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Sample records for aspirin acetylsalicylic acid

  1. The kinetics of hydrolysis of acetylsalicylic acid (Aspirin) in different ...

    African Journals Online (AJOL)

    The kinetics of hydrolysis of Acetylsalicylic acid (Aspirin) to salicylic acid was followed by the direct spectrophotometric measurement of the amount of salicylic acid produced with time. Salicylic acid was complexed with ferric ion giving a characteristic purple colour (λlm 523nm). The kinetics of hydrolysis was found to follow ...

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

    Science.gov (United States)

    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.

  3. Interaction of aspirin (acetylsalicylic acid) with lipid membranes.

    Science.gov (United States)

    Barrett, Matthew A; Zheng, Songbo; Roshankar, Golnaz; Alsop, Richard J; Belanger, Randy K R; Huynh, Chris; Kučerka, Norbert; Rheinstädter, Maikel C

    2012-01-01

    We studied the interaction of Aspirin (acetylsalicylic acid) with lipid membranes using x-ray diffraction for bilayers containing up to 50 mol% of aspirin. From 2D x-ray intensity maps that cover large areas of reciprocal space we determined the position of the ASA molecules in the phospholipid bilayers and the molecular arrangement of the molecules in the plane of the membranes. We present direct experimental evidence that ASA molecules participate in saturated lipid bilayers of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) and preferably reside in the head group region of the membrane. Up to 50 mol% ASA molecules can be dissolved in this type of bilayer before the lateral membrane organization is disturbed and the membranes are found to form an ordered, 2D crystal-like structure. Furthermore, ASA and cholesterol were found to co-exist in saturated lipid bilayers, with the ASA molecules residing in the head group region and the cholesterol molecules participating in the hydrophobic membrane core.

  4. Interaction of aspirin (acetylsalicylic acid with lipid membranes.

    Directory of Open Access Journals (Sweden)

    Matthew A Barrett

    Full Text Available We studied the interaction of Aspirin (acetylsalicylic acid with lipid membranes using x-ray diffraction for bilayers containing up to 50 mol% of aspirin. From 2D x-ray intensity maps that cover large areas of reciprocal space we determined the position of the ASA molecules in the phospholipid bilayers and the molecular arrangement of the molecules in the plane of the membranes. We present direct experimental evidence that ASA molecules participate in saturated lipid bilayers of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine and preferably reside in the head group region of the membrane. Up to 50 mol% ASA molecules can be dissolved in this type of bilayer before the lateral membrane organization is disturbed and the membranes are found to form an ordered, 2D crystal-like structure. Furthermore, ASA and cholesterol were found to co-exist in saturated lipid bilayers, with the ASA molecules residing in the head group region and the cholesterol molecules participating in the hydrophobic membrane core.

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

    Science.gov (United States)

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

    2010-02-28

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

  6. Simultaneous high-performance liquid chromatography assay of acetylsalicylic acid and salicylic acid in film-coated aspirin tablets.

    Science.gov (United States)

    Fogel, J; Epstein, P; Chen, P

    1984-12-28

    A reversed-phase high-performance liquid chromatography (HPLC) method has been developed for the simultaneous assay of acetylsalicylic acid (I) and salicylic acid (II) in film-coated aspirin tablets. As little as 0.1% II (relative to I) can be quantitatively determined. Using a 5-microns octadecylsilane column with water-acetonitrile-phosphoric acid (76:24:0.5) as the mobile phase enabled the chromatographic separation to be completed in 4 min. Due to the slow rate of decomposition of I to II in the extraction solvent, acetonitrile-methanol-phosphoric acid (92:8:0.5), the analysis of many samples was routinely performed by means of automated HPLC equipment. Other compounds (non-aspirin salicylates, caffeine and acetaminophen) were also separated by the chromatographic system.

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

    Science.gov (United States)

    updated 3/10/08 Medications Containing Aspirin (Acetylsalicylate) and Aspirin-Like Products © National Reye's Syndrome Foundation Inc. 2008 Epidemiologic research has shown an association between the development of Reye's ...

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

    Science.gov (United States)

    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.

  9. Simultaneous determination of acetylsalicylic and salicylic acids in human serum and aspirin formulations by second-derivative synchronous fluorescence spectrometry.

    Science.gov (United States)

    Konstantianos, D G; Ioannou, P C; Efstathiou, C E

    1991-04-01

    A second-derivative synchronous scanning spectrofluorimetric method for the simultaneous determination of acetylsalicylic acid (ASA) and salicylic acid (SA) is described. The method is based on the native fluorescence of both acids in a 1% acetic acid-chloroform solution. Both ASA and SA can be determined within the concentration ranges 0.2-70 and 0.03-10 micrograms ml-1, respectively. The effect of each acid on the signal of the other has been studied in detail. Empirical equations have been used to overcome this effect, thus allowing the accurate determination of both acids in binary mixtures, without a separation step. The method has been applied to the determination of ASA and SA in blood serum and to the determination of SA impurities in aspirin formulations. Recoveries from sera spiked with both ASA (2.5-50 micrograms ml-1) and SA (100-160 micrograms ml-1) varied from 99.5 to 106.7% (mean = 102.6%) and from 93.0 to 98.0% (mean = 95.8%), respectively. Recoveries of SA from spiked aspirin solutions (0.25-1.5 mg g-1 of aspirin) varied from 98.0 to 102.0% (mean = 100.3%).

  10. Combined embryotoxic action of toluene, a widely used industrial chemical, and acetylsalicylic acid (aspirin).

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    Ungváry, G; Tátrai, E; Lõrincz, M; Barcza, G

    1983-04-01

    CFY rats were exposed to inhalation of fresh air at days 10-13 of gestation; at day 12 the dams were given 0, 125, 250, 500, or 1,000 mg/kg acetylsalicylic acid (ASA) by gavage. During the same period of gestation (days 10-13) further groups of rats were exposed to toluene at 1,000, 2,000, and 3,600 mg/m3 atmospheric concentration and were given 250 mg/kg ASA by gavage; two subgroups of animals treated with 250 mg/kg ASA in combination with 3,600 mg/m3 toluene inhalation were given 0, 2.5, or 5 gm/kg glycine 2 hours before the ASA dose. At day 21 the animals were killed and examined for teratogenic effects and histological changes. After 48 hours toluene exposure other groups of rats were treated with ASA or with ASA plus glycine (administered 2 hours earlier) on day 20 of gestation. These animals were killed 2 hours later and the salicylic acid concentration in maternal and embryonic plasma and in amniotic fluid was measured by gas chromatography. With the rising ASA doses both maternal toxicity (increased mortality, decreased food consumption, and weight gain) and embryonic toxicity (postimplantation loss, increased incidence of weight-retarded fetuses, increased minor anomalies and malformations, decreased average weight of fetuses) increased. Toluene was found to potentiate the toxic effect of ASA and to increase both maternal and embryonic toxicity. The type of ASA-induced minor anomalies and malformations was also found to be altered under the effect of toluene pretreatment. By raising the toluene concentration the salicylic acid level in the maternal and embryonic plasma and in the amniotic fluid was increased above the expected concentration. The mechanism of the potentiating interaction should be looked for in the depletion of the glycine pool by toluene (and its metabolites) and in the resultant increase of salicylic acid level. Increasing ASA embryotoxicity caused by toluene can be warded off by glycine administration.

  11. 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.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

    Kristensen, David Møbjerg; Lesné, L.; Fol, V. Le

    2012-01-01

    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??m to 100??m. Similar results were obtained for aspirin (1?100??m) and indomethacin (10??m). The production of the other Leydig cell hormone, Insl3, was not disrupted by exposure...... 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...

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

    Science.gov (United States)

    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. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.

  15. Spherical agglomeration of acetylsalicylic acid

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    Polowczyk Izabela

    2016-01-01

    Full Text Available In this paper spherical agglomeration of acetylsalicylic acid was described. In the first step, the system of good and poor solvents as well as bridging liquid was selected. As a result of a preliminary study, ethyl alcohol, water and carbon tetrachloride were used as the good solvent, poor one, and bridging liquid, respectively. Then, the amount of acetylsalicylic acid and the ratio of the solvents as well as the volume of the bridging liquid were examined. In the last step, the agglomeration conditions, such as mixing intensity and time, were investigated. The spherical agglomerates obtained under optimum conditions could be subjected to a tableting process afterwards.

  16. Acetylsalicylic acid: Incoming 150 years of the first synthesis

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    Mijin Dušan Ž.

    2002-01-01

    Full Text Available Acetylsalicylic acid is one of the most fascinating and versatile drugs known to medicine, as well as one of the oldest. Acetylsalicylic acid is a drug which is safe, with analgetic, antirheumatic, anti-inflammatory antiplatelet and antithrombotic action. It may be applied not only in clinical practice, but also as prevention. The first known use of an acetylsalicylic acid-like preparation can be traced to ancient Greece. In 1853 Charles Gerhardt published the first synthesis of acetylsalicylic acid. Felix Hoffmann, a chemist for Friedrich Bayer, a German dye company obtained a patent on acetylsalicylic acid some 40 years later. Bayer coined the name Aspirin for the new product. The 20 in century was the century in which many researchers in many companies tried to improve the synthesis of acetylsalicylic acid not only in terms of yield but also purity. This paper describes the history, use, mechanism of action, synthesis and production as well as the purification and stability of acetylsalicylic acid.

  17. Simultaneous determination of salicylic acid and acetylsalicylic acid in aspirin delayed-release tablet formulations by second-derivative UV spectrophotometry.

    Science.gov (United States)

    Kokot, Z; Burda, K

    1998-12-01

    A rapid, simple assay procedure was developed for simultaneous analysis of aspirin (ASA) and salicylic acid (SA) in aspirin delayed-release tablet formulation by 'zero crossing' second-derivative UV spectrophotometry. The zero-order absorption spectra and second derivative spectra of ASA and SA were recorded in diluting solution acetonitrile-formic acid (99:1). The accuracy of the method was demonstrated by the determination of ASA and SA in five tablets formulations (each 20 tablets of the same batch) by the described method and by high performance liquid chromatographic method, and the results were in good agreement.

  18. 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

    Science.gov (United States)

    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.) effervescent tablet.

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

    Science.gov (United States)

    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. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Maternal use of acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy and risk of cryptorchidism

    DEFF Research Database (Denmark)

    Jensen, Morten Søndergaard; Rebordosa, Cristina; Thulstrup, Ane Marie

    2010-01-01

    Cyclooxygenase (COX) inhibitors-acetaminophen, ibuprofen and acetylsalicylic acid-have endocrine-disruptive properties in the rainbow trout. In humans, aspirin blocks the androgen response to human chorionic gonadotropin (hCG), and, because hCG-stimulated androgen production in utero is crucial...... for normal testicular descent, exposure to COX inhibitors at vulnerable times during gestation may impair testicular descent. We examined whether prenatal exposure to acetaminophen, ibuprofen, and acetylsalicylic acid was associated with increased occurrence of cryptorchidism....

  1. Burden of upper gastrointestinal symptoms in patients receiving low-dose acetylsalicylic acid for cardiovascular risk management

    DEFF Research Database (Denmark)

    Bytzer, Peter; Pratt, Stephen; Elkin, Eric

    2013-01-01

    Continuous low-dose acetylsalicylic acid (aspirin; ASA) is a mainstay of cardiovascular (CV) risk management. It is well established, however, that troublesome upper gastrointestinal (GI) symptoms are commonly experienced among low-dose ASA users.......Continuous low-dose acetylsalicylic acid (aspirin; ASA) is a mainstay of cardiovascular (CV) risk management. It is well established, however, that troublesome upper gastrointestinal (GI) symptoms are commonly experienced among low-dose ASA users....

  2. [Acetylsalicylic acid and prevention of preeclampsia].

    Science.gov (United States)

    Villa, Pia M; Kajantie, Eero; Laivuori, Hannele

    2014-01-01

    Two to six percent of all pregnant women develop preeclampsia. In the worst case its complications threaten the life of both the fetus and the mother. It seems that especially an early and severe preeclampsia diagnosed before 34 weeks of pregnancy can be prevented by using low-dose acetylsalicylic acid medication, which shall be started sufficiently early, not later than pregnancy week 16. Acetylsalicylic acid is safe during pregnancy at a daily dose of 100 mg. For the prevention of preeclampsia, it is worth considering for women who are at high risk of developing the disease.

  3. [Acetylsalicylic acid in the treatment of cardiovascular and cerebrovascular diseases].

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    Landmark, K

    1997-12-10

    This year acetylsalicylic acid (aspirin) celebrates its 100-year anniversary. While the drug was previously used mainly as an antipyretic and a pain-killer, aspirin has, during the last 10-15 years, become one of the most important agents in the treatment of cardiovascular and cerebrovascular diseases. In addition to being one of our oldest drugs, aspirin is one of the most interesting and widely used remedies. The antithrombotic property of aspirin is mainly related to its irreversible inhibition of the production of platelet-derived thromboxane A2, which possesses aggregatory and vasoconstrictive properties. Aspirin reduces the risk in patients with overt cardiovascular and cerebrovascular diseases, i.e. chronic stable and unstable angina pectoris. It also reduces the risk in the acute phase of and following a myocardial infarction and after a transient ischemic attack or stroke. The use of the drug is controversial in primary cardiovascular prevention. Overall mortality is not reduced, and side-effects, such as increased bleeding tendency, may be serious. This side-effect is dose-dependent, and smaller doses (75-160 mg) which have the same effect as higher doses should be preferred.

  4. [The forensic chemical investigation of acetylsalicylic acid].

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    Shormanov, V K; Chupak, V V; Pobedonstseva, M N; Maslov, S V; Kibets, N A; Tikhopoeva, N N

    2015-01-01

    The objective of the present study was to develop the universal approach to the quantitative determination of acetylsalicylic acid in biological tissues and fluids to be applied in the practice of forensic chemical expertise with the use of thin-layer chromatography, gas chromatography and mass spectrometry, low-pressure column chromatography, and spectrophotometry. A system of solvents consisting of acetone and ethyl acetate (7:3) was proposed as a universal agent for extracting acetylsalicylic acid from the cadaveric tissues and blood. It was shown that acetylsalicylic acid and its principal metabolite, salicylic acid, can be purified from the endogenous admixtures present in the biological materials by column chromatography on silica gel L 40/100 mcm. Salicylic acid in extracts from biological materials was identified and quantified with the use of thin-layer chromatography, gas chromatography/mass spectrometry, and electronic spectrophotometry. The method for forensic chemical investigation of acetylsalicylic acid has been developed and applied in the analysis of the material provided for expertise.

  5. Simultaneous determination of acetylsalicylic and salicylic acids by first derivative spectrometry in pharmaceutical preparations

    Science.gov (United States)

    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. Synthesis and transdermal properties of acetylsalicylic acid and selected esters

    OpenAIRE

    Gerber, Minja; Breytenbach, Jaco C.; Hadgraft, Jonathan; du Plessis, Jeanetta

    2006-01-01

    The primary aim of this study was to determine the transdermal penetration of acetylsalicylic acid and some of its derivatives, to establish a correlation, if any, with selected physicochemical properties and to determine if transdermal application of acetylsalicylic acid and its derivatives will give therapeutic drug concentrations with respect to transdermal flux. Ten derivatives of acetylsalicylic acid were prepared by esterification of acetylsalicyloyl chloride with ten different alcohols...

  7. Acetylsalicylic acid resistance risk factors in patients with myocardial infarction.

    Science.gov (United States)

    Stolarek, Wioleta; Kasprzak, Michał; Obońska, Karolina; Ostrowska, Małgorzata; Wiciński, Michał; Kubica, Aldona; Kubica, Jacek; Grześk, Grzegorz

    2015-10-01

    Despite its commonly recognized benefits in the cardiovascular disease setting, an issue of resistance to this drug has lately emerged. The aim of this research was assessment of the phenomenon of acetylsalicylic acid (ASA) resistance and its risk factors in patients treated for myocardial infarction. This study is a post-hoc analysis of a previous prospective study with approximately 200 patients treated for myocardial infarction with a coated formulation of ASA. The population was divided into two subgroups according to the response to ASA. ASA responsiveness was assessed using the arachidonic acid-dependent platelet aggregation (ASPI-test). The measurements were performed using the technique of impedance aggregometry. The prevalence of aspirin resistance among the study population was 6.2%. All analyzed aggregometric parameters (including ASPI-test, adenosine diphosphate dependent platelet aggregation - ADP-test, bleeding time measurement) showed significant differences between both subgroups. ASA resistant patients had higher concentrations of brain natriuretic peptide (BNP), high-sensitivity C-reactive protein (hs-CRP), leukocytes (WBC) and platelets (PLT) but lower concentrations of hemoglobin (HGB). The temporal point analysis for both subgroups showed aspirin resistance incidence peak in patients at 9 months after myocardial infarction. The prevalence of aspirin resistance in our study population is comparable with rates reported in literature among patients with cardiovascular diseases. There is a possible relation between aspirin resistance and clopidogrel resistance. Presence did not affect the incidence of the clinical end-points. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  8. Synthesis and transdermal properties of acetylsalicylic acid and selected esters.

    Science.gov (United States)

    Gerber, Minja; Breytenbach, Jaco C; Hadgraft, Jonathan; du Plessis, Jeanetta

    2006-03-09

    The primary aim of this study was to determine the transdermal penetration of acetylsalicylic acid and some of its derivatives, to establish a correlation, if any, with selected physicochemical properties and to determine if transdermal application of acetylsalicylic acid and its derivatives will give therapeutic drug concentrations with respect to transdermal flux. Ten derivatives of acetylsalicylic acid were prepared by esterification of acetylsalicyloyl chloride with ten different alcohols. The experimental aqueous solubility, logD and transdermal flux values were determined for acetylsalicylic acid and its derivatives at pH 4.5. In vitro penetration was measured through excised female human abdominal skin in diffusion cells. The experimental aqueous solubility of acetylsalicylic acid (6.56 mg/ml) was higher than that of the synthesised acetylsalicylate derivatives (ranging from 1.76 x 10(-3) to 3.32 mg/ml), and the logD of acetylsalicylic acid (-0.85) was lower than that of its derivatives (ranging from -0.25 to 1.95). There was thus an inverse correlation between the aqueous solubility data and the logD values. The experimental transdermal flux of acetylsalicylic acid (263.83 nmol/cm(2)h) was much higher than that of its derivatives (ranging from 0.12 to 136.02 nmol/cm(2)h).

  9. [Effect of ammonium succinate on pharmacological effects of acetylsalicylic acid].

    Science.gov (United States)

    Saratikov, A S; Bulatnikov, A P; Vengerovskiĭ, A I; Prishchep, T P; Sibileva, L A

    2000-01-01

    Ammonia succinate potentiates the main pharmacological properties and reduces the toxic effects (ulcerogenic action and general toxicity) of acetylsalicylic acid. The new preparation astam, representing a combination of acetylsalicylic acid with ammonia succinate in a 2:1 ratio, is proposed. Astam exhibits antiexudative, capillary-reinforcing, antiproliferative, pain-relieving, antipyretic, antiaggregant, and antioxidant properties. In addition, the drug inhibits the development of structural-metabolic disorders in the case of chronic immune inflammation of joints and various internal organs.

  10. Acetylsalicylic acid and acetaminophen protect against oxidative neurotoxicity.

    Science.gov (United States)

    Maharaj, H; Maharaj, D S; Daya, S

    2006-09-01

    Due to the implication of oxidative stress in neurodegenerative disorders we decided to investigate the antioxidant properties of acetylsalicylic acid and acetaminophen either alone or in combination. The thiobarbituric acid assay (TBA) and the nitroblue tetrazolium (NBT) assay were used to investigate quinolinic acid (QA)-induced: lipid peroxidation and superoxide anion generation in the rat hippocampus, in vivo. The study also shows, using cresyl violet staining, the preservation of structural integrity of neuronal cells following treatment with acetylsalicylic acid and acetaminophen in QA-lesioned rat hippocampus. Furthermore the study sought to determine whether these agents have any effect on endogenous (QA) formation. This study shows that acetylsalicylic acid and acetaminophen inhibit QA-induced superoxide anion generation, lipid peroxidation and cell damage, in vivo, in the rat hippocampus. In addition these agents inhibit the enzyme, 3-hydroxyanthranilic acid oxygenase (3-HAO), responsible for the synthesis of endogenous QA.

  11. Acetylsalicylic acid provides cerebrovascular protection from oxidant damage in salt-loaded stroke-prone rats.

    Science.gov (United States)

    Ishizuka, Toshiaki; Niwa, Atsuko; Tabuchi, Masaki; Ooshima, Kana; Higashino, Hideaki

    2008-03-26

    Inflammatory processes may play a pivotal role in the pathogenesis of cerebrovascular injury in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). Recent reports revealed that acetylsalicylic acid (aspirin) has anti-oxidative properties and elicits nitric oxide release by a direct activation of the endothelial NO synthase. The present study was designed to determine whether low-dose aspirin might prevent cerebrovascular injury in salt-loaded SHRSP by protecting oxidative damage. Nine-week-old SHRSP were fed a 0.4% NaCl or a 4% NaCl diet with or without treatment by naproxen (20 mg/kg/day), salicylic acid (5 mg/kg/day), or aspirin (5 mg/kg/day) for 5 weeks. Blood pressure, blood brain barrier impairment, mortality, and the parameters of cerebrovascular inflammation and damage were compared among them. High salt intake in SHRSP significantly increased blood brain barrier impairment and early mortality, which were suppressed by treatment with aspirin independent of changes in blood pressure. Salt loading significantly increased superoxide production in basilar arteries of SHRSP, which were significantly suppressed by treatment with aspirin. Salt loading also significantly decreased NOS activity in the basilar arteries of SHRSP, which were significantly improved by treatment with aspirin. At 5 weeks after salt loading, macrophage accumulation and matrix metalloproteinase-9 activity at the stroke-negative area in cerebral cortex of SHRSP were significantly reduced by treatment with aspirin. These results suggest that low-dose aspirin may exert protective effects against cerebrovascular inflammation and damage by salt loading through down-regulation of superoxide production and induction of nitric oxide synthesis.

  12. [Clopidogrel plus acetylsalicylic acid: a deadly combination

    NARCIS (Netherlands)

    Rongen, G.A.P.J.M.

    2013-01-01

    In the recently published SPS3 trial, clopidogrel plus aspirin increased mortality compared with aspirin alone in patients with lacunar cerebral infarcts. A detailed review of currently available trial data on this dual-antiplatelet strategy, having taken the between-trial variation in mortality in

  13. Determination of acetylsalicylic acid and salicylic acid in foods, using HPLC with fluorescence detection.

    NARCIS (Netherlands)

    Venema, D.P.; Hollman, P.C.H.; Janssen, P.L.T.M.K.; Katan, M.B.

    1996-01-01

    We developed a specific and sensitive HPLC method with fluorescence detection for the determination of free acetylsalicylic acid, free salicylic acid, and free salicylic acid plus salicylic acid after alkaline hydrolysis (free-plus-bound) in foods. Acetylsalicylic acid was detected after postcolumn

  14. In vitro teratogenicity of acetylsalicylic acid on rat embryos: studies with various culture conditions.

    Science.gov (United States)

    Cicurel, L; Schmid, B

    1986-04-01

    Rat embryos taken at day 9.5 of gestation were exposed in vitro to acetylsalicylic acid (aspirin) using various culture conditions. It was observed that embryos were sensitive to aspirin emulsified in olive oil at concentrations greater than or equal to 150 micrograms/ml. Between 43% and 66% of the embryos exhibited multiple malformations depending on the culture medium, 100% homologous rat serum or Waymouth medium supplemented with 50% rat serum, respectively. At concentrations greater than or equal to 400 micrograms/ml aspirin induced further toxic effects on embryo growth and differentiation. When gelatin was used as the drug-delivery system, aspirin at concentrations of greater than or equal to 150 micrograms/ml induced some malformations (mainly irregular somite shapes) in 57% of the embryos cultured in Waymouth medium, but in only 13% of the embryos grown in 100% serum. At concentrations which were greater than or equal to 400 micrograms/ml aspirin induced dysmorphogenic effects in all embryos, without any concomittant toxicity.

  15. Maternal use of acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy and risk of cryptorchidism.

    Science.gov (United States)

    Jensen, Morten Søndergaard; Rebordosa, Cristina; Thulstrup, Ane Marie; Toft, Gunnar; Sørensen, Henrik Toft; Bonde, Jens Peter; Henriksen, Tine Brink; Olsen, Jørn

    2010-11-01

    Cyclooxygenase (COX) inhibitors-acetaminophen, ibuprofen and acetylsalicylic acid-have endocrine-disruptive properties in the rainbow trout. In humans, aspirin blocks the androgen response to human chorionic gonadotropin (hCG), and, because hCG-stimulated androgen production in utero is crucial for normal testicular descent, exposure to COX inhibitors at vulnerable times during gestation may impair testicular descent. We examined whether prenatal exposure to acetaminophen, ibuprofen, and acetylsalicylic acid was associated with increased occurrence of cryptorchidism. Our study used data on 47,400 live-born singleton sons of mothers enrolled in the Danish National Birth Cohort during 1996-2002. Cryptorchidism was identified in 980 boys during childhood, of whom 565 underwent orchiopexy. The use of acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy was assessed in 3 computer-assisted telephone interviews and 1 self-administered questionnaire. We estimated adjusted hazard ratios (HRs) of cryptorchidism by Cox regression analysis. Exposure to acetaminophen during both the first and second trimesters was associated with increased occurrence of cryptorchidism (HR = 1.33 [95% confidence interval = 1.00-1.77]). Exposure for more than 4 weeks within the postulated time-window of programming testicular descent (gestational weeks 8-14) was associated with a HR of 1.38 (1.05-1.83) for cryptorchidism. Exposure to ibuprofen and acetylsalicylic acid was not associated with cryptorchidism. Maternal intake of acetaminophen for more than 4 weeks during pregnancy, especially during the first and second trimesters, may moderately increase the occurrence of cryptorchidism.

  16. Quantifying the Effects of Prior Acetyl-Salicylic Acid on Sepsis-Related Deaths: An Individual Patient Data Meta-Analysis Using Propensity Matching

    NARCIS (Netherlands)

    Trauer, James; Muhi, Stephen; McBryde, Emma S.; Al Harbi, Shmeylan A.; Arabi, Yaseen M.; Boyle, Andrew J.; Cartin-Ceba, Rodrigo; Chen, Wei; Chen, Yung-Tai; Falcone, Marco; Gajic, Ognjen; Godsell, Jack; Gong, Michelle Ng; Kor, Daryl; Lösche, Wolfgang; McAuley, Daniel F.; O'Neal, Hollis R.; Osthoff, Michael; Otto, Gordon P.; Sossdorf, Maik; Tsai, Min-Juei; Valerio-Rojas, Juan C.; van der Poll, Tom; Violi, Francesco; Ware, Lorraine; Widmer, Andreas F.; Wiewel, Maryse A.; Winning, Johannes; Eisen, Damon P.

    2017-01-01

    Objective: The primary objective was to conduct a meta-analysis on published observational cohort data describing the association between acetyl-salicylic acid (aspirin) use prior to the onset of sepsis and mortality in hospitalized patients. Study Selection: Studies that reported mortality in

  17. ON THE 125TH ANNIVERSARY OF ACETYLSALICYLIC ACID

    Directory of Open Access Journals (Sweden)

    I. N. Bokarev

    2011-01-01

    Full Text Available An experience of acetylsalicylic acid (ASA clinical use since its synthesis in 1887 is highlighted. ASA modes of action and its position among the modern antiplatelet agents are considered. The evidence based clinical data on ASA treatment and the problem of antiplatelet therapy resistance are discussed. ASA interaction with other drugs and ASA pleiotropic effects are reviewed 

  18. [Acetylsalicylic acid in primary prevention of cardiovascular events; literature study

    NARCIS (Netherlands)

    Bredie, S.J.H.; Wollersheim, H.C.H.; Verheugt, F.W.A.; Thien, Th.

    2002-01-01

    OBJECTIVE: To evaluate literature data on the use of acetylsalicylic acid (ASA) as a primary prevention measure for cardiovascular events. DESIGN: Literature search. METHOD: Using Medline, all randomised placebo-controlled trials of ASA published between 1985 and 1 May 2001, and which used

  19. Acetylsalicylic Acid Treatment Improves Differentiation and Immunomodulation of SHED

    OpenAIRE

    Liu, Y; Chen, C.; Liu, S.; Liu, D.; Xu, X.; Chen, X.; Shi, S

    2015-01-01

    Stem cells from exfoliated deciduous teeth (SHED) possess multipotent differentiation and immunomodulatory properties. They have been used for orofacial bone regeneration and autoimmune disease treatment. In this study, we show that acetylsalicylic acid (ASA) treatment is able to significantly improve SHED-mediated osteogenic differentiation and immunomodulation. Mechanistically, ASA treatment upregulates the telomerase reverse transcriptase (TERT)/Wnt/β-catenin cascade, leading to improvemen...

  20. ACETYLSALICYLIC ACID IN THE PREVENTION OF ATHEROTHROMBOTIC EVENTS

    Directory of Open Access Journals (Sweden)

    A. V. Govorin

    2012-01-01

    Full Text Available The results of large-scale clinical trials have convincingly demonstrated the effectiveness of acetylsalicylic acid (ASA in primary and secondary prevention of atherothrombotic events. Studies on the safety of different ASA formulations have been continuing. Magnesium hydroxide included in combined medicine, Сardiomagnil, prevents ASA adverse effects on the gastric mucosa and reduces in severity of dyspeptic symptoms.

  1. ACETYLSALICYLIC ACID IN THE PREVENTION OF ATHEROTHROMBOTIC EVENTS

    Directory of Open Access Journals (Sweden)

    A. V. Govorin

    2015-12-01

    Full Text Available The results of large-scale clinical trials have convincingly demonstrated the effectiveness of acetylsalicylic acid (ASA in primary and secondary prevention of atherothrombotic events. Studies on the safety of different ASA formulations have been continuing. Magnesium hydroxide included in combined medicine, Сardiomagnil, prevents ASA adverse effects on the gastric mucosa and reduces in severity of dyspeptic symptoms.

  2. Regulation on RhoA in vascular smooth muscle cells under inflammatory stimulation proposes a novel mechanism mediating the multiple-beneficial action of acetylsalicylic acid.

    Science.gov (United States)

    Li, Dong-Bo; Yang, Guo-Jie; Xu, Hong-Wei; Fu, Zhi-Xuan; Wang, Shan-Wei; Hu, Shen-Jiang

    2013-12-01

    Recent studies have revealed the additional beneficial effects of acetylsalicylic acid (aspirin) in the medication of cardiovascular diseases. The small GTPase RhoA as an important signaling factor is implicated in a wide range of cell functions. This study aimed to investigate the regulatory effect of acetylsalicylic acid on RhoA in vascular smooth muscle cells (VSMCs). We found that aspirin at 300 μM suppressed VSMCs proliferation stimulated by LPS, and this inhibitory effect was partially mediated by inhibiting the iNOS/NO pathway. RhoA overexpression was downregulated by aspirin (both 30 and 300 μM) because of enhanced degradation of RhoA protein. The effect of LPS on increasing active RhoA level was significantly attenuated by aspirin (300 μM), which exerted no effect on RhoA translocation. The promoted RhoA phosphorylation under LPS stimulation, coupled with RhoA protein expression, was greatly decreased by aspirin treatment. No effect of aspirin was found on the expression, activation, and phosphorylation of RhoA in VSMCs devoid of inflammatory stimulation. Our investigation indicates that the regulation of RhoA by aspirin in VSMCs under inflammatory stimulus could be a novel mechanism via which aspirin, apart from the COX-dependent action, exerted the multiple beneficial effects.

  3. Chemometrical exploration of an isotopic ratio data set of acetylsalicylic acid

    Energy Technology Data Exchange (ETDEWEB)

    Stanimirova, I. [ChemoAC, FABI, Analytical Chemistry and Pharmaceutical Technology, Vrije Universiteit Brussel-VUB, Laarbeeklaan 103, B-1090 Brussels (Belgium); Daszykowski, M. [ChemoAC, FABI, Analytical Chemistry and Pharmaceutical Technology, Vrije Universiteit Brussel-VUB, Laarbeeklaan 103, B-1090 Brussels (Belgium); Van Gyseghem, E. [Eurofins Scientific Analytics, Rue Pierre Adolphe Bobierre, 44323 Nantes Cedex 3 (France); Bensaid, F.F. [Eurofins Scientific Analytics, Rue Pierre Adolphe Bobierre, 44323 Nantes Cedex 3 (France); Lees, M. [Eurofins Scientific Analytics, Rue Pierre Adolphe Bobierre, 44323 Nantes Cedex 3 (France); Smeyers-Verbeke, J. [ChemoAC, FABI, Analytical Chemistry and Pharmaceutical Technology, Vrije Universiteit Brussel-VUB, Laarbeeklaan 103, B-1090 Brussels (Belgium); Massart, D.L. [ChemoAC, FABI, Analytical Chemistry and Pharmaceutical Technology, Vrije Universiteit Brussel-VUB, Laarbeeklaan 103, B-1090 Brussels (Belgium); Vander Heyden, Y. [ChemoAC, FABI, Analytical Chemistry and Pharmaceutical Technology, Vrije Universiteit Brussel-VUB, Laarbeeklaan 103, B-1090 Brussels (Belgium)]. E-mail: yvanvdh@vub.ac.be

    2005-11-03

    A data set consisting of fourteen isotopic ratios or quantities derived from such ratios for samples of acetylsalicylic acid (aspirin), commercialized by various pharmaceutical companies from different countries, was analyzed. The goal of the data analysis was to explore whether results can be linked to geographical origin or other features such as different manufacturing processes, of the samples. The methods of data analysis used were principal component analysis (PCA), robust principal component analysis (RPCA), projection pursuit (PP) and multiple factor analysis (MFA). The results do not seem to depend on geographic origin, except for some samples from India. They do depend on the pharmaceutical companies. Moreover, it seems that the samples from certain pharmaceutical companies form clusters of similar samples, suggesting that there is some common feature between those pharmaceutical companies. Variable selection performed by means of MFA showed that the number of variables can be reduced to five without loss of information.

  4. The stability and degradation kinetics of acetylsalicylic acid in different organic solutions revisited – an UHPLC–ESI-QTOF spectrometry study

    Directory of Open Access Journals (Sweden)

    Skibinski Robert

    2016-04-01

    Full Text Available Ultra high performance liquid chromatography (UHPLC, coupled with accurate quadrupole-time-of-flight (Q-TOF mass spectrometry, was used for the stability study of acetylsalicylic acid within a variety of different organic solutions: methanol, ethanol, propan-2-ol, acetonitrile, tetrahydrofuran and 1,4-dioxane. With the use of gradient elution chromatography and mass spectrometry detection in negative ionization, MS and MS/MS spectra were recorded simultaneously. In addition, quantitative, as well as qualitative analysis was performed during one assay. The stability of acetylsalicylic acid in such solutions was tested at room temperature, in a 12h period. In the work, in all cases, only one main degradation product, salicylic acid, was found. What is more, the work revealed that the degradation of aspirin in the tested organic solutions yields apparent second-order kinetics. The study also demonstrated that acetonitrile and 1,4-dioxane turned out to be the most stable solvents, and an above 80% of initial concentration of acetylsalicylic acid was found in this case. Furthermore, the most popular analytical solvents, methanol and ethanol, were found to be very unstable media. Herein, below 40% of initial concentration of acetylsalicylic acid was seen after 12h. The obtained results were also compared with the degradation of acetylsalicylic acid in a water solution. In this situation, only about 25% of the analyzed compound was resolved to salicylic acid in the same time frame.

  5. The effect of acetylsalicylic acid and meloxicamon hematological parameters in rats

    Directory of Open Access Journals (Sweden)

    Ćupić Vitomir

    2015-01-01

    Full Text Available In this work there was investigated the effect of two nonsteroidal antiinflammatory drugs (NSAIDs, acetylsalicylic acid or aspirin (nonselective cyclooxygenase inhibitor - COX1 i COX2 and meloxicam (selective cyclooxygenase inhibitor - COX2 on certain hematological parameters in rats. The objective of the work was to determine whether (and to which extent, these drugs, after multiple peroral application, influence erythrocyte number, concentration of hemoglobin, hematological indices (mean corpuscular value - MCV; mean concentration of hemoglobin in erythrocytes - MCH; mean corpuscular hemoglobin concentration - MCHC, hematocrit, number of platelets, leukocytes, neutrophilic leukocytes, lymphocytes and monocytes. The experiment was conducted in in vivo conditions on 70 clinically healthy Wistar strain male rats, 10 to 12 weeks of age and body weight 250 to 300 g. The rats were divided into seven groups and they were daily perorally (by probe given aspirin (ASCOPIR at doses of 30, 40 and 80 mg/kg b.m. (I, II and III groups, or meloxicam (METACAM at doses of 100, 125 and 250 μg/kg b.m. (IV, V and VI groups, for seven days. The seventh group was a control one and they were given only saline. The obtained results showed that: acetylsalicylic acid in maximum dose tested (80 mg/kg b.m. statistically significantly reduced the number of platelets (p<0,05, the number of leukocytes (p<0,05, the number of lymphocytes (p<0,05 and the number of monocytes (p<0,05, while on the other side, meloxicam in maximum dose tested (250 μg/kg, statistically significantly reduced the mean corpuscular value (MCV, and increased the number of platelets (p<0,05, relative to the control value.

  6. Immunogenicity of aryl esters of salicylic or acetylsalicylic acid in guinea pigs.

    Science.gov (United States)

    Schlumberger, H D

    1975-01-01

    A variety of derivatives of acetylsalicylic and salicylic acid have been investigated for their immunogenic properties in guinea pigs including salicylsalicylic acid (SSA), acetylsalicylsalicylic acid (ASSA), disalicylide (DI), trisalicylide (TRI), acetylsalicylic acid paracetamol ester (ASPE) and acetylsalicylic acid guajacol ester (ASGE). Contact sensitivity could be elicited by the sensitizing agent, however, with acetylsalicylic acid anhydride (ASAN) a more pronounced contact reaction could consistently be observed. Systemic anaphylactic reactions elicited by intravenous injection of N-salicyloyl bovine serum albumin could only be induced by ASAN, DI, TRI and ASSA, whereas SSA, ASPE and ASGE did not induce an anaphylactic state at a comparable dose level. From these results it is anticipated that all aryl esters of acetylsalicylic or salicylic acid are immunogenic when applied intradermally, leading to a N-salicyloyl specific immune response.

  7. Simultaneous determination of acetylsalicylic acid and caffeine in pharmaceutical formulation by first derivative synchronous fluorimetric method.

    Science.gov (United States)

    Karim, Mohammad Mainul; Jeon, Chi Wan; Lee, Hyun Sook; Alam, Seikh Mafiz; Lee, Sang Hak; Choi, Jong Ha; Jin, Seung Oh; Das, Ajoy Kumar

    2006-09-01

    A sensitive, rapid, and specific assay has been developed for the simultaneous determination of acetylsalicylic acid and caffeine in commercial tablets based on their natural fluorescence. The mixture of these drugs was resolved by first derivative synchronous fluorimetric technique using two scans. At Deltalambda=106 nm, using first derivative synchronous scanning, only acetylsalicylic acid yields a detectable signal at 316 nm (peak to zero method) which is unaffected by caffeine. At Deltalambda=30 nm, the signal of caffeine at 288 nm (peak to zero method) is not affected by acetylsalicylic acid. The range of application is between 0.021 and 41.62 microg ml(-1) (correlation coefficient, R=0.9995) for acetylsalicylic acid and between 0.4486 and 44.86 microg ml(-1) (correlation coefficient, R=0.99786) for caffeine. The recovery range of 98.40-102% for acetylsalicylic acid and 90-100.5% for caffeine from their synthetic mixture was reported. Overall recovery of both compounds about 97-99% for acetylsalicylic acid and 97-98% for caffeine was obtained from real sample analysis. The detection limits are 0.0013 microg ml(-1) and 0.0306 microg ml(-1) for acetylsalicylic acid and caffeine, respectively. The relative standard deviation (n=10) for 20 microg ml(-1) of acetylsalicylic acid is 2.75% and for 2.2 microg ml(-1)of caffeine is 1.7%.

  8. [Clarification on publications concerning the synthesis of acetylsalicylic acid].

    Science.gov (United States)

    Lafont, O

    1996-01-01

    Charles Frédéric Gerhardt (1816-1856) mentioned in his Traité de chimie Organique (1854) a publication, in French (realized in 1852 but published in 1853) entitled "Researches on anhydrous organic acids" in which, was reported the reaction of sodium salicylate with acetyl chloride. He thought that the reaction product was an acid anhydride, but obtained really crude acetylsalicylic acid. Later on, but also in 1853, a publication in german, by the same author related the same experiments. Surprisingly only the second publication has been mentioned in most of the historical studies on the subject. Acetyl salicylic acid was identified and synthesised in 1859 by von Gilm by another method and the product obtained by Gerhardt was identified to it in 1869.

  9. Thermodynamics of inclusion complexes of natural and modified cyclodextrins with acetylsalicylic acid and ibuprofen in aqueous solution at 298 K

    Energy Technology Data Exchange (ETDEWEB)

    Castronuovo, Giuseppina, E-mail: giuseppina.castronuovo@unina.it [Department of Chemistry, University Federico II of Naples, Complesso Universitario a Monte S. Angelo, via Cintia, 80126 Naples (Italy); Niccoli, Marcella [Department of Chemistry, University Federico II of Naples, Complesso Universitario a Monte S. Angelo, via Cintia, 80126 Naples (Italy)

    2013-04-10

    Graphical abstract: Complexation forces acting in the association between natural and modified α- and β-cyclodextrins and acetylsalicylic acid (aspirin) or ibuprofen are examined through the analysis of the thermodynamic parameters obtained by isothermal calorimetry. Highlights: ► A calorimetric method is reported to study the association of natural and substituted cyclodextrins with acetylsalicylic acid and ibuprofen. ► The study aims to propose a hypothesis about the forces involved in the interaction. That can be useful for designing new cyclodextrins having suitable characteristics to include specific drugs. ► Enthalpic and entropic contributions on the association are discussed. The differences in the cavity dimensions of the cyclodextrins determine the values of the thermodynamic properties to be very different. - Abstract: Thermodynamic parameters for the association of natural and substituted α-, β-, and γ-cyclodextrins with acetylsalicylic acid, salicylic acid and ibuprofen have been determined by isothermal titration calorimetry. Analysis of the data shows that complexes form, all having 1:1 stoichiometry. The shape-matching between the host and guest is the factor determining the values of the thermodynamic quantities. In the case of the smallest cyclodextrin interacting with acetylsalicylic acid and salicylic acid, the parameters indicate that hydrophobic interactions play the major role. Association occurs through the shallow inclusion of the benzene ring into the cavity. In the case of substituted β-cyclodextrins, instead, inclusion of the benzene ring is deeper and the tight fitting of the guest molecule to the cavity makes the enthalpy and entropy to be both negative. Ibuprofen interacts through its isobutyl group: the values of the association constants are very high for β-cyclodextrins as determined by the large and positive entropies due to the relaxation of water molecules from the cavity and the hydration spheres of the interacting

  10. Aspirin: yesterday, today, and tomorrow

    OpenAIRE

    Marina Nikołajewna Dołżenko

    2014-01-01

    Clinical utility of aspirin (acetylsalicylic acid, ASA) is one of the more important issues in the primary and secondary prevention of cardiovascular disease. The present paper provides analysis of aspirin history, mechanisms of its antiplatelet activity, and expediency of the use of low- and high-dose aspirin in the groups including patients after myocardial revascularization, and requiring secondary prevention of stroke. Also gender-specific aspirin properties were mentioned, hi...

  11. Central effects of acetylsalicylic acid on trigeminal-nociceptive stimuli.

    Science.gov (United States)

    Kröger, Inga L; May, Arne

    2014-09-09

    Acetylsalicylic acid is one of the most used analgesics to treat an acute migraine attack. Next to the inhibitory effects on peripheral prostaglandin synthesis, central mechanisms of action have also been discussed. Using a standardized model for trigeminal-nociceptive stimulation during fMRI scanning, we investigated the effect of acetylsalicylic acid on acute pain compared to saline in 22 healthy volunteers in a double-blind within-subject design. Painful stimulation was applied using gaseous ammonia and presented in a pseudo-randomized order with several control stimuli. All participants were instructed to rate the intensity and unpleasantness of every stimulus on a VAS scale. Based on previous results, we hypothesized to find an effect of ASA on central pain processing structures like the ACC, SI and SII as well as the trigeminal nuclei and the hypothalamus. Even though we did not find any differences in pain ratings between saline and ASA, we observed decreased BOLD signal changes in response to trigemino-nociceptive stimulation in the ACC and SII after administration of ASA compared to saline. This finding is in line with earlier imaging results investigating the effect of ASA on acute pain. Contrary to earlier findings from animal studies, we could not find an effect of ASA on the trigeminal nuclei in the brainstem or within the hypothalamic area. Taken together our study replicates earlier findings of an attenuating effect of ASA on pain processing structures, which adds further evidence to a possibly central mechanism of action of ASA.

  12. Acidosis, magnesium and acetylsalicylic acid: Effects on thrombin

    Science.gov (United States)

    Borisevich, Nikolaj; Loznikova, Svetlana; Sukhodola, Aleksandr; Halets, Inessa; Bryszewska, Maria; Shcharbin, Dzmitry

    2013-03-01

    Thrombin, an enzyme from the hydrolase family, is the main component of the blood coagulation system. In ischemic stroke it acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin forming blood clots in the brain. It has been found to phosphoresce at room temperature in the millisecond and microsecond ranges. The phosphorescence of thrombin was studied under physiological conditions, in acidosis (decrease of pH from 8.0 to 5.0) and on the addition of salts (magnesium sulfate and sodium chloride) and of acetylsalicylic acid, and its connection with thrombin function is discussed. Acidosis significantly increased the internal dynamics of thrombin. We propose that lactate-acidosis plays a protective role in stroke, preventing the formation of clots. The addition of NaCl and MgSO4 in different concentrations increased the internal dynamics of thrombin. Also, the addition of MgSO4 decreased thrombin-induced platelet aggregation. However, magnesium sulfate and acetylsalicylic acid in the therapeutic concentrations used for treatment of ischemic stroke had no effect on thrombin internal dynamics. The data obtained will help to elucidate the conformational stability of thrombin under conditions modulating lactate-acidosis and in the presence of magnesium sulfate.

  13. Aspirin in pregnancy : clinical and biochemical studies

    NARCIS (Netherlands)

    H.A. Bremer (Henk)

    1994-01-01

    textabstractAspirin, acetylsalicylic acid, is the most frequently consumed drug in pregnancy,47 mostly taken without a prescription because of headache or a minor ailment. 226,277 Numerous preparations containing acetylsalicylic acid are freely available over the counter under a variety of

  14. Vanadocene reactions with hydroxy acids. [Hydroxy acids: acetylsalicylic, gallic, lactic, salicyclic, orotic,. gamma. -hydroxybutyric acids

    Energy Technology Data Exchange (ETDEWEB)

    Latyaeva, V.N.; Lineva, A.N.; Zimina, S.V.; Ehllert, O.G.; Arsen' eva, T.I. (Gor' kovskij Meditsinskij Inst. (USSR))

    1984-03-01

    To prepare a series of vanadium cyclopentadienylcarboxylates soluble in water, the vanadocene reactions with lactic, ..gamma..-oxybutyric-, salicylic,- gallic-, orotic-, and acetylsalicylic acids have been studied. To determine the influence of cyclopentadienyl groups, bound with a vanadium atom, on the physiological activity of the complexes formed, vanadium halides are made to react with lactic acid. Only the vanadocene reaction with orotic acid was conducted in an aqueous medium, other interactions were realized in the diethyl ether, toluene, T, H, P medium. The interaction of vanadocene and vanadium halides with lactic-, salicylic-, acetylsalicylic- and gallic acids was found to lead to the formation of water-soluble vanadium complexes of Cp/sub 2/, VOCOR or CpV (OCOR)/sub 2/ type. The data on the produced compounds yield, their IR spectra, decomposition temperatures, solubility, effective magnetic moments are presented.

  15. Dissolution test of various low-dose acetylsalicylic acid preparations marketed in Indonesia

    Directory of Open Access Journals (Sweden)

    Yeyet C. Sumirtapura

    2009-09-01

    Full Text Available Aim To compare the dissolution profi les of various enteric-coated low-dose acetylsalicylic acid (ASA tablets marketed in Indonesia.Methods The dissolution study was carried out according to US Pharmacocopoeiae (USP /European Pharmacopoeiae, method A, using USP apparatus 1 (basket 100 rpm, with 2 media: 0.1 N HCl, 120 minutes for acid stage, and phosphate buffer pH 6.8, 90 minutes for buffer stage. The sampling points were 120 minutes for the acid stage, and every 10 minutes until 90 minutes for the buffer stage. The acetylsalicylic acid was assayed using spectrophotometry at 280 nm for the acid stage, and at 265 nm for the buffer stage. The free salicylic acid was determined only at the end of the buffer stage with HPLC method. There were 6 test products (Cardio Aspirin® 100 mg, Aptor® 100 mg, Ascardia® 80 mg, Thrombo Aspilet® 80 mg, Astika® 100 mg and Farmasal® 100 mg, 3 batches for each product, and 6 units for each batch.Results The amount of ASA released from each ASA product tested at the end of acid stage (120 minutes ranged from 1.79% for Cardio Aspirin® to 6.92% for Thrombo Aspilet®, all conformed to the compendial requirement for enteric-coated product (< 10%. The amount of salicylic acid observed at the end of the dissolution test ranged from 3.47% for Cardio Aspirin® to 10.90% for Astika® and 11.90 % for Thrombo Aspilet®. Thrombo Aspilet® showed sustained-release properties, causing high variability in ASA release, such that one of the 3 batches tested did not fulfill the compendial requirement of more than 75% (the release was only 55.11%. High variability in ASA release between batches was also found with Farmasal® at 10, 20, and 30 minutes in buffer medium. The lowest effective dose of ASA as an antiplatelet drug for longterm use is 75 mg of plain ASA, and this is equivalent to 100 mg of enteric-coated ASA.Conclusions All of the low-dose ASA preparations marketed in Indonesia are enteric-coated products

  16. Acetylsalicylic acid treatment improves differentiation and immunomodulation of SHED.

    Science.gov (United States)

    Liu, Y; Chen, C; Liu, S; Liu, D; Xu, X; Chen, X; Shi, S

    2015-01-01

    Stem cells from exfoliated deciduous teeth (SHED) possess multipotent differentiation and immunomodulatory properties. They have been used for orofacial bone regeneration and autoimmune disease treatment. In this study, we show that acetylsalicylic acid (ASA) treatment is able to significantly improve SHED-mediated osteogenic differentiation and immunomodulation. Mechanistically, ASA treatment upregulates the telomerase reverse transcriptase (TERT)/Wnt/β-catenin cascade, leading to improvement of SHED-mediated bone regeneration, and also upregulates TERT/FASL signaling, leading to improvement of SHED-mediated T-cell apoptosis and ameliorating disease phenotypes in dextran sodium sulfate-induced colitis mice. These data indicate that ASA treatment is a practical approach to improving SHED-based cell therapy. © International & American Associations for Dental Research 2014.

  17. [Haemorrhagic exanthema due to dengue virus induced by acetylsalicylic acid].

    Science.gov (United States)

    Valerio, L; de Balanzó, X; Jiménez, O; Pedro-Bolet, M L

    2006-01-01

    Dengue fever, a viral infectious disease characteristic of tropical climates, is considered to be a re-emergent pathology responsible for several serious outbreaks in the last decade. Some factors have been involved in the spread of the virus and its vectorial mosquito carrier: human alteration of the ecosystems, improvement and speed in the transit of goods and people and climate changes. As a reflection of this, an increase in imported cases is probable, especially in tourists coming from endemic areas, considering its short period of incubation (7-10 days). The recognition of personal antecedents of journeys, the main symptoms of the disease and the potential presence of complications (haemorrhagic dengue) should be included in the examination of fever of unknown origin or feverish exanthema. The case of a patient is presented whose clinical picture of classic dengue fever was worsened by self-treatment with acetylsalicylic acid.

  18. EFFECT OF ACETYLSALICYCLIC ACID (ASPIRIN ) AND ...

    African Journals Online (AJOL)

    LIVINGSTON

    Aspirin as such, irreversibly blocks the enzyme cyclo-oxygenase (prostaglandin synthase) which catalyzes the conversion of. Archidonic acid to endoperoxide compounds. In addition to reducing the synthesis of eicosanoid mediators, ASA also interferes with the chemical mediators of the kalikrein system. As a result, aspirin ...

  19. Solvation and hydration characteristics of ibuprofen and acetylsalicylic acid.

    Science.gov (United States)

    Perlovich, German L; Kurkov, Sergey V; Kinchin, Andrey N; Bauer-Brandl, Annette

    2004-01-26

    Ibuprofen and acetylsalicylic acid were studied by thermoanalytical methods: sublimation calorimetry, solution calorimetry, and with respect to solubility. Upon measuring the temperature dependences of the saturated vapor pressure, enthalpies of sublimation, DeltaH(0) (sub), as well as the entropies of sublimation, DeltaS(0) (sub), and their respective relative fractions in the total process were calculated. The Gibbs energy of solvation in aliphatic alcohols as well as the enthalpic and entropic fractions thereof were also studied and compared with the respective properties of model substances and other nonsteroidal antiinflammatory drugs (benzoic acid, diflunisal, flurbiprofen, ketoprofen, and naproxen). In all cases, enthalpy was found to be the driving force of the solvation process. Correlations were derived between Gibbs energy of solvation in octanol, DeltaG(Oct) (solv), and the transfer Gibbs energy from water to octanol, DeltaG(0) (tr). Influence of mutual octanol and water solubilities on the driving force of partitioning is discussed. An enthalpy-entropy-compensation effect in octanol was observed, and consequences of deviation from the general trend are also discussed.

  20. Inhibition of isotretinoin teratogenicity by acetylsalicylic acid pretreatment in mice.

    Science.gov (United States)

    Kubow, S

    1992-01-01

    Although isotretinoin (ITR) has been suggested to cause malformations via cytopathic effects on embryonic cells, the molecular mechanisms of ITR cytotoxicity in teratogenesis are not clear. Since ITR undergoes metabolism by prostaglandin synthase to a potentially cytotoxic peroxyl free radical, the possible role of prostaglandin synthase metabolism as a modulator of ITR teratogenicity was evaluated. Craniofacial and limb abnormalities were noted in fetuses on day 18.5 of gestation following administration of ITR to pregnant CD-1 mice in a three dose regimen of 100 mg/kg at 4 hr intervals on day 10.5 of gestation (plug day = day 0.5 of gestation). Mice were also treated with acetylsalicylic acid (ASA), an irreversible inhibitor of the cyclooxygenase component of prostaglandin synthase, at doses of 20 and 60 mg/kg body weight 2 hr prior to each ITR dose. ASA pretreatment of mice receiving ITR treatment showed a dose-dependent decrease in the overall incidence of malformations, number of defects per fetus, and the incidence of specific craniofacial and limb defects. Equivalent doses of ASA given to control mice did not cause malformations or alter the incidence of resorptions. These results demonstrate that ASA is able to ameliorate the teratogenic effects of ITR observed in fetal mice near term and indicate that prostaglandin metabolism could play a mechanistic role in ITR teratogenicity.

  1. Prevention of small black spots on sugar-coated tablets containing aluminum acetylsalicylic acid.

    Science.gov (United States)

    Tomida, Y; Makino, T

    1999-04-01

    Sugar-coated tablets containing aluminum acetylsalicylate gradually developed black spots on their surface. A factorial experiment was performed based on an L32 orthogonal array table in an attempt to halt this phenomenon. The factor responsible proved to be talc used to formulate the smooth coating layer over the subcoating layer containing aluminum acetylsalicylate. When HCl-treated talc was used as a filler for the smoothing layer, the black spots were markedly decreased. The spotting mechanism was considered to be due to hydrolysis of aluminum acetylsalicylate in the subcoating layer to salicylic acid and acetic acid, which sublimated into the pores of the smoothing layer. Then, ferrous ion substituted from magnesium ion in the talc molecule center was extracted by salicylic acid, acetic acid, and moisture. Finally, the ferrous ion was oxidized to ferric ion, and this produced an Fe3+ chelate compound together with salicylic acid.

  2. Acetylsalicylic acid regulates overexpressed small GTPase RhoA in vascular smooth muscle cells through prevention of new synthesis and enhancement of protein degradation.

    Science.gov (United States)

    Li, Dong-Bo; Fu, Zhi-Xuan; Ruan, Shu-Qin; Hu, Shen-Jiang; Li, Xia

    2012-04-01

    RhoA has been shown to play a major role in vascular processes and acetylsalicylic acid (aspirin) is known to exert a cytoprotective effect via multiple mechanisms. In the present study, we aimed at investigating the effect of aspirin on RhoA expression under a stress state in rat VSMCs (vascular smooth muscle cells) and the underlying mechanisms. The expression of iNOS (inducible nitric oxide synthase) and iNOS activity as well as NO concentration was significantly promoted by LPS (lipopolysaccharide) accompanying the elevation of RhoA expression, which was blocked by the addition of the iNOS inhibitor L-NIL [L-N6-(1-iminoethyl)lysine dihydrochloride]. Aspirin (30 μM) significantly attenuated the elevation of RhoA, while indomethacin and salicylate had no similar effect. The sGC (soluble guanylate cyclase) inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) showed the same effect as aspirin in down-regulating RhoA but was reversed by the addition of the cGMP analogue 8-Br-PET-cGMP (β-phenyl-1,N2-ethano-8-bromoguanosine 3',5'-cyclic monophosphorothioate). 8-Br-PET-cGMP solely enhanced the RhoA expression that was abrogated by preincubation with aspirin. Degradation analysis indicated that aspirin enhanced the protein degradation rate of RhoA and GDP-bound RhoA seemed to be more susceptible to aspirin-enhanced degradation compared with the GTP-bound form. Our results indicate that aspirin attenuates the LPS-induced overexpression of RhoA both by inhibiting new synthesis and accelerating protein degradation, which may help elucidate the multiple beneficial effects of aspirin.

  3. Acetylsalicylic acid and labeling of blood constituents with technetium-99m

    Energy Technology Data Exchange (ETDEWEB)

    Fonseca, Adenilson de Souza da [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Dept. de Farmacologia e Psicobiologia; Frydman, Jacques Natan Grinapel; Rocha, Vanessa Camara da; Bernardo-Filho, Mario [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Dept. de Biofisica e Biometria

    2005-10-15

    Acetylsalicylic acid is the drug most used an anti-inflammatory agent and for secondary prevention of thrombotic phenomenon. Drugs can modify the labeling of blood constituents with technetium-99m (99m Tc). The aim of this work was to evaluate the effect of in vitro or in vivo assays with acetylsalicylic acid on the labeling of the blood constituents with 99m Tc. In vitro assay was performed with samples of whole blood from Wistar rats incubated with acetylsalicylic acid (1.0 mg/ml) for one hour before the 99m Tc-labeling process. For in vivo assay, Wistar rats were treated with acetylsalicylic acid (1.5 mg/kg) during one hour, and the whole blood was withdrawn for the 99m Tc-labeling process. Saline was used in control groups. Data showed that the fixation of 99m Tc to the blood constituents was not significantly (p>0.05) modified in in vitro and in vivo assays with acetylsalicylic acid, at least not when the experiments were carried out with the doses normally used in human beings. (author)

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

    Science.gov (United States)

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

    2015-05-01

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

  5. Antioxidative properties of acetylsalicylic Acid on vascular tissues from normotensive and spontaneously hypertensive rats.

    Science.gov (United States)

    Wu, Rong; Lamontagne, Daniel; de Champlain, Jacques

    2002-01-22

    The mechanisms of the beneficial cardiovascular effects of acetylsalicylic acid (ASA, aspirin) therapy are not completely understood. Oxidative stress and inflammation play important roles in the development of cardiovascular diseases. In this study, we tested the hypothesis that ASA treatment could reduce superoxide anion (O(2)(-)) generation in aortic ring and in cultured aortic smooth muscle cells (SMCs) from normotensive (WKY) and hypertensive (SHRs) rats by means of the Lucigenin-enhanced chemiluminescence method. Although ASA did not show any short-term effect in vitro and in vivo, long-term oral treatment (100 mg/kg/day, 12 days) significantly reduced the basal O(2)(-) production by 27% and 45% in aorta of normotensive and hypertensive rats, respectively, in association with a reduction of the NAD(P)H oxidase activity in both groups. These effects were dose-dependent from 10 to 100 mg/kg/day. Similar effects were observed in SMCs following long-term incubation (48 hours) with ASA. ASA treatment also completely inhibited the angiotensin II-induced hypertension and O(2)(-) production. Moreover, ASA treatment significantly improved the impaired aortic relaxation response to acetylcholine and markedly attenuated the age-dependent development of hypertension in SHRs. Long-term ASA treatment in vivo markedly reduced vascular O(2)(-) production through lowering the NAD(P)H oxidase activity in both normotensive and hypertensive rats. These antioxidative properties of ASA are likely involved in the restoration of aortic vasorelaxation, in the attenuation of the development of hypertension in young SHRs, and in the prevention of hypertension following long-term angiotensin II infusion.

  6. Antibacterial activity of dipeptide constructs of acetylsalicylic acid and nicotinic acid.

    Science.gov (United States)

    Bartzatt, Ronald; Cirillo, Suat L G; Cirillo, Jeffrey D

    2007-02-01

    Two dipeptide drugs are synthesized utilizing an acetylsalicylic acid or nicotinic acid molecule for the framework. A D-alanine-D-alanine dipeptide moiety is attached to the carbonyl carbon of acetylsalicylic acid (I) and nicotinic acid (II). Dipeptide derivatives (I) and (II) showed significant reduction of Escherichia coli (E. coli) bacterial growth and colony-forming units. A mixture of (I) and (II) induced growth inhibition of 8%, 17.5%, 28%, and 42.5% at concentrations of 100, 200, 300, and 400 microg/mL, respectively. Ampicillin demonstrated much less growth inhibition of this penicillin-resistant E. coli bacteria. Derivatives (I) and (II) showed significant reduction of colony-forming units at concentrations higher than 200 microg/mL, whereas ampicillin showed no significant affect on colony-forming units. Both (I) and (II) produced no violations of the Rule of 5, indicating favorable characteristics for bioavailability. Molecular properties were determined and showed (I) to have a Log Kow of -0.22 with aqueous solubility of 683.8 mg/L, whereas (II) had a Log Kow of -1.00 and aqueous solubility of 6859 mg/L. A mixture of the parent compounds acetyl salicylic acid and nicotinic acid demonstrated some antibacterial activity.

  7. Use and Safety of Non-Steroidal Inflammatory Drugs and Aspirin

    NARCIS (Netherlands)

    V.E. Valkhoff (Vera)

    2012-01-01

    textabstractThe use of acetylsalicylic acid, better known as aspirin, dates back to the Egyptians in 1534 BC. Aspirin-like compounds are naturally derived from willow tree bark and myr-tle. At the end of the 19th century aspirin was patented by Bayer as the world’s first syn-thetic drug. The

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Low-dose acetylsalicylic acid (ASA) is widely used as antithrombotic prophylaxis. Enteric coated ASA has been developed in order to decrease the risk of gastrointestinal side effects. The consequences of enteric coating on pharmacokinetics and antiplatelet effect of ASA have not systematically be....... Therefore, low dose enteric coated ASA might not be bioequivalent to plain ASA, entailing the risk of insufficient cardiovascular prophylaxis....

  9. ACETYLSALICYLIC ACID IN LOW DOSES FOR SECONDARY PREVENTION OF CARDIO-VASCULAR COMPLICATIONS

    Directory of Open Access Journals (Sweden)

    N. A. Dmitrieva

    2009-01-01

    Full Text Available Data of evidence based medicine which confirm efficacy of acetylsalicylic acid (ACA in cardiologic practice are presented. The special attention is given to generic drugs of ACA. Their application has increased essentially recently. Some of generics are comparable with original drugs on clinical efficacy but have economic advantages.

  10. Synovial distribution of ?systemically? administered acetylsalicylic acid in the isolated perfused equine distal limb

    OpenAIRE

    Friebe, Maren; Schumacher, Stephan; Stahl, Jessica; Kietzmann, Manfred

    2013-01-01

    Background This study investigated synovial concentrations of acetylsalicylic acid (ASA) and its metabolite salicylic acid (SA) in the equine fetlock joint following systemic administration of ASA. Salicylates were chosen because SA is the only nonsteroidal anti-inflammatory drug for which threshold levels exist for plasma and urine in equine sports. To avoid animal experiments, the study was conducted using an ex vivo model of the isolated perfused equine distal limb in combination with plas...

  11. COST-EFFECTIVENESS OF APIXABAN AS COMPARED WITH WARFARIN AND ACETYLSALICYLIC ACID IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION IN THE RUSSIAN FEDERATION

    Directory of Open Access Journals (Sweden)

    A. V. Rudakova

    2015-09-01

    -adjusted life year (QALY gained and corresponded to the three times GDP per capita in 2013 in the Russian Federation. Sensitivity analysis explored the impact of the treatment discontinuation rates, patients’ age and quality of INR monitoring on the cost-effectiveness of apixaban.Results. In the base case analysis it was demonstrated that apixaban as compared with warfarin and acetylsalicylic acid provided additional 0.187 and 0.255 life years as well as additional 0.187 and 0.214 QALYs respectively. Over lifetime horizon apixaban as compared with warfarin and aspirin required additional treatment costs equal to 112.72 and 101.35 thousands rubles, respectively. With that estimated incremental cost-effectiveness ratio for apixaban as compared with warfarin and acetylsalicylic acid was 603.92 and 473.02 thousands rubles per QALY respectively. The results were robust in sensitivity analysis.Conclusions. Apixaban is expected to be a cost-effective alternative to warfarin and acetylsalicylic acid in patients with NVAF from the Russian Federation national health care system perspective. Apixaban may be recommended for inclusion into formulary reimbursement lists as an alternative to warfarin.

  12. COST-EFFECTIVENESS OF APIXABAN AS COMPARED WITH WARFARIN AND ACETYLSALICYLIC ACID IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION IN THE RUSSIAN FEDERATION

    Directory of Open Access Journals (Sweden)

    A. V. Rudakova

    2014-01-01

    -adjusted life year (QALY gained and corresponded to the three times GDP per capita in 2013 in the Russian Federation. Sensitivity analysis explored the impact of the treatment discontinuation rates, patients’ age and quality of INR monitoring on the cost-effectiveness of apixaban.Results. In the base case analysis it was demonstrated that apixaban as compared with warfarin and acetylsalicylic acid provided additional 0.187 and 0.255 life years as well as additional 0.187 and 0.214 QALYs respectively. Over lifetime horizon apixaban as compared with warfarin and aspirin required additional treatment costs equal to 112.72 and 101.35 thousands rubles, respectively. With that estimated incremental cost-effectiveness ratio for apixaban as compared with warfarin and acetylsalicylic acid was 603.92 and 473.02 thousands rubles per QALY respectively. The results were robust in sensitivity analysis.Conclusions. Apixaban is expected to be a cost-effective alternative to warfarin and acetylsalicylic acid in patients with NVAF from the Russian Federation national health care system perspective. Apixaban may be recommended for inclusion into formulary reimbursement lists as an alternative to warfarin.

  13. Pharmacological Correction of the Negative Effect of Acetylsalicylic Acid on the Energy-Generating System

    Directory of Open Access Journals (Sweden)

    Vladimir V. Udut, ScD

    2012-03-01

    Full Text Available The present paper demonstrates the effect of ASA and its combination with SUC on the energy-producing system of rat heart mitochondria as well as an assessment of SUC preventive application effect on ASA pharmacokinetic parameters. Experiments conducted on outbred male albino rats (200-250 g on a model of a xenobiotic load induced by seven days of intragastric injections of acetylsalicylic acid at a dose of 250 mg/kg have shown inhibition of the oxygen consumption rates in the heart mitochondria as well as a limitation of the succinate-dependent substrate oxidation pathways and a decrease in the mitochondria ATP/ADP coefficient. Succinic acid (50 mg/kg for 7 days was injected as a preventive medication to correct the mitochondrial bioenergetics revealed. A comparative research of the pharmacokinetics of acetylsalicylic acid and acetylsalicylic acid against the background of succinic acid performed on the model of rabbits has shown total similarity in the parameters analyzed. This fact demonstrates the possibility of prevention of mitochondrial dysfunction using the intermediate Krebs cycle. SUC as preventive medication promotes the elimination of ASA-induced negative metabolic shifts in the rat heart mitochondria by normalizing the succinate- and NAD-dependent respiration, oxidative phosphorylation, and therefore, it finds good use in the correction of ASA-induced negative side-effects of an energy-generating system

  14. Acetylsalicylate and salicylates in foods.

    NARCIS (Netherlands)

    Janssen, P.L.T.M.K.; Katan, M.B.; Staveren, van W.A.; Hollman, P.C.H.; Venema, D.P.

    1997-01-01

    Acetylsalicylic acid is effective in the prevention of cardiovascular disease. It was suggested that fruits and vegetables provide unknown amounts of acetylsalicylic acid. We could not find any acetylsalicylic acid in 30 foods using HPLC with fluorescence detection (detection limits: 0.02 mg/kg for

  15. Acetylsalicylic Acid Compared to Placebo in Treating High-Risk Patients With Subsolid Lung Nodules | Division of Cancer Prevention

    Science.gov (United States)

    This randomized phase II trial studies acetylsalicylic acid compared to placebo in treating high-risk patients with subsolid lung nodules. A nodule is a growth or lump that may be malignant (cancer) or benign (not cancer). Chemoprevention is the use of drugs to keep cancer from forming or coming back. The use of acetylsalicylic acid may keep cancer from forming in patients with subsolid lung nodules. |

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

    Science.gov (United States)

    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.

  17. Effects of meloxicam compared to acetylsalicylic acid in human articular chondrocytes.

    Science.gov (United States)

    Bassleer, C; Magotteaux, J; Geenen, V; Malaise, M

    1997-01-01

    Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID) derived from enolic acid, which has displayed potent anti-inflammatory properties in animal studies combined with low gastrointestinal toxicity. Other NSAIDs have been shown, in vitro, to have a variety of effects on cartilage repair processes in diseased articular cartilage. The aim of this study was to ascertain the effects of meloxicam on some of these processes using in vitro models. Acetylsalicylic acid, a NSAID whose characteristics have been previously elucidated in the models, was used as an active comparator. The effects of meloxicam were different from those of acetylsalicylic acid on chondrocyte clusters. At pharmacologically active concentrations, meloxicam was a potent inhibitor of prostaglandin-E2 production. However, all chondroformative processes were unaffected by meloxicam as indicated by a lack of effect on DNA synthesis and on type-II collagen and proteoglycan levels in chondrocyte culture medium and clusters, while acetylsalicylic acid decreased proteoglycan production and cell proliferation. Consequently, these in vitro findings suggest that meloxicam does not adversely affect the reparative processes active within the cartilage matrix of a diseased joint. This study represents a sound basis for future studies to establish the effects of meloxicam on osteoarthritis disease progression.

  18. Teratogenicity studies with methotrexate, aminopterin, and acetylsalicylic acid in domestic cats.

    Science.gov (United States)

    Khera, K S

    1976-08-01

    Pregnancy was timed in cats following induced ovulation. Methotrexate, (0.5 mg/kg), aminopterin, (0.1 mg/kg), and acetylsalicylic acid, (25 or 50 mg/kg) were administered orally in gelatin capsules in single daily doses on different days of gestation, methotrexate (MTX) on days 11-14, 14-17, or 17-20, aminopterin on day 12, 14, or 16, and acetylsalicylic acid (ASA) on days 10-15 or 15-20. Maternal toxicity was produced only by MTX. MTX given on days 11-14 and 14-17 produced high frequencies of malformations including umbilical hernia. Aminopterin caused no conclusive teratogenic response. An overall increased frequency of anomalies occurred after 50 mg/kg ASA but no single anomaly predominated.

  19. Aspirin: yesterday, today, and tomorrow

    Directory of Open Access Journals (Sweden)

    Marina Nikołajewna Dołżenko

    2014-06-01

    Full Text Available Clinical utility of aspirin (acetylsalicylic acid, ASA is one of the more important issues in the primary and secondary prevention of cardiovascular disease. The present paper provides analysis of aspirin history, mechanisms of its antiplatelet activity, and expediency of the use of low- and high-dose aspirin in the groups including patients after myocardial revascularization, and requiring secondary prevention of stroke. Also gender-specific aspirin properties were mentioned, highlighting the especially important role of aspirin in women at the age of >65 years, and its utility in all women, irrespectively of age, and those who are at high risk of cardiovascular disease, including atherosclerosis-related cardiovascular disease. Moreover, the mechanisms of aspirin resistance, characterized by inability of aspirin to prevent thromboembolic complications or inadequate platelet inhibition showed in laboratory results, were mentioned. Prevalence of resistance in aspirin-treated patients is estimated to be between 1 and 68%. Stress was also put on the aspirin safety, associated with prophylaxis of peptic ulcer disease, which can be achieved i.e. by the use of the enteric-coated aspirin. This form of aspirin is associated with lower risk of gastrointestinal mucosae damage and bleeding from the gastrointestinal tract. At the end of the article, the importance of the adherence to therapeutic guidelines of aspirin use, including assessment of variation in aspirin bioavailability associated with improper dosing and altered absorption in the gastrointestinal tract, was stressed.

  20. Chronic aspirin treatment affects collagen deposition in non-infarcted myocardium during remodeling after coronary artery ligation in the rat

    NARCIS (Netherlands)

    E.A.J. Kalkman (Ed); R-J. van Suylen (Robert-Jan); J.P.M. van Dijk (J. P M); P.R. Saxena (Pramod Ranjan); R.G. Schoemaker (Regien)

    1995-01-01

    textabstractLow-dose aspirin (acetylsalicylic acid; ASA), inhibiting platelet thromboxane production in favor of endothelium formation of prostaglandins, is successfully used as primary or secondary prophylaxis against myocardial infarction. Although prognosis may be improved, effects of long-term

  1. FAST DETECTION OF ACETYLSALICYLIC ACID BY LIQUID CHROMATOGRAPHY TANDEM MASS SPECTROMETRY(LC-MSMS)

    OpenAIRE

    Abusoglu, Sedat; Unlu, Ali; Sivrikaya, Abdullah

    2018-01-01

    ObjectivesAcetylsalicylic acid (ASA) is themost widely used as an analgesic, anti-inflammatory and antipyretic drug, andalso used to inhibit cyclooxygenase dependent platelet aggregation.   The aimof this study was to develop a simple, fast and accurate tandem mass method fordetermination and quantification of ASA.  MethodsChromatographic seperation was performedusing an Shimadzu LC-20-AD (Kyoto, Japan) coupledwith a ABSCIEX API 3200 triple quadrupole massspectromete...

  2. Low dose acetylsalicylic acid and shedding of microparticles in vivo in humans.

    Science.gov (United States)

    Lubsczyk, Barbara; Kollars, Marietta; Hron, Gregor; Kyrle, Paul A; Weltermann, Ansgar; Gartner, Verena

    2010-06-01

    Microparticles (MPs) have procoagulant properties as shown in vitro and in animal models. Their role in haemostatic system activation at the site of a vascular injury in vivo in humans has not been studied. In a prospective randomized crossover study, 13 healthy volunteers were given 100 mg acetylsalicylic acid or placebo daily for 7 days. Number and cellular origin, expression of tissue factor (TF) and phosphatidylserine on MPs, and platelet and coagulation activation markers [beta-thromboglobulin (beta-TG), prothrombin fragment f1.2 (f1.2)] were measured in venous blood and in blood from a vascular injury (shed blood) by flow cytometry and immunoassays, respectively. The number of MPs was significantly higher in shed blood than in venous blood. The majority of MPs were platelet derived. The expression of TF on MPs was low, but higher in shed blood than in venous blood. TF positive MPs were significantly higher in shed blood, which was due to an increase of MPs from platelets (PMPs). In shed blood, the number of TF expressing platelet-derived MPs correlated with beta-TG, but not with f1.2. Low dose acetylsalicylic acid did not affect shedding of PMPs, neither in venous blood nor in shed blood. The release of PMPs locally at the site of platelet plug formation in humans indicates a possible role of MPs for haemostatic system activation in vivo. Low dose acetylsalicylic acid might not be strong enough to suppress shedding of PMPs in the microcirculation.

  3. Mechanism of Acetyl Salicylic Acid (Aspirin) Degradation under Solar Light in Presence of a TiO2-Polymeric Film Photocatalyst

    OpenAIRE

    Debjani Mukherjee; Ajay K. Ray; Shahzad Barghi

    2016-01-01

    Application of titanium dioxide (TiO2) as a photocatalyst has presented a promising avenue for the safe photocatalytic degradation of pollutants. Increasing levels of the release of pharmaceuticals in the environment and formation of the intermediates during their degradation may impose health and environmental risks and therefore require more attention. Photocatalytic degradation of acetylsalicylic acid (aspirin) was carried out in the presence of the TiO2-filled polymeric film as a photocat...

  4. Impact of aspirin on the transcriptome of Streptococcus pneumoniae D39

    OpenAIRE

    Afzal, Muhammad; Shafeeq, Sulman

    2017-01-01

    Aspirin or acetylsalicylic acid (ASA) is a medicine used to treat pain, fever, and inflammation. Here, we for the very first time reported the genome-wide transcriptional profiling of aspirin-regulated genes in Streptococcus pneumoniae in the presence of 5?mM aspirin in chemically-defined medium (CDM) using microarray analysis. Our results showed that expression of several genes was differentially expressed in the presence of aspirin. These genes were further grouped into COG (Clusters of Ort...

  5. Acetylsalicylic acid and labeling of blood constituents with technetium-99m

    Directory of Open Access Journals (Sweden)

    Adenilson de Souza da Fonseca

    2005-10-01

    Full Text Available Acetylsalicylic acid is the drug most used an anti-inflammatory agent and for secondary prevention of thrombotic phenomenon. Drugs can modify the labeling of blood constituents with technetium-99m (99mTc. The aim of this work was to evaluate the effect of in vitro or in vivo assays with acetylsalicylic acid on the labeling of the blood constituents with 99mTc. In vitro assay was performed with samples of whole blood from Wistar rats incubated with acetylsalicylic acid (1.0 mg/ml for one hour before the 99mTc-labeling process. For in vivo assay, Wistar rats were treated with acetylsalicylic acid (1.5 mg/kg during one hour, and the whole blood was withdrawn for the 99mTc-labeling process. Saline was used in control groups. Data showed that the fixation of 99mTc to the blood constituents was not significantly (p>0.05 modified in in vitro and in vivo assays with acetylsalicylic acid, at least not when the experiments were carried out with the doses normally used in human beings.Ácido acetilsalicílico é a droga mais usada como antiinflamatório e para prevenção de fenômenos trombóticos. Drogas podem modificar a marcação de constituintes sangüíneos com tecnécio-99m (99mTc. O objetivo deste trabalho foi avaliar o efeito do ácido acetilsalicílico in vitro ou in vivo na marcação dos constituintes sangüíneos com 99mTc. Ensaios in vitro foram realizados com amostras de sangue total de ratos Wistar incubadas com ácido acetilsalicílico (1.0mg/ml 1 hora antes do processo de marcação com 99mTc. Para ensaios in vivo, ratos Wistar foram tratados com ácido acetilsalicílico (1.5mg/kg durante 1 hora e, em seguida, o sangue total foi retirado para o processo de marcação com 99mTc. Salina foi usada nos grupos controles. Dados mostraram que nos ensaios in vitro e in vivo com ácido acetilsalicílico, a fixação do 99mTc nos constituintes sangüíneos não foi significativamente (p>0.05 modificada, pelo menos, quando os experimentos foram

  6. An investigation about the solid state thermal degradation of acetylsalicylic acid: polymer formation

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Edna M. de A; Melo, Dulce M. de A; Moura, Maria de F.V. de; Farias, Robson F. de

    2004-05-06

    An investigation about the thermal degradation of acetylsalicylic acid (ASA) is performed. It is verified that the thermal degradation of ASA produces not only salicylic acid (SA) and acetic acid (AA) as products but also an ASA polymer, which is transparent and solid. And also verified that the temperature in which the polymer is obtained influences its physical consistence (solid or semi-solid). Furthermore, the ASA polymer is very stable from a thermic point of view, as verified by TG and DSC analysis. X-ray diffraction patterns obtained for the ASA polymer show that it exhibits a low crystallinity.

  7. Induction of (omega-1)-oxidation of monocarboxylic acids by acetylsalicylic acid.

    Science.gov (United States)

    Kundu, R K; Getz, G S; Tonsgard, J H

    1993-07-01

    Monocarboxylic acids may be oxidized at the omega- and (omega-1)- positions to form dicarboxylic acids (DCAs) and (omega-1)-hydroxy- or (omega-1)-oxoacids. The significance of this pathway under normal conditions is unknown, but DCAs and (omega-1)-hydroxyacids are prominent features of disease states. The stimulation of this pathway has been linked to induction of fatty acid-binding protein and peroxisomal proliferation. In this study, we examined the effect of acetylsalicylic acid (ASA) on (omega-1)-oxidation. (Omega-1)-oxidation was assessed in subcellular fractions of rat liver. Rats were fed a normal diet or an ASA-supplemented diet. Products were identified by gas chromatography-mass spectrometry (GC-MS) and by comparison with the properties of authentic synthetic standards. Doses of ASA that produced relatively low serum concentrations (12-24 mg/dl) resulted in as much as a 20-fold increase in the capacity for (omega-1)-oxidation of medium (C12-C15) and long chain (C16-C20) monocarboxylic acids. Normal rat liver oxidizes monocarboxylic acids to (omega-1)-oxoacids, while liver from ASA-treated rats converts these substrates to (omega-1)-oxodicarboxylic acids and (omega-1)-oxoacids. The formation of oxoacids and oxodicarboxylic acids may be due to different enzymes. The formation of oxodicarboxylic acids appears to be more labile than the formation of oxoacids. These two processes also are differentially induced by ASA and have different substrate specificities. These results demonstrate that ASA is a potent stimulant of (omega-1)-oxidation and induces the formation of products that can be shortened in peroxisomes to key metabolic intermediates.

  8. UV imaging of Multiple Unit Pellet System (MUPS) tablets: A case study of acetylsalicylic acid stability

    DEFF Research Database (Denmark)

    Novikova, Anna; Carstensen, Jens Michael; Rades, Thomas

    2017-01-01

    for estimation of the salicylic acid (SA) concentration as degradation product of ASA in the tablets were compared to the SA concentration measured by high performance liquid chromatography with a partial least squares regression resulting in an RMSEP of 4.86% and an R2 of 0.9812. The estimation of the SA......The applicability of multispectral ultraviolet (UV) imaging in combination with multivariate image analysis was investigated to monitor API degradation within multiple unit pellet system (MUPS) tablets during storage. For this purpose, acetylsalicylic acid (ASA) layered pellets were coated...

  9. Pharmacokinetics and in vitro efficacy of salicylic acid after oral administration of acetylsalicylic acid in horses.

    Science.gov (United States)

    Buntenkötter, Kathrin; Osmers, Maren; Schenk, Ina; Schänzer, Wilhelm; Machnik, Marc; Düe, Michael; Kietzmann, Manfred

    2017-01-19

    Although acetylsalicylic acid (ASA) is not frequently used as a therapeutic agent in horses, its metabolite SA is of special interest in equestrianism since it is a natural component of many plants used as horse feed. This led to the establishment of thresholds by horse sport organizations for SA in urine and plasma. The aim of this study was to investigate plasma and urine concentrations of salicylic acid (SA) after oral administration of three different single dosages (12.5 mg/kg, 25 mg/kg and 50 mg/kg) of acetylsalicylic acid (ASA) to eight horses in a cross-over designed study. In the 12.5 mg/kg group, SA concentrations in urine peaked 2 h after oral administration (2675 μg/mL); plasma concentrations peaked at 1.5 h (17 μg/mL). In the 25 mg/kg group, maximum concentrations were detected after 2 h (urine, 2785 μg/mL) and 1.5 h (plasma, 23 μg/mL). In the 50 mg/kg group, maximum concentrations were observed after 5 h (urine, 3915 μg/mL) and 1.5 h (plasma, 45 μg/mL). The plasma half-life calculated for SA varied between 5.0 and 5.7 h. The urine concentration of SA fell below the threshold of 750 μg/mL (set by the International Equestrian Federation FEI and most of the horseracing authorities) between 7 and 26 h after administration of 12.5 and 25 mg/kg ASA and between 24 and 36 h after administration of 50 mg/kg ASA. For ASA, IC50 were 0.50 μg/mL (COX-1) and 5.14 μg/mL (COX-2). For salicylic acid, it was not possible to calculate an IC50 for either COX due to insufficient inhibition of both cyclooxygenases. The established SA thresholds of 750 μg//mL urine and 6.5 μg/mL plasma appear too generous and are leaving space for misuse of the anti-inflammatory and analgetic compound ASA in horses.

  10. HPLC assay of acetylsalicylic acid, paracetamol, caffeine and phenobarbital in tablets.

    Science.gov (United States)

    Franeta, J T; Agbaba, D; Eric, S; Pavkov, S; Aleksic, M; Vladimirov, S

    2002-09-01

    This paper present a HPLC method for simultaneous determination of acetylsalicylic acid, paracetamol, caffeine and phenobarbital in tablets, using chromatographic system consisting a Bio Rad 18 01 solvent pump, Rheodine 71 25 injector and Bio Rad 18 01 UV-Vis Detector. Separation was achieved using Bio SiL HL C18, 5 microm, 250 x 4.6 mm column. Mixture of acetonitrile-water (25:75 v/v) adjusted to pH 2.5 with phosphoric acid was used as a mobile phase at a flow rate of 2.0 ml min(-1). UV detection was at 207 nm range 0.01 AUFS. Under the same conditions it was possible to determine the level of salicylic acid. The chromatographic parameters such as retention times, capacity factor, peak asymmetry, selectivity factor and resolution factor was determined. The validation parameters: linearity (r > 0.998), intra-day precision (RSD: 0.36-1.89%) and inter-day precision (RSD: 0.58-2.18%), sensitivity (LOD: 9 x 10(-5)-1.7 x 10(-4) mg ml(-1) and LOQ: 2.5 x 10(-4)-5.6 x 10(-4) mg ml(-1)), accuracy (recoveries: 98.35-99.14%) and reproducibility (recovery values: 98.74-102.08% for acetylsalicylic acid, 99.93-102.11% for paracetamol, 98.25-102.12% for caffeine and 98.15-102.3% for phenobarbital) (RSD: 1.21-1.85%) were found to be satisfactory. The proposed HPLC method has been applied for the determination of acetylsalicylic acid, paracetamol, caffeine and phenobarbital in Malophenum tablets. The obtained RSD values were within 0.99-1.21%. The developed method is rapid and sensitive and therefore suitable for routine control of these drugs in dosage form.

  11. Similar effect of sodium nitroprusside and acetylsalicylic acid on antioxidant system improvement in mouse liver but not in the brain.

    Science.gov (United States)

    Wróbel, Maria; Góralska, Joanna; Jurkowska, Halina; Sura, Piotr

    2017-04-01

    The aim of the present study was to analyze the relative antioxidant effects of acetylsalicylic acid (ASA) and sodium nitroprusside (SNP) in mouse liver and brain. The activity of rhodanese, 3-mercaptopyruvate sulfurtransferase (MPST) and γ-cystathionase (CSE), functioning as antioxidant proteins and capable of producing H2S, was investigated in mouse liver and brain after intraperitoneal once a day administration of sodium nitroprusside (5 mg/kg body weight) or acetylsalicylic acid (500 mg/kg body weight) continued for 5 days. The tissues were homogenized and then the obtained supernatants were used for further determinations. At the same time, the levels of sulfane sulfur, reduced and oxidized glutathione, cysteine, cystine, and cystathionine were also studied in these tissues. Both ASA and SNP show a statistically significant increase of sulfurtransferases activities in liver. The mechanism of action of sodium nitroprusside appears to consist in liberation of nitric oxide (NO), an important signaling molecule in the mammalian body. SNP also releases cyanide ions, which are converted in the liver to thiocyanate by the enzyme rhodanese and/or MPST and/or γ-cystathionase - the activities of all the enzymes were elevated in reaction to SNP. The action of γ-cystathionase is dependent upon converting cystathionine to cysteine, a precursor of the major cellular antioxidant, glutathione. Under oxidizing conditions, an increase in cystathionine β-synthase activity might indirectly result in an increase in the antioxidant glutathione level; this was reflected by the increased GSH/GSSG ratio in the liver, but not in the brain, where a trace activity of γ-cystathionase is normally detected. The results of the present investigations show that ASA and SNP may stimulate the GSH-dependent antioxidant system and protect liver cells from oxidative stress. An increased activity of the H2S-producing enzymes and the increased GSH/GSSG ratio may lead to an elevated level of H2

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

    Science.gov (United States)

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

    2016-03-01

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

  13. Effect of common single-nucleotide polymorphisms in acetylsalicylic acid metabolic pathway genes on platelet reactivity in patients with diabetes

    Science.gov (United States)

    Postula, Marek; Janicki, Piotr K.; Rosiak, Marek; Kaplon-Cieslicka, Agnieszka; Kondracka, Agnieszka; Trzepla, Ewa; Filipiak, Krzysztof J.; Kosior, Dariusz A.; Czlonkowski, Andrzej; Opolski, Grzegorz

    2013-01-01

    Background Platelet reactivity in patients on acetylsalicylic acid (ASA) therapy can be influenced by physiological or pathological conditions affecting ASA pharmacokinetics or pharmacodynamics. The mechanism of such variability in the therapeutic response to ASA, particularly in diabetic patients, is poorly understood. The rate of elimination of ASA and its metabolite, salicylic acid (SA), is likely a major factor determining drug efficacy. The objective of this study was to investigate the effect of genetic polymorphisms in the selected candidate genes within the ASA metabolic pathway on the platelet reactivity and concentration of ASA and thromboxane A2 (TxA2) metabolites in a population of patients with type 2 diabetes mellitus (T2DM). Material/Methods The study cohort consisted of 287 Caucasians with T2DM who had been taking ASA tablets at the dose of 75 mg per day for at least 3 months. Platelet reactivity analyses were performed using VerifyNow Aspirin and PFA-100 assays. The measured ASA metabolite included salicylic acid (ASA), and TxA2 metabolites included serum TxB2 and urinary 11-dh-TxB2. Genotyping for the selected 18 single-nucleotide polymorphisms (SNPs) within 5 genes of the ASA metabolic pathway was performed using a Sequenom iPLEX platform. Results No statistically significant association was observed between the investigated SNPs genotypes, platelet reactivity, and measured metabolites in the investigated cohort of patients. Conclusions The results of our study failed to confirm that the selected variants in the genes within the ASA metabolic pathway might contribute to platelet reactivity in a diabetic population treated with ASA. PMID:23715170

  14. Does the use of acetylsalicylic acid have an influence on our vision?

    Directory of Open Access Journals (Sweden)

    Michalska-Małecka K

    2016-11-01

    Full Text Available Katarzyna Michalska-Małecka,1,2 Agnieszka Regucka,2 Dorota Śpiewak,2 Magdalena Sosnowska-Pońska,2 Alfred Niewiem2 1Department of Ophthalmology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland; 2University Clinical Center, University Hospital Medical University of Silesia, Katowice, Poland Purpose: Acetylsalicylic acid (ASA is one of the most commonly used drugs in the world due to its anti-inflammatory, analgesic, and antipyretic properties. This review aims to describe the relationship between acetylsalicylic acid and age-related macular degeneration (AMD – a chronic disease that causes deterioration of visual acuity and is one of the most common ophthalmological diseases these days. Methods: Data presented in this review were collected from both research and review articles concerning ophthalmology and pharmacology. Results: The results of the studies analyzed in this review are not unambiguous. Moreover, the studies are not homogenous. They differed from one another in terms of the number of patients, the age criteria, the ASA dose, and the duration of control period. The reviewed studies revealed that ASA therapy, which is applied as a protection in cardiovascular diseases in patients with early forms of AMD and geographic atrophy, should not be discontinued. Conclusion: On the basis of the present studies, it cannot be unequivocally said whether ASA influences people’s vision and if people endangered with AMD progression or who are diagnosed with AMD should use this drug. It may increase the risk of AMD, but it can also reduce the risk of life-threatening conditions. The authors suggest that in order to avoid possible risks of AMD development, people who frequently take ASA should have their vision checked regularly. Keywords: acetylsalicylic acid, AMD, lipofuscin genesis, drusen genesis, retinal pigment epithelium cells, geographic atrophy

  15. Aspirin desensitization for cardiovascular disease.

    Science.gov (United States)

    Woessner, Katharine M

    2015-08-01

    The use of aspirin in coronary artery disease and address the unmet need of aspirin therapy in patients with history of hypersensitivity reactions to aspirin (acetylsalicylic acid; ASA) or other nonsteroidal inflammatory drugs (NSAIDs). Aspirin hypersensitivity is reported in 1.5% of patients with cardiovascular disease. However, many of those labeled as allergic to aspirin had experienced side-effects and could be safely treated with aspirin. Those with true hypersensitivity reactions were often not placed on appropriate antiplatelet therapy. A number of protocols of varying complexity exist in the literature for aspirin desensitization. The focus of this review is to identify the types of aspirin reactions that can occur and provide a rational approach to oral aspirin challenge and desensitization. In summary, with rare exceptions, patients with a history of 'aspirin/NSAID allergy' who need ASA for cardiovascular issues will be able to safely take aspirin either after a graded challenge or desensitization providing a central role of the allergist in the management of these patients.

  16. [Treatment of acute inner ear diseases (sudden deafness and vestibular disorder) with meclofenoxate and acetylsalicylic acid].

    Science.gov (United States)

    Weinaug, P

    1988-06-01

    Sixty patients suffering from an acute inner ear disease were treated by a combination of acetylsalicylic acid (Micristin), an inhibitor of platelet aggregation, and meclofenoxate (Cerutil), a nootropic drug. The success rate in 26 patients with acute isolated unilateral vestibular disorder was 73% (69% with complete recovery), and 83% (57% complete remission) in 34 patients with sudden deafness, with an average hearing improvement of 22.4 dB. The success rate of this therapy was similar to that achieved by the usual therapy or no treatment in subjects with sudden deafness and vestibular disorder which we reported in 1984.

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

    Science.gov (United States)

    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. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  18. Does the use of acetylsalicylic acid have an influence on our vision?

    OpenAIRE

    Michalska-Małecka K; Regucka A; Śpiewak D; Sosnowska-Pońska M; Niewiem A

    2016-01-01

    Katarzyna Michalska-Małecka,1,2 Agnieszka Regucka,2 Dorota Śpiewak,2 Magdalena Sosnowska-Pońska,2 Alfred Niewiem2 1Department of Ophthalmology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland; 2University Clinical Center, University Hospital Medical University of Silesia, Katowice, Poland Purpose: Acetylsalicylic acid (ASA) is one of the most commonly used drugs in the world due to its anti-inflammatory, analgesic, and antipyretic properties. This review a...

  19. DFT studies on the vibrational and electronic spectra of acetylsalicylic acid

    Science.gov (United States)

    Ye, Yunfeng; Tang, Guodong; Han, Yonghong; Culnane, Lance F.; Zhao, Jianyin; Zhang, Yu

    2016-05-01

    The following is a theoretical and experimental study on the vibrational and electronic properties of acetylsalicylic acid (ASA). Vibrational information was obtained by FT-IR and Raman spectroscopy which agree well with harmonic vibrational frequency calculations. The calculations were carried out using density functional theory B3LYP methods with 6-311G** and LANL2DZ basis sets. The vibrational assignments were calculated by Gaussview. Absorption UV-Vis experiments of ASA reveal three maximum peaks at 203, 224 and 277 nm, which are in agreement with calculated electronic transitions using TD-B3LYP/6-311G**.

  20. The localization and some properties of the acetylsalicylic acid O-deacetylases of Ascaris lumbricoides var suum and Moniezia expansa.

    Science.gov (United States)

    Douch, P G

    1978-03-01

    1. Enzymes hydrolysing acetylsalicylic acid were found in the cytosol of the cestode, Moniezia expansa, and in the cytosol of the intestinal epithelial cells and cytosol of the reproductive tract of the nematode, Ascaris lumbricoides var suum. 2. Enzymes hydrolysing 2-naphthyl acetate and 4-methylumbelliferyl acetate were found throughout the proglottid of the cestode and in the reproductive tract, intestine, mesenchyme fluid and cuticle of the nematode. These enzymes had mol. wt. of 30 000-300 000 whereas those hydrolysing acetylsalicylic acid in both species had mol. wt. of about 87 000. 3. The acetylsalicylic acid hydrolases from both helminths showed pH optima of about 7.0, and activity was enhanced by Ca2+ and low-mol. wt. thiols. Cu2+, Cd2+, Hg2+, Zn2+, La3+, F- and EDTA at 1 mM inhibited activity. N-Ethylmaleimide, p-chloromercuribenzoate, haloxon and paraoxon also inhibited hydrolase activity.

  1. Use of the oral platelet inhibitors dipyridamole and acetylsalicylic acid is associated with increased risk of fracture

    DEFF Research Database (Denmark)

    Vestergaard, Peter; Steinberg, Thomas H; Schwarz, P

    2012-01-01

    BACKGROUND: Platelet inhibitors are widely used in the treatment and prevention of coronary artery disease. In addition to acetylsalicylic acid, two major groups of platelet inhibitors are used; phosphodiesterase inhibitors including dipyridamole, and thienopyridines (ticlopidine and clopidogrel)...... is not associated with increased fracture risk. CONCLUSIONS: Use of some oral platelet inhibitors is associated with increased risk of fractures, and more studies are warranted to determine the potential effect of platelet inhibitors on bone metabolism in vivo.......BACKGROUND: Platelet inhibitors are widely used in the treatment and prevention of coronary artery disease. In addition to acetylsalicylic acid, two major groups of platelet inhibitors are used; phosphodiesterase inhibitors including dipyridamole, and thienopyridines (ticlopidine and clopidogrel......). Clopidogrel is the most widely used, and in combination with acetylsalicylic acid it is the standard of care for acute coronary syndromes and percutaneous coronary interventions. However, the modes of action involve pathways that are involved in the metabolic activity in bone cells and pharmacologic...

  2. Aspirin and its related non-steroidal anti-inflammatory drugs

    African Journals Online (AJOL)

    Aspirin and its related non-steroidal anti-inflammatory drugs. Aspirin or acetylsalicylic acid has been utilised by physicians for hundreds of years as an analgesic, anti-inflammatory and antipyretic (1). Derived from plant sources, such as the willow tree, it has the ability to induce apoptosis in cancer cells and stimulate.

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

    Science.gov (United States)

    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%; pproperties of ASA therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Protective Effect of Melatonin on the Quality of Spermatogenesis and Sperm Parameters in the Mice Treated with Acetylsalicylic Acid

    Directory of Open Access Journals (Sweden)

    F. Mohammad Ghasemi

    2012-01-01

    Full Text Available Introduction & Objective: Melatonin, the most important secretary hormone of pineal gland, as a powerful antioxidant has a high potent for neutralizing the toxicity of drugs. In the present study we aimed to demonstrate the effect of melatonin on testicular damage and sperm parameters deficiency induced by acetylsalicylic acid, in adult male mice. Materials & Methods: Male NMRI mice were divided into 4 groups: 1 control 2 acetylsalicylic acid treated group 3 melatonin treated group 4 Melatonin-acetylsalicylic acid treated group. Acetylsalicylic acid was administered at a dose of 50mg/kg orally through gavage for 14 days. Melatonin was administered in dose of 10 mg/kg for 5 days intraperitoneally. The control mice were received vehicle (normal saline orally through gavage. The animals were sacrificed and their testes and epididymis were dissected on the 15th day after the treatment. Evaluations were made by determining Johnson's score, epididymal sperm count, and sperm morphology and sperm motility. Statistical analysis was performed by ANOVA test. Results: Acetylsalicylic acid treated mice showed a reduction in Johnson's score and quality of spermatogenesis (P<0.05, sperm count, normal morphology and motility percent (P<0.001, compared to the control. Melatonin in group 4, significantly increased maturation of seminiferous tubules (P<0.05, and quality and quantity of sperm parameters (P<0.05 in comparison with group 2. Conclusion: It seems that intraperitoneal administration of melatonin for 5 days is a potentially beneficial agent to improve the quality of spermatogenesis and sperm parameters in testis damaged by acetylsalicylic acid, probably by decreasing oxidative stresses. (Sci J Hamadan Univ Med Sci 2012;18(4:29-36

  5. Does the use of acetylsalicylic acid have an influence on our vision?

    Science.gov (United States)

    Michalska-Małecka, Katarzyna; Regucka, Agnieszka; Śpiewak, Dorota; Sosnowska-Pońska, Magdalena; Niewiem, Alfred

    2016-01-01

    Acetylsalicylic acid (ASA) is one of the most commonly used drugs in the world due to its anti-inflammatory, analgesic, and antipyretic properties. This review aims to describe the relationship between acetylsalicylic acid and age-related macular degeneration (AMD) - a chronic disease that causes deterioration of visual acuity and is one of the most common ophthalmological diseases these days. Data presented in this review were collected from both research and review articles concerning ophthalmology and pharmacology. The results of the studies analyzed in this review are not unambiguous. Moreover, the studies are not homogenous. They differed from one another in terms of the number of patients, the age criteria, the ASA dose, and the duration of control period. The reviewed studies revealed that ASA therapy, which is applied as a protection in cardiovascular diseases in patients with early forms of AMD and geographic atrophy, should not be discontinued. On the basis of the present studies, it cannot be unequivocally said whether ASA influences people's vision and if people endangered with AMD progression or who are diagnosed with AMD should use this drug. It may increase the risk of AMD, but it can also reduce the risk of life-threatening conditions. The authors suggest that in order to avoid possible risks of AMD development, people who frequently take ASA should have their vision checked regularly.

  6. Chlorpheniramine Potentiates the Analgesic Effect in Migraine of Usual Caffeine, Acetaminophen, and Acetylsalicylic Acid Combination.

    Science.gov (United States)

    Voicu, Victor A; Mircioiu, Ion; Sandulovici, Roxana; Mircioiu, Constantin; Plesa, Cristina; Velescu, Bruno S; Anuta, Valentina

    2017-01-01

    Previous studies indicated that addition of the antihistaminic chlorpheniramine to the usual combination of acetylsalicylic acid, acetaminophen, and caffeine further increases their synergism both in terms of anti-inflammatory and analgesic effect. The present non-interventional study tested the superiority of two Algopirin® tablets, containing a total of 250 mg acetylsalicylic acid (ASA), 150 mg acetaminophen (paracetamol, PAR), 30 mg caffeine (CAF) and 4 mg chlorpheniramine (CLF) vs. a combination containing 250 mg ASA, 250 mg PAR, and 65 mg CAF recognized as "safe and effective" by FDA in treating migraine. Patients evaluated their pain intensity on the Visual Analog Scale-VAS(PI) before and 30, 60, 120, 180, and 240 min after drug intake. Interpretation of the pain curves as "survival pain curves" was considered as a method for direct comparison of the pain curves. This interpretation permitted the application of the log rank test for comparison of pain hazards. The results of the applied parametric and non-parametric statistical tests indicated significant differences between the main endpoints: both Areas Under Pain Curves and time to decrease of the pain intensity to less than 50% of the initial value comparisons highlighted that Algopirin® was more efficient in spite of smaller doses of PAR and CAF. Comparison of "survival of pain" led to the same conclusion concerning the superiority of Algopririn. Consequently, the addition of CLF permitted decreasing of ASA, PAR, and CAF doses as well as their potential side effects, without a loss of analgesic effect.

  7. Transfer of Low Dose Aspirin Into Human Milk.

    Science.gov (United States)

    Datta, Palika; Rewers-Felkins, Kathleen; Kallem, Raja Reddy; Baker, Teresa; Hale, Thomas W

    2017-05-01

    Aspirin has antipyretic and anti-inflammatory properties and is frequently used by pregnant and lactating women. However, its transfer in human milk when administered at low dose has not been reported. Research aim: This study aimed to evaluate the transfer of acetylsalicylic acid and its metabolite, salicylic acid, into human milk following the use of low dose aspirin. In this study, milk samples were collected at 0, 1, 2, 4, 8, 12, and 24 hours from seven breastfeeding women after a steady-state daily dose of 81 mg of aspirin. Milk levels of acetylsalicylic acid and salicylic acid were determined by liquid chromatography-tandem mass spectrometry. Acetylsalicylic acid levels were below the limit of quantification (0.61 ng/ml) in all the milk samples, whereas salicylic acid was detected at very low concentrations. The average concentration of salicylic acid observed was 24 ng/ml and the estimated relative infant dose was 0.4%. Acetylsalicylic acid transfer into milk is so low that it is undetectable even by highly sophisticated methodology. Salicylic acid does appear in the human milk in comparatively low amounts, which are probably subclinical in infants. Thus, the daily use of an 81-mg dose of aspirin should be considered safe during lactation.

  8. Quality and antioxidant properties on sweet cherries as affected by preharvest salicylic and acetylsalicylic acids treatments.

    Science.gov (United States)

    Giménez, María José; Valverde, Juan Miguel; Valero, Daniel; Guillén, Fabián; Martínez-Romero, Domingo; Serrano, María; Castillo, Salvador

    2014-10-01

    The effects of salicylic acid (SA) or acetylsalicylic acid (ASA) treatments during on-tree cherry growth and ripening on fruit quality attributes, especially those related with the content on bioactive compounds and antioxidant activity were analysed in this research. For this purpose, two sweet cherry cultivars, 'Sweet Heart' and 'Sweet Late', were used and SA or ASA treatments, at 0.5, 1.0 and 2.0mM concentrations, were applied at three key points of fruit development (pit hardening, initial colour changes and onset of ripening). These treatments increased fruit weight and ameliorated quality attributes at commercial harvest, and led to cherries with higher concentration in total phenolics and in total anthocyanins, as well as higher antioxidant activity, in both hydrophilic and lipophilic fractions. Thus, preharvest treatments with SA or ASA could be promising tools to improve sweet cherry quality and health beneficial effects for consumers. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Numerical simulation of the solvate structures of acetylsalicylic acid in supercritical carbon dioxide containing polar co-solvents

    Science.gov (United States)

    Petrenko, V. E.; Antipova, M. L.; Gurina, D. L.; Odintsova, E. G.; Kumeev, R. S.; Golubev, V. A.

    2016-07-01

    Hydrogen-bonded complexes of acetylsalicylic acid with polar co-solvents in supercritical carbon dioxide, modified by methanol, ethanol, and acetone of 0.03 mole fraction concentration, are studied by numerical methods of classical molecular dynamics simulation and quantum chemical calculations. The structure, energy of formation, and lifetime of hydrogen-bonded complexes are determined, along with their temperature dependences (from 318 to 388 K at constant density of 0.7 g cm-3). It is shown that the hydrogen bonds between acetylsalicylic acid and methanol are most stable at 318 K and are characterized by the highest value of absolute energy. At higher supercritical temperatures, however, the longest lifetime is observed for acetylsalicylic acid-ethanol complexes. These results correlate with the known literature experimental data showing that the maximum solubility of acetylsalicylic acid at density values close to those considered in this work and at temperatures of 318 and 328 K is achieved when using methanol and ethanol as co-solvents, respectively.

  10. Cost Effectiveness of Gastroprotection with Proton Pump Inhibitors in Older Low-Dose Acetylsalicylic Acid Users in the Netherlands

    NARCIS (Netherlands)

    Chau, S.H.; Sluiter, R.L.; Kievit, W.; Wensing, M.; Teichert, M.; Hugtenburg, J.G.

    2017-01-01

    PURPOSE: The present study aimed to assess the cost effectiveness of concomitant proton pump inhibitor (PPI) treatment in low-dose acetylsalicylic acid (LDASA) users at risk of upper gastrointestinal (UGI) adverse effects as compared with no PPI co-medication with attention to the age-dependent

  11. Pharmacokinetics and in vivo scintigraphic monitoring of a sustained release acetylsalicylic acid formulation

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, C.G.; Hardy, J.C. (Queen' s Medical Centre, Nottingham (UK)); Parr, G.D.; Kennerley, J.W.; Taylor, M.J.; Davis, S.S. (Nottingham Univ. (UK)); Rees, J.A. (Boots Research Laboratories, Nottingham (UK))

    1984-01-01

    The in vivo dissolution and pharmacokinetics of a sustained release aspirin formulation labelled with (sup(99m)Tc)diethylenetriaminepentaacetic acid has been monitored in 5 subjects by the use of gamma scintigraphy and drug analysis undertaken of blood and urine samples. The data obtained enabled the position of the tablet in vivo to be related to the plasma and urinary salicylate levels. The study confirms the sustained release properties of the cellulose acetate phthalate formulation.

  12. Modified clotting properties of fibrinogen in the presence of acetylsalicylic acid in a purified system.

    Science.gov (United States)

    He, S; Blombäck, M; Yoo, G; Sinha, R; Henschen-Edman, A H

    2001-01-01

    To assess how treatment with acetylsalicylic acid (ASA) alters the fibrin network structure, clotting was initiated in purified fibrinogen incubated with ASA by adding thrombin. Clotting time and maximum absorbance of the fibrin aggregation curve were used to demonstrate the potential of fibrin generation. The results showed that the clotting properties of fibrinogen decreased and that the affinity of plasminogen to fibrin or thrombin inhibition by antithrombin increased if plasminogen or antithrombin, respectively, were present in the reaction system. The effect of ASA varied in a dose dependent manner. It was concluded that ASA may directly or indirectly confer positive or negative effects on the stability of the fibrin clot and that the balance between these effects may be regulated by the ASA dose.

  13. Promoting endothelial recovery and reducing neointimal hyperplasia using sequential-like release of acetylsalicylic acid and paclitaxel-loaded biodegradable stents

    National Research Council Canada - National Science Library

    Lee, Cheng-Hung; Yu, Chia-Ying; Chang, Shang-Hung; Hung, Kuo-Chun; Liu, Shih-Jung; Wang, Chao-Jan; Hsu, Ming-Yi; Hsieh, I-Chang; Chen, Wei-Jan; Ko, Yu-Shien; Wen, Ming-Shien

    2014-01-01

    This work reports on the development of a biodegradable dual-drug-eluting stent with sequential-like and sustainable drug-release of anti-platelet acetylsalicylic acid and anti-smooth muscle cell (SMC...

  14. Antiinflammatory properties of a hydroperoxide compound, structurally related to acetylsalicylic acid.

    Science.gov (United States)

    Killackey, J J; Killackey, B A; Cerskus, I; Philp, R B

    1984-06-01

    3-Hydroperoxy-3-methylphthalide (3-HMP), a structural analog of acetylsalicylic acid (ASA), was found to have some antiinflammatory properties which are distinct from those of ASA. 3-HMP inhibits human platelet aggregation and ATP release in response to low concentrations of collagen but is less effective than ASA. 3-HMP inhibits prostaglandin and thromboxane production from exogenous [14C]arachidonic acid by human platelet lysates in vitro and does so at lower concentrations than ASA (3-HMP IC50 = 10 microM; ASA IC50 = 50 microM). 3-HMP is also more effective than ASA as an inhibitor of prostacyclin-like activity production by rings of rabbit aorta. Human polymorphonuclear (PMN) leukocyte [14C]arachidonic acid metabolism is inhibited by 3-HMP but not ASA. In urethane-anesthetized rats, 3-HMP (10 mg/kg intravenously) is effective in inhibiting PMN leukocyte accumulation in response to intrapleural carrageenan administration whereas ASA is ineffective (100 mg/kg intravenously). This hydroperoxy analog of ASA has antiinflammatory activity which may result from a combination of the ASA-like and hydroperoxide-related pharmacological properties.

  15. Protective effects of electroacupuncture on acetylsalicylic acid-induced acute gastritis in rats.

    Science.gov (United States)

    Hwang, Hye-Suk; Han, Kyung-Ju; Ryu, Yeon-Hee; Yang, Eun-Jin; Kim, Yoo-Sung; Jeong, Sang-Yong; Lee, Young-Seop; Lee, Myeong-Soo; Koo, Sung-Tae; Choi, Sun-Mi

    2009-02-28

    To investigate the protective effects of electroacupuncture (EA) pretreatment on acetylsalicylic acid (ASA)-induced ulceration in rats. We randomly divided 72 rats into three groups including control (administered with distilled water), ASA group (administered 100 mg/kg ASA) and EA group (administered EA + 100 mg/kg ASA). Each rat was fasted for 18 to 24 h before experimentation, and lesion scores, gastric acidity, cyclooxygenase (COX)-1 and -2 mRNA levels, and total nitric oxide (NO) concentration were measured. The lesion scores of the EA group were significantly lower than those of the ASA group. Gastric acidity of the ASA and EA groups was reduced compared to the control group. COX-1 and -2 mRNA levels were significantly increased in the EA group as compared to the control and ASA groups, and NO levels were also significantly increased in the EA group as compared to the ASA group. These results suggest that EA-mediated protection against ASA-induced ulceration in rats may occur via gastric defense components.

  16. Faecal blood loss during administration of acetylsalicylic acid, ketoprofen and two new ketoprofen sustained-release compounds.

    Science.gov (United States)

    Ranløv, P J; Nielsen, S P; Bärenholdt, O

    1983-01-01

    The influence of one week's treatment with acetylsalicylic acid, ketoprofen, ketoprofen sustained-release capsules (Biovail capsules), and ketoprofen sustained-release tablets (IBP tablet) on gastrointestinal bleeding was investigated in 41 healthy male volunteers by means of a radiochromium assay. The physiological faecal bleeding was 0.10 to 0.90 ml/day (99% confidence limits). It appeared that faecal bleeding during treatment with acetylsalicylic acid medication was greater than bleeding during medication with ketoprofen capsules in equipotent dosage, the latter being in turn causing significantly more bleeding than during medication with the newly developed Biovail capsules. The most modest faecal bleeding (0.8 ml/day) was seen with IBP tablets.

  17. Synovial distribution of "systemically" administered acetylsalicylic acid in the isolated perfused equine distal limb.

    Science.gov (United States)

    Friebe, Maren; Schumacher, Stephan; Stahl, Jessica; Kietzmann, Manfred

    2013-03-26

    This study investigated synovial concentrations of acetylsalicylic acid (ASA) and its metabolite salicylic acid (SA) in the equine fetlock joint following systemic administration of ASA. Salicylates were chosen because SA is the only nonsteroidal anti-inflammatory drug for which threshold levels exist for plasma and urine in equine sports. To avoid animal experiments, the study was conducted using an ex vivo model of the isolated perfused equine distal limb in combination with plasma concentrations obtained from literature.Salicylate concentrations in the joint were determined using microdialysis and high performance liquid chromatography (HPLC). Any anti-inflammatory effect of synovial ASA concentrations was assessed using an ASA EC50 (half maximal effective concentration) determined in equine whole blood. The ASA concentration in the synovial fluid (n=6) reached a maximum of 4 μg/mL, the mean concentration over the entire perfusion period was 2 μg/mL. Maximum SA concentration was 17 μg/mL, the average was 14 μg/mL. ASA and SA concentration in the synovial fluid exceeded systemic concentrations 2 h and 3.5 h after "systemic" administration, respectively. ASA and SA accumulated in the in the synovial fluid of the ex vivo model despite decreasing systemic concentrations. This suggests a prolonged anti-inflammatory effect within the joint that remains to be further elucidated.

  18. Synovial distribution of “systemically” administered acetylsalicylic acid in the isolated perfused equine distal limb

    Science.gov (United States)

    2013-01-01

    Background This study investigated synovial concentrations of acetylsalicylic acid (ASA) and its metabolite salicylic acid (SA) in the equine fetlock joint following systemic administration of ASA. Salicylates were chosen because SA is the only nonsteroidal anti-inflammatory drug for which threshold levels exist for plasma and urine in equine sports. To avoid animal experiments, the study was conducted using an ex vivo model of the isolated perfused equine distal limb in combination with plasma concentrations obtained from literature. Salicylate concentrations in the joint were determined using microdialysis and high performance liquid chromatography (HPLC). Any anti-inflammatory effect of synovial ASA concentrations was assessed using an ASA EC50 (half maximal effective concentration) determined in equine whole blood. Results The ASA concentration in the synovial fluid (n = 6) reached a maximum of 4 μg/mL, the mean concentration over the entire perfusion period was 2 μg/mL. Maximum SA concentration was 17 μg/mL, the average was 14 μg/mL. ASA and SA concentration in the synovial fluid exceeded systemic concentrations 2 h and 3.5 h after “systemic” administration, respectively. Conclusions ASA and SA accumulated in the in the synovial fluid of the ex vivo model despite decreasing systemic concentrations. This suggests a prolonged anti-inflammatory effect within the joint that remains to be further elucidated. PMID:23531229

  19. Influence of cellulose powder structure on moisture-induced degradation of acetylsalicylic acid.

    Science.gov (United States)

    Mihranyan, A; Strømme, M; Ek, R

    2006-02-01

    The stability of crystalline acetylsalicylic acid (ASA) powder in binary mixtures with cellulose powders was investigated to reveal information about the influence of the cellulose structural properties on the moisture-induced ASA degradation. Different cellulose powder samples were manufactured and characterized by X-ray diffraction and N2 BET gas adsorption. The degradation patterns in ASA/cellulose mixtures were monitored as a function of salicylic acid increase versus time under various relative humidity conditions at 50 degrees C. The crystallinity index of cellulose samples varied between approximately 49 and 95%. The results indicated that cellulose powder with the lowest crystallinity index exhibited lower degradation rates than the samples with the higher crystallinity index. It should be noted that higher ASA degradation rates were observed in the samples with comparably lower moisture contents. This effect was most pronounced in the 1:3 (w/w), ASA/cellulose mixtures, whereas in 3:1 (w/w), ASA/cellulose mixtures the effect was less obvious. The findings emphasise the importance of cellulose structural organisation when governing the moisture's partition between cellulose and ASA during the hydrolytic degradation.

  20. Aspirin: a history, a love story.

    Science.gov (United States)

    Wick, Jeannette Y

    2012-05-01

    Most pharmacists know that aspirin's origins lie with willow bark, but they may be unaware of its role in the development of the pharmaceutical industry. Evolving from salacin (the active ingredient in many plant remedies) to salicylic acid (an analgesic in its own right) to the more effective, less toxic acetylsalicylic acid, this pain reliever cornered the nonsteroidal anti-inflammatory market for more than 70 years. It helped the dye industry branch into pharmaceuticals, and is now used in multiple indications.

  1. Intracranial hemorrhages related with warfarin use and comparison of warfarin and acetylsalicylic acid.

    Science.gov (United States)

    Seçil, Yaprak; Ciftçi, Yeliz; Tokuçoğlu, Figen; Beckmann, Yeşim

    2014-02-01

    Acetylsalicylic acid (ASA) and warfarin are used to prevent ischemic cerebrovascular events. They have serious complications including intracranial hemorrhages (ICHs). Warfarin-related intracerebral hemorrhage (ich) incidence is .2%-5% in population that accounts for 10%-12% of all ichs. In this article, we investigated the profile of ASA and warfarin-related spontaneous ICHs in comparison with ICHs without any drug use (WADU) with their clinical, radiological, and biochemical properties. In all, 486 patients aged 18-101 years with spontaneous ICHs were included. Patients constituted 4 separate groups: users of warfarin, ASA, ASA + warfarin, and WADU. Clinical, neurological, etiological, and radiological data of these patients were compared. There were 32 patients in warfarin, 58 patients in ASA, and 7 in warfarin + ASA group. Most of the patients were in no drug group (389 patients). The most frequent type of hemorrhage was supratentorial intraparenchymal hemorrhage. The most common accompanying disease was hypertension. The number of female patients was statistically significant in the warfarin group. Glasgow Coma Scale (GCS), accompanying diseases, opening of the hematoma to the ventricle, localization of the hemorrhage, age of the patient, and activated partial thromboplastin time level are all related to the outcome of patients. Warfarin users had worst mortality rate. Use of warfarin, low GCS score, opening to ventricle, older age, accompanying diabetes, and/or hypertension were worse prognostic factors. It is possible that patients with these unfavorable prognostic factors cannot survive. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  2. Microcrystalline cellulose from soybean husk: effects of solvent treatments on its properties as acetylsalicylic acid carrier.

    Science.gov (United States)

    Uesu, N Y; Pineda, E A; Hechenleitner, A A

    2000-09-25

    Microcrystalline cellulose (MCC) is a very important product in pharmaceutic, food, cosmetic and other industries. In this work, MCC was prepared from soybean husk, produced in large quantities in soybean oil processing industries. It was characterized through various techniques (scanning electron microscopy (SEM), infrared spectroscopy (FTIR), thermogravimetry analysis (TGA) and differential scanning calorimetry (DSC)) and compared with a commercial MCC. The results obtained show that the prepared sample has similar crystallinity and lower particle size than the commercial MCC. Both MCC samples were treated with organic solvents (chloroform, acetone, ethanol and ethyl ether), for structural modifications to be introduced, and used as acetylsalicylic acid (ASA) carrier. Pretreated MCC and MCC/ASA 1:1 mixtures were analyzed through FTIR and thermal analysis. The drug release was evaluated in buffer solution of pH 4.5 and in pure water, at 37 degrees C. The MCC pretreated with different solvents show different thermal properties and ASA release rates, each MCC showing a particular behavior.

  3. Acetylsalicylic acid inhibits cell proliferation by involving transforming growth factor-beta.

    Science.gov (United States)

    Redondo, Santiago; Santos-Gallego, Carlos G; Ganado, Patricia; García, Marta; Rico, Laura; Del Rio, Marcela; Tejerina, Teresa

    2003-02-04

    Acetylsalicylic acid (ASA) inhibits cell proliferation. This may be mediated by transforming growth factor-beta (TGF-beta). TGF-beta directly stops cell proliferation, restrains cells in G(0), and inhibits the uptake of platelet-derived growth factor and insulin-like growth factor. These effects are identical to those observed with ASA treatment. We cultured rat thoracic aorta vascular smooth muscle cells and measured cytotoxicity, cell proliferation, cell cycle, transcription of TGF-beta1, and concentration of TGF-beta1 in supernatant medium. ASA dose-dependently restrained cells in G(0) phase with no cytotoxic effect and inhibited cell proliferation by 30.86%. Anti-TGF-beta1 reversed this inhibition by 30.21%. However, ASA treatment decreased TGF-beta1 transcription and had no significant effect on TGF-beta1 concentration. TGF-beta seems to play an important role in ASA-mediated inhibition of cell proliferation. Therefore, treatment with ASA prevents coronary disease not only by means of its antiplatelet properties but also by an important inhibition of plaque growth. This relationship between ASA and TGF-beta explains many other effects, such as cancer chemoprevention, immunomodulation, and wound healing. The aim of this study was to demonstrate this link.

  4. Antiplatelet effect of acetylsalicylic acid, metamizole and their combination - in vitro and in vivo comparisons.

    Science.gov (United States)

    Papp, J; Sandor, B; Vamos, Z; Botor, D; Toth, A; Rabai, M; Kenyeres, P; Cseplo, P; Juricskay, I; Mezosi, E; Koller, A; Toth, K

    2014-01-01

    Acetylsalicylic acid (ASA) plays an important role in the treatment and prevention of cardiovascular diseases. Metamizole (MET) is an analgesic and antipyretic medicine, it is not used as an antiplatelet drug. We aimed to examine the antiplatelet effect of MET and the possible interactions between the drugs. In our in vitro investigations different concentrations of ASA and MET solutions were added to blood. To examine the interactions MET and ASA were added together. In our in vivo crossover study intravenous MET, oral ASA or both drugs together were administered. Epinephrine and adenosine-diphosphate induced platelet aggregation was determined by optical aggregometry. Epinephrine-induced aggregation was completely inhibited in all ASA and MET concentrations in vitro. Lower, ineffective concentration of MET prevented the antiplatelet effect of ASA. The inhibition was completely restored when higher concentration of ASA was used or when ASA was added first. Our in vivo study showed that in the MET group rapid onset of inhibition was developed and there was no inhibition after one day. In the ASA group platelet aggregation decreased slowly but still had significant inhibitory effect after 72 hours. Combined therapy showed similar changes to the MET group. Antiplatelet effect of MET and ASA did not differ significantly in vitro. The observations may indicate a competitive interaction between the two drugs. The in vivo experiments showed that intravenously administered MET is an effective antiplatelet drug and can be considered as a therapeutic alternative, when ASA cannot be used in oral form.

  5. Acetylsalicylic acid enhances and synchronizes thidiazuron-induced somatic embryogenesis in geranium (Pelargonium x hortorum Bailey) tissue cultures.

    Science.gov (United States)

    Hutchinson, M J; Saxena, P K

    1996-03-01

    Thidiazuron (TDZ) effectively induced somatic embryogenesis in cultured hypocotyl explants of geranium (Pelargonium x hortorum Bailey) during only a 3-day period of induction. The presence of acetylsalicylic acid (ASA) during this period caused a two-fold increase in the number of somatic embryos and enhanced synchronization of embryo development compared to the TDZ treatment alone. Salicylic acid was ineffective in modulating similar embryogenic responses as ASA. The ASA-induced enhancement and synchronization of somatic embryogenesis could possibly be used as an experimental system to study the interplay of growth regulators in somatic embryogenesis.

  6. Effects of caffeine and paracetamol alone or in combination with acetylsalicylic acid on prostaglandin E(2) synthesis in rat microglial cells.

    Science.gov (United States)

    Fiebich, B L; Lieb, K; Hüll, M; Aicher, B; van Ryn, J; Pairet, M; Engelhardt, G

    2000-08-23

    Paracetamol has mild analgesic and antipyretic properties and is, along with acetylsalicylic acid, one of the most popular "over the counter" analgesic agents. However, the mechanism underlying its clinical effects is unknown. Another drug whose mechanism of action is unknown is caffeine, which is often used in combination with other analgesics, augmenting their effect. We investigated the inhibitory effect of paracetamol and caffeine on lipopolysaccharide (LPS)-induced cyclooxygenase (COX)- and prostaglandin (PG)E(2)-synthesis in primary rat microglial cells and compared it with the effect of acetylsalicylic acid, salicylic acid, and dipyrone. Furthermore, combinations of these drugs were used to investigate a possible synergistic inhibitory effect on PGE(2)-synthesis. Both paracetamol (IC(50)=7.45 microM) and caffeine (IC(50)=42.5 microM) dose-dependently inhibited microglial PGE(2) synthesis. In combination with acetylsalicylic acid (IC(50)=3.12 microM), both substances augmented the inhibitory effect of acetylsalicylic acid on LPS-induced PGE(2)-synthesis. Whereas paracetamol inhibited only COX enzyme activity, caffeine also inhibited COX-2 protein synthesis. These results are compatible with the view that the clinical activity of paracetamol and caffeine is due to inhibition of COX. Furthermore, these results may help explain the clinical experience of an adjuvant analgesic effect of caffeine and paracetamol when combined with acetylsalicylic acid.

  7. Aspirin, 110 years later.

    Science.gov (United States)

    Patrono, C; Rocca, B

    2009-07-01

    Although conceived at the end of the 19th century as a synthetic analgesic agent with improved gastric tolerability vs. naturally occurring salicylates, acetylsalicylic acid (marketed as aspirin in 1899) turned out to be an ideal antiplatelet agent about 90 years later, following the understanding of its mechanism of action, the development of a mechanism-based biomarker for dose-finding studies, and the initiation of a series of appropriately sized, randomized clinical trials to test its efficacy and safety at low doses given once daily. At the turn of its 110th anniversary, aspirin continues to attract heated debates on a number of issues including (i) the optimal dose to maximize efficacy and minimize toxicity; (ii) the possibility that some patients may be 'resistant' to its antiplatelet effects; and (iii) the balance of benefits and risks in primary vs. secondary prevention.

  8. Gastroprotective effects of sulforaphane and thymoquinone against acetylsalicylic acid-induced gastric ulcer in rats.

    Science.gov (United States)

    Zeren, Sezgin; Bayhan, Zulfu; Kocak, Fatma Emel; Kocak, Cengiz; Akcılar, Raziye; Bayat, Zeynep; Simsek, Hasan; Duzgun, Sukru Aydin

    2016-06-15

    Nonsteroidal anti-inflammatory drugs (NSAIDs) commonly cause gastric ulcers (GUs). We investigated the effects of sulforaphane (SF) and thymoquinone (TQ) in rats with acetylsalicylic acid (ASA)-induced GUs. Thirty-five male Wistar-Albino rats were divided into five groups: control; ASA; ASA with vehicle; ASA + SF; and ASA + TQ. Compounds were administered by oral gavage before GU induction. GUs were induced by intragastric administration of ASA. Four hours after GU induction, rats were killed and stomachs excised. Total oxidant status, total antioxidant status, total thiol, nitric oxide, asymmetric dimethylarginine, tumor necrosis factor-alpha levels, superoxide dismutase activity, and glutathione peroxidase activity in tissue were measured. Messenger RNA expression of dimethylarginine dimethylaminohydrolases, heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2, and nuclear factor kappa-light-chain-enhancer of activated B cells were analyzed. Renal tissues were evaluated by histopathologic and immunohistochemical means. SF and TQ reduced GU indices, apoptosis, total oxidant status, asymmetric dimethylarginine, and tumor necrosis factor-alpha levels, nuclear factor kappa-light-chain-enhancer of activated B cells, and inducible nitric oxide synthase expressions (P < 0.001, P = 0.001). Both examined compounds increased superoxide dismutase activity, glutathione peroxidase activity, total antioxidant status, total thiol, nitric oxide levels, endothelial nitric oxide synthase, dimethylarginine dimethylaminohydrolases, HO-1, nuclear factor erythroid 2-related factor 2, and HO-1 expressions (P < 0.001). These results suggest that pretreatment with SF or TQ can reduce ASA-induced GUs via anti-inflammatory, antioxidant, and antiapoptotic effects. These compounds may be useful therapeutic strategies to prevent the gastrointestinal adverse effects that limit nonsteroidal anti-inflammatory drugs use. Copyright © 2016 Elsevier Inc. All rights

  9. Intravenous acetylsalicylic acid, magnesium and their combination in experimental arterial thrombosis in rats.

    Science.gov (United States)

    Fuglsang, J; Ravn, H B; Toft, G E; Thorwest, M; Husted, S E; Hjortdal, V E

    1999-09-01

    Intravenous acetylsalicylic acid (ASA) and magnesium (Mg) both possess antiplatelet properties and are thus potential inhibitors of the formation of arterial thrombi. Their effect on the dynamic aspects of arterial thrombus formation was investigated following intravenous administration of both substances alone and in combination. A blinded, placebo-controlled, in-vivo study was performed in 71 rats. Thrombus formation was induced by a standardized arteriotomy in the right femoral artery with inversion of the vessel wall during subsequent closure. Thrombus formation was recorded on video tapes and analysed off-line for 30 min. Animals were randomly assigned to one of four groups: 20 mg bolus of ASA followed by 0.3 mmol/h Mg (ASA/Mg group); NaCl followed by 0.3 mmol/h Mg (Mg group); 20 mg bolus of ASA followed by NaCl (ASA group); or NaCl throughout the experiment (control group). In the ASA-treated groups, serum levels of thromboxane B2 were reduced significantly, and the Mg-treated groups reached a serum level of Mg just above 2.0 mmol/l. No significant differences were observed in initial or maximum thrombus area or in mean thrombus area during the study period. In the ASA/Mg group, a trend towards reduced thrombus formation was observed (P = 0.06). In the same group, seven of 22 animals developed an occlusive thrombus (P < 0.01), an unexpected adverse event possibly related to the combined administration of ASA and Mg.

  10. Acetylsalicylic acid exhibits anticlastogenic effects on cultured human lymphocytes exposed to doxorubicin.

    Science.gov (United States)

    Antunes, Lusânia Maria Greggi; de Barros E Lima Bueno, Rafaela; da Luz Dias, Francisca; de Lourdes Pires Bianchi, Maria

    2007-01-10

    Acetylsalicylic acid (ASA) is a non-steroidal anti-inflammatory drug (NSAID) with many pharmacological properties, such as anti-inflammatory, antipyretic and analgesic. Many studies have suggested the possible efficiency of ASA and other NSAIDs in preventing cancer. ASA could also have antimutagenic and antioxidant properties. The aim of this study was to investigate the possible clastogenic and anticlastogenic effects of different concentrations of ASA on doxorubicin-induced chromosomal aberrations in human lymphocytes. Human blood samples were obtained from six healthy, non-smoking volunteers; and the chromosomal aberration assay was carried out using conventional techniques. The parameters analyzed were mitotic index, total number of chromosomal aberrations and percentage of aberrant metaphases. The concentrations of ASA (25, 50 or 100 microg/mL) tested in combination with DXR (0.2 microg/mL) were established on the basis of the results of the mitotic index. The treatment with ASA alone was neither cytotoxic nor clastogenic (p>0.01). In lymphocyte cultures treated with different combinations of ASA and DXR, a significant decrease in the total number of chromosome aberrations was observed compared with DXR alone (p<0.01). This protective effect of ASA on DXR-induced chromosomal damage was obtained for all combinations, and it was most evident when ASA was at 25.0 microg/mL. In our experiments, ASA may have acted as an antioxidant and inhibited the chromosomal damage induced by the free radicals generated by DXR. The identification of compounds that could counteract the free radicals produced by doxorubicin could be of possible benefits against the potential harmful effects of anthracyclines. The results of this study show that there is a relevant need for more investigations in order to elucidate the mechanisms underlying the anticlastogenic effect of ASA.

  11. Acetylsalicylic acid interferes with embryonic kidney growth and development by a prostaglandin-independent mechanism.

    Science.gov (United States)

    Welham, Simon J M; Sparrow, Alexander J; Gardner, David S; Elmes, Matthew J

    2017-01-06

    To evaluate the effects of the non-selective, non-steroidal anti-inflammatory drug (NSAID) acetylsalicylic acid (ASA), on ex vivo embryonic kidney growth and development. Pairs of fetal mouse kidneys at embryonic day 12.5 were cultured ex vivo in increasing concentrations of ASA (0.04-0.4 mg/mL) for up to 7 d. One organ from each pair was grown in control media and was used as the internal control for the experimental contralateral organ. In some experiments, organs were treated with ASA for 48 h and then transferred either to control media alone or control media containing 10 μmol/L prostaglandin E2 (PGE2) for a further 5 d. Fetal kidneys were additionally obtained from prostaglandin synthase 2 homozygous null or heterozygous (PTGS2(-/-) and PTGS2(-/+)) embryos and grown in culture. Kidney cross-sectional area was used to determine treatment effects on kidney growth. Whole-mount labelling to fluorescently detect laminin enabled crude determination of epithelial branching using confocal microscopy. Increasing ASA concentration (0.1, 0.2 and 0.4 mg/mL) significantly inhibited metanephric growth (P growth area to control levels. Application of control media alone after cessation of ASA exposure showed no benefit on kidney growth. Despite the apparent recovery of growth area with 10 μmol/L PGE2, no obvious renal tubular structures were formed. The number of epithelial tips generated after 48 h exposure to ASA was reduced by 40% (0.2 mg/mL; P growth of PTGS2(-/-) and PTGS2(+/-) kidneys in organ culture showed no differences, indicating that PTGS2 derived PGE2 may at best have a minor role. ASA reduces early renal growth and development but the role of prostaglandins in this may be minor.

  12. Effects of oral prednisone administration with or without ultralow-dose acetylsalicylic acid on coagulation parameters in healthy dogs.

    Science.gov (United States)

    O'Kell, Allison L; Grant, David C; Panciera, David L; Troy, Gregory C; Weinstein, Nicole M

    2012-10-01

    To determine the effects of oral prednisone administration with or without ultralow-dose acetylsalicylic acid on coagulation parameters in healthy dogs and to assess intraindividual variation in thromboelastography results. 14 healthy research dogs and 10 healthy client-owned dogs. In a randomized controlled trial, research dogs underwent thromboelastography twice (3 days apart), and intraindividual variation in test results was calculated. Dogs were given prednisone (2 mg/kg/d, PO) plus acetylsalicylic acid (0.5 mg/kg/d, PO) or prednisone (2 mg/kg/d, PO) plus a placebo for 14 days, after which thromboelastography and other tests were repeated. Differences from preadministration (baseline) test results between and within groups were compared. In a separate trial, client-owned dogs also underwent thromboelastography twice 2 days apart to assess intraindividual variation in untreated dogs. Intraindividual variation in thromboelastography results for research dogs was ≤ 10% for maximum amplitude (MA) and α angle. In the research dogs, MA and fibrinogen values significantly increased from baseline, whereas percentage lysis 30 minutes after attainment of the MA as well as antithrombin activity significantly decreased within each group. In the dogs that received prednisone plus a placebo, percentage lysis 60 minutes after attainment of the MA was significantly lower than at baseline. For all parameters for research dogs, there was no difference between groups for change from baseline. Intraindividual variation in findings for client-owned dogs was similar to the variation for research dogs. Prednisone administration resulted in hypercoagulability in healthy dogs as indicated by an increase in MA and plasma fibrinogen concentration and a decrease in antithrombin activity. Concurrent ultralow-dose acetylsalicylic acid use had no effect on measured thromboelastography values. The high intraindividual variation in some thromboelastography parameters may preclude routine

  13. Determination of acetylsalicylic acid in tablets with salicylate ion selective electrode in a Batch Injection Analysis system

    Directory of Open Access Journals (Sweden)

    Fernandes Julio Cesar B.

    1998-01-01

    Full Text Available The feasibility of the use of a Batch Injection Analysis (BIA system for potentiometric determination of acetylsalicylic acid in tablets, with a membrane ion selective electrode, was investigated. There is no significant difference between the results obtained by the proposed method and those obtained by the Standard British Pharmacopaeia method12 at the 95% confidence level. Values of 4% and 2.5% for R.S.D. were obtained by the application of the BIA-potentiometric method and for the injections respectively. About 90 determinations per hour can be performed with the proposed BIA potentiometric method.

  14. Characterization of a dextran–coated layered double hydroxide acetylsalicylic acid delivery system and its pharmacokinetics in rabbit

    OpenAIRE

    Dong, Li-e; Gou, Guojing; Jiao, Lin

    2013-01-01

    The aim of this study was to prepare a dextran–coated layered double hydroxide acetylsalicylic acid (DEX–LDH–ASA) delivery system by co-precipitation of LDH–ASA and its in-situ compositing with DEX. The structure of the system was investigated using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and thermogravimetry (TG). Its in vitro drug release properties and in vivo pharmacokinetics in rabbit were also determined. The results show that the DEX–LDH–ASA system reta...

  15. Resistencia al ácido acetil salicílico en pacientes con enfermedad coronaria Acetylsalicylic acid resistance in patients with chronic ischemic heart disease

    Directory of Open Access Journals (Sweden)

    Boris E. Vesga

    2006-08-01

    agregación plaquetaria en pacientes de alto riesgo y el asociar otro fármaco anti-agregante (terapia dual que garantice una mejor protección anti-trombótica en pacientes con enfermedad coronaria.Introduction: platelet anti-aggregation is the "corner stone" in the treatment of cardiovascular disease. Acetylsalicylic acid is the therapy of choice in the prevention and treatment of coronary disease, in doses of 81 - 325 mg. Objective: to assess platelet aggregation in subjects with stable coronary disease receiving acetylsalicylic acid, in order to determine its prevalence resistance. Methods: cross-sectional descriptive study in 71 subjects of 40 or more years of age with diagnosis of stable angina, who were admitted for coronary angiography performance. A peripheral venous blood sample was obtained in order to determine the platelet aggregation through arachidonic acid, epinephrine, collagen and ADP in a HELENA PACKS-4 aggregometer. Resistance to the acetylsalicylic acid was defined when having aggregations greater than 20% with arachidonic acid. The statistical analysis was developed with the exact Fisher t test of Student and Mann-Whitney according to variable distribution. Results: 71 subjects were included; 51 were male (71.8%; mean age 63.5 ± 9.4 years. Risk factors: 52 (73.2% had dyslipidemia, 48 (67.6% arterial hypertension, 15 (21.1% diabetes mellitus and 9 (12.7% were cigarette smokers; in 31 (15.9% arteriography showed one-vessel coronary disease, and multi-vessel disease in 58 (81.7%. The platelet aggregometric values obtained were: ADP: 64 ± 19.1%, collagen 72 ± 18.9%, epinephrine 43.8± 23.9% and arachidonic acid 26.1 ± 33.7%, being this one the best marker in the acetylsalicylic acid's effect. The prevalence of aspirin resistance was 28.2% (IC 95%: 18.1 -40.1. Conclusion: in our population, acetylsalicylic acid resistance is highly prevalent; for this reason, routine measurement of platelet aggregation in high risk patients must be considered, as well

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

    Science.gov (United States)

    Zhang, Ren-gang; Zhang, Jun-ping

    2007-05-01

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

  17. [The effect of exercise on the pharmacokinetics of acetaminophen and acetylsalicylic acid].

    Science.gov (United States)

    Sawrymowicz, M

    1997-01-01

    The influence of exercise on the pharmacokinetics of drugs is not sufficiently apparent. Therefore the purpose of my study was to evaluate the influence of standardized exercise on pharmacokinetics of acetaminophen and acetylsalicylic acid (ASA) and also to establish whether moderate (submaximal) exercise demands modification involving the doses of these drugs. That was studied in 20 healthy young (ranging in age 22-42 years) male subjects receiving acetaminophen or ASA, 1 g orally. All subjects were non-smokers who abstained from using caffeine and alcohol 2 weeks before and in the period of study, which consisted of two parts: resting trials and exercise trials. Exercise trials: treadmill walking--3 mph (4.8 km/h), 20 minutes per half an hour for 3 hours (50% VO2max). On the rest day volunteers stayed in the supine or sitting position for the same period. Blood samples were collected from a forearm (antecubital) vein through an indwelling cannula. Acetaminophen and ASA plasma concentrations were determined by FPIA. The plasma level-time curves were fitted according to one compartment open pharmacokinetic model. Plasma concentrations measured (7 days) before and after the physical exercise, did not demonstrate statistically significant differences (Fig. 1, 2). The results of this study indicate that the pharmacokinetics of single doses of acetaminophen and ASA are independent of submaximal physical exercise. There were no significant differences between the rest and the exercise day in the pharmacokinetic parameters of acetaminophen and ASA (Fig. 3). Since both drugs belong to the group whose elimination is not due to the liver flow, it is not surprising that its total body clearance, and its half-life of elimination were unaffected by physical exercise. The minor changes in haematocrit, plasma protein, free fatty acids, levels which were reported are probably not sufficient to modify the disposition of these drugs. Therefore, there is no need for dose adjustment

  18. [Aspirin: Indications and use during pregnancy].

    Science.gov (United States)

    Belhomme, N; Doudnikoff, C; Polard, E; Henriot, B; Isly, H; Jego, P

    2017-12-01

    Aspirin (acetylsalicylic acid) has been used ever since the Antiquity for its painkilling and anti-inflammatory effects. Its antiplatelet properties have then extended its indications to the field of coronaropathy and vascular cerebral disease, and finally to vascular placental disease. Aspirin has been widely prescribed since the 1980's to prevent pre-eclampsia, intra-uterine growth retardation and fetal death of vascular origin. It has also been proposed to prevent unexplained recurrent miscarriages. Its use during pregnancy is considered as safe, provided the daily doses do not exceed 100mg. Aspirin has been proven efficient to prevent pre-eclampsia and fetal growth restriction in high-risk patients. The benefits of prescribing aspirin have been demonstrated neither for vascular placental disease prevention in low risk patients, nor in cases of unexplained recurrent miscarriages. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  19. Acetylsalicylic acid and salicylic acid decrease tumor cell viability and glucose metabolism modulating 6-phosphofructo-1-kinase structure and activity.

    Science.gov (United States)

    Spitz, Guilherme A; Furtado, Cristiane M; Sola-Penna, Mauro; Zancan, Patricia

    2009-01-01

    The common observation that cancer cells present higher glycolytic rates when compared to control cells leads to the proposal of glycolysis as a potential target for the development of anti-tumoral agents. Anti-inflammatory drugs, such as acetylsalicylic acid (ASA) and salicylic acid (SA), present anti-tumoral properties, inducing apoptosis and altering tumor glucose utilization. The present work aims at evaluating whether ASA could directly decrease cell glycolysis through inhibition of the major regulatory enzyme within this pathway, 6-phosphofructo-1-kinase (PFK). We show that ASA and SA inhibit purified PFK in a dose-dependent manner, and that this inhibition occurs due to the modulation of the enzyme quaternary structure. ASA and SA promote the dissociation of the enzyme active tetramers into quite inactive dimers, a common regulatory mechanism of this enzyme. The inhibitory effects of ASA and SA on PFK are fully reversible and can be prevented or reverted by the binding of the enzyme to the actin filaments. Both drugs are also able to decrease glucose consumption by human breast cancer cell line MCF-7, as well as its viability, which decrease parallelly to the inhibition of PFK on these cells. In the end, we demonstrate the ability of ASA and SA to directly modulate an important regulatory intracellular enzyme, and propose that this is one of their mechanisms promoting anti-tumoral effects.

  20. An examination of binding motifs associated with inter-particle interactions between facetted nano-crystals of acetylsalicylic acid and ascorbic acid through the application of molecular grid-based search methods.

    Science.gov (United States)

    Hammond, R B; Jeck, S; Ma, C Y; Pencheva, K; Roberts, K J; Auffret, T

    2009-12-01

    Grid-based intermolecular search methods using atom-atom force fields are used to assess the structural nature of potential crystal-crystal interfacial binding associated with the examination of representative pharmaceutical formulation components, viz acetylsalicylic acid (aspirin) and ascorbic acid (vitamin C). Molecular models of nano-sized molecular clusters for these two compounds, shaped in accordance with an attachment energy model of the respective particle morphologies, are constructed and used together with a grid-based search method to model the likely inter-particle interactions. The most-stable, mutual alignments of the respective nano-clusters based on their interaction energies are identified in the expectation that these are indicative of the most likely inter-particle binding configurations. The stable inter-particle binding configurations identified reveal that the number of interfacial hydrogen bonds formed between the binding particles is, potentially, an important factor in terms of the stability of inter-particle cohesion. All preferred inter-particle alignments are found to involve either the (1 0 0) or the (1 1 0) face of aspirin crystals interacting with a number of the growth forms of ascorbic acid. Four main types of interfacial hydrogen bonds are found to be associated with inter-particle binding and involve acceptor-donor interactions between hydroxyl, carbonyl, ester and lactone acceptor groups and hydroxyl donor groups. This hydrogen bonding network is found to be consistent with the surface chemistry of the interacting habit faces with, in general, the number of hydrogen bonds increasing for the more stable alignments. The likely usefulness of this approach for predicting solid-state formulation properties is reviewed. 2009 Wiley-Liss, Inc. and the American Pharmacists Association

  1. [Experimental model for the study of the teratogenic interaction of chemical agents and drugs (toluene and acetylsalicylic acid)].

    Science.gov (United States)

    Tátrai, E; Hudák, A; Ungváry, G

    1979-10-01

    On the 10th-13th days of pregnancy toluene (3600 mg/m3) by inhalation) and on 12th day acetylsalicylic acid (500 mg/kg of body weight per os) were administered to CFY rats and the common effect of these agents was studied. It was established that: 1. the maternal toxicity increased, i.e. increased the mortality rate, decreased the consumption of the food and the gain of weight, increased the relative weight of the liver; 2. the foetal toxicity increased, i.e. increased the mortality rate of foetuses, the rate of the loss of the body weight, the number of the anomalies of the sternum and the incidence of the supernumerary ribs. It is believed, that the non-teratogenic toluene rises the utilization of the glycine and the level of the free salicylic-acid, consequently the embryotoxic effect of the acetylsalicylic-acid. The danger of the occurrence of malformations as an effect of interaction of chemical agents and drugs taken in therapeutic doses is stressed.

  2. Mechanism of Acetyl Salicylic Acid (Aspirin Degradation under Solar Light in Presence of a TiO2-Polymeric Film Photocatalyst

    Directory of Open Access Journals (Sweden)

    Debjani Mukherjee

    2016-04-01

    Full Text Available Application of titanium dioxide (TiO2 as a photocatalyst has presented a promising avenue for the safe photocatalytic degradation of pollutants. Increasing levels of the release of pharmaceuticals in the environment and formation of the intermediates during their degradation may impose health and environmental risks and therefore require more attention. Photocatalytic degradation of acetylsalicylic acid (aspirin was carried out in the presence of the TiO2-filled polymeric film as a photocatalyst under solar light irradiation. The polymeric film incorporates TiO2 in the matrix, which acts as a photocatalyst under solar illumination and degrades the acetyl salicylic acid (ASA into a range of organic compounds before complete demineralization (formation of carbon dioxide and water as final products. Among the intermediates, acetic acid was found to be present in a larger amount compared to other organic acids. The qualitative/quantitative analyses of the intermediates resulted in the determination of the most probable reaction’s mechanism in the degradation process. The mechanism of degradation of acetylsalicylic acid and its reaction pathway were developed from liquid chromatography/mass spectroscopy (LC/MS, Fourier Transform Infra Red (FTIR and UV spectrophotometric analysis. It was found that hydroxyl groups were dominant in the degradation process compared to electrons and holes generated by TiO2. The total organic carbon (TOC analysis was also carried out to analyze the organic carbon content of the intermediates formed during the course of degradation.

  3. Low-dose aspirin and rupture of abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Wemmelund, Holger; Jørgensen, Trine M M; Høgh, Annette

    2016-01-01

    OBJECTIVE: The use of low-dose aspirin (acetylsalicylic acid [ASA]) has been suggested to attenuate growth of abdominal aortic aneurysms (AAAs), yet solid clinical evidence of this hypothesis is still missing. This study aimed to investigate whether preadmission ASA use influenced the risk...

  4. Low-dose aspirin and rupture ofabdominal aortic aneurysm: A nationwide, population-based study

    DEFF Research Database (Denmark)

    Wemmelund, H.; Jørgensen, T.; Høgh, A.

    OBJECTIVE: The use of low-dose aspirin (acetylsalicylic acid [ASA]) has been suggested to attenuate growth of abdominal aortic aneurysms (AAAs), yet solid clinical evidence of this hypothesis is still missing. This study aimed to investigate whether preadmission ASA use influenced the risk...

  5. [From the willow to aspirin].

    Science.gov (United States)

    Lafont, Olivier

    2007-07-01

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

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

    Science.gov (United States)

    El-Shahawy, Anwar S.

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

  7. Novel {beta}-cyclodextrin modified CdTe quantum dots as fluorescence nanosensor for acetylsalicylic acid and metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Algarra, M. [Centro de Geologia do Porto, Faculdade de Ciencias, Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto (Portugal); Campos, B.B.; Aguiar, F.R.; Rodriguez-Borges, J.E. [Centro de Investigacao em Quimica (CIQ-UP), Faculdade de Ciencias da Universidade do Porto, Rua do Campo Alegre 687, 169-007 Porto (Portugal); Esteves da Silva, J.C.G., E-mail: jcsilva@fc.up.pt [Centro de Investigacao em Quimica (CIQ-UP), Faculdade de Ciencias da Universidade do Porto, Rua do Campo Alegre 687, 169-007 Porto (Portugal)

    2012-05-01

    {beta}-Cyclodextrin was modified with 11-[(ethoxycarbonyl)thio]undecanoic acid and used as a capping agent, together with mercaptosuccinic acid, to prepare water-stable CdTe quantum dots. The water soluble quantum dot obtained displays fluorescence with a maximum emission at 425 nm (under excitation at 300 nm) with lifetimes of 0.53, 4.8, 181, and 44.1 ns, respectively. The S-{beta}CD-MSA-CdTe can act as a nanoprobe that is due to the affinity of the cyclodextrin moiety for selected substances such as acetylsalicylic acid (ASA) and its metabolites as foreign species. The fluorescence of the S-{beta}CD-MSA-CdTe is enhanced on addition of ASA. Linear calibration plots are observed with ASA in concentrations between 0 and 1 mg/l, with a limit of detection at 8.5 Multiplication-Sign 10{sup -9} mol/l (1.5 ng/ml) and a precision as relative standard deviation of 1% (0.05 mg/l). The interference effect of certain compounds as ascorbic acid and its main metabolites such as salicylic, gentisic and salicyluric acid upon the obtained procedure was studied. Highlights: Black-Right-Pointing-Pointer Nanosensors constituted by CdTe quantum dots capped with modified cyclodextrin. Black-Right-Pointing-Pointer This nanomaterial shows fluorescence properties compatible with a semiconductor quantum dot. Black-Right-Pointing-Pointer The nanosensor shows fluorescence enhancement when inclusion complexes are formed with acetylsalicylic acid. Black-Right-Pointing-Pointer This nanomaterial has nanosensor potential taking into consideration the formation stability of the inclusion complex.

  8. Stopping versus continuing acetylsalicylic acid before coronary artery bypass surgery: A systematic review and meta-analysis of 14 randomized controlled trials with 4499 patients.

    Science.gov (United States)

    Sá, Michel Pompeu Barros Oliveira; Soares, Artur Freire; Miranda, Rodrigo Gusmão Albuquerque; Araújo, Mayara Lopes; Menezes, Alexandre Motta; Silva, Frederico Pires Vasconcelos; Lima, Ricardo Carvalho

    2017-11-01

    This study aimed to evaluate the efficacy and safety of continuing versus stopping aspirin [acetylsalicylic acid (ASA)] preoperatively in patients undergoing coronary artery bypass graft surgery. MEDLINE, EMBASE, CENTRAL/Cochrane Controlled Trials Register (CCTR), ClinicalTrials.gov, Scientific Electronic Library Online (SciELO), Literatura Latino Americana em Ciências da Saúde (LILACS), Google Scholar and reference lists of relevant articles were searched for randomized controlled trials that reported efficacy outcomes of myocardial infarction and mortality, and safety outcomes of blood loss, packed red blood cell transfusion and surgical re-exploration were compared between groups. Fourteen studies fulfilled our eligibility criteria and included a total of 4499 patients (2329 for 'continuing ASA' and 2170 for 'stopping ASA'). In the pooled analysis, continuing aspirin therapy did not reduce the risk of myocardial infarction [risk ratio 0.834, 95% confidence interval (CI) 0.688-1.010; P = 0.063] or operative mortality (risk ratio 1.384, 95% CI 0.727-2.636; P = 0.323). Preoperative ASA increased postoperative chest tube drainage (mean difference 143 ml, 95% CI 39-248 ml; P = 0.007) and packed red blood cell transfusion (mean difference 142 ml, 95% CI 55-228; P = 0.001) but did not increase the risk of surgical re-exploration (risk ratio 1.316, 95% CI 0.910-1.905; P = 0.145). This meta-analysis found no statistically significant difference regarding the risk of operative mortality and myocardial infarction between the 'continuing ASA' and 'stopping ASA' strategies. On the other hand, the mean volume of blood loss and packed red blood cell transfusion was higher in the 'continuing ASA' group, but this finding did not translate into higher risk of reoperation for bleeding. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  9. Is aspirin a cause of Reye's syndrome? A case against.

    Science.gov (United States)

    Orlowski, James P; Hanhan, Usama A; Fiallos, Mariano R

    2002-01-01

    Reye's syndrome was a rare disease which appeared suddenly in the early 1950s and disappeared just as suddenly in the late 1980s. An association between Reye's syndrome and the ingestion of aspirin (acetylsalicylic acid) was claimed, although no proof of causation was ever established. The presence of salicylates in the blood or urine of Reye's syndrome patients has not been demonstrated, and no animal model of Reye's syndrome has been developed where aspirin causes the disease. It is clear from epidemiological data that the incidence of Reye's syndrome was decreasing well before warning labels were placed on aspirin products. Reye's syndrome disappeared from countries where aspirin was not used in children as well as from countries which continued to use aspirin in children. Reye's syndrome was probably either a viral mutation which spontaneously disappeared, or a conglomeration of metabolic disorders that had not been recognized or described at that time.

  10. Structure, stability, and antiplatelet activity of O-acyl derivatives of salicylic acid and lipophilic esters of acetylsalicylate.

    Science.gov (United States)

    Zavodnik, Ilya B; Lapshina, Elena; Sudnikovich, Elena; Boncler, Magdalena; Luzak, Bogusława; Rózalski, Marcin; Helińska, Magdalena; Watała, Cezary

    2009-01-01

    The anti-thrombotic activity of acetylsalicylic acid (ASA) has been shown to be due to specific irreversible acetylation of blood platelet cyclooxygenase. The aim of our study was to investigate the associations between the antiplatelet activities of derivatives of both ASA and salicylic acid (SA), as well as the structure, stability, and molecular properties of these compounds. Homologous series of O-acyl derivatives of salicylic acid (propionyl-, butyrylsalicylic acids, PSA, BSA) and lipophilic dodecyl (C12)-, hexadecyl (C16)-, and cholesteryl acetylsalicylates were synthesized and tested for structure-activity relationships. The molecular properties (heat of formation, molecular surface area, dipole moment) of ASA and SA derivatives obtained by theoretical calculations changed with the increasing length of the acyl or alkyl residue. The inhibition of whole blood platelet aggregation and the reduction in thromboxane (TX) generation by O-acyl derivatives were concentration-dependent and decreased along with increasing the length of acyl hain. These effects correlated with the extent of platelet reactivity and P-selectin expression inhibition in collagen-activated platelets. In contrast to ASA and O-acyl derivatives of SA, none of the lipophilic ASA derivatives had a significant inhibitory effect on platelet aggregation. In conclusion, all SA and ASA derivatives studied under in vitro conditions showed much lower antiplatelet activities than ASA itself, despite their higher affinity to plasma proteins or membrane components and their equivalent ability to acetylate protein free amino groups.We suggest the significance of the carboxylic group, dipole moment, geometry, and size of these pharmaceuticals in their ability to bind to the active site of cyclooxygenase and their antiplatelet efficacy.

  11. The Effect of Roux-en-Y Gastric Bypass Surgery in Morbidly Obese Patients on Pharmacokinetics of (Acetyl)Salicylic Acid and Omeprazole : the ERY-PAO Study

    NARCIS (Netherlands)

    Mitrov-Winkelmolen, Lieke; van Buul-Gast, Marie-Christine W; Swank, Dingeman J; Overdiek, Hans W P M; van Schaik, Ron H N; Touw, Daan J

    Data on the absorption of orally administered drugs following Roux-en-Y gastric bypass (RYGB) surgery in obese patients are limited and inconclusive. As it is difficult to predict changes in absorption, studies on frequently used drugs in this population are necessary. Acetylsalicylic acid (ASA) and

  12. Promoting endothelial recovery and reducing neointimal hyperplasia using sequential-like release of acetylsalicylic acid and paclitaxel-loaded biodegradable stents.

    Science.gov (United States)

    Lee, Cheng-Hung; Yu, Chia-Ying; Chang, Shang-Hung; Hung, Kuo-Chun; Liu, Shih-Jung; Wang, Chao-Jan; Hsu, Ming-Yi; Hsieh, I-Chang; Chen, Wei-Jan; Ko, Yu-Shien; Wen, Ming-Shien

    2014-01-01

    This work reports on the development of a biodegradable dual-drug-eluting stent with sequential-like and sustainable drug-release of anti-platelet acetylsalicylic acid and anti-smooth muscle cell (SMC) proliferative paclitaxel. To fabricate the biodegradable stents, poly-L-lactide strips are first cut from a solvent-casted film. They are rolled onto the surface of a metal pin to form spiral stents. The stents are then consecutively covered by acetylsalicylic acid and paclitaxel-loaded polylactide-polyglycolide nanofibers via electrospinning. Biodegradable stents exhibit mechanical properties that are superior to those of metallic stents. Biodegradable stents sequentially release high concentrations of acetylsalicylic acid and paclitaxel for more than 30 and 60 days, respectively. In vitro, the eluted drugs promote endothelial cell numbers on days 3 and 7, and reduce the proliferation of SMCs in weeks 2, 4, and 8. The stents markedly inhibit the adhesion of platelets on days 3, 7, and 14 relative to a non-drug-eluting stent. In vivo, the implanted stent is intact, and no stent thrombosis is observed in the stent-implanted vessels without the administration of daily oral acetylsalicylic acid. Promotion of endothelial recovery and inhibition of neointimal hyperplasia are also observed on the stented vessels. The work demonstrates the efficiency and safety of the biodegradable dual-drug-eluting stents with sequential and sustainable drug release to diseased arteries.

  13. An alkyne-aspirin chemical reporter for the detection of aspirin-dependent protein modification in living cells.

    Science.gov (United States)

    Bateman, Leslie A; Zaro, Balyn W; Miller, Stephanie M; Pratt, Matthew R

    2013-10-02

    Aspirin (acetylsalicylic acid) is widely used for the acute treatment of inflammation and the management of cardiovascular disease. More recently, it has also been shown to reduce the risk of a variety of cancers. The anti-inflammatory properties of aspirin in pain-relief, cardio-protection, and chemoprevention are well-known to result from the covalent inhibition of cyclooxygenase enzymes through nonenzymatic acetylation of key serine residues. However, any additional molecular mechanisms that may contribute to the beneficial effects of aspirin remain poorly defined. Interestingly, studies over the past 50 years using radiolabeled aspirin demonstrated that other proteins are acetylated by aspirin and enrichment with antiacetyl-lysine antibodies identified 33 potential targets of aspirin-dependent acetylation. Herein we describe the development of an alkyne-modified aspirin analogue (AspAlk) as a chemical reporters of aspirin-dependent acetylation in living cells. When combined with the Cu(I)-catalyzed [3 + 2] azide-alkyne cycloaddition, this chemical reporter allowed for the robust in-gel fluorescent detection of acetylation and the subsequent enrichment and identification of 120 proteins, 112 of which have not been previously reported to be acetylated by aspirin in cellular or in vivo contexts. Finally, AspAlk was shown to modify the core histone proteins, implicating aspirin as a potential chemical-regulator of transcription.

  14. Simultaneous Determination of Acetylsalicylic Acid, Hydrochlorothiazide, Enalapril, and Atorvastatin in a Polypill-Based Quaternary Mixture by TLC.

    Science.gov (United States)

    Maślanka, Anna; Stolarczyk, Mariusz; Apola, Anna; Kwiecień, Anna; Hubicka, Urszula; Opoka, Włodzimierz

    2017-09-07

    A new chromatographic-densitometric method has been developed for the qualitative and quantitative determination of the active ingredients in a simulated mixture corresponding to the PolyIran polypill, composed of acetylsalicylic acid, hydrochlorothiazide (HCT), enalapril (ENA), and atorvastatin (ATR), whose efficacy in the treatment and prevention of cardiovascular disease has been documented in clinical trials. Chromatographic separation was performed using TLC silica gel 60 plates with fluorescent indicator F254 as the stationary phase and a mixture of n-hexane-ethyl acetate-methanol-water-acetic acid (8.4 + 8 + 3 + 0.4 + 0.2, v/v/v/v/v) as the mobile phase. Densitometric measurements were carried out at λ = 210 nm when determining ENA and at λ = 265 nm in the case of the other drugs. Peaks of examined substances were well separated in the recorded chromatograms, enabling the evaluation of the results in terms of both qualitative and quantitative analysis. The method was specific for the analyzed components and was characterized by high sensitivity. The LOD was between 0.043 and 0.331 μg/spot, and LOQ was between 0.100 and 0.942 μg/spot. Recovery was in the range of 97.02-101.34%. The linearity range was broad and ranged from 0.600 to 6.000 μg/spot for acetylsalicylic acid, from 0.058 to 1.102 μg/spot for HCT, from 0.505 to 6.560 μg/spot for ENA, and from 0.100 to 1.000 μg/spot for ATR. The method was characterized by good precision, with RSD values ​that ranged from 0.10 to 2.26%.

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

    Science.gov (United States)

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

    2015-09-01

    Ascorbic acid in combination with aspirin has been used to prevent aspirin-induced oxidative GI damage. We aimed to determine whether ascorbic acid reduces or prevents aspirin-induced changes in intestinal permeability over a 6-hr period using saccharidic probes mannitol and lactulose. The effects of administration of 600 mg aspirin alone, 500 mg ascorbic acid alone and simultaneous dosage of both agents were compared in a cross-over study in 28 healthy female volunteers. These effects were also compared with that of a placebo. The ability of ascorbic acid to mitigate the effects of aspirin when administered either half an hour before or after dosage with aspirin was also assessed in 19 healthy female volunteers. The excretion of lactulose over the 6-hr period was augmented after consumption of either aspirin or ascorbic acid compared with that after consumption of placebo. Dosage with ascorbic acid alone augmented the excretion of lactulose more than did aspirin alone. Simultaneous dosage with both agents augmented the excretion of lactulose in an additive manner. The timing of dosage with ascorbic acid in relation to that with aspirin had no significant effect on the excretion of the two sugars. These findings indicate that ascorbic acid does not prevent aspirin-induced increase in gut permeability rather that both agents augment it to a similar extent. The additive effect on simultaneous dosage with both agents in augmenting the absorption of lactulose suggests that each influences paracellular permeability by different pathways. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  16. One-step synthesis of porous copper oxide for electrochemical sensing of acetylsalicylic acid in the real sample.

    Science.gov (United States)

    Sivakumar, Mani; Sakthivel, Mani; Chen, Shen-Ming; Cheng, Yi-Hui; Pandi, Karuppiah

    2017-09-01

    A Facile approach of one-step synthesis was employed to prepare porous CuO at different annealing temperature and characterized by using numerous analytical techniques. Moreover, the electrochemical sensing application of CuO modified glassy carbon electrode was studied and recorded using various electrochemical techniques. From the results, it was interpreted that the CuO prepared at 350°C exhibits satisfactorily electrochemical determination of Acetylsalicylic acid (ASA) with unique sensitivity, linear range and limit of detection of about 831.65µA mM(-1)cm(-2), 0.1-714µM and 0.037µM respectively. The proposed sensor also shows good electrocatalytic performance in real sample analysis with acceptable results. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Novel metal complexes of mixed piperaquine-acetaminophen and piperaquine-acetylsalicylic acid: Synthesis, characterization and antimicrobial activities

    Directory of Open Access Journals (Sweden)

    Yusuf Oloruntoyin Ayipo

    2016-11-01

    Full Text Available Synthesis of coordination compounds of Zinc(II, Copper(II, Nickel(II, Cobalt(II and Iron(II with mixed piperaquine-acetaminophen and piperaquine-acetylsalicylic acid has been studied. The complexes were characterized via: solubility test, melting point determination, conductivity measurement, Atomic Absorption Spectroscopy, UV-Visible Spectroscopy, FTIR Spectroscopy and magnetic susceptibility. The complexes were proposed to have a stoichiometry ratio of 1:1:1 between each metal salt and the ligands with tetrahedral and octahedral geometry following the reaction pattern of MX.yH2O + L1L2/3 to give ML1L2/3X.yH2O. Biological activities of the synthesized complexes have been evaluated against Escherichia coli and Staphylococcus aureus.

  18. Simultaneous determination of acetylsalicylic acid, paracetamol and caffeine using solid-phase molecular fluorescence and parallel factor analysis.

    Science.gov (United States)

    Alves, Julio Cesar L; Poppi, Ronei J

    2009-05-29

    This paper describes the determination of acetylsalicylic acid (ASA), paracetamol and caffeine in pharmaceutical formulations using solid-phase molecular fluorescence and second order multivariate calibration. This methodology is applicable even in the presence of unknown interferences and with spectral overlap of the components in the mixture. Parallel factor analysis (PARAFAC) was used for model development, whose effectiveness was demonstrated by analysis of variance (ANOVA). Errors below 10% were obtained for all compounds using an external validation set. Benefits of the new procedures not included in the reference methods such as low cost, no need of sample preparation, simple and fast analysis using fluorescence spectrometer and no generation of waste, make this method very attractive, allowing for the simultaneous determination of compounds with good reproducibility and accuracy.

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

    National Research Council Canada - National Science Library

    Andersen, V; Vogel, U

    2014-01-01

    ... may be considered. Nonsteroidal anti‐inflammatory drugs (NSAIDs) include aspirin (acetylsalicylic acid, ASA). Long‐term use of NSAIDs has been associated with lowered risk of CRC in prospective population‐based studies. The primary anti‐inflammatory effects of NSAIDs is competitive inhibition of cyclooxygenases (COX) 1 and 2 which catalyse t...

  20. Dose-dependent immunomodulatory effects of acetylsalicylic acid and indomethacin in human whole blood: potential role of cyclooxygenase-2 inhibition.

    Science.gov (United States)

    Härtel, C; von Puttkamer, J; Gallner, F; Strunk, T; Schultz, C

    2004-10-01

    The aim of the study was to characterize the in vitro effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the production of pro-inflammatory cytokines in a human whole blood assay. Whole blood samples were pre-incubated with acetylsalicylic acid, indomethacin, selective cyclooxygenase (COX)-1 inhibitor (SC-560), COX-2 inhibitor (NS-398) or prostaglandin E2 (PGE2) before stimulation with lipopolysaccharide (LPS). Pro-inflammatory and anti-inflammatory cytokines were determined directly at the cell level with the help of flow cytometry and/or in the plasma supernatant with the help of ELISA. High doses of acetylsalicylic acid were needed to inhibit pro-inflammatory cytokine production. In contrast, low-to-moderate doses induced a modestly enhanced production of pro-inflammatory cytokines. Moreover, indomethacin was demonstrated to increase the expression of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) in a dose-dependent fashion. Upon addition of PGE2, however, LPS-induced IL-6 and TNF-alpha production was suppressed regardless of indomethacin presence. Interestingly, selective COX-2 inhibition (NS-398), but not selective COX-1 inhibition (SC-560), exerted a stimulatory effect on the expression of pro-inflammatory cytokines. These data emphasize that the immunomodulating effects of NSAIDs in whole blood are dose-dependent. Furthermore, the induction of pro-inflammatory cytokine expression by NSAIDs is potentially mediated by COX-2 inhibition. Although NSAIDs are successfully used in clinical practice for their net anti-inflammatory properties, our observations may contribute to the understanding of side effects induced by NSAIDs and selective COX-2 inhibitors.

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

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaofei; Zhu, Yanshuang [Department of Infectious Diseases, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China); He, Huabin [Department of Orthopedics, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China); Lou, Lianqing; Ye, Weiwei; Chen, Yongxin [Department of Infectious Diseases, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China); Wang, Jinghe, E-mail: Xiaofeili2000@163.com [Department of Infectious Diseases, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China)

    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.

  2. Impact of aspirin on the transcriptome ofStreptococcus pneumoniaeD39.

    Science.gov (United States)

    Afzal, Muhammad; Shafeeq, Sulman

    2017-06-01

    Aspirin or acetylsalicylic acid (ASA) is a medicine used to treat pain, fever, and inflammation. Here, we for the very first time reported the genome-wide transcriptional profiling of aspirin-regulated genes in Streptococcus pneumoniae in the presence of 5 mM aspirin in chemically-defined medium (CDM) using microarray analysis. Our results showed that expression of several genes was differentially expressed in the presence of aspirin. These genes were further grouped into COG (Clusters of Orthologous Groups) functional categories based on the putative functions of the corresponding proteins. Most of affected genes belong to COG category E (Amino acid transport and metabolism), G (Carbohydrate transport and metabolism), J (Translation, ribosomal structure and biogenesis), and I (Lipid transport and metabolism). Transcriptional profiling data of aspirin-regulated genes was deposited to Gene Expression Omnibus (GEO) database under accession number GSE94514.

  3. Impact of aspirin on the transcriptome of Streptococcus pneumoniae D39

    Directory of Open Access Journals (Sweden)

    Muhammad Afzal

    2017-06-01

    Full Text Available Aspirin or acetylsalicylic acid (ASA is a medicine used to treat pain, fever, and inflammation. Here, we for the very first time reported the genome-wide transcriptional profiling of aspirin-regulated genes in Streptococcus pneumoniae in the presence of 5 mM aspirin in chemically-defined medium (CDM using microarray analysis. Our results showed that expression of several genes was differentially expressed in the presence of aspirin. These genes were further grouped into COG (Clusters of Orthologous Groups functional categories based on the putative functions of the corresponding proteins. Most of affected genes belong to COG category E (Amino acid transport and metabolism, G (Carbohydrate transport and metabolism, J (Translation, ribosomal structure and biogenesis, and I (Lipid transport and metabolism. Transcriptional profiling data of aspirin-regulated genes was deposited to Gene Expression Omnibus (GEO database under accession number GSE94514.

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

    Science.gov (United States)

    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

  5. Strong and long-lasting antinociceptive and anti-inflammatory conjugate of naturally occurring oleanolic acid and aspirin

    Directory of Open Access Journals (Sweden)

    Barbara Bednarczyk-Cwynar

    2016-07-01

    Full Text Available 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

  6. Short- and long-term effects of acetylsalicylic acid treatment on the proliferation and lipid peroxidation of skin cultured melanocytes of active vitiligo.

    Science.gov (United States)

    Zailaie, Mohammad Z

    2004-11-01

    Recent in vitro and in vivo studies have shown that the nonsteroidal anti-inflammatory agent, acetylsalicylic acid (ASA) or aspirin has antioxidant properties on various cell lines and tissues. Hence, the aim of the present study is to investigate the effects of ASA at 2 different concentrations (75 and 300 microg/ml) on the proliferative capacities and lipid peroxidation of in vitro skin cultured melanocytes obtained from patients with active vitiligo. The present work was carried out from February 2001 through to November 2001, at the Vitiligo Unit, King Abdul-Aziz University Medical Center, Jeddah, Kingdom of Saudi Arabia. Employing methods described in this section, cryopreserved primary cultured melanocytes that were originally cultured from skin biopsies of normal healthy individuals and patients with active vitiligo (n=7), were subcultured to confluence. The malondialdehyde (MDA) concentrations in the cell culture medium were determined at 6 hours and 21 days following cultured melanocytes treatment with ASA (75 and 300 microg/ml). Also, the number of viable melanocytes was determined 21 days following the treatment of melanocytes with ASA (75 and 300 microg/ml). Following ASA treatment at 75 microg/ml, the cultured melanocytes from the normal and active vitiligo donors showed significant increase in the proliferative capacities as judged by the increase in the number of viable melanocytes after 21 days of cell culture (28.2% and 26.9%, p<0.001). Concomitantly, the same ASA concentration resulted in significant decrease in the concentrations of MDA in the cell culture medium of the normal and active vitiligo melanocytes 6 hour and 21-day period following the ASA treatment [6 hour: 16.2% (p<0.05) and 18.4% (p<0.001); 21 day: 32% and 38.6% (p<0.001)]. However, the long-term (21 days) treatment of cultured melanocytes from the normal and active vitiligo donors with ASA at 300 microg/ml resulted in a significant reduction in the number of viable melanocytes (33

  7. Pharmacokinetics and pharmacodynamics of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran, are not influenced by acetylsalicylic acid.

    Science.gov (United States)

    Fager, Gunnar; Cullberg, Marie; Eriksson-Lepkowska, Maria; Frison, Lars; Eriksson, Ulf G

    2003-08-01

    The aim of this study was to evaluate the effect of acetylsalicylic acid (ASA or aspirin) on the pharmacokinetics (PK) and pharmacodynamics (PD) of melagatran in healthy volunteers. Melagatran is the active form of the oral direct thrombin inhibitor, ximelagatran. This was a double-blind, randomised, two-way, crossover study consisting of two treatment periods separated by a washout period of at least 2 weeks. Twelve subjects received, in a randomised order, either melagatran plus ASA in the first treatment period and melagatran plus placebo in the second treatment period or vice versa. Two single doses of ASA were given, first 450 mg on the day before (day 1) and then 150 mg just before administration of melagatran on day 2. Melagatran 4.12 mg was administered as an intravenous (i.v.) infusion over 4 h on day 2 of both treatment periods. Serial blood samples were collected over the course of the study for the determination of melagatran plasma concentration and coagulation analyses [activated partial thromboplastin time (APTT) and activated clotting time (ACT)]. Capillary bleeding time was measured before ASA/placebo on day 1 and before and after the start of the melagatran infusion on day 2. The plasma concentration of melagatran during the i.v. infusion was maintained at about 0.2 micro mol/l, and ASA did not influence the PK parameters of melagatran. APTT and ACT increased with increasing melagatran plasma concentration, and the observed increases were similar whether melagatran was administered on top of ASA or placebo. Administration of ASA significantly prolonged the capillary bleeding time (by 41% relative to placebo). Melagatran also prolonged the bleeding time significantly (by 25% relative to placebo alone), but this prolongation was not significantly different from the observed prolongation when melagatran was administered on top of ASA (by 17% relative to ASA alone). In young healthy volunteers, ASA had no effect on the PK or PD properties of

  8. Up-regulation of Ciliary Neurotrophic Factor in Astrocytes by Aspirin

    Science.gov (United States)

    Modi, Khushbu K.; Sendtner, Michael; Pahan, Kalipada

    2013-01-01

    Ciliary neurotrophic factor (CNTF) is a promyelinating trophic factor, and the mechanisms by which CNTF expression could be increased in the brain are poorly understood. Acetylsalicylic acid (aspirin) is one of the most widely used analgesics. Interestingly, aspirin increased mRNA and protein expression of CNTF in primary mouse and human astrocytes in a dose- and time-dependent manner. Aspirin induced the activation of protein kinase A (PKA) but not protein kinase C (PKC). H-89, an inhibitor of PKA, abrogated aspirin-induced expression of CNTF. The activation of cAMP-response element-binding protein (CREB), but not NF-κB, by aspirin, the abrogation of aspirin-induced expression of CNTF by siRNA knockdown of CREB, the presence of a consensus cAMP-response element in the promoter of CNTF, and the recruitment of CREB and CREB-binding protein to the CNTF promoter by aspirin suggest that aspirin increases the expression of the Cntf gene via the activation of CREB. Furthermore, we demonstrate that aspirin-induced astroglial CNTF was also functionally active and that supernatants of aspirin-treated astrocytes of wild type, but not Cntf null, mice increased myelin-associated proteins in oligodendrocytes and protected oligodendrocytes from TNF-α insult. These results highlight a new and novel myelinogenic property of aspirin, which may be of benefit for multiple sclerosis and other demyelinating disorders. PMID:23653362

  9. Aspirin Inhibits Colon Cancer Cell and Tumor Growth and Downregulates Specificity Protein (Sp) Transcription Factors

    Science.gov (United States)

    Pathi, Satya; Jutooru, Indira; Chadalapaka, Gayathri; Nair, Vijayalekshmi; Lee, Syng-Ook; Safe, Stephen

    2012-01-01

    Acetylsalicylic acid (aspirin) is highly effective for treating colon cancer patients postdiagnosis; however, the mechanisms of action of aspirin in colon cancer are not well defined. Aspirin and its major metabolite sodium salicylate induced apoptosis and decreased colon cancer cell growth and the sodium salt of aspirin also inhibited tumor growth in an athymic nude mouse xenograft model. Colon cancer cell growth inhibition was accompanied by downregulation of Sp1, Sp3 and Sp4 proteins and decreased expression of Sp-regulated gene products including bcl-2, survivin, VEGF, VEGFR1, cyclin D1, c-MET and p65 (NFκB). Moreover, we also showed by RNA interference that β-catenin, an important target of aspirin in some studies, is an Sp-regulated gene. Aspirin induced nuclear caspase-dependent cleavage of Sp1, Sp3 and Sp4 proteins and this response was related to sequestration of zinc ions since addition of zinc sulfate blocked aspirin-mediated apoptosis and repression of Sp proteins. The results demonstrate an important underlying mechanism of action of aspirin as an anticancer agent and, based on the rapid metabolism of aspirin to salicylate in humans and the high salicylate/aspirin ratios in serum, it is likely that the anticancer activity of aspirin is also due to the salicylate metabolite. PMID:23110215

  10. Aspirin inhibits colon cancer cell and tumor growth and downregulates specificity protein (Sp) transcription factors.

    Science.gov (United States)

    Pathi, Satya; Jutooru, Indira; Chadalapaka, Gayathri; Nair, Vijayalekshmi; Lee, Syng-Ook; Safe, Stephen

    2012-01-01

    Acetylsalicylic acid (aspirin) is highly effective for treating colon cancer patients postdiagnosis; however, the mechanisms of action of aspirin in colon cancer are not well defined. Aspirin and its major metabolite sodium salicylate induced apoptosis and decreased colon cancer cell growth and the sodium salt of aspirin also inhibited tumor growth in an athymic nude mouse xenograft model. Colon cancer cell growth inhibition was accompanied by downregulation of Sp1, Sp3 and Sp4 proteins and decreased expression of Sp-regulated gene products including bcl-2, survivin, VEGF, VEGFR1, cyclin D1, c-MET and p65 (NFκB). Moreover, we also showed by RNA interference that β-catenin, an important target of aspirin in some studies, is an Sp-regulated gene. Aspirin induced nuclear caspase-dependent cleavage of Sp1, Sp3 and Sp4 proteins and this response was related to sequestration of zinc ions since addition of zinc sulfate blocked aspirin-mediated apoptosis and repression of Sp proteins. The results demonstrate an important underlying mechanism of action of aspirin as an anticancer agent and, based on the rapid metabolism of aspirin to salicylate in humans and the high salicylate/aspirin ratios in serum, it is likely that the anticancer activity of aspirin is also due to the salicylate metabolite.

  11. Aspirin inhibits colon cancer cell and tumor growth and downregulates specificity protein (Sp transcription factors.

    Directory of Open Access Journals (Sweden)

    Satya Pathi

    Full Text Available Acetylsalicylic acid (aspirin is highly effective for treating colon cancer patients postdiagnosis; however, the mechanisms of action of aspirin in colon cancer are not well defined. Aspirin and its major metabolite sodium salicylate induced apoptosis and decreased colon cancer cell growth and the sodium salt of aspirin also inhibited tumor growth in an athymic nude mouse xenograft model. Colon cancer cell growth inhibition was accompanied by downregulation of Sp1, Sp3 and Sp4 proteins and decreased expression of Sp-regulated gene products including bcl-2, survivin, VEGF, VEGFR1, cyclin D1, c-MET and p65 (NFκB. Moreover, we also showed by RNA interference that β-catenin, an important target of aspirin in some studies, is an Sp-regulated gene. Aspirin induced nuclear caspase-dependent cleavage of Sp1, Sp3 and Sp4 proteins and this response was related to sequestration of zinc ions since addition of zinc sulfate blocked aspirin-mediated apoptosis and repression of Sp proteins. The results demonstrate an important underlying mechanism of action of aspirin as an anticancer agent and, based on the rapid metabolism of aspirin to salicylate in humans and the high salicylate/aspirin ratios in serum, it is likely that the anticancer activity of aspirin is also due to the salicylate metabolite.

  12. Impact of low-dose acetylsalicylic acid on kidney function in type 2 diabetic patients with elevated urinary albumin excretion rate

    DEFF Research Database (Denmark)

    Gaede, Peter; Hansen, Henrik Post; Parving, Hans-Henrik

    2003-01-01

    Low-dose treatment with acetylsalicylic acid (ASA) is widely recommended to type 2 diabetic patients as primary prevention against cardiovascular disease. High-dose treatment with cyclooxygenase inhibitors reduces urinary albumin excretion rate (AER) in type 1 diabetic patients with micro......- or macroalbuminuria. Whether a similar effect on AER exists during low-dose ASA treatment, which may confound the diagnosis and monitoring of micro- and macroalbuminuria in type 2 diabetic patients, remains to be elucidated....

  13. On the origin of surface imposed anisotropic growth of salicylic and acetylsalicylic acids crystals during droplet evaporation.

    Science.gov (United States)

    Przybyłek, Maciej; Cysewski, Piotr; Pawelec, Maciej; Ziółkowska, Dorota; Kobierski, Mirosław

    2015-03-01

    In this paper droplet evaporative crystallization of salicylic acid (SA) and acetylsalicylic acid (ASA) crystals on different surfaces, such as glass, polyvinyl alcohol (PVA), and paraffin was studied. The obtained crystals were analyzed using powder X-ray diffraction (PXRD) technique. In order to better understand the effect of the surface on evaporative crystallization, crystals deposited on glass were scraped off. Moreover, evaporative crystallization of a large volume of solution was performed. As we found, paraffin which is non-polar surface promotes formation of crystals morphologically similar to those obtained via bulk evaporative crystallization. On the other hand, when crystallization is carried out on the polar surfaces (glass and PVA), there is a significant orientation effect. This phenomenon is manifested by the reduction of the number of peaks in PXRD spectrum recorded for deposited on the surface crystals. Noteworthy, reduction of PXRD signals is not observed for powder samples obtained after scraping crystals off the glass. In order to explain the mechanism of carboxylic crystals growth on the polar surfaces, quantum-chemical computations were performed. It has been found that crystal faces of the strongest orientation effect can be characterized by the highest surface densities of intermolecular interactions energy (IIE). In case of SA and ASA crystals formed on the polar surfaces the most dominant faces are characterized by the highest adhesive and cohesive properties. This suggests that the selection rules of the orientation effect comes directly from surface IIE densities.

  14. Design, synthesis and evaluation of aspirin analogues having an additional carboxylate substituent for antithrombotic activity.

    Science.gov (United States)

    Alagha, Ahmed; Moman, Edelmiro; Adamo, Mauro F A; Nolan, Kevin B; Chubb, Anthony J

    2009-08-01

    Acetylsalicylic acid (aspirin) is an effective long-term prophylaxis of thrombotic events such as heart attacks and strokes. It covalently inhibits prostaglandin-H-synthase by interacting with Arg120 or Tyr385 at the active site allowing delivery of its acetyl group to Ser530. However the structure has not been optimized to fit the active site. We have designed acetylsalicylate analogues with an additional carboxylate substituent which allows simultaneous interaction with Arg120 and Tyr385 whilst positioning the acetyl group in close proximity to Ser530. One of these, an ester derivative which unlike acetylsalicylic acid is non-acidic, may act as useful lead compound for further exploitation of this approach.

  15. Characterization of a dextran–coated layered double hydroxide acetylsalicylic acid delivery system and its pharmacokinetics in rabbit

    Directory of Open Access Journals (Sweden)

    Li-e Dong

    2013-12-01

    Full Text Available The aim of this study was to prepare a dextran–coated layered double hydroxide acetylsalicylic acid (DEX–LDH–ASA delivery system by co-precipitation of LDH–ASA and its in-situ compositing with DEX. The structure of the system was investigated using X-ray diffraction (XRD, Fourier transform infrared spectroscopy (FT-IR and thermogravimetry (TG. Its in vitro drug release properties and in vivo pharmacokinetics in rabbit were also determined. The results show that the DEX–LDH–ASA system retained the crystal structure of LDH–ASA and gave a marked improvement in its dispersion. It also prolonged the release of ASA and shifted the release pattern from first-order to zero-order kinetics. The pharmacokinetics of ASA administered in the DEX–LDH–ASA system to rabbits produced two absorption peaks with a Cmax of 14.8±1.7 mg/L at 2.11±0.69 h and an elimination half-life of 2.25±0.84 h for the first peak. The fact that delivery of ASA in the DEX–LDH–ASA system was sustained with improved bioavailability indicates the potential of the system as a controlled release formulation with application to other drugs.

  16. In vitro dissolution study of acetylsalicylic acid solid dispersions. Tunable drug release allowed by the choice of polymer matrix.

    Science.gov (United States)

    Policianova, Olivia; Brus, Jiri; Hruby, Martin; Urbanova, Martina

    2014-07-22

    Abstract Due to their high versatility and diverse excipient options, solid dispersions (SDs) are an elegant choice for the formulation of active pharmaceutical ingredients with inconvenient solubility. Four distinct types of polymers with different physicochemical properties [polyvinylpyrrolidone, poly[N-(2-hydroxypropyl)-metacrylamide], poly(2-ethyl-2-oxazoline), and polyethylene glycol] and variable molecular weights were compared to investigate the influence of the polymer matrix on drug release. To probe the extent of intercomponent interactions, acetylsalicylic acid (ASA) was used as a model active substance. Controlled drug release was demonstrated for all four types of polymer-ASA SDs created by the freeze-drying method. While the polyethylene glycol-ASA SD exhibited an increased dissolution rate, the other polymer-ASA systems exhibited significantly reduced drug dissolution kinetics compared to free ASA. Furthermore, in contrast to physical mixtures, the prepared SDs all exhibited zero-order dissolution kinetics for ASA. The dissolution rate was strongly dependent on the molecular weight of the polymer. These results demonstrate that the type of SD may be controlled by the chemical constitutions of the polymers and that appropriate selection of the molecular weight of the polymer matrix enables finely tuned drug release over a wide range of dissolution rates.

  17. Potentiometric determination of acetylsalicylic acid by sequential injection analysis (SIA) using a tubular salicylate-selective electrode.

    Science.gov (United States)

    Paseková, H; Sales, M G; Montenegro, M C; Araújo, A N; Polásek, M

    2001-03-01

    This paper deals with the development of an automated procedure for formulation assays and dissolution tests based on a sequential injection analysis (SIA) system involving an ion-selective electrode as sensing device. Construction of a tubular salicylate (Sal) selective electrode suitable for potentiometric determination of acetylsalicylic acid (Asa) in pharmaceutical formulations is described. The flow-through electrode is formed by a PVC membrane containing 29.2% (w/w) PVC, 5.8% (w/w) tetraoctylammonium salicylate (ionic sensor), 58.5% o-nitrophenyloctylether (plasticizer) and 6.5% (w/w) p-tert-octylphenol (stabilising additive which increases electrode selectivity). The calibration range is 0.05--10 mM Sal, the limit of detection (LOD) is 0.05 mM Sal, the slope is 56.0 mV per decade at 22 degrees C. The R.S.D. is 0.20% (15 readings) when determining 2.5 mM Sal in standard solution. The electrode is used for sensing Asa after its on-line chemical hydrolysis to Sal in a SIA system. The sampling rate is 6 h(-1) but for the dissolution tests the frequency is increased to 20 h(-1). The SIA set-up is employed for the assay of Asa in plain tablets, composed tablets and effervescent tablets and for performing dissolution tests of normal and sustained release tablets. Results obtained by this technique compare well with those required by the US Pharmacopoeia XXIV.

  18. Drug resistance and secondary treatment of ischaemic stroke: The genetic component of the response to acetylsalicylic acid and clopidogrel.

    Science.gov (United States)

    Gallego-Fabrega, C; Krupinski, J; Fernandez-Cadenas, I

    2015-01-01

    Cerebrovascular diseases are among the leading causes of death and disability in developed countries. Acetylsalicylic acid (ASA) and clopidogrel are the most widely-used antiplatelet drugs for secondary prevention of recurrent thromboembolic events. However, there have been cases in which antiplatelet drugs did not inhibit platelet activity; this phenomenon is called resistance, and it may be modulated at the genetic level. Following a literature search, we reviewed the current state of antiplatelet therapy and covered the different types of resistance to antiplatelet therapy, how it is measured, current problems and limitations, and any genetic factors that have been associated with resistance. We mainly used the Genome Wide Association Studies in the field of ASA and clopidogrel resistance. We observed an association between different genetic factors and antiplatelet drug resistance as measured by platelet activity. However, there is no evident association between these genetic factors and risk of new thromboembolic events. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  19. Making bispirin: synthesis, structure and activity against Helicobacter pylori of bismuth(III) acetylsalicylate.

    Science.gov (United States)

    Andrews, Philip C; Blair, Victoria L; Ferrero, Richard L; Junk, Peter C; Kumar, Ish

    2013-04-11

    Reaction of Bi(O(t)Bu)3 with aspirin (acetylsalicylic acid = aspH) in dry toluene results in the bismuth(III) complex, [Bi(O2C(C6H4)OAc)3]∞ 1 (O2C(C6H4)OAc = asp), minimum inhibitory concentration (MIC) against Helicobacter pylori ≥ 6.25 μg mL(-1), while the inclusion of a stoichiometric equivalent of KO(t)Bu leads to crystals of the bismuthate salt [KBi(O2C(C6H4)OAc)4]∞ 2.

  20. Prevention of angiotensin II-induced hypertension, cardiovascular hypertrophy and oxidative stress by acetylsalicylic acid in rats.

    Science.gov (United States)

    Wu, Rong; Laplante, Marc-André; De Champlain, Jacques

    2004-04-01

    Angiotensin II (Ang II)-induced oxidative stress has been suspected to play an important part in the pathogenesis of many cardiovascular diseases. Our previous study demonstrated that acetylsalicylic acid (ASA) possesses potent antioxidative properties. To evaluate the pathogenetic role of oxidative stress in Ang II-induced hypertension and cardiovascular hypertrophy. Chronic infusion of Ang II (200 ng/kg per min for 12 days) increased the aortic and cardiac tissue production of superoxide anion (O2) (lucigenin-enhanced chemiluminescence method) by 77 and 35%, respectively. These effects were associated with progressive increases in systolic blood pressure (from 135 to 194 mmHg) and heart/body weight ratio (from 2.25 to 2.69). Chronic treatment with oral ASA alone (100 mg/kg per day for 12 days) significantly reduced aortic and cardiac production of O2 (by 31 and 33%, respectively), without alteration in blood pressure and heart/body weight ratio in control normotensive animals. However, concurrent treatment with ASA in Ang II-infused rats completely prevented the Ang II-induced production of O2, in addition to hypertension and cardiac hypertrophy. Similar protective effects were observed in cultured aortic smooth muscle cells, in which increases in O2 production and [H]leucine incorporation (221 and 38%, respectively) induced by Ang II (10 mol/l) were totally prevented by concurrent incubation with ASA (10 mol/l). Losartan, but not PD 123319, also blocked the Ang II-induced oxidative and hypertrophic effects in those cells. Other anti-inflammatory drugs, such as salicylic acid, indomethacin and ibuprofen, did not show similar anti-Ang II and antioxidative effects in vivo. Oxidative stress plays a major part in chronic Ang II-induced hypertension and cardiovascular hypertrophy. Chronic concurrent treatment with ASA was found to prevent those Ang II-induced effects on the cardiovascular system, presumably through its antioxidative properties.

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

    Science.gov (United States)

    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.

  2. Leukotriene-related Gene Polymorphisms in Patients with Aspirin-intolerant Urticaria and Aspirin-intolerant Asthma: Differing Contributions of ALOX5 Polymorphism in Korean Population

    OpenAIRE

    Kim, Seung-Hyun; Choi, Jeong-Hee; Holloway, J. W.; Suh, Chang-Hee; Nahm, Dong-Ho; Ha, Eun-Ho; Park, Choon-Sik; Park, Hae-Sim

    2005-01-01

    The pathogenesis of aspirin (acetylsalicylic acid, ASA)-intolerant urticaria (AIU) is still poorly understood but it has recently been suggested that it is associated with the overproduction of leukotriene (LT). This is supported by evidence that cyclooxygenase 2 inhibitor is given safely to patients with AIU. The present study was designed to investigate the role of genetic polymorphism of LT related genes in the pathogenesis of AIU via a case-control study. We screened single nucleotide pol...

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

    Science.gov (United States)

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

    2002-05-01

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

  4. Metabolism of arachidonic acid in hamster lung microsomes is not completely inhibited by aspirin and indomethacin

    Energy Technology Data Exchange (ETDEWEB)

    Uotila, P.; Paajanen, H.; Schalin, M.; Simberg, N.

    1983-10-01

    Aspirin (100 microM or 1 mM) or indomethacin (10 microM or 100 microM) was incubated with a microsomal preparation of hamster lungs in the presence of NADPH for 10 min. Then 14C-arachidonic acid (20 microM) was added and the incubation was continued for an additional 20 min. The metabolites were extracted with ethyl acetate first at pH 7.4 and then at pH 3.5 and analysed by thin layer chromatography. Both aspirin and indomethacin inhibited dose dependently the formation of all identified prostaglandins, including PGF2 alpha, 6-keto-PGF1 alpha, PGE2 and PGD2. The rate of formation of some unidentified metabolites extracted at pH 7.4 and 3.5 was, however, not changed by aspirin or indomethacin. We have earlier reported that in isolated perfused hamster lungs the formation of all arachidonate metabolites is inhibited by both aspirin and indomethacin. As the present study indicates that in the microsomes of hamster lungs all metabolic pathways of arachidonic acid are not inhibited by aspirin or indomethacin, it is possible that in isolated tissues and in vivo aspirin-like drugs have some other inhibitory effects on arachidonate metabolism than the inhibition of the cyclo-oxygenase enzyme.

  5. Up-regulation of ciliary neurotrophic factor in astrocytes by aspirin: implications for remyelination in multiple sclerosis.

    Science.gov (United States)

    Modi, Khushbu K; Sendtner, Michael; Pahan, Kalipada

    2013-06-21

    Ciliary neurotrophic factor (CNTF) is a promyelinating trophic factor, and the mechanisms by which CNTF expression could be increased in the brain are poorly understood. Acetylsalicylic acid (aspirin) is one of the most widely used analgesics. Interestingly, aspirin increased mRNA and protein expression of CNTF in primary mouse and human astrocytes in a dose- and time-dependent manner. Aspirin induced the activation of protein kinase A (PKA) but not protein kinase C (PKC). H-89, an inhibitor of PKA, abrogated aspirin-induced expression of CNTF. The activation of cAMP-response element-binding protein (CREB), but not NF-κB, by aspirin, the abrogation of aspirin-induced expression of CNTF by siRNA knockdown of CREB, the presence of a consensus cAMP-response element in the promoter of CNTF, and the recruitment of CREB and CREB-binding protein to the CNTF promoter by aspirin suggest that aspirin increases the expression of the Cntf gene via the activation of CREB. Furthermore, we demonstrate that aspirin-induced astroglial CNTF was also functionally active and that supernatants of aspirin-treated astrocytes of wild type, but not Cntf null, mice increased myelin-associated proteins in oligodendrocytes and protected oligodendrocytes from TNF-α insult. These results highlight a new and novel myelinogenic property of aspirin, which may be of benefit for multiple sclerosis and other demyelinating disorders.

  6. Aspirin use and endometrial cancer risk and survival.

    Science.gov (United States)

    Takiuchi, Tsuyoshi; Blake, Erin A; Matsuo, Koji; Sood, Anil K; Brasky, Theodore M

    2018-01-01

    The role of acetylsalicylic acid (aspirin) as a chemo-preventive and adjuvant therapeutic agent for cancers is generating attention. Mounting evidence indicates that aspirin reduces the incidence and mortality of certain obesity-related cancers, particularly colorectal cancer. In endometrial cancer, previous studies examining the effect of aspirin remain inconsistent as to the reduction in the risk of endometrial cancer. While some evidence indicates protective effects in obese women, other studies have showed a potential deleterious effect of these medications on endometrial cancer outcomes. However, exposure measurement across studies has been inconsistent in recording dose, duration, and frequency of use; thus making comparisons difficult. In this article, we review the evidence for the association between endometrial cancer and obesity, the pharmacological differences between regular- and low-dose aspirin, as well as the potential anti-tumor mechanism of aspirin, supporting a possible therapeutic effect on endometrial cancer. A proposed mechanism behind decreased cancer mortality in endometrial cancer may be a result of inhibition of metastasis via platelet inactivation and possible prostaglandin E 2 suppression by aspirin. Additionally, aspirin use in particular may have a secondary benefit for obesity-related comorbidities including cardiovascular disease in women with endometrial cancer. Although aspirin-related bleeding needs to be considered as a possible adverse effect, the benefits of aspirin therapy may exceed the potential risk in women with endometrial cancer. The current evidence reviewed herein has resulted in conflicting findings regarding the potential effect on endometrial cancer outcomes, thus indicating that future studies in this area are needed to resolve the effects of aspirin on endometrial cancer survival, particularly to identify specific populations that might benefit from aspirin use. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Effect of esomeprazole with/without acetylsalicylic acid, omeprazole and lansoprazole on pharmacokinetics and pharmacodynamics of clopidogrel in healthy volunteers.

    Science.gov (United States)

    Andersson, Tommy; Nagy, Peter; Niazi, Mohammad; Nylander, Sven; Galbraith, Hal; Ranjan, Santosh; Wallentin, Lars

    2014-06-01

    The effect of proton pump inhibitors (PPIs) on the pharmacokinetics and pharmacodynamics of clopidogrel was assessed in two healthy volunteer crossover studies. Study 1: subjects received clopidogrel alone (300-mg loading dose, then 75 mg/day for 28 days) and two of three PPIs (omeprazole 80 mg, esomeprazole 40 mg or lansoprazole 60 mg) plus clopidogrel for 29 days in three treatment periods (randomized treatment sequence assignment). Study 2: subjects received clopidogrel alone (75 mg/day for 9 days) and clopidogrel alone for 4 days followed by clopidogrel plus fixed-combination esomeprazole 20 mg/low-dose acetylsalicylic acid (ASA) 81 mg for 5 days in two treatment periods (randomized treatment sequence assignment). Pharmacokinetic effects were estimated by measuring active metabolite of clopidogrel, and pharmacodynamic effects by inhibition of adenosine diphosphate (ADP)-induced platelet aggregation. There was a relative decrease of up to 50 % in exposure to the active metabolite of clopidogrel with the different PPIs (study 1), and close to 40 % with esomeprazole/low-dose ASA (study 2), compared with clopidogrel alone. There was an absolute decrease of up to 17 % in inhibition of ADP-induced platelet aggregation with co-administration of different PPIs, compared with clopidogrel alone; however, no differences in platelet inhibition were observed during co-administration with the esomeprazole/low-dose ASA fixed-dose combination. Omeprazole, esomeprazole and lansoprazole decreased systemic exposure to the active metabolite of clopidogrel in healthy volunteers, leading to modest decreases in its antiplatelet effect. However, no apparent differences in platelet inhibition were observed when esomeprazole was co-administered with low-dose ASA as a fixed-dose combination.

  8. Genetic determinants of platelet reactivity during acetylsalicylic acid therapy in diabetic patients: evaluation of 27 polymorphisms within candidate genes.

    Science.gov (United States)

    Postula, M; Kaplon-Cieslicka, A; Rosiak, M; Kondracka, A; Serafin, A; Filipiak, K J; Czlonkowski, A; Opolski, G; Janicki, P K

    2011-11-01

    Decreased platelet responsiveness to acetylsalicylic acid (ASA) reported previously in diabetic patients could be attributed to patient-based, clinical, genetic and cellular factors. The objective of the present study was to investigate the effect of the genomic polymorphism on the platelet reactivity in diabetic patients treated with ASA. The study cohort consisted of 295 Caucasians with diabetes type 2 who had been taking ASA tablets at the dose of 75 mg per day for at least 3 months for primary or secondary prevention of myocardial infarction (MI). Platelet reactivity analyzes were performed using VerifyNow ASA and PFA-100 assays. Genotyping for the selected 27 single nucleotide polymorphisms (SNPs) within 19 genes was performed using a Sequenom iPLEX platform. The results indicate that the statistically significant differences in platelet reactivity were observed in the PFA-100 assay for SNPs in following genes: TXBA2R (rs1131882), ADRA2A (rs4311994), PLA2G7 (rs7756935) and 9p21.3 (rs10120688) (P = 0.02, P = 0.03, P = 0.02, P = 0.03, respectively, all significance levels corrected for multiple comparisons). When using the VerifyNow ASA test, a weak nominal statistical significance (i.e. before multiple comparison testing) was observed for two SNPs in the GPVI gene: rs1671152 and rs1613662 [P = 0.025 (0.5) for both SNPs, corrected for multiple comparisons test]. The results from the present study suggest that the four analyzed genes may contribute to platelet reactivity measured with the PFA-100 assay in the diabetic population treated with ASA. © 2011 International Society on Thrombosis and Haemostasis.

  9. Acetylsalicylic acid inhibits the growth of melanoma tumors via SOX2-dependent-PAF-R-independent signaling pathway.

    Science.gov (United States)

    Thyagarajan, Anita; Saylae, Jeremiah; Sahu, Ravi P

    2017-07-25

    Acquired resistance to standard therapies remains a serious challenge, requiring novel therapeutic approaches that incorporate potential factors involved in tumor resistance. As cancers including melanoma express inflammatory cyclooxygenases generating prostaglandins implicated in tumor growth, we investigated mechanism of anti-inflammatory drug, acetylsalicylic acid (ASA) which has been shown to inhibit various tumor types, however, its effects against highly aggressive melanoma model are unclear. Given our reports that an activation of platelet-activating factor-receptor (PAF-R) augments the growth and impede efficacies of therapeutic agents in experimental melanoma, we also sought to determine if PAF-R mediates anti-melanoma activity of ASA. The current studies using stably PAF-R-positive (B16-PAFR) and negative (B16-MSCV) murine melanoma cells and PAF-R-expressing and deficient mice, demonstrate that ASA inhibits the in-vitro and in-vivo growth of highly aggressive B16F10 melanoma via bypassing tumoral or stromal PAF-R signaling. Similar ASA-induced effects in-vitro were seen in human melanoma and nasopharyngeal carcinoma cells positive or negative in PAF-R. Mechanistically, the ASA-induced decrease in cell survival and increase in apoptosis were significantly blocked by prostaglandin F2 alpha (PGF2α) agonists. Importantly, PCR array and qRT-PCR analysis of B16-tumors revealed significant downregulation of sry-related high-mobility-box-2 (SOX2) oncogene by ASA treatment. Interestingly, modulation of SOX2 expression by PGF2α agonists and upregulation by fibroblast growth factor 1 (FGF-1) rescued melanoma cells from ASA-induced decreased survival and increased apoptosis. Moreover, PGF2α-receptor antagonist, AL8810 mimics ASA-induced decreased melanoma cells survival which was significantly blocked by PGF2α and FGF-1. These findings indicate that ASA inhibits the growth of aggressive melanoma via SOX2-dependent-PAF-R-indepedent pathway.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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. Decomposition of aspirin in the solid state in the presence of limited amounts of moisture II: Kinetics and salting-in of aspirin in aqueous acetic acid solutions.

    Science.gov (United States)

    Carstensen, J T; Attarchi, F

    1988-04-01

    The solubility of aspirin in saturated solutions of salicylic acid (and vice versa) was studied in 0 to 16 M aqueous solutions of acetic acid. The solubilities, when expressed in molarity, go through a maximum at an acetic acid concentration of approximately 12 M. The temperature dependence of the solubilities is such that the logarithm of the solubility is linear in reciprocal absolute temperature. The calculated enthalpies are of the order of 11 kcal/mol. The kinetics of aspirin decomposition was also studied at the different acetic acid concentrations, and it was found that the second-order hydrolysis rate constant is fairly independent of acetic acid concentration. Aspirin decomposition follows an Arrhenius equation and has an activation energy of 18 kcal/mol.

  13. Quantification of ascorbic acid and acetylsalicylic acid in effervescent tablets by CZE-UV and identification of related degradation products by heart-cut CZE-CZE-MS.

    Science.gov (United States)

    Neuberger, Sabine; Jooß, Kevin; Ressel, Christian; Neusüß, Christian

    2016-12-01

    Capillary electrophoresis is commonly applied for the analysis of pharmaceutical products due to its high separation efficiency and selectivity. For this purpose, electrospray-ionization-(ESI)-interfering additives or electrolytes are often required, which complicates the identification of impurities and degradation products by mass spectrometry (MS). Here, a capillary zone electrophoresis (CZE) method with ultraviolet (UV) absorption detection for the simultaneous determination and quantification of ascorbic acid and acetylsalicylic acid in effervescent tablets was developed. Related degradation products were identified via CZE-CZE-MS. Systematic optimization yielded 100 mM tricine (pH = 8.8) as appropriate background electrolyte, resulting in baseline separation of ascorbic acid, acetylsalicylic acid, and related anionic UV-active degradation products. The CZE-UV method was successfully validated regarding the guidelines of the Food and Drug Administration. The validated method was applied to trace the degradation rate of the active pharmaceutical ingredients at defined ambient conditions. A heart-cut CZE-CZE-MS approach, including a 4-port-nL-valve, was performed for the identification of the observed degradation products. This 2D setup enables a precise cutting of accurate sample volumes (20 nL) and the independent operation of two physically separated CZE dimensions, which is especially beneficial regarding MS detection. Hence, the ESI-interfering tricine electrolyte components were separated from the analytes in a second electrophoretic dimension prior to ESI-MS detection. The degradation products were identified as salicylic acid and mono- and diacetylated ascorbic acid. This setup is expected to be generally applicable for the mass spectrometric characterization of CZE separated analytes in highly ESI-interfering electrolyte systems. Graphical Abstract A CZE-UV method for the quantification of effervescent tablet ingredients and degradation products

  14. Mechanism of the irreversible inhibition of human cyclooxygenase-1 by aspirin as predicted by QM/MM calculations.

    Science.gov (United States)

    Tóth, L; Muszbek, L; Komáromi, I

    2013-03-01

    Acetylsalicylic acid (aspirin) suppresses the generation of prostaglandin H2, which is the precursor of thromboxane A2. Aspirin acts as an acetylating agent in which its acetyl group is covalently attached to a serine residue (S530) in the active site of the cyclooxygenase-1 enzyme. The exact reaction mechanism has not been revealed by experimental methods. In this study the putative structure of human cyclooxygenase-1 was constructed from ovine cyclooxygenase-1 by homology modeling, and the acetylsalicylic acid was docked into the arachidonic acid binding cavity of the enzyme. To characterize the shape of the potential energy surface of the acetylating reaction and to determine the relative energies of the stationary points on the surface, a series of ONIOM-type quantum mechanical/molecular mechanical (QM/MM) calculations were carried out at different QM levels of theories applying electronic embedding approximations. The acetylsalicylic acid and the surrounding amino acids were included in these calculations. Frequency analyses were performed to prove the existence of first order saddle points (representing transition states) and local minima on the potential energy surface. It was found that all levels of theories predicted similar transition state geometries. The activation energy values, however, demonstrated significant dependence on the methods that were applied. All the applied "dependable" ab initio and DFT methods predicted that the breakage of the S530 Oγ--Hγ and formation of the Oγ--C(acetylsalicylic acid carbonyl) bonds occur in a single elementary step. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Aspirin and Other COX-1 inhibitors.

    Science.gov (United States)

    Patrono, Carlo; Rocca, Bianca

    2012-01-01

    Currently available antiplatelet drugs interfere with the process of platelet activation and aggregation by selectively blocking key enzymes involved in the synthesis of platelet agonists, or membrane receptors mediating activation signals. Pharmacological interference with critical molecular pathways of platelet activation and aggregation may reduce the risk of atherothrombotic complications through mechanisms that are also responsible for an increased risk of bleeding. Acetylsalicylic acid (aspirin) represents a prototypic antiplatelet agent. The aim of this chapter is to integrate our current understanding of the molecular mechanism of action of aspirin with the results of clinical trials and epidemiological studies assessing its efficacy and safety. Moreover, the antiplatelet properties of reversible inhibitors of the same drug target will also be reviewed.

  16. Low-dose and high-dose acetylsalicylic acid, with and without dipyridamole: a review of clinical trial results

    NARCIS (Netherlands)

    Tijssen, J. G.

    1998-01-01

    Publication of the results of the second European Stroke Prevention Study (ESPS-2) provided the incentive for an update of the meta-analyses of aspirin and dipyridamole in the secondary prevention of stroke. After review of published randomized trials of prolonged treatment with aspirin,

  17. Acetylsalicylic acid-induced changes in the chemical coding of extrinsic sensory neurons supplying the prepyloric area of the porcine stomach.

    Science.gov (United States)

    Rytel, L; Calka, J

    2016-03-23

    Acetylsalicylic acid is a popular drug that is commonly used to treat fever and inflammation, but which can also negativity affect the mucosal layer of the stomach, although knowledge concerning its influence on gastric innervation is very scarce. Thus, the aim of the present study was to study the influence of prolonged acetylsalicylic acid supplementation on the extrinsic primary sensory neurons supplying the porcine stomach prepyloric region. Fast Blue (FB) was injected into the above-mentioned region of the stomach. Acetylsalicylic acid was then given orally to the experimental gilts from the seventh day after FB injection to the 27th day of the experiment. After euthanasia, the nodose ganglia (NG) and dorsal root ganglia (DRG) were collected. Sections of these ganglia were processed for routine double-labelling immunofluorescence technique for substance P (SP), calcitonine gene related peptide (CGRP), galanin (GAL), neuronal isoform of nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP). Under physiological conditions within the nodose ganglia, the percentage of the FB-labeled neurons immunoreactive to particular substances ranged between 17.9 ± 2.7% (VIP-like immunoreactive (LI) neurons in the right NG) and 60.4 ± 1.7% (SP-LI cells within the left NG). Acetylsalicylic acid supplementation caused a considerable increase in the expression of all active substances studied within both left and right NG and the percentage of neurons positive to particular substances fluctuated from 47.2 ± 3.6% (GAL-LI neurons in the right NG) to 67.2 ± 2.0% (cells immunoreactive to SP in the left NG). All studied substances were also observed in DRG neurons supplying the prepyloric region of the stomach, but the number of immunoreactive neurons was too small to conduct a statistical analysis. The obtained results show that ASA may influence chemical coding of the sensory neurons supplying the porcine stomach, but the exact mechanisms of this action still

  18. Development of spherical crystals of acetylsalicylic acid for direct tablet-making.

    Science.gov (United States)

    Göczõ, H; Szabó-Révész, P; Farkas, B; Hasznos-Nezdei, M; Serwanis, S F; Pintye-Hódi, A K; Kása, P; Erõs, I; Antal, I; Marto, S

    2000-12-01

    The production of spherical crystals has recently gained great attention due to the fact that the crystal habit (form, surface, size, etc.) can be modified during the crystallization process. Spherical crystals of ASA were developed by non-typical and typical spherical crystallization techniques. The non-typical spherical crystallization process (conventional stirred tank method) resulted in few monocrystals and non-spherical crystal agglomerates. The typical spherical crystallization process was carried out by the three solvent-system (ethanol-water-carbon tetrachloride). The products were qualified by morphological study, NIR investigation, salicylic acid content, dissolution rate, studies on flowability, compactibility, cohesivity and tablettability. The results demonstrate that only typical spherical crystallization can be recommended for the production of spherical crystals of ASA. Only product made by this technique shows excellent flow properties and favourable compactibility, cohesiveness and tablettability values.

  19. Interactions of gallic acid, resveratrol, quercetin and aspirin at the platelet cyclooxygenase-1 level. Functional and modelling studies.

    Science.gov (United States)

    Crescente, Marilena; Jessen, Gisela; Momi, Stefania; Höltje, Hans-Dieter; Gresele, Paolo; Cerletti, Chiara; de Gaetano, Giovanni

    2009-08-01

    While resveratrol and quercetin possess antiplatelet activity, little is known on the effect of gallic acid on platelets. We studied the interactions of these three different polyphenols among themselves and with aspirin, at the level of platelet cyclooxygenase-1 (COX-1). Both functional (in vitro and in vivo) and molecular modelling approaches were used. All three polyphenols showed comparable antioxidant activity (arachidonic acid [AA]-induced intraplatelet ROS production); however, resveratrol and quercetin, but not gallic acid, inhibited AA-induced platelet aggregation. Gallic acid, similarly to salicylic acid, the major aspirin metabolite, prevented inhibition of AA-induced platelet function by aspirin but, at variance with salicylic acid, also prevented inhibition by the other two polyphenols. Molecular modelling studies, performed by in silico docking the polyphenols into the crystal structure of COX-1, suggested that all compounds form stable complexes into the COX-1 channel, with slightly different but functionally relevant interaction geometries. Experiments in mice showed that gallic acid administered before aspirin, resveratrol or quercetin fully prevented their inhibitory effect on serum TxB(2). Finally, a mixture of resveratrol, quercetin and gallic acid, at relative concentrations similar to those contained in most red wines, did not inhibit platelet aggregation, but potentiated sub-inhibitory concentrations of aspirin. Gallic acid interactions with other polyphenols or aspirin at the level of platelet COX-1 might partly explain the complex, and possibly contrasting, effects of wine and other components of the Mediterranean diet on platelets and on the pharmacologic effect of low-dose aspirin.

  20. Cost Effectiveness of Gastroprotection with Proton Pump Inhibitors in Older Low-Dose Acetylsalicylic Acid Users in the Netherlands.

    Science.gov (United States)

    Chau, Sek Hung; Sluiter, Reinier L; Kievit, Wietske; Wensing, Michel; Teichert, Martina; Hugtenburg, Jacqueline G

    2017-05-01

    The present study aimed to assess the cost effectiveness of concomitant proton pump inhibitor (PPI) treatment in low-dose acetylsalicylic acid (LDASA) users at risk of upper gastrointestinal (UGI) adverse effects as compared with no PPI co-medication with attention to the age-dependent influence of PPI-induced adverse effects. We used a Markov model to compare the strategy of PPI co-medication with no PPI co-medication in older LDASA users at risk of UGI adverse effects. As PPIs reduce the risk of UGI bleeding and dyspepsia, these risk factors were modelled together with PPI adverse effects for LDASA users 60-69, 70-79 (base case) and 80 years and older. Incremental cost-utility ratios (ICURs) were calculated as cost per quality-adjusted life-year (QALY) gained per age category. Furthermore, a budget impact analysis assessed the expected changes in expenditure of the Dutch healthcare system following the adoption of PPI co-treatment in all LDASA users potentially at risk of UGI adverse effects. PPI co-treatment of 70- to 79-year-old LDASA users, as compared with no PPI, resulted in incremental costs of €100.51 at incremental effects of 0.007 QALYs with an ICUR of €14,671/QALY. ICURs for 60- to 69-year-old LDASA users were €13,264/QALY and €64,121/QALY for patients 80 years and older. Initiation of PPI co-treatment for all Dutch LDASA users of 60 years and older at risk of UGI adverse effects but not prescribed a PPI (19%) would have cost €1,280,478 in the first year (year 2013 values). PPI co-medication in LDASA users at risk of UGI adverse effects is generally cost effective. However, this strategy becomes less cost effective with higher age, particularly in patients aged 80 years and older, mainly due to the increased risks of PPI-induced adverse effects.

  1. Food sensitivity reported by patients with asthma and hay fever. A relationship between food sensitivity and birch pollen-allergy and between food sensitivity and acetylsalicylic acid intolerance.

    Science.gov (United States)

    Eriksson, N E

    1978-08-01

    Among adult patients with bronchial asthma and/or allergic rhinitis undergoing allergological investigation with skin test, nasal provocation test and RAST, 1129 answered a questionaire regarding food sensitivity (FS). 276 (24%) of the patients reported some kind of allergic symptoms on eating or handling various foods, of which hazel nut, apple and shell fish were the most often named. Females reported FS more often than males. A correlation was found between birch pollen allergy and FS with nuts, apple, peach, cherry, pear, plum, carrot and new potato. The higher the degree of birch pollen allergy, according to skin test, RAST or provocation test, the higher the frequency of FS. A correlation was found too between acetylsalicylic acid intolerance and FS with some foods, e.g. nuts, strawberry, almond, green pepper, hip, chocolate, egg, cabbage, milk and wine. The connection between birch pollen allergy and FS is probably explained by the structural relationship between birch pollen allergen and some allergens of the foodstuffs, whereas the high incidence of FS in acetylsalicylic acid-intolerant patients is probably explained by additives in foods as well as salicylates or benzoates naturally occurring in some food.

  2. Multivariate spectral calibration technique based on regression analysis for the quantitative multiresolution of a ternary mixture containing paracetamol, ascorbic acid and acetylsalicylic acid in effervescent tablets.

    Science.gov (United States)

    Dinç, E; Ozdemir, A

    2004-09-01

    Multivariate spectral calibration techniques based on regression analysis were established for the quantitative multiresolution of a ternary mixture containing parecetamol (PAR) ascorbic acid (AA) and acetylsalicylic acid (ASP) having closely overlapping spectra. The mathematical algorithms of multivariate spectral calibrations as namely tri-linear regression calibration (TLRC) and multi-linear regression calibration (MLRC) are based on the use of the linear regression equations at a three-wavelength set and a ten-wavelength set in the range of 215-305 nm. These calibration techniques do not require any chemical pre-treatment and a graphical procedure of the overlapping spectra. The mathematical content of TLRC and MLRC approaches were briefly formulated for the quantitative analysis of three- or multi-component mixtures. The applicability of the formulated calibration models were tested by analysing the various synthetic ternary mixtures consisting of these active compounds and then these models were applied to real pharmaceutical formulations. It was observed that TLRC and MLRC models give a successful quantitative multiresolution. The experimental results of these techniques were compared with each other as well as with those obtained by literature methods.

  3. Comparative bioavailability studies of citric acid and malonic acid based aspirin effervescent tablets

    Directory of Open Access Journals (Sweden)

    Anju Gauniya

    2010-01-01

    Full Text Available Purpose: The present investigation is aimed at comparing the pharmacokinetic profile (Bioavailability of aspirin in tablet formulations, which were prepared by using different effervescent excipients such as citric acid and malonic acid. Materials and Methods: The relative bioavailability and pharmacokinetics of citric acid based aspirin effervescent tablet (Product A and malonic acid based aspirin effervescent tablet (Product B formulations were evaluated for an in-vitro dissolution study and in-vivo bioavailability study, in 10 normal healthy rabbits. The study utilized a randomized, crossover design with a one-week washout period between doses. Blood samples were collected at 0, 1, 2, 4, 6, 8, 12 and 24 hours following a 100 mg/kg dose. Plasma samples were assayed by High Performance Liquid Chromatography. T max , C max , AUC 0-24 , AUC 0- ∞, MRT, K a, and relative bioavailability were estimated using the traditional pharmacokinetic methods and were compared by using the paired t-test. Result: In the present study, Products A and B showed their T max , C max , AUC 0-24 , AUC 0- ∞, MRT, and K a values as 2.5 h, 2589 ± 54.79 ng/ml, 9623 ± 112.87 ng.h/ml, 9586 ± 126.22 ng.h/ml, 3.6 ± 0.10 h, and 0.3698 ± 0.003 h -1 for Product A and 3.0 h, 2054 ± 55.79 ng/ml, 9637 ± 132.87 ng.h/ml, 9870 ± 129.22 ng.h/ml, 4.76 ± 0.10 h, and 0.3812 ± 0.002 h -1 for Product B, respectively. Conclusion: The results of the paired t-test of pharmacokinetics data showed that there was no significant difference between Products A and B. From both the in vitro dissolution studies and in vivo bioavailability studies it was concluded that products A and B had similar bioavailability.

  4. Comparative bioavailability studies of citric acid and malonic acid based aspirin effervescent tablets.

    Science.gov (United States)

    Gauniya, Anju; Das, Sanjita; Mallick, Subrata; Basu, S P

    2010-04-01

    The present investigation is aimed at comparing the pharmacokinetic profile (Bioavailability) of aspirin in tablet formulations, which were prepared by using different effervescent excipients such as citric acid and malonic acid. The relative bioavailability and pharmacokinetics of citric acid based aspirin effervescent tablet (Product A) and malonic acid based aspirin effervescent tablet (Product B) formulations were evaluated for an in-vitro dissolution study and in-vivo bioavailability study, in 10 normal healthy rabbits. The study utilized a randomized, crossover design with a one-week washout period between doses. Blood samples were collected at 0, 1, 2, 4, 6, 8, 12 and 24 hours following a 100 mg/kg dose. Plasma samples were assayed by High Performance Liquid Chromatography. T(max), C(max), AUC(0-24), AUC(0- ∞,) MRT, K(a,) and relative bioavailability were estimated using the traditional pharmacokinetic methods and were compared by using the paired t-test. In the present study, Products A and B showed their T(max), C(max), AUC(0-24), AUC(0- ∞,) MRT, and K(a) values as 2.5 h, 2589 ± 54.79 ng/ml, 9623 ± 112.87 ng.h/ml, 9586 ± 126.22 ng.h/ml, 3.6 ± 0.10 h, and 0.3698 ± 0.003 h (-1) for Product A and 3.0 h, 2054 ± 55.79 ng/ml, 9637 ± 132.87 ng.h/ml, 9870 ± 129.22 ng.h/ml, 4.76 ± 0.10 h, and 0.3812 ± 0.002 h (-1) for Product B, respectively. The results of the paired t-test of pharmacokinetics data showed that there was no significant difference between Products A and B. From both the in vitro dissolution studies and in vivo bioavailability studies it was concluded that products A and B had similar bioavailability.

  5. Multinational, double-blind, randomised, placebo-controlled, prospective study of esomeprazole in the prevention of recurrent peptic ulcer in low-dose acetylsalicylic acid users: the LAVENDER study.

    Science.gov (United States)

    Sugano, Kentaro; Choi, Myung-Gyu; Lin, Jaw-Town; Goto, Shinya; Okada, Yasushi; Kinoshita, Yoshikazu; Miwa, Hiroto; Chiang, Chern-En; Chiba, Tsutomu; Hori, Masatsugu; Fukushima, Yasushi; Kim, Hyun-Soo; Chang, Chi-Yang; Date, Masataka

    2014-07-01

    To evaluate if esomeprazole prevents recurrent peptic ulcer in adult patients with a history of peptic ulcer receiving low-dose acetylsalicylic acid (ASA, aspirin) for cardiovascular protection in East Asia. In this prospective, randomised, double-blind, placebo-controlled trial conducted in Japan, Korea and Taiwan, eligible patients receiving low-dose ASA for cardiovascular protection (81-324 mg/day) were randomised to esomeprazole 20 mg/day or placebo for ≤72 weeks. All patients received concomitant mucosal protection (gefarnate 100 mg/day). The primary endpoint was time to ulcer recurrence (Kaplan-Meier analysis). Efficacy findings are presented up to week 48, as per a planned interim analysis within the study protocol. A total of 364 patients (79.9% men; mean age, 67.1 years) comprised the full analysis set (esomeprazole, n=182; placebo, n=182). There was a statistically significant difference in the time to ulcer recurrence between esomeprazole and placebo (HR 0.09; 96.65% CI 0.02 to 0.41; pesomeprazole) and 89.0% (placebo). The high estimated ulcer-free rate for esomeprazole was maintained through to week 48 (98.3% vs. 81.2% of placebo-treated patients). No factors, other than female gender, reduced time to ulcer recurrence in addition to the effect of esomeprazole (pesomeprazole was generally well tolerated. Daily esomeprazole 20 mg is efficacious and well tolerated in reducing the recurrence of peptic ulcer in East-Asian patients with a history of ulcers who are taking low-dose ASA for cardiovascular protection. NCT01069939. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  6. Modulation of phenytoin teratogenicity and embryonic covalent binding by acetylsalicylic acid, caffeic acid, and alpha-phenyl-N-t-butylnitrone: implications for bioactivation by prostaglandin synthetase

    Energy Technology Data Exchange (ETDEWEB)

    Wells, P.G.; Zubovits, J.T.; Wong, S.T.; Molinari, L.M.; Ali, S.

    1989-02-01

    Teratogenicity of the anticonvulsant drug phenytoin is thought to involve its bioactivation by cytochromes P-450 to a reactive arene oxide intermediate. We hypothesized that phenytoin also may be bioactivated to a teratogenic free radical intermediate by another enzymatic system, prostaglandin synthetase. To evaluate the teratogenic contribution of this latter pathway, an irreversible inhibitor of prostaglandin synthetase, acetylsalicylic acid (ASA), 10 mg/kg intraperitoneally (ip), was administered to pregnant CD-1 mice at 9:00 AM on Gestational Days 12 and 13, 2 hr before phenytoin, 65 mg/kg ip. Other groups were pretreated 2 hr prior to phenytoin administration with either the antioxidant caffeic acid or the free radical spin trapping agent alpha-phenyl-N-t-butylnitrone (PBN). Caffeic acid and PBN were given ip in doses that respectively were up to 1.0 to 0.05 molar equivalents to the dose of phenytoin. Dams were killed on Day 19 and the fetuses were assessed for teratologic anomalies. A similar study evaluated the effect of ASA on the in vivo covalent binding of radiolabeled phenytoin administered on Day 12, in which case dams were killed 24 hr later on Day 13. ASA pretreatment produced a 50% reduction in the incidence of fetal cleft palates induced by phenytoin (p less than 0.05), without significantly altering the incidence of resorptions or mean fetal body weight. Pretreatment with either caffeic acid or PBN resulted in dose-related decreases in the incidence of fetal cleft palates produced by phenytoin, with maximal respective reductions of 71 and 82% at the highest doses of caffeic acid and PBN (p less than 0.05).

  7. Determination of free salicylic acid in chewing aspirin tablets by HPLC.

    Science.gov (United States)

    Tian, Jun; Chen, Xin-shan; Wang, Rui-dong

    2003-07-01

    To establish a HPLC method for determining the content of free salicylic acid in chewing aspirin tablets. The determination was conducted on a HPLC column (C(18), 150 mm x 4.6 mm x 5 microm) with methanol-water-glacial acetic acid (8.0 5.5 1.0) as the mobile phase and the detection wavelength of 302 nm. The calibration curve was linear within the concentration range of 2.65 to 31.77 microg/ml (r=0.999 97) of salicylic acid. The average recovery rate was 100.21% with relative standard deviation of 0.53% (n=6). HPLC is quick and accurate of determining the content of free salicylic acid for chewing aspirin tablets.

  8. Low dose aspirin like analgesic and anti-inflammatory activities of mono-hydroxybenzoic acids in stressed rodents.

    Science.gov (United States)

    Khan, Saba Anjum; Chatterjee, Shyam Sunder; Kumar, Vikas

    2016-03-01

    To compare analgesic and anti-inflammatory activities of aspirin and mono-hydroxybenzoic acids after their daily oral doses. Efficacies of repeated daily stress response suppressing low oral doses (20mg/kg) of aspirin and 2-, 3-, and 4-hydroxybenzoic acids in mice hot plate test for centrally acting analgesics, and in acetic acid induced writing test were compared. Effects of their same daily doses and treatment regimen in cotton pellet granuloma and carrageenan edema test for anti-inflammatory drugs in stressed rats were compared in a second experiment. Effects of treatments on body weights, basal rectal temperatures, organ weights and plasma glucose, insulin and cortisol levels in stressed animals were compared also. Although stress response suppressing effects of aspirin and all the three hydroxybenzoic acids in both mice and rats were almost equal, effectiveness of 3- and 4-hydroxybenzoic acids as analgesic and anti-inflammatory agents were lower than those of aspirin or salicylic acid. Observations made after single oral doses of aspirin or of mono-hydroxybenzoic acids are not very reliable predictors of their pharmacologically interesting bioactivity profiles and efficacies. Prostaglandin synthesis inhibition is not involved in low dose anti-inflammatory activities of 3- and 4-hydroxybenzoic acids. After their repeated daily low oral doses they are almost as potent stress response desensitizers as aspirin or salicylic acid. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Effect of formulation parameters on the drug release and floating properties of gastric floating two-layer tablets with acetylsalicylic acid.

    Science.gov (United States)

    Hasçiçek, Canan; Yüksel-Tilkan, Günseli; Türkmen, Berna; Ozdemir, Nurten

    2011-09-01

    Floating dosage forms of acetylsalicylic acid, used for its antithrombotic effect, were developed to prolong gastric residence time and increase bioavailability. In the two-layer tablet formulation, hydroxypropyl methylcellulose (HPMC) of high viscosity and an effervescent mixture of citric acid and sodium bicarbonate formed the floating layer. The release layer contained the drug, direct tableting agent and different types of matrix-forming polymers such as HPMC of low viscosity, sodium carboxymethylcellulose and chitosan. Tablets were prepared using a direct compression technique. The effect of formulation variables on physicochemical and floating properties and the drug release from tablets were investigated. Floating ability was dependent on the amount of effervescent agent and gel-forming polymer of the floating layer. Drug release was prolonged to 8 hours by changing the type and viscosity of the matrix-forming polymer in the drug-loading layer and all formulations showed a diffusion release mechanisms.

  10. Raman spectroscopy and capillary zone electrophoresis for the analysis of degradation processes in commercial effervescent tablets containing acetylsalicylic acid and ascorbic acid.

    Science.gov (United States)

    Neuberger, Sabine; Jooß, Kevin; Flottmann, Dirk; Scriba, Gerhard; Neusüß, Christian

    2017-02-05

    In order to ensure the stability of pharmaceutical products appropriate manufacturing and storage conditions are required. In general, the degradation of active pharmaceutical ingredients (APIs) and subsequent formation of degradation products affect the pharmaceutical quality. Thus, a fast and effective detection and characterization of these substances is mandatory. Here, the applicability of Raman spectroscopy and CZE for the characterization of the degradation of effervescent tablets containing acetylsalicylic acid (ASA) and ascorbic acid (AA) was evaluated. Therefore, a degradation study was performed analyzing tablets from two different manufacturers at varying conditions (relative humidity (RH) 33%, 52% and 75% at 30°C). Raman spectroscopy combined with principal component analysis could be successfully applied for the fast and easy discrimination of non-degraded and degraded effervescent tablets after a storage period of approximately 24h (RH 52%). Nevertheless, a clear identification or quantification of APIs and degradation products within the analyzed tablets was not possible, i.a. due to missing reference materials. CZE-UV enabled the quantification of the APIs (ASA, AA) and related degradation products (salicylic acid (SA); semi-quantitative also mono- and diacetylated AA) within the complex tablet mixtures. The higher the RH, the faster the degradation of ASA and AA as well as the formation of the degradation products. Mono- and diacetylated AA are major primary degradation products of AA for the applied effervescent tablets. A significant degradation of the APIs was detected earlier by CZE (6-12h, RH 52%) than by Raman spectroscopy. Summarized, Raman spectroscopy is well-suited as quick test to detect degradation of these tablets and CZE can be utilized for further detailed characterization and quantification of specific APIs and related degradation products. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Effects of paracetamol, non-steroidal anti-inflammatory drugs, acetylsalicylic acid, and opioids on bone mineral density and risk of fracture: results of the Danish Osteoporosis Prevention Study (DOPS)

    DEFF Research Database (Denmark)

    Vestergaard, Peter; Hermann, P; Jensen, J-E B

    2012-01-01

    Pain medication has been associated with fractures. We found higher weight in paracetamol and non-steroidal anti-inflammatory drugs (NSAID) users and lower vitamin D levels in opioid and acetylsalicylic acid users. None of the pain medications influenced bone mineral density or loss. NSAID were a...

  12. Modulating the inflammatory properties of activated microglia with Docosahexaenoic acid and Aspirin

    Science.gov (United States)

    2013-01-01

    Background Microglia are considered the “resident macrophages” of the brain. When in their resting state, microglia perform routine maintenance and immune surveillance. Once activated, either by injury or an immune stimulus, microglia secrete a variety of pro-inflammatory molecules, such as Nitric Oxide, superoxide, and inflammatory cytokines. Up-regulation of pro-inflammatory molecules is transient, and does not cause neurodegeneration. However, if up-regulation lasts for an extended period of time, neurodegeneration ensues. Many neurodegenerative diseases are characterized by chronic inflammation due to microglial activation. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) have been proposed as possible preventative treatments for neurodegenerative diseases, due to their anti-inflammatory properties. Docosahexaenoic Acid (DHA) is an omega-3 polyunsaturated fatty acid (PUFA) that has potent anti-inflammatory properties.This research work sought to elucidate whether microglial activation can be modulated by combining Aspirin, a classical NSAID, with Docosahexaenoic Acid, a natural anti-inflammatory agent. The combined ability of Aspirin and DHA to modulate microglial activation was determined in the context of pro-inflammatory cytokines, Nitric Oxide levels, as well as total Glutathione levels. Results Docosahexaenoic Acid increased total Glutathione levels in microglia cells and enhanced their anti-oxidative capacity. It reduced production of the pro-inflammatory cytokines TNF-α and IL-6 induced through TLR-3 and TLR-4 activation. Furthermore, it reduced production of Nitric Oxide. Aspirin showed similar anti-inflammatory effects with respect to TNF-α during TLR-3 and TLR-7 stimulation. Aspirin did not show any redection in terms of Nitric Oxide production. Combination of Aspirin and Docosahexaenoic Acid showed augmentation in total Glutathione production during TLR-7 stimulation as well as a reduction in IL-6, TNF-α and Nitric Oxide. Conclusions

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

    Directory of Open Access Journals (Sweden)

    Kunal Kanani

    2015-08-01

    Full Text Available 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.

  14. Impact of low-dose acetylsalicylic acid on kidney function in type 2 diabetic patients with elevated urinary albumin excretion rate

    DEFF Research Database (Denmark)

    Gaede, Peter; Hansen, Henrik Post; Parving, Hans-Henrik

    2003-01-01

    BACKGROUND: Low-dose treatment with acetylsalicylic acid (ASA) is widely recommended to type 2 diabetic patients as primary prevention against cardiovascular disease. High-dose treatment with cyclooxygenase inhibitors reduces urinary albumin excretion rate (AER) in type 1 diabetic patients...... with micro- or macroalbuminuria. Whether a similar effect on AER exists during low-dose ASA treatment, which may confound the diagnosis and monitoring of micro- and macroalbuminuria in type 2 diabetic patients, remains to be elucidated. METHODS: In a randomized, double-blind, crossover trial, 31 type 2...... diabetic patients with elevated levels of AER (>30 mg/24 h) were, in random order, given ASA (150 mg/day) for 4 weeks followed by placebo for 4 weeks with a 2 week washout period or vice versa. At the end of each treatment period AER, glomerular filtration rate (GFR), blood pressure (BP), transcapillary...

  15. Ultra-fast determination of caffeine, dipyrone, and acetylsalicylic acid by capillary electrophoresis with capacitively coupled contactless conductivity detection and identification of degradation products.

    Science.gov (United States)

    Marra, Mariana Cardoso; Cunha, Rafael Rodrigues; Vidal, Denis Tadeu Rajh; Munoz, Rodrigo Alejandro Abarza; do Lago, Claudimir Lucio; Richter, Eduardo Mathias

    2014-01-31

    Capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C(4)D) was used for fast, simultaneous determination of dipyrone (DIP), caffeine (CAF), and acetylsalicylic acid (ASA). In the same run and in less than 1min, the degradation products from DIP and ASA were also detected. In addition, the usage of the CE-C(4)D system allowed, for the first time, the detection of methylamine as a degradation product of DIP. Capillary electrophoresis with electrospray mass spectrometry experiments were carried out in order to confirm the formation of methylamine. The limits of detection by CE-C(4)D were 5, 5, and 6μmolL(-1) for CAF, DIP, and ASA, respectively. The proposed method was applied to the analysis of these compounds in pharmaceutical formulations with similar results to those achieved by HPLC (p<0.05). Copyright © 2013 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2007-02-01

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

  17. The nitric oxide-donating derivative of acetylsalicylic acid, NCX 4016, stimulates glucose transport and glucose transporters translocation in 3T3-L1 adipocytes.

    Science.gov (United States)

    Kaddai, V; Gonzalez, T; Bolla, M; Le Marchand-Brustel, Y; Cormont, M

    2008-07-01

    NCX 4016 is a nitric oxide (NO)-donating derivative of acetylsalicylic acid. NO and salicylate, in vivo metabolites of NCX 4016, were shown to be potential actors in controlling glucose homeostasis. In this study, we evaluated the action of NCX 4016 on the capacity of 3T3-L1 adipocytes to transport glucose in basal and insulin-stimulated conditions. NCX 4016 induced a twofold increase in glucose uptake in parallel with the translocation of the glucose transporters GLUT1 and GLUT4 to the plasma membrane, leaving unaffected their total expression levels. Importantly, NCX 4016 further increased glucose transport induced by a physiological concentration of insulin. The stimulatory effect of NCX 4016 on glucose uptake appears to be mediated by its NO moiety. Indeed, it is inhibited by a NO scavenger and treatment with acetylsalicylic or salicylic acid had no effect. Although NO is involved in the action of NCX 4016, it did not mainly depend on the soluble cGMP cyclase/protein kinase G pathway. Furthermore, NCX 4016-stimulated glucose transport did not involve the insulin-signaling cascade required to stimulate glucose transport. NCX 4016 induces a small activation of the mitogen-activated protein kinases p38 and c-Jun NH(2)-terminal kinase and no activation of other stress-activated signaling molecules, including extracellular signal-regulated kinase, inhibitory factor kappaB, or AMP-activated kinases. Interestingly, NCX 4016 modified the content of S-nitrosylated proteins in adipocytes. Taken together, our results indicate that NCX 4016 induced glucose transport in adipocytes through a novel mechanism possibly involving S-nitrosylation. NCX 4016 thus possesses interesting characteristics to be considered as a candidate molecule for the treatment of patients suffering from metabolic syndrome and type 2 diabetes.

  18. A retrospective study on IVF outcome in euthyroid patients with anti-thyroid antibodies: effects of levothyroxine, acetyl-salicylic acid and prednisolone adjuvant treatments

    Science.gov (United States)

    2009-01-01

    Background Anti-thyroid antibodies (ATA), even if not associated with thyroid dysfunction, are suspected to cause poorer outcome of in vitro fertilization (IVF). Methods We retrospectively analyzed: (a) the prevalence of ATA in euthyroid infertile women, (b) IVF outcome in euthyroid, ATA+ patients, and (c) the effect of adjuvant treatments (levothyroxine alone or associated with acetylsalicylic acid and prednisolone) on IVF results in ATA+ patients. One hundred twenty-nine euthyroid, ATA+ women undergoing IVF were compared with 200 matched, ATA-controls. During IVF cycle, 38 ATA+ patients did not take any adjuvant treatment, 55 received levothyroxin (LT), and 38 received LT +acetylsalicylic acid (ASA)+prednisolone (P). Results The prevalence of ATA among euthyroid, infertile patients was 10.5%, similar to the one reported in euthyroid women between 18 and 45 years. ATA+ patients who did not receive any adjuvant treatment showed significantly poorer ovarian responsiveness to stimulation and IVF results than controls. ATA+ patients receiving LT responded better to ovarian stimulation, but had IVF results as poor as untreated ATA+ women. Patients receiving LT+ASA+P had significantly higher pregnancy and implantation rates than untreated ATA+ patients (PR/ET 25.6% and IR 17.7% vs. PR/ET 7.5% and IR 4.7%, respectively), and overall IVF results comparable to patients without ATA (PR/ET 32.8% and IR 19%). Conclusion These observations suggest that euthyroid ATA+ patients undergoing IVF could have better outcome if given LT+ASA+P as adjuvant treatment. This hypothesis must be verified in further randomized, prospective studies. PMID:19941670

  19. Effect of Low-Dose Aspirin on Chronic Acid Reflux Esophagitis in Rats.

    Science.gov (United States)

    Masuda, Takahiro; Yano, Fumiaki; Omura, Nobuo; Tsuboi, Kazuto; Hoshino, Masato; Yamamoto, Se Ryung; Akimoto, Shunsuke; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

    2018-01-01

    Clinical role of low-dose aspirin (LDA) in pathogenesis of gastroesophageal reflux disease is by far controversial. This can be attributed to the paucity of basic research detailing the mechanism of LDA-induced esophageal mucosal injury (EI) on underlying chronic acid reflux esophagitis (RE). The aim of this study was to clarify the effect of LDA on chronic RE in rats. Esophagitis was induced in 8-week-old male Wistar rats by ligating the border between forestomach and glandular portion with a 2-0 silk tie and covering the duodenum with a small piece of 18-Fr Nélaton catheter. Seventy-eight chronic RE rat models were divided into five treatment groups, consisting of orally administered vehicle (controls), and aspirin doses of 2, 5, 50 or 100 mg/kg once daily for 28 days. EI was assessed by gross area of macroscopic mucosal injury, severity grade of esophagitis and microscopic depth of infiltration by inflammatory cells. Area of esophagitis in animals with aspirin dose of 100 mg/kg/day showed a 36.5% increase compared with controls, although it failed to achieve statistical significance (p = 0.812). Additionally, the rate of severe EI was increased in animals with aspirin dose of 100 mg/kg/day as compared with controls (p < 0.05). The grade of severity correlated with the depth of inflammation (r s = 0.492, p < 0.001). Maximal dose aspirin (100 mg/kg/day) contributed in exacerbating preexisting EI. LDA (2 and 5 mg/kg/day), on the other hand, did not affect chronic RE in this model. LDA seems to be safe for use in patients with chronic RE.

  20. Effects of acetylsalicylic acid and acetic acid solutions in VX2 carcinoma cells: In vitro analysis Efeito da solução de ácido acetilsalicílico e de ácido acético sobre o carcinoma vx-2: Análise in vitro

    Directory of Open Access Journals (Sweden)

    Rogério Saad-Hossne

    2006-06-01

    Full Text Available PURPOSE: To analyze, in vitro, the effects of acetylsalicylic acid (aspirin and acetic acid solutions on VX2 carcinoma cells in suspension and to examine the correlation between these effects and neoplastic cell death. METHODS: The VX2 tumor cells (10(7 cells/ml were incubated in solutions containing differing concentrations (2.5% and 5% of either acetylsalicylic acid or acetic acid, or in saline solution (controls. Every five minutes, cell viability was tested (using the trypan blue test and analyzed under light microscopy. RESULTS: Tumor cell viability (in % decreased progressively and, by 30 minutes, neoplastic cell death had occurred in all solutions. CONCLUSION: Based on this experimental model and the methodology employed, we conclude that these solutions cause neoplastic cell death in vitro.OBJETIVO: Analisar os efeitos das soluções de ácido acetil salicílico (aspirina e de ácido acético, in vitro, sobre células em suspensão do carcinoma VX-2, verificando-se as mesmas causam a morte das células neoplásicas. MÉTODOS: Procedeu-se a incubação das células tumorais VX-2 (10(7 células/ml com diferentes concentrações do ácido acetil salicílico (2,5% e 5% e de ácido acético (2,5% e 5%, sendo estudada a viabilidade celular pelo teste do azul tripian a cada 5 minutos; procedeu-se à análise à microscopia ótica. RESULTADOS: Observou-se que o percentual de viabilidade das células tumorais foi progressivamente diminuindo, sendo que ao final de 30 minutos todas as células neoplásicas estavam inviáveis em todas as soluções e concentrações utilizadas. CONCLUSÃO: Com base neste modelo experimental e com a metodologia empregada, concluiu-se que in vitro, estas soluções causam a morte (inviabilidade das células neoplásicas.

  1. Preharvest salicylic acid and acetylsalicylic acid treatments preserve quality and enhance antioxidant systems during postharvest storage of sweet cherry cultivars.

    Science.gov (United States)

    Giménez, M José; Serrano, María; Valverde, Juan Miguel; Martínez-Romero, Domingo; Castillo, Salvador; Valero, Daniel; Guillén, Fabián

    2017-03-01

    Sweet cherries are much appreciated by consumers as a result of their organoleptic quality attributes and antioxidant properties, although they deteriorate rapidly after harvest. Different preharvest strategies have been carried out to increase their quality at the time of harvest. We present data regarding the effect of preharvest salicylic acid (SA) and acetyl salicylic acid (ASA) treatments on sweet cherry quality during postharvest storage. At harvest and during postharvest storage, sweet cherry fruits ('Sweet Heart', 'Sweet Late' and 'Lapins') from SA (0.5 mmol L-1 ) and ASA (1 mmol L-1 ) treated trees had a higher colour (lower chroma index), firmness, total soluble solids, total phenolics, total anthocyanins and hydrophilic total antioxidant activity. In addition, the activity of the antioxidant enzymes catalase, peroxidase, superoxide dismutase and ascorbate peroxidase was also enhanced in SA- and ASA-treated cherries. Both SA and ASA preharvest treatments could be promising tools for improving sweet cherry quality at harvest and after storage, with an additional effect on delaying the postharvest ripening process by increasing the levels of antioxidant compounds and the activity of the antioxidant enzymes. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  2. Experiments with Aspirin.

    Science.gov (United States)

    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…

  3. Simultaneous determination of salicylic, 3-methyl salicylic, 4-methyl salicylic, acetylsalicylic and benzoic acids in fruit, vegetables and derived beverages by SPME-LC-UV/DAD.

    Science.gov (United States)

    Aresta, Antonella; Zambonin, Carlo

    2016-03-20

    Salicylic and benzoic acid are phenolic acids occurring in plant cells, thus they can be present in fruit and vegetables at various levels. They possess anti-inflammatory and antimicrobial properties, however they may induce symptoms and health problems in a small percentage of the population. Therefore, a low phenolic acid diet may be of clinical benefit to such individuals. In order to achieve this goal, the concentration of these substances in different food and beverages should be assessed. The present work describes for the first time a new method, based on solid phase microextraction (polydimethylsiloxane-divinylbenzene fiber) coupled to liquid chromatography with UV diode array detection, for the simultaneous determination of salicylic acid, 3-methyl salicylic acid, 4-methyl salicylic acid, acetylsalicylic acid and benzoic acid in selected fruit, vegetables and beverages. All the aspects influencing fiber adsorption (time, temperature, pH, salt addition) and desorption (desorption and injection time, desorption solvent mixture composition) of the analytes have been investigated. An isocratic separation was performed using an acetonitrile-phosphate buffer (pH 2.8; 2 mM) mixture (70:30, v/v) as the mobile phase. The estimated LOD and LOQ values (μg/mL) were in the range 0.002-0.028 and 0.007-0.095. The within-day and day-to-day precision values (RSD%) were between 4.7-6.1 and 6.6-9.4, respectively. The method has been successfully applied to the analysis of fava beans, blueberries, kiwi, tangerines, lemons, oranges and fruit juice (lemon and blueberry) samples. The major advantage of the method is that it only requires simple homogenization and/or centrifugation and dilution steps prior to SPME and injection in the LC system. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Dynamic study of interaction between beta-cyclodextrin and aspirin by the ultrasonic relaxation method.

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    Fukahori, Takanori; Kondo, Minako; Nishikawa, Sadakatsu

    2006-03-09

    A single ultrasonic relaxational phenomenon was observed in aqueous solutions containing both beta-cyclodextrin (beta-CD) as host and nonionized or ionized acetylsalicylic acid (aspirin) as guest. The observed relaxation was responsible for a dynamic complexation reaction between beta-CD and aspirin molecules, concomitant with a volume change during the reaction. The kinetic and equilibrium constants for the complexation in the acid (nonionized) form of the aspirin system were derived from the guest concentration dependence of the relaxation frequency. The equilibrium constant for the carboxylate (ionized) form of aspirin was determined from the concentration dependence of a maximum absorption per wavelength, and the rate constants were calculated by using the determined equilibrium constant and the observed relaxation frequencies, which remained nearly almost constant over the concentration range studied. The results showed that the effect of charge on the aspirin molecule was reflected only in the dissociation process from the beta-CD cavity, while no remarkable change was seen in the association process whose rate was diffusion controlled. The results could be explained on the basis of the difference of the hydrophobic moieties in the two guests that were included in the host cavity. The results of the standard volume change for the complexation reaction were closely related to the number of expelled water molecules originally located in the beta-CD cavity and the volume of the aspirin molecule incorporated into the beta-CD cavity.

  5. Gender differences in the activities of aspirin-esterases in rat tissues

    Directory of Open Access Journals (Sweden)

    Benedito M.A.C.

    1998-01-01

    Full Text Available The activities of aspirin (acetylsalicylic acid-esterases were measured in several tissues (liver, kidney, adrenal glands, brain and serum from adult male and female Wistar rats. In males, both aspirin-esterase I (assayed at pH 5.5 and II (assayed at pH 7.4 activities were higher in liver homogenates when compared to females (aspirin-esterase I: males 48.9 ± 4.8 (N = 8 and females 29.3 ± 4.2 (N = 8 nmol of salicylic acid formed min-1 mg protein-1; aspirin-esterase II: males 41.4 ± 4.1 (N = 8 and females 26.1 ± 4.5 (N = 8 nmol of salicylic acid formed min-1 mg protein-1, P<0.001. In serum, enzyme activity was higher in females than in males (aspirin-esterase I: males 0.85 ± 0.06 (N = 6 and females 1.18 ± 0.11 (N = 6 nmol of salicylic acid formed min-1 mg protein-1; aspirin-esterase II: males 1.03 ± 0.13 (N = 6 and females 1.34 ± 0.11 (N = 6 nmol of salicylic acid formed min-1 mg protein-1, P<0.001. In the other tissues assayed, no statistically significant difference between males and females was found. There were no statistically significant differences when the enzymes were assayed in different phases of the estrous cycle in liver and serum. These results show that the differences in aspirin-esterase activity observed between males and females are not due to the estrous cycle. The gender difference obtained in our study may indicate an involvement of gonadal hormones in the control of the hydrolysis of aspirin. This possibility is currently under investigation.

  6. Prospective, randomised trial of the time dependent antiplatelet effects of 500 mg and 250 mg acetylsalicylic acid i. v. and 300 mg p. o. in ACS (ACUTE).

    Science.gov (United States)

    Zeymer, Uwe; Hohlfeld, Thomas; Vom Dahl, Jürgen; Erbel, Raimund; Münzel, Thomas; Zahn, Ralf; Roitenberg, Alexander; Breitenstein, Stefanie; Pap, Ákos Ferenc; Trenk, Dietmar

    2017-02-28

    Little is known about the onset of action after intravenous or oral administration of acetylsalicylic acid (ASA) in patients with acute coronary syndromes (ACS). The aim of the study was to compare intravenous 250 or 500 mg acetylsalicylic acid (ASA) with oral 300 mg in ASA naïve patients with ACS concerning the onset of antiplatelet effects measured by time dependent thromboxane inhibition. A total of 270 patients with ACS 300 mg oral ASA (geometric means: from 652.0 to 223.7 ng/ml) (p-value, ANCOVA: 300 mg oral ASA from mean 87.18 to 75.56 U (p-value, ANCOVA: 300 mg orally is associated with a faster and more complete inhibition of thromboxane generation and platelet aggregation. Bleeding complications were comparable between the groups.

  7. Effects of acetylsalicylic acid and acetic acid solutions on VX2 liver carcinoma in rabbits: in vivo analysis Efeitos das soluções de aspirina e de ácido acético em fígado de coelhos portadores de tumor hepático VX2: análise in vivo

    Directory of Open Access Journals (Sweden)

    Rogério Saad-Hossne

    2007-08-01

    Full Text Available PURPOSE: To analyze, in vitro, the effects of acetylsalicylic acid (aspirin and acetic acid solutions on VX2 carcinoma cells in the liver of rabbits with VX2 hepatic tumors; to determine the histolytic and anatomopathological characteristics of the solutions; and to evaluate the eventual biochemical and hepatic changes. METHODS: A total of 48 rabbits were evaluated. The animals were randomized into two groups, protocol 3 (study group and protocol 4 (controls, and each group was then subdivided into 3 subgroups. Four days after implantation of the tumor in the liver, median laparotomy was performed with a 0.4-ml injection of a solution of either aspirin (5.0%, acetic acid (5.0% or saline. The animals were sacrificed after 24 hours (protocol 3 or after 11 days (protocol 4. Body weight, clinical evolution and biochemical levels, as well as the abdominal and thoracic cavities, were evaluated, and liver microscopy was performed. RESULTS: No changes in clinical evolution, body weight or biochemical levels were reported. However, an increase in alkaline phosphatase was observed in protocol 4 (controls. The tumor was eliminated in both protocols. CONCLUSION: Acetylsalicylic acid and acetic acid solutions cause the destruction of experimental hepatic tumors.OBJETIVO: Analisar os efeitos das soluções de aspirina e de ácido acético, in vivo, em fígado de coelhos portadores de tumor hepático VX2, verificando o efeito histolítico e anatomo-patológico das soluções e eventuais alterações bioquímicas hepáticas. MÉTODOS: Utilizou-se 48 coelhos, divididos em 2 protocolos experimentais(3 e 4, subdivididos em 3 grupos cada. Após 4 dias da implantação do tumor no fígado, procedeu-se a laparotomia mediana, com injeção de 0,4 ml da solução de aspirina (5,0%, de ácido acético (5,0% e solução salina; o sacrifício ocorreu apos 24 horas (protocolo 3 e 11 dias (protocolo 4; avaliou-se o peso, evolução clinica, dosagens bioquímicas, cavidade

  8. Effect of aspirin on the metabolism of exogenous arachidonic acid in human polymorphonuclear leukocytes

    Energy Technology Data Exchange (ETDEWEB)

    Punnonen, K.; Uotila, P.

    1984-08-01

    When human polymorphonuclear leukocytes (PMNL) were incubated with exogenous /sup 14/C-arachidonic acid (/sup 14/C-AA), both lipoxygenase and cyclo-oxygenase metabolites were detected. The amount of the 5-lipoxygenase metabolites formed, including 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), was small. The amount of other mono-HETE's (migrating in the vicinity of 12-HETE) was greater, but this was obviously mainly due to the small amount of contaminating platelets. In the presence of calcium ionophore A23187 the rate of formation of 5-HETE was increased, but the formation of other metabolites remained unchanged. When PMNL were incubated with aspirin in the presence of A23187 the formation of the cyclo-oxygenase products was decreased but that of 5-HETE was unchanged. The present study indicates that the calcium ionophore A23187 stimulates specifically the 5-lipoxygenase in human PMNL and that aspirin has no effect on the formation of the 5-lipoxygenase metabolites of arachidonic acid in human PMNL.

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

    Science.gov (United States)

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

    We use ab intio density functional theory to investigate the adsorption properties of acetylsalicylic acid or aspirin on a (10, 0) carbon nanotube (CNT) and a (8, 0) triazine-based graphitic carbon nitride nanotube (CNNT). It is found that an aspirin molecule binds stronger to the CNNT with its adsorption energy of 0.67 eV than to the CNT with 0.51 eV. The stronger adsorption energy on the CNNT is ascribed to the high reactivity of its N atoms with high electron affinity. The CNNT exhibits local electric dipole moments, which cause strong charge redistribution in the aspirin molecule adsorbed on the CNNT than on the CNT. We also explore the influence of an external electric field on the adsorption properties of aspirin on these nanotubes by examining the modifications in their electronic band structures, partial densities of states, and charge distributions. It is found that an electric field applied along a particular direction induces aspirin molecular states in the in-gap region of the CNNT implying a potential application of aspirin detection.

  10. [The prevention of thrombus formation and the improvement of the blood rheological properties during operations with a microsurgical technic. I. The possibilities for using acelysin--an acetylsalicylic acid derivative].

    Science.gov (United States)

    Vabishchevich, A V; Smirnova, L A; Roĭtman, E V; Shibaev, E Iu; Mikhaĭlova, O M; Svetlov, V A

    1999-01-01

    Changes in the blood clotting system and rheology were studied in 39 patients during reconstructive operations making use of microsurgical methods. Effects of various doses of water soluble acelysine, an acetylsalicylic acid preparations (DL-lysine acetylsalicylate and glycine) have been evaluated during surgery and the immediate postoperative period. Clinical and laboratory changes in blood coagulation were determined at different doses (1000, 500, and 250 mg). Even in low doses (3.94 +/- 0.25 mg/kg) acelysine ensured chronometric and structural hypocoagulation as early as 1 h after dosed infusion and throughout the entire intervention, preventing thrombosis of microvascular anastomoses. Administration of acelysine in doses higher than 250 mg is not recommended, because higher doses involve the risk of hypocoagulation complications.

  11. The influence of adding tomato extract and acetylsalicylic acid to hypotensive therapy on the daily blood pressure profiles of patients with arterial hypertension and high cardiovascular risk.

    Science.gov (United States)

    Osińska, Angelika N; Begier-Krasińska, Beata; Rzymski, Piotr; Krasińska, Aleksandra; Tykarski, Andrzej; Krasiński, Zbigniew

    2017-12-01

    Arterial hypertension (HT) is one of the most common diseases around the world and constitutes a significant medical, social, and economic problem. Lifestyle changes, including adequate fruit and vegetable consumption, play an important role in controlling blood pressure (BP) and other cardiovascular risk factors. To compare the influence of adding acetylsalicylic acid (ASA) or standardized tomato extract (STE) to standard hypotensive therapy on the values of arterial pressure and the daily blood pressure profiles of patients with hypertension and high cardiovascular risk. The study included 65 patients with arterial hypertension and high cardiovascular risk. High-risk patients with primary hypertension were randomly allocated in a blinded fashion to one of two groups (ASA or STE). In each case, two visits were made: the first - before the treatment, and the second - after 4 weeks of treatment. During each visit, the patients underwent a clinical measurement of arterial pressure and an ambulatory blood pressure measurement (ABPM). Blood platelet aggregation was assessed using the VerifyNow analyzer. After 4 weeks of treatment, the blood pressure values during the day (p blood pressure (DBP) (by 6.5%) and mean arterial pressure (MAP) (by 3.3%). The use of STE is significant in HT patients with high total cardiovascular risk; it is associated with better BP control and improvements in the daily BP profile.

  12. Low-Dose Acetylsalicylic Acid Treatment Modulates the Production of Cytokines and Improves Trophoblast Function in an in Vitro Model of Early-Onset Preeclampsia.

    Science.gov (United States)

    Panagodage, Shanika; Yong, Hannah E J; Da Silva Costa, Fabricio; Borg, Anthony J; Kalionis, Bill; Brennecke, Shaun P; Murthi, Padma

    2016-12-01

    Preeclampsia (PE), a serious hypertensive disorder of pregnancy, remains a leading cause of perinatal morbidity and mortality worldwide. Perturbed trophoblast function and impaired placental development early in pregnancy are key features. Low-dose acetylsalicylic acid (LDA) administered before 16 weeks' gestation significantly reduces the risk for PE. However, the exact mechanisms of action of LDA, particularly on trophoblast function, are unclear. We hypothesized that LDA influences placental trophoblast function and reverses PE-associated abnormalities. This study aimed to determine the effects of serum from normotensive women and from those with PE with or without LDA treatment on a model of placental syncytium. On cytokine profiling, LDA increased placental growth factor production and selectively restored PE serum-induced alterations in levels of cytokines [activated leukocyte cell adhesion molecule, CXCL-16, and ErbB3] to those in normotensive serum-treated cells. PE serum-induced increases in the apoptotic markers P53 mRNA expression, IKBKE mRNA expression, caspase 3 activity, and decreased BIRC8 mRNA expression, were attenuated by LDA treatment. LDA treatment also reduced abnormal differentiation caused by PE serum administration. Possible mechanisms by which LDA influences PE-affected trophoblast cells in vitro are by modulating cytokine secretion, reducing apoptosis to levels seen in normotensive serum-treated cells, and preventing the premature trophoblast differentiation commonly observed in PE. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  13. Binary mixtures of diclofenac with paracetamol, ibuprofen, naproxen, and acetylsalicylic acid and these pharmaceuticals in isolated form induce oxidative stress on Hyalella azteca.

    Science.gov (United States)

    Gómez-Oliván, Leobardo Manuel; Neri-Cruz, Nadia; Galar-Martínez, Marcela; Islas-Flores, Hariz; García-Medina, Sandra

    2014-11-01

    Toxicity in natural ecosystems is usually not due to exposure to a single substance, but is rather the result of exposure to mixtures of toxic substances. Knowing the effects of contaminants as a mixture compared to their effects in isolated form is therefore important. This study aimed to evaluate the oxidative stress induced by binary mixtures of diclofenac with paracetamol, ibuprofen, naproxen, and acetylsalicylic acid and by these nonsteroidal anti-inflammatory drugs (NSAIDs) in isolated form, using Hyalella azteca as a bioindicator. The median lethal concentration (LC50) and the lowest observed adverse effect level (LOAEL) of each NSAID were obtained. Amphipods were exposed for 72 h to the latter value in isolated form and as binary mixtures. The following biomarkers were evaluated: lipid peroxidation (LPX), protein carbonyl content (PCC), and activity of the antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Significant increases in LPX and PCC with respect to the control group (p ≤ 0.05) were induced by NSAIDs both in isolated form and as binary mixtures. Changes in SOD, CAT, and GPx activity likewise occurred with NSAIDs in isolated form and as binary mixtures. In conclusion, NSAIDs used in this study induce oxidative stress on H. azteca both in isolated form and as binary mixtures, and the interactions occurring between these pharmaceuticals are probably antagonistic in type.

  14. The effect of microcrystalline cellulose crystallinity on the hydrophilic property of tablets and the hydrolysis of acetylsalicylic acid as active pharmaceutical ingredient inside tablets.

    Science.gov (United States)

    Awa, Kimie; Shinzawa, Hideyuki; Ozaki, Yukihiro

    2015-08-01

    The crystal structures of active pharmaceutical ingredients and excipients should be strictly controlled because they influence pharmaceutical properties of products which cause the change in the quality or the bioavailability of the products. In this study, we investigated the effects of microcrystalline cellulose (MCC) crystallinity on the hydrophilic properties of tablets and the hydrolysis of active pharmaceutical ingredient, acetylsalicylic acid (ASA), inside tablets by using tablets containing 20% MCC as an excipient. Different levels of grinding were applied to MCC prior to tablet formulation, to intentionally cause structural variation in the MCC. The water penetration and moisture absorbability of the tablets increased with decreasing the crystallinity of MCC through higher level of grinding. More importantly, the hydrolysis of ASA inside tablets was also accelerated. These results indicate that the crystallinity of MCC has crucial effects on the pharmaceutical properties of tablets even when the tablets contain a relatively small amount of MCC. Therefore, controlling the crystal structure of excipients is important for controlling product qualities.

  15. Inhibition of thalidomide teratogenicity by acetylsalicylic acid: evidence for prostaglandin H synthase-catalyzed bioactivation of thalidomide to a teratogenic reactive intermediate.

    Science.gov (United States)

    Arlen, R R; Wells, P G

    1996-06-01

    Thalidomide is a teratogenic sedative-hypnotic drug that is structurally similar to phenytoin, which is thought to be bioactivated by prostaglandin H synthase (PHS) and other peroxidases to a teratogenic reactive intermediate. The relevance of this mechanism to thalidomide teratogenicity was evaluated in pregnant New Zealand White rabbits treated with thalidomide at 11:00 A.M. on gestational days 8 to 11, with day 0 indicating the time when sperm were observed in the vaginal fluid. Thalidomide (7.5 mg/kg i.v.) produced mainly fetal limb anomalies analogous to those observed in humans. Thalidomide (25-200 mg/kg i.p.), produced a dose-related increase in a spectrum of fetal anomalies, and in postpartum lethality, but did not produce a reliable incidence of limb anomalies. In subsequent studies, pregnant does received the irreversible PHS inhibitor acetylsalicylic acid (ASA), 75 mg/kg i.p., or its vehicle, followed 2 hr later by thalidomide, 7.5 mg/kg i.v., or its vehicle. ASA pretreatment was remarkably embryoprotective, resulting in respective 61.2 and 61.4% decreases in thalidomide-initiated fetal limb anomalies (P = .002) and postpartum fetal lethality (P teratogenicity, suggesting that thalidomide may be bioactivated by PHS to a teratogenic reactive intermediate.

  16. Histopathological, Ultrastructural, and Immunohistochemical Assessment of Hippocampus Structures of Rats Exposed to TCDD and High Doses of Tocopherol and Acetylsalicylic Acid

    Directory of Open Access Journals (Sweden)

    Joanna Rosińczuk

    2015-01-01

    Full Text Available The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD on central nervous system consists of changing expression of estrogen receptors, whereas the result of chronic inflammatory reaction caused by dioxin is occurrence of destructive changes in various organs connected with disturbed metabolism of connective tissue and damage of cells. The aim of the study was to determine the effect of dioxins on function, ultrastructure, and cytological and histological structure of hippocampus, particularly on expression of estrogen receptors in central nervous system as well as to define protective influence of tocopherol (TCP and acetylsalicylic acid (ASA on the decrease in activity of proinflammatory effects in central nervous system. It was shown that TCDD contributes to destructive and inflammatory changes along with demyelization of myelin sheaths and atrophy of estrogen receptors in hippocampus. Dioxin contributes to atrophy of estrogen receptors in hippocampus, in which also destructive and inflammatory changes were found along with demyelination of myelin sheaths. Histopathological and ultrastructural image of hippocampus areas in rats, in which both TCP and ASA were used, is characterized by poorly expressed degenerative changes and smaller inflammatory reactivity. Using both TCP and ASA has a protective effect on functions of central nervous system.

  17. Esomeprazole for prevention and resolution of upper gastrointestinal symptoms in patients treated with low-dose acetylsalicylic acid for cardiovascular protection: the OBERON trial.

    Science.gov (United States)

    Scheiman, James M; Herlitz, Johan; Veldhuyzen van Zanten, Sander J; Lanas, Angel; Agewall, Stefan; Nauclér, Emma C; Svedberg, Lars-Erik; Nagy, Péter

    2013-03-01

    Although low-dose acetylsalicylic acid (ASA) is recommended for prevention of cardiovascular events in at-risk patients, its long-term use can be associated with the risk of peptic ulcer and upper gastrointestinal (GI) symptoms that may impact treatment compliance. This prespecified secondary analysis of the OBERON study (NCT00441727) determined the efficacy of esomeprazole for prevention/resolution of low-dose ASA-associated upper GI symptoms. A post hoc analysis of predictors of symptom prevention/resolution was also conducted. Helicobacter pylori-negative patients taking low-dose ASA (75-325 mg) for cardiovascular protection who had ≥1 upper GI risk factor were eligible. The patients were randomized to once-daily esomeprazole 40 mg, 20 mg, or placebo, for 26 weeks; 2303 patients (mean age 67.6 years; 36% aged >70 years) were evaluable for upper GI symptoms. The proportion of patients with dyspeptic or reflux symptoms (self-reported Reflux Disease Questionnaire) was significantly lower (P esomeprazole versus in those treated with placebo. Treatment with esomeprazole (P 70 years (P esomeprazole is effective in preventing and resolving patient-reported upper GI symptoms in low-dose ASA users at increased GI risk.

  18. Reye's syndrome: the case for a causal link with aspirin.

    Science.gov (United States)

    Glasgow, John F T

    2006-01-01

    Reye's syndrome is a serious, acute encephalopathy that has been linked with aspirin (acetylsalicylic acid) use in children and teenagers Reye's syndrome and ingestion of aspirin during the febrile prodrome. The drug appears to act as a co-factor in susceptible individuals. Although some of the epidemiological data indicate an association between the two, the burden of evidence suggests actual causality and is both consistent and specific as well as strong and time related. Some of the evidence points to illness severity being dose related although it seems that in the presence of a viral infection, no dose of aspirin can be considered safe. No published work, using methodology that can be critically evaluated, has shown evidence to contradict these conclusions and they have been widely accepted. Since government health warnings were appended to aspirin-containing formulations, the decline in case numbers on both sides of the Atlantic has been nothing short of remarkable. Recent in vitro findings have pinpointed the site of action of the drug on the long chain hydroxyacyl-CoA dehydrogenase enzyme (a component of the mitochondrial trifunctional enzyme) and, even at therapeutic concentrations, oxidation is impaired in cultured fibroblasts from patients who have recovered from the disorder. This is quite unlike that seen in cells from normal controls. Even when major influenza outbreaks occur in the future, Reye's syndrome is preventable provided government health warnings are heeded and the cogent evidence set forth here is acted upon by the parents of feverish children and self-medicating teenagers.

  19. Antitumor-active cobalt-alkyne complexes derived from acetylsalicylic acid: studies on the mode of drug action.

    Science.gov (United States)

    Ott, Ingo; Schmidt, Kathrin; Kircher, Brigitte; Schumacher, Petra; Wiglenda, Thomas; Gust, Ronald

    2005-01-27

    Cobalt-alkyne complexes are drugs with remarkable cytotoxicity. From the complexes tested up to now we selected the aspirin derivative [2-acetoxy-(2-propynyl)benzoate]hexacarbonyldicobalt (Co-ASS) as the lead compound. To get more insight into the mode of action, we systematically modified the alkyne ligand and determined the cytotoxic properties of the resulting cobalt complexes. Further investigations were performed on the drug lipophilicity, the cellular uptake into MCF-7 and MDA-MB 231 breast cancer cells, the DNA-binding efficacy, and the nuclear drug content. The ability to inhibit glutathione reductase and cyclooxygenase (COX) enzymes, the binding to the estrogen receptor, and the induction of apoptotic processes were examined for selected compounds. Interestingly, the most antitumor active compounds were potent COX inhibitors (COX-1 and COX-2). The presented results indicate that cobalt-alkyne complexes of the Co-ASS type, represent a new class of organometallic cytostatics with a mode of drug action in which COX inhibition probably plays a major role.

  20. Assay of effervescent tablets by near-infrared spectroscopy in transmittance and reflectance mode: acetylsalicylic acid in mono and combination formulations.

    Science.gov (United States)

    Merckle, P; Kovar, K A

    1998-07-01

    Near-infrared spectroscopy (NIRS) was used to determine acetylsalicylic acid (ASA) in three different effervescent tablet formulations. The nominal ASA concentrations were 14.9% in the single substance formulation (ASA Mono), 17.4% in the combination with ascorbic acid (ASA + C) and 8.7% in the combination with paracetamol and ascorbic acid (ASA Combi). In each case the tablet matrix was composed of seven excipients typical of effervescent tablets. All three formulations were measured as intact tablets in diffuse transmittance and reflectance and as powdered tablets in diffuse reflectance. Calibration was carried out by partial least square (PLS) regression of second derivative spectra. High-performance liquid chromatography (HPLC) was used as the reference method. The relative standard errors of calibration (RSEC) achieved for the three NIR methods were between 1.20 and 2.01% for ASA Mono, between 1.91 and 2.21% for ASA + C and between 2.41 and 4.50% for ASA Combi. The results obtained in transmittance mode were comparable with those obtained in reflectance mode, which is normally used in NIRS. In the test sets of ASA Mono and ASA + C relative root mean square (RRMS) values between 2.21 and 3.13% were obtained. The three NIR methods applied are thus suitable for the quantitative determination of ASA in effervescent tablets and have the advantage over HPLC of being rapid and simply carried out with little sample preparation; they are nondestructive and do not require any environmentally harmful reagents.

  1. Features of the Hemostasis and Platelets Enzyme Activity in Patients with Different Sensitivity to Acetylsalicylic Acid by the Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    I. Yu. Grinshtein

    2016-01-01

    Full Text Available Aim. To study the features of the state of hemostasis and platelet enzymes activity in acetylsalicylic acid (ASA sensitive and resistant patients with acute coronary syndrome (ACS.Material and methods. The study included 53 patients (25 men and 28 women with ACS during the first 24 hours and after 10 days. The control group included 50 healthy volunteers. Before treatment the patients were tested on the sensitivity and resistance to ASA. The indicators of vascularplatelet and plasma hemostasis were evaluated as well as the NAD(P- dependent dehydrogenases activity in platelets was assessed by the bioluminescent method in the first day of ACS before antiplatelet therapy and on day 10.Results. Increase in spontaneous [1.72 U (1.28-2.72 U and 1.60 U (1.49-2.78 U, respectively] and ADP-induced [24.4% (21.1-29.8% and 19.2% (16.1-22.9%, respectively] platelet aggregation, von Willebrand factor activity [159.0% (108.0-190.0% and 155.0% (149.0-185.1%, respectively] was found in ASA-resistant patients with ACS in 1 and 10 day. Besides the ASA-resistant patients with ACS had very low pentose phosphate cycle and lactate dehydrogenase aerobic activity. They also demonstrated, compared with ASA-sensitive patients, higher intensity of aerobic respiration and the level of NADP-dependent substrate exchange between the tricarboxylic acid cycle and reactions of amino acid metabolism.Conclusion. Despite the dual antiplatelet therapy with ASA and clopidogrel, risk of thrombotic events is saved in ASA resistant patients with ACS. The metabolic changes in platelet influence their aggregation activity and cause an inadequate response to the antiplatelet therapy in ACS patients.

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

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Jin Young [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)

    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. Cyclin A2 and CDK2 as Novel Targets of Aspirin and Salicylic Acid: A Potential Role in Cancer Prevention.

    Science.gov (United States)

    Dachineni, Rakesh; Ai, Guoqiang; Kumar, D Ramesh; Sadhu, Satya S; Tummala, Hemachand; Bhat, G Jayarama

    2016-03-01

    Data emerging from the past 10 years have consolidated the rationale for investigating the use of aspirin as a chemopreventive agent; however, the mechanisms leading to its anticancer effects are still being elucidated. We hypothesized that aspirin's chemopreventive actions may involve cell-cycle regulation through modulation of the levels or activity of cyclin A2/cyclin-dependent kinase-2 (CDK2). In this study, HT-29 and other diverse panel of cancer cells were used to demonstrate that both aspirin and its primary metabolite, salicylic acid, decreased cyclin A2 (CCNA2) and CDK2 protein and mRNA levels. The downregulatory effect of either drugs on cyclin A2 levels was prevented by pretreatment with lactacystin, an inhibitor of proteasomes, suggesting the involvement of 26S proteasomes. In-vitro kinase assays showed that lysates from cells treated with salicylic acid had lower levels of CDK2 activity. Importantly, three independent experiments revealed that salicylic acid directly binds to CDK2. First, inclusion of salicylic acid in naïve cell lysates, or in recombinant CDK2 preparations, increased the ability of the anti-CDK2 antibody to immunoprecipitate CDK2, suggesting that salicylic acid may directly bind and alter its conformation. Second, in 8-anilino-1-naphthalene-sulfonate (ANS)-CDK2 fluorescence assays, preincubation of CDK2 with salicylic acid dose-dependently quenched the fluorescence due to ANS. Third, computational analysis using molecular docking studies identified Asp145 and Lys33 as the potential sites of salicylic acid interactions with CDK2. These results demonstrate that aspirin and salicylic acid downregulate cyclin A2/CDK2 proteins in multiple cancer cell lines, suggesting a novel target and mechanism of action in chemoprevention. Biochemical and structural studies indicate that the antiproliferative actions of aspirin are mediated through cyclin A2/CDK2. ©2015 American Association for Cancer Research.

  4. Pharmacokinetic interaction study of a fixed combination of 500 mg acetylsalicylic acid/30 mg pseudoephedrine versus each of the single active ingredients in healthy male volunteers.

    Science.gov (United States)

    Lücker, Peter Wolfgang; Birkel, Manfred; Hey, Bernhard; Loose, Irene; Schaefer, Andrea

    2003-01-01

    Acetylsalicylic acid (CAS 50-78-2, ASA) and pseudoephedrine (CAS 90-82-4, PSE) both are remedies given together for the treatment of the symptoms of a common cold, i.e. mainly nasal congestion, running nose, sore throat and headache. The aim of this open, randomized, three-factorial (three-treatment, three-period, six-sequence) Latin Square clinical study was to investigate if there were any pharmacokinetic interactions between ASA and PSE when given as fixed combination of 500 mg ASA/30 mg PSE.HCl. Lack of interaction was assessed by determination of pharmacokinetic characteristics and relative bioavailability of both substances and salicylic acid (CAS 69-72-7, SA), administered in combination and as equally single dosed drugs. In total, the data of 12 healthy male volunteers were included into the pharmacokinetic evaluation. Primary target parameters were ratios combination/equally dosed single drugs of AUCnorm and Cmax, norm of ASA, its metabolite SA and PSE. The primary target parameters were analyzed using an analysis of variance (ANOVA) after logarithmic transformation of the data. 90% confidence intervals were calculated for the geometric means of ratios using the mean square error term of the ANOVA. Bioequivalence was given for AUCnorm and Cmax, norm for all ratios calculated. No interaction was found for AUCnorm and Cmax, norm between the fixed combination ASA/PSE and the equally single dosed drugs as reference. The supplementary evaluation for the non-normalized original parameters AUC and Cmax also revealed bioequivalence. All treatments were safe and well tolerated.

  5. [Aspirin in primary and secondary prevention of colorectal carcinomas].

    Science.gov (United States)

    Schrör, Karsten; Rauch, Bernhard

    2013-11-01

    Observational but also some randomized trials suggest that regular long-term use of aspirin (acetylsalicylic acid) might reduce the risk of colorectal carcinomas by 15-40%. The efficacy appears to be increased with longer duration of treatment, i.e. beyond 5-10 years, but not with increasing doses. Aspirin at 75-100 mg daily appears to be sufficient in both primary as well as secondary prevention of recurrent tumors in sensitive persons, including prevention of distant metastases. The pharmacological mode of aspirin action is unclear as is the question whether only one or more sites of action exist. In any case, the mechanism(s) in charge should work at aspirin plasma levels of 10 microM or less which is the maximum concentration to be expected after antiplatelet doses. Inhibition of COX-1 and/or COX-2 is most likely involved. Follow-up reactions, such as inhibition of platelet-dependent thromboxane formation and action, release of storage products such as VEGF or sphingosine-1-phosphate and acetylation of COX-2 with subsequent generation of antioncogenic lipid mediators, such as lipoxins, are also possible. There is not much likelihood for "direct" actions of aspirin, shown in vitro at concentrations of 5 mM and more, which uncouple oxidative phosphorylation and paralyse the cell energy metabolism. benefit/risk profile, specifically regarding severe or fatal bleedings (GI-tract, cerebral). Accordingly, the actual German guideline "colorectal carcinoma" does not recommend aspirin use for prophylactic purposes. What is strongly needed are definitions of risk patients in terms of biomarkers or genetic profiling as well as data from long-term prospective randomized trials--both are underway.

  6. [Study of acetylsalicylic acid role in the potentiation of antiamnesic and neuroprotective properties of piracetam in rats with alloxan diabetes].

    Science.gov (United States)

    Zhiliuk, V I; Levykh, A E; Mamchur, V I

    2013-01-01

    It has been established that prolonged alloxan-induced hyperglycemia in rats potentiates amnesic properties of scopolamine hydrobromide. It was characterized by shortening of the latent period by 44% (pacetylsalicylic acid was accompanied by an expressed antiamnetic potential - the reduction of early markers of proteins degradation (aldehydephenylhydrazones, APH) by 21,7% (pacetylsalicylic acid to improve microcirculation in the ischemic areas of the brain in diabetes and probably to its neuroprotective potential.

  7. Bleeding peptic ulcer. Prevalence of Helicobacter pylori and use of nonsteroidal anti-inflammatory drugs/acetylsalicylic acid

    DEFF Research Database (Denmark)

    Vestergard, A.; Bredahl, K.; Muckadell, O.B. de

    2009-01-01

    INTRODUCTION: Helicobacter pylori (HP) infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs)/acetyl salicylic acid (ASA) are risk factors for bleeding peptic ulcer. HP eradication reduces the risk of rebleeding. Antibiotics, proton pump inhibitors (PPI) and presence of blood in the s......INTRODUCTION: Helicobacter pylori (HP) infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs)/acetyl salicylic acid (ASA) are risk factors for bleeding peptic ulcer. HP eradication reduces the risk of rebleeding. Antibiotics, proton pump inhibitors (PPI) and presence of blood...

  8. Aspirin down-regulates tryptophan degradation in stimulated human peripheral blood mononuclear cells in vitro.

    Science.gov (United States)

    Schroecksnadel, K; Winkler, C; Wirleitner, B; Schennach, H; Fuchs, D

    2005-04-01

    Acetylsalicylic acid (aspirin) is one of the most widely used drugs worldwide, due mainly to its broad therapeutic spectrum with anti-inflammatory, antipyretic, antithrombotic and analgesic effects. However, the exact mechanisms by which aspirin influences inflammation, pain and immune system activation are only partly understood. Within activation of the cellular immune system, Th1-type cytokine interferon (IFN)-gamma induces enzyme indoleamine-2,3-dioxygenase (IDO) which converts tryptophan to kynurenine. In parallel, IFN-gamma induces enzyme GTP-cyclohydrolase I, which gives rise to neopterin production by activated human macrophages. Similarly, tryptophan degradation and neopterin formation increase during several disease states involving Th1-type immune activation. Using stimulated human peripheral blood mononuclear cells (PBMC), the effect of aspirin on tryptophan degradation and neopterin production was investigated. Stimulation of PBMC with mitogens concanavalin A, phytohaemagglutinin and pokeweed mitogen induced significant tryptophan catabolism as was reflected by a decline in tryptophan levels and a parallel increase in kynurenine concentrations compared with unstimulated cells. In parallel, neopterin production was enhanced. Treatment of stimulated PBMC with increasing doses of 1-5 mM aspirin significantly decreased stimulation-induced tryptophan degradation and neopterin production as well. All the effects of aspirin were dose-dependent. The parallel influence of aspirin on both biochemical pathways implies that there was no direct inhibitory effect of aspirin on IDO; rather, it inhibits production of IFN-gamma in mitogen-treated PBMC. The influence of aspirin on biochemical pathways induced by IFN-gamma may represent an important part of its broad pharmacological effect.

  9. Aspirin dose for the prevention of cardiovascular disease: a systematic review.

    Science.gov (United States)

    Campbell, Charles L; Smyth, Susan; Montalescot, Gilles; Steinhubl, Steven R

    2007-05-09

    More than 50 million US adults take aspirin regularly for long-term prevention of cardiovascular disease, typically either 81 mg/d or 325 mg/d. Controversy remains regarding the most appropriate long-term daily dose. To review the mechanism of action of aspirin and the clinical literature for relationships among aspirin dosage, efficacy, and safety. A systematic review of the English-language literature was undertaken using MEDLINE and EMBASE (searched through February 2007) and the search term aspirin or acetylsalicylic acid and dose. The search was limited to clinical trials and was extended by a review of bibliographies of pertinent reports of original data and review articles. Published prospective studies using different aspirin dosages in the setting of cardiovascular disease were included. Although pharmacodynamic data demonstrate that long-term aspirin dosages as low as 30 mg/d are adequate to fully inhibit platelet thromboxane production, dosages as high as 1300 mg/d are approved for use. In the United States, 81 mg/d of aspirin is prescribed most commonly (60%), followed by 325 mg/d (35%). The available evidence, predominantly from secondary-prevention observational studies, supports that dosages greater than 75 to 81 mg/d do not enhance efficacy, whereas larger dosages are associated with an increased incidence of bleeding events, primarily related to gastrointestinal tract toxicity. Currently available clinical data do not support the routine, long-term use of aspirin dosages greater than 75 to 81 mg/d in the setting of cardiovascular disease prevention. Higher dosages, which may be commonly prescribed, do not better prevent events but are associated with increased risks of gastrointestinal bleeding.

  10. Cyclin A2 and CDK2 as Novel Targets of Aspirin and Salicylic acid: a Potential Role in Cancer Prevention

    Science.gov (United States)

    Dachineni, Rakesh; Ai, Guoqiang; Kumar, D. Ramesh; Sadhu, Satya S.; Tummala, Hemachand; Bhat, G. Jayarama

    2015-01-01

    Data emerging from the past 10 years have consolidated the rationale for investigating the use of aspirin as a chemopreventive agent; however, the mechanisms leading to its anti-cancer effects are still being elucidated. We hypothesized that aspirin’s chemopreventive actions may involve cell cycle regulation through modulation of the levels or activity of cyclin A2/cyclin dependent kinase-2 (CDK2). In this study, HT-29 and other diverse panel of cancer cells were used to demonstrate that both aspirin and its primary metabolite, salicylic acid, decreased cyclin A2 (CCNA2) and CDK2 protein and mRNA levels. The down regulatory effect of either drugs on cyclin A2 levels was prevented by pretreatment with lactacystin, an inhibitor of proteasomes, suggesting the involvement of 26S proteasomes. In-vitro kinase assays showed that lysates from cells treated with salicylic acid had lower levels of CDK2 activity. Importantly, three independent experiments revealed that salicylic acid directly binds to CDK2. Firstly, inclusion of salicylic acid in naïve cell lysates, or in recombinant CDK2 preparations, increased the ability of the anti-CDK2 antibody to immunoprecipitate CDK2, suggesting that salicylic acid may directly bind and alter its conformation. Secondly, in 8-anilino-1-naphthalene-sulfonate (ANS)-CDK2 fluorescence assays, pre-incubation of CDK2 with salicylic acid, dose-dependently quenched the fluorescence due to ANS. Thirdly, computational analysis using molecular docking studies identified Asp145 and Lys33 as the potential sites of salicylic acid interactions with CDK2. These results demonstrate that aspirin and salicylic acid down-regulate cyclin A2/CDK2 proteins in multiple cancer cell lines, suggesting a novel target and mechanism of action in chemoprevention. Implications Biochemical and structural studies indicate that the anti-proliferative actions of aspirin are mediated through cyclin A2/CDK2. PMID:26685215

  11. Bleeding peptic ulcer. Prevalence of Helicobacter pylori and use of nonsteroidal anti-inflammatory drugs/acetylsalicylic acid

    DEFF Research Database (Denmark)

    Vestergard, A.; Bredahl, K.; Muckadell, O.B. de

    2009-01-01

    INTRODUCTION: Helicobacter pylori (HP) infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs)/acetyl salicylic acid (ASA) are risk factors for bleeding peptic ulcer. HP eradication reduces the risk of rebleeding. Antibiotics, proton pump inhibitors (PPI) and presence of blood...

  12. CLINICAL AND LABORATORY CHARACTERISTICS OF PATIENTS WITH ISCHEMIC HEART DISEASE RESISTANT TO ACETYLSALICYLIC ACID IN PERIOPERATIVE PERIOD OF CORONARY ARTERY BYPASS GRAFT: RESULTS OF AN OPEN PROSPECTIVE STUDY

    Directory of Open Access Journals (Sweden)

    Yu. I. Grinshtein

    2016-01-01

    Full Text Available Aim. To study the clinical and laboratory characteristics of patients with stable angina that are sensitive or resistant to acetylsalicylic acid (ASA before and after coronary artery bypass graft (CABG surgery. Material and methods. Patients (n=60 with stable angina III-IV functional class, undergoing CABG, were included into the study. In the first postoperative day all patients started to take ASA in enteric form at a dose of 100 mg. To determine the sensitivity to ASA platelet aggregation induced by adenosine diphosphate (ADP 5μM and arachidonic acid (1 mM before and after incubation with ASA in vitro was studied one day before CABG and at the 1st and 10th days after CABG using an optical aggregometer. Dielectric properties of blood and its components were also studied with the original Fourier spectrometer. Results. The ASA-resistance rate was 26.7%. The ASA-resistant patients as compared with ASA-sensitive patients more often received selective cyclooxygenase 2 (COX-2 inhibitors (44% vs. 17%, respectively, p<0.05 after CABG. They had higher serum creatinine levels at the 1st day after CABG (153.7±49.9mmol/L vs 115.3±29mmol/L, respectively, p=0.028, >and very high erythrocyte sedimentation rate at 10th day after CABG (80.625±21.3 mm/h vs 54.6±26.5 mm/h; respectively, p=0.028. 33% of patients had resistance to en-teric form of ASA during 10-day therapy after CABG, however, platelet aggregation induced by arachidonic acid was low in in vitro platelet incubation with ASA. This points at decreased bioavailability of enteric forms of ASA. “Transient” ASA-resistance was detected in 12.5% of ASA-resistant patients on the 1st day after CABG due to cardiopulmonary bypass. Significant differences in the dielectric characteristics of blood and platelets were found in the groups of ASA-resistant and ASA-sensitive patients 10 days after CABG. Conclusion. Cardiopulmonary bypass, COX-2 inhibitors, renal dysfunction, the inflammatory response, may

  13. Aspirin overdose

    Science.gov (United States)

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

  14. Aspirin Desensitization

    Science.gov (United States)

    ... Nerve Decompression Dacryocystorhinostomy (DCR) Disclosure Statement Printer Friendly Aspirin Desensitization Kevin C. Welch, MD Zara Patel, MD Introduction The term "aspirin-sensitive asthma" (also known as "aspirin triad" or " ...

  15. Quasi-Elastic Neutron Scattering Studies of the Slow Dynamics of Supercooled and Glassy Aspirin

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yang [ORNL; Tyagi, M. [NCNR and University of Maryland; Mamontov, Eugene [ORNL; Chen, Sow-hsin H [ORNL

    2011-01-01

    Aspirin, also known as acetylsalicylic acid (ASA), is not only a wonderful drug, but also a good glass former. Therefore, it serves as an important molecular system to study the near-arrest and arrested phenomena. In this paper, a high-resolution quasi-elastic neutron scattering (QENS) technique is used to investigate the slow dynamics of supercooled liquid and glassy aspirin from 410 K down to 350 K. The measured QENS spectra can be analyzed with a stretched exponential model. We find that (i) the stretched exponent (Q) is independent of the wave vector transfer Q in the measured Q-range, and (ii) the structural relaxation time (Q) follows a power law dependence on Q. Consequently, the Q-independent structural relaxation time 0 can be extracted for each temperature to characterize the slow dynamics of aspirin. The temperature dependence of 0 can be fitted with the mode coupling power law, the Vogel-Fulcher-Tammann equation and a universal equation for fragile glass forming liquids recently proposed by M. Tokuyama in the measured temperature range. The calculated dynamic response function T(Q,t) using the experimentally determined self-intermediate scattering function of the hydrogen atoms of aspirin shows a direct evidence of the enhanced dynamic fluctuations as the aspirin is increasingly supercooled, in agreement with the fixed-time mean squared displacement x2 and non-Gaussian parameter 2 extracted from the elastic scattering.

  16. Quasi-elastic neutron scattering studies of the slow dynamics of supercooled and glassy aspirin

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Archana Vyas

    2016-01-01

    Full Text Available 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.

  18. Role of the double-contrast barium enema in rectal stenosis due to suppositories containing paracetamol and acetylsalicylic acid

    Energy Technology Data Exchange (ETDEWEB)

    Tannouri, F.; Lalmand, B.; Zalcman, M.; Gansbeke, D. van; Gevenois, P.A.; Struyven, J. [Department of Radiology, Hopital Erasme, University of Brussels (Belgium); Peny, M.O. [Department of Pathology, University of Brussels (Belgium); Gossum, A. van [Department of Gastroenterology, University of Brussels (Belgium)

    1998-09-01

    Self-treatment of chronic headache with suppositories containing paracetamol and acetylsalaicylic acid may lead to serious complications. We report the radiological features of five cases of rectal stenosis following the use of such suppositories. The role of the double-contrast barium enema in suggesting the diagnosis of this complication of a chronic and often unrecognized self-treatment is emphasized. (orig.) With 6 figs., 20 refs.

  19. SNX3-dependent regulation of epidermal growth factor receptor (EGFR) trafficking and degradation by aspirin in epidermoid carcinoma (A-431) cells.

    Science.gov (United States)

    Chiow, Kher Hsin; Tan, Yingrou; Chua, Rong Yuan; Huang, Dachuan; Ng, Mah Lee Mary; Torta, Federico; Wenk, Markus R; Wong, Siew Heng

    2012-05-01

    Since being introduced globally as aspirin in 1899, acetylsalicylic acid has been widely used as an analgesic, anti-inflammation, anti-pyretic, and anti-thrombotic drug for years. Aspirin had been reported to down-regulate surface expression of CD40, CD80, CD86, and MHCII in myeloid dendritic cells (DC), which played essential roles in regulating the immune system. We hypothesized that the down-regulation of these surface membrane proteins is partly due to the ability of aspirin in regulating trafficking/sorting of endocytosed surface membrane proteins. By using an established epidermoid carcinoma cell line (A-431), which overexpresses the epidermal growth factor receptor (EGFR) and transferrin receptor (TfnR), we show that aspirin (1) reduces cell surface expression of EGFR and (2) accumulates endocytosed-EGFR and -TfnR in the early/sorting endosome (ESE). Further elucidation of the mechanism suggests that aspirin enhances recruitment of SNX3 and SNX5 to membranes and consistently, both SNX3 and SNX5 play essential roles in the aspirin-mediated accumulation of endocytosed-TfnR at the ESE. This study sheds light on how aspirin may down-regulate surface expression of EGFR by inhibiting/delaying the exit of endocytosed-EGFR from the ESE and recycling of endocytosed-EGFR back to the cell surface.

  20. Soluble P-selectin level correlates with acetylsalicylic acid but not with clopidogrel response in patients with stable coronary artery disease after a percutaneous coronary intervention.

    Science.gov (United States)

    Kaufmann, Jan; Wellnhofer, Ernst; Kappert, Kai; Urban, Daniel; Meyborg, Heike; Hauptmann, Tobias; Müller, Aline; Meixner, Martin; Graf, Kristof; Fleck, Eckart; Stawowy, Philipp

    2013-06-01

    Impaired response to dual antiplatelet therapy is associated with worse cardiovascular outcome. Besides antiplatelet effects, there is evidence that both clopidogrel and acetylsalicylic acid (ASA) have anti-inflammatory properties. However, little is known about the relationship between platelet function and inflammation under dual antiplatelet therapy in patients with stable coronary artery disease. The purpose of the study was to investigate the correlation of platelet function with soluble (s)P-selectin and soluble (s)CD40L in patients undergoing elective percutaneous coronary intervention. Poor response to ASA and clopidogrel could lead to increased levels of inflammatory markers. A total of 148 patients were included. Eighty percent of the patients were on 100 mg ASA and all patients were clopidogrel naive. They underwent percutaneous coronary intervention and received a loading dose of 600 mg clopidogrel. Platelet function was assessed by light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein analysis at baseline, 24 h after loading, and after 1 month of maintenance therapy, respectively. Plasma levels of sP-selectin and sCD40L were measured. To classify low responders to clopidogrel, patients were screened for genetic variants determining clopidogrel absorption and metabolization. sP-selectin levels correlated with LTA findings after stimulation with arachidonic acid (P=0.012). Further, in addition to decreased platelet reactivity observed on LTA, lower sP-selectin levels were seen in patients under ASA therapy (P=0.004). CYP2C19*2 allele carriers had a higher platelet reactivity after clopidogrel loading measured by adenosine diphosphate-induced aggregation in LTA (P=0.008) and vasodilator-stimulated phosphoprotein phosphorylation (P=0.035); however, there was no difference in the inflammatory markers. Multiple regression analysis showed that variables significantly related to sP-selectin plasma levels were sCD40L (Pacid (P<0

  1. Prevention of peptic ulcers with esomeprazole in patients at risk of ulcer development treated with low-dose acetylsalicylic acid: a randomised, controlled trial (OBERON)

    Science.gov (United States)

    Devereaux, P J; Herlitz, Johan; Katelaris, Peter H; Lanas, Angel; Veldhuyzen van Zanten, Sander; Nauclér, Emma; Svedberg, Lars-Erik

    2011-01-01

    Objective To determine whether once-daily esomeprazole 40 mg or 20 mg compared with placebo reduces the incidence of peptic ulcers over 26 weeks of treatment in patients taking low-dose acetylsalicylic acid (ASA) and who are at risk for ulcer development. Design Multinational, randomised, blinded, parallel-group, placebo-controlled trial. Setting Cardiology, primary care and gastroenterology centres (n=240). Patients Helicobacter pylori-negative patients taking daily low-dose ASA (75–325 mg), who fulfilled one or more of the following criteria: age ≥18 years with history of uncomplicated peptic ulcer; age ≥60 years with either stable coronary artery disease, upper gastrointestinal symptoms and five or more gastric/duodenal erosions, or low-dose ASA treatment initiated within 1 month of randomisation; or age ≥65 years. All patients were ulcer-free at study entry. Interventions Once-daily, blinded treatment with esomeprazole 40 mg, 20 mg or placebo for 26 weeks. Main outcome measures The primary end point was the occurrence of endoscopy-confirmed peptic ulcer over 26 weeks. Results A total of 2426 patients (52% men; mean age 68 years) were randomised. After 26 weeks, esomeprazole 40 mg and 20 mg significantly reduced the cumulative proportion of patients developing peptic ulcers; 1.5% of esomeprazole 40 mg and 1.1% of esomeprazole 20 mg recipients, compared with 7.4% of placebo recipients, developed peptic ulcers (both pEsomeprazole was generally well tolerated. Conclusions Acid-suppressive treatment with once-daily esomeprazole 40 mg or 20 mg reduces the occurrence of peptic ulcers in patients at risk for ulcer development who are taking low-dose ASA. Clinical trial registration number ClinicalTrials.gov identifier: NCT00441727. PMID:21415072

  2. Synthesis, spectral properties and thermal behaviour of zinc(II) acetylsalicylate

    Energy Technology Data Exchange (ETDEWEB)

    Lambi, John N.; Nsehyuka, Alfred T.; Egbewatt, Nkongho; Cafferata, Lazaro F.R.; Arvia, Alejandro J

    2003-03-05

    The thermal behaviour of zinc(II) acetylsalicylate [Zn(acsa){sub 2}(H{sub 2}O){sub 2}] with respect to phase transitions, pyrolysis both in air and inert (N{sub 2}) atmosphere, and product identification has been investigated. The complex was synthesised by metathesis in hot ethanol solution using aspirin (acetylsalicylic acid) as precursor and characterised via electronic and IR spectral analyses. Optical observations showed that the white salt does not undergo a direct transition from the solid to the liquid phase but rather goes slowly through an intermediate mesophase around 80 deg. C before melting rapidly to the brick-brown isotropic liquid around 134-136 deg. C. No liquid crystalline phases are however formed. This result was complemented by that from thermogravimetric (TG) studies in the ca. 25-600 deg. C range, which showed three main weight-loss phases of 8.0, 50.0 and 14.0% (around 200, 250 and 400 deg. C) corresponding, respectively, to the elimination of CO{sub 2}, xanthone and acetic acid. The pyrolysis products, as identified using a combination of instrumental (GC-MS) and wet chemical techniques are: CO{sub 2}; non-stoichiometric zinc oxide, most likely in the form: Zn{sub 1+x}O (where 0.0000{<=}x{<=}0.0003); and a mixture of organic products resulting from further decomposition, charring and other attendant thermal effects at the relatively high temperatures (ca. 600 deg. C) involved. Six of the principal organic products were identified and included salsalate and benorylate which are pro-drugs of salicylic acid, a well-known pharmaceutical.

  3. Relative bioavailability and bioequivalence of a newly developed fixed combination sachet of acetylsalicylic acid and pseudoephedrine compared with a preliminary combination.

    Science.gov (United States)

    Lücker, P W; Birkel, M; Hey, B; Loose, I; Schaefer, A

    2003-10-01

    Acetylsalicylic acid (ASA) and pseudoephedrine (PSE) are often administered together for the treatment of symptoms of the common cold, i.e., nasal congestion, runny nose, sore throat and headache. Based on this fact we developed a fixed combination of 500 mg ASA and 30 mg PSE, the recommended doses for both drugs for treating symptoms of the common cold, as granulate to be dissolved in water for administration. The purpose of this open, randomized, three-factorial (three-treatment, three-period, six-sequence) Latin Square clinical study was to investigate the relative bioavailability of ASA and PSE as well as the establishment of bioequivalence after single administration of the fixed combination (final formulation for approval) of 500 mg ASA/30 mg PSE*HCl and the preliminary formulation of this combination. Pharmacokinetic characteristics AUC(norm) and C(max,norm) of ASA, its metabolite SA, and PSE, were determined as measure of rate and extent of absorption of the two formulations. The treatment ratios final/preliminary formulation and their corresponding 90% confidence intervals were calculated to establish bioequivalence. Additionally, descriptive statistics were calculated for the parameters t(max), t((1/2)), and mean residence time (MRT). In total, data from 18 healthy male volunteers were included in the pharmacokinetic evaluation. The primary target parameters were analyzed using an analysis of variance (ANOVA) after logarithmic transformation of the data. Confidence intervals of 90% were calculated for the geometric means of ratios using the mean square error term of the ANOVA. Bioequivalence criteria were fulfilled for AUC(norm) and C(max,norm). Geometric means of individual ratios of AUC(norm) and of C(max,norm) showed equal bioavailability of the new formulation compared with the preliminary. Furthermore, a relative bioavailability of approximately 100% of the preliminary formulation was shown for the newly developed formulation for all parameters. The

  4. Inhibition of trimethadione and dimethadione teratogenicity by the cyclooxygenase inhibitor acetylsalicylic acid: a unifying hypothesis for the teratologic effects of hydantoin anticonvulsants and structurally related compounds.

    Science.gov (United States)

    Wells, P G; Nagai, M K; Greco, G S

    1989-03-01

    Teratogenicity of the anticonvulsant phenytoin may be due in part to its bioactivation by prostaglandin synthetase, forming a reactive free radical intermediate. We examined whether teratogenicity of the structurally similar oxazolidinedione anticonvulsants, trimethadione and its N-demethylated metabolite dimethadione, could be inhibited by the prostaglandin synthetase inhibitor acetylsalicylic acid (ASA). Trimethadione, 700 or 1000 mg/kg intraperitoneally (ip), was given to pregnant CD-1 mice during (Gestational Days 12 and 13) or before (Days 11 and 12) the critical period of susceptibility to phenytoin-induced fetal cleft palates. Dimethadione was given similarly on Days 11 and 12, or 12 and 13, in a dose (900 mg/kg ip) that was equimolar to 1000 mg/kg of trimethadione. ASA, 10 or 1 mg/kg ip, was given 2 hr before trimethadione or dimethadione on Days 11 and 12, and before trimethadione on Day 11 only. Dams were killed on Day 19 and fetuses were examined for anomalies. Either dose of trimethadione given on Days 12 and 13 was negligibly teratogenic, as evidenced by a non-dose-related, 1.1% mean incidence of fetal cleft palates. However, when given earlier on Days 11 and 12, trimethadione 1000 mg/kg caused an 8.9% incidence of cleft palates (p less than 0.05). Similarly, dimethadione caused a 3.9-fold higher incidence of cleft palates when given earlier on Days 11 and 12 (17.3-34.9%) than on Days 12 and 13 (4.4%) (p less than 0.05). At equimolar doses, dimethadione caused a 1.9- to 3.9-fold higher incidence of cleft palates compared to trimethadione (p less than 0.05), suggesting that dimethadione may be the proximate teratogen. Either dose of ASA given on both days before trimethadione totally prevented cleft palates, and ASA 10 mg/kg given only on Day 11 reduced the incidence of trimethadione-induced cleft palates to 1.1% (p less than 0.05). ASA reduced the incidence of cleft palates caused by dimethadione given on Days 11 and 12 from 34.9 to 20.3% (p less than

  5. Simultaneous Determination of Ascorbic Acid, L-Dopa, Uric Acid, Insulin, and Acetylsalicylic Acid on Reactive Blue 19 and Multi-Wall Carbon Nanotube Modified Glassy Carbon Electrode

    OpenAIRE

    Nasirizadeh, Navid; Shekari, Zahra; Tabatabaee, Masoumeh; Ghaani,Masoud

    2015-01-01

    A trifunctional electrochemical sensor was fabricated for simultaneous determination of ascorbic acid (AA), levodopa (LD), and insulin. This was done by modifying a glassy carbon electrode (GCE) with multi-walled carbon nanotubes and reactive blue 19 (RB-MWCNT-GCE). Cyclic voltammetry was used to investigate the redox properties of this modified electrode. The electro-catalytic activity of the modified electrode was studied for the oxidation of AA, LD, and insulin. By differential pulse volta...

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

    Science.gov (United States)

    Pasero, G; Marson, P

    2010-01-01

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

  7. Effects of volumetric expansion in molecular crystals: A quantum mechanical investigation on aspirin and paracetamol most stable polymorphs

    Science.gov (United States)

    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.

  8. Aspirin and paracetamol removal using a commercial micro-sized TiO2catalyst in deionized and tap water.

    Science.gov (United States)

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

    2017-05-01

    Micro-sized TiO 2 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.

  9. Use of a fixed combination of acetylsalicylic acid, acetaminophen and caffeine compared with acetaminophen alone in episodic tension-type headache: meta-analysis of four randomized, double-blind, placebo-controlled, crossover studies

    Science.gov (United States)

    2014-01-01

    Background Most patients with episodic tension-type headache treat headache episodes with over-the-counter medication. Combination analgesics containing caffeine may be more effective and as well tolerated as monotherapy. The aim of this study was to evaluate the efficacy of the combination of acetylsalicylic acid, acetaminophen (paracetamol) and caffeine in episodic tension-type headache using recently recommended endpoints. Methods Four randomized, controlled trials of identical design in 1,900 patients with episodic tension-type headache comparing acetylsalicylic acid, acetaminophen and caffeine vs. acetaminophen or placebo were pooled. Analysis populations were ‘all headache episodes’ and those with ‘severe pain at baseline’. Post-hoc defined primary endpoint: headache episodes pain-free at 2 h. Secondary endpoints: headache episodes pain-free at 1 h, headache response at 2 h (mild or no pain), degree of interference with daily activities. Results 6,861 headache episodes were treated, including 2,215 severe headache episodes. The proportion of headache episodes pain-free at 2 h was significantly higher with the triple combination (28.5%) vs. acetaminophen (21.0%) and placebo (18.0%) (p pain-free at 2 h, headache response at 2 h and ability to return to daily activities, even in those with pain rated severe at baseline. PMID:25406671

  10. Influence of fulvic acid and hydroxy propyl-beta-cyclodextrin on aspirin degradation.

    Science.gov (United States)

    Anwer, Mohammad Khalid; Agarwal, Suraj Prakash; Ali, Asgar; Sultana, Yasmin

    2010-04-01

    The degradation of aspirin (ASA) was investigated to reveal information about the influence of complexation with fulvic acid (FA), as a new complexing agent and compared with hydroxy propyl-beta-cyclodextrin complex. ASA was complexed with FA in the molar ratio 1:0.5, 1:1, and 1:2 by different methods through lyophilization, solvent evaporation, and spray drying. Spray-dried (1:1) ASA-hydroxy propyl-beta-cyclodextrin complex was prepared and compared with optimized complex of FA. All the complexes and ASA alone were packaged in well-labeled sealed polythene-lined aluminum pouches and stored in stability chamber at 40 +/- 2 degrees C and 75 +/- 5% relative humidity for 120 days. Samples were analyzed for salicylic acid content at 0, 30, 60, 90, and 120 days. Overall 4.31% salicylic acid was formed in 1:1 ASA-FA spray-dried complex, which was optimized stable complex among other complexes of FA prepared by different methods in different molar ratios. However, 2.35% salicylic acid was measured with 1:1 spray-dried ASA-hydroxy propyl-beta-cyclodextrin complex. Stability of ASA increased more when complexed with hydroxy propyl-beta-cyclodextrin as compared to FA. A novel complexing agent in the form of FA was investigated to increase the stability of ASA. A marked improvement in stability of ASA was observed when complexed with hydroxy propyl-beta-cyclodextrin (1:1) by spray drying as compared to 1:1 spray-dried ASA-FA complex.

  11. Medroxyprogesterone - valproic acid - aspirin. MVA regime to reduce transfusion associated mortality in late-term hemoglobinopathies. Hypothesis and rationale.

    Science.gov (United States)

    Altinoz, Meric A; Ozdilli, Kursat; Carin, Mahmut N; Gedikoglu, Gunduz

    2007-01-01

    Medroxyprogesterone acetate (MPA) - a safe depot contraceptive - is shown previously to reduce painful crises of sickle cell anemia, which is parallel with the recent findings showing progesterone induction of fetal hemoglobin genes. This would be a way to reduce transfusions for late term thalassemia major and sickle cell-disease cases with no chances left for a stem cell transplantation. In these patients, transfusional hemosiderosis causes irreversible damage to many organs despite the available iron-chelating agents. Pharmacological strategies either target the conformal structure of the defective adult hemoglobin or aim to activate fetal hemoglobin concentrations. The only concern on MPA may be its thromboembolic risks, which may be uncoupled with agents acting both anti-coagulant and inductive on the blood oxygen-carrying affinity. Such agents could be valproic acid and aspirin. Valproic acid is being safely used to treat epilepsy and its histone acetylating function may lead its induction of fetal hemoglobin. Aspirin was shown to increase oxygen affinity of hemoglobin via acetylating lysine residues and its general acetylating activity on proteins such as histones makes it also an interesting candidate to activate fetal hemoglobin. We propose that combining MPA with clinically available doses of valproic acid and aspirin would be beneficial in terms of both reduced coagulation risks and increased oxygen affinity to decrease the transfusions and to improve the prognosis in late-phase hemoglobin disorders.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  13. Comparative study of the continuous wavelet transform, derivative and partial least squares methods applied to the overlapping spectra for the simultaneous quantitative resolution of ascorbic acid and acetylsalicylic acid in effervescent tablets.

    Science.gov (United States)

    Dinç, Erdal; Ozdemir, Abdil; Baleanu, Dumitru

    2005-03-09

    The simultaneous spectrophotometric determination of ascorbic acid (AA) and acetylsalicylic acid (ASA) in effervescent tablets in the presence of the overlapping spectra was accomplished by the continuous wavelet transform (CWT), derivative spectrophotometry (DS) and partial least squares (PLS) approaches without using any chemical pre-treatment. CWT and DS calibration equations for AA and ASA were obtained by measuring the CWT and DS amplitudes corresponding to zero-crossing points of spectra obtained by plotting continuous wavelet coefficients and first-derivative absorbance values versus the wavelengths, respectively. The PLS calibration was constructed by using the concentration set and its full absorbance data consisting of 850 points from 220 to 305 nm in the range of 210-310 nm. These three methods were tested by analyzing the synthetic mixtures of the above drugs and they were applied to the real samples containing two commercial pharmaceutical preparations of subjected drugs. A comparative study was carried out by using the experimental results obtained from three analytical methodologies and precise and accurate results were obtained.

  14. Electrochemical study on inhibitory effect of Aspirin on mild steel in 1 M hydrochloric acid

    Directory of Open Access Journals (Sweden)

    B.M. Prasanna

    2017-02-01

    Full Text Available Aspirin was investigated as a good corrosion inhibitor for mild steel in 1 M hydrochloric acid at a temperature region from 303 to 333 K. The computed inhibition efficiency increases by increasing the inhibitor concentration and decreases by increasing the temperature. The investigation was done by weight loss, electrochemical measurements such as Tafel polarization and electrochemical impedance spectroscopy. Inhibition effect is attributed to the adsorption of inhibitor on the surface of the mild steel. The Tafel method reveals that the Aspirin acts as a mixed type inhibitor. Activation parameters suggest that the adsorption process is exothermic in nature. SEM photographs of mild steel in the absence and presence of inhibitor visualize the adsorption layer on the surface of the mild steel.

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

    Science.gov (United States)

    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.

  16. Reappraisal of the clinical pharmacology of low-dose aspirin by comparing novel direct and traditional indirect biomarkers of drug action.

    Science.gov (United States)

    Patrignani, P; Tacconelli, S; Piazuelo, E; Di Francesco, L; Dovizio, M; Sostres, C; Marcantoni, E; Guillem-Llobat, P; Del Boccio, P; Zucchelli, M; Patrono, C; Lanas, A

    2014-08-01

    Even though the acetylation of platelet cyclooxygenase (COX)-1 at serine-529 is the direct mechanism of action of low-dose aspirin, its antiplatelet effect has been characterized using indirect indexes of COX-1 activity. We performed a clinical study with enteric-coated low-dose aspirin (EC-aspirin), in healthy subjects, to evaluate the effects on the extent and duration of platelet COX-1 acetylation, using a novel proteomic strategy for absolute protein quantification (termed AQUA), as compared with traditional pharmacokinetic and pharmacodynamic parameters. In a phase I, single-arm, open-label study of EC aspirin (100 mg day(-1) ) administered to 24 healthy subjects, we compared, over a 24 h-period on day 1 and 7, % platelet acetylated COX-1 (AceCOX-1) with traditional pharmacokinetic and pharmacodynamics [i.e. serum thromboxane (TX) B2 , platelet function by monitoring CEPI(collagen/epinephrine) closure time (CT) using whole-blood PFA-100 and urinary excretion of 11-dehydro-TXB2 ] parameters. Acetylation of platelet COX-1 was measurable before detection of aspirin levels in the systemic circulation and increased in a cumulative fashion upon repeated dosing. After the last dose of EC-aspirin, %AceCOX-1, serum TXB2 and CEPI-CT values were maximally and persistently modified throughout 24 h; they averaged 76 ± 2%, 99.0 ± 0.4% and 271 ± 5 s, respectively. EC-aspirin caused 75% reduction in urinary 11-dehydro-TXB2 excretion. After chronic dosing with aspirin, the pharmacokinetics of acetylsalicylic acid was completely dissociated from pharmacodynamics. The demonstrated feasibility of quantifying the extent and duration of platelet COX-1 acetylation will allow characterizing the genetic, pharmacokinetic and pharmacodynamic determinants of the inter-individual variability in the antiplatelet response to low-dose aspirin as well as identifying extra-platelet sites of drug action. © 2014 International Society on Thrombosis and Haemostasis.

  17. The effect of salicylic acid and acetylsalicylic acid on red pigment formation in mechanically wounded scales of Hippeastrum x hybr. hort. and on the growth and development of Phoma narcissi

    Directory of Open Access Journals (Sweden)

    Alicja Saniewska

    2012-12-01

    Full Text Available Various organs of Hippeastrum infected by Phoma narcissi, infested with mite, Steneotarsonemus laticeps or mechanically wounded, produce red pigment on the surface of injured tissues. The aim of the present work was to study the effect of salicylic (SA and acetylsalicylic acids (ASA (inhibitors of biosynthesis of jasmonates and ethylene on red pigment formation in wounded scales of bulbs of Hippeastrum and on the mycelium growth of P. narcissi in vivo and in vitro. SA and ASA at a concentration of 1 and 2 mM partially inhibited the formation of red pigment in wounded scales, first of all in first 2 days after treatment. The growth and development of P. narcissi on basal plate and scales of longitudinally cut Hippeastrum bulb treated with SA and ASA (1 and 2 mM was similar as in control. SA (50 µg·cm-3 and ASA (250 µg·cm-3 inhibited the mycelium growth of P. narcissi on PDA medium, and concentration of 1000 µg·cm-3 of both almost totally inhibited the mycelium growth of the pathogen. Inhibitory effect of SA and ASA on the formation of red pigment in wounded scales of Hippeastrum may be caused by lowered biosynthesis and accumulation of jasmonates.

  18. Aspirin revealed

    Science.gov (United States)

    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.

  19. Mapping sites of aspirin-induced acetylations in live cells by quantitative acid-cleavable activity-based protein profiling (QA-ABPP).

    Science.gov (United States)

    Wang, Jigang; Zhang, Chong-Jing; Zhang, Jianbin; He, Yingke; Lee, Yew Mun; Chen, Songbi; Lim, Teck Kwang; Ng, Shukie; Shen, Han-Ming; Lin, Qingsong

    2015-01-20

    Target-identification and understanding of mechanism-of-action (MOA) are challenging for development of small-molecule probes and their application in biology and drug discovery. For example, although aspirin has been widely used for more than 100 years, its molecular targets have not been fully characterized. To cope with this challenge, we developed a novel technique called quantitative acid-cleavable activity-based protein profiling (QA-ABPP) with combination of the following two parts: (i) activity-based protein profiling (ABPP) and iTRAQ™ quantitative proteomics for identification of target proteins and (ii) acid-cleavable linker-based ABPP for identification of peptides with specific binding sites. It is known that reaction of aspirin with its target proteins leads to acetylation. We thus applied the above technique using aspirin-based probes in human cancer HCT116 cells. We identified 1110 target proteins and 2775 peptides with exact acetylation sites. By correlating these two sets of data, 523 proteins were identified as targets of aspirin. We used various biological assays to validate the effects of aspirin on inhibition of protein synthesis and induction of autophagy which were elicited from the pathway analysis of Aspirin target profile. This technique is widely applicable for target identification in the field of drug discovery and biology, especially for the covalent drugs.

  20. The pharmacokinetics and safety of a fixed-dose combination of acetylsalicylic acid and clopidogrel compared with the concurrent administration of acetylsalicylic acid and clopidogrel in healthy subjects: a randomized, open-label, 2-sequence, 2-period, single-dose crossover study.

    Science.gov (United States)

    Jung, Jin Ah; Kim, Tae-Eun; Kim, Jung-Ryul; Kim, Min-Ji; Huh, Wooseong; Park, Kyung-Mi; Lee, Soo-Youn; Ko, Jae-Wook

    2013-07-01

    Dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid (ASA) is used for the treatment of acute coronary syndrome. A combined formulation of ASA and clopidogrel has been developed to provide dosing convenience and improve adherence. This study was designed to compare the pharmacokinetic properties and safety profile of a fixed-dose combination formulation of ASA and clopidogrel with concurrent administration of each agent in healthy male Korean volunteers. This single-dose, randomized, open-label, 2-period crossover study was conducted in 64 healthy Korean volunteers. Equal numbers of eligible participants were randomly assigned to receive either the fixed-dose combination of ASA 100 mg and clopidogrel 75 mg or the free combination of each agent followed by a 7-day washout period and then administration of the alternate formulation. Serial blood samples were collected immediately before and after dosing for 24 hours. The safety profile was evaluated by using adverse events (AEs), which were assessed by physical examination, vital signs, ECGs, clinical laboratory tests, and interviews. The 2 formulations were considered to be bioequivalent if the 90% CIs for the log-transformed C(max) and AUC(0-last) values were within the predetermined range of 0.8 to 1.25. Sixty-four volunteers (mean [SD] age, 27.51 [8.15] years; weight, 68.55 [7.86] kg; height, 173.80 [5.94] cm) were enrolled, and 63 completed the study. For ASA, the 90% CIs for the geometric mean ratios of C(max) and AUC(0-last) were 0.9483 to 1.1717 and 0.9946 to 1.1020, respectively. For salicylic acid, the 90% CIs were 0.9614 to 1.0396 for C(max) and 0.9778 to 1.0163 for AUC(0-last). For clopidogrel, the 90% CIs were 0.9809 to 1.2562 for C(max) and 0.9674 to 1.2073 for AUC(0-last). Six of the 20 AEs reported were drug related: decreased hemoglobin levels (n = 2), fever (n = 1), and headache (n = 1) with the test formulation and increased alanine aminotransferase levels (n = 1) and dyspepsia (n

  1. A combination treatment of folic acid, aspirin, doxycycline and progesterone for women with recurrent early pregnancy loss; hospital based study

    Directory of Open Access Journals (Sweden)

    Kamal M. Zahran

    2016-03-01

    Full Text Available Objective: The study aims to state the effectiveness of a new combination treatment composed of folic acid, doxycycline, low dose aspirin and natural progesterone in cases of recurrent early pregnancy loss. Study design: A clinical comparative hospital-based study. Setting: Women Health Hospital – Assiut University – Egypt. Materials and methods: All patients with recurrent early pregnancy loss at 10 weeks or less attending our antenatal care unit were included. The patients were recruited over a period of 16 months and allocated into two groups. The study group received a regimen of folic acid, doxycycline, aspirin, and progesterone. The control group did not receive the previous regimen in the proposed way. The main outcome measures the live birth rate and complications of pregnancy in both groups. Results: Three hundred patients were recruited, with 150 women in each group. A high rate of live births was found in the study group (76.0% more than the control group (59.3%. Women in the Control Group reported more complications (76.0% vs. 51.3%. These were mainly abortion (40.0% vs. 23.3%, pre-eclampsia (16.0% vs. 10.7% and oligohydramnios (10.0% vs. 6.7%. Conclusion: The implementation of combination treatment of folic acid, doxycycline, low dose aspirin and natural progesterone resulted in a significant increase in the live birth rate, a significant reduction in miscarriages, and lower incidence of complications in patients with recurrent early pregnancy loss.

  2. Simultaneous extraction of acetylsalicylic acid and salicylic acid from human plasma and simultaneous estimation by liquid chromatography and atmospheric pressure chemical ionization/tandem mass spectrometry detection. Application to a pharmacokinetic study.

    Science.gov (United States)

    Nirogi, Ramakrishna; Kandikere, Vishwottam; Mudigonda, Koteshwara; Ajjala, Devender; Suraneni, Ramakrishna; Thoddi, Parthasarathi

    2011-01-01

    A simple analytical method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in atmospheric chemical ionization mode (APCI) for the simultaneous estimation of acetylsalicylic acid (ASA, CAS 50-78-2) and its active metabolite salicylic acid (SA, CAS 69-72-7) in human plasma has been developed and validated. ASA and SA were analyzed simultaneously despite differences in plasma concentration ranges of ASA and SA after oral administration of ASA. In spite of having different chemical, ionization and chromatographic properties, ASA and SA were extracted simultaneously from the plasma sample using acetonitrile protein precipitation followed by liquid-liquid extraction. The analytes were separated on a reversed phase column with rapid gradient program using mobile phase consisting of ammonium acetate buffer and methanol. The structural analogue diclofenac was used as an internal standard. The multiple reaction monitoring (MRM) transitions m/z 179 --> 137 for ASA, m/z 137 --> 65 for SA and m/z 294 --> 250 for IS were used. The assay exhibited a linear dynamic range of 0.02-10 microg/mL for ASA and 0.1-50 microg/mL for SA. The between-batch precision (%CV) ranged from 2.1 to 7.9% for ASA and from 0.2 to 5.2% for SA. The between-batch accuracy ranged from 95.4 to 96.7% for ASA and from 94.6 to 111.3% for SA. The validated method was successfully applied for the evaluation of pharmacokinetics of ASA after single oral administration of 650 mg test formulation versus two 325 mg reference formulations of ASA in human subjects.

  3. The aspirin metabolite salicylate enhances neuronal excitation in rat hippocampal CA1 area through reducing GABAergic inhibition.

    Science.gov (United States)

    Gong, Neng; Zhang, Min; Zhang, Xiao-Bing; Chen, Lin; Sun, Guang-Chun; Xu, Tian-Le

    2008-02-01

    Salicylate is the major metabolite and active component of aspirin (acetylsalicylic acid), which is widely used in clinical medicine for treating inflammation, pain syndromes and cardiovascular disorders. The well-known mechanism underlying salicylate's action mainly involves the inhibition of cyclooxygenase and subsequent decrease in prostaglandin production. Recent evidence suggests that salicylate also affects neuronal function through interaction with specific membrane channels/receptors. However, the effect of salicylate on synaptic and neural network function remains largely unknown. In this study, we investigated the effect of sodium salicylate on the synaptic transmission and neuronal excitation in the hippocampal CA1 area of rats, a key structure for many complex brain functions. With electrophysiological recordings in hippocampal slices, we found that sodium salicylate significantly enhanced neuronal excitation through reducing inhibitory GABAergic transmission without affecting the basal excitatory synaptic transmission. Salicylate significantly inhibited the amplitudes of both evoked and miniature inhibitory postsynaptic currents, and directly reduced gamma-aminobutyric acid type A (GABA(A)) receptor-mediated responses in cultured rat hippocampal neurons. Together, our results suggest that the widely used aspirin might impair hippocampal synaptic and neural network functions through its actions on GABAergic neurotransmission. Given the capability of aspirin to penetrate the blood-brain barrier, the present data imply that aspirin intake may cause network hyperactivity and be potentially harmful in susceptible subpopulations.

  4. Formulation of aspirin-magaldrate double-layer tablets: in vitro evaluation and cytoprotective activity in rats.

    Science.gov (United States)

    al Gohary, O M; el Din, K; el Tahir, H

    1996-01-01

    Double layer 325 mg oral aspirin tablets buffered with magaldrate antacid, 100, 150, 175 and 200 mg (F1, F2, F3 and F4, respectively) were prepared by direct compression. The new formulae were of remarkable hardness and friability. The tablets complied with the requirements of the acid neutralizing capacity, uniformity of dosage units, disintegration and dissolution tests (USP XXIII) for buffered aspirin tablets. The in vitro release pattern of F1 and F1 followed first order kinetics (r = 0.999), while F3 and F4 were released according to a zero order model (r = 0.993). Formulations F2, F3 and F4 as well as the marketed preparations, pure Aspro tablets (Acetylsalicylic acid 320 mg per tablet), or Ascriptin tablets (aspirin 325 mg plus 150 mg Maalox per tablet) were administered to fasted rats by gavage at doses that provided 400 mg aspirin kg-1 and the extent of the induced gastric damage was quantified 6 h later. Ascriptin, F3 and F4 preparations produced significantly less gastric damage (p < 0.05, n = 6) when compared with pure Aspro tablets. There was a clear dose-dependent decrease in the gastric damage following treatment with F2, F3 and F4 preparations, but there was no significant difference between the effects of F3 and F4 which were equipotent with Ascriptin.

  5. NSAIDs, Mitochondria and Calcium Signaling: Special Focus on Aspirin/Salicylates

    Directory of Open Access Journals (Sweden)

    Yoshihiro Suzuki

    2010-05-01

    Full Text Available Aspirin (acetylsalicylic acid is a well-known nonsteroidal anti-inflammatory drug (NSAID that has long been used as an anti-pyretic and analgesic drug. Recently, much attention has been paid to the chemopreventive and apoptosis-inducing effects of NSAIDs in cancer cells. These effects have been thought to be primarily attributed to the inhibition of cyclooxygenase activity and prostaglandin synthesis. However, recent studies have demonstrated unequivocally that certain NSAIDs, including aspirin and its metabolite salicylic acid, exert their anti-inflammatory and chemopreventive effects independently of cyclooxygenase activity and prostaglandin synthesis inhibition. It is becoming increasingly evident that two potential common targets of NSAIDs are mitochondria and the Ca2+ signaling pathway. In this review, we provide an overview of the current knowledge regarding the roles of mitochondria and Ca2+ in the apoptosis-inducing effects as well as some side effects of aspirin, salicylates and other NSAIDs, and introducing the emerging role of L-type Ca2+ channels, a new Ca2+ entry pathway in non-excitable cells that is up-regulated in human cancer cells.

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

    Science.gov (United States)

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

    2008-03-27

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

  7. A short history of anti-rheumatic therapy. II. Aspirin

    Directory of Open Access Journals (Sweden)

    P. Marson

    2011-06-01

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

  8. Dgroup: DG01950 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 15 ... Acetylsalicylic acid ... D00109 ... Aspirin (JP17/USP); Aspalon (JAN) ... D05181 ... Aspirin aluminum (JP17) ... D07579 ... Aspirin... calcium salt ... D07580 ... Aspirin DL-lysine (JAN) ... D07581 ... Aspirin magnesium salt ... D07582 ... Aspirin

  9. Resistencia al ácido acetil salicílico y al clopidogrel: una entidad clínica emergente Resistance to acetylsalicylic acid and to clopidogrel: an emergent clinical entity

    Directory of Open Access Journals (Sweden)

    José J Lugo

    2008-08-01

    pacientes expuestos a estos fármacos. Datos actuales muestran que cerca de 4% a 30% de los pacientes tratados con dosis convencionales de clopidogrel, no tienen una adecuada respuesta antiplaquetaria. La resistencia al clopidogrel es un término muy usado que aún precisa de una definición clara. Aun así, se emplea para reflejar que el clopidogrel falla en alcanzar su efecto antiagregante. Esta revisión discute la evidencia actual con relación a la variabilidad de la respuesta antiplaquetaria de estos dos medicamentos.Acetylsalicylic acid is perhaps one of the most antique drugs known worldwide since the time of Hippocrates, when willow bark was used for its analgesic and antipyretic effects. Its antiplatelet properties were known for the first time in 1967 and its mechanism of action was explained in 1971. Since then it is used mostly for its antiplatelet properties than for its analgesic or antipyretic effect. Platelet activation and aggregation play an important role in arterial thrombosis pathogenesis, which leads to acute coronary syndrome and thrombotic complications during and after percutaneous coronary interventions; for this reason, acetylsalicylic acid is the most used antiplatelet agent. Clinical trials have shown its efficacy both in primary and secondary prevention of myocardial infarction, stroke and cardiovascular death. Despite its proven benefits, the relative risk of recurrent vascular events among patients taking it remains relatively high and is estimated in 8% to 18% after two years. Therapeutic resistance to acetylsalicylic acid could partially explain this risk. Even though formal diagnostic criteria and a valid measurement system are not yet established, resistance to acetylsalicylic acid may affect 5% to 45% of the population. Given the prevalence of cardiovascular disease, the potential impact of resistance to this drug is wide. Another kind of agents that act blocking platelet aggregation are the thienopyridine derivates, that include

  10. Greener Methods for Aspirin Synthesis

    OpenAIRE

    Barilone, Jessica

    2013-01-01

    In this semester long study, I used microwave irradiation to synthesize aspirin. I compared this method to a traditional method that utilizes a strong acid. I compared the percent yield and the purity of the methods to pure aspirin

  11. Increased platelet expression of glycoprotein IIIa following aspirin treatment in aspirin-resistant but not aspirin-sensitive subjects

    Science.gov (United States)

    Floyd, Christopher N; Goodman, Timothy; Becker, Silke; Chen, Nan; Mustafa, Agnesa; Schofield, Emma; Campbell, James; Ward, Malcolm; Sharma, Pankaj; Ferro, Albert

    2014-01-01

    Aims Aspirin is widely used as an anti-platelet agent for cardiovascular prophylaxis. Despite aspirin treatment, many patients experience recurrent thrombotic events, and aspirin resistance may contribute to this. We examined the prevalence of aspirin resistance in a healthy population, and investigated whether the platelet proteome differed in aspirin-resistant subjects. Methods Ninety-three healthy subjects received aspirin 300 mg daily for 28 days. Before and at the end of treatment, urine was taken to determine 11-dehydrothromboxane B2, and blood was taken to measure arachidonic acid (AA)-induced aggregation of platelet-rich plasma and to interrogate the platelet proteome by mass spectrometric analysis with further confirmation of findings using Western blotting. Results In two of the 93 subjects, neither AA-induced aggregation nor urinary 11-dehydrothromboxane B2 was effectively suppressed by aspirin, despite measurable plasma salicylate concentrations, suggesting the presence of true aspirin resistance. Despite no detectable differences in the platelet proteome at baseline, following aspirin a marked increase was seen in platelet glycoprotein IIIa expression in the aspirin-resistant but not aspirin-sensitive subjects. An increase in platelet glycoprotein IIIa expression with aspirin resistance was confirmed in a separate cohort of 17 patients with stable coronary artery disease on long term aspirin treatment, four of whom exhibited aspirin resistance. Conclusions In a healthy population, true aspirin resistance is uncommon but exists. Resistance is associated with an increase in platelet glycoprotein IIIa expression in response to aspirin. These data shed new light on the mechanism of aspirin resistance, and provide the potential to identify aspirin-resistant subjects using a novel biomarker. PMID:25099258

  12. Aspirin treatment improved mesenchymal stem cell immunomodulatory properties via the 15d-PGJ2/PPARγ/TGF-β1 pathway.

    Science.gov (United States)

    Tang, Jianxia; Xiong, Jimin; Wu, Tingting; Tang, Zhangui; Ding, Gang; Zhang, Chunmei; Wang, Songlin; Liu, Yi

    2014-09-01

    Bone marrow mesenchymal stem cells (BMMSCs) have been used to treat a variety of autoimmune diseases in clinics. However, the therapeutic effects are largely dependent on the immunomodulatory capacity of culture-expanded BMMSCs. In the present study, we show that aspirin (acetylsalicylic acid, ASA)-treated BMMSCs have significantly improved immunomodulatory function, as indicated by upregulation of regulatory T cells (Tregs) and downregulation of Th17 cells via the 15d-PGJ2/PPARγ/TGF-β1 pathway. Furthermore, the therapeutic effect of ASA-pretreated BMMSCs was confirmed in a dextran sodium sulfate-induced experimental colitis mouse model, in which systemic infusion of ASA-pretreated BMMSCs significantly ameliorated disease activity index and colonic inflammation, along with an increased number of Tregs and decreased number of Th17 cells. Taken together, our results suggest that aspirin treatment is a feasible strategy to promote BMMSC-based immunomodulation.

  13. Preventing AVF thrombosis: the rationale and design of the Omega-3 fatty acids (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study.

    Science.gov (United States)

    Irish, Ashley; Dogra, Gursharan; Mori, Trevor; Beller, Elaine; Heritier, Stephane; Hawley, Carmel; Kerr, Peter; Robertson, Amanda; Rosman, Johan; Paul-Brent, Peta-Anne; Starfield, Melissa; Polkinghorne, Kevan; Cass, Alan

    2009-01-21

    Haemodialysis (HD) is critically dependent on the availability of adequate access to the systemic circulation, ideally via a native arteriovenous fistula (AVF). The Primary failure rate of an AVF ranges between 20-54%, due to thrombosis or failure of maturation. There remains limited evidence for the use of anti-platelet agents and uncertainty as to choice of agent(s) for the prevention of AVF thrombosis. We present the study protocol for a randomised, double-blind, placebo-controlled, clinical trial examining whether the use of the anti-platelet agents, aspirin and omega-3 fatty acids, either alone or in combination, will effectively reduce the risk of early thrombosis in de novo AVF. The study population is adult patients with stage IV or V chronic kidney disease (CKD) currently on HD or where HD is planned to start within 6 months in whom a planned upper or lower arm AVF is to be the primary HD access. Using a factorial-design trial, patients will be randomised to aspirin or matching placebo, and also to omega-3 fatty acids or matching placebo, resulting in four treatment groups (aspirin placebo/omega-3 fatty acid placebo, aspirin/omega-3 fatty acid placebo, aspirin placebo/omega-3 fatty acid, aspirin/omega-3 fatty acid). Randomisation will be achieved using a dynamic balancing method over the two stratification factors of study site and upper versus lower arm AVF. The medication will be commenced pre-operatively and continued for 3 months post surgery. The primary outcome is patency of the AVF at three months after randomisation. Secondary outcome measures will include functional patency at six and twelve months, primary patency time, secondary (assisted) patency time, and adverse events, particularly bleeding. This multicentre Australian and New Zealand study has been designed to determine whether the outcome of surgery to create de novo AVF can be improved by the use of aspirin and/or omega-3 fatty acids. Recently a placebo-controlled trial has shown that

  14. Preventing AVF thrombosis: the rationale and design of the Omega-3 fatty acids (Fish Oils and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED study

    Directory of Open Access Journals (Sweden)

    Rosman Johan

    2009-01-01

    Full Text Available Abstract Background Haemodialysis (HD is critically dependent on the availability of adequate access to the systemic circulation, ideally via a native arteriovenous fistula (AVF. The Primary failure rate of an AVF ranges between 20–54%, due to thrombosis or failure of maturation. There remains limited evidence for the use of anti-platelet agents and uncertainty as to choice of agent(s for the prevention of AVF thrombosis. We present the study protocol for a randomised, double-blind, placebo-controlled, clinical trial examining whether the use of the anti-platelet agents, aspirin and omega-3 fatty acids, either alone or in combination, will effectively reduce the risk of early thrombosis in de novo AVF. Methods/Design The study population is adult patients with stage IV or V chronic kidney disease (CKD currently on HD or where HD is planned to start within 6 months in whom a planned upper or lower arm AVF is to be the primary HD access. Using a factorial-design trial, patients will be randomised to aspirin or matching placebo, and also to omega-3 fatty acids or matching placebo, resulting in four treatment groups (aspirin placebo/omega-3 fatty acid placebo, aspirin/omega-3 fatty acid placebo, aspirin placebo/omega-3 fatty acid, aspirin/omega-3 fatty acid. Randomisation will be achieved using a dynamic balancing method over the two stratification factors of study site and upper versus lower arm AVF. The medication will be commenced pre-operatively and continued for 3 months post surgery. The primary outcome is patency of the AVF at three months after randomisation. Secondary outcome measures will include functional patency at six and twelve months, primary patency time, secondary (assisted patency time, and adverse events, particularly bleeding. Discussion This multicentre Australian and New Zealand study has been designed to determine whether the outcome of surgery to create de novo AVF can be improved by the use of aspirin and/or omega-3 fatty

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

    Science.gov (United States)

    Grove, Erik Lerkevang

    2012-09-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  17. Experimental and mathematical studies on the drug release properties of aspirin loaded chitosan nanoparticles.

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yixiang Shi

    2014-01-01

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

  19. Management of chronic hypertension during pregnancy with furosemide, amlodipine or aspirin: a pilot clinical trial.

    Science.gov (United States)

    Vigil-De Gracia, Paulino; Dominguez, Leyvis; Solis, Alcibiades

    2014-09-01

    To determine the maternal and neonatal efficacy and safety with furosemide, amlodipine or aspirin in women with mild/moderate chronic hypertension during pregnancy. A pilot clinical trial was performed in a tertiary teaching hospital in Panama. Pregnant patients with mild/moderate chronic hypertension at ≤20 weeks of gestation were invited to take part in the study. Mild/moderate chronic hypertension was defined as a pregnancy with systolic blood pressure of 140-159 mmHg or diastolic blood pressure of 90-109 mmHg. Women in the furosemide group received 20 mg of furosemide oral each day, those in the amlodipine group received 5 mg of amlodipine oral each day and those in the aspirin group received 75 mg of orally-administered acetylsalicylic acid each day. We enrolled 63 patients during the study period, 21 women were randomised to each group (aspirin, amlodipine and furosemide). We found no difference in maternal complications, pre-term births, mean birth weight or in the proportion of small for gestational age infants among treatment groups. Severe hypertension and aggregate pre-eclampsia were similar among treatment groups. This pilot trial demonstrates that both furosemide and amlodipine might have the same effect during pregnancy. However, a large clinical trial is necessary to prove this.

  20. Treatment with low doses of aspirin during chronic phase of experimental Chagas' disease increases oesophageal nitrergic neuronal subpopulation in mice.

    Science.gov (United States)

    Massocatto, Cristina Lorena; Martins Moreira, Neide; Muniz, Eliane; Marques de Araújo, Silvana; Pinge-Filho, Phileno; Rossi, Robson Marcelo; de Almeida Araújo, Eduardo José; de Mello Gonçales Sant'ana, Débora

    2018-01-19

    Patients with Chagas' disease may develop dysfunctions of oesophageal and colonic motility resulting from the degeneration or loss of the myenteric neurons of the enteric nervous system. Studies have shown that the use of aspirin, also known as acetylsalicylic acid (ASA), influences the pathogenesis of the disease. However, this remains controversial. The aim of this study was to evaluate the consequences of treatment with low doses of aspirin during the chronic phase of Chagas' disease on oesophageal function. Twenty male Swiss mice, 60 days of age, were used. The animals were infected with Y strain of Trypanosoma cruzi, injected intraperitoneally. Aspirin was given at a dose of 50 mg/kg to some of the infected animals, from the 55th to 63rd day after inoculation on consecutive days, and from the 65th to 75th day on alternate days. We investigated food passage of time, wall structure and nitrergic neuronal population of the distal oesophagus. Our data revealed that the use of low doses of aspirin in chronic Chagas' disease caused an increase in the number of nitrergic neurons and partially prevented hypertrophy of the oesophagus. In addition, the aspirin administration impeded Chagas' diseases associated changes in intestinal transit time. Thus treatment with aspirin in the chronic phase of Chagas' disease changes the natural history of the disease and raises the possibility of using it as a new therapeutic approach to the treatment of this aspect of Chagas' disease pathology. © 2018 The Authors. International Journal of Experimental Pathology © 2018 International Journal of Experimental Pathology.

  1. Twisted aspirin crystals.

    Science.gov (United States)

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

    2013-03-06

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

  2. [Prevention of atherosclerosis in children--the role of statins and aspirin].

    Science.gov (United States)

    Stolarz-Skrzypek, Katarzyna; Bednarski, Adam; Drozdz, Dorota; Czarnecka, Danuta

    2013-01-01

    Cardiovascular diseases remain the leading cause of death in Poland and in Europe. Children rarely suffer from them, although most of the risk factors which accelerate progression of atherosclerosis commence in childhood, including: dyslipidemias, hypertension, diabetes, and obesity. Moreover during last few years the incidence of some of risk factors in children, such as obesity, diabetes and dyslipidemia has increased significantly. It is known from the autopsy studies that atherosclerosis can be identified at very young age in healthy children. In adult population medications such as HMG-CoA reductase inhibitors (statins) and acetylsalicylic acid (ASA, aspirin) have strong position confirmed by many multicenter clinical trials. They significantly reduce cardiovascular risk and increase life expectancy. Latest recommendations on management of hyperlipidemias in children expand indications for screening of lipid level imbalances and indicate statins as main pharmacotherapy after failure of life style changes. On the other hand acetylsalicylic acid is not used so broadly. Only children at high risk of thrombosis may benefit from its antiplatelet property. This review presents the latest recommendations and the therapeutic role of these medications in pediatric population.

  3. Protective effects of levamisole, acetylsalicylic acid, and α-tocopherol against dioxin toxicity measured as the expression of AhR and COX-2 in a chicken embryo model.

    Science.gov (United States)

    Gostomska-Pampuch, Kinga; Ostrowska, Alicja; Kuropka, Piotr; Dobrzyński, Maciej; Ziółkowski, Piotr; Kowalczyk, Artur; Łukaszewicz, Ewa; Gamian, Andrzej; Całkosiński, Ireneusz

    2017-04-01

    Polychlorinated dibenzo-p-dioxins and dibenzofurans (dioxins) are classed as persistent organic pollutants and have adverse effects on multiple functions within the body. Dioxins are known carcinogens, immunotoxins, and teratogens. Dioxins are transformed in vivo, and interactions between the products and the aryl hydrocarbon receptor (AhR) lead to the formation of proinflammatory and toxic metabolites. The aim of this study was to determine whether α-tocopherol (vitamin E), acetylsalicylic acid (ASA), and levamisole can decrease the amount of damage caused by dioxins. Fertile Hubbard Flex commercial line chicken eggs were injected with solutions containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or containing TCDD and the test compounds. The chicken embryos and organs were analyzed after 7 and 13 days. The levels at which AhR and cyclooxygenase-2 (COX-2) proteins (which are induced during inflammation) were expressed were evaluated by performing immunohistochemical analyses on embryos treated with TCDD alone or with TCDD and the test compounds. TCDD caused developmental disorders and increased AhR and COX-2 expression in the chicken embryo tissues. Vitamin E, levamisole, ASA, and ASA plus vitamin E inhibited AhR and COX-2 expression in embryos after 7 days and decreased AhR and COX-2 expression in embryos after 13 days. ASA, levamisole, and ASA plus vitamin E weakened the immune response and prevented multiple organ changes. Vitamin E was not fully protective against developmental changes in the embryos.

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

    Science.gov (United States)

    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.

  5. Aspirin and the prevention of venous thromboembolism following total joint arthroplasty: commonly asked questions.

    Science.gov (United States)

    Azboy, I; Barrack, R; Thomas, A M; Haddad, F S; Parvizi, J

    2017-11-01

    The number of arthroplasties being performed increases each year. Patients undergoing an arthroplasty are at risk of venous thromboembolism (VTE) and appropriate prophylaxis has been recommended. However, the optimal protocol and the best agent to minimise VTE under these circumstances are not known. Although many agents may be used, there is a difference in their efficacy and the risk of bleeding. Thus, the selection of a particular agent relies on the balance between the desire to minimise VTE and the attempt to reduce the risk of bleeding, with its undesirable, and occasionally fatal, consequences. Acetylsalicylic acid (aspirin) is an agent for VTE prophylaxis following arthroplasty. Many studies have shown its efficacy in minimising VTE under these circumstances. It is inexpensive and well-tolerated, and its use does not require routine blood tests. It is also a 'milder' agent and unlikely to result in haematoma formation, which may increase both the risk of infection and the need for further surgery. Aspirin is also unlikely to result in persistent wound drainage, which has been shown to be associated with the use of agents such as low-molecular-weight heparin (LMWH) and other more aggressive agents. The main objective of this review was to summarise the current evidence relating to the efficacy of aspirin as a VTE prophylaxis following arthroplasty, and to address some of the common questions about its use. There is convincing evidence that, taking all factors into account, aspirin is an effective, inexpensive, and safe form of VTE following arthroplasty in patients without a major risk factor for VTE, such as previous VTE. Cite this article: Bone Joint J 2017;99-B:1420-30. ©2017 Azboy et al.

  6. Implications of altered glutathione metabolism in aspirin-induced oxidative stress and mitochondrial dysfunction in HepG2 cells.

    Directory of Open Access Journals (Sweden)

    Haider Raza

    Full Text Available We have previously reported that acetylsalicylic acid (aspirin, ASA induces cell cycle arrest, oxidative stress and mitochondrial dysfunction in HepG2 cells. In the present study, we have further elucidated that altered glutathione (GSH-redox metabolism in HepG2 cells play a critical role in ASA-induced cytotoxicity. Using selected doses and time point for ASA toxicity, we have demonstrated that when GSH synthesis is inhibited in HepG2 cells by buthionine sulfoximine (BSO, prior to ASA treatment, cytotoxicity of the drug is augmented. On the other hand, when GSH-depleted cells were treated with N-acetyl cysteine (NAC, cytotoxicity/apoptosis caused by ASA was attenuated with a significant recovery in oxidative stress, GSH homeostasis, DNA fragmentation and some of the mitochondrial functions. NAC treatment, however, had no significant effects on the drug-induced inhibition of mitochondrial aconitase activity and ATP synthesis in GSH-depleted cells. Our results have confirmed that aspirin increases apoptosis by increased reactive oxygen species production, loss of mitochondrial membrane potential and inhibition of mitochondrial respiratory functions. These effects were further amplified when GSH-depleted cells were treated with ASA. We have also shown that some of the effects of aspirin might be associated with reduced GSH homeostasis, as treatment of cells with NAC attenuated the effects of BSO and aspirin. Our results strongly suggest that GSH dependent redox homeostasis in HepG2 cells is critical in preserving mitochondrial functions and preventing oxidative stress associated complications caused by aspirin treatment.

  7. Implications of altered glutathione metabolism in aspirin-induced oxidative stress and mitochondrial dysfunction in HepG2 cells.

    Science.gov (United States)

    Raza, Haider; John, Annie

    2012-01-01

    We have previously reported that acetylsalicylic acid (aspirin, ASA) induces cell cycle arrest, oxidative stress and mitochondrial dysfunction in HepG2 cells. In the present study, we have further elucidated that altered glutathione (GSH)-redox metabolism in HepG2 cells play a critical role in ASA-induced cytotoxicity. Using selected doses and time point for ASA toxicity, we have demonstrated that when GSH synthesis is inhibited in HepG2 cells by buthionine sulfoximine (BSO), prior to ASA treatment, cytotoxicity of the drug is augmented. On the other hand, when GSH-depleted cells were treated with N-acetyl cysteine (NAC), cytotoxicity/apoptosis caused by ASA was attenuated with a significant recovery in oxidative stress, GSH homeostasis, DNA fragmentation and some of the mitochondrial functions. NAC treatment, however, had no significant effects on the drug-induced inhibition of mitochondrial aconitase activity and ATP synthesis in GSH-depleted cells. Our results have confirmed that aspirin increases apoptosis by increased reactive oxygen species production, loss of mitochondrial membrane potential and inhibition of mitochondrial respiratory functions. These effects were further amplified when GSH-depleted cells were treated with ASA. We have also shown that some of the effects of aspirin might be associated with reduced GSH homeostasis, as treatment of cells with NAC attenuated the effects of BSO and aspirin. Our results strongly suggest that GSH dependent redox homeostasis in HepG2 cells is critical in preserving mitochondrial functions and preventing oxidative stress associated complications caused by aspirin treatment.

  8. Can the previous therapeutic control of the main risk factors of cerebrovascular disease influence the acetylsalicylic Acid-nonresponsive status in acute ischemic stroke patients? Results from a portuguese prospective cohort study.

    Science.gov (United States)

    Freitas-Silva, Margarida; Gonçalves, Luciana; Medeiros, Rui; Nunes, José Pedro

    2015-06-01

    Acute ischemic stroke (AIS) is a complex disease, and the therapeutic control of its risk factors may influence the efficacy of acetylsalicylic acid (ASA) and the occurrence of new vascular events. The aim of this study was to investigate the potential in vivo properties of a previous treatment controlling the main risk factors of cerebrovascular disease, in the ASA-nonresponsive status in a Portuguese population. We conducted a prospective cohort study with the recruitment of 90 patients diagnosed with AIS and a follow-up protocol was set up with recurrent stroke as the main clinical end point under evaluation. At admission, PFA-100 (platelet function analyzer) test was evaluated in blood samples from AIS patients treated with 100 mg/day of ASA and previously treated with antihypertensive, antidiabetic, or statin drugs. We observed that 30% of patients were ASA nonresponders. Multivariate regression analysis indicated that the previous treatment with antihypertensive drugs emerged with a significant risk reduction of an ASA-nonresponsive status (odds ratio, .119; 95% confidence interval, .026-.538; P = .006). Furthermore, our results indicated an influence of ASA-nonresponsive status in a decreased period to a new recurrent stroke event in the time frame of 24 months (P = .005, log-rank test). ASA is an important part of treatment of AIS, and its efficacy may be improved in previous high-risk cerebrovascular patients, particularly with antihypertensive therapeutic control. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2010-01-01

    Biosynthesis of the prostaglandin endoperoxide by the cyclooxygenase (COX) enzymes is accompanied by formation of a small amount of 11R-hydroxyeicosatetraenoic acid (HETE), 15R-HETE, and 15S-HETE as by-products. Acetylation of COX-2 by aspirin abrogates prostaglandin synthesis and triggers formation of 15R-HETE as the sole product of oxygenation of arachidonic acid. Here, we investigated the formation of by-products of the transformation of 5S-HETE by native COX-2 and by aspirin-acetylated COX-2 using HPLC-ultraviolet, GC-MS, and LC-MS analysis. 5S,15S- dihydroxy (di)HETE, 5S,15R-diHETE, and 5S,11R-diHETE were identified as by-products of native COX-2, in addition to the previously described di-endoperoxide (5S,15S-dihydroxy-9S,11R,8S,12S-diperoxy-6E,13E-eicosadienoic acid) as the major oxygenation product. 5S,15R-diHETE was the only product formed by aspirin-acetylated COX-2. Both 5,15-diHETE and 5,11-diHETE were detected in CT26 mouse colon carcinoma cells as well as in lipopolysaccharide-activated RAW264.7 cells incubated with 5S-HETE, and their formation was attenuated in the presence of the COX-2 specific inhibitor, NS-398. Aspirin-treated CT26 cells gave 5,15-diHETE as the most prominent product formed from 5S-HETE. 5S,15S-diHETE has been described as a product of the cross-over of 5-lipoxygenase (5-LOX) and 15-LOX activities in elicited rat mononuclear cells and human leukocytes, and our studies implicate cross-over of the 5-LOX and COX-2 pathways as an additional biosynthetic route. PMID:19752399

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

    Energy Technology Data Exchange (ETDEWEB)

    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).

  11. 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.

    Science.gov (United States)

    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.

  12. [Effectiveness and safety of tranexamic acid in patients receiving on-pump coronary artery bypass grafting without clopidogrel and aspirin cessation].

    Science.gov (United States)

    Shi, Jia; Wang, Yue-Fu; Xue, Qing-Hua; Yuan, Su; Wang, Gu-Yan; Li, Li-Huan

    2013-06-01

    To evaluate the effectiveness and safty of tranexamic acid in patients receiving on-pump coronary artery bypass grafting (CABG) without clopidogrel and aspirin cessation. The current study is a prospective, randomized and placebo-control trial. A total of 116 patients receiving selective on-pump CABG with their last ingestion of clopidogrle and aspirin within 7 days preoperatively were recruited. Despite 6 patients withdrawal their consent, the rest 110 were randomized to receive tranexamic acid or placebo. The tranexamic acid regimen was a bolus of 10 mg/kg followed by a maintenance of 10 mg·kg(-1)·h(-1) throughout the surgery. The primary outcome was the volume of allogeneic erythrocyte transfused perioperatively. Baseline characteristics were comparable between the groups. In patients receiving tranexamic acid and placebo respectively, the volume of allogeneic erythrocyte transfused was 4.0 (7.5) units and 6.0(6.0) units (W = 1021, P < 0.01). In these 2 groups respectively, blood loss was 930 (750) ml and 1210 (910) ml (W = 1042, P < 0.01), the incidence of major bleeding was 50.9% and 76.4% (χ(2) = 7.70, P < 0.01), the incidence of reoperation was 0 and 9.1% (χ(2) = 5.24, P = 0.02); the volume of plasma transfused was 400 (600) ml and 600 (650) ml (W = 1072, P = 0.01), the exposure of plasma was 60.0% and 85.5% (χ(2) = 8.98, P < 0.01) and the exposure to any allogeneic blood products was 85.5% and 98.2% (χ(2) = 5.93, P = 0.01). Perioperative mortality, morbidity and the incidence of adverse events were balanced between the groups without statistical significance. Tranexamic acid reduced significantly postoperative bleeding and transfusion in patients receiving on-pump CABG without clopidogrel and aspirin cessation.

  13. Aspirin and Omeprazole

    Science.gov (United States)

    The combination of aspirin and omeprazole is used to reduce the risk of stroke or heart attack in patients who have had or ... risk of developing a stomach ulcer when taking aspirin. Aspirin is in a class of medications called ...

  14. Aspirin Resistance

    OpenAIRE

    Khaled Mansour; Ali T. Taher; Khaled M. Musallam; Samir Alam

    2009-01-01

    The development of adverse cardiovascular events despite aspirin use has established an interest in a possible resistance to the drug. Several definitions have been set and various laboratory testing modalities are available. This has led to a wide range of prevalence reports in different clinical entities. The etiologic mechanism has been related to clinical, genetic, and other miscellaneous factors. The clinical implications of this phenomenon are significant and warrant concern. Management...

  15. Comparison between zofenopril and ramipril in combination with acetylsalicylic acid in patients with left ventricular systolic dysfunction after acute myocardial infarction: results of a randomized, double-blind, parallel-group, multicenter, European study (SMILE-4).

    Science.gov (United States)

    Borghi, Claudio; Ambrosioni, Ettore; Novo, Salvatore; Vinereanu, Dragos; Ambrosio, Giuseppe

    2012-01-01

    Angiotensin-converting enzyme inhibitors (ACEIs) are largely employed for treating patients with left ventricular dysfunction (LVD), but their efficacy may be negatively affected by concomitant administration of acetylsalicylic acid (ASA), with some difference among the different compounds. The interaction between ASA and the two ACEIs zofenopril and ramipril may result in a different impact on survival of cardiac patients, due to differences in the pharmacological properties of the two ACEIs. This phase IIIb, randomized, double-blind, parallel-group, multicenter, European study compared the safety and efficacy of zofenopril (60 mg/day) and ramipril (10 mg/day) plus ASA (100 mg/day), in 771 patients with LVD (clinical signs of heart failure or a left ventricular ejection fraction <45%) following acute myocardial infarction (AMI). The primary study end point was 1-year combined occurrence of death or hospitalization for cardiovascular causes. In the intention-to-treat population, the primary outcome was significantly reduced by zofenopril (n = 365) vs ramipril (n = 351) (odds ratio [OR]: 0.70, and 95% confidence interval [CI]: 0.51-0.96; P = 0.028) as a result of a decrease in cardiovascular hospitalization (OR: 0.64,95% CI: 0.46-0.88; P = 0.006). Mortality rate was not significantly different between the 2 treatments (OR: 1.51, 95% CI: 0.70-3.27; P = 0.293). Blood pressure values did not significantly change during the 1-year follow-up. N-terminal pro-brain natriuretic peptide levels were progressively reduced during the study, with no statistically significant between-treatment differences. Proportion of patients with deterioration of renal function during the study was similar between the 2 groups. Drug safety profile was comparable between treatments. In patients with LVD following AMI, the efficacy of zofenopril associated with ASA was superior to that of ramipril plus ASA, indicating some important clinical implications for the future use of ACEIs in patients

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    L. Mastalerz

    2012-01-01

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

  18. Desensitization to acetyl-salicylic acid as a treatment for non-steroid anti-inflammatory drugs (NSAIDs-exacerbated respiratory disease = Desensibilización al ácido acetil-salicílico como tratamiento para la enfermedad respiratoria exacerbada por antiinflamatorios no esteroides

    Directory of Open Access Journals (Sweden)

    Cardona Villa, Ricardo

    2014-07-01

    Full Text Available Desensitization to acetyl-salicylic acid as a treatment for non-steroid anti-inflammatory drugs (NSAIDs-exacerbated respiratory disease The coexistence of hypersensitivity to acetylsalicylic acid (ASA and other NSAIDs with disease of the upper or the lower airways (rhinosinusitis/sinonasal polyposis, or asthma is defined as NSAIDs-exacerbated respiratory disease. Treatment options include the avoidance of all analgesics that inhibit COX-1 or ASA desensitization, continuing its daily consumption. The latter treatment has shown to improve quality of life, reduce the formation of sinonasal polyps, the episodes of sinus infection, the frequency of hospitalizations and surgeries for resection of polyps and the need for systemic steroid treatment. Multiple desensitization schedules have been used, trying to reduce the risk associated with the procedure and the adverse effects of chronic use of ASA. In this paper we present a review of the different methods of desensitization and two illustrative clinical cases to help understand the factors that influence the choice of treatment for these patients.

  19. The Effect of Low-Dose Aspirin on Dry Eye Parameters and Ocular Surface Disease Index Questionnaire.

    Science.gov (United States)

    Yazıcı, Alper; Sarı, Esin; Ayhan, Erkan; Şahin, Gözde; Tıskaoğlu, Nesime Setge; Gürbüzer, Taha; Kurt, Hüseyin; Ermiş, Sıtkı Samet

    2018-02-01

    To evaluate the effects of acetylsalicylic acid (aspirin) on tear film parameters and dry eye disease. Fifty-seven patients using low-dose aspirin regularly for antiaggregant purposes as well as 49 controls, who required antiaggregant treatment but who had not yet started, were included in the study. Tear osmolarity, tear break-up time (TBUT), Schirmer and Oxford grading of ocular surface staining were performed on all patients and dry eye symptomatology was assessed using the ocular surface disease index questionnaire (OSDI). The mean osmolarity was 302.11 ± 16.22 mOsm/L in the aspirin group and 313.88 ± 19.57 mOsm/L in the control group (P < 0.01). The mean Schirmer's score was 24.16 ± 10.52 mm and 21.94 ± 10.11 mm (P = 0.232), TBUT was 13.61 ± 3.31 s and 10.39 ± 4.46 s (P < 0.01), OSDI score was 5.15 ± 5.98 and 16.94 ± 14.17 (P < 0.01), and Oxford score was 0.12 ± 0.33 and 0.12 ± 0.44 in aspirin and control groups, respectively (P = 0.99). Dry eye diagnosis was lower in the aspirin group, but statistical significance was present only in TBUT and osmolarity-based dry eye diagnosis (P ≤ 0.01). In terms of symptom-based dry eye diagnosis with the threshold of OSDI ≥23, none of the aspirin group had dry eye diagnosis, whereas 32.6% of the control group had the diagnosis (P < 0.01). The use of low-dose aspirin might be great option for treatment of ocular surface inflammatory disease through increasing TBUT and decreasing tear osmolarity with a resultant symptomatic satisfaction.

  20. Effect of aspirin in "aspirin sensitive" patients.

    OpenAIRE

    Asad, S I; Kemeny, D M; Youlten, L J; Frankland, A W; Lessof, M H

    1984-01-01

    Eighteen patients with a history of urticaria or asthma, or both, induced by aspirin were studied before and after provocation of symptoms with aspirin. The plasma prostaglandin F2 alpha concentration, which was characteristically raised before challenge, fell significantly at the time of adverse reactions. Repeated administration of aspirin up to a dose of 650 mg daily induced tolerance in most of the patients, and several developed bronchodilator responses to aspirin. Although median total ...

  1. Effects of aspirin on pathways of ion permeation in Necturus antrum: role of nutrient HCO3.

    Science.gov (United States)

    Soybel, D I; Davis, M B; West, A B

    1992-11-01

    Intracellular microelectrodes were used to evaluate electrical properties of the cell membranes in Necturus antral mucosa during exposure to luminal acid alone (pH 4) or to 5 mmol/L aspirin [acetylsalicylic acid (ASA)] in the presence of luminal acid. When nutrient solutions were buffered by HCO3- (pH 7.3), ASA moderately depolarized and increased the resistances of both cell membranes. When nutrient solutions were buffered by HEPES (pH 7.3), ASA induced even greater depolarizations of the cell membranes. In addition, resistance of the apical membrane did not increase and resistance of the basolateral membrane decreased. The changes in basolateral membrane resistance were observed when tissues were exposed to 5 mmol/L salicylate but not during exposure to luminal acid alone or to acidified luminal solutions containing 5 mmol/L acetate, a small and permeable organic acid. Electron microscopy confirmed that these initial electrophysiological changes precede alterations in cell morphology. The findings suggest that nutrient HCO3- attenuates changes in membrane potentials caused by ASA. Loss of nutrient HCO3- seems to accelerate alterations in basolateral membrane resistance caused by ASA and its salicylate moiety.

  2. Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells.

    Science.gov (United States)

    Kastrati, Irida; Delgado-Rivera, Loruhama; Georgieva, Gergana; Thatcher, Gregory R J; Frasor, Jonna

    2017-01-18

    Inflammation is a cancer hallmark that underlies cancer incidence and promotion, and eventually progression to metastasis. Therefore, adding an anti-inflammatory drug to standard cancer regiments may improve patient outcome. One such drug, aspirin (acetylsalicylic acid, ASA), has been explored for cancer chemoprevention and anti-tumor activity. Besides inhibiting the cyclooxygenase 2-prostaglandin axis, ASA's anti-cancer activities have also been attributed to nuclear factor ĸB (NFĸB) inhibition. Because prolonged ASA use may cause gastrointestinal toxicity, a prodrug strategy has been implemented successfully. In this prodrug design the carboxylic acid of ASA is masked and additional pharmacophores are incorporated. This protocol describes how we synthesized an aspirin-fumarate prodrug, GTCpFE, and characterized its inhibition of the NFĸB pathway in breast cancer cells and attenuation of the cancer stem-like properties, an important NFĸB-dependent phenotype. GTCpFE effectively inhibits the NFĸB pathway in breast cancer cell lines whereas ASA lacks any inhibitory activity, indicating that adding fumarate to ASA structure significantly contributes to its activity. In addition, GTCpFE shows significant anti-cancer stem cell activity by blocking mammosphere formation and attenuating the cancer stem cell associated CD44 + CD24 - immunophenotype. These results establish a viable strategy to develop improved anti-inflammatory drugs for chemoprevention and cancer therapy.

  3. Theoretical modeling of infrared spectra of the hydrogen and deuterium bond in aspirin crystal

    Science.gov (United States)

    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.

  4. Aspirin Resistance

    Directory of Open Access Journals (Sweden)

    Khaled Mansour

    2009-01-01

    Full Text Available The development of adverse cardiovascular events despite aspirin use has established an interest in a possible resistance to the drug. Several definitions have been set and various laboratory testing modalities are available. This has led to a wide range of prevalence reports in different clinical entities. The etiologic mechanism has been related to clinical, genetic, and other miscellaneous factors. The clinical implications of this phenomenon are significant and warrant concern. Management strategies are currently limited to dosing alteration and introduction of other anitplatelet agents. However, these measures have not met the expected efficacy or safety.

  5. [Therapeutic use of acetylsalicylic acid in diabetics].

    Science.gov (United States)

    Zácková, V

    2003-12-01

    Aterosclerosis is a leading cause of morbidity and mortality in diabetics. Macrovascular diseases--myocardial infarction, cerebral vascular accident, ischemic lower extremities--start in persons with diabetes earlier and in a bigger scope then in non-diabetics. Development of these changes is determined by diabetic vasculopathy which is connected with endothelial dysfunction, hypercoagulation state, and platelet abnormalities. Treatment of a patient with diabetes is based on compensation of diabetes and management of hypertension and dyslipidaemia. Drugs that inhibit platelets constitute an important part of prevention of cardiovascular disabilities in diabetics.

  6. Relation of aspirin failure to clinical outcome and to platelet response to aspirin in patients with acute myocardial infarction.

    Science.gov (United States)

    Beigel, Roy; Hod, Hanoch; Fefer, Paul; Asher, Elad; Novikov, Ilia; Shenkman, Boris; Savion, Naphtaly; Varon, David; Matetzky, Shlomi

    2011-02-01

    Aspirin failure, defined as occurrence of an acute coronary syndrome despite aspirin use, has been associated with a higher cardiovascular risk profile and worse prognosis. Whether this phenomenon is a manifestation of patient characteristics or failure of adequate platelet inhibition by aspirin has never been studied. We evaluated 174 consecutive patients with acute myocardial infarction. Of them, 118 (68%) were aspirin naive and 56 (32%) were regarded as having aspirin failure. Platelet function was analyzed after ≥72 hours of aspirin therapy in all patients. Platelet reactivity was studied by light-transmitted aggregometry and under flow conditions. Six-month incidence of major adverse coronary events (death, recurrent acute coronary syndrome, and/or stroke) was determined. Those with aspirin failure were older (p = 0.002), more hypertensive (p aspirin-failure group (14.3% vs 2.5% p aspirin failure had lower arachidonic acid-induced platelet aggregation (32 ± 24 vs 45 ± 30, p = 0.003) after aspirin therapy compared to their aspirin-naive counterparts. However, this was not significant after adjusting for differences in baseline characteristics (p = 0.82). Similarly, there were no significant differences in adenosine diphosphate-induced platelet aggregation and platelet deposition under flow conditions. In conclusion, our results suggest that aspirin failure is merely a marker of higher-risk patient profiles and not a manifestation of inadequate platelet response to aspirin therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Technetium-aspirin molecule complexes

    Energy Technology Data Exchange (ETDEWEB)

    El-Shahawy, A.S.; Mahfouz, R.M.; Aly, A.A.M.; El-Zohry, M. (Assiut Univ. (Egypt))

    1993-01-01

    Technetium-aspirin and technetium-aspirin-like molecule complexes were prepared. The structure of N-acetylanthranilic acid (NAA) has been decided through CNDO calculations. The ionization potential and electron affinity of the NAA molecule as well as the charge densities were calculated. The electronic absorption spectra of Tc(V)-Asp and Tc(V)-ATS complexes have two characteristic absorption bands at 450 and 600 nm, but the Tc(V)-NAA spectrum has one characteristic band at 450 nm. As a comparative study, Mo-ATS complex was prepared and its electronic absorption spectrum is comparable with the Tc-ATS complex spectrum. (author).

  8. Aspirin: past, present and future.

    Science.gov (United States)

    Elwood, P C

    2001-01-01

    Many folk remedies used since pre-historic times have depended upon salicylates for their effect. One hundred years ago aspirin was formulated from salicylic and acetic acids. It was the first drug to be synthesised and its formulation is regarded as the foundation of the modern pharmaceutical industry. The benefit of low-dose aspirin as a prophylactic after a thrombotic event was first reported 25 years ago. Its use after coronary or cerebral thrombosis is virtually mandatory, unless there are signs of intolerance. A 'loading dose' of soluble aspirin should be given on first contact with a patient who may be suffering from myocardial infarction. Patients considered to be at increased risk of a vascular event should also be advised to carry their own aspirin and, if they experience sudden severe chest pain, to chew and swallow a 300 mg tablet or a soluble preparation immediately. The current phase of the aspirin story is, however, not over, and its possible value in a variety of conditions, including dementia and certain cancers, seems likely to ensure that it will long continue to play a remarkable part in clinical practice.

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

    Directory of Open Access Journals (Sweden)

    H. Ariel Alvarez

    2012-01-01

    Full Text Available 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.

  10. Aspirin, Butalbital, and Caffeine

    Science.gov (United States)

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

  11. Aspirin (single dose) for perineal pain in the early postpartum period.

    Science.gov (United States)

    Molakatalla, Sujana; Shepherd, Emily; Grivell, Rosalie M

    2017-02-09

    Perineal trauma (due to spontaneous tears, surgical incision (episiotomy) or in association with operative vaginal birth) is common after vaginal birth, and is often associated with postpartum perineal pain. Birth over an intact perineum may also lead to perineal pain. There are adverse health consequences associated with perineal pain for the women and their babies in the short- and long-term, and the pain may interfere with newborn care and the establishment of breastfeeding. Aspirin has been used in the management of postpartum perineal pain and its effectiveness and safety should be assessed. To determine the efficacy of a single dose of aspirin (acetylsalicylic acid), including at different doses, in the relief of acute postpartum perineal pain. We searched Cochrane Pregnancy and Childbirth's Trials Register (30 August 2016), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (31 May 2016) and reference lists of retrieved studies. Randomised controlled trials (RCTs) assessing single dose aspirin compared with placebo, no treatment, a different dose of aspirin, or single dose paracetamol/acetaminophen for women with perineal pain in the early postpartum period. We planned to include cluster-RCTs but none were identified. Quasi-RCTs and cross-over studies were not eligible for inclusion in this review. Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of the included RCTs. Data were checked for accuracy. The quality of the evidence for the main comparison (aspirin versus placebo) was assessed using the GRADE approach. We included 17 RCTs, with 16 involving 1132 women randomised to aspirin or placebo (one RCT did not report numbers of women). Two RCTs (of 16) did not contribute data to review meta-analyses. All women had perineal pain post-episiotomy, and were not breastfeeding. Studies were published between 1967 and 1997, and the risk of bias was often unclear due to poor

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

    Science.gov (United States)

    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.

  13. Aspirin in Neurology

    OpenAIRE

    Yolanda Aburto-Murrieta; Dulce Bonifacio-Delgadillo; Juan Marquez

    2011-01-01

    Aspirin is widely used for the prevention of recurrent stroke in patients with transient ischaemic attack (TIA) of arterial origin, because it is effective and inexpensive. Clopidogrel and the combination of aspirin and extended-release dipyridamole are more effective than aspirin, but are also much more expensive. No other antithrombotic regimens provide significant advantages over aspirin, although cilostazol and the novel platelet protease-activated receptor-1 antagonist, SCH 530348, are c...

  14. Synthesis of peptide derivatives of aspirin and their antibiogram ...

    African Journals Online (AJOL)

    Peptide derivatives of Aspirin (1 to 8) were synthesized by using Ac2O/AcOH reaction with Salicyclic acid. Aspirin was coupled with amino acid amide and dipeptide amide and tripeptide amide using its p-nitro phenyl (NP) ester. The ester (Aspirin–ONP) was prepared using p-nitro phenol and DCC in EtOAc and was ...

  15. Nitric oxide-donating aspirin derivatives suppress microsatellite instability in mismatch repair-deficient and hereditary nonpolyposis colorectal cancer cells.

    Science.gov (United States)

    McIlhatton, Michael A; Tyler, Jessica; Burkholder, Susan; Ruschoff, Josef; Rigas, Basil; Kopelovich, Levy; Fishel, Richard

    2007-11-15

    Nitric oxide-donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are an emergent class of pharmaceutical derivatives with promising utility as cancer chemopreventive agents. Aspirin and sulindac have been shown to be effective in selecting for cells with reduced microsatellite instability (MSI) that is inherent in mismatch repair (MMR)-deficient hereditary nonpolyposis colorectal cancer (HNPCC) cells. The effect of NO-NSAIDs on MSI in MMR-deficient HNPCC cells is unknown. Here, we have examined genetically defined MMR-deficient murine embryo fibroblasts, murine colonocytes, and isogenic human HNPCC tumor cell lines treated with acetylsalicylic acid (aspirin; ASA) and three isomeric derivatives of NO-aspirin (NO-ASA). The MSI profiles were determined and compared with the Bethesda Criteria. We found that the ASA- and NO-ASA-treated MMR-deficient cell lines displayed a dose-dependent suppression of MSI that appeared as early as 8 weeks and gradually increased to include up to 67% of the microsatellite sequences examined after 19 to 20 weeks of continuous treatment. Residual resistance to microsatellite stabilization was largely confined to mononucleotide repeat sequences. Control (MMR-proficient) cells showed no changes in microsatellite status with or without treatment. The relative dose-dependent stabilization selection was: ortho-NO-ASA approximately para-NO-ASA > meta-NO-ASA > ASA. Moreover, the doses required for stabilization by the ortho- and para-NO-ASA were 300- to 3,000-fold lower than ASA. These results suggest that NO-ASA derivatives may be more effective at suppressing MSI in MMR-deficient cell lines than ASA and should be considered for chemopreventive trials with HNPCC carriers.

  16. Mechanisms of aggregation inhibition by aspirin and nitrate-aspirin prodrugs in human platelets.

    Science.gov (United States)

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

    2012-01-01

    Aspirin is the mainstay of anti-platelet therapy in the secondary prevention of cardiovascular disease. However, problems with aspirin safety and resistance demand clinical strategies based on multiple pharmacological approaches. Prodrugs of aspirin may offer beneficial effects in terms of gastro-intestinal safety and multiple pharmacological approaches. However, the pharmacological profile of aspirin prodrugs in human platelets has not been completed yet. We aimed to compare the effects of aspirin and prodrugs of aspirin (1-5) on human platelet aggregation stimulated by ADP and collagen and associated receptor expression (GPIIb/IIIa and P-selectin) in platelet-rich plasma (PRP) and washed platelets (WP). As aspirin is released from prodrugs following esterase hydrolysis we studied the expression and activity of butyrylcholineterase (BuChE) and carboxyesterase (CE) in plasma and platelets. The mechanism of prodrug-induced platelet aggregation inhibition was explored by studying the effects of plasma and purified human BuChE on aggregation. Finally, the relative contribution of nitric oxide (NO) bioactivity to nitrate-containing prodrugs of aspirin-induced inhibition of aggregation was determined using 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ,) a selective inhibitor of the soluble guanylyl cyclase. ST0702, 2, a nicotinic acid-aspirin codrug was equipotent with aspirin with respect to inhibition of collagen-induced platelet aggregation. Compound 4, a NO releasing aspirin was the most potent inhibitor of ADP-induced platelet aggregation, an effect partially reversed by ODQ. The platelet inhibitory effects of aspirin prodrugs were time-dependent as the maximal inhibitory effects against collagen-induced aggregation were achieved by aspirin at 2 min, 1 at 5 min and ST0702 at 15 min. The aspirin prodrugs were significantly less potent in WP than in PRP and the reverse was true of aspirin. In the presence of complete BuChE inhibition in PRP, there was almost

  17. Paradoxical Effect of Aspirin

    Directory of Open Access Journals (Sweden)

    Christian Doutremepuich

    2012-01-01

    Full Text Available Low-dose aspirin is an important therapeutic option in the secondary prevention of myocardial infarction (MI and ischemic stroke, basedon its unique cost-effectiveness and widespread availability. In addition, based on the results of a number of large studies, aspirin is also widely used in the primary prevention of MI. This paper provides an update of the available data to offer greater clarity regarding the risks of aspirin with respect to hemorrhagic stroke. In the secondary prevention of cardiovascular, cerebrovascular, and ischemic events, the evidence supports that the benefits of aspirin treatment significantly outweigh the risk of a major hemorrhage. When considering whether aspirin is appropriate, the absolute therapeutic cardiovascular benefits of aspirin must be balanced with the possible risks associated with its use, being hemorrhagic stroke. Regarding these clinical facts, normal, COX 1 −/−, and COX 2 −/− mice were treated with a wide range of doses of aspirin and studied by induced hemorrhagic time. The results outlined three major conclusions: high doses of aspirin induce hemorrhage, while low doses of aspirin do not. In the absence of COX 1, ultra low doses of aspirin produce an antihemorrhagic effect not observed with intermediate doses. The absence of COX 2 induced a hemorrhagic effect that needs further research, probably originated in compensatory phenomena.

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

    Science.gov (United States)

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

    2015-08-27

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

  19. Structure, molecular simulation, and release of aspirin from intercalated Zn-Al-layered double hydroxides.

    Science.gov (United States)

    Meng, Zilin; Li, Xiaowei; Lv, Fengzhu; Zhang, Qian; Chu, Paul K; Zhang, Yihe

    2015-11-01

    Aspirin or acetylsalicylic acid (AA), a non-steroidal anti-inflammatory drug, is intercalated into Zn-Al-layered double hydroxides (ZnAl-LDHs) by co-precipitation and reconstruction methods. The composition, structure, and morphology of the intercalated products as well as their release behavior are determined experimentally and theoretically by Material Studio 5.5. Experimental results disclose the strong interaction between the LDHs sheets and AA in the intercalated ZnAl-LDHs produced by co-precipitation and slow release of AA from the intercalated ZnAl-LDHs in both phosphate buffered saline (PBS) and borate buffered saline (BBS) solutions. The percentage of AA released from the ZnAl-LDHs prepared by both methods in PBS (96.87% and 98.12%) are much more than those in BBS (68.59% and 81.22%) implying that both H4BO4(-) and H2PO4(-) can exchange with AA in the ZnAl-LDHs. After AA is released to PBS, ZnAl-LDHs break into small pieces. The experimental results are explained theoretically based on the calculation of the bonding energy between the anions and LDHs sheets as well as the AlO bond length change in the LDHs sheets. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Mohammad Hashemi

    2016-01-01

    Full Text Available 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.

  1. COMPARISON OF ANTIPLATELET EFFECT AND SAFETY OF ORIGINAL DRUG «ASPIRIN CARDIO» AND GENERIC«ACECARDOL» IN PATIENTS WITH ARTERIAL HYPERTENSION 1-2 GRADE

    Directory of Open Access Journals (Sweden)

    N. A. Belolipetskiy

    2008-01-01

    Full Text Available Aim. To compare antiplatelet effect of two acetylsalicylic acid medicines, Acecardol ("Synthesis Co. Ltd", Russia and Aspirin cardio («Bayer AG», Germany, in patients with arterial hypertension (AH 1-2 stage with increased risk of cardiovascular events.Material and methods. The study was double-blind, randomized, cross-over one. 32 hypertensive patients (12 men and 20 women aged 59,4±14,4 y.o. were included in the study. They took investigated ASA medicines one after another during 4 weeks each. Antiplatelet efficacy of ASA medicines were estimated by effects on spontaneous and ADP-induced platelet aggregation at every visit.Results. 4-week therapy with both ASA medicines did not have significant effects on spontaneous platelet aggregation and the aggregation induced with low ADP concentrations (0,5 and 1,0 µM. However platelet aggregation induced with ADP in concentration of 2 µM was significantly reduced by therapies. There were not significant inter-group differences.Conclusion. ASA generic medicine Acecardol ("Synthesis Co.Ltd.", Russia and original medicine Aspirin cardio («Bayer AG», Germany are equivalent on antiplatelet effect.

  2. In vivo quantitation of platelet deposition on human peripheral arterial bypass grafts using indium-111-labeled platelets. Effect of dipyridamole and aspirin

    Energy Technology Data Exchange (ETDEWEB)

    Pumphrey, C.W.; Chesebro, J.H.; Dewanjee, M.K.; Wahner, H.W.; Hollier, L.H.; Pairolero, P.C.; Fuster, V.

    1983-03-01

    Indium-111-labeled autologous platelets, injected 48 hours after operation, were used to evaluate the thrombogenicity of prosthetic material and the effect of platelet inhibitor therapy in vivo. Dacron double-velour (Microvel) aortofemoral artery bifurcation grafts were placed in 16 patients and unilateral polytetrafluoroethylene femoropopliteal grafts were placed in 10 patients. Half the patients in each group received platelet inhibitors before operation (dipyridamole, 100 mg 4 times a day) and after operation (dipyridamole, 75 mg, and acetylsalicylic acid, 325 mg 3 times a day); the rest of the patients served as control subjects. Five-minute scintigrams of the graft region were taken with a gamma camera interfaced with a computer 48, 72, and 96 hours after injection of the labeled platelets. Platelet deposition was estimated from the radioactivities of the grafts and expressed as counts per 100 pixels per microcurie injected. Dipyridamole and aspirin therapy significantly reduced the number of platelets deposited on Dacron grafts and prevented platelet accumulation over 3 days. With the small amount of platelet deposition on polytetrafluoroethylene femoropopliteal artery grafts even in control patients, platelet inhibitor therapy had no demonstrable effect on platelet deposition on these grafts. It is concluded that (1) platelet deposition on vascular grafts in vivo can be quantitated by noninvasive methods, and (2) dipyridamole and aspirin therapy reduced platelet deposition on Dacron aortofemoral artery grafts.

  3. Role of TGF-beta1 and MAP kinases in the antiproliferative effect of aspirin in human vascular smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Santiago Redondo

    2010-03-01

    Full Text Available We aimed to test the antiproliferative effect of acetylsalicylic acid (ASA on vascular smooth muscle cells (VSMC from bypass surgery patients and the role of transforming growth factor beta 1 (TGF-beta1.VSMC were isolated from remaining internal mammary artery from patients who underwent bypass surgery. Cell proliferation and DNA fragmentation were assessed by ELISA. Protein expression was assessed by Western blot. ASA inhibited BrdU incorporation at 2 mM. Anti-TGF-beta1 was able to reverse this effect. ASA (2 mM induced TGF-beta1 secretion; however it was unable to induce Smad activation. ASA increased p38(MAPK phosphorylation in a TGF-beta1-independent manner. Anti-CD105 (endoglin was unable to reverse the antiproliferative effect of ASA. Pre-surgical serum levels of TGF-beta1 in patients who took at antiplatelet doses ASA were assessed by ELISA and remained unchanged.In vitro antiproliferative effects of aspirin (at antiinflammatory concentration on human VSMC obtained from bypass patients are mediated by TGF-beta1 and p38(MAPK. Pre-surgical serum levels of TGF- beta1 from bypass patients who took aspirin at antiplatelet doses did not change.

  4. Aspirin-Exacerbated Asthma

    OpenAIRE

    Varghese, Mathew; Lockey, Richard F

    2008-01-01

    This review focuses on aspirin-exacerbated asthma (AEA). The review includes historical perspective of aspirin, prevalence, pathogenesis, clinical features and treatment of AEA. The pathogenesis of AEA involves the cyclooxygenase and lipooxygenase pathway. Aspirin affects both of these pathways by inhibiting the enzyme cycooxygenase-1 (COX-1). Inhibition of COX-1 leads to a decrease in prostaglandin E2 (PGE2). The decrease in PGE2 results in an increase in cysteinyl leukotrienes by the lipoo...

  5. Aspirin for Primary Prevention.

    Science.gov (United States)

    Richman, Ilana B; Owens, Douglas K

    2017-07-01

    Aspirin reduces the risk of nonfatal myocardial infarction and stroke, and the risk of colorectal cancer. Aspirin increases the risk of gastrointestinal and intracranial bleeding. The best available evidence supports initiating aspirin in select populations. In 2016, the US Preventive Services Task Force recommended initiating aspirin for the primary prevention of both cardiovascular disease and colorectal cancer among adults ages 50 to 59 who are at increased risk for cardiovascular disease. Adults 60 to 69 who are at increased cardiovascular disease risk may also benefit. There remains considerable uncertainty about whether younger and older patients may benefit. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. [Aspirin and colorectal cancer].

    Science.gov (United States)

    Grancher, Adrien; Michel, Pierre; Di Fiore, Frédéric; Sefrioui, David

    2018-02-01

    Colorectal cancer is a worldwide public health problem. Aspirin has been identified as a protective factor against the apparition of colorectal cancer. There are several mechanisms about the actions by aspirin on colorectal tumorogenesis. These are not perfectly known nowadays. On one hand, there are direct mechanisms on colorectal mucosa, on the other hand there are indirect mechanisms through platelet functions. Aspirin also plays a role by its anti-inflammatory action and the stimulation of antitumor immunity. Several studies show that long-term treatment with low-doses of aspirin decreases the incidence of adenomas and colorectal cancers. In the United States, aspirin is currently recommended for primary prevention of the risk of colorectal cancer in all patients aged 50 to 59, with a 10-year risk of cardiovascular event greater than 10 %. However, primary prevention with aspirin should not be a substitute for screening in colorectal cancer. Furthermore, aspirin seems to be beneficial when used in post-diagnosis of colorectal cancer. It could actually decrease the risk of metastasis in case of a localized colorectal cancer, and increase the survival in particular, concerning PIK3CA mutated tumors. The association of aspirin with neoadjuvant treatment of colorectal cancer by radiochimiotherapy seems to have beneficial effects. French prospective randomized study is currently being conducted to investigate postoperative aspirin in colorectal cancers with a PIK3CA mutation. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  7. Protocatechualdehyde synergizes with aspirin at the platelet cyclooxygenase-1 level.

    Science.gov (United States)

    Sun, Shiqing; Hao, Haiping; Gong, Ping; Tang, Zhiyuan; Li, Feiyan; Chen, Xiaohu; Shi, Haibo; Wang, Guangji

    2011-11-01

    Polyphenol-aspirin interactions were recently identified; however, the interaction mode and underlying mechanisms remained elusive. Here, we quantitatively assessed the potential interactions among two important polyphenolic compounds, caffeic acid (CA) and protocatechualdehyde (Pro), and aspirin in the AA-induced platelet aggregation model by applying the isobologram and universal response surface approach (URSA) methods. A molecular docking approach and an originally developed platelet-associated aspirin clearance approach (PAACA) were then applied to explore the potential interaction mechanisms. Although Pro and CA themselves exhibited weak inhibitory effect on arachidonic acid (AA)-induced platelet aggregation and the production of thromboxane B₂ (TXB₂), both Pro and CA potentiated aspirin action in a synergistic manner. The most prominent synergism was found between Pro and aspirin. Pro formed a stable complex into the cyclooxygenase-1 (COX-1) channel by in silico docking and significantly promoted the platelet-associated aspirin clearance, suggesting that the Pro interaction with COX-1 was favorable to the binding of aspirin with COX-1. Taken together, our findings suggest that the capacity of Pro and potentially other structurally similar polyphenolic compounds on promoting the binding of aspirin on platelet COX-1 might be the main mechanism of their synergism with aspirin. © Georg Thieme Verlag KG Stuttgart · New York.

  8. A randomized controlled trial of eicosapentaenoic acid and/or aspirin for colorectal adenoma prevention during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme (The seAFOod Polyp Prevention Trial): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Hull, Mark A; Sandell, Anna C; Montgomery, Alan A; Logan, Richard F A; Clifford, Gayle M; Rees, Colin J; Loadman, Paul M; Whitham, Diane

    2013-07-29

    The naturally-occurring omega (ω)-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA) reduces colorectal adenoma (polyp) number and size in patients with familial adenomatous polyposis. The safety profile and potential cardiovascular benefits associated with ω-3 PUFAs make EPA a strong candidate for colorectal cancer (CRC) chemoprevention, alone or in combination with aspirin, which itself has recognized anti-CRC activity. Colorectal adenoma number and size are recognized as biomarkers of future CRC risk and are established as surrogate end-points in CRC chemoprevention trials. The seAFOod Polyp Prevention Trial is a randomized, double-blind, placebo-controlled, 2×2 factorial 'efficacy' study, which will determine whether EPA prevents colorectal adenomas, either alone or in combination with aspirin. Participants are 55-73 year-old patients, who have been identified as 'high risk' (detection of ≥5 small adenomas or ≥3 adenomas with at least one being ≥10 mm in diameter) at screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Exclusion criteria include the need for more than one repeat endoscopy within the three-month BCSP screening period, malignant change in an adenoma, regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs, regular use of fish oil supplements and concomitant warfarin or anti-platelet agent therapy. Patients are randomized to either EPA-free fatty acid 1 g twice daily or identical placebo AND aspirin 300 mg once daily or identical placebo, for approximately 12 months. The primary end-point is the number of participants with one or more adenomas detected at routine one-year BCSP surveillance colonoscopy. Secondary end-points include the number of adenomas (total and 'advanced') per patient, the location (left versus right colon) of colorectal adenomas and the number of participants re-classified as 'intermediate risk' for future surveillance. Exploratory end-points include levels of

  9. Estudo comparativo entre agregação plaquetária por turbidimetria e impedância elétrica em pacientes sob terapia antiplaquetária à base de ácido acetilsalicílico Comparative study of platelet aggregation by turbidimetric and impedance methods in patients under acetylsalicylic acid antiplatelet therapy

    Directory of Open Access Journals (Sweden)

    Leonardo Lorenzo da Silva

    2010-01-01

    Full Text Available INTRODUÇÃO: A hiperagregação (agregação excessiva das plaquetas pode causar a formação de um trombo e a posterior oclusão dos vasos sanguíneos levando à isquemia. Esse fenômeno é responsável por doenças isquêmicas cardiovasculares, como angina pectoris e aterosclerose, bem como outras formas de isquemia, como o acidente vascular cerebral. Visando diminuir a função das plaquetas para reduzir a formação de trombos, o ácido acetilsalicílico vem sendo utilizado para tratamento antitrombótico, com diversos estudos mostrando sua eficácia. Dessa forma faz-se mister o uso de uma ferramenta laboratorial para o monitoramento da efetividade do tratamento, o que é feito por meio do teste de agregação plaquetária. O objetivo desse estudo foi comparar duas metodologias para esse exame (impedância elétrica e turbidimetria em relação a trinta pacientes adultos de ambos os sexos em uso do fármaco. CONCLUSÃO: Os resultados mostraram uma boa correlação entre os métodos, possibilitando o uso concomitante de ambas as técnicas em laboratórios clínicos de rotina.INTRODUCTION: Hyperaggregation of platelets can cause the formation of thrombi and subsequent occlusion of blood vessels leading to ischemia. This phenomenon can be responsible for ischemic cardiovascular diseases such as angina pectoris and atherosclerosis as well as other forms of ischemia such as stroke. To decrease platelet function and reduce the formation of thrombi, acetylsalicylic acid has been used for antithrombotic treatment, with several studies showing its effectiveness. Therefore it is necessary to use a laboratory tool to monitor the effectiveness of treatment, which is achieved through laboratory testing of platelet aggregation. The aim of this study was to compare two different methods (impedance and turbidimetry to test platelet aggregation in 30 adult patients of both genders taking acetylsalicylic acid. CONCLUSION: The results show that there is a

  10. Aspirin and heart disease

    Science.gov (United States)

    ... attack . Your provider may recommend to take daily aspirin if: You do not have a history of heart disease or stroke, but you are at high risk for a heart attack or stroke. You have been diagnosed ... already. Aspirin helps get more blood flowing to your legs. ...

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

    Science.gov (United States)

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

    2008-07-01

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

  12. Platelet-rich fibrin/aspirin complex promotes alveolar bone regeneration in periodontal defect in rats.

    Science.gov (United States)

    Du, J; Mei, S; Guo, L; Su, Y; Wang, H; Liu, Y; Zhao, Z; Wang, S; Liu, Y

    2018-02-01

    The efficacy and outcomes of aspirin in local defects and the use of platelet-rich fibrin (PRF) in periodontal defects were investigated. Whether the PRF/aspirin complex is a suitable scaffold and delivery system to carry sustained-release aspirin/salicylic acid to promote periodontal bone regeneration was determined. PRF and PRF/aspirin complex were prepared. The concentrations of aspirin/salicylic acid released from the PRF/aspirin complex were calculated at 37°C. Periodontal ligament mesenchymal cells were cultured on six-well plates with PRF or PRF/aspirin complex gel to analyze proliferation and migration. The alveolar bone between the inferior buccal mesial root and anterior buccal distal root of the first maxillary molar was removed in 15 rats randomly divided into three groups: no treatment, PRF or PRF/aspirin complex. Twelve weeks post-transplantation, 2D/3D micro-computed tomography and histomorphometric technique were used for quantitative analyses. The PRF/aspirin complex provided a sustained-release aspirin/salicylic acid. Peak concentrations occurred 4 hours after transplantation and were sustained to 48 hours at 37°C; the total concentration of released aspirin/salicylic acid was 83.5 mg/mL, respectively. The sustained-release promoted the proliferation and migration of periodontal ligament mesenchymal cells. Micro-computed tomography and histological data showed that both the PRF and PRF/aspirin complex enhanced periodontal bone formation (P<.05). Moreover, the new bone formation was two times greater in the PRF/aspirin complex group than the PRF group. Aspirin/salicylic acid could be sustained-released from PRF/aspirin complex, which could inhibit inflammation and improve the function of mesenchymal cells. The data might provide a new safe and easy clinical therapeutic strategy to promote periodontal bone reparation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Dgroup: DG01504 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ory drug, salicylic acid derivatives ... DG00015 ... Acetylsalicylic acid ... D00109 ... Aspirin (JP17/USP); Aspalon (JAN) ... D05181 ... Aspirin... aluminum (JP17) ... D07579 ... Aspirin calcium salt ... D07580 ... Aspirin DL-lysine (JAN) ... D07581 ... Aspirin... magnesium salt ... D07582 ... Aspirin sodium ... DG00099 ... Olsalazine ... D0

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

    Science.gov (United States)

    Fiorucci, S; Del Soldato, P

    2003-05-01

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

  15. Willow species and aspirin: different mechanism of actions.

    Science.gov (United States)

    Vlachojannis, J; Magora, F; Chrubasik, S

    2011-07-01

    Many believe that willow is the natural source of aspirin. However, willow species contain only a low quantity of the prodrug salicin which is metabolized during absorption into various salicylate derivatives. If calculated as salicylic acid, the daily salicin dose is insufficient to produce analgesia. Salicylic acid concentrations following an analgesic dose of aspirin are an order of magnitude higher. Flavonoids and polyphenols contribute to the potent willow bark analgesic and anti-inflammatory effect. The multi-component active principle of willow bark provides a broader mechanism of action than aspirin and is devoid of serious adverse events. In contrast to synthetic aspirin, willow bark does not damage the gastrointestinal mucosa. An extract dose with 240 mg salicin had no major impact on blood clotting. In patients with known aspirin allergy willow bark products are contraindicated. Copyright © 2011 John Wiley & Sons, Ltd.

  16. The role of aspirin-triggered lipoxins in the mechanism of action of aspirin.

    Science.gov (United States)

    Gilroy, Derek W

    2005-01-01

    Few drugs have treated so many diseases, provided us with so much understanding of their pathogenesis, and tested our scientific creativity over the last 100 years as much as aspirin. Originally, the beneficial effects of aspirin were shown to stem from its inhibition of cyclooxygenase (COX 2)-derived prostanoids, fatty acid metabolites that modulate host defense and regulate the cardiovascular system. However, the inhibition of COX 2 enzyme activity and prostaglandin synthesis has never fully explained aspirin's repertoire of anti-inflammatory effects, leaving many questions pertaining to its true mechanism of action unanswered. Here, data from a series of comparatively recent experiments exploring aspirin's unique ability to acetylate the active site of inducible COX 2 and generate a family of lipid mediators called the epi-Lipoxins will be discussed in light of their ability to exert profound modulatory effects on the innate and adaptive immune systems.

  17. The mechanism of action of aspirin.

    Science.gov (United States)

    Vane, J R; Botting, R M

    2003-06-15

    The therapy of rheumatism began thousands of years ago with the use of decoctions or extracts of herbs or plants such as willow bark or leaves, most of which turned out to contain salicylates. Following the advent of synthetic salicylate, Felix Hoffman, working at the Bayer company in Germany, made the acetylated form of salicylic acid in 1897. This drug was named "Aspirin" and became the most widely used medicine of all time. In 1971, Vane discovered the mechanism by which aspirin exerts its anti-inflammatory, analgesic and antipyretic actions. He proved that aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) inhibit the activity of the enzyme now called cyclooxygenase (COX) which leads to the formation of prostaglandins (PGs) that cause inflammation, swelling, pain and fever. However, by inhibiting this key enzyme in PG synthesis, the aspirin-like drugs also prevented the production of physiologically important PGs which protect the stomach mucosa from damage by hydrochloric acid, maintain kidney function and aggregate platelets when required. This conclusion provided a unifying explanation for the therapeutic actions and shared side effects of the aspirin-like drugs. Twenty years later, with the discovery of a second COX gene, it became clear that there are two isoforms of the COX enzyme. The constitutive isoform, COX-1, supports the beneficial homeostatic functions, whereas the inducible isoform, COX-2, becomes upregulated by inflammatory mediators and its products cause many of the symptoms of inflammatory diseases such as rheumatoid and osteoarthritis.

  18. Molecular targets of aspirin and cancer prevention

    Science.gov (United States)

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

    2014-01-01

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

  19. Aspirin treatment reduces platelet resistance to deformation.

    Science.gov (United States)

    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.

  20. NAC attenuates LPS-induced toxicity in aspirin-sensitized mouse macrophages via suppression of oxidative stress and mitochondrial dysfunction.

    Directory of Open Access Journals (Sweden)

    Haider Raza

    Full Text Available Bacterial endotoxin lipopolysaccharide (LPS induces the production of inflammatory cytokines and reactive oxygen species (ROS under in vivo and in vitro conditions. Acetylsalicylic acid (ASA, aspirin is a commonly used anti-inflammatory drug. Our aim was to study the effects of N-acetyl cysteine (NAC, an antioxidant precursor of GSH synthesis, on aspirin-sensitized macrophages treated with LPS. We investigated the effects of LPS alone and in conjunction with a sub-toxic concentration of ASA, on metabolic and oxidative stress, apoptosis, and mitochondrial function using J774.2 mouse macrophage cell line. Protection from LPS-induced toxicity by NAC was also studied. LPS alone markedly induced ROS production and oxidative stress in macrophage cells. When ASA was added to LPS-treated macrophages, the increase in oxidative stress was significantly higher than that with LPS alone. Similarly, alteration in glutathione-dependent redox metabolism was also observed in macrophages after treatment with LPS and ASA. The combination of LPS and ASA selectively altered the CYP 3A4, CYP 2E1 and CYP 1A1 catalytic activities. Mitochondrial respiratory complexes and ATP production were also inhibited by LPS-ASA treatment. Furthermore a higher apoptotic cell death was also observed in LPS-ASA treated macrophages. NAC pre-treatment showed protection against oxidative stress induced apoptosis and mitochondrial dysfunction. These effects are presumed, at least in part, to be associated with alterations in NF-κB/Nrf-2 mediated cell signaling. These results suggest that macrophages are more sensitive to LPS when challenged with ASA and that NAC pre-treatment protects the macrophages from these deleterious effects.

  1. [Cyclooxigenase-1 gene polymorphism and aspirin resistance].

    Science.gov (United States)

    Bondar', T N; Kravchenko, N A

    2012-01-01

    The literature data concerning structure of cyclo-oxigenase-1--the key enzyme in prostaglandin biosynthesis and the main target of anti-platelet therapy with the use of acetylsalicilic acid are presented in the review. The data on cyclooxigenase-1 gene polymorphism, distribution of the revealed variants in various populations and their possible correlation with biochemical and functional aspirin resistance are presented.

  2. New single-nucleotide polymorphisms associated with differences in platelet reactivity and their influence on survival in patients with type 2 diabetes treated with acetylsalicylic acid: an observational study.

    Science.gov (United States)

    Milanowski, Lukasz; Pordzik, Justyna; Janicki, Piotr K; Kaplon-Cieslicka, Agnieszka; Rosiak, Marek; Peller, Michal; Tyminska, Agata; Ozieranski, Krzysztof; Filipiak, Krzysztof J; Opolski, Grzegorz; Mirowska-Guzel, Dagmara; Postula, Marek

    2017-04-01

    Genetic polymorphisms may contribute to platelet reactivity in diabetic patients; however, the information on their influence on long-term antiplatelet therapy is lacking. Our aim was to evaluate the role of previously described genetic variants and platelet reactivity on risk of all-cause mortality and cardiovascular events. Blood samples were obtained from 303 Caucasian patients. Genome-wide genotyping was performed using Illumina Human Omni 2.5-Quad microarrays, and individual genotyping of selected SNPs was performed using a custom Sequenom iPLEX assay in conjunction with the Mass ARRAY platform. Platelet reactivity was measured with VerifyNow Aspirin Assay and PFA-100 Assay. Univariate and multivariate Cox regression analyses were performed to determine the impact of genetic variants and platelets reactivity on risk of all-cause mortality and cardiovascular events. Among the 237 patients included in the follow-up, death from any cause occurred in 34 (14.3%) patients and cardiovascular events occurred in 51 (21.5%) patients within a median observation time of 71 months (5.9 years). In univariate analyses, significant association in the presence of minor alleles in TXBA2R (rs1131882) with primary (HR 2.54, 95% CI 1.15-5.60, p = 0.021) and secondary endpoint (HR 2.06, 95% CI 1.06-4.04, p = 0.034) was observed. In addition, multivariate analyses revealed the impact of this polymorphism on primary (HR 2.34, 95% CI 1.09-5.00, p = 0.029) and secondary endpoint (HR 1.89, 95% CI 1.00-3.57, p = 0.048). Results of the study demonstrate for the first time an association between genetic polymorphism within TXBA2R gene encoding platelet's surface receptor and long-term survival of diabetic patients treated with ASA.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. Dgroup: DG00015 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available DG00015 Chemical ... DGroup Acetylsalicylic acid ... D00109 ... Aspirin (JP17/USP); Aspalon (JAN) ... D05181 ... Aspiri...n aluminum (JP17) D07579 ... Aspirin calcium salt D07580 ... Aspirin DL-lysine (JAN) D07581 ... Aspirin... magnesium salt D07582 ... Aspirin sodium Cardiovascular agent ... DG01712 ... Antiplatelet agent ... DG01950

  6. Aspirin and lipid mediators in the cardiovascular system.

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  8. 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.

    Science.gov (United States)

    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. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Synthesis of a nano-crystalline solid acid catalyst from fly ash and its catalytic performance

    Energy Technology Data Exchange (ETDEWEB)

    Chitralekha Khatri; Ashu Rani [Government P.G. College, Kota (India). Environmental Chemistry Laboratory

    2008-10-15

    The synthesis of nano-crystalline activated fly ash catalyst (AFAC) with crystallite size of 12 nm was carried out by chemical and thermal treatment of fly ash, a waste material generated from coal-burning power plants. Fly ash was chemically activated using sulfuric acid followed by thermal activation at 600{sup o}C. The variation of surface and physico-chemical properties of the fly ash by activation methods resulted in improved acidity and therefore, catalytic activity for acid catalyzed reactions. The AFAC was characterized by X-ray diffraction, FT-IR spectroscopy, N{sub 2}-adsorption-desorption isotherm, scanning electron microscopy, flame atomic absorption spectrophotometry and sulfur content by CHNS/O elemental analysis. It showed amorphous nature due to high silica content (81%) and possessed high BET surface area (120 m{sup 2}/g). The catalyst was found to be highly active solid acid catalyst for liquid phase esterification of salicylic acid with acetic anhydride and methanol giving acetylsalicylic acid and methyl salicylate respectively. A maximum yield of 97% with high purity of acetylsalicylic acid (aspirin) and a very high conversion 87% of salicylic acid to methyl salicylate (oil of wintergreen) was obtained with AFAC. The surface acidity and therefore, catalytic activity in AFAC was originated by increased silica content, hydroxyl content and higher surface area as compared to fly ash. The study shows that coal generated fly ash can be converted into potential solid acid catalyst for acid catalyzed reactions. Furthermore, this catalyst may replace conventional environmentally hazardous homogeneous liquid acids making an ecofriendly; solvent free, atom efficient, solid acid based catalytic process. 27 refs., 5 figs., 2 tabs.

  10. Low dose aspirin and pregnancy: how important is aspirin resistance?

    OpenAIRE

    Navaratnam, K; Alfirevic, A; Alfirevic, Z

    2016-01-01

    Antiplatelet agents are pivotal for prevention of coronary artery disease and cerebrovascular disease worldwide. Individual patient data meta?analysis indicates that low?dose aspirin causes a 10% risk reduction in pre?eclampsia for women at high individual risk. However, in the last 15 years it has emerged that a significant proportion of aspirin?treated individuals exhibit suboptimal platelet response, determined biochemically and clinically, termed ?aspirin non?responsiveness?, ?aspirin res...

  11. Determination of aspirin by pre-column transacetylation reaction of 3-aminophenol and reversed-phase high-performance liquid chromatography: simultaneous determination of aspirin, acetaminophen, and caffeine.

    Science.gov (United States)

    Verma, K K; Sanghi, S K; Jain, A; Gupta, D

    1987-07-01

    The accuracy of the measurement of aspirin by high-performance liquid chromatography (HPLC) is reduced by its hydrolysis into salicylic and acetic acids during sample preparation. The ready and quantitative transacetylation of 3-aminophenol by aspirin, giving 3-hydroxyacetanilide (which is stable), has been utilized as a pre-column reaction for the determination of aspirin either alone or in the presence of acetaminophen and caffeine by reversed-phase HPLC.

  12. Once- versus twice-daily aspirin treatment in patients with essential thrombocytosis

    DEFF Research Database (Denmark)

    Larsen, Mads Lamm; Pedersen, Oliver Heidmann; Hvas, Anne-Mette

    2018-01-01

    Insufficient platelet inhibition has been reported in up to 40% of aspirin-treated patients, including patients with essential thrombocytosis. To maintain sufficient platelet inhibition, a shorter dosing interval with aspirin has been suggested. We aimed to investigate the antiplatelet effect...... of low-dose aspirin given twice-daily compared to standard once-daily dosing in patients with essential thrombocytosis. We included 22 patients, who were treated for 7 days with standard once-daily aspirin (75 mg once-daily) followed by 7 days treatment of twice-daily aspirin (37.5 mg twice......-daily). The two regimens were separated by 14 days aspirin washout. Blood samples were obtained 1h and 24h/12h after the last pill intake in each regimen. The effect of aspirin was evaluated by: (1) platelet aggregation measured by whole blood impedance aggregometry (Multiplate® Analyser) using arachidonic acid...

  13. Aspirin-Exacerbated Asthma

    Directory of Open Access Journals (Sweden)

    Varghese Mathew

    2008-06-01

    Full Text Available This review focuses on aspirin-exacerbated asthma (AEA. The review includes historical perspective of aspirin, prevalence, pathogenesis, clinical features and treatment of AEA. The pathogenesis of AEA involves the cyclooxygenase and lipooxygenase pathway. Aspirin affects both of these pathways by inhibiting the enzyme cycooxygenase-1 (COX-1. Inhibition of COX-1 leads to a decrease in prostaglandin E2 (PGE2. The decrease in PGE2 results in an increase in cysteinyl leukotrienes by the lipooxygenase pathway involving the enzyme 5-lipooxygenase (5-LO. Leukotriene C4 (LTC4 synthase is the enzyme responsible for the production of leukotriene C4, the chief cysteinyl leukotriene responsible for AEA. There have been familial occurences of AEA. An allele of the LTC4 synthase gene in AEA is known as allele C. Allele C has a higher frequency in AEA. Clinical presentation includes a history of asthma after ingestion of aspirin, nasal congestion, watery rhinorrhea and nasal polyposis. Treatment includes leukotriene receptor antagonists, leukotriene inhibitors, aspirin desinsitaztion and surgery. AEA is the most well-defined phenotype of asthma. Although AEA affects adults and children with physician-diagnosed asthma, in some cases there is no history of asthma and AEA often goes unrecognized and underdiagnosed.

  14. Aspirin and Cancer.

    Science.gov (United States)

    Patrignani, Paola; Patrono, Carlo

    2016-08-30

    The place of aspirin in primary prevention remains controversial, with North American and European organizations issuing contradictory treatment guidelines. More recently, the U.S. Preventive Services Task Force recommended "initiating low-dose aspirin use for the primary prevention of cardiovascular disease (CVD) and colorectal cancer in adults aged 50 to 59 years who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years." This recommendation reflects increasing evidence for a chemopreventive effect of low-dose aspirin against colorectal (and other) cancer. The intent of this paper is to review the evidence supporting a chemopreventive effect of aspirin, discuss its potential mechanism(s) of action, and provide a conceptual framework for assessing current guidelines in the light of ongoing studies. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  15. Influence of non-steroidal anti-inflammatory drugs on antiplatelet effect of aspirin.

    Science.gov (United States)

    Yokoyama, H; Ito, N; Soeda, S; Ozaki, M; Suzuki, Y; Watanabe, M; Kashiwakura, E; Kawada, T; Ikeda, N; Tokuoka, K; Kitagawa, Y; Yamada, Y

    2013-02-01

    It has been reported that ibuprofen interferes with the antiplatelet effect of low-dose aspirin. This interaction is ascribed to steric hindrance at the active site of cyclooxygenase-1 by ibuprofen, when aspirin is administered after ibuprofen. However, whether other non-steroidal anti-inflammatory drugs (NSAIDs) interact with aspirin similarly is not well defined. The aim of this study was to assess the influence of nine NSAIDs on the antiplatelet effect of aspirin. We investigated the antiplatelet effect of NSAIDs using steady-state plasma concentration reported after usual doses. We studied the in vitro antiplatelet effect of NSAID alone, aspirin alone, aspirin before NSAID addition and aspirin after NSAID addition to platelet-rich plasma. The rates of platelet aggregation induced by collagen were determined. The final concentration of aspirin used was the 50% effective concentration (EC(50)) previously estimated in vitro. Ibuprofen and mefenamic acid interfere with the antiplatelet effect of aspirin when added before the latter. The rate of platelet aggregation was reduced by 48·1% and 22·7%, respectively. The other NSAIDs tested did not significantly affect the aspirin antiplatelet effect when exposure was prior to aspirin. None of the nine NSAIDs altered the aspirin effect if administration followed that of aspirin. Naproxen and flurbiprofen have significant antiplatelet effects at plasma concentrations seen with usual doses. Our in vitro model suggests that the antiplatelet effect of aspirin is significantly diminished when taken after, but not before, ibuprofen or mefenamic acid. None of the other NSAIDs tested had any effect irrespective of the timing of dosing. © 2012 Blackwell Publishing Ltd.

  16. Analgesic choice in dentistry Part II : The toxicity

    National Research Council Canada - National Science Library

    Marcos Luciano Pimenta Pinheiro; Filipe Polese Branco; Maria Cristina Volpato; Eduardo Dias De Andrade

    2006-01-01

    Nonopioid analgesics are widely prescribed in dentistry. The first article of this series reviewed the mechanism of action of acetylsalicylic acid (aspirin), acetaminophen (paracetamol) and dipyrone...

  17. Effect of omega 3 fatty acids plus low-dose aspirin on both clinical and biochemical profiles of patients with chronic periodontitis and type 2 diabetes: a randomized double blind placebo-controlled study.

    Science.gov (United States)

    Elwakeel, N M; Hazaa, H H

    2015-12-01

    The aim of this study was, first, to investigate the effect of omega 3 (ω3) fatty acids plus low-dose aspirin with closed debridement in the treatment of patients with periodontitis and type 2 diabetes mellitus (DM), and second, to estimate the expression of monocyte chemoattractant protein-3 (MCP-3) in response to the supposed modulatory therapy. Forty patients with chronic periodontitis and type 2 DM were equally divided into groups 1 (patients received ω3 plus low-dose aspirin for 6 mo) and 2 (patients received placebo during the same period). Evaluation was done clinically (pocket depth, clinical attachment loss, gingival index and plaque index) and biochemically by estimating levels of interleukin 1β and MCP-3 in gingival crevicular fluid, plus investigating the effect of treatment on glycemic control by levels of glycated hemoglobin A1c in serum. All data were collected at baseline, 3 and 6 mo after treatment. Subjects of group 1 showed a highly significant reduction in pocket depth, clinical attachment loss, gingival index (p ≤ 0.01) after 3 and 6 mo compared to group 2. Glycated hemoglobin A1c levels showed a reduction in both groups at the end of the study period, with a non-significant difference (p > 0.05). Furthermore, the treatment protocol showed a significant reduction in levels of MCP-3 and interleukin 1β at 3 and 6 mo compared to the placebo group. Within the limits of the present study, ω3 plus low-dose aspirin proved effective as an adjunct to closed periodontal therapy in the management of patients with periodontitis and type 2 DM. Moreover, MCP-3 was proven to be effective both in the pathogenesis of the disease and as a biomarker in evaluating the response to periodontal treatment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. An Efficient Microscale Procedure for the Synthesis of Aspirin

    Science.gov (United States)

    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).

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

    Science.gov (United States)

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

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

  20. Monitoring the hydrolyzation of aspirin during the dissolution testing for aspirin delayed-release tablets with a fiber-optic dissolution system

    Directory of Open Access Journals (Sweden)

    Yan Wang

    2012-10-01

    Full Text Available The purpose of this study was to investigate the hydrolyzation of aspirin during the process of dissolution testing for aspirin delayed-release tablets. Hydrolysis product of salicylic acid can result in adverse effects and affect the determination of dissolution rate assaying. In this study, the technique of differential spectra was employed, which made it possible to monitor the dissolution testing in situ. The results showed that the hydrolyzation of aspirin made the percentage of salicylic acid exceed the limit of free salicylic acid (4.0, and the hydrolyzation may affect the quality detection of aspirin delayed-release tablets. Keywords: Aspirin delayed-release tablets, Drug dissolution test, Fiber-optic dissolution system, UV–vis spectrum

  1. Reye Syndrome and Aspirin

    OpenAIRE

    J Gordon Millichap

    1987-01-01

    Twenty-six cases of Reye syndrome occurring between 1973 and 1982 have been reviewed in relation to aspirin ingestion at the Children’s Hospital, Camperdown, Australia (formerly the Royal Alexandra Hospital for Children in Sydney), where Reye first described his syndrome of encephalopathy and fatty degeneration of the viscera in 1963.

  2. Tailored antiplatelet therapy can overcome clopidogrel and aspirin resistance - The BOchum CLopidogrel and Aspirin Plan (BOCLA-Plan to improve antiplatelet therapy

    Directory of Open Access Journals (Sweden)

    Pepinghege Fenena

    2011-01-01

    Full Text Available Abstract Background Dual antiplatelet therapy using acetylsalicylic acid (ASA, aspirin and clopidogrel is of great importance following coronary stenting. However, the variable platelet inhibitory effectiveness compromises the antithrombotic advantages provided by dual antiplatelet therapy. The aim of this single-center prospective study was to reduce the low response incidence of dual antiplatelet therapy with ASA and clopidogrel according to a prespecified therapy algorithm. Methods Platelet function testing using whole blood aggregometry (Chronolog 590 was performed 48 hours following coronary stenting (for either acute coronary syndromes or stable coronary artery disease on 504 patients. The antiplatelet therapy included a loading dose of 600 mg clopidogrel and 500 mg ASA, followed by 75 mg clopidogrel and 100 mg ASA once daily. Clopidogrel low responders (CLR: >5 ohm; adenosine diphosphate (ADP 5 μM and/or ASA low responders (ALR: >0 ohm; arachidonic acid 10 μM were treated according to a structured therapy plan: in the case of CLR, the maintenance + dose was doubled (repeated loading dose followed by 150 mg daily, and when still ineffective ticlopidine or prasugrel, if available and not contraindicated, were used. ALR was treated by increasing the dose to 300 mg in a first step or to 500 mg ASA when the first modification did not take effect sufficiently. In addition, ADP receptor antagonist 2-methylthioadenosine 5'-monophosphate triethylammonium salt (MeSAMP testing and ASA incubation were performed to rule out either a platelet ADP-receptor defect or an ASA pharmacokinetic resistance. Results Of the total cohort of 504 patients, we detected 30.8% clopidogrel low-responders and 19.4% aspirin low-responders. For ALR, with a dose adjustment of 300 mg ASA daily, 94.6% of ALR were effectively treated and the residual 5.4% by administration of daily dosages of 500 mg ASA. This means that after modification of the ASA maintenance dose, all

  3. Tailored antiplatelet therapy can overcome clopidogrel and aspirin resistance - The BOchum CLopidogrel and Aspirin Plan (BOCLA-Plan) to improve antiplatelet therapy

    Science.gov (United States)

    2011-01-01

    Background Dual antiplatelet therapy using acetylsalicylic acid (ASA, aspirin) and clopidogrel is of great importance following coronary stenting. However, the variable platelet inhibitory effectiveness compromises the antithrombotic advantages provided by dual antiplatelet therapy. The aim of this single-center prospective study was to reduce the low response incidence of dual antiplatelet therapy with ASA and clopidogrel according to a prespecified therapy algorithm. Methods Platelet function testing using whole blood aggregometry (Chronolog 590) was performed 48 hours following coronary stenting (for either acute coronary syndromes or stable coronary artery disease) on 504 patients. The antiplatelet therapy included a loading dose of 600 mg clopidogrel and 500 mg ASA, followed by 75 mg clopidogrel and 100 mg ASA once daily. Clopidogrel low responders (CLR: >5 ohm; adenosine diphosphate (ADP) 5 μM) and/or ASA low responders (ALR: >0 ohm; arachidonic acid 10 μM) were treated according to a structured therapy plan: in the case of CLR, the maintenance + dose was doubled (repeated loading dose followed by 150 mg daily), and when still ineffective ticlopidine or prasugrel, if available and not contraindicated, were used. ALR was treated by increasing the dose to 300 mg in a first step or to 500 mg ASA when the first modification did not take effect sufficiently. In addition, ADP receptor antagonist 2-methylthioadenosine 5'-monophosphate triethylammonium salt (MeSAMP) testing and ASA incubation were performed to rule out either a platelet ADP-receptor defect or an ASA pharmacokinetic resistance. Results Of the total cohort of 504 patients, we detected 30.8% clopidogrel low-responders and 19.4% aspirin low-responders. For ALR, with a dose adjustment of 300 mg ASA daily, 94.6% of ALR were effectively treated and the residual 5.4% by administration of daily dosages of 500 mg ASA. This means that after modification of the ASA maintenance dose, all initial ALRs had an

  4. Aspirin Prophylaxis for the Prevention of Thrombosis: Expectations and Limitations

    Directory of Open Access Journals (Sweden)

    Gundu H. R. Rao

    2012-01-01

    Full Text Available Platelets play a very important role in the pathogenesis of acute vascular events leading to thrombosis of the coronary and cerebral arteries. Blockage of these arteries leading to regional ischemia of heart and brain tissues precipitate heart attacks and stroke. Acetyl salicylic acid (Aspirin has been the drug of choice for over half a century for the primary and secondary prophylaxis of thrombotic events. In spite of its extensive use as an antiplatelet drug for the prevention of vascular thrombosis, there is considerable concern about the degree of protection it offers, to patients under aspirin therapy. In this paper, we explain the phenomenon of aspirin resistance, discuss the limitations of aspirin therapy, and suggest methods to monitor “at-risk” individuals. Ability to monitor and determine at risk patients will provide opportunities for the clinicians to customize antiplatelet therapies.

  5. Assessment of platelet function in acute ischemic stroke patients previously treated with aspirin.

    Science.gov (United States)

    Lago, Aida; Parkhutik, Vera; Tembl, Jose Ignacio; Vallés, Juana; Santos, Maria Teresa; Moscardó, Antonio

    2014-01-01

    Platelet inhibition measured by platelet function tests could be critical to understand the reasons for early recurrence and to guide therapeutic recommendations. We assess the platelet function during the acute phase of ischemic stroke in patients pretreated with aspirin who continue their treatment with aspirin only, are started on clopidogrel only, or add clopidogrel to aspirin. Sixty-four patients were taking aspirin before the stroke. Depending on the administered antiplatelet, 3 groups were defined: ASA: patients who continued on aspirin orally or intravenous acetylsalicylate of lysine, n = 30; CLO: patients who discontinued aspirin and were started on clopidogrel, n = 16; and ASA + CLO: patients who were prescribed both aspirin and clopidogrel, n = 10. Collagen-induced thromboxane A2 (TXA2) synthesis, ADP (adenosine diphosphate)-induced aggregation, and occlusion time (PF-100) were measured. CLO group only had a marked elevation of TXA2 (17.44 ± 15.62 ng/mL, P = .000) and a shortening of the platelet function analyzer (PFA)-100 closure time (157.13 ± 88 seconds, P = .047) compared with the other 2 groups (ASA: TXA2, .62 ± 1.59 ng/mL; ASA + CLO: TXA2 1.79 ± 4.59 ng/mL). They achieved a small (13%) but significant reduction of ADP-induced aggregation (87.00 ± 23.06 mm, P = .008) compared with the ASA group (102.82 ± 22.38 seconds). Stopping aspirin intake within the first 72 hours of the acute stroke drastically increases TXA2 synthesis. During the same time window, the freshly prescribed clopidogrel manages to reduce the ADP-induced aggregation only slightly (13%). This study offers analytic proof that the common practice of replacing aspirin with clopidogrel does not leave stroke patients fully protected during the first days after an ischemic stroke. Possible solutions could be to preserve aspirin during a few days or to use loading doses of clopidogrel at hospital admission. Copyright © 2014 National Stroke Association. Published by Elsevier Inc

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

    Science.gov (United States)

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

    2015-05-01

    Aspirin is now recommended for splenectomized thalassemia patients with high platelet counts. However, aspirin resistance defined by arachinodic acid (ACA) induced platelet aggregation ≥20%, has never been reported in this group of patients. In this study, twenty-four splenectomized thalassemia patients (15.7±4.1years), with platelet counts ≥800x10(9)/L, and 21 non-splenectomized severe thalassemia patients (14.3±3.2years), were enrolled. After taking aspirin (2mg/kg/day), seven patients (29.2%) displayed aspirin resistance. Serum thromboxane B2 (TXB2) levels in the aspirin responsive group decreased significantly [52.6(8.8-174.6) vs 4.0(1.6-7.3) mcg/mL, paspirin resistant group. Having increased aspirin to 4mg/kg/day, three of the seven aspirin resistant patients responded, while one developed upper GI bleeding from esophageal varices and was withdrawn from the study. For the three remaining patients, their doses were increased to the maximum of 300mg/day, and two of the three responded. Thrombin antithrombin complex and D-dimer levels were significantly decreased after taking aspirin (2mg/kg/day), although D-dimer level was still significantly higher than that in non-splenectomized group. Therefore, aspirin dosage can be adjusted individually to reach maximum effect of platelet inhibition. In addition, aspirin can reduce the levels of coagulation markers. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Patient characteristics among users of analgesic over-the-counter aspirin in a Danish pharmacy setting

    DEFF Research Database (Denmark)

    Pottegård, Anton; Kviesgaard, Ann-Katrine; Hesse, Ulrik

    2014-01-01

    BACKGROUND: Use of over-the-counter (OTC) high-dose acetylsalicylic acid (ASA) is a risk factor for experiencing gastric bleeding. However, more detailed knowledge on the characteristics of users of OTC ASA is needed. OBJECTIVE: To characterise users of OTC high-dose ASA in a Danish pharmacy sett...

  8. Dgroup: DG01909 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available salazide DG01909.gif DG00015 ... Acetylsalicylic acid ... D00109 ... Aspirin (JP17/USP); Aspalon (JAN) ... D05181 ... Aspirin... aluminum (JP17) ... D07579 ... Aspirin calcium salt ... D07580 ... Aspirin DL-lysine (JAN) ... D07581 ... Aspirin magnesium salt ... D07582 ... Aspiri

  9. Fabrication, characterization, thermal stability and nanoassemblies of novel pullulan-aspirin conjugates

    OpenAIRE

    Muhammad A. Hussain; Khawar Abbas; Bilal A. Lodhi; Muhammad Sher; Muhammad Ali; Muhammad N. Tahir; Wolfgang Tremel; Saima Iqbal

    2017-01-01

    Present study deals with homogeneous and one-pot synthesis of novel macromolecular prodrugs (MPDs) of aspirin onto naturally occurring hydrophilic biopolymer pullulan. Pullulan-aspirin conjugates were synthesized by using green carboxylic acid activating reagent 1,1′-carbonyldiimidazole (CDI). The aspirin was first reacted with CDI to prepare aspirin-imidazolide at RT for 24 h which in situ reacted with pre-dissolved pullulan and the reaction preceded further for 24 h at 80 °C under nitrogen....

  10. 24-hour antiplatelet effect of aspirin in patients with previous definite stent thrombosis

    DEFF Research Database (Denmark)

    Würtz, Morten; Hvas, Anne-Mette; Jensen, Lisette O

    2014-01-01

    OBJECTIVE: Once-daily aspirin is standard treatment, but recent studies point towards increased platelet function at the end of the dosing interval. Stent thrombosis (ST) has been linked with reduced antiplatelet effect of aspirin, so we investigated if platelet inhibition by aspirin declines...... with 100 patients with stable coronary artery disease and 50 healthy volunteers. All participants were on aspirin 75 mg/day mono antiplatelet therapy. Platelet aggregation was measured 1 and 24 h after aspirin intake using platelet aggregometry (Multiplate® Analyzer). Cyclooxygenase-1 activity, platelet...... activation, immature platelets, and thrombopoietin were measured. RESULTS: Platelet aggregation increased by 109±150 (arachidonic acid) and 47±155 (collagen) aggregation units per minute from 1 to 24 h after aspirin intake (p-values

  11. The evolution of antiplatelet therapy in the treatment of acute coronary syndromes: from aspirin to the present day.

    Science.gov (United States)

    Angiolillo, Dominick J

    2012-11-12

    Our knowledge of the mechanisms of platelet-mediated thrombosis has increased dramatically over the last 40 years. This increased understanding has identified treatment strategies for acute coronary syndromes (ACS) by targeting key mediators of platelet activation and aggregation processes. Aspirin (acetylsalicylic acid) monotherapy improves patient outcomes by irreversibly inhibiting the cyclooxygenase (COX)-1 enzyme in the arachidonic acid pathway. The later-developed thienopyridines, prodrugs that irreversibly inhibit the P2Y(12) receptor, and therefore adenosine diphosphate (ADP) binding, further enhance platelet inhibition and patient outcomes. The thienopyridine clopidogrel has been the standard of care, but it is limited by variable response and treatment failure. A more potent thienopyridine, prasugrel, requires fewer hepatic metabolic steps for activation, and elicits significantly improved outcomes for patients with ACS. The increased potency of prasugrel is associated with an increase in Thrombolysis in Myocardial Infarction (TIMI)-defined major bleeding compared with clopidogrel. Ticagrelor represents a new chemical class of agents called the cyclopentyltriazolopyrimidines. It interacts reversibly with the platelet P2Y(12) receptor, and does not require metabolic bioactivation for activity. Data show a significant improvement in ischaemic outcomes, including mortality, for ticagrelor compared with clopidogrel, without an increase in overall major bleeding, although non-coronary artery bypass graft bleeding is increased. Glycoprotein IIb/IIIa targeted agents (abciximab, tirofiban and eptifibatide) are also used in ACS patients undergoing percutaneous coronary interventions. These inhibitors utilize a different mechanism of action by preventing fibrinogen-mediated platelet aggregation. Other therapeutic strategies for platelet inhibition are being evaluated, including the investigative protease-activated receptor (PAR)-1 and thromboxane A(2) antagonists

  12. Synthesis and transdermal properties of acetylsalicylic acid derivates / Minja Gerber

    OpenAIRE

    Gerber, Minja

    2003-01-01

    The skin is an amazing elastic and relatively impermeable barrier that provides protective, perceptive and communication functions to the body. The stratum corneum is widely accepted as the barrier of the skin - limiting the transport of molecules into and across the skin. It is evident that the transdermal permeation of drugs depend on a number of factors of which the physicochemical properties play the most prevalent role. The potential of using intact skin as the site of adm...

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

    Science.gov (United States)

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

    2011-12-02

    Vitamin C (L-ascorbic acid) has a major biological role as a natural antioxidant. Aspirin belongs to the nonsteroidal anti-inflammatory drugs and functions as an antioxidant via its ability to scavenge-OH radicals. Bovine serum albumin (BSA) is the major soluble protein constituent of the circulatory system and has many physiological functions including transport of a variety of compounds. In this report, the competitive binding of vitamin C and aspirin to bovine serum albumin has been studied using constant protein concentration and various drug concentrations at pH 7.2. FTIR and UV-Vis spectroscopic methods were used to analyze vitamin C and aspirin binding modes, the binding constants and the effects of drug complexation on BSA stability and conformation. Spectroscopic evidence showed that vitamin C and aspirin bind BSA via hydrophilic interactions (polypeptide and amine polar groups) with overall binding constants of K(vitamin C-BSA)=1.57×10(4)M(-1) and K(aspirin-BSA)=1.15×10(4)M(-1); assuming that there is one drug molecule per protein. The BSA secondary structure was altered with major decrease of α-helix from 64% (free protein) to 57% (BSA-vitamin C) and 54% (BSA-aspirin) and β-sheet from 15% (free protein) to 6-7% upon drug complexation, inducing a partial protein destabilization. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events

    NARCIS (Netherlands)

    Squizzato, Alessandro; Bellesini, Marta; Takeda, Andrea; Middeldorp, Saskia; Donadini, Marco Paolo

    2017-01-01

    Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. Adding a second antiplatelet drug to aspirin may produce additional benefit for people at high risk and people with established cardiovascular disease. This is an update to a previously published review

  15. Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular disease

    NARCIS (Netherlands)

    Squizzato, Alessandro; Keller, Tymen; Romualdi, Erica; Middeldorp, Saskia

    2011-01-01

    Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. Adding a second antiplatelet drug to aspirin may produce additional benefit for those at high risk and those with established cardiovascular disease. To quantify the benefit and harm of adding clopidogrel

  16. Complexity in Estimation of Esomeprazole and its Related Impurities' Stability in Various Stress Conditions in Low-Dose Aspirin and Esomeprazole Magnesium Capsules

    OpenAIRE

    REDDY, Palavai; HOTHA, Kishore; 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 asp...

  17. Antiplatelet effects of aspirin in chronic kidney disease patients.

    Science.gov (United States)

    Polzin, A; Dannenberg, L; Sansone, R; Levkau, B; Kelm, M; Hohlfeld, T; Zeus, T

    2016-02-01

    ESSENTIALS: Chronic kidney disease (CKD) patients have a high risk of cardiovascular events. A pharmacodynamic evaluation of the effects of aspirin in 116 patients was carried out. The antiplatelet effects of aspirin are associated with impaired renal function. The optimal antithrombotic regimen in CKD patients must be investigated on a larger scale. The pharmacodynamic response to aspirin varies significantly between individuals. Insufficient antiplatelet effects of aspirin are associated with increased risk of ischemic events. Chronic kidney disease (CKD) is suggested to affect the pharmacodynamic response to antiplatelet medication. High on-treatment platelet reactivity (HTPR) to clopidogrel has been reported to partially account for the enhanced risk of death and cardiovascular events in CKD patients. Objective To investigate the antiplatelet effects of aspirin in patients with CKD. We conducted a cross-sectional study in 116 patients on permanent aspirin medication. The pharmacodynamic response to aspirin was determined by arachidonic acid-induced thromboxane formation. HTPR to aspirin was more frequent in patients with impaired renal function (47% vs. 22%; odds ratio, 3.16; 95% confidence interval [CI], 1.34-7.41; P = 0.008). The pharmacodynamic response to aspirin was impaired in patients with moderate/severe CKD (92; interquartile range [IQR], 282 ng mL(-1) ) as compared to patients with normal/mildly reduced renal function (36; IQR, 100 ng mL(-1) ; difference in medians, 57; CI, 5-110 ng mL(-1) ; P = 0.013). Bivariate Pearson analysis showed residual thromboxane formation to be correlated with glomerular filtration rate (R = -0.303; R(2) = 0.092; P = 0.001). Patients with CKD were older and more frequently female. Multivariate linear regression analysis revealed that the correlation was independent of age (R = -0.314; R(2) = 0.082; P = 0.002) and gender (R = -0.305; R(2) = 0.077; P = 0.006). Renal function is correlated with pharmacodynamic response to

  18. Acetylsalycylic Acid Resistance and Risk Factors in Acute Ischemic Stroke Patients

    Directory of Open Access Journals (Sweden)

    Yıldız Arslan

    2015-04-01

    Full Text Available OBJECTIVE: The aim of the study was to investigate prevalence of acetylsalicylic acid (ASA resistance in acute ischemic stroke patients by using Platelet Function Analyzer (PFA 100 test and to determine the effect of risk factors that may be responsible for ASA resistance. METHODS: Fifty acute ischemic stroke patients (mean age: 66.32±12.983 years, 34 male were given 300 mg/day aspirin for at least 10 days and all risk factors were investigated for a correlation to ASA resistance by using PFA 100 test. These factors were; age, gender, hemoglobin(Hgb, hematocrit(Htc, platelet (plt total cholesterol, von Willebrand Factor (vWF levels, hypertension(HT, diabetes mellitus(DM, coronary artery disease(CAD, smoking and previous cerebrovascular disease (CVD. In PFA-100 system, a collagen/epinephrine (C/EPI closure time in the range of 85-157 sec. and a collagen/ADP closure time of 65-125sec. were considered normal. Maximal test duration was 300 s. C/EPI closure time is sensitive for ASA resistance. Subjects with duration shorter than 300 s. were accepted as ASA-resistant or non-responder. RESULTS: ASA resistance was apparent in 32% of the study group. vWF levels were higher in ASA resistant patients group. All risk factors were compared in ASA sensitive and resistant group. vWF levels and mean age were higher in ischemic stroke ASA non responder group, but not statistically significant. CONCLUSION: In 50 acute ischemic patient aspirin resistance rate was 32%, this means aspirin was pharmacologically non effective in those. Clinical outcome for aspirin non responders may be revealed through the follow up at least six months.

  19. MACULAR DEGENERATION AND ASPIRIN USE.

    Science.gov (United States)

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

    2017-09-01

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

  20. Fabrication, characterization, thermal stability and nanoassemblies of novel pullulan-aspirin conjugates

    Directory of Open Access Journals (Sweden)

    Muhammad A. Hussain

    2017-05-01

    Full Text Available Present study deals with homogeneous and one-pot synthesis of novel macromolecular prodrugs (MPDs of aspirin onto naturally occurring hydrophilic biopolymer pullulan. Pullulan-aspirin conjugates were synthesized by using green carboxylic acid activating reagent 1,1′-carbonyldiimidazole (CDI. The aspirin was first reacted with CDI to prepare aspirin-imidazolide at RT for 24 h which in situ reacted with pre-dissolved pullulan and the reaction preceded further for 24 h at 80 °C under nitrogen. Degree of substitution (DS 0.32–0.40 of aspirin onto pullulan was calculated from 1H NMR spectroscopy. Spectroscopic techniques confirmed the high covalent drug loading and purity. Thermal analysis has revealed that new MPDs of aspirin are thermally more stable than pure aspirin. The activation energy, order and frequency factor of the degradation reactions were calculated using Broido, Friedman and Chang models. The amphiphilic pullulan-aspirin conjugates self-assembled in nanoparticles without further structural modifications at solvent interface in the range of 500–680 nm as examined by transmission electron microscopy. These novel pullulan-aspirin conjugates with masked COOH functional group could be potentially safe prodrugs for the stomach.

  1. Comparative bioequivalence assessment of aspirin tablets marketed ...

    African Journals Online (AJOL)

    Purpose: In the last few years, aspirin has become a life saver against cardiovascular accidents. This investigation was carried out to determine possible bioequivalence between regular aspirin and soluble aspirin tablets marketed in Nigeria. Methods: The in vivo bioavailability profiles of three commercial brands of aspirin ...

  2. Taking Aspirin to Protect Your Heart

    Science.gov (United States)

    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 ...

  3. Aspirin-Induced Acute Liver Injury

    OpenAIRE

    Laster, Janese; Satoskar, Rohit

    2014-01-01

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

  4. Platelets, aspirin, and cardiovascular disease.

    Science.gov (United States)

    Elwood, P C; Hughes, C; O'Brien, J R

    1998-10-01

    Aspirin was first synthesised 100 years ago and its preparation and marketing is generally reckoned to have been the foundation of the pharmaceutical industry. For most of the time since then it has been used for the relief of pain and fever. The modern phase of aspirin use commenced with the reporting in 1974 of a randomised controlled trial in the secondary prevention of death by low-dose aspirin given to patients who had suffered a myocardial infarct. Reports of other trials followed and an overview of the first six trials was presented to the inaugural meeting of the Society for Clinical Trials in Philadelphia in 1980. There have been two further major overviews and the most recent, based on 145 trials, established that low-dose aspirin reduces vascular events by around one third. It has been estimated that, used appropriately, aspirin could prevent 100,000 premature deaths each year worldwide, at a cost of about 250 Pounds ($400) per life saved, and about 80 Pounds ($130) per cardiovascular event prevented. The evidence indicates that it is seriously underused at present. The aspirin story continues and trials are in progress to test other possible uses of aspirin, in vascular dementia, colorectal cancer, and cataract.

  5. Gastrointestinal symptoms in low-dose aspirin users: a comparison between plain and buffered aspirin

    NARCIS (Netherlands)

    Jaspers Focks, J.; Tielemans, M.M.; Rossum, L.G.M. van; Eikendal, T.; Brouwer, M.A.; Jansen, J.B.M.J.; Laheij, R.J.F.; Verheugt, F.W.A.; Oijen, M.G.H. van

    2014-01-01

    BACKGROUND: Aspirin is associated with gastrointestinal side effects such as gastric ulcers, gastric bleeding and dyspepsia. High-dose effervescent calcium carbasalate (ECC), a buffered formulation of aspirin, is associated with reduced gastric toxicity compared with plain aspirin in healthy

  6. Platelets, aspirin, and cardiovascular disease.

    OpenAIRE

    Elwood, P. C.; Hughes, C.; O'Brien, J. R.

    1998-01-01

    Aspirin was first synthesised 100 years ago and its preparation and marketing is generally reckoned to have been the foundation of the pharmaceutical industry. For most of the time since then it has been used for the relief of pain and fever. The modern phase of aspirin use commenced with the reporting in 1974 of a randomised controlled trial in the secondary prevention of death by low-dose aspirin given to patients who had suffered a myocardial infarct. Reports of other trials followed and a...

  7. Low prevalence and assay discordance of "aspirin resistance" in children.

    Science.gov (United States)

    Yee, D L; Dinu, B R; Sun, C W; Edwards, R M; Justino, H; Teruya, J; Bray, P F; Bomgaars, L

    2008-07-01

    Although "aspirin resistance" (AR-inadequate platelet inhibition as suggested by in vitro testing of aspirin-treated patients) has been widely studied in adults and linked to increased risk of adverse outcomes, its prevalence and clinical significance are largely unknown in children. To determine AR prevalence in children and its relationship to assay methodology, we undertook a cross-sectional study of 44 children (1-17 years, 24 male) on aspirin for various indications and considered three published definitions of AR in adults: platelet aggregation >/=70% to 10 microM adenosine diphosphate and >/=20% to 0.5 mg/ml arachidonic acid (AA), normal PFA-100(R) closure time and elevated urinary 11-dehydro thromboxane B(2) (11dhTxB(2)) concentration. Six subjects exhibited AR according to at least one of the criteria (5 by PFA-100(R), 1 by aggregometry and 11dhTxB(2) criteria); nearly all subjects had low levels of 11dhTxB(2) compared with controls. Subjects studied prior to therapy showed pronounced changes in AR parameters after aspirin dosing (e.g., mean aggregation to AA decreased from 82% to 6%, P aspirin effect. Subjects with AR did not differ from aspirin responsive subjects in terms of age, race, platelet count, or aspirin dose, indication or therapy duration. There was minimal correlation between assays. In this initial prevalence study of a clinically diverse group of pediatric patients, frequencies of AR were assay-dependent; however, the prevalence of true AR is likely low in children (2.3%; 95% CI 0.1-10.7%), in agreement with adult studies. To better define the clinical relevance of AR in children, multicenter, prospective cohort studies are imperative. (c) 2008 Wiley-Liss, Inc.

  8. Aspirin induces nitric oxide release from vascular endothelium: a novel mechanism of action.

    Science.gov (United States)

    Taubert, D; Berkels, R; Grosser, N; Schröder, H; Gründemann, D; Schömig, E

    2004-09-01

    1. The study was designed to test the hypothesis that aspirin may stimulate nitric oxide (NO) release from vascular endothelium, a pivotal factor for maintenance of vascular homeostasis. 2. Clinical evidence suggests that low-dose aspirin may improve vascular endothelial function. Since other cyclooxygenase (COX) inhibitors showed no beneficial vascular effects, aspirin may exhibit a vasculoprotective, COX-independent mechanism. 3. Luminal NO release was monitored in real time on dissected porcine coronary arteries (PCA) by an amperometric, NO-selective sensor. Additionally, endothelial NO synthase (eNOS) activity was measured in EA.hy 926 cell homogenates by an l-[(3)H]citrulline/l-[(3)H]arginine conversion assay. Superoxide scavenging capacity was assessed by lucigenin-enhanced luminescence. 4. Aspirin induced an immediate concentration-dependent NO release from PCA with an EC(50) of 50 nm and potentiated the NO stimulation by the receptor-dependent agonist substance P. These effects were independent of an increase in intracellular calcium and could be mimicked by stimulation with acetylating aspirin derivatives. The aspirin metabolite salicylic acid or the reversible cyclooxygenase inhibitor indomethacin failed to modulate NO release. Incubation of soluble eNOS for 15 min with 100 microm aspirin or acetylating aspirin analogues increased the l-[(3)H]citrulline yield by 40-80%, while salicylic acid had no effect. Aspirin and salicylic acid showed a similar, but only modest, magnitude and velocity of superoxide scavenging. 5. Our findings demonstrate that therapeutically relevant concentrations of aspirin elicit NO release from vascular endothelium. This effect appears to be due to a direct acetylation of the eNOS protein, but is independent of COX inhibition or inhibition of superoxide-mediated NO degradation.

  9. Aspirin provocation increases 8-iso-PGE2 in exhaled breath condensate of aspirin-hypersensitive asthmatics.

    Science.gov (United States)

    Mastalerz, Lucyna; Januszek, Rafał; Kaszuba, Marek; Wójcik, Krzysztof; Celejewska-Wójcik, Natalia; Gielicz, Anna; Plutecka, Hanna; Oleś, Krzysztof; Stręk, Paweł; Sanak, Marek

    2015-09-01

    Isoprostanes are bioactive compounds formed by non-enzymatic oxidation of polyunsaturated fatty acids, mostly arachidonic, and markers of free radical generation during inflammation. In aspirin exacerbated respiratory disease (AERD), asthmatic symptoms are precipitated by ingestion of non-steroid anti-inflammatory drugs capable for pharmacologic inhibition of cyclooxygenase-1 isoenzyme. We investigated whether aspirin-provoked bronchoconstriction is accompanied by changes of isoprostanes in exhaled breath condensate (EBC). EBC was collected from 28 AERD subjects and 25 aspirin-tolerant asthmatics before and after inhalatory aspirin challenge. Concentrations of 8-iso-PGF2α, 8-iso-PGE2, and prostaglandin E2 were measured using gas chromatography/mass spectrometry. Leukotriene E4 was measured by immunoassay in urine samples collected before and after the challenge. Before the challenge, exhaled 8-iso-PGF2α, 8-iso-PGE2, and PGE2 levels did not differ between the study groups. 8-iso-PGE2 level increased in AERD group only (p=0.014) as a result of the aspirin challenge. Urinary LTE4 was elevated in AERD, both in baseline and post-challenge samples. Post-challenge airways 8-iso-PGE2 correlated positively with urinary LTE4 level (p=0.046), whereas it correlated negatively with the provocative dose of aspirin (p=0.027). A significant increase of exhaled 8-iso-PGE2 after inhalatory challenge with aspirin was selective and not present for the other isoprostane measured. This is a novel finding in AERD, suggesting that inhibition of cyclooxygenase may elicit 8-iso-PGE2 production in a specific mechanism, contributing to bronchoconstriction and systemic overproduction of cysteinyl leukotrienes. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. High platelet reactivity on aspirin in patients with acute ST elevation myocardial infarction.

    Science.gov (United States)

    Dillinger, Jean-Guillaume; Saeed, Alaa; Spagnoli, Vincent; Sollier, Claire Bal Dit; Sideris, Georgios; Silberman, Stephane Manzo; Voicu, Sebastian; Drouet, Ludovic; Henry, Patrick

    2016-08-01

    Despite dual antiplatelet treatment, major ischemic events are common following ST elevation myocardial infarction (STEMI). We aimed to assess high platelet reactivity on aspirin (HPR-aspirin) and its association with P2Y12i (HPR-P2Y12i) during the acute phase of STEMI. We included all consecutive patients admitted for STEMI treated by primary angioplasty in our center for 1year. All patients received a loading dose followed by a maintenance dose of aspirin (75mg/day) and prasugrel (ticagrelor or clopidogrel if contraindicated). Platelet reactivity was assessed 4±1days and 75±15days after admission using light transmission aggregometry with arachidonic acid (LTA-AA-HPR-aspirin) and VASP (HPR-P2Y12i) to define HPR as well as serum Thromboxane-B2 and LTA-ADP. Major cardiac and cerebrovascular events were recorded for 1year. We included 106 patients - mean age was 61y.o., 76% were male and 20% had diabetes. STEMI was anterior in 52% and LV ejection fraction at discharge was 51±9%. 50% of patients were treated with prasugrel and 34% with ticagrelor. At day 4 after STEMI, HPR-aspirin was found in 26% patients and HPR-P2Y12i in 7%. HPR- both aspirin and P2Y12i was found in 4%. Diabetes and age were predictors of HPR-aspirin. HPR-aspirin was persistent 75days later in 36% patients. At 1year, 7.9% patients had experienced major adverse cardiovascular and cerebrovascular events (MACCE). HPR-aspirin and HPR on both aspirin and P2Y12i were significantly associated with MACCE. HPR-aspirin is frequent just after STEMI and associated with MACCE especially when associated with HPR-P2Y12i. Copyright © 2016. Published by Elsevier Ltd.

  11. Daily Aspirin Therapy: Understand the Benefits and Risks

    Science.gov (United States)

    Daily aspirin therapy: Understand the benefits and risks Daily aspirin therapy can be a lifesaving option, but it's not ... everyone. Get the facts before considering a daily aspirin. By Mayo Clinic Staff Daily aspirin therapy may ...

  12. High glucose inhibits the aspirin-induced activation of the nitric oxide/cGMP/cGMP-dependent protein kinase pathway and does not affect the aspirin-induced inhibition of thromboxane synthesis in human platelets.

    Science.gov (United States)

    Russo, Isabella; Viretto, Michela; Barale, Cristina; Mattiello, Luigi; Doronzo, Gabriella; Pagliarino, Andrea; Cavalot, Franco; Trovati, Mariella; Anfossi, Giovanni

    2012-11-01

    Since hyperglycemia is involved in the "aspirin resistance" occurring in diabetes, we aimed at evaluating whether high glucose interferes with the aspirin-induced inhibition of thromboxane synthesis and/or activation of the nitric oxide (NO)/cGMP/cGMP-dependent protein kinase (PKG) pathway in platelets. For this purpose, in platelets from 60 healthy volunteers incubated for 60 min with 5-25 mmol/L d-glucose or iso-osmolar mannitol, we evaluated the influence of a 30-min incubation with lysine acetylsalicylate (L-ASA; 1-300 μmol/L) on 1) platelet function under shear stress; 2) aggregation induced by sodium arachidonate or ADP; 3) agonist-induced thromboxane production; and 4) NO production, cGMP synthesis, and PKG-induced vasodilator-stimulated phosphoprotein phosphorylation. Experiments were repeated in the presence of the antioxidant agent amifostine. We observed that platelet exposure to 25 mmol/L d-glucose, but not to iso-osmolar mannitol, 1) reduced the ability of L-ASA to inhibit platelet responses to agonists; 2) did not modify the L-ASA-induced inhibition of thromboxane synthesis; and 3) prevented the L-ASA-induced activation of the NO/cGMP/PKG pathway. Preincubation with amifostine reversed the high-glucose effects. Thus, high glucose acutely reduces the antiaggregating effect of aspirin, does not modify the aspirin-induced inhibition of thromboxane synthesis, and inhibits the aspirin-induced activation of the NO/cGMP/PKG pathway. These results identify a mechanism by which high glucose interferes with the aspirin action.

  13. Oxylipid Profile of Low-Dose Aspirin Exposure: A Pharmacometabolomics Study.

    Science.gov (United States)

    Ellero-Simatos, Sandrine; Beitelshees, Amber L; Lewis, Joshua P; Yerges-Armstrong, Laura M; Georgiades, Anastasia; Dane, Adrie; Harms, Amy C; Strassburg, Katrin; Guled, Faisa; Hendriks, Margriet M W B; Horenstein, Richard B; Shuldiner, Alan R; Hankemeier, Thomas; Kaddurah-Daouk, Rima

    2015-10-26

    While aspirin is a well-established and generally effective anti-platelet agent, considerable inter-individual variation in drug response exists, for which mechanisms are not completely understood. Metabolomics allows for extensive measurement of small molecules in biological samples, enabling detailed mapping of pathways involved in drug response. We used a mass-spectrometry-based metabolomics platform to investigate the changes in the serum oxylipid metabolome induced by an aspirin intervention (14 days, 81 mg/day) in healthy subjects (n=156). We observed a global decrease in serum oxylipids in response to aspirin (25 metabolites decreased out of 30 measured) regardless of sex. This decrease was concomitant with a significant decrease in serum linoleic acid levels (-19%, P=1.3×10(-5)), one of the main precursors for oxylipid synthesis. Interestingly, several linoleic acid-derived oxylipids were not significantly associated with arachidonic-induced ex vivo platelet aggregation, a widely accepted marker of aspirin response, but were significantly correlated with platelet reactivity in response to collagen. Together, these results suggest that linoleic acid-derived oxylipids may contribute to the non-COX1 mediated variability in response to aspirin. Pharmacometabolomics allowed for more comprehensive interrogation of mechanisms of action of low dose aspirin and of variation in aspirin response. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  14. Influence of renal function and platelet turnover on the antiplatelet effect of aspirin.

    Science.gov (United States)

    Würtz, Morten; Wulff, Lise N; Grove, Erik L; Kristensen, Steen D; Hvas, Anne-Mette

    2012-04-01

    Kidney disease predisposes to cardiovascular events. This study investigated the influence of renal function and platelet turnover on the antiplatelet effect of aspirin in patients with coronary artery disease. We included 124 aspirin-treated patients with coronary artery disease and normal to moderately reduced renal function. All tests were performed one hour after aspirin ingestion. Renal function was assessed using creatinine, estimated glomerular filtration rate (eGFR), and cystatin C. The antiplatelet effect of aspirin was evaluated using the VerifyNow Aspirin assay and multiple electrode aggregometry (MEA, Multiplate) induced by collagen (1.0 μg/mL) and arachidonic acid (1.0 mmol/L). Von Willebrand factor was measured as a marker of endothelial dysfunction. Platelet turnover was evaluated by measurements of immature, reticulated platelets. Renal function did not influence the antiplatelet effect of aspirin evaluated by MEA (r=-0.2-0.09, p=0.03-0.77) or the VerifyNow (r=-0.12-0.11, all p-values>0.1). In contrast, renal function correlated inversely with von Willebrand factor levels (r(creatinine)=0.48, pantiplatelet effect of aspirin may be explained by an increased number of immature platelets. Moderately impaired renal function was associated with high levels of von Willebrand factor, but not with a reduced antiplatelet effect of aspirin. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Aspirin increases metabolism through germline signalling to extend the lifespan of Caenorhabditis elegans.

    Science.gov (United States)

    Huang, Xiao-Bing; Mu, Xiao-Hui; Wan, Qin-Li; He, Xiao-Ming; Wu, Gui-Sheng; Luo, Huai-Rong

    2017-01-01

    Aspirin is a prototypic cyclooxygenase inhibitor with a variety of beneficial effects on human health. It prevents age-related diseases and delays the aging process. Previous research has shown that aspirin might act through a dietary restriction-like mechanism to extend lifespan. To explore the mechanism of action of aspirin on aging, we determined the whole-genome expression profile of Caenorhabditis elegans treated with aspirin. Transcriptome analysis revealed the RNA levels of genes involved in metabolism were primarily increased. Reproduction has been reported to be associated with metabolism. We found that aspirin did not extend the lifespan or improve the heat stress resistance of germline mutants of glp-1. Furthermore, Oil Red O staining showed that aspirin treatment decreased lipid deposition and increased expression of lipid hydrolysis and fatty acid β-oxidation-related genes. The effect of germline ablation on lifespan was mainly mediated by DAF-12 and DAF-16. Next, we performed genetic analysis with a series of worm mutants and found that aspirin did not further extend the lifespans of daf-12 and daf-16 single mutants, glp-1;daf-12 and glp-1;daf-16 double mutants, or glp-1;daf-12;daf-16 triple mutants. The results suggest that aspirin increase metabolism and regulate germline signalling to activate downstream DAF-12 and DAF-16 to extend lifespan.

  16. 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.

    Science.gov (United States)

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

    2016-11-08

    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.

  17. Aspirin resistance may be identified by miR-92a in plasma combined with platelet distribution width

    DEFF Research Database (Denmark)

    Binderup, Helle Glud; Houlind, Kim; Madsen, Jonna Skov

    2016-01-01

    OBJECTIVE: Aspirin is a widely used drug for prevention of thrombotic events in cardiovascular patients, but approximately 25% of patients experience insufficient platelet inhibition due to aspirin, and remain in risk of cardiovascular events. This study aimed to investigate the value...... of circulating miR-92a and platelet size as biomarkers of the individual response to aspirin therapy. METHODS: Blood samples were collected from 50 healthy blood donors without antithrombotic medication and 50 patients with intermittent claudication on daily aspirin therapy. Based on results from the arachidonic...... acid stimulated aggregation test on Multiplate®analyzer (ASPItest), patients were defined as aspirin resistant (n=10) or aspirin responders (n=40). Plasma levels of miR-92a were evaluated by RT-qPCR analysis and platelet distribution width (PDW) was used to assess platelet size variability. Receiver...

  18. Effect of atorvastatin on platelet thromboxane A(2) synthesis in aspirin-treated patients with acute myocardial infarction.

    Science.gov (United States)

    Santos, M Teresa; Fuset, M Paz; Ruano, Miguel; Moscardó, Antonio; Valles, Juana

    2009-12-15

    Inhibition of platelet thromboxane A(2) (TXA(2)) by aspirin is critical in patients with acute myocardial infarction (AMI), but some patients have persistent platelet TXA(2) production within 48 hours of the onset of AMI. Statins are known to reduce TXA(2) in aspirin-free patients with hypercholesterolemia. We hypothesized that treatment with aspirin plus atorvastatin could reduce persistent TXA(2) synthesis and aspirin resistance in patients with AMI. We evaluated platelet function in 184 aspirin-treated patients within 48 hours of the onset of AMI. Patients were divided into group A (treated with aspirin alone, n = 139) and group B (treated with aspirin plus atorvastatin, n = 45). We studied collagen-induced platelet TXA(2) synthesis, serotonin ((14)C-5HT) release and recruitment, and adenosine diphosphate-, arachidonic acid-, and collagen-induced platelet aggregation. Persistent TXA(2) synthesis was detected in 25% and 9% of groups A and B, respectively (p = 0.03). TXA(2), arachidonic acid-aggregation, and collagen-induced responses were significantly reduced in patients receiving dual treatment compared to those receiving aspirin monotherapy. Atorvastatin did not modify platelet reactivity in patients with efficiently blocked TXA(2) synthesis. These results strongly suggest a direct effect of the statin on platelet eicosanoid synthesis. This was confirmed in vitro by incubating washed aspirin-free and aspirin (1 muM)-treated platelets from normal subjects with 1 to 20 microM atorvastatin. Atorvastatin in vitro significantly reduced platelet TXA(2) synthesis and collagen-induced aggregation. In conclusion, atorvastatin combined with aspirin early in the onset of the acute event significantly reduced persistent TXA(2) and TXA(2)-dependent aspirin resistance. This could contribute to the clinical benefit of atorvastatin in patients with AMI.

  19. Aspirin and aneurysmal subarachnoid hemorrhage.

    Science.gov (United States)

    Gross, Bradley A; Rosalind Lai, Pui Man; Frerichs, Kai U; Du, Rose

    2014-12-01

    Recent evidence has suggested a potential beneficial effect of aspirin on the risk of aneurysm rupture. This benefit must be weighed against its potential adverse effects as an antiplatelet agent in the setting of acute aneurysmal subarachnoid hemorrhage (SAH). A total of 747 consecutive patients with cerebral aneurysms were reviewed, comparing demographics, aneurysm features, presenting clinical and radiographic grades, vasospasm, and outcome at 1 year between patients with aneurysmal SAH taking aspirin on presentation and those who were not. The rate of hemorrhagic presentation was significantly greater in patients not taking aspirin (40% vs. 28%; P = 0.016). Among 274 patients presenting with aneurysmal SAH, there was no significant difference in presenting clinical (Hunt and Hess) and radiographic (Fisher) grade between patients taking aspirin and those who were not. There was also no significant difference in the rate of subsequent angiographic and delayed cerebral ischemia. Multivariate analysis of outcome at 1 year found only increasing age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.04-1.12), Hunt and Hess grade (OR 3.01, 95% CI 1.81-5.03), and associated hypertension (OR 3.30, 95% CI 1.39-7.81) to be statistically significant risk factors for poor outcome (death or dependence), whereas aspirin use was not associated with poor outcome (OR 1.19, 95% CI 0.35-4.09; P = 0.78). In the present study, patients taking aspirin had a lower rate of hemorrhagic presentation. In addition, taking aspirin did not adversely impact presenting clinical grade or radiographic grade, vasospasm, and outcome in the setting of aneurysmal SAH. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Novel Proresolving Aspirin-Triggered DHA Pathway

    National Research Council Canada - National Science Library

    Serhan, Charles N; Fredman, Gabrielle; Yang, Rong; Karamnov, Sergey; Belayev, Ludmila S; Bazan, Nicolas G; Zhu, Min; Winkler, Jeremy W; Petasis, Nicos A

    2011-01-01

    .... We report an aspirin-triggered DHA metabolome that biosynthesizes a potent product in inflammatory exudates and human leukocytes, namely aspirin-triggered Neuroprotectin D1/Protectin D1 [AT-(NPD1/PD1...

  1. Aspirin to Zoloft: Ways Medicines Work

    Science.gov (United States)

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

  2. Aspirin during Pregnancy: Is It Safe?

    Science.gov (United States)

    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/ ...

  3. Aspirin resistant patients with recent ischemic stroke.

    Science.gov (United States)

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

    2014-04-01

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

  4. Is there an ideal way to initiate antiplatelet therapy with aspirin? A crossover study on healthy volunteers evaluating different dosing schemes with whole blood aggregometry

    Directory of Open Access Journals (Sweden)

    Overbeck Ursula

    2011-04-01

    Full Text Available Abstract Background Guidelines recommend an early initiation of aspirin treatment in patients with acute cerebral ischemia. Comparative studies on the best starting dose for initiating aspirin therapy to achieve a rapid antiplatelet effect do not exist. This study evaluated the platelet inhibitory effect in healthy volunteers by using three different aspirin loading doses to gain a model for initiating antiplatelet treatment in acute strokes patients. Methods Using whole blood aggregometry, this study with a prospective, uncontrolled, open, crossover design examined 12 healthy volunteers treated with three different aspirin loading doses: intravenous 500 mg aspirin, oral 500 mg aspirin, and a course of 200 mg aspirin on two subsequent days followed by a five-day course of 100 mg aspirin. Aspirin low response was defined as change of impedance exceeding 0 Ω after stimulation with arachidonic acid. Results Sufficient antiplatelet effectiveness was gained within 30 seconds when intravenous 500 mg aspirin was used. The mean time until antiplatelet effect was 74 minutes for 500 mg aspirin taken orally and 662 minutes (11.2 hours for the dose scheme with 200 mg aspirin with a high inter- and intraindividual variability in those two regimes. Platelet aggregation returned to the baseline range during the wash-out phase within 4 days. Conclusion Our study reveals that the antiplatelet effect differs significantly between the three different aspirin starting dosages with a high inter- and intraindividual variability of antiplatelet response in our healthy volunteers. To ensure an early platelet inhibitory effect in acute stroke patients, it could be advantageous to initiate the therapy with an intravenous loading dose of 500 mg aspirin. However, clinical outcome studies must still define the best way to initiate antiplatelet treatment with aspirin.

  5. The role of aspirin in women's health

    NARCIS (Netherlands)

    Verheugt, F.W.A.; Bolte, A.C.

    2011-01-01

    BACKGROUND: The aim of this review is to discuss the role of aspirin for various conditions in women. METHODS: A nonsystematic review of articles published on PubMed((R)) that examines the role of aspirin in women. RESULTS: Aspirin is associated with a significant reduction of stroke risk in women,

  6. Aspirin: Pharmacology and Clinical Applications

    Directory of Open Access Journals (Sweden)

    Enma V. Paez Espinosa

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Deepak Voora, MD

    2016-09-01

    Full Text Available 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.

  8. Update on Recent Advances in the Management of Aspirin Exacerbated Respiratory Disease

    OpenAIRE

    Palikhe, Nami Shrestha; Kim, Joo-Hee; Park, Hae-Sim

    2009-01-01

    Aspirin intolerant asthma (AIA) is frequently characterized as an aspirin (ASA)-exacerbated respiratory disease (AERD). It is a clinical syndrome associated with chronic severe inflammation in the upper and lower airways resulting in chronic rhinitis, sinusitis, recurrent polyposis, and asthma. AERD generally develops secondary to abnormalities in inflammatory mediators and arachidonic acid biosynthesis expression. Upper and lower airway eosinophil infiltration is a key feature of AERD; howev...

  9. Lipoxin and Aspirin-Triggered Lipoxins

    Directory of Open Access Journals (Sweden)

    Mario Romano

    2010-01-01

    Full Text Available Lipoxins and their 15 epimers, aspirin triggered lipoxins (ATL, are eicosanoids derived from sequential lipoxygenase (LO metabolism of arachidonic acid. The main routes of lipoxin biosynthesis involve cooperation between 15- and 5-LO, and between 12- and 5-LO. ATL are generated by interactions between 5-LO and aspirin-acetylated cyclooxygenase-2. Cellular models recapitulating these interactions involve leukocytes, platelets, vascular endothelium, and epithelium. To circumvent rapid lipoxin and ATL metabolism and inactivation, stable analogs, bearing potent and long-lasting biological activity, have been synthesized. Some of these analogs displayed therapeutic potential by showing strong anti-inflammatory activity in a number of animal models of disease, including reperfusion injury; arthritis; gastrointestinal, renal, respiratory, and vascular inflammatory disorders; eye damage; periodontitis; and selected infectious diseases. Counter-regulatory signaling by lipoxin A4 and 15-epi-lipoxin A4 is triggered by the activation of a seven-transmembrane domain receptor, termed FPR2/ALX, which is highly expressed in myeloid cells and has been recognized as a main anti-inflammatory receptor.

  10. TRUE RESISTANCE AND PSEUDORESISTANCE TO ASPIRIN

    Directory of Open Access Journals (Sweden)

    A. I. Martynov

    2013-01-01

    Full Text Available 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. Researchers from university of Pennsylvania (Philadelphia, the USA, led by Dr. Tilo Grosser, aimed to determine the specific phenotype of true pharmacological resistance to aspirin — such as might be explained by genetic causes. However the 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.

  11. Compound list: aspirin [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available aspirin ASA 00014 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/aspirin....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/aspirin....Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/aspirin....Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/aspirin.Rat.in_vivo.Liver.Repeat.zip ...

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

    Science.gov (United States)

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

    2015-07-01

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

  13. 24-hour antiplatelet effect of aspirin in patients with previous definite stent thrombosis.

    Science.gov (United States)

    Würtz, Morten; Hvas, Anne-Mette; Jensen, Lisette O; Kaltoft, Anne K; Tilsted, Hans H; Kristensen, Steen D; Grove, Erik L

    2014-08-01

    Once-daily aspirin is standard treatment, but recent studies point towards increased platelet function at the end of the dosing interval. Stent thrombosis (ST) has been linked with reduced antiplatelet effect of aspirin, so we investigated if platelet inhibition by aspirin declines through 24 h in patients with previous definite ST. Furthermore, we explored whether increased levels of immature platelets and thrombopoietin are associated with a particularly rapid recovery of platelet function. This case-control study included 50 patients with previous definite ST matched with 100 patients with stable coronary artery disease and 50 healthy volunteers. All participants were on aspirin 75 mg/day mono antiplatelet therapy. Platelet aggregation was measured 1 and 24 h after aspirin intake using platelet aggregometry (Multiplate® Analyzer). Cyclooxygenase-1 activity, platelet activation, immature platelets, and thrombopoietin were measured. Platelet aggregation increased by 109±150 (arachidonic acid) and 47±155 (collagen) aggregation units per minute from 1 to 24 h after aspirin intake (p-values aspirin-treated patients with previous definite ST or stable coronary artery disease and in healthy individuals. Increased levels of immature platelets and thrombopoietin were observed in patients with previous definite ST. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Aspirin in patients undergoing noncardiac surgery

    DEFF Research Database (Denmark)

    Devereaux, P J; Mrkobrada, Marko; Sessler, Daniel I

    2014-01-01

    BACKGROUND: There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not. METHODS: Using a 2-by-2 factorial trial design, we randomly assigned 10......,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before...... the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum...

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

    Science.gov (United States)

    Cook, Kevin A; White, Andrew A

    2016-02-01

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

  16. Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events.

    Science.gov (United States)

    Squizzato, Alessandro; Bellesini, Marta; Takeda, Andrea; Middeldorp, Saskia; Donadini, Marco Paolo

    2017-12-14

    Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. Adding a second antiplatelet drug to aspirin may produce additional benefit for people at high risk and people with established cardiovascular disease. This is an update to a previously published review from 2011. To review the benefit and harm of adding clopidogrel to aspirin therapy for preventing cardiovascular events in people who have coronary disease, ischaemic cerebrovascular disease, peripheral arterial disease, or were at high risk of atherothrombotic disease, but did not have a coronary stent. We updated the searches of CENTRAL (2017, Issue 6), MEDLINE (Ovid, 1946 to 4 July 2017) and Embase (Ovid, 1947 to 3 July 2017) on 4 July 2017. We also searched ClinicalTrials.gov and the WHO ICTRP portal, and handsearched reference lists. We applied no language restrictions. We included all randomised controlled trials comparing over 30 days use of aspirin plus clopidogrel with aspirin plus placebo or aspirin alone in people with coronary disease, ischaemic cerebrovascular disease, peripheral arterial disease, or at high risk of atherothrombotic disease. We excluded studies including only people with coronary drug-eluting stent (DES) or non-DES, or both. We collected data on mortality from cardiovascular causes, all-cause mortality, fatal and non-fatal myocardial infarction, fatal and non-fatal ischaemic stroke, major and minor bleeding. The overall treatment effect was estimated by the pooled risk ratio (RR) with 95% confidence interval (CI), using a fixed-effect model (Mantel-Haenszel); we used a random-effects model in cases of moderate or severe heterogeneity (I 2 ≥ 30%). We assessed the quality of the evidence using the GRADE approach. We used GRADE profiler (GRADE Pro) to import data from Review Manager to create a 'Summary of findings' table. The search identified 13 studies in addition to the two studies in the previous version of our systematic review. Overall

  17. Genetic determinants of on-aspirin platelet reactivity: focus on the influence of PEAR1.

    Directory of Open Access Journals (Sweden)

    Morten Würtz

    Full Text Available Platelet aggregation during aspirin treatment displays considerable inter-individual variability. A genetic etiology likely exists, but it remains unclear to what extent genetic polymorphisms determine platelet aggregation in aspirin-treated individuals.To identify platelet-related single nucleotide polymorphisms (SNPs influencing platelet aggregation during aspirin treatment. Furthermore, we explored to what extent changes in cyclooxygenase-1 activity and platelet activation may explain such influence.We included 985 Danish patients with stable coronary artery disease treated with aspirin 75 mg/day mono antiplatelet therapy. Patients were genotyped for 16 common SNPs in platelet-related genes using standard PCR-based methods (TaqMan. Platelet aggregation was evaluated by whole blood platelet aggregometry employing Multiplate Analyzer (agonists: arachidonic acid and collagen and VerifyNow Aspirin. Serum thromboxane B2 was measured to confirm aspirin adherence and was used as a marker of cyclooxygenase-1 activity. Soluble P-selectin was used as marker of platelet activation. Platelet aggregation, cyclooxygenase-1 activity, and platelet activation were compared across genotypes in adjusted analyses.The A-allele of the rs12041331 SNP in the platelet endothelial aggregation receptor-1 (PEAR1 gene was associated with reduced platelet aggregation and increased platelet activation, but not with cyclooxygenase-1 activity. Platelet aggregation was unaffected by the other SNPs analyzed.A common genetic variant in PEAR1 (rs12041331 reproducibly influenced platelet aggregation in aspirin-treated patients with coronary artery disease. The exact biological mechanism remains elusive, but the effect of this polymorphism may be related to changes in platelet activation. Furthermore, 14 SNPs previously suggested to influence aspirin efficacy were not associated with on-aspirin platelet aggregation.ClinicalTrials.gov NCT01383304.

  18. The role of aspirin in cancer prevention.

    Science.gov (United States)

    Thun, Michael J; Jacobs, Eric J; Patrono, Carlo

    2012-04-03

    Clinical guidelines for prophylactic aspirin use currently only consider the cardiovascular benefits of aspirin, weighed against the potential harm from aspirin-induced bleeding. Daily aspirin use has been convincingly shown to reduce the risk of colorectal cancer and recurrence of adenomatous polyps, but in average-risk populations, these benefits alone do not outweigh harms from aspirin-induced bleeding. Recently published secondary analyses of cardiovascular trials provide the first randomized evidence that daily aspirin use may also reduce the incidence of all cancers combined, even at low doses (75-100 mg daily). This Review considers the general mechanism of action that defines aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) as a class, the specific advantages of aspirin over other NSAIDs for prophylactic use, the current evidence concerning the main health outcomes affected by aspirin use, and the hypothesis that inhibition of platelet activation may mediate both the cardioprotective and cancer-preventive effects of low-dose aspirin. It also considers how even a 10% reduction in overall cancer incidence beginning during the first 10 years of treatment could tip the balance of benefits and risks favourably in average-risk populations.

  19. Aspirin resistance following pediatric cardiac surgery.

    Science.gov (United States)

    Cholette, Jill M; Mamikonian, Lara; Alfieris, George M; Blumberg, Neil; Lerner, Norma B

    2010-09-01

    Aspirin is often used to prevent thrombosis in pediatric cardiac surgery. The primary study aim was to assess aspirin resistance in this context. Secondary aims were to evaluate (1) the relationship between elevated inflammatory markers and thrombosis and (2) aspirin's effect on these levels. This was a prospective observational study of children undergoing cardiac surgery managed with and without aspirin. Aspirin response was assessed using the VerifyNow system and urinary 11-dehydrothromboxane B2 (uTxB2) measurements. Laboratory studies of inflammation were also obtained. 101 subjects were studied; 50 received aspirin. Six subjects (5.9%), 5 aspirin-treated, experienced symptomatic thrombosis. When measured by VerifyNow resistance was 43% after aspirin suppositories and 14% after additional days of oral aspirin. There was no correlation with thrombosis. Upper quartile post-operative day (POD) #5 uTxB2 was correlated with thrombosis in aspirin treated subjects (paspirin-treated subjects who experienced thrombosis had higher POD#5 uTxB2. This finding did not reach statistical significance (p=0.07). Elevated pre-operative C-reactive protein (CRP) was independently associated with thrombosis (paspirin. Aspirin inhibited ex-vivo platelet function with a low incidence of resistance. Elevated POD#5 uTxB2 and pre-operative CRP were correlated with thrombosis in aspirin treated subjects. Further studies are needed to determine whether children with high levels of uTxB2 despite aspirin therapy and/or those with elevated preoperative CRP are at increased risk for thrombosis. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2008-01-01

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

  1. Talk with Your Doctor about Taking Aspirin Every Day

    Science.gov (United States)

    ... En español Talk with Your Doctor about Taking Aspirin to Prevent Disease Browse Sections The Basics Overview ... and Risks What are the benefits of taking aspirin regularly? Low-dose aspirin can reduce your risk ...

  2. Aspirin to Prevent a First Heart Attack or Stroke

    Science.gov (United States)

    ... 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 ...

  3. Interference of NSAIDs with the thrombocyte inhibitory effect of aspirin: A placebo-controlled, ex vivo, serial placebo-controlled serial crossover study

    NARCIS (Netherlands)

    Meek, I.L.; Vonkeman, Harald Erwin; Kasemier, J.; Movig, K.L.L.; van de Laar, Mart A F J

    2013-01-01

    Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA) are often prescribed concurrently in patients with nociceptive pain and cardiovascular comorbidity. NSAIDs and ASA inhibit the same COX-enzymes, and thus may interact. ASA’s cardioprotective antiplatelet effect is

  4. Interference of NSAIDs with the thrombocyte inhibitory effect of aspirin: a placebo-controlled, ex vivo, serial placebo-controlled serial crossover study

    NARCIS (Netherlands)

    Meek, I.L.; Vonkeman, H.E.; Kasemier, J.; Movig, K.L.L.; Laar, M.A. van der

    2013-01-01

    PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA) are often prescribed concurrently in patients with nociceptive pain and cardiovascular comorbidity. NSAIDs and ASA inhibit the same COX-enzymes, and thus may interact. ASA's cardioprotective antiplatelet effect is

  5. Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actions

    OpenAIRE

    Undas, Anetta; Brummel-Ziedins, Kathleen E.; Mann, Kenneth G.

    2007-01-01

    Aspirin is effective in the prevention of cardiovascular events in high-risk patients. The primary established effect of aspirin on hemostasis is to impair platelet aggregation via inhibition of platelet thromboxane A2 synthesis, thus reducing thrombus formation on the surface of the damaged arterial wall. Growing evidence also indicates that aspirin exerts additional antithrombotic effects, which appear to some extent unrelated to platelet thromboxane A2 production. Aspirin can reduce thromb...

  6. Effects of Aspirin on Rheological Properties of Erythrocytes In Vitro

    OpenAIRE

    Elblbesy, Mohamed A.; Hereba, Abdel Rahman M.; Shawki, Mamdouh M.

    2012-01-01

    Aspirin is of proven value as an antithrombotic drug. In unstable angina it reduces the risk of death and myocardial infarction by half. Most studies on the mechanism of action of aspirin have concentrated on the effect of aspirin on platelets. In the present study we have tried to prove that there is another biophysical mechanism of aspirin, and that is through the effect of aspirin on erythrocytes. In this study ten blood samples were incubated with aspirin at different concentrations. The ...

  7. Genetic Markers for Differentiating Aspirin-Hypersensitivity

    OpenAIRE

    Kim, Seung-Hyun; Park, Hae-Sim

    2006-01-01

    Aspirin-induced asthma (AIA) and aspirin-induced urticaria/angioedema (AIU) are two major aspirin-related allergies. We summarize recent findings related to their molecular genetic mechanisms in order to identify genetic susceptibility markers for differentiating AIU and AIA. The overproduction of cysteinyl leukotriene has been suggested as a mechanism in both AIU and AIA. Increased expression of CYSLTR1 with CYLSTR1 and CYSLTR2 polymorphisms are new findings in AIA, while the ALOX5 promoter ...

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

    Science.gov (United States)

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

    2016-02-01

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

  9. Comparison of the developmental toxicity of aspirin in rabbits when administered throughout organogenesis or during sensitive windows of development.

    Science.gov (United States)

    Cappon, G D; Gupta, U; Cook, J C; Tassinari, M S; Hurtt, M E

    2003-02-01

    A review of the nonsteroidal anti-inflammatory drug (NSAID) literature suggested occurrences of low-level incidences of cardiovascular and midline defects in rabbit fetuses exposed in utero. Aspirin (acetylsalicylic acid, ASA) is a widely used NSAID that irreversibly inhibits cyclooxygenases (COXs) 1 and 2. ASA has been studied extensively in rats and has consistently increased low-incidence cardiovascular malformations and defects in midline closure. The objectives of the current study were to comprehensively define the developmental toxicology profile of ASA in rabbits by using a dosing paradigm encompassing the period of organogenesis and to test the hypothesis that maternal gastrointestinal toxicity after repeated dose administrations hampers the detection of low-incidence malformations with ASA in rabbits by limiting ASA administration to sensitive windows for cardiovascular development and midline closure. ASA was administered to pregnant New Zealand White rabbits from gestation days (GDs) 7 to 19 at dose levels of 125, 250, and 350 mg/kg per day and as single doses of 500, 750, or 1000 mg/kg on GD 9, 10, or 11. Cesarean sections were performed on GD 29, and the fetuses were examined for external, visceral and skeletal development. In the repeated dose study, maternal toxicity was exhibited in the 250- and 350-mg/kg per day groups by mortality and decreased food consumption and body weight gain. In the single dose studies, maternal toxicity was exhibited at all doses by reductions in body weight gain and food consumption for 3 days after treatment. Fetal body weight was significantly reduced in the repeated dose study at 350 mg/kg per day. Fetal weights were not affected by single doses of ASA on GD 9, 10, or 11. There were no treatment-related external, visceral or skeletal malformations associated with ASA administration throughout organogenesis or with single doses administered during critical developmental windows. These findings supported previous work

  10. Efeito da solução de ácido acetilsalicílico e de ácido acético em fígado de coelhos Effect of acetylsalicylic acid and acetic acid solutions in liver of rabbits

    Directory of Open Access Journals (Sweden)

    Rogério Saad-Hossne

    2004-12-01

    Full Text Available Objetivo: Analisar os efeitos das soluções de aspirina e de ácido acético, in vivo, em fígado de coelhos sadios, verificando o efeito histolítico e o resultado anatomo-patológico das lesões e eventuais alterações bioquímicas hepáticas. Métodos: Utilizou-se 80 coelhos, divididos em 2 protocolos experimentais (1 e 2, subdivididos em 5 grupos cada, sendo os mesmos submetidos a laparotomia mediana, com injeção de 0,4 ml da solução de aspirina (2,5 e 5,0%, de ácido acético (2,5 e 5,0% e solução salina; o sacrifício ocorreu apos 24 horas (protocolo1 e 14 dias (protocolo 2; avaliou-se o peso, evolução clinica, dosagens bioquímicas, cavidade abdominal e torácica e microscopia do fígado. Resultados: Não foram observadas alterações na evolução clinica, peso e nas dosagens bioquímicas, apenas elevação da AST e ALT no grupo 24 horas(Protocolo 1. À macroscópica mostrou que nos animais tratados, em ambos os grupos, a presença de lesão hepática localizada na área infiltrada, correspondente a necrose (24 horas e fibrose (14 dias. Conclusão: Ambas as soluções (aspirina e ácido acético acarretaram destruição localizada do órgão substituída por fibrose apos 14 dias.Purpose: In the present work, 2.5% and 5% acetyl salicylic acid solution and acetic acid solutions were tested in vivo. Methods: In all tests control animals were used and given salt solution. 80 male rabbits were employed and randomly distributed among the different experimental groups. Results: When injected in the liver of healthy rabbits (in vivo, both solutions produced localized destruction (coagulative necrosis of the hepatic parenchyma in 24 hours. After 14 days, these lesions either disappeared or were replaced by mild scars (fibrosis. The lesions were not followed by clinical alterations and the only observed biochemical alteration was an increase in the amount of alanine amino transferase after 24 hours. Conclusion: In vivo, the effects of

  11. Impact of aspirin and clopidogrel interruption on platelet function in patients undergoing major vascular surgery.

    Directory of Open Access Journals (Sweden)

    Yannick Le Manach

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

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

    Science.gov (United States)

    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.

  13. Influence of aspirin and non-aspirin NSAID use on ovarian and endometrial cancer

    DEFF Research Database (Denmark)

    Verdoodt, F.; Kjaer, S. K.; Friis, S.

    2017-01-01

    Increasing evidence supports a role for aspirin use in reducing the incidence and mortality of several cancer types. This has spurred a new wave of interest in this widely used drug. In this review, we present and evaluate the epidemiologic evidence of the association between the use of aspirin....... Overall, observational studies indicate modest reductions in risk of ovarian and endometrial cancer with aspirin use, whereas the results for non-aspirin NSAID use are equivocal. The strongest inverse associations have been reported for long-term consistent aspirin use, notably among subgroups of users (e.......g., those with high body mass index). Few studies have evaluated the influence of NSAID use on the mortality of ovarian or endometrial cancer, and substantial heterogeneity of study characteristics and results preclude any conclusions. Additional studies of aspirin and non-aspirin NSAID use and ovarian...

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

    Science.gov (United States)

    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. Copyright © 2015 The Authors. Published by Elsevier B.V. All

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

    OpenAIRE

    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 exter...

  16. Pharmacogenetics of the antiplatelet effect of aspirin.

    Science.gov (United States)

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

    2012-01-01

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

  17. An Analysis of Changes in Threshold Limit Values Over Time

    Science.gov (United States)

    1993-01-01

    Paper and Allied Products 27 Printing and Publishing 28 Chemicals and Allied Products 29 Petroleum and Coal Products 30 Rubber and Miscellaneous...Acetylene tetrabromide 79-27-6 1 1959 1959 Acetylsalicylic acid ( Aspirin ) 50-78-2 t1980 1980 Acrolein 107-02-8 1946 1963 Acrylamide 79-06-1 1967 1987 i y...Acetone 1953 0.5 Acetonitrile Acetylene tetrabromide _ Acetylsalicylic acid ( Aspirin ) _ Acrolein Acrylamide _ _ _ Acrylic acid _ Acrylonitrile T Aldrin

  18. Effect of aspirin on nasal resistance to airflow.

    OpenAIRE

    Jones, A S; Lancer, J M; Moir, A A; Stevens, J C

    1985-01-01

    The effect of aspirin on nasal resistance to airflow was investigated by rhinomanometry in 25 healthy subjects before and after ingestion of aspirin or vitamin C in a double blind crossover trial. Aspirin caused a significant increase in nasal resistance compared with vitamin C. The effect of aspirin may be due to its inhibition of the synthesis of prostaglandins.

  19. High-on-Aspirin Residual Platelet Reactivity Evaluated Using the Multiplate® Point-of-Care Device

    Directory of Open Access Journals (Sweden)

    Mărginean Alina

    2016-03-01

    Full Text Available Objective: The aim of this study was to evaluate the prevalence of aspirin non-responsiveness using whole blood multiple electrode aggregometry and to investigate the role of different clinical and laboratory variables associated with the lack of response. Methods: The present study included 116 aspirin treated patients presented with acute coronary syndromes or stroke. Response to aspirin was assessed by impedance aggregometry using arachidonic acid as agonist, in a final concentration of 0.5 mM (ASPI test. Results: In our data set 81% (n=94 were responders and 19% (n=22 non-responders showing high-on-aspirin platelet reactivity. Correlation analysis showed that the ward of admittance, low-density lipoproteins (LDL, concomitant antibiotic treatment, beta-adrenergic receptor blockers, history of myocardial infarction as well as PCI performed on Cardiology patients have different degrees of association with aspirin response. Conclusion: Concomitant treatment with beta-adrenergic receptor inhibitors, history of myocardial infarction and Cardiology ward admittance significantly increased the chance of responding to aspirin treatment whereas antibiotic therapy and low-density lipoproteins cholesterol seemed to increase the risk of high-on-aspirin residual platelet reactivity.

  20. [The use of acetylsalicylic acid in patients with ischemic cardiomyopathy cared for in Spanish emergency services (results of the EVICURE Study). Evaluacion del Manejo de la cardiopatia isquemica en los Servicios de Urgencias Hospitalarios of the Sociedad Espanola de Medicina de Urgencias y Emergencias (SEMES)].

    Science.gov (United States)

    Epelde, F; Garca-Castrillo Riesgo, L; Loma-Osorio, A; Verdier, J; Recuerda Martnez, E

    2000-10-14

    Acetyl salicylic acid is a drug with demonstrated effectiveness in ischemic cardiomyopathy. The objective of our study was to know the use of this drug in the emergency services of Spain. The EVICURE study analyzes the use of acetyl salicylic acid in 35 emergency services of Spanish hospitals. 2,168 patients were studied. Of the 473 patients with stable angina, 9.2% received acetyl salicylic acid before going to the hospital and 90,7% at the arrival to the hospital, of 1,067 with unstable angina 13% received acetyl salicylic acid before the arrival to the hospital and 56% at the arrival to the hospital. Of 600 patients affected of myocardial infarction only 17% received acetyl salicylic acid before the arrival to the hospital and 59.8% received this drug in the emergency room. The use of acetyl salicylic acid in patients affected of ischemic cardiopathy assisted in the emergency services of Spain is improperly low.

  1. The Aspirin Foundation Scientific Conference: the history, the present state and the future of aspirin prophylaxis

    OpenAIRE

    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 pot...

  2. Determinants of reduced antiplatelet effect of aspirin in patients with stable coronary artery disease.

    Science.gov (United States)

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

    2015-01-01

    Aspirin is a cornerstone in management of coronary artery disease (CAD). However, considerable variability in the antiplatelet effect of aspirin has been reported. To investigate independent determinants of reduced antiplatelet effect of aspirin in stable CAD patients. 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. 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). 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.

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

    Science.gov (United States)

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

    2010-01-01

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

  4. Thromboxane Formation Assay to Identify High On-Treatment Platelet Reactivity to Aspirin.

    Science.gov (United States)

    Mohring, Annemarie; Piayda, Kerstin; Dannenberg, Lisa; Zako, Saif; Schneider, Theresa; Bartkowski, Kirsten; Levkau, Bodo; Zeus, Tobias; Kelm, Malte; Hohlfeld, Thomas; Polzin, Amin

    2017-01-01

    Platelet inhibition by aspirin is indispensable in the secondary prevention of cardiovascular events. Nevertheless, impaired aspirin antiplatelet effects (high on-treatment platelet reactivity [HTPR]) are frequent. This is associated with an enhanced risk of cardiovascular events. The current gold standard to evaluate platelet hyper-reactivity despite aspirin intake is the light-transmittance aggregometry (LTA). However, pharmacologically, the most specific test is the measurement of arachidonic acid (AA)-induced thromboxane (TX) B2 formation. Currently, the optimal cut-off to define HTPR to aspirin by inhibition of TX formation is not known. Therefore, in this pilot study, we aimed to calculate a TX formation cut-off value to detect HTPR defined by the current gold standard LTA. We measured platelet function in 2,507 samples. AA-induced TX formation by ELISA and AA-induced LTA were used to measure aspirin antiplatelet effects. TX formation correlated nonlinearly with the maximum of aggregation in the AA-induced LTA (Spearman's rho R = 0.7396; 95% CI 0.7208-0.7573, p < 0.0001). Receiver operating characteristic analysis and Youden's J statistics revealed 209.8 ng/mL as the optimal cut-off value to detect HTPR to aspirin with the TX ELISA (area under the curve: 0.92, p < 0.0001, sensitivity of 82.7%, specificity of 90.3%). In summary, TX formation ELISA is reliable in detecting HTPR to aspirin. The calculated cut-off level needs to be tested in trials with clinical end points. © 2017 S. Karger AG, Basel.

  5. How to test the effect of aspirin and clopidogrel in patients on dual antiplatelet therapy?

    Science.gov (United States)

    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.

  6. Reduced antiplatelet effect of aspirin during 24 hours in patients with coronary artery disease and type 2 diabetes.

    Science.gov (United States)

    Christensen, Kristian H; Grove, Erik L; Würtz, Morten; Kristensen, Steen D; Hvas, Anne-Mette

    2015-01-01

    Reduced antiplatelet effect of aspirin has been reported in patients with type 2 diabetes, and recent studies suggest that once-daily aspirin provides insufficient platelet inhibition. We investigated if the effect of aspirin declined during the 24-hour dosing interval in patients with coronary artery disease and type 2 diabetes, and whether this correlated with increased platelet turnover. Furthermore, the intra-individual variation in platelet aggregation was determined during a 28-day period. We included 47 patients with coronary artery disease and type 2 diabetes treated with aspirin 75 mg daily. Blood samples were obtained 1 and 24 hours after aspirin intake, and this was repeated three times with a 2-week interval between each visit. Platelet aggregation was evaluated by impedance aggregometry (Multiplate® Analyzer) using arachidonic acid (1.0 mM) and collagen (3.2 µg/ml) as agonists. Markers of platelet turnover were measured by flow cytometry. Compliance was confirmed by serum thromboxane B2. Platelet aggregation levels measured 1 and 24 hours after aspirin intake were compared using the mean of 1- and 24-hour measurements at the three study visits. The difference in platelet aggregation was 70 ± 97 AU × min (p aspirin intake (p values 0.06 and 0.07). Median intra-individual variation of platelet aggregation was 9-16%. Patients with coronary artery disease and type 2 diabetes had increased platelet aggregation at the end of the 24-hour aspirin dosing interval. Platelet turnover did not correlate significantly with residual platelet aggregation, although a trend was observed. The intra-individual variation of platelet aggregation after aspirin intake was low.

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

    Science.gov (United States)

    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…

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

    OpenAIRE

    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 C 18 (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 fo...

  9. Reduction of Platelet Aggregation From Ingestion of Oleic and Linoleic Acids Found in Vitis vinifera and Arachis hypogaea Oils.

    Science.gov (United States)

    Bazán-Salinas, Irma Leticia; Matías-Pérez, Diana; Pérez-Campos, Eduardo; Pérez-Campos Mayoral, Laura; García-Montalvo, Iván Antonio

    The purpose of this study was to evaluate the effect of the consumption of seed oils from Vitis vinifera and Arachis hypogaea in platelet aggregation. The initial hypothesis suggested that subjects who have consumed these seed oils undergo modified platelet aggregation. This study was performed using a pre-post test design, with a control group, and double blind. The effects of the consumption of grape seed and peanut oils were measured for platelet aggregation in clinical and laboratory tests in 30 healthy subjects. In addition to this group, a control group of 4 health subjects received no treatment with oils, just 500 mg oral administration acetylsalicylic acid for 7 days. Platelet aggregation was assessed by the Born turbidimetric method, using 3 different concentrations of adenosine diphosphate as agonists (2, 54; 1, 17; and 0, 58 μM). The study subjects had very similar results; both oils were shown to have a significant reduction in platelet aggregation. Grape seed oil showed a decrease of 8.4 ± 1% in aggregation, compared with peanut oil, which decreased aggregation by 10.4 ± 1%. The control group, taking 500 mg OD aspirin for 7 days, showed a significant decrease in platelet aggregation, similar to that of oil ingestion. Each of the oils was analyzed for fatty acids, to determine which particular acids were presents in greater levels, which could explain the reduction in platelet aggregation. The oil found to be most abundant in grape seeds was linoleic acid (omega-6), and in peanuts, it was oleic acid (omega-9). However, in fact, both acids reduced platelet aggregation. Consumption of plant oils from grape seeds and peanuts had a lowering effect on platelet aggregation, in addition to containing a high content of unsaturated fatty acids. However, omega-3, omega-6, and omega-9 fatty acids were not specifically responsible for the reductions mentioned above.

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

    Science.gov (United States)

    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. © 2014, The American College of Clinical Pharmacology.

  11. Aspirin

    Science.gov (United States)

    ... Circulation My alerts Sign In Join Sign out Facebook Twitter Home About this Journal Editorial Board General Statistics Circulation Doodle Information for Advertisers Author Reprints Commercial Reprints Customer Service and Ordering ...

  12. Aspirin

    Science.gov (United States)

    ... not make sense fear or nervousness dizziness double vision uncontrollable shaking of a part of the body confusion abnormally excited mood hallucination (seeing things or hearing voices that are not ...

  13. Low dose aspirin therapy and renal function in elderly patients

    Directory of Open Access Journals (Sweden)

    Akinwusi PO

    2013-01-01

    Full Text Available Patience Olayinka Akinwusi,1,2 Rotimi Oluyombo,2 Paul Sunday Ogunro,3 Adetunji Oladeni Adeniji,4 Oluyomi Olusola Okunola,5 Olugbenga Edward Ayodele21Department of Medicine, Osun State University, Osogbo, Osun State, Nigeria; 2Department of Medicine, LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria; 3Department of Chemical Pathology, LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria; 4Department of Obstetrics and Gynecology, LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria; 5Department of Medicine, Obafemi Awolowo University, Ile-Ife, Osun State, NigeriaPurpose: To determine whether low dose aspirin has any deleterious effects on renal function in elderly patients.Methods: We conducted a prospective pilot study of 30 Nigerians older than 60 years with various chronic ailments necessitating the use of low dose aspirin. Patients gave their consent, and institutional ethical clearance was obtained. Each patient's baseline samples at enrolment (before commencing aspirin use served as a control, and subsequent weekly samples were compared. The weekly mean of each parameter was calculated, and the differences of means from baseline were determined, and values were compared for statistical differences with the Statistical Package for the Social Sciences, version 16.Results: We found that a majority of patients (86.67% had basal renal functions at chronic kidney disease stages 1 and 2. When compared with the corresponding baseline parameters, the mean weekly serum and urinary electrolytes, urea, creatinine, and uric acid parameters did not change, and the P-value did not show any statistical significance. However, there was positive statistical significance for the creatinine clearance (P = 0.025. Also, unlike in previous studies, anemia and hypoalbuminemia did not affect the renal function parameters.Conclusion: This study did not show any deleterious effects with short-term, low dose (75 mg daily aspirin use on kidney functions in

  14. PEMBUATAN DAN UJI AKTIVITAS SEDIAAN UNGUENTA SCARLESS WOUND DENGAN EKSTRAK BINAHONG DAN ZAT AKTIF ASPIRIN

    Directory of Open Access Journals (Sweden)

    Maria Faustina Sari

    2015-11-01

    Full Text Available Wound is a defect of skin caused by physical or thermal damage. The inflammatory phase in the wound healing usually causes scars. Aspirin is a nonsteroidal anti-inflammatory drug (NSAID that has the ability to inhibit the activity of cyclooxygenase (COX leading to reduced prostaglandin amount. Binahong (Anredera cordifolia is one of the plants that is used as a wound healer. Binahong contains ascorbic acid which has an important role in collagen formation phase. In this study, binahong leaf extract ointment will be combined with aspirin to produce scarless wound ointment. The method used is a purely experimental method. The test method used is histopathology tests then processed by the method of calculating the area of collagen. The data are analyzed using T-test. The addition of aspirin in the preparation of wound healing ointment can’t reduce scar formation allegedly with an incision method of white mice (Mus musculus Swiss Webster. Statistically, the results showed that binahong ointment (UB produces the least scar than ointment base (B, followed binahong-aspirin ointment (UBA, and aspirin ointment (UA.

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Inhibitory Effect of Aspirin on Cholangiocarcinoma Cells

    Science.gov (United States)

    Boueroy, Parichart; Aukkanimart, Ratchadawan; Boonmars, Thidarut; Sriraj, Pranee; Ratanasuwan, Panaratana; Juasook, Amornrat; Wonkchalee, Nadchanan; Vaeteewoottacharn, Kulthida; Wongkham, Sopit

    2017-11-26

    Aspirin and other non-steroidal anti-inflammatory drugs reduce the risk of cancer due to their anti-proliferative and apoptotic effects, which are the important mechanisms for their anti-tumor activity. Here, the effect of aspirin on human cholangiocarcinoma cells (KKU-214) and the underlying mechanisms of its action were explored. Cell proliferation was measured by sulforhodamine B (SRB) assay, while cell cycle distribution and apoptosis were determined by flow cytometry. Western blotting was used to explore protein expression underlying molecular mechanisms of anti-cancer treatment of aspirin. Aspirin reduced cell proliferation in a dose- and time-dependent manner, and altered the cell cycle phase distribution of KKU-214 cells by increasing the proportion of cells in the G0/G1 phase and reducing the proportion in the S and G2/M phases. Consistent with its effect on the cell cycle, aspirin also reduced the expression of cyclin D1 and cyclin‑dependent kinase 4 (Cdk-4), which are important for G0/G1 cell cycle progression. Treatment with aspirin led to increased induction of apoptosis in a dose-dependent manner. Further analysis of the mechanism underlying the effect of this drug showed that aspirin induced the expression of the tumor-suppressor protein p53 while inhibiting the anti-apoptotic protein B‑cell lymphoma-2 (Bcl-2). Correspondingly, the activation of caspase-9 and -3 was also increased. These findings suggest that aspirin causes cell cycle arrest and apoptosis, both of which could contribute to its anti-proliferative effect. Creative Commons Attribution License

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

    Science.gov (United States)

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

    2016-01-01

    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. 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. 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. 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.

  18. 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.

    Science.gov (United States)

    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. © 2015, The American College of Clinical Pharmacology.

  19. Inactivation of ovine cyclooxygenase-1 by bromoaspirin and aspirin: a quantum chemistry description.

    Science.gov (United States)

    Barroso-Neto, Ito L; Marques, João Paulo C; da Costa, Roner F; Caetano, Ewerton W S; Cavada, Benildo S; Gottfried, Carmem; Freire, Valder N

    2012-03-15

    The resulting noncovalent bonding of the salicylic acid to ovine COX-1 after bromoaspirin and aspirin acetylation by Ser530 is investigated within the scope of density functional theory considering a 6.5 Å radius binding pocket. We have not only took full advantage of published X-ray structural data for the ovine COX-1 cocrystallized with bromoaspirin, but we also have improved that data through computation, finding good estimates for the hydrogen atom positions at the residues of the binding pocket, and repositioning the Ser530Ac[Br;H] lateral chain and salicylic acid by total energy minimization procedures employing LDA and GGA+D exchange-correlation functionals. Using bromoaspirin as a template, we have simulated the positioning of aspirin in the binding pocket, estimating its interaction energy with each of its neighbor COX-1 residues. We demonstrate that the binding energies of bromoaspirin and aspirin to COX-1 are very close when second-order quantum refinements of the structural data are performed, which points to an explanation on why the IC(50) values for the 126 μM COX-1 activity of both bromoaspirin and aspirin are practically the same. Attracting and repelling residues were identified, being shown that Arg120 is the most effective residue attracting the salicylic acid, followed by Ala527, Leu531, Leu359, and Ser353. On the other hand, Glu524 was found the most effective repulsive residue (strength interaction comparable to Arg120). © 2012 American Chemical Society

  20. High dose aspirin and left ventricular remodeling after myocardial infarction: aspirin and myocardial infarction.

    Science.gov (United States)

    Adamek, Anna; Hu, Kai; Bayer, Barbara; Wagner, Helga; Ertl, Georg; Bauersachs, Johann; Frantz, Stefan

    2007-07-01

    Proinflammatory proteins like inflammatory cytokines are implicated in myocardial depression and left ventricular remodeling after myocardial infarction. High-dose aspirin inhibits cytokine activation. Therefore, we tested the influence of high-dose aspirin treatment on left ventricular remodeling in mice after myocardial infarction. Mice were treated for 4 weeks with placebo or aspirin (120 mg/kg per day) by Alzet mini-osmotic pumps after ligation of the left anterior descending coronary artery. Serial transthoracic echocardiography was performed at days 1, 7, and 28. Over the 4 weeks, mortality was not different between the groups (placebo 30.8%, aspirin 30.8%). On echocardiography, animals after myocardial infarction exhibited left ventricular dilatation (week 4, end-systolic area, placebo sham 8.9 +/- 1.7 vs. placebo MI 15.9 +/- 2.5 mm(2)), which was not changed by aspirin treatment (week 4, end-systolic area, aspirin MI 14.5 +/- 1.3 mm(2), p= ns vs. placebo MI). The expression of the proinflammatory cytokines TNF and IL-1beta were markedly upregulated in mice with myocardial infarction on placebo. Cytokine expression was significantly reduced by aspirin treatment while collagen deposition was not influenced. Continuous aspirin treatment (120 mg/kg/d) reduces the expression of proinflammatory cytokines after myocardial infarction, but does not affect post-infarct cardiac remodeling and cardiac function.

  1. Is clopidogrel better than aspirin following breakthrough strokes while on aspirin? A retrospective cohort study

    Science.gov (United States)

    Lee, Meng; Wu, Yi-Ling; Saver, Jeffrey L; Lee, Hsuei-Chen; Lee, Jiann-Der; Chang, Ku-Chou; Wu, Chih-Ying; Lee, Tsong-Hai; Wang, Hui-Hsuan; Rao, Neal M; Ovbiagele, Bruce

    2014-01-01

    Objective There is insufficient evidence on which to base a recommendation for optimal antiplatelet therapy following a stroke while on aspirin. The objective was to compare clopidogrel initiation vs aspirin reinitiation for vascular risk reduction among patients with ischaemic stroke on aspirin at the time of their index stroke. Design Retrospective. Setting We conducted a nationwide cohort study by retrieving all hospitalised patients (≥18 years) with a primary diagnosis of ischaemic stroke between 2003 and 2009 from Taiwan National Health Insurance Research Database. Participants Among 3862 patients receiving aspirin before the index ischaemic stroke and receiving either aspirin or clopidogrel after index stroke during follow-up period, 1623 were excluded due to a medication possession ratio aspirin was prescribed during the follow-up period. Follow-up was from time of the index stroke to admission for recurrent stroke or myocardial infarction, death or the end of 2010. Primary and secondary outcome measures The primary end point was hospitalisation due to a new-onset major adverse cardiovascular event (MACE: composite of any stroke or myocardial infarction). The leading secondary end point was any recurrent stroke. Results Compared to aspirin, clopidogrel was associated with a lower occurrence of future MACE (HR=0.54, 95% CI 0.43 to 0.68, paspirin, clopidogrel initiation was associated with fewer recurrent vascular events than aspirin reinitiation. PMID:25468508

  2. Dietary non-nutrients and haemostasis in humans : effects of salicylates, flavonoids and ginger

    NARCIS (Netherlands)

    Janssen, P.L.T.M.K.

    1997-01-01

    In this thesis we studied the content of acetylsalicylate and total salicylates in foods, and we studied the effects of the dietary non-nutrients salicylates and flavonoids and of certain foods on haemostatic parameters in humans.

    Acetylsalicylic acid -aspirin- irreversibly inhibits

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

    Science.gov (United States)

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

    2016-08-01

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

  4. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial.

    Science.gov (United States)

    Halkes, P H A; van Gijn, J; Kappelle, L J; Koudstaal, P J; Algra, A

    2006-05-20

    Results of trials of aspirin and dipyridamole combined versus aspirin alone for the secondary prevention of vascular events after ischaemic stroke of presumed arterial origin are inconsistent. Our aim was to resolve this uncertainty. We did a randomised controlled trial in which we assigned patients to aspirin (30-325 mg daily) with (n=1363) or without (n=1376) dipyridamole (200 mg twice daily) within 6 months of a transient ischaemic attack or minor stroke of presumed arterial origin. Our primary outco