a substudy of ASPirin in Reducing Events in the Elderly (ASPREE). ANTISEPSIS primarily aims to determine whether low-dose aspirin reduces sepsis-related deaths in older people. Additionally, it will assess whether low-dose aspirin reduces sepsis-related hospitalisations and sepsis-related Intensive Care Unit (ICU) admissions. Methods and analysis ASPREE is a double-blinded, randomised, placebo-controlled primary prevention trial that will determine whether daily low-dose aspirin extends disability-free longevity in 19 000 healthy older people recruited in Australia and the USA. The ANTISEPSIS substudy involves additional ASPREE trial data collection to assess the impact of daily low-dose aspirin on sepsis-related events in the 16 703 ASPREE participants aged 70 years and over, recruited in Australia. The intervention is a daily 100 mg dose of enteric-coated aspirin versus matching placebo, with 1:1 randomisation. The primary outcome for the ANTISEPSIS substudy is the incidence of sepsis-related death in eligible patients. The incidence of sepsis-related hospital and ICU admissions are secondary outcomes. ANTISEPSIS is to be conducted between 2012 and 2018. Discussion This substudy will determine whether aspirin, an inexpensive and accessible therapy, safely reduces sepsis-related deaths and hospitalisations in older Australians. If shown to be the case, this would have profound effects on the health of older Australians. Trial registration number Pre-results, ACTRN12613000349741. PMID:28110287

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

    PubMed

    Landolfi, R; Patrono, C

    1996-09-01

    The role of aspirin in the antithrombotic strategy of patients with polycythemia vera (PV) and essential thrombocythemia (ET) is highly controversial. Long considered unsafe on the basis of a single clinical trial testing very high doses in PV patients, aspirin is being increasingly used at lower dosage. The rationale for the use of aspirin in patients with PV and ET is provided by the efficacy of this agent in the treatment of microcirculatory disturbances of thrombocythemic states associated with myeloproliferative disorders and by recent evidence that asymptomatic PV and ET patients have persistently increased thromboxane (TX) A