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Sample records for aspirin esterase activity

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

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    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.

  2. Distribution of esterase activity in porcine ear skin, and the effects of freezing and heat separation.

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    Lau, Wing Man; Ng, Keng Wooi; Sakenyte, Kristina; Heard, Charles M

    2012-08-20

    Porcine ear skin is widely used to study skin permeation and absorption of ester compounds, whose permeation and absorption profiles may be directly influenced by in situ skin esterase activity. Importantly, esterase distribution and activity in porcine ear skin following common protocols of skin handling and storage have not been characterised. Thus, we have compared the distribution and hydrolytic activity of esterases in freshly excised, frozen, heated and explanted porcine ear skin. Using an esterase staining kit, esterase activity was found to be localised in the stratum corneum and viable epidermis. Under frozen storage and a common heating protocol of epidermal sheet separation, esterase staining in the skin visibly diminished. This was confirmed by a quantitative assay using HPLC to monitor the hydrolysis of aspirin, in freshly excised, frozen or heated porcine ear skin. Compared to vehicle-only control, the rate of aspirin hydrolysis was approximately three-fold higher in the presence of freshly excised skin, but no different in the presence of frozen or heated skin. Therefore, frozen and heat-separated porcine ear skin should not be used to study the permeation of ester-containing permeants, in particular co-drugs and pro-drugs, whose hydrolysis or degradation can be modulated by skin esterases. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Phenol esterase activity of porcine skin.

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    Laszlo, Joseph A; Smith, Leslie J; Evans, Kervin O; Compton, David L

    2015-01-01

    The alkyl esters of plant-derived phenols may serve as slow-release sources for cutaneous delivery of antioxidants. The ability of skin esterases to hydrolyze phenolic esters was examined. Esters of tyrosol and hydroxytyrosol were prepared from decanoic and lipoic acids. Ferulic acid was esterified with octadecanol, glycerol, and dioleoylglycerol. These phenolic derivatives were treated in taurodeoxycholate microemulsion and unilamellar liposomes with ex vivo porcine skin and an aqueous extract of the skin. Extracted esterases hydrolyzed the microemulsions at rates in the order: tyrosyl lipoate > tyrosyl decanoate > hydroxytyrosyl lipoate > hydroxytyrosyl decanoate. The tyrosyl decanoate was subject to comparatively little hydrolysis (10-30% after 24h) when incorporated into liposomes, while hydroxytyrosyl decanoate in liposomes was not hydrolyzed at all by the skin extract. Ferulate esters were not hydrolyzed by the extract in aqueous buffer, microemulsion, nor liposomes. Tyrosyl decanoate applied topically to skin explants in microemulsion were readily hydrolyzed within 4h, while hydrolysis was minimal when applied in liposomes. These findings indicate that porcine skin displays a general esterase activity toward medium-chain esters of tyrosol and hydroxytyrosol, which can be moderated by the physiochemical properties of the lipid vehicle, but no feruloyl esterase activity. Published by Elsevier B.V.

  4. Characterization and distribution of esterase activity in activated sludge

    NARCIS (Netherlands)

    Boczar, BA; Forney, LJ; Begley, WM; Larson, RJ; Federle, TW

    2001-01-01

    The location and activity of esterase enzymes in activated Sludge from three Municipal wastewater treatment plants were characterized using model Substrate, and denaturing and nondenaturing polyacrylamide gel electrophoresis (PAGE) Of particulate, freeze thaw (primarily periplasmic enzymes and those

  5. Serum aspirin esterase is strongly associated with glucose and lipids in healthy subjects: different association patterns in subjects with type 2 diabetes mellitus

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    Kotani Kazuhiko

    2010-07-01

    Full Text Available Abstract Background Aspirin esterase (AE activity can account for part of aspirin pharmacokinetics in the circulation, possibly being associated with the impairment of aspirin effectiveness as an inhibitor of platelet aggregation. Aims The study was aimed at investigating the correlations of serum AE activity with cholinesterase (ChE and metabolic variables in healthy subjects in comparison to subjects with type 2 diabetes mellitus (T2DM. Methods In cardiovascular disease-free T2DM subjects and healthy controls, the AE activity levels and/or the correlation patterns between AE and the other variables were analyzed. Results Neither AE nor ChE activities were higher in the subjects with T2DM. Serum AE activity strongly correlated with ChE as well as glucose/lipids variables such as total cholesterol and triglyceride in healthy subjects, while the correlations between AE and glucose/lipids variables were not present in T2DM subjects. Conclusions These data may reflect the pathophysiological changes between healthy and T2DM subjects. Our data may thus provide the basis for future studies to unravel the mechanisms.

  6. Characterization of esterase activity in Geobacillus sp. HBB-4.

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    Metin, Kubilay; Burcu Bakir Ateslier, Z; Basbulbul, Gamze; Halil Biyik, H

    2006-01-01

    A thermophilic esterase producing bacterium (Bacillus sp. 4), recently isolated from Alangüllü thermal spring in Aydin (Turkey), was analyzed using 16S rRNA and classified as Geobacillus sp. HBB-4, most closely related to Bacillus sp. BGSC W9A59 (0.70% sequence divergence) which belongs to the newly described genus Geobacillus. The effects of several chemicals on the activity of thermostable esterase from Geobacillus sp. HBB-4 were examined. Among the various metal ions tested, esterase activity was enhanced by Mn(+2) and Ni(+2), but was inhibited by Hg(+2) and Cu(+2), whereas Ca(+2), Mg(+2) and Co(+2) had no effect. In addition, other metal ions studied have caused a slight inhibition on the esterase activity. EDTA partially inhibited the HBB-4 esterase. The activator metal ions, Mn(+2) and Ni(+2) have restored partial inhibition of EDTA. The activity of HBB-4 esterase was inhibited by ionic detergents while non-ionic detergents activated the enzyme. However, a zwitterionic detergent, CHAPS, has caused a slight inhibition in the enzyme activity. HBB-4 esterase activity was inhibited at the high concentrations of all the organic solvents tested in the present study. However, 50% final concentration of DMSO increased the enzyme activity about 7%. The HBB-4 esterase has shown more than about 50% of activity in the presence of ethanol and methanol solutions. These characteristics of the enzyme along with its significant thermostability make the Geobacillus sp. HBB-4 esterase a potent candidate for future industrial applications.

  7. Human serum albumin nanotubes with esterase activity.

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    Komatsu, Teruyuki; Sato, Takaaki; Boettcher, Christoph

    2012-01-02

    A nanocylindrical wall structure was obtained by layer-by-layer (LbL) assembly of poly-L-arginine (PLA) and human serum albumin (HSA) and characterized by scanning electron microscopy (SEM), scanning force microscopy (SFM), and cryogenic transmission electron microscopy (cryo-TEM). SEM and SFM measurements of a lyophilized powder of (PLA/HSA)(3) nanotubes yielded images of round, chimney-like architectures with approximately 100 nm wall thickness. Cryo-TEM images of the hydrated sample revealed that the tube walls are composed of densely packed HSA molecules. Moreover, when small-angle X-ray scattering was used to characterize the individual PLA and HSA components in aqueous solutions, maximum diameters of approximately 28 nm and 8 nm were obtained, respectively. These values indicate the minimum thickness of wall layers consisting of PLA and HSA. It can also be concluded from SEM as well as from cryo-TEM images that the protein cylinders are considerably swollen in the presence of water. Furthermore, HSA retains esterase activity if assembled in nanotubes, as indicated by measurements of para-nitrophenyl acetate hydrolysis under semi-physiological conditions (pH 7.4, 22 °C). The enzyme activity parameters (Michaelis constant, K(m), and catalytic constant, k(cat)) were comparable to those of free HSA. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Alicyclobacillus acidocaldarius Thermophilic Esterase EST2's Activity in Milk and Cheese Models

    NARCIS (Netherlands)

    Mandrich, L.; Manco, M.; Rossie, M.; Floris, E.; Jansen-van den Bosch, T.; Smit, G.; Wouters, J.A.

    2006-01-01

    The aim of this work was to investigate the behavior of thermophilic esterase EST2 from Alicyclobacillus acidocaldarius in milk and cheese models. The pure enzyme was used to compare the EST2 hydrolytic activity to the activity of endogenous esterase EstA from Lactococcus lactis. The results

  9. Esterase activity able to hydrolyze dietary antioxidant hydroxycinnamates is distributed along the intestine of mammals

    DEFF Research Database (Denmark)

    Andreasen, Mette Findal; Kroon, P A; Williamson, G

    2001-01-01

    Hydroxycinnamic acids are effective antioxidants and are abundant components of plant cell walls, especially in cereal bran. For example, wheat and rye brans are rich sources of the hydroxycinnamates ferulic acid, sinapic acid, and p-coumaric acid. These phenolics are part of human and animal diets...... and may contribute to the beneficial effects derived from consumption of cereal bran. However, these compounds are ester linked to the main polymers in the plant cell wall and cannot be absorbed in this complex form. The present work shows that esterases with activity toward esters of the major dietary...... from human duodenum, jejunum, and ileum efficiently hydrolyzed various hydroxycinnamoyl esters, providing the first evidence of human cinnamoyl esterase(s). This study first demonstrates the release by human colonic esterase(s) (mostly of microbial origin) of sinapic acid and p-coumaric acid from rye...

  10. A Novel Cold Active Esterase from a Deep Sea Sponge Stelletta normani Metagenomic Library

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    Erik Borchert

    2017-09-01

    Full Text Available Esterases catalyze the hydrolysis of ester bonds in fatty acid esters with short-chain acyl groups. Due to the widespread applications of lipolytic enzymes in various industrial applications, there continues to be an interest in novel esterases with unique properties. Marine ecosystems have long been acknowledged as a significant reservoir of microbial biodiversity and in particular of bacterial enzymes with desirable characteristics for industrial use, such as for example cold adaptation and activity in the alkaline pH range. We employed a functional metagenomic approach to exploit the enzymatic potential of one particular marine ecosystem, namely the microbiome of the deep sea sponge Stelletta normani. Screening of a metagenomics library from this sponge resulted in the identification of a number of lipolytic active clones. One of these encoded a highly, cold-active esterase 7N9, and the recombinant esterase was subsequently heterologously expressed in Escherichia coli. The esterase was classified as a type IV lipolytic enzyme, belonging to the GDSAG subfamily of hormone sensitive lipases. Furthermore, the recombinant 7N9 esterase was biochemically characterized and was found to be most active at alkaline pH (8.0 and displays salt tolerance over a wide range of concentrations. In silico docking studies confirmed the enzyme's activity toward short-chain fatty acids while also highlighting the specificity toward certain inhibitors. Furthermore, structural differences to a closely related mesophilic E40 esterase isolated from a marine sediment metagenomics library are discussed.

  11. Multiple nucleophilic elbows leading to multiple active sites in a single module esterase from Sorangium cellulosum

    DEFF Research Database (Denmark)

    Udatha, D.B.R.K. Gupta; Madsen, Karina Marie; Panagiotou, Gianni

    2015-01-01

    was used to generate variants with deactivated nucleophilic elbows and the functional promiscuity was analyzed. In silico analysis together with enzymological characterization interestingly showed that each nucleophilic elbow formed a local active site with varied substrate specificities and affinities....... To our knowledge, this is the first report presenting the role of multiple nucleophilic elbows in the catalytic promiscuity of an esterase. Further structural analysis at protein unit level indicates the new evolutionary trajectories in emerging promiscuous esterases....

  12. Impaired liver cytochrome P450 2C11 activity after dual antiplatelet therapy with aspirin and clopidogrel in rats.

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    Qian, Chenyu; Luo, Xi; Yang, Mengbi; Jin, Jing; Zuo, Zhong

    2018-01-10

    1. Aspirin (ASA) and clopidogrel (CLP) are used in combination as dual antiplatelet therapy (DAPT) for acute coronary syndrome based on their complementary mechanisms for platelet aggregation inhibition. However, the pharmacokinetics of such drug combination usage has not been thoroughly investigated. 2. In the current study, an LC-MS/MS method was developed to simultaneously determine the plasma concentrations of ASA and its metabolite salicylic acid (SA) with CLP and its metabolites, clopidogrel carboxylic acid (CLPM) and clopidogrel active metabolite derivative (CAMD). The pharmacokinetics of ASA, SA, CLP, CLPM and CAMD in rats receiving two-week DAPT with ASA and CLP were then determined. 3. After two-week DAPT with ASA and CLP in rats, the activities of aspirin esterase and rCyp2c11, enzymes mediating rat metabolism of ASA and CLP, respectively, in prepared rat liver microsomes were measured followed by further determination of rCyp2c11 mRNA expressions. The results demonstrated that DAPT led to minimal impact on aspirin esterase activity but significant decrease in rCyp2c11 activity and mRNA expression. 4. In conclusion, our findings on impairment in rCyp2C11 activity and mRNA expression by DAPT in rats could provide guidance on its safe clinical use with other CYP 2C19 substrates.

  13. Characterization of esterase activity in the Bianchetta trevigiana grape variety under reducing conditions

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    Lomolino G

    2012-10-01

    Full Text Available Giovanna Lomolino, Anna LanteDepartment of Agronomy Food Natural Resources Animals and Environment, Agripolis, Università di Padova Viale dell'Università, Padova, ItalyBackground and methods: While extensive research has been carried out on the enzymes responsible for ester synthesis and hydrolysis by wine strains of Saccharomyces cerevisiae, grape esterase activity is limited. In this study, the autochthonous grape variety, Bianchetta trevigiana, widespread in the Prosecco wine production area of Treviso, Conegliano, and Asolo, Italy, was characterized according to its esterase activity. Because grape skin is very rich in compounds which impart qualitative characteristics to wine, the study of esterase was carried out on this part of the fruit.Results: During enzyme extraction from grape skin, the presence of the reducing agent, β-mercaptoethanol, allowed a better protein yield but reduced esterase activity. Further addition of increasing doses of reducing agents to grape skin protein extract, such as of K2S2O5 (used in winemaking and DTT, reduced or inhibited esterase activity. Even though the zymographic profiles of the extracts obtained with and without β-mercaptoethanol were qualitatively equal, the intensity of enzymatic bands, measured by densitometry, was different.Conclusion: The presence of reducing agents affected the activity of grape skin esterase, and given that this enzyme is involved in the hydrolysis and synthesis of esters, which are important compounds responsible for the flavor of wine, addition of reducing agents could affect the aromatic profile of wine.Keywords: esterase, grape, reducing agent, wine

  14. Esterase Active in Polar Organic Solvents from the Yeast Pseudozyma sp. NII 08165

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    Deepthy Alex

    2014-01-01

    Full Text Available Esterases/lipases active in water miscible solvents are highly desired in biocatalysis where substrate solubility is limited and also when the solvent is desired as an acyl acceptor in transesterification reactions, as with the case of biodiesel production. We have isolated an esterase from the glycolipid producing yeast-Pseudozyma sp. NII 08165 which in its crude form was alkali active, thermo stable, halo tolerant and also capable of acting in presence of high methanol concentration. The crude enzyme which maintained 90% of its original activity after being treated at 70°C was purified and the properties were characterized. The partially purified esterase preparation had temperature and pH optima of 60°C and 8.0 respectively. The enzyme retained almost complete activity in presence of 25% methanol and 80% activity in the same strength of ethanol. Conditions of enzyme production were optimized, which lead to 9 fold increase in the esterase yield. One of the isoforms of the enzyme LIP1 was purified to homogeneity and characterized. Purified LIP1 had a Km and Vmax of 0.01 and 1.12, respectively. The purified esterase lost its thermo and halo tolerance but interestingly, retained 97% activity in methanol.

  15. Organophosphate and pyrethroid hydrolase activities of mutant Esterases from the cotton bollworm Helicoverpa armigera.

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    Li, Yongqiang; Farnsworth, Claire A; Coppin, Chris W; Teese, Mark G; Liu, Jian-Wei; Scott, Colin; Zhang, Xing; Russell, Robyn J; Oakeshott, John G

    2013-01-01

    Two mutations have been found in five closely related insect esterases (from four higher Diptera and a hymenopteran) which each confer organophosphate (OP) hydrolase activity on the enzyme and OP resistance on the insect. One mutation converts a Glycine to an Aspartate, and the other converts a Tryptophan to a Leucine in the enzymes' active site. One of the dipteran enzymes with the Leucine mutation also shows enhanced activity against pyrethroids. Introduction of the two mutations in vitro into eight esterases from six other widely separated insect groups has also been reported to increase substantially the OP hydrolase activity of most of them. These data suggest that the two mutations could contribute to OP, and possibly pyrethroid, resistance in a variety of insects. We therefore introduced them in vitro into eight Helicoverpa armigera esterases from a clade that has already been implicated in OP and pyrethroid resistance. We found that they do not generally enhance either OP or pyrethroid hydrolysis in these esterases but the Aspartate mutation did increase OP hydrolysis in one enzyme by about 14 fold and the Leucine mutation caused a 4-6 fold increase in activity (more in one case) of another three against some of the most insecticidal isomers of fenvalerate and cypermethrin. The Aspartate enzyme and one of the Leucine enzymes occur in regions of the H. armigera esterase isozyme profile that have been previously implicated in OP and pyrethroid resistance, respectively.

  16. Organophosphate and pyrethroid hydrolase activities of mutant Esterases from the cotton bollworm Helicoverpa armigera.

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    Yongqiang Li

    Full Text Available Two mutations have been found in five closely related insect esterases (from four higher Diptera and a hymenopteran which each confer organophosphate (OP hydrolase activity on the enzyme and OP resistance on the insect. One mutation converts a Glycine to an Aspartate, and the other converts a Tryptophan to a Leucine in the enzymes' active site. One of the dipteran enzymes with the Leucine mutation also shows enhanced activity against pyrethroids. Introduction of the two mutations in vitro into eight esterases from six other widely separated insect groups has also been reported to increase substantially the OP hydrolase activity of most of them. These data suggest that the two mutations could contribute to OP, and possibly pyrethroid, resistance in a variety of insects. We therefore introduced them in vitro into eight Helicoverpa armigera esterases from a clade that has already been implicated in OP and pyrethroid resistance. We found that they do not generally enhance either OP or pyrethroid hydrolysis in these esterases but the Aspartate mutation did increase OP hydrolysis in one enzyme by about 14 fold and the Leucine mutation caused a 4-6 fold increase in activity (more in one case of another three against some of the most insecticidal isomers of fenvalerate and cypermethrin. The Aspartate enzyme and one of the Leucine enzymes occur in regions of the H. armigera esterase isozyme profile that have been previously implicated in OP and pyrethroid resistance, respectively.

  17. Studies on the oxidizing system in Holt's medium for histochemical demonstration of esterase activity

    DEFF Research Database (Denmark)

    Kirkeby, S; Blecher, S R

    1978-01-01

    are used as oxidizing agents in the incubation medium. The intensity of the coloured reaction product is increased when cobalt or manganese are added to the incubation medium. Activity is depressed by high concentrations of FFC when resent in incubation medium or preincubational buffer only. Epididymis...... cells contain an esterase activity which is not inhibited by conventional SH blocking agents, nor by high concentrations of FFC. From these results it appears that the mode of action of FFC in Holt's medium is as follows. At low concentrations FFC appears to act primarily as a catalytic agent...... in oxidation of indoxyl to indigoid. At high concentration FFC acts as an inhibitor of guinea-pig thyroid esterase, by oxidation of SH groups in the active centre. The esterase of mouse epididymis cell type EH 1 is not subject to this inhibition by FFC, presumably because it does not contain accessible SH...

  18. Mechanistic Explanation of the Weak Carbonic Anhydrase’s Esterase Activity

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    Paolo Piazzetta

    2017-06-01

    Full Text Available In order to elucidate the elementary mechanism of the promiscuous esterase activity of human carbonic anhydrase (h-CA, we present an accurate theoretical investigation on the hydrolysis of fully-acetylated d-glucose functionalized as sulfamate. This h-CA’s inhibitor is of potential relevance in cancer therapy. The study has been performed within the framework of three-layer ONIOM (QM-high:QM’-medium:MM-low hybrid approach. The computations revealed that the hydrolysis process is not energetically favored, in agreement with the observed weak carbonic anhydrase’s esterase activity.

  19. Esterase and protease activities of Bacillus spp. from afitin, iru and ...

    African Journals Online (AJOL)

    The electrophoretic profiles of fermented African locust bean protein (ALBP), using strains presenting the highest protease activities in casein agar, were analyzed by SDS-PAGE to select strains with good ability to be used as starter cultures. All the Bacillus spp. tested showed esterase activity against tributyrin with high ...

  20. Cholesterol esterase inhibitory activity of bioactives from leaves of Mangifera indica L.

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    Gururaja, G M; Mundkinajeddu, Deepak; Dethe, Shekhar M; Sangli, Gopala K; Abhilash, K; Agarwal, Amit

    2014-01-01

    In the earlier studies, methanolic extract of Mangifera indica L leaf was exhibited hypocholesterol activity. However, the bioactive compounds responsible for the same are not reported so far. To isolate the bioactive compounds with hypocholesterol activity from the leaf extract using cholesterol esterase inhibition assay which can be used for the standardization of extract. The leaf methanolic extract of M. indica (Sindoora variety) was partitioned with ethyl acetate and chromatographed on silica gel to yield twelve fractions and the activity was monitored by using cholesterol esterase inhibition assay. Active fractions were re-chromatographed to yield individual compounds. A major compound mangiferin present in the extract was screened along with other varieties of mango leaves for cholesterol esterase inhibition assay. However, the result indicates that compounds other than mangiferin may be active in the extract. Invitro pancreatic cholesterol esterase inhibition assay was used for bioactivity guided fractionation (BAGF) to yield bioactive compound for standardization of extract. Bioactivity guided fractionation afford the active fraction containing 3b-taraxerol with an IC50 value of 0.86μg/ml. This study demonstrates that M. indica methanol extract of leaf have significant hypocholesterol activity which is standardized with 3b-taraxerol, a standardized extract for hypocholesterol activity resulted in development of dietary supplement from leaves of Mangifera indica.

  1. The effect of EDTA and metal cations on the 5-bromoindoxyl acetate esterase activity in the thyroid of the guinea pig

    DEFF Research Database (Denmark)

    Kirkeby, S

    1976-01-01

    Miscellaneous metal cations and EDTA have been used as activators and inhibitors of esterase activity in the thyroid of the guinea-pig. The results indicate that the 5-bromoiondoxyl acetate esterase in the epithelial cells probably consists of two different A-esterase isoenzymes, one present in g...... in group I cells. EDTA and Mn2+, on the other hand, activated the esterase activity in group II cells....

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

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    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.

  3. Mechanism-Guided Discovery of an Esterase Scaffold with Promiscuous Amidase Activity

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    Charlotte Kürten

    2016-06-01

    Full Text Available The discovery and generation of biocatalysts with extended catalytic versatilities are of immense relevance in both chemistry and biotechnology. An enhanced atomistic understanding of enzyme promiscuity, a mechanism through which living systems acquire novel catalytic functions and specificities by evolution, would thus be of central interest. Using esterase-catalyzed amide bond hydrolysis as a model system, we pursued a simplistic in silico discovery program aiming for the identification of enzymes with an internal backbone hydrogen bond acceptor that could act as a reaction specificity shifter in hydrolytic enzymes. Focusing on stabilization of the rate limiting transition state of nitrogen inversion, our mechanism-guided approach predicted that the acyl hydrolase patatin of the α/β phospholipase fold would display reaction promiscuity. Experimental analysis confirmed previously unknown high amidase over esterase activity displayed by the first described esterase machinery with a protein backbone hydrogen bond acceptor to the reacting NH-group of amides. The present work highlights the importance of a fundamental understanding of enzymatic reactions and its potential for predicting enzyme scaffolds displaying alternative chemistries amenable to further evolution by enzyme engineering.

  4. Effect of selenium on cadmium-induced oxidative stress and esterase activity in rat organs

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    Kevin Dzobo

    2013-05-01

    Full Text Available Metal toxicity is a threat mainly in the industrialised world where industry discharges many toxic metals into the environment. We investigated the effects of two metals cadmium and selenium on the cytosolic antioxidant enzymes and esterases in the liver, kidneys and testes of rats. Male Sprague-Dawley rats (n=28 were divided equally into four groups: control, cadmium, selenium and cadmium/selenium. Salts of the metals were administered intraperitoneally for 15 days. In the liver, cadmium treatment (1.67 mg/kg per day resulted in a decrease in catalase activity and an increase superoxide dismutase (SOD activity. Selenium treatment (0.23 mg/kg per day resulted in increases in glutathione s-transferase, catalase and DT-diaphorase activities. Treatment with both cadmium and selenium resulted in an increase in glutathione peroxidase (GPx activity. Esterase activities were significantly lower in the presence of cadmium. In the kidney, cadmium treatment caused a decrease in catalase, DT-diaphorase, and SOD activities and selenium supplementation reversed the cadmium-induced decrease in these enzyme activities. Selenium treatment increased catalase and SOD activities in the kidney. In the testis, cadmium treatment decreased GPx and SOD activities, but at the same time increased catalase and DT-diaphorase activities. Esterase activities increased in the presence of selenium in both the kidney and testis. These results suggest that selenium might be toxic to the liver while at the same time play a protective role against cadmium-induced oxidative stress and toxicity in the kidney and testis.

  5. Characterization of digestive gland esterase-lipase activity of juvenile redclaw crayfish Cherax quadricarinatus.

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    López-López, Silverio; Nolasco, Héctor; Vega-Villasante, Fernando

    2003-06-01

    Investigation of esterase-lipase activity in the digestive gland of redclaw crayfish Cherax quadricarinatus showed that the optimum enzyme activity occurred between 35 and 40 degrees C, with 100 mM NaCl at pH 8.5. Heavy metals completely inhibited and calcium ions partially inhibited enzyme activity. The enzyme activity diminished as the length of the fatty acid chain of substrates increased. Molecular masses for four isozymes were 43, 46, 63 and 118 kDa, respectively, as determined by PAGE.

  6. Glucose-aspirin: Synthesis and in vitro anti-cancer activity studies.

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    Jacob, James N; Tazawa, Makio J

    2012-05-01

    Glucose-aspirin (GA) was synthesized by conjugating aspirin (ASA) to glucose. The water solubility and biological activity of GA was studied in comparison to aspirin. The human serum protease activity on the ester showed a slower hydrolysis rate, compared to ASA. Glucose-aspirin was sevenfold more water soluble than aspirin and it was about 8- to 9-fold more active in inhibiting cell growth than aspirin in their anti-cancer cell culture activity on breast (SKBR3), pancreatic (PANC-1), and prostate (PC3) cell lines, whereas the activity was similar on a benign non-cancerous cell line (WI 38). In conclusion, GA is a highly water soluble derivative of aspirin. Although the serum hydrolysis for GA was slower, there was significant anti-cancer activity at the doses studied under the experimental conditions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. A comparison between activities for non-specific esterases and esterproteases

    DEFF Research Database (Denmark)

    Kirkeby, S; Moe, D

    1988-01-01

    activity was located to all parts of the proximal tubule. In male kidneys, esterprotease activity was present in the 2nd segment of the convoluted tubule which is not connected to glomeruli and in the descending part of the proximal tubule. In female kidney only the descending part of the proximal tubule......Electrophoretic separation of non-specific esterases and esterproteases from kidney, lung, and liver have been carried out in polyacrylamide gels. By use of zone electrophoresis, isoelectric focusing, and 2-dimensional electrophoresis it was found that most of the esterprotease bands had the same...

  8. Serum Albumin Binding and Esterase Activity: Mechanistic Interactions with Organophosphates

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    Nikolay V. Goncharov

    2017-07-01

    Full Text Available The albumin molecule, in contrast to many other plasma proteins, is not covered with a carbohydrate moiety and can bind and transport various molecules of endogenous and exogenous origin. The enzymatic activity of albumin, the existence of which many scientists perceive skeptically, is much less studied. In toxicology, understanding the mechanistic interactions of organophosphates with albumin is a special problem, and its solution could help in the development of new types of antidotes. In the present work, the history of the issue is briefly examined, then our in silico data on the interaction of human serum albumin with soman, as well as comparative in silico data of human and bovine serum albumin activities in relation to paraoxon, are presented. Information is given on the substrate specificity of albumin and we consider the possibility of its affiliation to certain classes in the nomenclature of enzymes.

  9. Inactive methyl indole-3-acetic acid ester can be hydrolyzed and activated by several esterases belonging to the AtMES esterase family of Arabidopsis.

    Science.gov (United States)

    Yang, Yue; Xu, Richard; Ma, Choong-Je; Vlot, A Corina; Klessig, Daniel F; Pichersky, Eran

    2008-07-01

    The plant hormone auxin (indole-3-acetic acid [IAA]) is found both free and conjugated to a variety of carbohydrates, amino acids, and peptides. We have recently shown that IAA could be converted to its methyl ester (MeIAA) by the Arabidopsis (Arabidopsis thaliana) enzyme IAA carboxyl methyltransferase 1. However, the presence and function of MeIAA in vivo remains unclear. Recently, it has been shown that the tobacco (Nicotiana tabacum) protein SABP2 (salicylic acid binding protein 2) hydrolyzes methyl salicylate to salicylic acid. There are 20 homologs of SABP2 in the genome of Arabidopsis, which we have named AtMES (for methyl esterases). We tested 15 of the proteins encoded by these genes in biochemical assays with various substrates and identified several candidate MeIAA esterases that could hydrolyze MeIAA. MeIAA, like IAA, exerts inhibitory activity on the growth of wild-type roots when applied exogenously. However, the roots of Arabidopsis plants carrying T-DNA insertions in the putative MeIAA esterase gene AtMES17 (At3g10870) displayed significantly decreased sensitivity to MeIAA compared with wild-type roots while remaining as sensitive to free IAA as wild-type roots. Incubating seedlings in the presence of [(14)C]MeIAA for 30 min revealed that mes17 mutants hydrolyzed only 40% of the [(14)C]MeIAA taken up by plants, whereas wild-type plants hydrolyzed 100% of absorbed [(14)C]MeIAA. Roots of Arabidopsis plants overexpressing AtMES17 showed increased sensitivity to MeIAA but not to IAA. Additionally, mes17 plants have longer hypocotyls and display increased expression of the auxin-responsive DR5:beta-glucuronidase reporter gene, suggesting a perturbation in IAA homeostasis and/or transport. mes17-1/axr1-3 double mutant plants have the same phenotype as axr1-3, suggesting MES17 acts upstream of AXR1. The protein encoded by AtMES17 had a K(m) value of 13 microm and a K(cat) value of 0.18 s(-1) for MeIAA. AtMES17 was expressed at the highest levels in shoot

  10. Association of sick building syndrome with neuropathy target esterase (NTE) activity in Japanese.

    Science.gov (United States)

    Matsuzaka, Yasunari; Ohkubo, Tomoichi; Kikuti, Yukie Y; Mizutani, Akiko; Tsuda, Michio; Aoyama, Yoshiko; Kakuta, Kazuhiko; Oka, Akira; Inoko, Hidetoshi; Sakabe, Kou; Ishikawa, Satoshi; Kulski, Jerzy K; Kimura, Minoru

    2014-10-01

    Sick building syndrome (SBS) is a set of several clinically recognizable symptoms reported by occupants of a building without a clear cause. Neuropathy target esterase (NTE) is a membrane bound serine esterase and its reaction with organophosphates (OPs) can lead to OP-induced delayed neuropathy (OPIDN) and nerve axon degeneration. The aim of our study was to determine whether there was a difference in NTE activity in the peripheral blood mononuclear cells (PBMCs) of Japanese patients with SBS and healthy controls and whether PNPLA6 (alias NTE) gene polymorphisms were associated with SBS. We found that the enzymatic activity of NTE was significantly higher (P < 0.0005) in SBS patients compared with controls. Moreover, population with an AA genotype of a single nucleotide polymorphism (SNP), rs480208, in intron 21 of the PNPLA6 gene strongly reduced the activity of NTE. Fifty-eight SNP markers within the PNPLA6 gene were tested for association in a case-control study of 188 affected individuals and 401 age-matched controls. Only one SNP, rs480208, was statistically different in genotype distribution (P = 0.005) and allele frequency (P = 0.006) between the cases and controls (uncorrected for testing multiple SNP sites), but these were not significant by multiple corrections. The findings of the association between the enzymatic activity of NTE and SBS in Japanese show for the first time that NTE activity might be involved with SBS. Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.

  11. 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

  12. 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

  13. Inhibitory effects of four neonicotinoid active ingredients on acetylcholine esterase activity.

    Science.gov (United States)

    Győri, János; Farkas, Anna; Stolyar, Oksana; Székács, András; Mörtl, Mária; Vehovszky, Ágnes

    2017-12-01

    There is a great concern about the decline of pollinators, and neonicotinoids emerging bee disorders are assumed to play a significant role. Since changes in learning ability has been observed in honey bees exposed to some acetylcholine esterase (AChE) inhibitors, we therefore, tested in vitro the effect of four neonicotinoids on purified eel AChE. AChE activity was inhibited in a concentration-dependent manner, and calculated IC 50 values for thiamethoxam (IC 50 = 414 μM) and clothianidin (IC 50 = 160 μM) were found to be much higher compared to acetamiprid (IC 50 = 75.2 μM) and thiacloprid (IC 50 = 87.8 μM). The Lineweaver-Burk reciprocal plots for acetamiprid shows unchanged V max and increased K m values with inhibitor concentrations, while analysis of Michaelis-Menten plots shows predominantly competitive mechanism. The inhibition constant value (K i = 24.3 μM) indicates strong binding of the acetamiprid complex to AChE. Finally, the four tested neonicotinoids are not a uniform group regarding their blocking ability. Our results suggest a previously not established, direct AChE blocking mechanism of neonicotinoids tested, thus the neuronal AChE enzyme is likely among the direct targets of the neonicotinoid insecticides. We conclude, that these AChE inhibitory effects may also contribute to toxic effects on the whole exposed animal.

  14. Monitoring Lipase/Esterase Activity by Stopped Flow in a Sequential Injection Analysis System Using p-Nitrophenyl Butyrate

    Directory of Open Access Journals (Sweden)

    Jorge Pliego

    2015-01-01

    Full Text Available Lipases and esterases are biocatalysts used at the laboratory and industrial level. To obtain the maximum yield in a bioprocess, it is important to measure key variables, such as enzymatic activity. The conventional method for monitoring hydrolytic activity is to take out a sample from the bioreactor to be analyzed off-line at the laboratory. The disadvantage of this approach is the long time required to recover the information from the process, hindering the possibility to develop control systems. New strategies to monitor lipase/esterase activity are necessary. In this context and in the first approach, we proposed a lab-made sequential injection analysis system to analyze off-line samples from shake flasks. Lipase/esterase activity was determined using p-nitrophenyl butyrate as the substrate. The sequential injection analysis allowed us to measure the hydrolytic activity from a sample without dilution in a linear range from 0.05–1.60 U/mL, with the capability to reach sample dilutions up to 1000 times, a sampling frequency of five samples/h, with a kinetic reaction of 5 min and a relative standard deviation of 8.75%. The results are promising to monitor lipase/esterase activity in real time, in which optimization and control strategies can be designed.

  15. Inhibition of Activator Protein 1 Activity and Neoplastic Transformation by Aspirin*

    OpenAIRE

    Dong, Zigang; Huang, Chuanshu; Brown, Rhoderick E.; Ma, Wei-Ya

    1997-01-01

    Aspirin, along with its analgesic-antipyretic uses, is now also being considered for prevention of cardiovascular disease, cancer, and treatment of human immunodeficiency virus infection. Although many of aspirin's pharmacological actions are related to its ability to inhibit prostaglandin biosynthesis, some of its beneficial therapeutic effects are not completely understood. Transcription factor activator protein 1 (AP-1) is critical for the induction of neoplastic transformation and inducti...

  16. Feruloyl Esterase Activity from Coffee Pulp in Solid-State Fermentation

    Directory of Open Access Journals (Sweden)

    Gerardo Saucedo-Castañeda

    2011-01-01

    Full Text Available Hydroxycinnamic acids (HAs have a potential application in the food and pharmaceutical industry because they are rich in phenolics. Feruloyl esterases release phenolic compounds from plant cell walls. Coffee pulp is rich in HAs linked to polysaccharides. A solvent extraction of free HAs was performed with aqueous methanol (80 %. A response surface methodology was applied to optimise the extraction of these compounds from coffee pulp, and the best results were obtained at 56 °C for 34 min. Alkaline and acid hydrolyses were performed to evaluate the content of linked HAs. Treated (extracted coffee pulp was used to produce feruloyl esterases in solid-state fermentation by Aspergillus tamarii V12307, previously selected by a hydrolysis plate assay. Different dilutions of a culture medium were added to the coffee pulp, and the diluted medium with half the nutrients allowed for higher CO2 production. A specific growth rate (μCO2 of 0.25 h^–1 and a lag phase (tlag of 14.3 h were observed under the selected conditions. Finally, enzymatic activities were 14.0 and 10.8 nkat per g of dried matter when methyl and ethyl ferulate were used as substrates, respectively. Productivities (9.3 and 7.2 nkat per g of dried matter per day, respectively were higher when compared to other studies carried out in solid-state fermentation. Utilisation of coffee pulp for enzyme production improves the added value of this abundant by-product of the coffee industry.

  17. Esterase Isoenzyme Variants in Barley

    DEFF Research Database (Denmark)

    Hvid, S.; Nielsen, G.

    1977-01-01

    Gene symbols are proposed for 27 esterase isoenzyme alleles representing 10 loci in barley. Two new esterase loci, Est 9 and Est 10, each with an active and a silent allele, and three new alleles in previously described loci were found. A few chemical and physical characteristics of the different...

  18. Analysing deltamethrin susceptibility and pyrethroid esterase activity variations in sylvatic and domestic Triatoma infestans at the embryonic stage

    Directory of Open Access Journals (Sweden)

    Pablo Luis Santo-Orihuela

    2013-12-01

    Full Text Available The aim of the present work was to study the deltamethrin susceptibility of eggs from Triatoma infestans populations and the contribution of pyrethroid esterases to deltamethrin degradation. Insects were collected from sylvatic areas, including Veinte de Octubre and Kirus-Mayu (Bolivia and from domiciliary areas, including El Palmar (Bolivia and La Pista (Argentina. Deltamethrin susceptibility was determined by dose-response bioassays. Serial dilutions of deltamethrin (0.0005-1 mg/mL were topically applied to 12-day-old eggs. Samples from El Palmar had the highest lethal dose ratio (LDR value (44.90 compared to the susceptible reference strain (NFS, whereas the Veinte de Octubre samples had the lowest value (0.50. Pyrethroid esterases were evaluated using 7-coumaryl permethrate (7-CP on individually homogenised eggs from each population and from NFS. The El Palmar and La Pista samples contained 40.11 and 36.64 pmol/min/mg protein, respectively, and these values were statistically similar to NFS (34.92 pmol/min/mg protein and different from Kirus-Mayu and Veinte de Octubre (27.49 and 22.69 pmol/min/mg protein, respectively. The toxicological data indicate that the domestic populations were resistant to deltamethrin, but no statistical contribution of 7-CP esterases was observed. The sylvatic populations had similar LDR values to NFS, but lower 7-CP esterase activities. Moreover, this is the first study of the pyrethroid esterases on T. infestans eggs employing a specific substrate (7-CP.

  19. Discrimination of esterase and peptidase activities of acylaminoacyl peptidase from hyperthermophilic Aeropyrum pernix K1 by a single mutation.

    Science.gov (United States)

    Wang, Qiuyan; Yang, Guangyu; Liu, Yanli; Feng, Yan

    2006-07-07

    It has been shown that highly conserved residues that form crucial structural elements of the catalytic apparatus may be used to account for the evolutionary history of enzymes. Using saturation mutagenesis, we investigated the role of a conserved residue (Arg(526)) at the active site of acylaminoacyl peptidase from hyperthermophilic Aeropyrum pernix K1 in substrate discrimination and catalytic mechanism. This enzyme has both peptidase and esterase activities. The esterase activity of the wild-type enzyme with p-nitrophenyl caprylate as substrate is approximately 7 times higher than the peptidase activity with Ac-Leu-p-nitroanilide as substrate. However, with the same substrates, this difference was increased to approximately 150-fold for mutant R526V. A more dramatic effect occurred with mutant R526E, which essentially completely abolished the peptidase activity but decreased the esterase activity only by a factor of 2, leading to a 785-fold difference in the enzyme activities. These results provide rare examples that illustrate how enzymes can be evolved to discriminate their substrates by a single mutation. The possible structural and energetic effects of the mutations on k(cat) and K(m) of the enzyme were discussed based on molecular dynamics simulation studies.

  20. Aspirin and metformin exhibit antitumor activity in murine breast cancer.

    Science.gov (United States)

    Zhao, Maoyuan; Wang, Yuyi; Du, Chi; Liu, Yanyang; Zhang, Nan; Luo, Feng

    2018-03-01

    Studies have shown that aspirin and metformin play important roles in chemoprevention and repression of breast cancers, even though the exact mechanism remains unclear. Aspirin is capable of stimulating apoptosis through prostaglandin-dependent or prostaglandin-independent pathways. Metformin inhibits cell growth by enhancing the tumor suppressive function of transforming growth factor (TGF-β). In the present study, we report a new link between aspirin, metformin, TGF-β1 and murine breast cancer inhibition. Specifically, we showed that aspirin and metformin enhanced 4T1 cell apoptosis by inducing secretion of TGF-β1, whereas estradiol weakened the effect.

  1. Pectin Methyl Esterase Activity Change in Intermediate Moisture Sun-Dried Figs after Storage

    Directory of Open Access Journals (Sweden)

    Dilek Demirbüker Kavak

    2015-12-01

    Full Text Available Intermediate moisture fruits can be obtained by rehydrating dried fruits. Intermediate moisture fruits are suitable for direct consumption compared to dry fruits and can be directly used in the production of various products such as bakery products, dairy products and candies. Aim of this study is to compare the pectin methyl esterase (PME activity of intermediate moisture figs which causes softening of the texture and to compare their microbial stability after 3 months storage period. For this purpose, dried figs were rehydrated in 30 and 80° C water until they reach 30% moisture content. Rehydrated samples were stored for 3 months at +4°C. Results showed that there was no statistically significant difference between the control samples and the samples rehydrated at 80°C according to the total viable counts. At the end of the storage period, results of residual PME activity in control samples was 24.1 μmol COOH min-1g-1, while it was found 17.4 μmol COOH min-1g-1 in samples rehydrated at 80°C. As a result rehydration conducted at 80°C provided 28% reduction in PME activity compared to the control samples rehydrated at 30°C, although it did not affect the microbial load significantly after storage.

  2. Acetylcholine esterase activity in mild cognitive impairment and Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Herholz, Karl [University of Manchester, Wolfson Molecular Imaging Centre, Clinical Neuroscience, Manchester (United Kingdom); University of Cologne, Cologne (Germany)

    2008-03-15

    Impairment of cholinergic neurotransmission is a well-established fact in Alzheimer's disease (AD), but there is controversy about its relevance at the early stages of the disease and in mild cognitive impairment (MCI). In vivo positron emission tomography imaging of cortical acetylcholine esterase (AChE) activity as a marker of cholinergic innervation that is expressed by cholinergic axons and cholinoceptive neurons has demonstrated a reduction of this enzyme activity in manifest AD. The technique is also useful to measure the inhibition of cerebral AChE induced by cholinesterase inhibitors for treatment of dementia symptoms. A reduction of cortical AchE activity was found consistently in all studies of AD and in few cases of MCI who later concerted to AD. The in vivo findings in MCI and very mild AD are still preliminary, and studies seem to suggest that cholinergic innervation and AChE as the main degrading enzyme are both reduced, which might result in partial compensation of their effect. (orig.)

  3. Biochemical characterization of a halotolerant feruloyl esterase from Actinomyces spp.: refolding and activity following thermal deactivation.

    Science.gov (United States)

    Hunt, Cameron J; Tanksale, Akshat; Haritos, Victoria S

    2016-02-01

    Ferulic acid esterases (FAE, EC. 3.1.1.73) hydrolyse the linkage between hemicellulose and lignin and thus have potential for use in mild enzymatic pretreatment of biomass as an alternative to thermochemical approaches. Here, we report the characterization of a novel FAE (ActOFaeI) obtained from the bacterium, Actinomyces sp. oral which was recombinantly expressed in Escherichia coli BL21 in two forms: with and without its putative signal peptide. The truncated form was found to have 90 % relative activity at pH 6.5 and an optimum reaction temperature of 30 °C. ActOFaeI increased activity by 15% in high salt conditions (1000 mMNaCl) and its thermal unfolding temperature improved from 41.5 °C in standard buffer to 74 °C in the presence of 2500 mM sodium malonate. ActOFaeI also released ferulic acid from destarched wheat bran when combined with a xylanase preparation. After treatment above the thermal denaturation temperature followed by cooling to room temperature, ActOFaeI demonstrated spontaneous refolding into an active state. ActOFaeI displays many useful characteristics for enzymatic pretreatment of lignocellulose and contributes to our understanding of this important family.

  4. Synthesis, characterization and antibacterial activity of aspirin and ...

    African Journals Online (AJOL)

    Dr J. T. Ekanem

    Novel complexes of Co (11), Ni (11) and Fe (111) with aspirin and paracetamol have synthesized and characterized using infrared, electronic and Hnmr spectral, melting point and conductivity measurements. The two ligands have been found to act as bidentate chelating agents. Aspirin complexes coordinate through the ...

  5. Vaginal Fornix Discharge Cellularity and Its Leukocyte Esterase Activity for Diagnosis of Endometritis in Dairy Cows

    Directory of Open Access Journals (Sweden)

    Abolfazl HAJIBEMANI

    2016-01-01

    Full Text Available The objective of the present study was to evaluate the application of some strip test markers (i.e., leukocyte esterase (LE activity, protein, nitrate and pH for diagnosis of endometritis in dairy cows using vaginal fornix discharge. Also, the total white blood cell count (t-WBC/l of this secretion and degenerative changes of neutrophils in cervical cytology were used as alternative methods to predict progression of the endometritis severity. Holstein cows (n=215 between 30-40 days in milk (DIM were included and examined. Giemsa-stained smear was prepared from cervical mucus. Cervical cytology test was considered as reference screening method for the detection of subclinical endometritis. The LE activity and t-WBC in the vaginal fornix discharge of subclinical endometritis cows were significantly higher than those from healthy cows. Sensitivity and specificity were 78% and 73% for LE10 activity (10 minutes after contacting with discharges and 60% and 69% for t-WBC (cut off point=210 cells/l for diagnosis of subclinical endometritis, respectively. There was a good agreement between LE10 activity, t-WBC and cervical cytology test with a Kappa coefficient of 0.4 and 0.42, respectively (P<0.0001. Total WBC count in discharge and degenerative neutrophils (DN percentages increase simultaneously with the degree and severity of endometritis. There was a highly significant (P<0.01 correlation between t-WBC and some reagent strip test markers (LE activity, protein and nitrate in clear discharge of studied cows. In conclusion, the present results suggest the LE activity and t-WBC in vaginal fornix discharge could be used as non-invasive reliable and valid methods for screening of subclinical endometritis in postpartum dairy herds.

  6. Hydrolytic Activity of Esterase-Antibody Complexes Retained Within Gel Capsules After Complex Isolation.

    Science.gov (United States)

    Shimazaki, Youji; Miyatsuka, Rino

    2017-07-01

    Delipidation in biological samples is important for some diagnostic tests and protein analyses. Lipids in the samples can be hydrolyzed by native esterases (ESs) within gel capsules after ES, and ES-antibody complexes are specifically trapped, extracted, and separated. Acrylamide and agarose gel capsules containing complexes of ES antibody were produced after the complexes were extracted using protein A-immobilized membranes, separated by non-denaturing electrophoresis, and stained by colloidal silver using glucose as a reductant. ES activity of ES-antibody complexes within the gel capsule was significantly higher than that in the complexes with the control antibodies upon isolation, separation, and detection of the complex. In addition, lipids bound to human serum albumin decreased after human plasma was treated with gel capsules containing ES-antibody complexes. We demonstrate that the gel capsule containing ES-antibody complexes can be successfully isolated using techniques described in this study. Furthermore, delipidation of human plasma is obtained by incubation with the gel capsule. These results indicate that surplus materials such as lipids in biological samples can be removed or reduced by gel capsule containing enzymes.

  7. Identification of novel esterase-active enzymes from hot environments by use of the host bacterium Thermus thermophilus

    Directory of Open Access Journals (Sweden)

    Benedikt eLeis

    2015-04-01

    Full Text Available Functional metagenomic screening strategies, which are independent of known sequence information, can lead to the identification of truly novel genes and enzymes. Since E. coli has been used exhaustively for this purpose as a host, it is important to establish alternative expression hosts and to use them for functional metagenomic screening for new enzymes. In this study we show that Thermus thermophilus HB27 is an excellent screening host and can be used as an alternative provider of truly novel biocatalysts. In a previous study we constructed the mutant strain BL03 that was no longer able to grow on defined minimal medium supplemented with tributyrin as the sole carbon source and could be used as a host to screen for metagenomic DNA fragments that could complement growth on tributyrin. Several thousand single fosmid clones from thermophilic metagenomic libraries from heated compost and hot spring water samples were subjected to a comparative screening for esterase activity in both T. thermophilus strain BL03 and E. coli EPI300. We scored a greater number of active clones in the thermophilic bacterium than in the mesophilic E. coli. From all clones functionally screened in E. coli, only two thermostable α/β-fold hydrolase enzymes with high amino acid sequence similarity to already characterized enzymes were identifiable. In contrast, five further fosmids were found that conferred lipolytic activities in T. thermophilus. Four open reading frames (ORFs were found which did not share significant similarity to known esterase enzymes. Two of the genes were expressed in both hosts and the novel thermophilic esterases, which based on their primary structures could not be assigned to known esterase or lipase families, were purified and preliminarily characterized. Our work underscores the benefit of using additional screening hosts other than E. coli for the identification of novel biocatalysts with industrial relevance.

  8. Nebulized C1-Esterase Inhibitor does not Reduce Pulmonary Complement Activation in Rats with Severe Streptococcus Pneumoniae Pneumonia.

    Science.gov (United States)

    de Beer, Friso; Lagrand, Wim; Glas, Gerie J; Beurskens, Charlotte J P; van Mierlo, Gerard; Wouters, Diana; Zeerleder, Sacha; Roelofs, Joris J T H; Juffermans, Nicole P; Horn, Janneke; Schultz, Marcus J

    2016-12-01

    Complement activation plays an important role in the pathogenesis of pneumonia. We hypothesized that inhibition of the complement system in the lungs by repeated treatment with nebulized plasma-derived human C1-esterase inhibitor reduces pulmonary complement activation and subsequently attenuates lung injury and lung inflammation. This was investigated in a rat model of severe Streptococcus pneumoniae pneumonia. Rats were intra-tracheally challenged with S. pneumoniae to induce pneumonia. Nebulized C1-esterase inhibitor or saline (control animals) was repeatedly administered to rats, 30 min before induction of pneumonia and every 6 h thereafter. Rats were sacrificed 20 or 40 h after inoculation with bacteria. Brochoalveolar lavage fluid and lung tissue were obtained for measuring levels of complement activation (C4b/c), lung injury and inflammation. Induction of pneumonia was associated with pulmonary complement activation (C4b/c at 20 h 1.24 % [0.56-2.59] and at 40 h 2.08 % [0.98-5.12], compared to 0.50 % [0.07-0.59] and 0.03 % [0.03-0.03] in the healthy control animals). The functional fraction of C1-INH was detectable in BALF, but no effect was found on pulmonary complement activation (C4b/c at 20 h 0.73 % [0.16-1.93] and at 40 h 2.38 % [0.54-4.19]). Twenty hours after inoculation, nebulized C1-esterase inhibitor treatment reduced total histology score, but this effect was no longer seen at 40 h. Nebulized C1-esterase inhibitor did not affect other markers of lung injury or lung inflammation. In this negative experimental animal study, severe S. pneumoniae pneumonia in rats is associated with pulmonary complement activation. Repeated treatment with nebulized C1-esterase inhibitor, although successfully delivered to the lungs, does not affect pulmonary complement activation, lung inflammation or lung injury.

  9. Multiple resistance to pirimiphos-methyl and bifenthrin in Tribolium castaneum involves the activity of lipases, esterases, and laccase2.

    Science.gov (United States)

    Julio, Alison Henrique Ferreira; Gigliolli, Adriana Aparecida Sinópolis; Cardoso, Kátia Aparecida Kern; Drosdoski, Sandro Daniel; Kulza, Rodrigo Amaral; Seixas, Flávio Augusto Vicente; Ruvolo-Takasusuki, Maria Claudia Colla; de Souza, Cristina Giatti Marques; Lapenta, Ana Silvia

    2017-05-01

    Several recent studies have elucidated the molecular mechanisms that confer insecticide resistance on insect pests. However, little is known about multiple resistance in red flour beetle (Tribolium castaneum) at molecular level. The multiple resistance is characterized as resistance to different classes of insecticides that have different target sites, and is mediated by several enzymatic systems. In this study, we investigated the biochemical and molecular mechanisms involved in multiple resistance of T. castaneum to bifenthrin (pyrethroid [Pyr]) and pirimiphos-methyl (organophosphate [Org]). We used artificial selection, biochemical and in silico approaches including structural computational biology. After five generations of artificial selection in the presence of bifenthrin (F5Pyr) or pirimiphos-methyl (F5Org), we found high levels of multiple resistance. The hierarchical enzymatic cluster revealed a pool of esterases (E), lipases (LIPs) and laccase2 (LAC2) potentially contributing to the resistance in different ways throughout development, after one or more generations in the presence of insecticides. The enzyme-insecticide interaction network indicated that E2, E3, LIP3, and LAC2 are enzymes potentially required for multiple resistance phenotype. Kinetic analysis of esterases from F5Pyr and F5Org showed that pirimiphos-methyl and specially bifenthrin promote enzyme inhibition, indicating that esterases mediate resistance by sequestering bifenthrin and pirimiphos-methyl. Our computational data were in accordance with kinetic results, indicating that bifenthrin has higher affinity at the active site of esterase than pirimiphos-methyl. We also report the capability of these insecticides to modify the development in T. castaneum. Our study provide insights into the biochemical mechanisms employed by T. castaneum to acquire multiple resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Effect of halogenated benzenes on acetanilide esterase, acetanilide hydroxylase and procaine esterase in rats.

    Science.gov (United States)

    Carlson, G P; Dziezak, J D; Johnson, K M

    1979-07-01

    1,2,4-Trichlorobenzene, 1,3,5-trichlorobenzene, hexachlorobenzene, 1,2,4-tribromobenzene, 1,3,5-tribromobenzene and hexabromobenzene were compared for their abilities to induce acetanilide esterase, acentailide hydroxylase and procaine esterase. Except for hexabromobenzene all induced acetanilide esterase whereas the hydroxylation of acetanilide was seen only with the fully halogenated benzenes and with 1,3,5-tribromobenzene. Hepatic procaine esterase activity was increased by the three chlorinated benzenes and 1,2,4-tribromobenzene.

  11. Aspirin Augments IgE-Mediated Histamine Release from Human Peripheral Basophils via Syk Kinase Activation

    Directory of Open Access Journals (Sweden)

    Hiroaki Matsuo

    2013-01-01

    Conclusions: Aspirin enhanced histamine release from basophils via increased Syk kinase activation, and that the augmentation of histamine release by NSAIDs or FAs may be one possible cause of worsening symptoms in patients with chronic urticaria and FDEIA.

  12. Histochemical studies on genetical control of hormonal enzyme inducibility in the mouse. I. Non-specific esterase activity and regional histology of the epididymis

    DEFF Research Database (Denmark)

    Blecher, S R; Kirkeby, S

    1978-01-01

    As a base line for future cell genetical studies the authors record the distribution of non-specific esterase reaction in the various histologically distinguishable cell types of the mouse epididymis. The findings are correlated with previous descriptions of the lobar structure of the organ....... Assuming the sequence of lobes of the head to be as implied in these classical descriptions, the esterase activity of the epithelial cells gradates between strong to weak several times along the length of the epididymal duct. The relationship of the lobes to each other, as seen in transverse sections......, is described. Methodological studies using different fixatives indicate that apparent similarity of esterase reaction at different sites may camouflage an underlying difference in the nature of the esterases at these sites....

  13. Aspirin suppresses neuronal apoptosis, reduces tissue inflammation, and restrains astrocyte activation by activating the Nrf2/HO-1 signaling pathway.

    Science.gov (United States)

    Wei, Wang; Shurui, Chen; Zipeng, Zhou; Hongliang, Dai; Hongyu, Wang; Yuanlong, Li; Kang, Zhou; Zhaoliang, Shen; Yue, Guo; Chang, Liu; Mei, Xifan

    2018-01-29

    The nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element signaling pathway plays a substantial role in preventing oxidative stress-related diseases. Aspirin has been shown to exert several pharmacological effects by inducing the expression of the heme oxygenase-1 (HO-1) protein. However, the effects of aspirin on spinal cord injury (SCI) have rarely been studied. Therefore, we sought to investigate the neuroprotective effects of aspirin after SCI. We employed a spinal cord contusion model in Sprague-Dawley rats, and aspirin was administered intraperitoneally for 7 days. Nissl staining showed that the aspirin treatment significantly reduced the loss of motor neurons after SCI compared with vehicle-treated animals. The expression of Nrf2, quinine oxidoreductase 1, and HO-1 proteins was increased in aspirin-treated animals after SCI compared with the vehicle group. In addition, aspirin simultaneously decreased the expression of inflammation-related proteins, such as tumor necrosis factor-α and interleukin-6 after SCI. Moreover, the ratio of apoptotic neurons in the anterior horn and the levels of the apoptosis-related proteins caspase-3, cleaved caspase-3, and Bax were significantly decreased in the aspirin group compared with the vehicle group. Immunofluorescence staining was used to detect the colocalization of NeuN and HO-1, and the results showed that aspirin significantly increased expression of the HO-1 protein in neurons. In addition, western blots and immunofluorescence staining showed aspirin restrained astrocyte activation. In conclusion, aspirin induces neuroprotective effects by inhibiting astrocyte activation and apoptosis after SCI through the activation of the Nrf2/HO-1 signaling pathway.

  14. Aspirin augments IgE-mediated histamine release from human peripheral basophils via Syk kinase activation.

    Science.gov (United States)

    Matsuo, Hiroaki; Yokooji, Tomoharu; Morita, Hironobu; Ooi, Mina; Urata, Kana; Ishii, Kaori; Takahagi, Shunsuke; Yanase, Yuhki; Hiragun, Takaaki; Mihara, Shoji; Hide, Michihiro

    2013-12-01

    Non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, and food additives (FAs) may exacerbate allergic symptoms in patients with chronic idiopathic urticaria and food-dependent exercise-induced anaphylaxis (FDEIA). Augmentation of histamine release from human mast cells and basophils by those substances is speculated to be the cause of exacerbated allergic symptoms. We sought to investigate the mechanism of action of aspirin on IgE-mediated histamine release. The effects of NSAIDs, FAs or cyclooxygenase (COX) inhibitors on histamine release from human basophils concentrated by gravity separation were evaluated. Benzoate and tartrazine, which have no COX inhibitory activity, augmented histamine release from basophils similar to aspirin. In contrast, ibuprofen, meloxicam, FR122047 and NS-398, which have COX inhibitory activity, did not affect histamine release. These results indicate that the augmentation of histamine release by aspirin is not due to COX inhibition. It was observed that aspirin augmented histamine release from human basophils only when specifically activated by anti-IgE antibodies, but not by A23187 or formyl-methionyl-leucyl-phenylalanine. When the IgE receptor signaling pathway was activated, aspirin increased the phosphorylation of Syk. Moreover, patients with chronic urticaria and FDEIA tended to be more sensitive to aspirin as regards the augmentation of histamine release, compared with healthy controls. Aspirin enhanced histamine release from basophils via increased Syk kinase activation, and that the augmentation of histamine release by NSAIDs or FAs may be one possible cause of worsening symptoms in patients with chronic urticaria and FDEIA.

  15. Relationship between esterase activity and acrinathrin and methiocarb resistance in field populations of western flower thrips, Frankliniella occidentalis.

    Science.gov (United States)

    Maymó, Ana C; Cervera, Amelia; Dolores Garcerá, M; Bielza, Pablo; Martínez-Pardo, Rafael

    2006-12-01

    The western flower thrips, Frankliniella occidentalis (Pergande), is a serious pest in the south-east of Spain owing to its direct feeding on crops, transmission of the tomato spotted wilt virus and its very high level of resistance to insecticides. Mechanisms of resistance were examined using field populations of F. occidentalis with different susceptibilities to acrinathrin, methiocarb (selective insecticides), endosulfan, metamidophos and deltamethrin (broad-spectrum insecticides). Esterase activity towards alpha-naphthyl acetate and p-nitrophenyl acetate in resistant strains was significantly higher than in the reference strain (MLFOM) for both model substrates. This higher activity was significantly correlated with acrinathrin and methiocarb resistance. Copyright 2006 Society of Chemical Industry.

  16. Increase of acetate ester-hydrolysing esterase activity in mixed cultures of Saccharomyces cerevisiae and Pichia anomala.

    Science.gov (United States)

    Kurita, O

    2008-04-01

    To examine the efficacy of mixed cultures with Saccharomyces cerevisiae and Pichia anomala on flavour profiles of alcoholic beverages, a Pichia mutant with low levels of ethyl acetate that negatively impact on the sensory quality was isolated. A petite mutant isolated from P. anomala NBRC 10213 treated with ethidium bromide had the lower activity of ethyl acetate-hydrolysing esterase (EAHase) than the wild-type in crude extracts. In the fermentation tests of pure cultures, the P. anomala mutant produced less ethanol, acetate and ethyl acetate than the wild-type. In mixed cultures with S. cerevisiae, the P. anomala mutant died quicker and produced lower amounts of ethyl acetate than the wild-type. Mixed cultures of S. cerevisiae and P. anomala showed higher activities of EAHase than pure culture of S. cerevisiae throughout the fermentation periods. The transition to the formation of acetate esters was considerably analogous to the transition to the activity of acetate ester-hydrolysing esterase with little time lag. The P. anomala mutant was superior to the wild-type in flavour profiles. The higher ethyl acetate concentrations formed mainly by P. anomala in mixed cultures are the primary stimulus for the EAHase in S. cerevisiae and the activity of acetate ester-hydrolysing esterase is crucial to the formation of acetate esters in mixed cultures of S. cerevisiae and P. anomala. An application of non-Saccharomyces yeast, P. anomala to enhance the sensory quality in alcoholic beverage and a mechanism of the formation of acetate esters in mixed cultures with S. cerevisiae and P. anomala were offered.

  17. Effect of selenium on cadmium-induced oxidative stress and esterase activity in rat organs

    OpenAIRE

    Kevin Dzobo; Yogeshkumar S. Naik

    2013-01-01

    Metal toxicity is a threat mainly in the industrialised world where industry discharges many toxic metals into the environment. We investigated the effects of two metals cadmium and selenium on the cytosolic antioxidant enzymes and esterases in the liver, kidneys and testes of rats. Male Sprague-Dawley rats (n=28) were divided equally into four groups: control, cadmium, selenium and cadmium/selenium. Salts of the metals were administered intraperitoneally for 15 days. In the liver, cadmium tr...

  18. Esterase profile of human masseter muscle

    DEFF Research Database (Denmark)

    Kirkeby, S; Moe, D; Vilmann, H

    1988-01-01

    The esterase profile of fresh human masseter muscle was investigated by use of histochemistry and electrophoresis. The histochemical methods included reactions for alpha-naphthyl esterase, myofibrillar ATPase, reverse myofibrillar ATPase and succinic dehydrogenase. In frozen sections of the muscle......C. iM and Type II A fibres showed a moderate esterase reaction and Type II B fibres had a low activity. The electrophoretic gels stained for esterase activity showed that the human masseter muscle possesses a slow migrating double band with high enzyme activity and a cascade of faster migrating...

  19. [BAME-Esterase activity in plasmas from blood of human placental interveillous space and umbilical cord vessels (author's transl)].

    Science.gov (United States)

    Matheus, M; Salles Meirelles, R

    1976-01-01

    The authors studied an enzymatic activity (BAME-esterase) from human plasma, intimately related with the bradykinin release mechanisms. The optimal conditions of evaluation of the different plasmas were determined. Lately, the authors showed the results obtained with plasma from maternal peripheral blood, umbilical vessels blood and human placental intervillous space blood. It was concluded: 1. The study of enzymatic kinetics allows to establish a reaction time of 30 minutes, and the enzymatic concentration contained within 0.5 ml. of plasma, as ideal parameters to determine the enzymatic activities into the different compartments. 2. In the cases studied, considered clinically normals, the enzymatic activity in plasma from the interveillous space, before and after the detachment of the placenta, was greater than in peripheral maternal and umbilical vessels bloods. The activity in umbilical artery plasma was greater than in umbilical vein and practically the same as in maternal plasma. 3. The esterase activity values into the compartments studied in pre-eclamptics, were similar to that found in the cases considered clinically normal.

  20. Synthesis, characterization and antibacterial activity of aspirin and ...

    African Journals Online (AJOL)

    Aspirin complexes coordinate through the carbonyl oxygen of the carboxyl and the ester groups, while paracetamol complexes coordinate through the oxygen of the hydroxyl and the amide groups. Antibacterial screening of the complexes against Bacillus substilis, Serratia species and Escherichia coli, was also ...

  1. Activity and stability of feruloyl esterase A from Aspergillus niger in ionic liquid systems

    DEFF Research Database (Denmark)

    Zeuner, Birgitte; Riisager, Anders; Meyer, Anne S.

    Feruloyl esterases (FAEs; EC 3.1.1.73) are accessory plant cell wall-degrading enzymes, which catalyse the hydrolysis of the ester bond between ferulic acid and the monosaccharide to which it is covalently linked. FAEs can however also be brought to catalyse the (trans)esterification reaction...... by the quantum chemistry-based COSMO-RS method, [BF4]- has a tendency to form hydrogen bonds and thus interfere with the secondary structure of the enzyme, while [PF6]-is unlikely to form hydrogen bonds and therefore does not cause denaturation of the enzyme. Similar results have been obtained for lipases [1...

  2. Isolation and characterization of EstC, a new cold-active esterase from Streptomyces coelicolor A3(2.

    Directory of Open Access Journals (Sweden)

    Guillaume Brault

    Full Text Available The genome sequence of Streptomyces coelicolor A3(2 contains more than 50 genes coding for putative lipolytic enzymes. Many studies have shown the capacity of this actinomycete to store important reserves of intracellular triacylglycerols in nutrient depletion situations. In the present study, we used genome mining of S. coelicolor to identify genes coding for putative, non-secreted esterases/lipases. Two genes were cloned and successfully overexpressed in E. coli as His-tagged fusion proteins. One of the recombinant enzymes, EstC, showed interesting cold-active esterase activity with a strong potential for the production of valuable esters. The purified enzyme displayed optimal activity at 35°C and was cold-active with retention of 25% relative activity at 10°C. Its optimal pH was 8.5-9 but the enzyme kept more than 75% of its maximal activity between pH 7.5 and 10. EstC also showed remarkable tolerance over a wide range of pH values, retaining almost full residual activity between pH 6-11. The enzyme was active toward short-chain p-nitrophenyl esters (C2-C12, displaying optimal activity with the valerate (C5 ester (k(cat/K(m = 737±77 s(-1 mM(-1. The enzyme was also very active toward short chain triglycerides such as triacetin (C2:0 and tributyrin (C4:0, in addition to showing good primary alcohol and organic solvent tolerance, suggesting it could function as an interesting candidate for organic synthesis of short-chain esters such as flavors.

  3. ESTERASE ACTIVITY AMONG PATIENTS WITH GASTROINTESTINAL DISEASES WORKING AT THE PLANTS PROVIDING STORAGE AND DISPOSAL OF ORGANOPHOSPHORUS COMPOUNDS

    Directory of Open Access Journals (Sweden)

    A. V. Fomichev

    2017-01-01

    Full Text Available Studies have shown that exposure to organophosphates (OPs is associated with increased frequency of gastrointestinal diseases. In order to evaluate the effect of dysfunction of detoxification system on the development of gastrointestinal pathology, we studied «esterase status» (activity of acetylcholinesterase, butyrylcholinesterase and paraoxonase 1 (PON1 among workers at the plants providing storage and disposal of OPs. The enzymatic activity of PON1 was significantly increased in individuals who had prolonged direct contact with the OPs. It was shown that among all gastrointestinal diseases included in this study PON1 activity was increased in patients with chronic esophagitis and chronic gastritis as compared to workers without gastrointestinal diseases (p<0.05, so and with diseased workers who had no direct contact with OPs (p<0.05. Thus, changes in PON1 activity may contribute to development of the gastrointestinal pathology among persons having direct contact with OPs. 

  4. Evaluation of antioxidant activity and electronic structure of aspirin and paracetamol

    Science.gov (United States)

    Motozaki, W.; Nagatani, Y.; Kimura, Y.; Endo, K.; Takemura, T.; Kurmaev, E. Z.; Moewes, A.

    2011-01-01

    We present a study of electronic structure, chemical bonding, and antioxidant activity of phenolic antioxidants (aspirin and paracetamol). X-ray photoelectron and emission spectra of the antioxidants have been simulated by deMon density functional theory (DFT) calculations of the molecules. The chemical bonding of aspirin is characterized by the formation of oxygen 'lone-pair' π-orbitals which can neutralize free radicals and thus be related to antioxidant properties of the drug. In the case of paracetamol the additional nitrogen 'lone pair' is formed which can explain toxicity of the drug. We propose an evaluation method of antioxidant activity based on the relationship between experimental half-wave oxidation potential ( Ep/2 ) and calculated ionization potentials ( IP) by the DFT calculations, and can conclude that paracetamol has the higher antioxidant activity than aspirin.

  5. Platelet activation patterns in platelet size sub-populations: differential responses to aspirin in vitro.

    Science.gov (United States)

    Mangalpally, Kiran Kumar R; Siqueiros-Garcia, Alan; Vaduganathan, Muthiah; Dong, Jing-Fei; Kleiman, Neal S; Guthikonda, Sasidhar

    2010-10-01

    Circulating platelets are heterogeneous in size and structure. Whether this translates into differences in platelet function and efficacy of antiplatelet therapy is unclear. Hence, we decided to investigate the activation patterns among different platelet populations differentiated by size, and to compare the inhibitory effects of aspirin in these populations. Circulating platelets from 9 healthy volunteers were separated by size and stratified into the largest and smallest quintiles. Platelets were stimulated with 75 μM arachidonic acid (AA), 10 μM ADP or 25 μM TRAP. Alpha-granule protein secretion and expression (P-selectin, VWF, fibrinogen), surface-protein activation (activated integrin αIIbβ3) were assessed. Platelet thromboxane B(2) (TxB(2)) synthesis following AA stimulation was measured in vitro before and after incubation with 265 μM aspirin. Reticulated (juvenile) platelets were assessed using thiazole orange staining. A greater number of large platelets in the largest quintile were reticulated compared with the smallest quintile (6.1 ± 2.8% vs. 1.2 ± 1.5% respectively, p aspirin (1029 ± 190 pg/mL vs. 851 ± 159 pg/mL, respectively, p = 0.03). After stimulation with each agonist, a greater proportion of large platelets bound fibrinogen, VWF, P-selectin and activated integrin αIIbβ3 than small platelets both in the presence and in the absence of in vitro aspirin. In an in vitro setting, large platelets appear to be more active than small platelets and continue to be more active even after in vitro aspirin. Platelets exhibit heterogeneity in size and structure. Whether this translates into platelet function and efficacy of antiplatelet therapy is unclear. We evaluated platelet functional properties and the effects of aspirin on separated platelet subpopulations in an in vitro setting. Platelets were sorted into the largest and smallest size quintiles using flow cytometry forward scatter. Alpha-granule protein release, dense granule content

  6. Leukocyte esterase urine test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003584.htm Leukocyte esterase urine test To use the sharing features on this page, please enable JavaScript. Leukocyte esterase is a urine test to look for ...

  7. 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...

  8. Esterase activity in the guinea pig thyroid under normal and pathological conditions (vitamin A deficiency) with special regard to cyst-like structures

    DEFF Research Database (Denmark)

    Kirkeby, S

    1977-01-01

    By use of different activators and inhibitors, TOCP(tri-o-cresyl phosphate), PCMB (parachloromercury benzoate), NiCl2, Pb(NO3)2, HgCl2, Hg(NO3)2, eserine and sodium taurocholate, it is shown that the esterase in the cyst cells and in group I cells of the guinea pig thyroid probably are A...... diet is given, the esterase in all thyroid epithelial cells is very sensitive to sodium taurocholate, while in cyst cells it is rather resistant to this inhibitor at vitamin-A-deficiency....

  9. Controlled release from aspirin based linear biodegradable poly(anhydride esters) for anti-inflammatory activity.

    Science.gov (United States)

    Dasgupta, Queeny; Movva, Sahitya; Chatterjee, Kaushik; Madras, Giridhar

    2017-08-07

    This work reports the synthesis of a novel, aspirin-loaded, linear poly (anhydride ester) and provides mechanistic insights into the release of aspirin from this polymer for anti-inflammatory activity. As compared to conventional drug delivery systems that rely on diffusion based release, incorporation of bioactives in the polymer backbone is challenging and high loading is difficult to achieve. In the present study, we exploit the pentafunctional sugar alcohol (xylitol) to provide sites for drug (aspirin) attachment at its non-terminal OH groups. The terminal OH groups are polymerized with a diacid anhydride. The hydrolysis of the anhydride and ester bonds under physiological conditions release aspirin from the matrix. The resulting poly(anhydride ester) has high drug loading (53%) and displays controlled release kinetics of aspirin. The polymer releases 8.5 % and 20%, of the loaded drug in one and four weeks, respectively and has a release rate constant of 0.0035h -0.61 . The release rate is suitable for its use as an anti-inflammatory agent without being cytotoxic. The polymer exhibits good cytocompatibility and anti-inflammatory properties and may find applications as injectable or as an implantable bioactive material. The physical insights into the release mechanism can provide development of other drug loaded polymers. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Antitumor effect of aspirin in glioblastoma cells by modulation of β-catenin/T-cell factor-mediated transcriptional activity.

    Science.gov (United States)

    Lan, Fengming; Yue, Xiao; Han, Lei; Yuan, Xubo; Shi, Zhendong; Huang, Kai; Yang, Yang; Zou, Jian; Zhang, Junxia; Jiang, Tao; Pu, Peiyu; Kang, Chunsheng

    2011-10-01

    The goal in this study was to investigate the antitumor effect of aspirin in glioblastoma cells and the molecular mechanism involved in its antineoplastic activities. The authors used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, flow cytometry, the annexin V method, and Transwell cell invasion test to detect the proliferation and invasive activity of U87 and A172 glioma cells before and after being treated with aspirin. To determine the effects of aspirin on β-catenin/T-cell factor (TCF) transcription activity, reporter constructs containing 3 repeats of the wild-type (TOPflash) or mutant (FOPflash) TCF-binding sites were used. Reverse transcriptase polymerase chain reaction and Western blot analyses were used to detect the expression of multiple β-catenin/TCF target genes following aspirin treatment. The transcriptional activity of the β-catenin/TCF complex was strongly inhibited by aspirin. Increasing the concentration of aspirin resulted in decreased expression of c-myc, cyclin D1, and fra-1 mRNA and protein in U87 and A172 cells in a dose-dependent manner. Aspirin inhibited glioma cell proliferation and invasive ability, and induced apoptotic cell death. The results suggest that aspirin is a potent antitumor agent, and that it exerts its antineoplastic action by inhibition of the β-catenin/TCF signaling pathway in glioma cells.

  11. Immunomodulatory activity of fucoidan against aspirin-induced gastric mucosal damage in rats.

    Science.gov (United States)

    Raghavendran, Hanumantha Rao Balaji; Srinivasan, Periasamy; Rekha, Sathyanath

    2011-02-01

    Gastric ulcers and related complications associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, represent a major global health problem. In the present study, we investigate the immunological activity of fucoidan against aspirin-induced gastric mucosal damage in rats. Thirty-six rats were randomly divided into the following, normal (Carboxy methyl cellulose 0.05 %), aspirin (Asp-400mg/kg) treated, fucoidan alone (Fu-0.02 g/kg, daily for 14 days) and Fu+Asp. Cytokines, total nitrite and nitrate (NOx) analysis and tissue localization of Cyclooxygenase 1, 2 and epidermal growth factor receptor (EGFR) were done using Elisa and immunohistochemistry respectively. Histopathology of gastric tissue, collagen deposition was performed using Hematoxylin and Eosin and Masson's trichrome were performed. Treatment of rats with a single dose of aspirin (400mg/kg, orally) led to significant alterations in the levels of total nitrite and nitrate (NOx), interleukins (IL-4, 6, 10, 12), tumor necrosis factor (TNF-α), and interferon gamma (IFN-γ). Notably, collagen deposition in glandular tissue and localization of cyclooxygenase 1, 2, and epidermal growth factor were considerably affected in aspirin-treated rats. These severities were prevented to a significant extent in rats pretreated with fucoidan (0.02 g/kg/day for two weeks orally). Our findings collectively indicate that the gastro-protective effect of fucoidan against aspirin-induced ulceration in rats is mediated through its immunomodulatory properties. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. High-dose aspirin in addition to daily low-dose aspirin decreases platelet activation in patients before and after percutaneous coronary intervention.

    NARCIS (Netherlands)

    Berg, J.M. ten; Gerritsen, W.B.M.; Haas, F.J.L.M.; Kelder, J.C.; Verheugt, F.W.A.; Plokker, H.W.M.

    2002-01-01

    BACKGROUND: Activated platelets play a major role in acute vessel closure after coronary angioplasty. Although aspirin is the routine therapy during angioplasty, it only incompletely prevents acute closure. This might be due to suboptimal dosing. OBJECTIVE: First, to study the effect of additional

  13. Cytostatic action of aspirin and its effect on mitomycin C activity. A study in vitro under irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kammerer, Cornelia; Getoff, Nikola E-mail: nikola.getoff@univie.ac.at

    2001-04-01

    Experiments in vitro using E. coli bacteria (AB 1157) proved that aspirin possesses a cytostatic ability under various experimental condition (pH=7.4) in airfree, aerated as well as in media containing N{sub 2}O (converting e{sub aq}{sup -} into OH- radicals). In the last case the highest effect of aspirin was observed. The combination of aspirin with the well-known cytostaticum, mitomycin C (MMC) leads in airfree as well as in aerated media to a significant decrease of the MMC activity. However, the mixture of aspirin and MMC in the presence of N{sub 2}O causes a synergistic effect, resulting in an enhancement of the MMC activity by a factor of 1.5. Probable reaction steps are presented and discussed. Using the pulse radiolysis method the rate constants for the reactions of e{sub aq}{sup -}, H and OH- species with aspirin were also determined.

  14. Detection of carboxylesterase and esterase activity in culturable gut bacterial flora isolated from diamondback moth, Plutella xylostella (Linnaeus, from India and its possible role in indoxacarb degradation

    Directory of Open Access Journals (Sweden)

    Shanivarsanthe Leelesh Ramya

    2016-06-01

    Full Text Available Abstract Diamondback moth (DBM, Plutella xylostella (Linnaeus, is a notorious pest of brassica crops worldwide and is resistant to all groups of insecticides. The insect system harbors diverse groups of microbiota, which in turn helps in enzymatic degradation of xenobiotic-like insecticides. The present study aimed to determine the diversity of gut microflora in DBM, quantify esterase activity and elucidate their possible role in degradation of indoxacarb. We screened 11 geographic populations of DBM in India and analyzed them for bacterial diversity. The culturable gut bacterial flora underwent molecular characterization with 16S rRNA. We obtained 25 bacterial isolates from larvae (n = 13 and adults (n = 12 of DBM. In larval gut isolates, gammaproteobacteria was the most abundant (76%, followed by bacilli (15.4%. Molecular characterization placed adult gut bacterial strains into three major classes based on abundance: gammaproteobacteria (66%, bacilli (16.7% and flavobacteria (16.7%. Esterase activity from 19 gut bacterial isolates ranged from 0.072 to 2.32 µmol/min/mg protein. Esterase bands were observed in 15 bacterial strains and the banding pattern differed in Bacillus cereus – KC985225 and Pantoea agglomerans – KC985229. The bands were characterized as carboxylesterase with profenofos used as an inhibitor. Minimal media study showed that B. cereus degraded indoxacarb up to 20%, so it could use indoxacarb for metabolism and growth. Furthermore, esterase activity was greater with minimal media than control media: 1.87 versus 0.26 µmol/min/mg protein. Apart from the insect esterases, bacterial carboxylesterase may aid in the degradation of insecticides in DBM.

  15. Detection of carboxylesterase and esterase activity in culturable gut bacterial flora isolated from diamondback moth, Plutella xylostella (Linnaeus), from India and its possible role in indoxacarb degradation.

    Science.gov (United States)

    Ramya, Shanivarsanthe Leelesh; Venkatesan, Thiruvengadam; Srinivasa Murthy, Kottilingam; Jalali, Sushil Kumar; Verghese, Abraham

    2016-01-01

    Diamondback moth (DBM), Plutella xylostella (Linnaeus), is a notorious pest of brassica crops worldwide and is resistant to all groups of insecticides. The insect system harbors diverse groups of microbiota, which in turn helps in enzymatic degradation of xenobiotic-like insecticides. The present study aimed to determine the diversity of gut microflora in DBM, quantify esterase activity and elucidate their possible role in degradation of indoxacarb. We screened 11 geographic populations of DBM in India and analyzed them for bacterial diversity. The culturable gut bacterial flora underwent molecular characterization with 16S rRNA. We obtained 25 bacterial isolates from larvae (n=13) and adults (n=12) of DBM. In larval gut isolates, gammaproteobacteria was the most abundant (76%), followed by bacilli (15.4%). Molecular characterization placed adult gut bacterial strains into three major classes based on abundance: gammaproteobacteria (66%), bacilli (16.7%) and flavobacteria (16.7%). Esterase activity from 19 gut bacterial isolates ranged from 0.072 to 2.32μmol/min/mg protein. Esterase bands were observed in 15 bacterial strains and the banding pattern differed in Bacillus cereus - KC985225 and Pantoea agglomerans - KC985229. The bands were characterized as carboxylesterase with profenofos used as an inhibitor. Minimal media study showed that B. cereus degraded indoxacarb up to 20%, so it could use indoxacarb for metabolism and growth. Furthermore, esterase activity was greater with minimal media than control media: 1.87 versus 0.26μmol/min/mg protein. Apart from the insect esterases, bacterial carboxylesterase may aid in the degradation of insecticides in DBM. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

  16. 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.

  17. Probiotic Ferulic Acid Esterase Active Lactobacillus fermentum NCIMB 5221 APA Microcapsules for Oral Delivery: Preparation and in Vitro Characterization

    Directory of Open Access Journals (Sweden)

    Catherine Tomaro-Duchesneau

    2012-02-01

    Full Text Available Probiotics possess potential therapeutic and preventative effects for various diseases and metabolic disorders. One important limitation for the oral delivery of probiotics is the harsh conditions of the upper gastrointestinal tract (GIT which challenge bacterial viability and activity. One proposed method to surpass this obstacle is the use of microencapsulation to improve the delivery of bacterial cells to the lower GIT. The aim of this study is to use alginate-poly-L-lysine-alginate (APA microcapsules to encapsulate Lactobacillus fermentum NCIMB 5221 and characterize its enzymatic activity and viability through a simulated GIT. This specific strain, in previous research, was characterized for its inherent ferulic acid esterase (FAE activity which could prove beneficial in the development of a therapeutic for the treatment and prevention of cancers and metabolic disorders. Our findings demonstrate that the APA microcapsule does not slow the mass transfer of substrate into and that of the FA product out of the microcapsule, while also not impairing bacterial cell viability. The use of simulated gastrointestinal conditions led to a significant 2.5 log difference in viability between the free (1.10 × 104 ± 1.00 × 103 cfu/mL and the microencapsulated (5.50 × 106 ± 1.00 × 105 cfu/mL L. fermentum NCIMB 5221 following exposure. The work presented here suggests that APA microencapsulation can be used as an effective oral delivery method for L. fermentum NCIMB 5221, a FAE-active probiotic strain.

  18. Probiotic Ferulic Acid Esterase Active Lactobacillus fermentum NCIMB 5221 APA Microcapsules for Oral Delivery: Preparation and in Vitro Characterization.

    Science.gov (United States)

    Tomaro-Duchesneau, Catherine; Saha, Shyamali; Malhotra, Meenakshi; Coussa-Charley, Michael; Kahouli, Imen; Jones, Mitchell L; Labbé, Alain; Prakash, Satya

    2012-02-16

    Probiotics possess potential therapeutic and preventative effects for various diseases and metabolic disorders. One important limitation for the oral delivery of probiotics is the harsh conditions of the upper gastrointestinal tract (GIT) which challenge bacterial viability and activity. One proposed method to surpass this obstacle is the use of microencapsulation to improve the delivery of bacterial cells to the lower GIT. The aim of this study is to use alginate-poly-L-lysine-alginate (APA) microcapsules to encapsulate Lactobacillus fermentum NCIMB 5221 and characterize its enzymatic activity and viability through a simulated GIT. This specific strain, in previous research, was characterized for its inherent ferulic acid esterase (FAE) activity which could prove beneficial in the development of a therapeutic for the treatment and prevention of cancers and metabolic disorders. Our findings demonstrate that the APA microcapsule does not slow the mass transfer of substrate into and that of the FA product out of the microcapsule, while also not impairing bacterial cell viability. The use of simulated gastrointestinal conditions led to a significant 2.5 log difference in viability between the free (1.10 × 104 ± 1.00 × 103 cfu/mL) and the microencapsulated (5.50 × 106 ± 1.00 × 105 cfu/mL) L. fermentum NCIMB 5221 following exposure. The work presented here suggests that APA microencapsulation can be used as an effective oral delivery method for L. fermentum NCIMB 5221, a FAE-active probiotic strain.

  19. Enhanced activity and enantioselectivity of a hyperthermophilic esterase from archaeon Aeropyrum pernix K1 by acetone treatment.

    Science.gov (United States)

    Cong, Fangdi; Xing, Kezhi; Gao, Renjun; Cao, Shugui; Zhang, Guirong

    2011-10-01

    To improve the activity and enantioselectivity of hyperthermophilic archaeon Aeropyrum pernix K1 esterase (APE1547) and its mutants, they were purified by acetone-treated method. It was found that the acetone treatment not only caused APE1547 and its mutants to display higher activity and enantioselectivity but also saved more than 90% of time spent in purifying them by Ni-chelating column. In hydrolysis of p-nitrophenyl caprylate, the acetone-treated APE1547 and mutant A containing the following substitutions R11G, L36P, V225A, I551L, and A564T showed 5.7- and 6.9-fold active increase, respectively. In the resolution of 2-octanol acetate, the acetone-treated mutant A had a 9-fold enantioselective increase relative to that purified by Ni-chelating column. In addition, the impact of pH, temperature, and chemical reagents on activity of APE1547 and mutant A was discussed in this paper.

  20. 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 ...

  1. 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 " ...

  2. 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

  3. 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.

  4. In vitro pancreatic lipase, cholesterol esterase and cholesterol micellization inhibitory activity of Sri Lankan low grown orthodox Orange Pekoe grade black tea (Camellia sinensis L.

    Directory of Open Access Journals (Sweden)

    Wanigasekera Daya Ratnasooriya

    2015-07-01

    Full Text Available Objective: To access the pancreatic lipase, cholesterol esterase and cholesterol micellization inhibitory activities of Sri Lankan low grown orthodox Orange Pekoe grade black tea made from uppermost tender leaves and unopened buds of Camellia sinensis L. Methods: Black tea brew (BTB was made according to International Organization for Standardization 3103 specifications and concentrations of BTB tested were 37.5, 75.0, 150.0, 300.0 and 600.0 µg/mL for antilipase and anti-cholesterol esterase assays and 0.25, 0.50 and 1.00 µg/mL for cholesterol micellization inhibitory assay. Results: The results showed that BTB of Sri Lankan low grown orthodox Orange Pekoe grade black tea has marked and dose-dependent (r 2 = 0.95 cholesterol micellization inhibitory activity in vitro comparable to epigallocatechin gallate, the reference drug used. In contrast, BTB had only mild but dose-dependent (r 2 = 0.94 inhibitory activity against pancreatic lipase and weak inhibitory effect (up to 13.17% on pancreatic cholesterol esterase. Conclusions: It is concluded that consumption of BTB of Sri Lankan low grown orthodox Orange Pekoe grade tea as a beverage may be a useful strategy in the management of hyperlipidaemia.

  5. 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.

  6. Functional characterisation of a metagenome derived family VIII esterase with a deacetylation activity on ß-lactam antibiotics

    CSIR Research Space (South Africa)

    Mokoena, N

    2013-08-01

    Full Text Available characterisation of a novel esterase (Est22) derived from an acidic Leachate environment. The enzyme is 423 amino acids in length and contained 22aa signal peptide. Analysis of the Est22 primary structure revealed the presence of N-terminus S-x-x-K sequence, which...

  7. Aspirin Inhibits IKK-β-mediated Prostate Cancer Cell Invasion by Targeting Matrix Metalloproteinase-9 and Urokinase-Type Plasminogen Activator.

    Science.gov (United States)

    Shi, Chongjun; Zhang, Nini; Feng, Yang; Cao, Jiewei; Chen, Xuyi; Liu, Bin

    2017-01-01

    Aspirin has been demonstrated to possess potent chemopreventive and anticancer effects on prostate cancer. However, the more detailed molecular mechanisms of aspirin to suppress prostate cancer cell invasion have not been clearly elucidated. Transwell assays were performed to evaluate the effects of aspirin on cell invasion. Matrix metalloproteinases (MMPs) and serine proteinases activities in cell media were examined by gelatin zymography and ELISA. In addition, inhibitor of κB (IκB) kinase-β (IKK-β) phosphorylation and IKK-β kinase activity were measured to assess the effects of aspirin on IKK-β activation. We found that aspirin suppressed the invasion and attachment in human prostate cancer cells. Aspirin treatment significantly resulted in reduction of matrix metalloproteinase-9 (MMP-9) and upregulation of tissue inhibitors of metalloproteinase-1 (TIMP-1) activity, which are the proteolytic enzymes contributing to the degradation of extracellular matrix and basement membrane in cell invasion and metastasis. Our data further showed that aspirin was able to inhibit both urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) expression in the cells. In addition, aspirin treatment caused a strong decrease in nuclear factor-kappa B (NF-κB) activation, inhibitor of κB (IκB)-α phosphorylation together with translocation of NF-κB p65 to nucleus and IκB kinase (IKK)- β activation. Moreover, the inhibitory effects of aspirin on cell invasion were reversed by IKK-β overexpression, while the IKK inhibitor sensitizes the anti-invasive effect of aspirin in prostate cancer cells. The present research concluded that aspirin suppressed prostate cancer cell invasion by reducing MMP-9 activity and uPA expression through decreasing of IKK-β-mediated NF-κB activation, indicating that the ability of aspirin to inhibit cell invasion might be useful in the chemoprevention of metastatic prostate cancer. © 2017 The Author(s)Published by

  8. Aspirin Inhibits IKK-β-mediated Prostate Cancer Cell Invasion by Targeting Matrix Metalloproteinase-9 and Urokinase-Type Plasminogen Activator

    Directory of Open Access Journals (Sweden)

    Chongjun Shi

    2017-03-01

    Full Text Available Background/Aims: Aspirin has been demonstrated to possess potent chemopreventive and anticancer effects on prostate cancer. However, the more detailed molecular mechanisms of aspirin to suppress prostate cancer cell invasion have not been clearly elucidated. Methods: Transwell assays were performed to evaluate the effects of aspirin on cell invasion. Matrix metalloproteinases (MMPs and serine proteinases activities in cell media were examined by gelatin zymography and ELISA. In addition, inhibitor of κB (IκB kinase-β (IKK-β phosphorylation and IKK-β kinase activity were measured to assess the effects of aspirin on IKK-β activation. Results: We found that aspirin suppressed the invasion and attachment in human prostate cancer cells. Aspirin treatment significantly resulted in reduction of matrix metalloproteinase-9 (MMP-9 and upregulation of tissue inhibitors of metalloproteinase-1 (TIMP-1 activity, which are the proteolytic enzymes contributing to the degradation of extracellular matrix and basement membrane in cell invasion and metastasis. Our data further showed that aspirin was able to inhibit both urokinase-type plasminogen activator (uPA and plasminogen activator inhibitor-1 (PAI-1 expression in the cells. In addition, aspirin treatment caused a strong decrease in nuclear factor-kappa B (NF-κB activation, inhibitor of κB (IκB-α phosphorylation together with translocation of NF-κB p65 to nucleus and IκB kinase (IKK- β activation. Moreover, the inhibitory effects of aspirin on cell invasion were reversed by IKK-β overexpression, while the IKK inhibitor sensitizes the anti-invasive effect of aspirin in prostate cancer cells. Conclusion: The present research concluded that aspirin suppressed prostate cancer cell invasion by reducing MMP-9 activity and uPA expression through decreasing of IKK-β-mediated NF-κB activation, indicating that the ability of aspirin to inhibit cell invasion might be useful in the chemoprevention of

  9. 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.

  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. Evaluation, partial characterization and purification of acetylcholine esterase enzyme and antiangiogenic activity from marine sponges

    Directory of Open Access Journals (Sweden)

    Maushmi Shailesh Kumar

    2014-11-01

    Full Text Available Objective: To test three marine sponges Halichondria glabrata Keller, 1891; Spirastrella pachyspira (S. pachyspira Levi, 1958 and Cliona lobata Hancock, 1849 for the presence of the acetylcholinesterase (AChE in both young and developed samples from western coastal area of India. S. pachyspira methanolic extract was selected for anti/pro angiogenic activity. Methods: They were evaluated for AChE activity using Ellman’s assay based on production of yellow colored 5-thio-2-nitrobenzoate. Purification of the enzyme was planned using ammonium sulphate precipitation and characterization by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Chorioallantoic membrane (ChAM assay model was used for angiogenic/ antiangiogenic testing. Results: All the three sponges showed good specific enzyme activity and S. pachyspira contained maximum specific enzyme activity. Sixty percent of ammonium sulphate precipitation of crude protein sample gave single band at 66 kDa corresponding to the true AChE. ChAM assay was performed at 62.5, 125.0 and 250.0 µg/mL. Dosage beyond 250 µg/mL extract showed toxic response with anti angiogenic activity at all the concentrations. Conclusions: AChE activity was detected in all samples. Extract showed good anti-angiogenic response at 62.5 µg/mL. Extract was highly toxic affecting microvasculature of ChAM as well as normal growth and development of the embryo at 500 µg/mL. With further characterization of bioactive compounds from the extract of S. pachyspira, the compounds can be developed for anti tumor activity.

  12. Determination of esterase activity and characterization of cholinesterases in the reef fish Haemulon plumieri.

    Science.gov (United States)

    Leticia, Alpuche-Gual; Gerardo, Gold-Bouchot

    2008-11-01

    White grunt (Haemulon plumieri) has been proposed by the Mesoamerican Barrier Reef System (MBRS) Synoptic Monitoring Program as a bioindicator species. It is in this sense that the present study has a main goal to evaluate this organism's suitability as an indicator species. Individuals were captured during three seasons at the port of Sisal, Yucatan, Mexico which is located in an area that is considered to be weakly impacted by human activities such as agriculture or industry. Both cholinesterase (ChE) and carboxylesterase (CbE) activities were measured in brain, muscle, liver and eye of sampled individuals. Results indicated that ChE and CbE activities were greatest in the brain (256.3 ± 43) and in the liver (191 ± 21), respectively. Furthermore, ChEs detected in brain, liver and muscle were characterized, and results suggested that the acetylcholinesterase (AChE) type was more abundant relative to pseudocholinesterase (BChE) which was rare. In addition, K(m) and V(max) and IC(50) values were calculated from the Michaelis-Menten equation. Finally, an additional experiment in vitro showed a significant decrease in both ChE and CbE activities when different tissues were exposed to model xenobiotics, such as benzo[a]pyrene and Chlorpyrifos. In conclusion, findings from this study confirm the potential suitability of H. plumieri as an organic pollution bioindicator species, and thus of practical use for environmental biomonitoring purposes.

  13. [Effect of a low-frequencey magnetic field on esterase activity and change in pH in wheat germ during swelling of wehat seeds].

    Science.gov (United States)

    Aksenov, S I; Bulychev, A A; Grunina, T Iu; Turovetskiĭ, V B

    2000-01-01

    The role of nonsteady phenomena determined by a low velocity of ion movements in a weak external field is considered in relation to their possible nonlinear effects on processes occurring in boundary layers near the membrane, particularly, on the release of membrane-bound proteins and pH value. It is shown that a short-term treatment of wheat seeds with low-frequency magnetic field at the stage of esterase activation during seed swelling enhances the activation of esterases; the effect observed at final stages of activation depends on the time after the treatment with electromagnetic field. Treatment of seeds with electromagnetic field at this stage changed qualitatively the time course of the release of reaction products into the medium: the reaction rate increased initially and then decreased below the control level. At earlier stages of swelling in treated seeds and at all stages in control seeds, the time course of the product release was linear. The retardation of the release of the reaction products at terminal stages of esterase activation is presumably related to the release of proteins and their complexes under the action of electromagnetic field and the resulting restoration of the barrier properties of membranes. Treatment with electromagnetic field also caused a noticeable acceleration of proton flow form the medium, which was judged from pH changes in the bulk medium and in the vicinity of germ surface. The difference between the treated and control samples after 23-24 h of imbibition became statistically significant and was as high as 0.4 pH units. By taking into account the nonsteady phenomena occurring upon action of low-frequency electromagnetic field, it is possible to explain unusual dependences of biological effects on the amplitude of the electromagnetic field, including the atypical enhancement of these effects by the action of weak low-frequency fields.

  14. Cell surface display of cold-active esterase EstPc with the use of a new autotransporter from Psychrobacter cryohalolentis K5(T).

    Science.gov (United States)

    Petrovskaya, L E; Novototskaya-Vlasova, K A; Kryukova, E A; Rivkina, E M; Dolgikh, D A; Kirpichnikov, M P

    2015-01-01

    We have cloned the gene coding for AT877-a new predicted member of the autotransporter protein family with an esterase passenger domain from permafrost bacterium Psychrobacter cryohalolentis K5(T). Expression of AT877 gene in Escherichia coli resulted in accumulation of the recombinant autotransporter in the outer membrane fraction and at the surface of the induced cells. AT877 displayed maximum hydrolytic activity toward medium-chain p-nitrophenyl esters (C8-C10) at 50 °C and was resistant to the presence of several metal ions, organic solvents and detergents. Previously, we have described a cold-active esterase EstPc from the same bacterium which possesses high activity at low temperatures and relatively high thermal stability. To construct a cell surface display system for EstPc, the hybrid autotransporter gene coding for EstPc with the α-helical linker and the translocator domain from AT877 was constructed and expressed in E. coli. According to the results of the cell fractionation studies and esterase activity measurements, the EstPc passenger was successfully displayed at the surface of the induced cells. It demonstrated a temperature optimum at 15-25 °C and a substrate preference toward p-nitrophenyl butyrate (C4). Obtained results provide a new example of the biotechnologically relevant enzyme from the permafrost microbial community with potential applications for the conversion of short- and medium-chain ester substrates and a basis for the construction of a new cell surface display platform.

  15. Residual cyclooxygenase-1 activity and epinephrine reduce the antiplatelet effect of aspirin in patients with acute myocardial infarction.

    Science.gov (United States)

    Moscardó, Antonio; Santos, María Teresa; Fuset, María Paz; Ruano, Miguel; Vallés, Juana

    2011-04-01

    Aspirin treatment is essential in patients with acute myocardial infarction (AMI) to block platelet thromboxane (TXA)₂ synthesis. Epinephrine is known to enhance platelet reactivity induced by other agonists and to be elevated in patients with AMI due to stress. Our objective was to study the influence of epinephrine on platelet TXA₂ synthesis in patients treated with aspirin for AMI at early onset (within 48 hours) and the potential biochemical mechanisms involved in the functional response. Washed platelets from 45 patients with AMI and 10 aspirin-free controls were stimulated with arachidonic acid (AA) or AA + epinephrine, and aggregation and TXA₂ synthesis were evaluated. Full platelet aggregation was recorded in 8/45 patients (18%) with a partial TXA₂ inhibition (86%) vs. the aspirin-free controls. Platelets from the remaining 37 patients did not aggregate to AA and had TXA₂ inhibition >95%. However, when platelets were simultaneously stimulated with AA + epinephrine, in 25/37 patients a large intensity of aggregation (73%) was observed and a 5.5-fold increase in TXA₂ synthesis, although this remained residual (aspirin-free controls). This residual-TXA₂ was critical in the functional response, as demonstrated by the complete inhibition by TXA₂ receptor blockade or additional aspirin in vitro. The phosphatidylinositol-3-kinase activity and the cytosolic calcium levels participated in this platelet response elicited by a receptor cooperation mechanism, while the Rho/p160(ROCK) pathway or the blockade of the ADP receptors (P2Y1, P2Y12) were without effect. Residual-cyclooxygenase -1 activity and epinephrine enhance TXA₂-dependent platelet function, which may reduce the clinical benefit of aspirin in patients with AMI.

  16. 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.

  17. Aspirin Inhibits IKK-β-mediated Prostate Cancer Cell Invasion by Targeting Matrix Metalloproteinase-9 and Urokinase-Type Plasminogen Activator

    OpenAIRE

    Chongjun Shi; Nini Zhang; Yang Feng; Jiewei Cao; Xuyi Chen; Bin Liu

    2017-01-01

    Background/Aims: Aspirin has been demonstrated to possess potent chemopreventive and anticancer effects on prostate cancer. However, the more detailed molecular mechanisms of aspirin to suppress prostate cancer cell invasion have not been clearly elucidated. Methods: Transwell assays were performed to evaluate the effects of aspirin on cell invasion. Matrix metalloproteinases (MMPs) and serine proteinases activities in cell media were examined by gelatin zymography and ELISA. In addition, inh...

  18. Endophytic fungi producing of esterases: evaluation in vitro of the enzymatic activity using pH indicator.

    Science.gov (United States)

    Lisboa, Helen Cristina Fávero; Biasetto, Carolina Rabal; de Medeiros, João Batista; Âraújo, Angela Regina; Silva, Dulce Helena Siqueira; Teles, Helder Lopes; Trevisan, Henrique Celso

    2013-01-01

    A sensitive and efficient colorimetric method was optimized for detection of esterase enzymes produced by endophytic fungi for development of High-Throughput Screening (HTS). The fungi were isolated and obtained previously from plant species of Cerrado and Atlantic Forest located in areas of environmental preservation in the State of Sao Paulo / Brazil, as part of the project "Chemical and biological prospecting endophytic fungi associated to plant species of Cerrado and Atlantic Forest". The compounds ethyl butyrate, ethyl acetate and methyl propionate were used as standards esters which were hydrolyzed by extracellular enzyme from endophytic fungi (EC. 3.1.1.1--carboxyl-esterases) for production of carboxylic acids. Thus, the reduction of the pH increases the protonated indicator concentration (bromothymol blue), changing the color of the reaction medium (from blue to yellow), that can be observed and measured by spectrophotometry at 616 nm. The methodology with acid-base indicator was performed on 13 microorganisms, aiming Periconia atropurpurea as a potential source of esterase for biotransformation of short chain esters. The results also evidenced that this methodology showed to be efficient, fast, cheap, having low consumption of reagents and easy development, and can be applied to screen carboxylic-ester hydrolases in a large number of microorganisms.

  19. Relationship between high esterase activity and in vitro degradation of /sup 14/C-malathion by organophosphate-resistant and susceptible strains of the Kanzawa spider mite, Tetranychus kanzawai Kishida (Acarina: Tetranychidae), and their inhibition with specific synergists

    Energy Technology Data Exchange (ETDEWEB)

    Kuwahara, M. (National Inst. of Agricultural Sciences, Yatabe, Ibaraki (Japan)); Miyata, T.; Saito, T.; Eto, M.

    1981-08-01

    The relationship between the enzymes which catalyze hydrolysis of ..beta..-naphthyl acetate and degradation of malathion was studied in resistant and susceptible strains of the Kanzawa spider mite, Tetranychus kanzawai Kishida. The homogenate of resistant mites exhibited higher activity in the degradation of malathion in vitro than that of susceptible mites, but such activity was remarkably inhibited by the compound K-1, which also manifested a prominent synergism with malathion to resistant mites. Six esterase bands and three peaks of malathion degradation were resolved by agar-gel electrophoresis. Resistance to malathion was associated with increased esterase activity at E/sub 3/ and E/sub 4/ bands on which the main peak of malathion degradation was detected. The compound K-1 selectively inhibited the esterase and degradation activities. Compounds K-9 and IBP, on the other hand, selectively inhibited E/sub 1/ and E/sub 2/ bands which overlapped with the minor peaks of malanthion degradation.

  20. Aspirin Hydrolysis in Plasma Is a Variable Function of Butyrylcholinesterase and Platelet-activating Factor Acetylhydrolase 1b2 (PAFAH1b2)*

    Science.gov (United States)

    Zhou, Gang; Marathe, Gopal K.; Hartiala, Jaana; Hazen, Stanley L.; Allayee, Hooman; Tang, W. H. Wilson; McIntyre, Thomas M.

    2013-01-01

    Aspirin is rapidly hydrolyzed within erythrocytes by a heterodimer of PAFAH1b2/PAFAH1b3 but also in plasma by an unidentified activity. Hydrolysis in both compartments was variable, with a 12-fold variation in plasma among 2226 Cleveland Clinic GeneBank patients. Platelet inhibition by aspirin was suppressed in plasma that rapidly hydrolyzed aspirin. Plasma aspirin hydrolysis was significantly higher in patients with coronary artery disease compared with control subjects (16.5 ± 4.4 versus 15.1 ± 3.7 nmol/ml/min; p = 3.4 × 10−8). A genome-wide association study of 2054 GeneBank subjects identified a single locus immediately adjacent to the BCHE (butyrylcholinesterase) gene associated with plasma aspirin hydrolytic activity (lead SNP, rs6445035; p = 9.1 × 10−17). However, its penetrance was low, and plasma from an individual with an inactivating mutation in BCHE still effectively hydrolyzed aspirin. A second aspirin hydrolase was identified in plasma, the purification of which showed it to be homomeric PAFAH1b2. This is distinct from the erythrocyte PAFAH1b2/PAFAH1b3 heterodimer. Inhibitors showed that both butyrylcholinesterase (BChE) and PAFAH1b2 contribute to aspirin hydrolysis in plasma, with variation primarily reflecting non-genetic variation of BChE activity. Therefore, aspirin is hydrolyzed in plasma by two enzymes, BChE and a new extracellular form of platelet-activating factor acetylhydrolase, PAFAH1b2. Hydrolytic effectiveness varies widely primarily from non-genetic variation of BChE activity that affects aspirin bioavailability in blood and the ability of aspirin to inhibit platelet aggregation. PMID:23508960

  1. Non-specific esterases in partly mineralized bovine enamel

    DEFF Research Database (Denmark)

    Moe, D; Kirkeby, S

    1990-01-01

    Activity for non-specific esterase was demonstrated in the matrix of developing bovine enamel with alpha-naphthyl acetate and 5-bromoindoxyl acetate as the esterase substrates. By use of high-performance liquid chromatography gel filtration, ion-exchange chromatography, and electrophoresis three...

  2. 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.

  3. 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.

  4. Endophytic fungi producing of esterases: evaluation in vitro of the enzymatic activity using pH indicator

    Directory of Open Access Journals (Sweden)

    Helen Cristina Fávero Lisboa

    2013-09-01

    Full Text Available A sensitive and efficient colorimetric method was optimized for detection of esterase enzymes produced by endophytic fungi for development of High-Throughput Screening (HTS. The fungi were isolated and obtained previously from plant species of Cerrado and Atlantic Forest located in areas of environmental preservation in the State of Sao Paulo / Brazil, as part of the project "Chemical and biological prospecting endophytic fungi associated to plant species of Cerrado and Atlantic Forest". The compounds ethyl butyrate, ethyl acetate and methyl propionate were used as standards esters which were hydrolyzed by extracellular enzyme from endophytic fungi (EC. 3.1.1.1 -carboxylesterases for production of carboxylic acids. Thus, the reduction of the pH increases the protonated indicator concentration (bromothymol blue, changing the color of the reaction medium (from blue to yellow, that can be observed and measured by spectrophotometry at 616 nm. The methodology with acid-base indicator was performed on 13 microorganisms, aiming Periconia atropurpurea asapotential source of esterase for biotransformation of short chain esters. The results also evidenced that this methodology showed to be efficient, fast, cheap, having low consumption of reagents and easy development, and can be applied to screen carboxylic-ester hydrolases in a large number of microorganisms.

  5. Novel recombinant ethyl ferulate esterase from Burkholderia multivorans

    CSIR Research Space (South Africa)

    Rashamuse, KJ

    2007-11-01

    Full Text Available Isolation and identification of bacterial isolates with specific ferulic acid (FA) esterase activity and cloning of a gene encoding activity. A micro-organism with ethyl ferulate hydrolysing (EFH) activity was isolated by culture enrichment...

  6. Aspirin disrupts the mTOR-Raptor complex and potentiates the anti-cancer activities of sorafenib via mTORC1 inhibition.

    Science.gov (United States)

    Sun, Danni; Liu, Hongchun; Dai, Xiaoyang; Zheng, Xingling; Yan, Juan; Wei, Rongrui; Fu, Xuhong; Huang, Min; Shen, Aijun; Huang, Xun; Ding, Jian; Geng, Meiyu

    2017-10-10

    Aspirin is associated with a reduced risk of cancer and delayed progression of malignant disease. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-mTOR signaling is believed to partially contribute to these anticancer effects, although the mechanism is unclear. In this study, we revealed the mechanism underlying the effects of aspirin on AMPK-mTOR signaling, and described a mechanism-based rationale for the use of aspirin in cancer therapy. We found that aspirin inhibited mTORC1 signaling through AMPK-dependent and -independent manners. Aspirin inhibited the AMPK-TSC pathway, thus resulting in the suppression of mTORC1 activity. In parallel, it directly disrupted the mTOR-raptor interaction. Additionally, the combination of aspirin and sorafenib showed synergetic effects via inhibiting mTORC1 signaling and the PI3K/AKT, MAPK/ERK pathways. Aspirin and sorafenib showed synergetic anticancer efficacy in the SMMC-7721 model. Our study provides mechanistic insights and a mechanism-based rationale for the roles of aspirin in cancer treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Evaluation of antiulcer activity of Boswellia serrata bark extracts using aspirin induced ulcer model in albino rats

    OpenAIRE

    Khaja Zeeyauddin; Mohammed Ibrahim; Muna Abid; Mangamoori Lakshmi Narsu

    2011-01-01

    The effect of bark extracts of Boswellia serrata (Family Bursera-ceae) was evaluated in aspirin induced ulceration (200mg/kg) in albino rats. Antiulcer activity was evaluated by measuring ulcer index and percentage of ulcer healing. The petroleum ether (250mg/kg) and aqueous extracts (250mg/kg) of bark of Boswellia serrata plant showed significant antiulcer activity as evidenced by the data obtained. Histopathological findings also confirm the anti-ulcer activity of Boswellia serrata bark ext...

  8. Limited influence of aspirin intake on mast cell activation in patients with food-dependent exercise-induced anaphylaxis: comparison using skin prick and histamine release tests.

    Science.gov (United States)

    Fukunaga, Atsushi; Shimizu, Hideki; Tanaka, Mami; Kikuzawa, Ayuko; Tsujimoto, Mariko; Sekimukai, Akiko; Yamashita, Junji; Horikawa, Tatsuya; Nishigori, Chikako

    2012-09-01

    Food-dependent exercise-induced anaphylaxis (FDEIA) is a severe systemic syndrome induced by physical exercise after ingesting causative food. Aspirin is a well-known trigger for anaphylaxis in patients with FDEIA. Possible mechanisms by which symptoms are aggravated by aspirin include enhanced antigen absorption and mast cell activation. The aim of this study was to determine whether aspirin intake has an influence on mast cell/basophil activation in patients with FDEIA. Provocation tests revealed that adding aspirin to the causative food challenge in 7 of 9 (77.8%) patients with FDEIA provoked symptoms. In most cases, pretreatment with aspirin did not enhance skin tests (71.4%) or histamine release tests (88.9%) with food allergen challenges. The study confirms that histamine release and skin prick tests can be adjunctive tools for diagnosing FDEIA. In addition, our results suggest that exacerbation of FDEIA symptoms by aspirin is not mediated by direct effects of aspirin on mast cell/basophil activation.

  9. 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.

  10. Structure-activity relationship study of novel anticancer aspirin-based compounds.

    Science.gov (United States)

    Joseph, Stancy; Nie, Ting; Huang, Liqun; Zhou, Hui; Atmakur, Krishnaiah; Gupta, Ramesh C; Johnson, Francis; Rigas, Basil

    2011-01-01

    We performed a structure-activity relationship (SAR) study of a novel aspirin (ASA) derivative, which shows strong anticancer activity in vitro and in vivo. A series of ASA-based benzyl esters (ABEs) were synthesized and their inhibitory activity against human colon (HT-29 and SW480) and pancreatic (BxPC-3 and MIA PaCa-2) cancer cell lines was evaluated. The ABEs that we studied largely comprise organic benzyl esters bearing an ASA or acyloxy group (X) at the meta or para position of the benzyl ring and one of four different leaving groups. The nature of the salicyloyl/acyloxy function, the leaving group, and the additional substituents affecting the electron density of the benzyl ring, all were influential determinants of the inhibitory activity on cancer cell growth for each ABE. Positional isomerism also played a significant role in this effect. The mechanism of action of these compounds appears consistent with the notion that they generate either a quinone methide or an m-oxybenzyl zwitterion (or an m-hydroxybenzyl cation), which then reacts with a nucleophile, mediating their biological effect. Our SAR study provides an insight into the biological properties of this novel class of compounds and underscores their potential as anticancer agents.

  11. New Extremophilic Lipases and Esterases from Metagenomics

    Science.gov (United States)

    López-López, Olalla; Cerdán, Maria E; González Siso, Maria I

    2014-01-01

    Lipolytic enzymes catalyze the hydrolysis of ester bonds in the presence of water. In media with low water content or in organic solvents, they can catalyze synthetic reactions such as esterification and transesterification. Lipases and esterases, in particular those from extremophilic origin, are robust enzymes, functional under the harsh conditions of industrial processes owing to their inherent thermostability and resistance towards organic solvents, which combined with their high chemo-, regio- and enantioselectivity make them very attractive biocatalysts for a variety of industrial applications. Likewise, enzymes from extremophile sources can provide additional features such as activity at extreme temperatures, extreme pH values or high salinity levels, which could be interesting for certain purposes. New lipases and esterases have traditionally been discovered by the isolation of microbial strains producing lipolytic activity. The Genome Projects Era allowed genome mining, exploiting homology with known lipases and esterases, to be used in the search for new enzymes. The Metagenomic Era meant a step forward in this field with the study of the metagenome, the pool of genomes in an environmental microbial community. Current molecular biology techniques make it possible to construct total environmental DNA libraries, including the genomes of unculturable organisms, opening a new window to a vast field of unknown enzymes with new and unique properties. Here, we review the latest advances and findings from research into new extremophilic lipases and esterases, using metagenomic approaches, and their potential industrial and biotechnological applications. PMID:24588890

  12. Identification of a new family of enzymes with potential O-acetylpeptidoglycan esterase activity in both Gram-positive and Gram-negative bacteria

    Directory of Open Access Journals (Sweden)

    Clarke Anthony J

    2005-08-01

    Full Text Available Abstract Background The metabolism of the rigid bacterial cell wall heteropolymer peptidoglycan is a dynamic process requiring continuous biosynthesis and maintenance involving the coordination of both lytic and synthetic enzymes. The O-acetylation of peptidoglycan has been proposed to provide one level of control on these activities as this modification inhibits the action of the major endogenous lytic enzymes, the lytic transglycosylases. The O-acetylation of peptidoglycan also inhibits the activity of the lysozymes which serve as the first line of defense of host cells against the invasion of bacterial pathogens. Despite this central importance, there is a dearth of information regarding peptidoglycan O-acetylation and nothing has previously been reported on its de-acetylation. Results Homology searches of the genome databases have permitted this first report on the identification of a potential family of O-Acetylpeptidoglycan esterases (Ape. These proteins encoded in the genomes of a variety of both Gram-negative and Gram-positive bacteria, including a number of important human pathogens such as species of Neisseria, Helicobacter, Campylobacter, and Bacillus anthracis, have been organized into three families based on amino acid sequence similarities with family 1 being further divided into three sub-families. The genes encoding these proteins are shown to be clustered with Peptidoglycan O-acetyltransferases (Pat and in some cases, together with other genes involved in cell wall metabolism. Representative bacteria that encode the Ape proteins were experimentally shown to produce O-acetylated peptidoglycan. Conclusion The hypothetical proteins encoded by the pat and ape genes have been organized into families based on sequence similarities. The Pat proteins have sequence similarity to Pseudomonas aeruginosa AlgI, an integral membrane protein known to participate in the O-acetylation of the exopolysaccaride, alginate. As none of the bacteria

  13. Aspirin suppresses growth in PI3K-mutant breast cancer by activating AMPK and inhibiting mTORC1 signaling

    Science.gov (United States)

    Henry, Whitney S.; Laszewski, Tyler; Tsang, Tiffany; Beca, Francisco; Beck, Andrew H.; McAllister, Sandra S.; Toker, Alex

    2016-01-01

    Despite the high incidence of oncogenic mutations in PIK3CA, the gene encoding the catalytic subunit of phosphoinositide 3-kinase (PI3K), PI3K inhibitors have yielded little clinical benefit for breast cancer patients. Recent epidemiological studies have suggested a therapeutic benefit from aspirin intake in cancers harboring oncogenic PIK3CA. Here we show that mutant PIK3CA-expressing breast cancer cells have greater sensitivity to aspirin-mediated growth suppression than their wild-type counterparts. Aspirin decreased viability and anchorage-independent growth of mutant PIK3CA breast cancer cells independently of its effects on cyclooxygenase-2 (COX-2) and nuclear factor-kappa B (NF-κB). We ascribed the effects of aspirin to AMP-activated protein kinase (AMPK) activation, mammalian target of rapamycin complex 1 (mTORC1) inhibition, and autophagy induction. In vivo, oncogenic PIK3CA-driven mouse mammary tumors treated daily with aspirin resulted in decreased tumor growth kinetics, while combination therapy of aspirin and a PI3K inhibitor further attenuated tumor growth. Our study supports evaluation of aspirin and PI3K pathway inhibitors as combination therapy for targeting breast cancer. PMID:27940576

  14. p-Nitrophenyl Acetate Esterase Activity and Cortisol as Biomarkers of Metal Pollution in Blood of Olive Ridley Turtles (Lepidochelys olivacea).

    Science.gov (United States)

    Cortés-Gómez, Adriana A; Tvarijonaviciute, Asta; Teles, Mariana; Cuenca, Rafaela; Fuentes-Mascorro, Gisela; Romero, Diego

    2017-10-17

    This study was designed to determine the concentrations of p-nitrophenyl acetate esterase activity (EA) and cortisol in serum of marine Olive Ridley turtles (Lepidochelys olivacea) from a Mexican Pacific population ("La Escobilla" beach) and to evaluate the possible relationship of inorganic elements with these biomarkers. EA, cortisol, and selected chemical elements (Cd, Pb, Ti, Sr, Se, Al, As, and Zn) were measured in the blood of 44 sea turtles from the Eastern Pacific (Southeast Mexico). Serum EA ranged from 0.4 to 3.9 UI mL -1 , and cortisol concentrations ranged from 0.07 to 2.5 μL dL -1 . A strong negative correlation between EA and cortisol was observed (r = - 0.59, p < 0.01), and significant correlations also were found between EA and important metals, such as Cd (r = - 0.31, p < 0.05) and Pb (r = - 0.27, p < 0.05), and elements of growing concern like Ti (r = - 0.37, p < 0.01) or Al (r = - 0.34, p < 0.05) and between cortisol and Sr (r = 0.29, p < 0.05), Se (r = - 0.38, p < 0.01), and As (r = - 0.26, p < 0.05). These results suggest that turtles chronically exposed to different inorganic elements (such as Pb and Cd), driving to a highly consume of esterase and to a prolonged cortisol elevation. The obtained results indicate the usefulness of these biomarkers in the assessment of inorganic elements pollution in this species.

  15. Pregastric esterase and other oral lipases--a review.

    Science.gov (United States)

    Nelson, J H; Jensen, R G; Pitas, R E

    1977-03-01

    The secretion of pregastric esterase and other oral lipases has been detected in 13 species. Research on secretion by the human, calf, kid goat, lamb, and rat of pregastric esterase has been significant. Secretion by calves is little affected by age or diet but is greater when calves are nipple fed than when pail fed. Whole milk sham-fed to calves exhibits immediate, sharp decreases in pH and rennet coagulation time resulting from liberation of free fatty acids by pregastric esterase. Bacterial counts in sham-fed products are higher than in control (nonfed) products, but during subsequent incubation bacterial numbers increase less rapidly in sham-fed products. Calf pregastric esterase is a major fat digestive enzyme in young calves but gradually becomes subsidiary to pancreatic lipase as secretion of the latter develops with age. Calf, kid goat, and lamb pregastric esterase exhibits optimum activity on milk fat but is capable of splitting other dietary fats. Data on oral and "gastric" lipases in calves, humans, and rats suggests that gastric lipase is oral lipase. Data on pH and temperature optima as well as activation and inhibition of oral lipases is contradictory but appears to vary considerably between species. Calf pregastric esterase exhibits a unique specificity for fatty acids 4:0 to 10:0 and preferentially hydrolyzes the primary ester position of glycerin. Preparations of calf, kid goat, and lamb pregastric esterase are used commercially to impar typical flavors to Italian-type and Feta cheeses and to accelerate flavor development in other cheeses and cheese-like products. Butterfat modified by pregastric esterase is utilized to impart dairy flavor character to a wide range of processed foods. Treatment with pregastric esterase of calf scours and human malabsorption of syndrome also has been reported.

  16. A novel hybrid aspirin-NO-releasing compound inhibits TNFalpha release from LPS-activated human monocytes and macrophages

    Directory of Open Access Journals (Sweden)

    Fox Sarah

    2008-07-01

    Full Text Available Abstract Background The cytoprotective nature of nitric oxide (NO led to development of NO-aspirins in the hope of overcoming the gastric side-effects of aspirin. However, the NO moiety gives these hybrids potential for actions further to their aspirin-mediated anti-platelet and anti-inflammatory effects. Having previously shown that novel NO-aspirin hybrids containing a furoxan NO-releasing group have potent anti-platelet effects, here we investigate their anti-inflammatory properties. Here we examine their effects upon TNFα release from lipopolysaccharide (LPS-stimulated human monocytes and monocyte-derived macrophages and investigate a potential mechanism of action through effects on LPS-stimulated nuclear factor-kappa B (NF-κB activation. Methods Peripheral venous blood was drawn from the antecubital fossa of human volunteers. Mononuclear cells were isolated and cultured. The resultant differentiated macrophages were treated with pharmacologically relevant concentrations of either a furoxan-aspirin (B8, B7; 10 μM, their respective furazan NO-free counterparts (B16, B15; 10 μM, aspirin (10 μM, existing nitroaspirin (NCX4016; 10 μM, an NO donor (DEA/NO; 10 μM or dexamethasone (1 μM, in the presence and absence of LPS (10 ng/ml; 4 h. Parallel experiments were conducted on undifferentiated fresh monocytes. Supernatants were assessed by specific ELISA for TNFα release and by lactate dehydrogenase (LDH assay for cell necrosis. To assess NF-κB activation, the effects of the compounds on the loss of cytoplasmic inhibitor of NF-κB, IκBα (assessed by western blotting and nuclear localisation (assessed by immunofluorescence of the p65 subunit of NF-κB were determined. Results B8 significantly reduced TNFα release from LPS-treated macrophages to 36 ± 10% of the LPS control. B8 and B16 significantly inhibited monocyte TNFα release to 28 ± 5, and 49 ± 9% of control, respectively. The B8 effect was equivalent in magnitude to that of

  17. The effect of increased yeast alcohol acetyltransferase and esterase activity on the flavour profiles of wine and distillates.

    Science.gov (United States)

    Lilly, Mariska; Bauer, Florian F; Lambrechts, Marius G; Swiegers, Jan H; Cozzolino, Daniel; Pretorius, Isak S

    2006-07-15

    The fruity odours of wine are largely derived from the synthesis of esters and higher alcohols during yeast fermentation. The ATF1- and ATF2-encoded alcohol acetyltransferases of S. cerevisiae are responsible for the synthesis of ethyl acetate and isoamyl acetate esters, while the EHT1-encoded ethanol hexanoyl transferase is responsible for synthesizing ethyl caproate. However, esters such as these might be degraded by the IAH1-encoded esterase. The objectives of this study were: (a) to overexpress the genes encoding ester-synthesizing and ester-degrading enzymes in wine yeast; (b) to prepare Colombard table wines and base wines for distillation using these modified strains; and (c) to analyse and compare the ester concentrations and aroma profiles of these wines and distillates. The overexpression of ATF1 significantly increased the concentrations of ethyl acetate, isoamyl acetate, 2-phenylethyl acetate and ethyl caproate, while the overexpression of ATF2 affected the concentrations of ethyl acetate and isoamyl acetate to a lesser degree. The overexpression of IAH1 resulted in a significant decrease in ethyl acetate, isoamyl acetate, hexyl acetate and 2-phenylethyl acetate. The overexpression of EHT1 resulted in a marked increase in ethyl caproate, ethyl caprylate and ethyl caprate. The flavour profile of the wines and distillates prepared using the modified strains were also significantly altered as indicated by formal sensory analysis. This study offers prospects for the development of wine yeast starter strains with optimized ester-producing capability that could assist winemakers in their effort to consistently produce wine and distillates such as brandy to definable flavour specifications and styles.

  18. Lactobacillus fermentum CRL1446 Ameliorates Oxidative and Metabolic Parameters by Increasing Intestinal Feruloyl Esterase Activity and Modulating Microbiota in Caloric-Restricted Mice

    Directory of Open Access Journals (Sweden)

    Matias Russo

    2016-07-01

    Full Text Available The purpose of this study was to determine whether the administration of the feruloyl esterase (FE-producing strain Lactobacillus fermentum CRL1446 enhances metabolic and oxidative parameters in caloric-restricted (CR mice. Balb/c male mice were divided into ad libitum fed Group (ALF Group, CR diet Group (CR Group and CR diet plus L. fermentum Group (CR-Lf Group. CR diet was administered during 45 days and CRL1446 strain was given in the dose of 108 cells/mL/day/mouse. FE activity was determined in intestinal mucosa and content at Day 1, 20 and 45. Triglyceride, total cholesterol, glucose, thiobarbituric acid reactive substances (TBARS levels and glutathione reductase activity were determined in plasma. Gut microbiota was evaluated by high-throughput sequencing of 16S rRNA gene amplicons. At Day 45, total intestinal FE activity in CR-Lf Group was higher (p = 0.020 than in CR and ALF groups and an improvement in both metabolic (reductions in triglyceride (p = 0.0025, total cholesterol (p = 0.005 and glucose (p < 0.0001 levels and oxidative (decrease of TBARS levels and increase of plasmatic glutathione reductase activity (p = 0.006 parameters was observed, compared to ALF Group. CR diet increased abundance of Bacteroidetes and CRL1446 administration increased abundance of Bifidobacterium and Lactobacillus genus. L. fermentun CRL1446 exerted a bifidogenic effect under CR conditions.

  19. Insecticidal and acetylcholine esterase inhibition activity of Apiaceae plant essential oils and their constituents against adults of German cockroach (Blattella germanica).

    Science.gov (United States)

    Yeom, Hwa-Jeong; Kang, Jae Soon; Kim, Gil-Hah; Park, Il-Kwon

    2012-07-25

    We evaluated the insecticidal and acetylcholine esterase (AChE) inhibition activity of 11 Apiaceae plant essential oils and their constituents in adult male and female Blattella germanica. Of the 11 Apiaceae plant essential oils tested, dill (Anethum graveolens), carvi (Carum carvi), and cumin (Cuminum cyminum) demonstrated >90% fumigant toxicity against adult male German cockroaches at a concentration of 5 mg/filter paper. In a contact toxicity test, dill (Anethum graveolens), carvi (Carum carvi), cumin (Cuminum cyminum), and ajowan (Trachyspermum ammi) produced strong insecticidal activity against adult male and female German cockroaches. Among the test compounds, (S)-(+)-carvone, 1,8-cineole, trans-dihydrocarvone, cuminaldehyde, trans-anethole, p-cymene, and γ-terpinene demonstrated strong fumigant toxicity against adult male and female B. germanica. In a contact toxicity test, carveol, cuminaldehyde, (S)-(+)-carvone, trans-anethole, thymol, and p-cymene showed strong contact toxicity against adult male and female B. germanica. IC(50) values of α-pinene, carvacrol, and dihydrocarvone against female AChE were 0.28, 0.17, and 0.78 mg/mL, respectively. The toxicity of the blends of constituents identified in 4 active oils indicated that carvone, cuminaldehyde, and thymol were major contributors to the fumigant activity or contact toxicity of the artificial blend.

  20. Appraisal of sildenafil binding on the structure and promiscuous esterase activity of native and histidine-modified forms of carbonic anhydrase II.

    Science.gov (United States)

    Mahdiuni, Hamid; Bijari, Nooshin; Varzandian, Masoud; Ghadami, Seyyed Abolghasem; Khazaei, Mozafar; Nikbakht, Mohammad Reza; Khodarahmi, Reza

    2013-01-01

    Sildenafil was investigated for its interaction with the native and modified human carbonic anhydrase II (hCA II). Modification of exposed histidine side chains with diethyl pyrocarbonate decreased esterase activity of the enzyme. The treatment of both native and modified CA with sildenafil revealed slight and moderate enzyme activation profiles, respectively. In addition, in the present study the effects of sildenafil on the structural properties of native and modified hCA II were investigated employing different computer simulation and spectroscopic techniques such as UV-vis, circular dichroism (CD), fluorescence spectroscopy and molecular dynamics. Fluorescence measurements showed that the sildenafil acts as a quencher of the native and modified enzyme fluorescence. Stern-Volmer analyses revealed the existence of one binding site on the native/modified enzyme for sildenafil. The thermodynamic parameters, enthalpy change (∆H) and entropy change (∆S) of drug binding were not also similar, which indicate that different interactions are responsible in CA-drug interaction. Calculation of the protein surface hydrophobicity (PSH), using 1,8-Anilinonaphtalene Sulfonate (ANS), indicated the increment of PSH of native and modified hCA II in the presence of sildenafil. Overall, sildenafil-CA interaction probably induces protein conformational changes and completes reorganization of both hydrogen bond networks within the active site cavity and hydration positions on the protein surface. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Evaluation of antiulcer activity of Boswellia serrata bark extracts using aspirin induced ulcer model in albino rats

    Directory of Open Access Journals (Sweden)

    Khaja Zeeyauddin

    2011-01-01

    Full Text Available The effect of bark extracts of Boswellia serrata (Family Bursera-ceae was evaluated in aspirin induced ulceration (200mg/kg in albino rats. Antiulcer activity was evaluated by measuring ulcer index and percentage of ulcer healing. The petroleum ether (250mg/kg and aqueous extracts (250mg/kg of bark of Boswellia serrata plant showed significant antiulcer activity as evidenced by the data obtained. Histopathological findings also confirm the anti-ulcer activity of Boswellia serrata bark extracts in albino rats.

  2. 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.

  3. A novel aspirin prodrug inhibits NFκB activity and breast cancer stem cell properties.

    Science.gov (United States)

    Kastrati, Irida; Litosh, Vladislav A; Zhao, Shuangping; Alvarez, Manuel; Thatcher, Gregory R J; Frasor, Jonna

    2015-11-04

    Activation of cyclooxygenase (COX)/prostaglandin and nuclear factor κB (NFκB) pathways can promote breast tumor initiation, growth, and progression to drug resistance and metastasis. Thus, anti-inflammatory drugs have been widely explored as chemopreventive and antineoplastic agents. Aspirin (ASA), in particular, is associated with reduced breast cancer incidence but gastrointestinal toxicity has limited its usefulness. To improve potency and minimize toxicity, ASA ester prodrugs have been developed, in which the carboxylic acid of ASA is masked and ancillary pharmacophores can be incorporated. To date, the effects of ASA and ASA prodrugs have been largely attributed to COX inhibition and reduced prostaglandin production. However, ASA has also been reported to inhibit the NFκB pathway at very high doses. Whether ASA prodrugs can inhibit NFκB signaling remains relatively unexplored. A library of ASA prodrugs was synthesized and screened for inhibition of NFκB activity and cancer stem-like cell (CSC) properties, an important PGE2-and NFκB-dependent phenotype of aggressive breast cancers. Inhibition of NFκB activity was determined by dual luciferase assay, RT-QPCR, p65 DNA binding activity and Western blots. Inhibition of CSC properties was determined by mammosphere growth, CD44(+)CD24(-)immunophenotype and tumorigenicity at limiting dilution. While we identified multiple ASA prodrugs that are capable of inhibiting the NFκB pathway, several were associated with cytotoxicity. Of particular interest was GTCpFE, an ASA prodrug with fumarate as the ancillary pharmacophore. This prodrug potently inhibits NFκB activity without innate cytotoxicity. In addition, GTCpFE exhibited selective anti-CSC activity by reducing mammosphere growth and the CD44(+)CD24(-)immunophenotype. Moreover, GTCpFE pre-treated cells were less tumorigenic and, when tumors did form, latency was increased and growth rate was reduced. Structure-activity relationships for GTCpFE indicate that

  4. Mercuric chloride-induced alterations of levels of noradrenaline, dopamine, serotonin and acetylcholine esterase activity in different regions of rat brain during postnatal development

    Energy Technology Data Exchange (ETDEWEB)

    Lakshmana, M.K. (Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore (India)); Desiraju, T. (Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore (India)); Raju, T.R. (Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore (India))

    1993-07-01

    Wistar rats were fed mercuric chloride, 4 mg/kg body weight per day chronically from postnatal day 2 to 60 by gastric intubation. Mercury consumption was then discontinued until 170 days to allow time for recovery. Since mercury caused reduction in body weight, an underweight group was also included besides the normal saline group. Levels of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT) and the activity of acetylcholine esterase (AChE) were assayed in various brain regions in different age groups. By 60 days of age, the mercury group showed elevations of NA levels in olfactory bulb (OB), visual cortex (VC) and brain stem (BS) but not in striatumaccumbens (SA) and hippocampus (HI). DA levels were also increased in OB, HI, VC and BS but not in SA. AChE activity was decreased in the mercury group only in HI and VC at 20 days of age. The Mercury group showed no behavioural abnormality outwardly; however, operant conditioning relevated a dificiency in performance. Nevertheless, all these changes disappeared after discontinuation of mercury intake. Thus the changes occurring in the brain at this level of oral mercuric chloride intake seem to reflect adaptive neural mechanisms rather than pathological damage. (orig.)

  5. Potential active-site residues in polyneuridine aldehyde esterase, a central enzyme of indole alkaloid biosynthesis, by modelling and site-directed mutagenesis.

    Science.gov (United States)

    Mattern-Dogru, Emine; Ma, Xueyan; Hartmann, Joachim; Decker, Heinz; Stöckigt, Joachim

    2002-06-01

    In the biosynthesis of the antiarrhythmic alkaloid ajmaline, polyneuridine aldehyde esterase (PNAE) catalyses a central reaction by transforming polyneuridine aldehyde into epi-vellosimine, which is the immediate precursor for the synthesis of the ajmalane skeleton. The PNAE cDNA was previously heterologously expressed in E. coli. Sequence alignments indicated that PNAE has a 43% identity to a hydroxynitrile lyase from Hevea brasiliensis, which is a member of the alpha/beta hydrolase superfamily. The catalytic triad, which is typical for this family, is conserved. By site-directed mutagenesis, the members of the catalytic triad were identified. For further detection of the active residues, a model of PNAE was constructed based on the X-ray crystallographic structure of hydroxynitrile lyase. The potential active site residues were selected on this model, and were mutated in order to better understand the relationship of PNAE with the alpha/beta hydrolases, and as well its mechanism of action. The results showed that PNAE is a novel member of the alpha/beta hydrolase enzyme superfamily.

  6. Studies of the Interaction between Isoimperatorin and Human Serum Albumin by Multispectroscopic Method: Identification of Possible Binding Site of the Compound Using Esterase Activity of the Protein

    Directory of Open Access Journals (Sweden)

    Samira Ranjbar

    2013-01-01

    Full Text Available Isoimperatorin is one of the main components of Prangos ferulacea as a linear furanocoumarin and used as anti-inflammatory, analgesic, antispasmodic, and anticancer drug. Human serum albumin (HSA is a principal extracellular protein with a high concentration in blood plasma and carrier for many drugs to different molecular targets. Since the carrying of drug by HSA may affect on its structure and action, we decided to investigate the interaction between HSA and isoimperatorin using fluorescence and UV spectroscopy. Fluorescence data indicated that isoimperatorin quenches the intrinsic fluorescence of the HSA via a static mechanism and hydrophobic interaction play the major role in the drug binding. The binding average distance between isoimperatorin and Trp 214 of HSA was estimated on the basis of the theory of Förster energy transfer. Decrease of protein surface hydrophobicity (PSH was also documented upon isoimperatorin binding. Furthermore, the synchronous fluorescence spectra show that the microenvironment of the tryptophan residues does not have obvious changes. Site marker compettive and fluorescence experiments revealed that the binding of isoimperatorin to HSA occurred at or near site I. Finally, the binding details between isoimperatorin and HSA were further confirmed by molecular docking and esterase activity inhibition studies which revealed that drug was bound at subdomain IIA.

  7. 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.

  8. Synthesis and Anticancer Activities of 4-[(Halophenyldiazenyl]phenol and 4-[(Halophenyldiazenyl]phenyl Aspirinate Derivatives against Nasopharyngeal Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Boon Kui Ho

    2017-01-01

    Full Text Available Aspirin and azo derivatives have been widely studied and have drawn considerable attention due to diverse biological activities. In this study, a series of 4-[(halophenyldiazenyl]phenyl aspirinate derivatives were synthesized from the reaction of aspirin with 4-[(halophenyldiazenyl]phenol via esterification, in the presence of DCC/DMAP in DCM with overall yield of 45–54%. 4-[(Halophenyldiazenyl]phenol was prepared prior to esterification from coupling reaction of aniline derivatives and phenol in basic solution. All compounds were characterized using elemental analysis, FTIR, and 1H and 13C NMR spectroscopies. All compounds were screened for their anticancer activities against nasopharyngeal cancer (NPC HK-1 cell lines and the viability of cultured cells was determined by MTS [3-(4,5-dimethylthiazol-2-yl-5-(3-carboxylmethoxylphenyl-2-(4-sulfophenyl-2H-tetrazolium]-based colorimetric assay. 4-[(E-(Fluorophenyldiazenyl]phenol showed the highest anticancer activity against NPC HK-1 cell lines compared to other synthesized compounds. 4-[(Halophenyldiazenyl]phenyl aspirinate showed low cytotoxicity against NPC HK-1 cell lines compared to 4-[(halophenyldiazenyl]phenol but better anticancer activity than aspirin alone.

  9. Aspirin inhibits lipopolysaccharide-induced COX-2 expression and PGE2 production in porcine alveolar macrophages by modulating protein kinase C and protein tyrosine phosphatase activity.

    Science.gov (United States)

    Duan, Yuzhong; Chen, Fanglin; Zhang, Anmei; Zhu, Bo; Sun, Jianguo; Xie, Qichao; Chen, Zhengtang

    2014-01-01

    Aspirin has been demonstrated to be effective in inhibiting COX-2 and PGE(2) in Alveolar macrophages (AMs). However, the mechanisms have not been fully understood. In the present study, we found that pretreatment with aspirin inhibited LPS-induced COX-2 and PGE(2) upregulation, IκBα degradation, NFκB activation and the increase of PKC activity, but elevated LPS-induced the decrease of PTP activity. The PKC inhibitor calphostin C dramatically reduced the COX-2 mRNA and PGE(2) levels, but the PTP inhibitor peroxovanadium (POV) significantly increased the COX-2 mRNA and PGE(2) levels. Furthermore, the PTP inhibitor mitigated the inhibitory effect of aspirin on COX-2 and PGE(2) upregulation and NF-κB activation, whereas the PKC inhibitor enhanced the inhibitory effects of aspirin on the production of COX-2 and PGE(2). Our data indicate a novel mechanism by which aspirin acts as a potent anti-inflammatory agent in alveolus macrophages and ALI.

  10. Acetyl Xylan Esterase Axe1 (T. reesei, Carbohydrate Esterase Family 5) Supplemented to a (Hemi)cellulolytic Preparation Enhances Degradation of Recalcitrant Corn Silage Polysaccharides

    NARCIS (Netherlands)

    Neumüller, K.G.; Streekstra, H.; Gruppen, H.; Schols, H.A.

    2014-01-01

    The increase in hydrolytic activity towards corn silage water unextractable solids by supplementation of acetyl xylan esterase 1 (T. reesei, TrAxe1), belonging to arbohydrate esterase (CE) family 5, to an A. niger / T. emersonii enzyme preparation is presented. TrAxe1 was cloned and expressed in A

  11. Aspirin inhibits lipopolysaccharide-induced COX-2 expression and PGE2 production in porcine alveolar macrophages by modulating protein kinase C and protein tyrosine phosphatase activity

    OpenAIRE

    Duan, Yuzhong; Chen, Fanglin; Zhang, Anmei; Zhu, Bo; Sun, Jianguo; Xie, Qichao; Chen, Zhengtang

    2014-01-01

    Aspirin has been demonstrated to be effective in inhibiting COX-2 and PGE2 in Alveolar macrophages (AMs). However, the mechanisms have not been fully understood. In the present study, we found that pretreatment with aspirin inhibited LPS-induced COX-2 and PGE2 upregulation, IκBα degradation, NFκB activation and the increase of PKC activity, but elevated LPS-induced the decrease of PTP activity. The PKC inhibitor calphostin C dramatically reduced the COX-2 mRNA and PGE2 levels, but the PTP inh...

  12. 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 ...

  13. Determinants and Prediction of Esterase Substrate Promiscuity Patterns.

    Science.gov (United States)

    Martínez-Martínez, Mónica; Coscolín, Cristina; Santiago, Gerard; Chow, Jennifer; Stogios, Peter J; Bargiela, Rafael; Gertler, Christoph; Navarro-Fernández, José; Bollinger, Alexander; Thies, Stephan; Méndez-García, Celia; Popovic, Ana; Brown, Greg; Chernikova, Tatyana N; García-Moyano, Antonio; Bjerga, Gro E K; Pérez-García, Pablo; Hai, Tran; Del Pozo, Mercedes V; Stokke, Runar; Steen, Ida H; Cui, Hong; Xu, Xiaohui; Nocek, Boguslaw P; Alcaide, María; Distaso, Marco; Mesa, Victoria; Peláez, Ana I; Sánchez, Jesús; Buchholz, Patrick C F; Pleiss, Jürgen; Fernández-Guerra, Antonio; Glöckner, Frank O; Golyshina, Olga V; Yakimov, Michail M; Savchenko, Alexei; Jaeger, Karl-Erich; Yakunin, Alexander F; Streit, Wolfgang R; Golyshin, Peter N; Guallar, Víctor; Ferrer, Manuel; The Inmare Consortium

    2018-01-19

    Esterases receive special attention because of their wide distribution in biological systems and environments and their importance for physiology and chemical synthesis. The prediction of esterases' substrate promiscuity level from sequence data and the molecular reasons why certain such enzymes are more promiscuous than others remain to be elucidated. This limits the surveillance of the sequence space for esterases potentially leading to new versatile biocatalysts and new insights into their role in cellular function. Here, we performed an extensive analysis of the substrate spectra of 145 phylogenetically and environmentally diverse microbial esterases, when tested with 96 diverse esters. We determined the primary factors shaping their substrate range by analyzing substrate range patterns in combination with structural analysis and protein-ligand simulations. We found a structural parameter that helps rank (classify) the promiscuity level of esterases from sequence data at 94% accuracy. This parameter, the active site effective volume, exemplifies the topology of the catalytic environment by measuring the active site cavity volume corrected by the relative solvent accessible surface area (SASA) of the catalytic triad. Sequences encoding esterases with active site effective volumes (cavity volume/SASA) above a threshold show greater substrate spectra, which can be further extended in combination with phylogenetic data. This measure provides also a valuable tool for interrogating substrates capable of being converted. This measure, found to be transferred to phosphatases of the haloalkanoic acid dehalogenase superfamily and possibly other enzymatic systems, represents a powerful tool for low-cost bioprospecting for esterases with broad substrate ranges, in large scale sequence data sets.

  14. Histochemical studies on genetical control of hormonal enzyme inducibility in the mouse. I. Non-specific esterase activity and regional histology of the epididymis

    DEFF Research Database (Denmark)

    Blecher, S R; Kirkeby, S

    1978-01-01

    As a base line for future cell genetical studies the authors record the distribution of non-specific esterase reaction in the various histologically distinguishable cell types of the mouse epididymis. The findings are correlated with previous descriptions of the lobar structure of the organ...

  15. 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...

  16. Distinct roles of carbohydrate esterase family CE16 acetyl esterases and polymer-acting acetyl xylan esterases in xylan deacetylation

    NARCIS (Netherlands)

    Koutaniemi, S.; Gool, van M.P.; Juvonen, M.; Hinz, S.W.A.; Schols, H.A.; Tenkanen, M.

    2013-01-01

    Mass spectrometric analysis was used to compare the roles of two acetyl esterases (AE, carbohydrate esterase family CE16) and three acetyl xylan esterases (AXE, families CE1 and CE5) in deacetylation of natural substrates, neutral (linear) and 4-O-methyl glucuronic acid (MeGlcA) substituted

  17. Cell-Bound Lipase and Esterase of Brevibacterium linens

    Science.gov (United States)

    Sørhaug, Terje; Ordal, Z. John

    1974-01-01

    The activities of glycerol ester hydrolase, lipase (EC 3.1.1.3) and carboxylesterase, and esterase (EC 3.1.1.1) were determined for whole cell preparations of Brevibacterium linens by using the pH-stat assay. The culture growth liquors were inactive against the three substrates, tributyrin emulsion, triacetin, and methyl butyrate. Cells washed in water had less activity than cells washed in 5% NaCl; the ratio of activities was close to 1:2 for all strains using tributyrin emulsion as the substrate. For the esterase substrates, this relationship varied widely and was strain dependent. The ability to hydrolyze the two esterase substrates varied independently of the level of lipase activity. PMID:4824883

  18. COMPARATIVE STUDY OF ANTI-INFLAMMATORY ACTIVITY OF ROSUVASTATIN WITH THAT OF ASPIRIN IN ALBINO RATS

    Directory of Open Access Journals (Sweden)

    Mohammed Abdul Majeed

    2017-09-01

    Full Text Available BACKGROUND Statins are HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors well known for their hypolipidemic action. More recently, there has been an increased interest in pleiotropic effects of statins like anti-inflammatory action that occurs independent of their lipid lowering effect. Statins exert anti-inflammatory action by preventing the isoprenylation of Rho proteins, a family of small G proteins and subsequent disruption of their functions. Hence, the present study was planned to compare the anti-inflammatory effect of rosuvastatin with that of aspirin on acute inflammation, so that it could be utilised in acute inflammatory conditions as an adjuvant or as a monotherapy avoiding adverse effects of commonly used antiinflammatory agents like NSAIDS (nonsteroidal anti-inflammatory drugs. The aim of the study is to compare anti-inflammatory effect of rosuvastatin with that of aspirin on carrageenan-induced inflammation in albino rats. MATERIALS AND METHODS 18 adult albino rats weighing between 100-150 g of either sex were divided into 3 groups. Control, Standard and test receiving oral normal saline (2 mL/kg, aspirin (100 mg/kg and rosuvastatin (5 mg/kg drug solutions, respectively. Acute inflammation model of carrageenan-induced paw oedema was used as tool. An hour after the administration of the drugs to each group, paw oedema was induced with intradermal injection of 0.1 mL of carrageenan (1% into the plantar surface of the right hind paw of each rat. Volume of inflamed paw was determined using a plethysmometer immediately and also at 30, 60, 120 and 180 minutes after injection. Finally, mean paw volumes at different time intervals were calculated and percentage inhibition of paw oedema with standard and test drugs were determined. RESULTS Data was analysed using by Analysis of Variance (ANOVA. Results showed that rosuvastatin has statistically significant (P<0.05 anti-inflammatory action reflected by percentage

  19. 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 ...

  20. A Comparison of Multiple Esterases as Biomarkers of Organophosphate Exposure and Effect in Two Earthworm Species

    Science.gov (United States)

    Schneider, Ashley; Stoskopf, Michael K.

    2011-01-01

    Two different earthworm species, Eisenia fetida and Lumbricus terrestris, were exposed to 5 μg/cm2 of malathion to evaluate their usefulness as sentinels of organophosphate exposure and to assess three different esterases, as biomarkers of malathion exposure and effect. Tissue xenobiotic burdens and esterase activity were determined for each species and each esterase in order to assess variability. E. fetida exhibited 4-fold less variability in tissue burdens than did L. terrestris and had less variable basal esterase activities. An attempt was made to correlate malathion and malaoxon tissue burdens with esterase activity post-exposure. There was no malaoxon present in the earthworm tissues. No significant correlations were determined by comparing acetylcholinesterase, butyrylcholinesterase, nor carboxylesterase activities with malathion burdens. PMID:21404045

  1. 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.

  2. Serum Specific IgE to Thyroid Peroxidase Activates Basophils in Aspirin Intolerant Urticaria.

    Science.gov (United States)

    Shin, Yoo Seob; Suh, Dong-Hyeon; Yang, Eun-Mi; Ye, Young-Min; Park, Hae-Sim

    2015-06-01

    Thyroid antibodies are frequently observed in urticaria patients, but their roles in urticaria are not clearly elucidated. We investigated the role of serum specific IgE to thyroid peroxidase (TPO) in patients with aspirin intolerant acute urticaria (AIAU) and aspirin intolerant chronic urticaria (AICU). We recruited 59 AIAU and 96 AICU patients with 69 normal controls (NC). Serum specific IgE to TPO was measured by manual direct ELISA, and CD203c expressions on basophil with additions of TPO were measured to prove a direct role of TPO in effector cells. The prevalences of serum specific IgE to TPO were significantly higher in AIAU (15.2%) and AICU groups (7.5%) compared to NC (0%, P=0.018: P=0.013, respectively). Flow cytometry showed CD203c induction in a dose dependent manner with serial additions of TPO in some AIAU and AICU patients having high specific IgE to TPO. Our findings show that the prevalence of serum specific IgE to TPO was significantly higher in both AIAU and AICU patients than in NC. It is suggested that specific IgE to TPO play a pathogenic role in AIAU and AICU.

  3. A New Functional Classification of Glucuronoyl Esterases by Peptide Pattern Recognition

    DEFF Research Database (Denmark)

    Wittrup Agger, Jane; Busk, Peter Kamp; Pilgaard, Bo

    2017-01-01

    different esterase activity. Hence, the CE15 family is likely to comprise other enzyme functions than glucuronoyl esterase alone. Gene annotation in a variety of fungal and bacterial microorganisms showed that coprophilic fungi are rich and diverse sources of CE15 proteins. Combined with the lifestyle...

  4. Crystal structure and biochemical properties of a novel thermostable esterase containing an immunoglobulin-like domain

    NARCIS (Netherlands)

    Levisson, M.; Sun, L.; Hendriks, S.N.A.; Swinkels, P.; Akveld, T.; Bultema, J.B.; Barendregt, A.; Heuvel, van den R.H.H.; Dijkstra, B.W.; Oost, van der J.; Kengen, S.W.M.

    2009-01-01

    Comparative analysis of the genome of the hyperthermophilic bacterium Thermotoga maritima revealed a hypothetical protein (EstA) with typical esterase features. The EstA protein was functionally produced in Escherichia coli and purified to homogeneity. It indeed displayed esterase activity with

  5. A novel esterase from Saccharomyces carlsbergensis, a possible function for the yeast TIP1 gene

    DEFF Research Database (Denmark)

    Horsted, M W; Dey, E S; Holmberg, S

    1998-01-01

    prefers esters of fatty acids from four to 16 carbon atoms. The esterase has lipolytical activity; olive oil (C-18:1), which is a classical substrate for lipase, was hydrolysed. N-terminal sequence analysis of the esterase yielded a sequence which was identical to the deduced amino acid sequence of the S...

  6. [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.

  7. 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.

  8. Agrobacterium tumefaciens estC, Encoding an Enzyme Containing Esterase Activity, Is Regulated by EstR, a Regulator in the MarR Family.

    Directory of Open Access Journals (Sweden)

    Surawach Rittiroongrad

    Full Text Available Analysis of the A. tumefaciens genome revealed estC, which encodes an esterase located next to its transcriptional regulator estR, a regulator of esterase in the MarR family. Inactivation of estC results in a small increase in the resistance to organic hydroperoxides, whereas a high level of expression of estC from an expression vector leads to a reduction in the resistance to organic hydroperoxides and menadione. The estC gene is transcribed divergently from its regulator, estR. Expression analysis showed that only high concentrations of cumene hydroperoxide (CHP, 1 mM induced expression of both genes in an EstR-dependent manner. The EstR protein acts as a CHP sensor and a transcriptional repressor of both genes. EstR specifically binds to the operator sites OI and OII overlapping the promoter elements of estC and estR. This binding is responsible for transcription repression of both genes. Exposure to organic hydroperoxide results in oxidation of the sensing cysteine (Cys16 residue of EstR, leading to a release of the oxidized repressor from the operator sites, thereby allowing transcription and high levels of expression of both genes. The estC is the first organic hydroperoxide-inducible esterase-encoding gene in alphaproteobacteria.

  9. Xylella fastidiosa esterase rather than hydroxynitrile lyase.

    Science.gov (United States)

    Torrelo, Guzman; Ribeiro de Souza, Fayene Zeferino; Carrilho, Emanuel; Hanefeld, Ulf

    2015-03-02

    In 2009, we reported that the product of the gene SCJ21.16 (XFa0032) from Xylella fastidiosa, a xylem-restricted plant pathogen that causes a range of diseases in several important crops, encodes a protein (XfHNL) with putative hydroxynitrile lyase activity. Sequence analysis and activity tests indicated that XfHNL exhibits an α/β-hydrolase fold and could be classified as a member of the family of FAD-independent HNLs. Here we provide a more detailed sequence analysis and new experimental data. Using pure heterologously expressed XfHNL we show that this enzyme cannot catalyse the cleavage/synthesis of mandelonitrile and that this protein is in fact a non-enantioselective esterase. Homology modelling and ligand docking simulations were used to study the active site and support these results. This finding could help elucidate the common ancestor of esterases and hydroxynitrile lyases with an α/β -hydrolase fold. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Spectroscopic study of drug-binding characteristics of unmodified and pNPA-based acetylated human serum albumin: Does esterase activity affect microenvironment of drug binding sites on the protein?

    Energy Technology Data Exchange (ETDEWEB)

    Moradi, Nastaran [Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Faculty of Pharmaceutical Sciences, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Ashrafi-Kooshk, Mohammad Reza [Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Ghobadi, Sirous [Department of Biology, Faculty of Sciences, Razi University, Kermanshah (Iran, Islamic Republic of); Shahlaei, Mohsen [Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Faculty of Pharmaceutical Sciences, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Khodarahmi, Reza, E-mail: rkhodarahmi@mbrc.ac.ir [Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Faculty of Pharmaceutical Sciences, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of)

    2015-04-15

    Human serum albumin (HSA) is the most prominent extracellular protein in blood plasma. There are several binding sites on the protein which provide accommodation for structurally-unrelated endogenous and exogenous ligands and a wide variety of drugs. “Esterase-like” activity (hydrolysis of p-nitrophenyl esters) by the protein has been also reported. In the current study, we set out to investigate the interaction of indomethacin and ibuprofen with the unmodified and modified HSA (pNPA-modified HSA) using various spectroscopic techniques. Fluorescence data showed that 1:1 binding of drug to HSA is associated with quenching of the protein intrinsic fluorescence. Decrease of protein surface hydrophobicity (PSH), alteration in drug binding affinity and change of the protein stability, after esterase-like activity and permanent acetylation of HSA, were also documented. Analysis of the quenching and thermodynamic parameters indicated that forces involved in drug–HSA interactions change upon the protein modification. - Highlights: • Binding propensity of indomethacin extremely decreased upon the protein acetylation. • There is no ibuprofen binding after protein acetylation. • Protein stability changes upon drug binding as well as protein acetylation. • Drug pharmacokinetics may be influenced under co-administration of HSA-modifier drugs.

  11. Eptifibatide provides additional platelet inhibition in non-ST-elevation myocardial infarction patients already treated with aspirin and clopidogrel. Results of the platelet activity extinction in non-Q-wave myocardial infarction with aspirin, clopidogrel, and eptifibatide (PEACE) study.

    Science.gov (United States)

    Dalby, Miles; Montalescot, Gilles; Bal dit Sollier, Claire; Vicaut, Eric; Soulat, Thierry; Collet, Jean Philippe; Choussat, Rémi; Gallois, Vanessa; Drobinski, Gérard; Drouet, Ludovic; Thomas, Daniel

    2004-01-21

    The present study hypothesis was that eptifibatide offered further antiplatelet efficacy above clopidogrel in non-ST-elevation myocardial infarction (NSTEMI) patients before an expeditive coronary intervention. Although thienopyridines and glycoprotein (GP) IIb/IIIa antagonists are often co-prescribed in the context of NSTEMI, the antiplatelet interaction of these agents is poorly described and the superiority of GP IIb/IIIa antagonists above thienopyridine treatment alone is not clear. Thirty-two NSTEMI patients treated with aspirin and enoxaparin were studied using flow cytometry to define parameters of platelet activation with a panel of agonists before clopidogrel, after clopidogrel, and during an eptifibatide infusion following the clopidogrel load. After platelet activation with adenosine diphosphate, thrombin receptor-activating peptide, or U46-619, relative reductions in conformationally activated GP IIb/IIIa receptor expression (evaluated with PAC-1) of 48%, 43%, and 33%, respectively (all p pro-inflammatory effect.

  12. Beneficial Effect of Ultra-Low-Dose Aspirin in Platelet Activity Alterations and Haemorrhage Observed in Experimental Portal Hypertension

    Directory of Open Access Journals (Sweden)

    F. X. Eizayaga

    2012-01-01

    Full Text Available Ultra-low-dose aspirin has shown a prothrombotic effect in the laser-induced thrombosis model. Several studies of our laboratory have shown a positive effect in rats with two different experimental models of portal hypertension: portal vein ligation, a model with an almost normal liver, and 30 days of bile duct ligation, a model with cirrhosis and presence of ascitis. In both models of portal hypertensive rats, bleeding time was prolonged and thrombi formation, in a laser-induced model of thrombi production, decreased. The hypotheses of the presented studies were that ultra-low-dose aspirin could decrease the bleeding complications in these models and that the mechanism for these effects could act thorough the COX pathway. In different studies, ultra-low dose of aspirin normalized the induced hemorrhage time, thrombi production, and platelet-endothelial cell interaction. The possible beneficial role of these doses of aspirin and mechanism of COX 2 inhibition are discussed.

  13. 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 ...

  14. Kinetic characterization and fed-batch fermentation for maximal simultaneous production of esterase and protease from Lysinibacillus fusiformis AU01.

    Science.gov (United States)

    Divakar, K; Suryia Prabha, M; Nandhinidevi, G; Gautam, P

    2017-04-21

    The simultaneous production of intracellular esterase and extracellular protease from the strain Lysinibacillus fusiformis AU01 was studied in detail. The production was performed both under batch and fed-batch modes. The maximum yield of intracellular esterase and protease was obtained under full oxygen saturation at the beginning of the fermentation. The data were fitted to the Luedeking-Piret model and it was shown that the enzyme (both esterase and protease) production was growth associated. A decrease in intracellular esterase and increase in the extracellular esterase were observed during late stationary phase. The appearance of intracellular proteins in extracellular media and decrease in viable cell count and biomass during late stationary phase confirmed that the presence of extracellular esterase is due to cell lysis. Even though the fed-batch fermentation with different feeding strategies showed improved productivity, feeding yeast extract under DO-stat fermentation conditions showed highest intracellular esterase and protease production. Under DO-stat fed-batch cultivation, maximum intracellular esterase activity of 820 × 10(3) U/L and extracellular protease activity of 172 × 10(3) U/L were obtained at the 16th hr. Intracellular esterase and extracellular protease production were increased fivefold and fourfold, respectively, when compared to batch fermentation performed under shake flask conditions.

  15. 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…

  16. The ATP-gated P2X1 receptor plays a pivotal role in activation of aspirin-treated platelets by thrombin and epinephrine.

    Science.gov (United States)

    Grenegård, Magnus; Vretenbrant-Oberg, Karin; Nylander, Martina; Désilets, Stéphanie; Lindström, Eva G; Larsson, Anders; Ramström, Ida; Ramström, Sofia; Lindahl, Tomas L

    2008-07-04

    Human platelets express protease-activated receptor 1 (PAR1) and PAR4 but limited data indicate for differences in signal transduction. We studied the involvement of PAR1 and PAR4 in the cross-talk between thrombin and epinephrine. The results show that epinephrine acted via alpha(2A)-adrenergic receptors to provoke aggregation, secretion, and Ca(2+) mobilization in aspirin-treated platelets pre-stimulated with subthreshold concentrations of thrombin. Incubating platelets with antibodies against PAR4 or the PAR4-specific inhibitor pepducin P4pal-i1 abolished the aggregation. Furthermore, platelets pre-exposed to the PAR4-activating peptide AYPGKF, but not to the PAR1-activating peptide SFLLRN, were aggregated by epinephrine, whereas both AYPGKF and SFLLRN synergized with epinephrine in the absence of aspirin. The roles of released ATP and ADP were elucidated by using antagonists of the purinergic receptors P2X(1), P2Y(1), and P2Y(12) (i.e. NF449, MRS2159, MRS2179, and cangrelor). Intriguingly, ATP, but not ADP, was required for the epinephrine/thrombin-induced aggregation. In Western blot analysis, a low concentration of AYPGKF, but not SFLLRN, stimulated phosphorylation of Akt on serine 473. Moreover, the phosphatidyl inositide 3-kinase inhibitor LY294002 antagonized the effect of epinephrine combined with thrombin or AYPGKF. Thus, in aspirin-treated platelets, PAR4, but not PAR1, interacts synergistically with alpha(2A)-adrenergic receptors, and the PI3-kinase/Akt pathway is involved in this cross-talk. Furthermore, in PAR4-pretreated platelets, epinephrine caused dense granule secretion, and subsequent signaling from the ATP-gated P2X(1)-receptor and the alpha(2A)-adrenergic receptor induced aggregation. These results suggest a new mechanism that has ATP as a key element and circumvents the action of aspirin on epinephrine-facilitated PAR4-mediated platelet activation.

  17. Extracellular fluid proteins of goldfish brain: evidence for the presence of proteases and esterases.

    Science.gov (United States)

    Shashoua, V E; Holmquist, B

    1986-09-01

    Preparations of enriched fractions of extracellular fluid (ECF) proteins from goldfish brain were found to contain protease(s) and esterase(s). The N-substituted furanacryloyl (FA) peptides FA-Phe-Gly-Gly and FA-Phe-OMe were used as model substrates for determining protease and esterase activity, respectively, in a spectrophotometric assay. Studies of the profile of substrate specificity and identification of the types of compounds that were effective as inhibitors showed that these ECF enzymes have some distinctive properties. GSH, but not GSSG, and EDTA inhibited the protease(s) without influencing the esterase(s), whereas L-1-tosylamide-2-phenylethylchloromethyl ketone blocked both protease and esterase activities of ECF. Most of the protease and esterase properties of ECF could be bound to concanavalin A-Sepharose affinity chromatographic columns in association with ependymin--a brain extracellular protein. These observations indicate that ECF may contain a metalloprotease(s) and raise the possibility that the ependymins might be a substrate for these ECF enzymes.

  18. A Zymogram technique for preliminary screening and characterization of feruloyl esterases.

    Science.gov (United States)

    Palaniswamy, Sakthi Kumaran; Govindaswamy, Vijayalakshmi

    2017-06-01

    We report here, for the first time, a zymogram technique designed for rapid screening of feruloyl esterase using ethyl ferulate as enzyme substrate and casein precipitation as enzyme activity indicator. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Identification of aspirin analogues that repress NF-κB signalling and demonstrate anti-proliferative activity towards colorectal cancer in vitro and in vivo.

    Science.gov (United States)

    Claudius, Ann-Katrin; Kankipati, Chandra S; Kilari, Rajagopal S; Hassan, Sadiya; Guest, Kerry; Russell, Steven T; Perry, Chris J; Stark, Lesley A; Nicholl, Iain D

    2014-10-01

    Substantial evidence indicates that aspirin and related non-steroidal anti-inflammatory drugs (NSAIDs) have potential as chemopreventative/therapeutic agents. However, these agents cannot be universally recommended for prevention purposes due to their potential side-effect profiles. Here, we compared the growth inhibitory and mechanistic activity of aspirin to two novel analogues, diaspirin (DiA) and fumaryl diaspirin (F-DiA). We found that the aspirin analogues inhibited cell proliferation and induced apoptosis of colorectal cancer cells at significantly lower doses than aspirin. Similar to aspirin, we found that an early response to the analogues was a reduction in levels of cyclin D1 and stimulation of the NF-κB pathway. This stimulation was associated with a significant reduction in basal levels of NF-κB transcriptional activity, in keeping with previous data for aspirin. However, in contrast to aspirin, DiA and F-DiA activity was not associated with nucleolar accumulation of RelA. For all assays, F-DiA had a more rapid and significant effect than DiA, identifying this agent as particularly active against colorectal cancer. Using a syngeneic colorectal tumour model in mice, we found that, while both agents significantly inhibited tumour growth in vivo, this effect was particularly pronounced for F-DiA. These data identify two compounds that are active against colorectal cancer in vitro and in vivo. They also identify a potential mechanism of action of these agents and shed light on the chemical structures that may be important for the antitumour effects of aspirin.

  20. Two glucuronoyl esterases of Phanerochaete chrysosporium

    NARCIS (Netherlands)

    Duranová, Miroslava; Spániková, Silvia; Wösten, Han A B; Biely, Peter; de Vries, Ronald P

    The white-rot fungus Phanerochaete chrysosporium produces glucuronoyl esterase, a recently discovered carbohydrate esterase, during growth on sugar beet pulp. Two putative genes encoding this enzyme, ge1 and ge2, were isolated and cloned. Heterologous expression in Aspergillus vadensis, Pycnoporus

  1. Correlation between serum esterase polymorphism and production ...

    African Journals Online (AJOL)

    The polymorphism of serum esterase (Es) of Henan Yuxi fat-tailed sheep was detected through polyacrylamide gel electrophoresis (PAGE), and the correlation between serum esterase and productivity was analyzed. The research result indicated that there are two alleles on the Es loci of Henan Yuxi fat-tailed sheep: Es+ ...

  2. Functional classification of esterases from leaves of Aspidosperma polyneuron M. Arg. (Apocynaceae

    Directory of Open Access Journals (Sweden)

    Carvalho Vanda Marilza de

    2003-01-01

    Full Text Available Polyacrylamide gel electrophoresis system (PAGE and inhibition tests for biochemical characterization of alpha- and beta-esterases were used to obtain a functional classification of esterases fromAspidosperma polyneuron. The characterization of alpha- and beta-esterases from young leaves of A. polyneuron by the PAGE system showed fourteen esterase isozymes. The differential staining pattern showed that Est-2 isozyme hydrolyzes beta-naphthyl acetate; Est-6, Est-7 and Est-8 isozymes hydrolyze alpha-naphthyl acetate, and Est-1, Est-3, Est-4, Est-5, Est-9, Est-10, Est-11, Est-12, Est-13, and Est-14 isozymes hydrolyze both alpha- and b-naphthyl acetate. Inhibition pattern of a- and beta-esterases showed that Folidol is a more potent inhibitor that Malathion, while Thiamethoxan (an insecticide with organophosphorus-like action acts as an Est-4 and Est-6 inhibitor and induces the appearance of Est-5 and Est-7 isozymes as more intensely stained bands. Inhibition tests showed that OPC insecticides inhibit or activate plant esterases. Thus, plant esterases may be used as bioindicators to detect the presence and toxicity of residues of topically applied insecticides in agriculture and may be valuable for monitoring pollutants in the environment.

  3. Production and partial characterisation of feruloyl esterase by Sporotrichum thermophile in solid-state fermentation

    DEFF Research Database (Denmark)

    Topakas, E.; Kalogeris, E.; Kekos, D.

    2003-01-01

    source were consecutively optimised. SSF in a laboratory horizontal bioreactor using the optimised medium allowed the production of 156 mU g(-1) of carbon source, which compared favourably with those reported for the other micro-organisms. Optimal esterase activity was observed at pH 8 and 60 degrees......C. The activity of the esterase was measured on an insoluble feruloylated hemicellulose substrate (de-starched wheat bran (DSWB)). De-esterifcation of wheat straw yielded loss of feruloyl esterase production even though the supplementation of free FA comparable to the alkali-extractable levels of FA found...... in wheat straw. Chromogenic (fluorogenic) 4-methylumbelliferyl ferulate was used to characterise the multienzyme component, after separation by isoelectric focusing and native PAGE electrophoresis. The zymograms indicated one major esterase activity exhibiting pI and molecular mass values 5 and 27 k...

  4. In vitro metabolism of isoline, a pyrrolizidine alkaloid from Ligularia duciformis, by rodent liver microsomal esterase and enhanced hepatotoxicity by esterase inhibitors.

    Science.gov (United States)

    Tang, Jun; Akao, Teruaki; Nakamura, Norio; Wang, Zheng-Tao; Takagawa, Kiyoshi; Sasahara, Masakiyo; Hattori, Masao

    2007-10-01

    Isoline, a major retronecine-type pyrrolizidine alkaloid (PA) from the Chinese medicinal herb Ligularia duciformis, was suggested to be the most toxic known PA. Its in vitro metabolism was thus examined in rat and mouse liver microsomes, and its toxicity was compared with that of clivorine and monocrotaline after i.p. injection in mice. Isoline was more rapidly metabolized by both microsomes than clivorine and monocrotaline and converted to two polar metabolites M1 and M2, which were spectroscopically determined to be bisline (a deacetylated metabolite of isoline) and bisline lactone, respectively. Both metabolites were formed in the presence or absence of an NADPH-generating system with liver microsomes but not cytosol. Their formation was completely inhibited by the esterase inhibitors, triorthocresyl phosphate (TOCP) and phenylmethylsulfonyl fluoride, but not at all or partially by cytochrome P450 (P450) inhibitors, alpha-naphthoflavone and proadifen (SKF 525A), respectively. These results demonstrated that both metabolites were produced by microsomal esterase(s) but not P450 isozymes. The esterase(s) involved showed not only quite different activities but also responses to different inhibitors in rat and mouse liver microsomes, suggesting that different key isozyme(s) or combinations might be responsible for the deacetylation of isoline. Isoline injected i.p. into mice induced liver-specific toxicity that was much greater than that with either clivorine or monocrotaline, as judged by histopathology as well as serum alanine aminotransferase and aspartate aminotransferase levels. Isoline-induced hepatotoxicity was remarkably enhanced by the esterase inhibitor TOCP but was reduced by the P450 inhibitor SKF 525A, indicating that rodent hepatic esterase(s) played a principal role in the detoxification of isoline via rapid deacetylation in vivo.

  5. Effect of concanavalin A on the aspirin concentration and distribution in the brain and plasma of rats.

    Science.gov (United States)

    Miyagi, N; Kondoh, H; Sakurai, E; Hikichi, N; Niwa, H

    1986-09-01

    The effects of concanavalin A (Con A) on plasma and brain concentration of aspirin (Asp) were investigated in rats. When Asp was administered in rats treated with Con A, the plasma and brain concentration of Asp and its metabolites (salicylic acid (SA), salicyluric acid (SU) and gentisic acid (GA)) were increased. Distribution of Asp and its metabolites into the hippocampus, striatum and hypothalamus were increased by treatment with Con A. Asp esterase activities in the small intestinal mucosa, liver and brain were increased by pretreatment with Con A, but these enzyme activities were decreased by a high dose of Con A. The inhibitory effect of Asp, SA, SU and GA on the writhing induced by acetic acid in Con A-pretreated mice was stronger than that in the control. A lowering of rectal temperature, after the administration of Asp, was stronger in Con A-treated rats than in control rats. These results suggested that Con A facilitated the absorption of Asp and enhanced the transfer of SA into the brain, and increased Asp esterase activities in various tissues.

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

    Science.gov (United States)

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

    2014-05-01

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

  7. Comparison of antiplatelet activity of garlic tablets with cardio-protective dose of aspirin in healthy volunteers: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Mojtaba Shafiekhani

    2016-08-01

    Full Text Available Objective: Some of the adverse effects of aspirin including peptic ulcers, gastrointestinal bleeding and aspirin resistance compelled researchers to find a suitable alternative with fewer adverse effects. In this clinical trial, we aimed to find the effective antiplatelet dose of garlic. Materials and Methods: This randomized controlled clinical trial (RCT was conducted on 62 healthy volunteers of 20-50 years old. All volunteers used 80 mg aspirin per day for 1 week and at the end of this time, platelet aggregation (PA induced by 4 agonists acting in aggregation pathway including adenosinediphosphate (20 μmol/l, epinephrine (20 μmol/l, collagen(0.19 mg/ ml and arachidonic acid (0.5mg/ ml was measured by Light Transmittance Aggregometry (LTA in all participants. After one month washout period, volunteers were randomized into 3 groups and each received 1, 2 or 3 garlic tablets (1250 mg a day for 1 month. After one month, PA was examined in all groups. Results: The mean ±SD of the age of all volunteers was 28.60 ± 9.00 years. In addition, 52.00 % of our volunteers were male and 48.00% of them were female. Garlic tablet didnot have significant effect on PA at any dose. However, 30% of volunteers in the group that used 3 garlic tablets/day reported adverse effect (i.e. bleeding. No significant association between sex, age and PA was observed. Conclusion:  In this study, we were unable to determine the effective anti-platelet dose of garlic which that could be equal to that of aspirin anti-platelet activity, as assessed LTA method.

  8. 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.

  9. Esterase inhibition by synergists in the western flower thrips Frankliniella occidentalis.

    Science.gov (United States)

    López-Soler, Neus; Cervera, Amelia; Quinto, Vicente; Abellán, Jaime; Bielza, Pablo; Martínez-Pardo, Rafael; Garcerá, Maria Dolores

    2011-12-01

    Western flower thrips (WFT), Frankliniella occidentalis (Pergande), is among the most important crop pests in the south-eastern region of Spain. Its increasing resistance to insecticides constitutes a serious problem, and understanding the mechanisms involved is therefore of great interest. Use of synergists to inhibit the enzymes involved in insecticide detoxification is widely used to determine their responsibility for insecticide resistance. However, they do not always act as intended or expected, and caution must be exercised when interpreting synergist results. Laboratory-selected strains of WFT were used to analyse the effects of the synergists piperonyl butoxide (PBO), S,S,S-tributyl phosphorotrithioate (DEF) and methiocarb on total esterase activity. Significant differences were found, indicating esterase activity inhibition by DEF, a lower effect for methiocarb and a small inhibition of the activity by PBO. Esterase isoenzyme inhibition by these compounds showed a similar result; this assay revealed an extreme sensitivity of Triplet A (resistance-associated esterases) to DEF. In an in vivo assay carried out with these compounds at different incubation times, only DEF caused posterior in vitro esterase activity inhibition, with a maximum effect 1 h after treatment. In this work, only DEF shows true synergistic inhibition of WFT esterases. Copyright © 2011 Society of Chemical Industry.

  10. 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.

  11. 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...

  12. 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.

  13. [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.

  14. 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.

  15. Anti-inflammatory and analgesic activity of novel oral aspirin-loaded nanoemulsion and nano multiple emulsion formulations generated using ultrasound cavitation.

    Science.gov (United States)

    Tang, Siah Ying; Sivakumar, Manickam; Ng, Angela Min-Hwei; Shridharan, Parthasarathy

    2012-07-01

    The present study investigated the anti-inflammatory and analgesic activities of novel aspirin oil-in-water (O/W) nanoemulsion and water-in-oil-in-water (W/O/W) nano multiple emulsion formulations generated using ultrasound cavitation techniques. The anti-inflammatory activities of nanoemulsion and nano multiple emulsion were determined using the λ-carrageenan-induced paw edema model. The analgesic activities of both nanoformulations were determined using acetic acid-induced writhing response and hot plate assay. For comparison, the effect of pretreatment with blank nanoemulsion and reference aspirin suspension were also studied for their anti-inflammatory and antinociceptive activities. The results showed that oral administration of nanoemulsion and nano multiple emulsion containing aspirin (60 mg/kg) significantly reduced paw edema induced by λ-carrageenan injection. Both nanoformulations decreased the number of abdominal constriction in acetic acid-induced writhing model. Pretreatment with nanoformulations led to a significant increase in reaction time in hot plate assay. Nanoemulsion demonstrated an enhanced anti-inflammatory and analgesic effects compared to reference suspension while nano multiple emulsion exhibited a mild inhibitory effects in the three experimental animal model tests. The results obtained for nano multiple emulsion were relatively lower than reference. However, administration of blank nanoemulsion did not alter the nociceptive response significantly though it showed slight anti-inflammatory effect. These experimental studies suggest that nanoemulsion and nano multiple emulsion produced a pronounced anti-inflammatory and analgesic effects in rats and may be candidates as new nanocarriers for pharmacological NSAIDs in the treatment of inflammatory disorders and alleviating pains. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Esterase resistant to inactivation by heavy metals

    KAUST Repository

    El, Dorry Hamza

    2014-09-25

    EstATII is an esterase that a halotolerant, thermophilic and resistant to a spectrum of heavy metals including toxic concentration of metals. It was isolated from the lowest convective layer of the Atlantis II Red Sea brine pool. The Atlantis II brine pool is an extreme environment that possesses multiple harsh conditions such as; high temperature, salinity, pH and high concentration of metals, including toxic heavy metals. A fosmid metagenomic library using DNA isolated from the lowest convective layer this pool was used to identify EstATII. Polynucleotides encoding EstATII and similar esterases are disclosed and can be used to make EstATII. EstATII or compositions or apparatuses that contain it may be used in various processes employing lipases/esterases especially when these processes are performed under harsh conditions that inactivate other kinds of lipases or esterases.

  17. Sonorheometry assessment of platelet function in cardiopulmonary bypass patients: Correlation of blood clot stiffness with platelet integrin αIIbβ3 activity, aspirin usage, and transfusion risk.

    Science.gov (United States)

    Viola, Francesco; Lin-Schmidt, Xiefan; Bhamidipati, Castigliano; Haverstick, Doris M; Walker, William F; Ailawadi, Gorav; Lawrence, Michael B

    2016-02-01

    Impaired platelet function may underlie bleeding associated with cardiopulmonary bypass (CPB) and at present is incompletely evaluated with existing diagnostic technologies. Sonorheometry (SR) is a recently developed ultrasound-based technology that quantifies hemostasis and platelet activity from a blood sample by measuring ex vivo clot stiffness (S). We hypothesized that impaired platelet-fibrin interactions as assessed by SR would correlate with transfusion during CPB and history of prior aspirin therapy. Thirty-nine patients undergoing elective cardiopulmonary bypass (CPB) were enrolled following informed consent (University of Virginia IRB#14050) in a prospective observational pilot study to assess pre-operative platelet function and transfusion frequency. To assess platelet activity, abciximab was added to blood prior to SR and native S versus abciximab treated S created a differential test for platelet activity. Patient blood samples were activated with kaolin and SR was then used to measure clot stiffness. Patients were transfused with blood products as directed by clinical practice, with the surgical team blinded to SR results. Blood clot stiffness with and without abciximab, was compared in a ratio test (S/Sabciximab) named the Platelet Function Index (PFI). PFI was hypothesized to be positively correlated with platelet contributions through integrin αIIbβ3 to clot stiffness. PFI for CPB subjects was lower for those receiving transfusions than those not receiving transfusions (paspirin therapy was lower than for those not on aspirin therapy (paspirin effects on risk of surgical bleeding. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Kok-Yong Chin

    2017-01-01

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

  19. 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. ...

  20. 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

  1. Drug Resistance and Pseudoresistance: An Unintended Consequence of Enteric Coating Aspirin

    Science.gov (United States)

    Grosser, Tilo; Fries, Susanne; Lawson, John A.; Kapoor, Shiv C.; Grant, Gregory R.; FitzGerald, Garret A.

    2013-01-01

    Background Low dose aspirin reduces the secondary incidence of myocardial infarction and stroke. Drug resistance to aspirin might result in treatment failure. Despite this concern, no clear definition of “aspirin resistance” has emerged and estimates of its incidence have varied remarkably. We aimed to determine the commonality of a mechanistically consistent, stable and specific phenotype of true pharmacological resistance to aspirin – such as might be explained by genetic causes. Methods and Results Healthy volunteers (n=400) were screened for their response to a single oral dose of 325 mg immediate release or enteric coated aspirin. Response parameters reflected the activity of aspirin's molecular target, cyclooxygenase-1. Individuals who appeared “aspirin resistant” on one occasion underwent repeat testing and if still “resistant” were exposed to low dose enteric coated aspirin (81 mg) and clopidogrel (75 mg) for one week each. Variable absorption caused a high frequency of apparent resistance to a single dose of 325 mg enteric coated aspirin (up to 49%) but not to immediate release aspirin (0%). All individuals responded to aspirin upon repeated exposure, extension of the post dosing interval or addition of aspirin to their platelets ex vivo. Conclusions Pharmacological resistance to aspirin is rare; this study failed to identify a single case of true drug resistance. Pseudoresistance, reflecting delayed and reduced drug absorption, complicates enteric coated but not immediate release aspirin administration. Clinical Trial Registration Information clinicaltrials.gov. Identifier: NCT00948987. PMID:23212718

  2. Rebound platelet activation after termination of prasugrel and aspirin therapy due to confirmed non-compliance in patient enrolled in the JUMBO Trial.

    Science.gov (United States)

    Serebruany, V L; Midei, M G; Meilman, H; Malinin, A I; Lowry, D R

    2006-07-01

    Therapy with aspirin and/or adenosine diphosphate (ADP) receptor blockers is associated with better outcomes via inhibition of platelet activity, and subsequent reduction of ischemic vascular events. Non-compliance (NC) is a well-recognised hazard limiting the clinical utility of antiplatelet agents, and, probably worsening outcomes. However, comprehensive platelet characteristics of a confirmed NC patient after acute vascular event have never been reported within a major randomised trial with ADP-receptor antagonists. A 48-year-old male patient, well-educated, was among patients enrolled in the platelet sub-study for the JUMBO trial. He received 325 mg of aspirin daily for 9 months, presented with unstable angina for urgent coronary intervention, and was successfully reperfused with two intracoronary stents. The patient was randomised to a 60 mg prasugrel loading dose, and 10 mg of prasugrel daily for 30 days. Platelets were assessed at baseline, 4 and 24 h, and at 30 days after acute coronary event utilising ADP-, and collagen-induced conventional aggregometry, rapid cartridge-based analyser and flow cytometry. Loading with prasugrel resulted in significant inhibition of platelet activity during and after stenting. However, after assessing platelet biomarkers at 30 days, voluntary withdrawal from the antiplatelet agents was suspected. Based on the platelet activity characteristics, NC was later confirmed, and the patient admitted that he stopped taking both prasugrel and aspirin shortly after discharge due to minor bleeding episodes after shaving. Major platelet activity biomarkers of the index NC patient were compared with those from compliant prasugrel-, clopidogrel-treated patients, and healthy controls. The platelet tests uniformly revealed rebound activation by all platelet measures (at least twofold increase) while being especially high for ADP-, and collagen-induced aggregation, platelet/endothelial cell adhesion molecule-1 (PECAM-1), glycoprotein (GP

  3. 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.

  4. Synthesis and gastroprotective activities of some zinc (II complexes derived from (E-2-(1-(2-(piperazin-1-ylethyliminoethylphenol and (E-4-(1-(2-(piperazin-1-ylethyliminoethylbenzene-1,3-diol Schiff bases against aspirin induced ulceration

    Directory of Open Access Journals (Sweden)

    Muhammad Saleh Salga

    2017-05-01

    Full Text Available This study describes the protective effects of piperazine derived compounds against aspirin induced gastric injuries and evaluated the role of nitric oxide, inflammatory cytokines and serum level of aspartate aminotransaminases (AST, alanine aminotransaminases (ALT, high density lipoprotein (HDL and malondialdehyde (MDA. The oral administration of the compounds at doses 30 and 60 mg/kg protected the gastric against the nectrotizing effects of aspirin. The level of nitric oxide (NO was elevated in the group pretreated with the compounds. The results also showed that pre-treatment with piperazine compounds has led to the decrease in the amount of MDA and increased the activity of AST, ALT and HDL. In conclusion, pre-treatment with piperazine derived compounds; (E-2-(1-(2-(piperazin-1-ylethyliminoethylphenol (2HP, (E-4-(1-(2-(piperazin-1-ylethyliminoethyl benzene-1,3-diol (DHP and their zinc complexes has provided a significant protection to the gastric from damaging effects of aspirin.

  5. 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.

  6. Solid-state fermentation as a potential technique for esterase/lipase production by halophilic archaea.

    Science.gov (United States)

    Martin del Campo, Martha; Camacho, Rosa M; Mateos-Díaz, Juan C; Müller-Santos, Marcelo; Córdova, Jesus; Rodríguez, Jorge A

    2015-11-01

    Halophilic archaea are extremophiles, adapted to high-salt environments, showing a big biotechnological potential as enzyme, lipids and pigments producers. Four inert supports (perlite, vermiculite, polyurethane foam and glass fiber) were employed for solid-state fermentation (SSF) of the halophilic archaeon Natronococcus sp. TC6 to investigate biomass and esterase production. A very low esterase activity and high water activity were observed when perlite, vermiculite and polyurethane were used as supports. When glass fiber was employed, an important moisture loss was observed (8.6%). Moreover, moisture retention was improved by mixing polyurethane and glass fiber, resulting in maximal biomass and esterase production. Three halophilic archaea: Natronococcus sp. TC6, Halobacterium sp. NRC-1 and Haloarcula marismortui were cultured by submerged fermentation (SmF) and by SSF; an improvement of 1.3- to 6.2-fold was observed in the biomass and esterase production when SSF was used. Growth was not homogeneous in the mixture, but was predominant in the glass fiber thus was probably because the glass fiber provides a holder to the cells, while the polyurethane acts as an impregnation medium reservoir. To the best of our knowledge, this work is the first report on haloarchaea cultivation by SSF aiming biomass and esterase/lipase activity production.

  7. Biochemical Characterization and Relative Expression Levels of Multiple Carbohydrate Esterases of the Xylanolytic Rumen Bacterium Prevotella ruminicola 23 Grown on an Ester-Enriched Substrate

    NARCIS (Netherlands)

    Kabel, M.A.; Yeoman, C.J.; Han, Y.; Dodd, D.; Abbas, C.A.; Bont, de J.A.M.; Morrison, M.; Cann, I.K.O.; Mackie, R.I.

    2011-01-01

    We measured expression and used biochemical characterization of multiple carbohydrate esterases by the xylanolytic rumen bacterium Prevotella ruminicola 23 grown on an ester-enriched substrate to gain insight into the carbohydrate esterase activities of this hemicellulolytic rumen bacterium. The P.

  8. A novel feruloyl esterase from rumen microbial metagenome: Gene cloning and enzyme characterization in the release of mono- and diferulic acids

    Science.gov (United States)

    A feruloyl esterase (FAE) gene was isolated from a rumen microbial metagenome, cloned into E. coli, and expressed in active form. The enzyme (RuFae4) was classified as a Type D feruloyl esterase based on its action on synthetic substrates and ability to release diferulates. The RuFae4 alone releas...

  9. 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 ...

  10. Dinitroglyceryl and diazen-1-ium-1,2-diolated nitric oxide donor ester prodrugs of aspirin, indomethacin and ibuprofen: synthesis, biological evaluation and nitric oxide release studies.

    Science.gov (United States)

    Abdellatif, Khaled R A; Chowdhury, Morshed Alam; Dong, Ying; Das, Dipankar; Yu, Gang; Velázquez, Carlos A; Suresh, Mavanur R; Knaus, Edward E

    2009-06-01

    A new group of hybrid nitric oxide (NO) releasing anti-inflammatory (AI) ester prodrugs (NONO-NSAIDs) wherein a 1,3-dinitrooxy-2-propyl (12a-c), or O(2)-acetoxymethyl-1-[2-(methyl)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (14a-c), NO-donor moiety is directly attached to the carboxylic acid group of aspirin, indomethacin or ibuprofen were synthesized. NO release from the dinitrooxypropyl, or diazen-1-ium-1,2-diolate, ester prodrugs was increased substantially upon incubation in the presence of l-cysteine (12a-c) or rat serum (14a-c). The ester prodrugs (12a-c, 14a-c), which did not inhibit the COX-1 isozyme, exhibited modest inhibitory activity against the COX-2 isozyme. The NONO-NSAIDs 12a-c and 14a-c exhibited in vivo AI activity that was similar to that exhibited by the parent drug aspirin, indomethacin or ibuprofen when the same oral dose (micromol/kg) was administered. These similarities in oral potency profiles suggest these NONO-NSAIDs act as classical prodrugs that require metabolic activation by esterase-mediated hydrolysis. Hybrid NO-donor/anti-inflammatory prodrugs of this type (NONO-NSAIDs) offer a potential drug design concept targeted toward the development of anti-inflammatory drugs with reduced adverse gastrointestinal effects.

  11. x ORIGINAL ARTICLE ASSESSMENT OF LEUKOCYTE ESTERASE ...

    African Journals Online (AJOL)

    Dr Oboro VO

    ABSTRACT. This is a prospective study of urinary tract infection in 65 children (38 males and 27 females, M: F ratio 1: 0.7). Urine samples were evaluated by culture, microscopy and leukocyte esterase dipstick test. Positive urine culture, with significant bacteriuria was found in 19(29.2%). Urine microscopy for leukocyturia ...

  12. Identification of genes encoding microbial glucuronoyl esterases

    NARCIS (Netherlands)

    Li, Xin-Liang; Spániková, Silvia; de Vries, Ronald P; Biely, Peter

    2007-01-01

    One type of covalent linkages connecting lignin and hemicellulose in plant cell walls is the ester linkage between 4-O-methyl-D-glucuronic acid of glucuronoxylan and lignin alcohols. An enzyme that could hydrolyze such linkages, named glucuronoyl esterase, occurs in the cellulolytic system of the

  13. 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...

  14. 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.

  15. Synergistic effect of nutlin-3 combined with aspirin in hepatocellular carcinoma HepG2 cells through activation of Bcl-2/Bax signaling pathway.

    Science.gov (United States)

    Miao, Runchen; Xu, Xinsen; Wang, Zhixin; Liu, Sushun; Qu, Kai; Chen, Wei; Liu, Chang

    2017-12-22

    Aspirin as an antitumor drug has been studied in various malignancies with regards to its effects on apoptosis, proliferation, metastasis and senescence of tumor cells. However, the clinical application is limited by its side effects. Nutlin‑3 is a novel antitumor compound, which has not been clinically approved. The present study investigated the value of combining aspirin and nutlin‑3 on hepatocellular carcinoma (HCC) cells. MTT was performed to detect the proliferation of HepG2 cells treated with aspirin or/and nutlin‑3. Transwell invasion assays were performed to estimate the invasion ability of HepG2 cells treated with aspirin or/and nutlin‑3. Then the apoptotic analysis of HepG2 cells evaluated the synergistic effect of aspirin and nutlin‑3. Apoptosis markers, including B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), caspase‑3, caspase‑8 and caspase‑9 were estimated by western blot analysis at various time points. In addition, a Xenograft mouse model was established by infection with HepG2 cells, and aspirin and/or nutlin‑3 was administrated to verify the anti‑apoptotic effect of the two drugs in vivo. A high dose of aspirin and nutlin‑3 inhibit the proliferation and apoptosis of HepG2 cells. The antitumor effect was enhanced with the combined treatment of the two drugs, particularly in the group with a low concentration of aspirin and nutlin‑3. Nutlin‑3 was able to increase the level of Bax in HepG2 cells treated with aspirin significantly after treatment for 8 h. When treated with a low concentration of aspirin and nutlin‑3, the level of Bax in HepG2 cells was enhanced for 2 h. In the animal model, tumor volume and tumor angiogenesis were significantly decreased in combination group compared with other groups (P<0.01). Although there were side effects in the group treated with aspirin alone, no side effects were observed in the combination group. Nutlin‑3 enhanced the apoptotic effect of a low dose of

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. Biocatalytic Resolution of Rac-α-Ethyl-2-Oxo-Pyrrolidineacetic Acid Methyl Ester by Immobilized Recombinant Bacillus cereus Esterase.

    Science.gov (United States)

    Zheng, Jian-Yong; Liu, Yin-Yan; Luo, Wei-Feng; Zheng, Ren-Chao; Ying, Xiang-Xian; Wang, Zhao

    2016-04-01

    A new esterase-producing strain (Bacillus cereus WZZ001) which exhibiting high hydrolytic activity and excellent enantioselectivity on rac-α-ethyl-2-oxo-pyrrolidineacetic acid methyl ester (R, S-1) has been isolated from soil sample by our laboratory. In this study, the stereoselective hydrolysis of (R, S-1) was performed using the recombinant Bacillus cereus esterase which expressed in Escherichia coli BL21 (DE3). Under the optimized conditions of pH 8.0, 35 °C, and concentration of substrate 400 mM, a successful enzymatic resolution was achieved with an e.e. s of 99.5 % and conversion of 49 %. Immobilization considerably increased the reusability of the recombinant esterase; the immobilized enzyme showed excellent reusability during 6 cycles of repeated 2 h reactions at 35 °C. Thereby, it makes the recombinant B. cereus esterase a usable biocatalyst for industrial application.

  1. Aspirin resistance in children with heart disease at risk for thromboembolism: prevalence and possible mechanisms.

    Science.gov (United States)

    Heistein, Lisa C; Scott, William A; Zellers, Thomas M; Fixler, David E; Ramaciotti, Claudio; Journeycake, Janna M; Lemler, Matthew S

    2008-03-01

    Aspirin is used to prevent thromboembolism in children with heart disease without evidence supporting its efficacy. Studies in adults report a 5%-51% prevalence of aspirin resistance, yet the mechanisms involved are poorly understood. Our aims were to determine its prevalence in these children and to explore its possible mechanisms. One hundred twenty-three cardiac patients routinely receiving aspirin were prospectively enrolled. Platelet function was measured by Platelet Function Analyzer (PFA)-100 using epinephrine and adenosine diphosphate (ADP) agonists. Aspirin resistance was defined as failure to prolong the epinephrine closure time following aspirin administration. Urine levels of 11-dehydro-thromboxane B(2) (11-dTXB(2)) were measured to determine inhibition of the cyclo-oxygenase pathway. The prevalence of aspirin resistance was 26%. Median ADP closure time was shorter for aspirin-resistant (79.60-115 s) than for aspirin-sensitive (100.60-240 s) patients (p aspirin resistance. Aspirin-resistant patients had higher 11-dTXB(2) levels before (7297 vs. 4160 pg/mg creatinine; p aspirin, with a similar percentage decrease in thromboxane (70.5% vs. 66.1%; p = 0.43). Our findings suggest that resistance is not entirely due to lack of inhibition of platelet thromboxane production. Alternative sources of thromboxane and thromboxane-independent mechanisms, such as ADP-induced platelet activation, may contribute to aspirin resistance.

  2. 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.

  3. Paraoxonase protection of LDL against peroxidation is independent of its esterase activity towards paraoxon and is unaffected by the Q-->R genetic polymorphism.

    Science.gov (United States)

    Cao, H; Girard-Globa, A; Berthezene, F; Moulin, P

    1999-01-01

    High density lipoprotein (HDL)-associated paraoxonase (PON) seems to play a major role in the protection of low density lipoprotein (LDL) against peroxidation by HDL, and the partly purified enzyme exerts a dose-dependent protective effect. A common polymorphism of the human gene (192 Q-->R) modulates paraoxonase activity but purified enzyme from either genotype is equally effective against LDL peroxidation. The inhibition of Cu2+-induced LDL peroxidation by HDL was monitored by lipid peroxide assay and change in LDL electrophoretic mobility. We show that HDL from type 2 diabetic patients with the QQ or RR genotype (n = 12 for each) reduce, to the same extent, both peroxide production (by 60.6 +/- 20.0 and 63.9 +/- 23.5%) and relative change in mobility (61.3 +/- 21.8 and 61.4 +/- 26.5%) despite a 6-fold difference in paraoxonase activity (47.4 +/- 4.4 vs. 299.7 +/- 23.7 U/l, P < 0.0001). Protection was, however, related to paraoxonase activity, but with a different efficiency in each group corresponding to a better protection per unit of enzyme in the QQ genotype group. Inactivation of PON activity by heating (56 degreesC, 10 min) or by EDTA was totally without effect on protection, which remained correlated with the paraoxonase activity measured prior to inactivation. In summary, these results suggest that the protein bearing both paraoxonase and arylesterase activities also possesses a third thermostable property, closely associated with paraoxon hydrolysis activity and unaffected by PON genetic variability.

  4. Aspirin as a Chemopreventive Agent for Cancer: a New Hope?

    Directory of Open Access Journals (Sweden)

    Isnatin Miladiyah

    2016-01-01

    Full Text Available Introduction: inflammation has been shown to play a major role in the pathogenesis of cancer. Inflammatory process activates the immune system through pro-inflammatory mediators and subsequent triggers transformation into malignant cells. Some tumors or cancers has been associated with chronic infections, such as hepatitis B and C viruses (hepatocellular carcinoma, human papilloma virus (cervical cancer, Helicobacter pylori (gastric cancer and lymphoma, and prostatitis (prostate cancer. A considerable study have investigated the benefits of aspirin for the prevention and treatment of cancer or tumors. Objectives: This paper aims to describe the relationship between inflammation and cancer incidence, so that use of aspirin as an anti-inflammatory agent is a rational choice in the treatment and prevention of cancer. Conclusion: Aspirin potential for chemoprevention of various types of cancer. Considering the high risk of side effects of aspirin, aspirin is not intended as a routine therapy to prevent the occurrence of cancer.

  5. 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.

  6. Vine Trimming Shoots as Substrate for Ferulic Acid Esterases Production.

    Science.gov (United States)

    Pérez-Rodríguez, N; Outeiriño, D; Torrado Agrasar, A; Domínguez, J M

    2017-02-01

    Ferulic acid esterases (FAE) possess a large variety of biotechnological applications mainly based on their ability to release ferulic acid from lignocellulosic matrixes. The use of vine trimming shoots (VTS), an agricultural waste, as substrate for the generation of this kind of esterases represents an attractive alternative to change the consideration of VTS from residue to resource. Furthermore, xylanase, cellobiase, and cellulase activities were quantified. Six microorganisms were screened for FAE production by solid-state fermentation, and the effects of the additional supplementation and substrate size were also tested. Finally, the process was scaled-up to a horizontal bioreactor where the influence of aeration in enzymatic activities was evaluated. Thus, the optimal FAE activity (0.44 U/g dry VTS) was attained by Aspergillus terreus CECT 2808, in non-additional supplementation media, using the larger particles size of substrate (≤ 5 mm) and at a flow rate of 0.7 L/min.

  7. 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

  8. 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.

  9. Hemagglutinin-esterase-fusion (HEF protein of influenza C virus

    Directory of Open Access Journals (Sweden)

    Mingyang Wang

    2015-07-01

    Full Text Available ABSTRACT Influenza C virus, a member of the Orthomyxoviridae family, causes flu-like disease but typically only with mild symptoms. Humans are the main reservoir of the virus, but it also infects pigs and dogs. Very recently, influenza C-like viruses were isolated from pigs and cattle that differ from classical influenza C virus and might constitute a new influenza virus genus. Influenza C virus is unique since it contains only one spike protein, the hemagglutinin-esterase-fusion glycoprotein HEF that possesses receptor binding, receptor destroying and membrane fusion activities, thus combining the functions of Hemagglutinin (HA and Neuraminidase (NA of influenza A and B viruses. Here we briefly review the epidemiology and pathology of the virus and the morphology of virus particles and their genome. The main focus is on the structure of the HEF protein as well as on its co- and post-translational modification, such as N-glycosylation, disulfide bond formation, S-acylation and proteolytic cleavage into HEF1 and HEF2 subunits. Finally, we describe the functions of HEF: receptor binding, esterase activity and membrane fusion.

  10. 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.

  11. Study of a sterol esterase secreted by Ophiostoma piceae: sequence, model and biochemical properties.

    Science.gov (United States)

    Calero-Rueda, Olga; Barba, Víctor; Rodríguez, Enrique; Plou, Francisco; Martínez, Angel T; Martínez, María Jesús

    2009-07-01

    An extracellular sterol esterase from Ophiostoma piceae efficiently hydrolyzes sterol esters, triglycerides and p-nitrophenol esters. cDNA was screened with a probe obtained by PCR using as primers oligonucleotides corresponding to the N-terminal and internal mature enzyme sequences and complete sequence was obtained by 3' rapid amplification of cDNA end (RACE) and inverse PCR. The O. piceae esterase gene had a length of 1.8 kbp and lacked introns. A search for proteins with related amino acid sequences revealed around 40% identity with lipases from Candida rugosa and Geotrichum candidum. Modelling the O. piceae enzyme, using the crystal structures of Lip1 and Lip3 from C. rugosa as templates, revealed a similar substrate-binding site, but some changes affecting the flap zone and the aromatic region of the tunnel may be responsible for the wide substrate specificity of this interesting sterol esterase. The ability of the new fungal esterase to hydrolyze triglycerides and esters of p-nitrophenol and cholesterol was compared with those of commercial lipases and cholesterol esterases showing the new enzyme the highest efficiency hydrolyzing triglycerides and sterol esters in the conditions assayed (in presence of Genapol X-100). Finally, the O. piceae gene was successfully expressed in Pichia pastoris, as a model organism to express fungal enzymes, resulting in higher levels of esterase activity than those obtained in the O. piceae cultures. In spite of its higher glycosylation degree, the recombinant enzyme was able to hydrolyze more efficiently than native enzyme the assayed substrates.

  12. Comparison of fungal carbohydrate esterases of family CE16 on artificial and natural substrates.

    Science.gov (United States)

    Puchart, Vladimír; Agger, Jane W; Berrin, Jean-Guy; Várnai, Anikó; Westereng, Bjørge; Biely, Peter

    2016-09-10

    The enzymatic conversion of acetylated hardwood glucuronoxylan to functional food oligomers, biochemicals or fermentable monomers requires besides glycoside hydrolases enzymes liberating acetic acid esterifying position 2 and/or 3 in xylopyranosyl (Xylp) residues. The 3-O-acetyl group at internal Xylp residues substituted by MeGlcA is the only acetyl group of hardwood acetylglucuronoxylan and its fragments not attacked by acetylxylan esterases of carbohydrate esterase (CE) families 1, 4, 5 and 6 and by hemicellulolytic acetyl esterases classified in CE family 16. Monoacetylated aldotetraouronic acid 3″-Ac(3)MeGlcA(3)Xyl3, generated from the polysaccharide by GH10 endoxylanases, appears to be one of the most resistant fragments. The presence of the two substituents on the non-reducing-end Xylp residue prevents liberation of MeGlcA by α-glucuronidase of family GH67 and blocks the action of acetylxylan esterases. The Ac(3)MeGlcA(3)Xyl3 was isolated from an enzymatic hydrolysate of birchwood acetylglucuronoxylan and characterized by (1)H NMR spectroscopy as a mixture of two positional isomers, 3″-Ac(3)MeGlcA(3)Xyl3 and 4″-Ac(3)MeGlcA(3)Xyl3, the latter being the result of acetyl group migration. The mixture was used as a substrate for three members of CE16 family of fungal origin. Trichoderma reesei CE16 esterase, inactive on polymeric substrate, deacetylated both isomers. Podospora anserina and Aspergillus niger esterases, active on acetylglucuronoxylan, deesterified effectively only the 4″-isomer. The results indicate catalytic diversity among CE16 enzymes, but also their common and unifying catalytic ability to exo-deacetylate positions 3 and 4 on non-reducing-end Xylp residues, which is an important step in plant hemicellulose saccharification. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. 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.

  14. Circulating Myeloid‐Related Protein–8/14 is Related to Thromboxane‐Dependent Platelet Activation in Patients With Acute Coronary Syndrome, With and Without Ongoing Low‐Dose Aspirin Treatment

    Science.gov (United States)

    Santilli, Francesca; Paloscia, Leonardo; Liani, Rossella; Di Nicola, Marta; Di Marco, Massimo; Lattanzio, Stefano; La Barba, Sara; Pascale, Silvia; Mascellanti, Marco; Davì, Giovanni

    2014-01-01

    Background Platelet activation is involved in acute coronary syndromes (ACS). Incomplete suppression by low‐dose aspirin treatment of thromboxane (TX) metabolite excretion (urinary 11‐dehydro‐TXB2) is predictive of vascular events in high‐risk patients. Myeloid‐related protein (MRP)‐8/14 is a heterodimer secreted on activation of platelets, monocytes, and neutrophils, regulating inflammation and predicting cardiovascular events. Among platelet transcripts, MRP‐14 has emerged as a powerful predictor of ACS. Methods and Results We enrolled 68 stable ischemic heart disease (IHD) and 63 ACS patients, undergoing coronary angiography, to evaluate whether MRP‐8/14 release in the circulation is related to TX‐dependent platelet activation in ACS and IHD patients and to residual TX biosynthesis in low‐dose aspirin–treated ACS patients. In ACS patients, plasma MRP‐8/14 and urinary 11‐dehydro‐TXB2 levels were linearly correlated (r=0.651, Paspirin. In aspirin‐treated ACS patients, MRP‐8/14 and 11‐dehydro‐TXB2 were lower versus those not receiving aspirin (Paspirin (Paspirin, TX biosynthesis in ACS (adjusted R2=0.384). Conclusions Circulating MRP‐8/14 is associated with TX‐dependent platelet activation in ACS, even during low‐dose aspirin treatment, suggesting a contribution of residual TX to MRP‐8/14 shedding, which may further amplify platelet activation. Circulating MRP‐8/14 may be a target to test different antiplatelet strategies in ACS. PMID:25037196

  15. Mechanisms of aspirin-sensitive asthma

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    Sun Ying

    2004-01-01

    Full Text Available It is now widely accepted that aspirin, along with other non-steroidal anti-inflammatory drugs (NSAIDs, may precipitate asthma attacks in a minority of susceptible individuals. The syndrome is part of a mucosal inflammatory disease that typically affects the nasal, as well as the bronchial, mucosa and sometimes the gut and skin also. Although the mucosal cellular infiltrate in aspirin-sensitive asthma and rhinitis resembles that of asthma and rhinitis in general, there is evidence of increased expression of asthma-relevant cytokines, such as interleukin-5 and granulocyte–macrophage colony stimulating factor, and a more intense infiltrate of mast cells and eosinophils. One key feature of aspirin-sensitive asthma is thought to be the overproduction of cysteinyl leukotrienes, principally by these local mast cells and eosinophils, but whether this represents a fundamental abnormality or is simply a consequence of greater numbers and activation of inflammatory cells is unclear. Genetic polymorphisms of the leukotriene C4 synthase gene, which result in elevated expression of this enzyme, may also play a role. In addition, overexpression of cysteinyl leukotriene receptors, particularly CysLT1, may contribute to an enhanced response of local inflammatory and structural cells to cysteinyl leukotrienes. Aspirin challenge in these patients is accompanied by acute further elevation of the already elevated baseline cysteinyl leukotriene synthesis, a phenomenon that is most closely related to the ability of aspirin and related NSAIDs to inhibit the cyclooxygenase enzyme COX-1. The reason for this is unknown, although it has been suggested that the COX-1 product prostaglandin E2 (PGE2 serves as a ‘brake’ to leukotriene synthesis and that somehow this mechanism is deficient in aspirin-sensitive asthmatics. A better understanding of the pathogenesis of aspirin-sensitive asthma will undoubtedly lead to better approaches to treatment. Aside from the use of

  16. Mode of action of aspirin as a chemopreventive agent.

    Science.gov (United States)

    Dovizio, Melania; Bruno, Annalisa; Tacconelli, Stefania; Patrignani, Paola

    2013-01-01

    Aspirin taken for several years at doses of at least 75 mg daily reduced long-term incidence and mortality due to colorectal cancer. The finding of aspirin benefit at low-doses given once daily, used for cardioprevention, locates the antiplatelet effect of aspirin at the center of its antitumor efficacy. In fact, at low-doses, aspirin acts mainly by an irreversible inactivation of platelet cyclooxygenase (COX)-1 in the presystemic circulation, which translates into a long-lasting inhibition of platelet function. Given the short half-life of aspirin in the human circulation(approximately 20 min) and the capacity of nucleated cells to resynthesize the acetylated COX-isozyme(s), it seems unlikely that a nucleated cell could be the target of aspirin chemoprevention. These findings convincingly suggest that colorectal cancer and atherothrombosis may share a common mechanism of disease, i.e. platelet activation in response to epithelial(in tumorigenesis) and endothelial(in tumorigenesis and atherothrombosis) injury. Activated platelets may also enhance the metastatic potential of cancer cells (through a direct interaction and/or the release of soluble mediators or exosomes) at least in part by inducing the overexpression of COX-2. COX-independent mechanisms of aspirin, such as the inhibition of NF-kB signaling and Wnt/β-catenin signaling and the acetylation of extra-COX proteins, have been suggested to play a role in its chemopreventive effects. However, their relevance remains to be demonstrated in vivo at clinical doses.

  17. Esterase isoenzymes and insecticide resistance in Frankliniella occidentalis populations from the south-east region of Spain.

    Science.gov (United States)

    López-Soler, Neus; Cervera, Amelia; Moores, Graham D; Martínez-Pardo, Rafael; Garcerá, M Dolores

    2008-12-01

    Frankliniella occidentalis (Pergande) is among the most important crop pests in the south-east region of Spain; its increasing resistance to insecticides constitutes a serious problem, and understanding the mechanisms involved is therefore of great interest. To this end, F. occidentalis populations, collected from the field at different locations in south-east Spain, were studied in terms of total esterase activity and esterase isoenzyme pattern. Individual thrips extracts were analysed by native polyacrylamide gel electrophoresis (PAGE) and stained for esterase activity with the model substrate alpha-naphthyl acetate. Significant correlations were found between resistance to the insecticides acrinathrin and methiocarb and the presence of a group of three intensely stained bands, named Triplet A. For each individual thrips extract, total esterase activity towards the substrates alpha-naphthyl acetate and alpha-naphthyl butyrate was also measured in a microplate reader. Insects possessing Triplet A showed a significantly higher alpha-naphthyl acetate specific activity and alpha-naphthyl acetate/alpha-naphthyl butyrate activity ratio. This observation allowed a reliable classification of susceptible or resistant insects either by PAGE analysis or by total esterase activity determination. The PAGE and microplate assays described can be used as a monitoring technique for detecting acrinathrin- and methiocarb-resistant individuals among F. occidentalis field populations.

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

    Directory of Open Access Journals (Sweden)

    Isabella Massimi

    2015-01-01

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

  19. 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

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

    Science.gov (United States)

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

    2015-01-01

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

  1. 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.

  2. 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.

  3. Platelet activity and aspirin efficacy after off-pump compared with on-pump coronary artery bypass surgery: results from the prospective randomized trial PRAGUE 11-Coronary Artery Bypass and REactivity of Thrombocytes (CABARET).

    Science.gov (United States)

    Bednar, Frantisek; Osmancik, Pavel; Vanek, Tomas; Mocikova, Heidi; Jares, Martin; Straka, Zbynek; Widimsky, Petr

    2008-10-01

    Changes in hemostasis after off-pump coronary artery bypass grafting are still being discussed. There is a lack of information about platelet activity and aspirin efficacy after coronary artery bypass grafting. The aim of this study was to assess and compare platelet activity and aspirin efficacy early and late after off-pump and on-pump coronary artery bypass grafting. Eighty patients were enrolled in a prospective randomized study. Platelet activity was determined based on membrane expression of antigen CD62P (P-selectin) by means of flow cytometric analysis. Aspirin efficacy was assessed by using arachidonic acid-induced platelet aggregation. Blood samples were collected before the operation, immediately postoperatively, and on days 1, 2, 5, and 30. In the off-pump group expression of P-selectin was markedly increased in comparison with preoperative values, with a maximum difference observed on day 2 (+53%, P = .02), and it was significantly higher compared with that seen in the on-pump group on days 2 and 5 (+53% vs +4%, P = .004, and +20% vs -16%, P = .005). On day 30, P-selectin expression was similar both between the groups and in comparison with the preoperative values. Arachidonic acid-induced platelet aggregation was gradually decreasing until day 30, but on day 2, there was an unexpected increase in aggregation that was more expressed in the off-pump group. The platelet activity is higher in the early postoperative period in off-pump compared with on-pump coronary artery bypass grafting. The present aspirin strategy seems to be insufficient in the early postoperative period, irrespective of the surgical technique used.

  4. 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.

  5. Peripheral nerve soluble esterases are spontaneously reactivated after inhibition by paraoxon: implications for a new definition of neuropathy target esterase.

    Science.gov (United States)

    Barril, J; Estévez, J; Escudero, M A; Céspedes, M V; Níguez, N; Sogorb, M A; Monroy, A; Vilanova, E

    1999-05-14

    Soluble extracts of chicken peripheral nerve contain detectable amounts of phenyl valerate esterase (PVase) activity (about 2000 nmol/min per g of fresh tissue). More than 95% of this activity is inhibited in assays where substrate has been added to a preincubated mixture of tissue with the non-neuropathic organophosphorus compound (OP) paraoxon (O,O'-diethyl p-nitrophenyl phosphate): residual activity includes soluble neuropathy target esterase (S-NTE) which, by definition, is considered resistant to long-term progressive (covalent) inhibition by paraoxon. However we have previously shown that paraoxon strongly interacts with S-NTE so interfering with its sensitivity to other inhibitors. We now show that, surprisingly, removal of paraoxon by ultrafiltration ('P' tissue) in order to avoid such an interference results in the reappearance of about 65% of total original soluble PVase activity which is inhibited in the presence of this OP. Although a purely reversible non-progressive inhibition might be suspected, kinetic analysis data show a time-progressive inhibition which suggests that such PVase(s) covalently bind paraoxon. Also a time-dependent recovery due to spontaneous reactivation of the PVase activity was observed after dilution of the inhibitor. Gel filtration chromatography of 'P' tissue in Sephacryl S-300 shows that the reactivated activity is associated with proteins of about 100-kDa mass which include S-NTE and an, as yet, unknown number of other PVases. The implications of these findings in the definition of NTE in a target tissue for the so-called organophosphorus-induced delayed polyneuropathy (OPIDP) are discussed.

  6. 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.

  7. 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.

  8. Study of molecular mechanisms of pro-apoptotic activity of NCX 4040, a novel nitric oxide-releasing aspirin, in colon cancer cell lines

    Directory of Open Access Journals (Sweden)

    Vannini Ivan

    2007-10-01

    Full Text Available Abstract Background Despite numerous studies aimed at verifying the antitumor activity of nitric oxide-releasing nonsteroidal antiflammatory drugs (NO-NSAIDs, little is known about the molecular targets responsible for their antineoplastic properties. In the present study, we investigated the mechanisms underlying the cytotoxicity of NCX 4040, a novel NO-aspirin with promising antineoplastic action, in in vitro human colon cancer models. Methods The effect on tumor growth was evaluated in four human colon cancer cell lines (LoVo, LRWZ, WiDr and LoVo Dx by sulforhodamine B assay, oxidative stress by immunohistochemistry, apoptosis by laddering assay, mitochondrial membrane potential (ΔΨm by flow cytometry, and apoptosis- and chemoresistance-related markers by western-blot and real-time method, respectively. Prostaglandin E2 levels were determined by ELISA. Results NCX 4040 produced a higher cytotoxic effect in all the cell lines than that produced by other NO donors tested. In particular, in LoVo and LRWZ cells, NCX 4040 induced a cytocidal effect and apoptosis through p53 and NAG-1 expression, an early ΔΨm collapse, and a sequential release of cytoplasmatic cytochrome c and caspase -9 and -3 active forms. 8-hydroxyguanine lesions, indicative of oxidative stress, were also observed. Conversely, in WiDr line, the drug caused a cytocidal effect, albeit not through apoptosis, and a concomitant increase in COX-2 activity. In LoVo Dx line, characterized by high levels drug resistance and DNA repair-related markers, only a cytostatic effect was observed, again in concomitance with the increase in COX-2 enzyme activity. Conclusion This study highlights the multiplicity of mechanisms involved in sensitivity or resistance to NCX 4040 and could provide useful indications for tailored therapy by identifying potentially drug-responsive tumors.

  9. 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

  10. 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

  11. Generation of transgenic wheat (Triticum aestivum L.) accumulating heterologous endo-xylanase or ferulic acid esterase in the endosperm

    DEFF Research Database (Denmark)

    Harholt, Jesper; Bach, Inga Christensen; Lind Bouquin, Solveig

    2010-01-01

    -expressing grains were also shrivelled, and the seed weight was decreased by 20%-50%. No ferulic acid esterase activity could be detected in wild-type grains whereas ferulic acid esterase activity was detected in transgenic lines. The grain cell walls had 15%-40% increase in water-unextractable arabinoxylan....... Transgenic plants were recovered in all four cases but no qualitative differences could be observed whether KDEL was added or not. Endo-xylanase activity in transgenic grains was increased between two and threefold relative to wild type. The grains were shrivelled and had a 25%-33% decrease in mass...

  12. 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.

  13. Characterization of a novel thermostable esterase from Thermus scotoductus SA-01: evidence of a new family of lipolytic esterases.

    Science.gov (United States)

    du Plessis, Erika M; Berger, Eldie; Stark, Therese; Louw, Maureen E; Visser, Daniel

    2010-04-01

    An esterase, designated EstTs1, was identified and characterized from a genomic library of Thermus scotoductus SA-01 (ATCC 700910). The library was screened in Escherichia coli for lipolytic activity on tributyrin agar plates. A 1.7-kb DNA fragment from a lipolytic positive clone was sequenced and two open reading frames (ORFs) were identified. A 774-bp ORF, designated EstTs1 with an estimated molecular mass of 28.6 kDa, and a 693-bp ORF, designated EstTs2 with an estimated molecular mass of 25.6 kDa, were identified. These two ORFs appear to form part of an operon. Sequence analysis showed that both proteins contained the G-X-S-X-G signature sequence motif present in most esterases and lipases. The deduced amino sequence of EstTs1 was found to display significant sequence identity with putative hydrolase proteins from both Thermus aquaticus Y51MC23 and Thermus thermophilus HB27. Similarly, EstTs2, also displayed significant homology to a second putative hydrolase protein present in the same two organisms. The cloning and characterization of these two ORFs from T. aquaticus Y51MC23 and T. thermophilus strain HB27 encoding putative hydrolase genes have not been reported. E. coli cells harbouring EstTs1 on a multicopy vector produced a clearing zone on tributyrin agar plates, whereas no enzymatic activity was observed for E. coli harbouring EstTs2 on a multicopy vector. EstTs1 displayed optimum activity at pH 7 and 80 degrees C with a half life of 48 h at 70 degrees C.

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

    Science.gov (United States)

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

    2009-04-01

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

  15. 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

  16. Increased platelet aggregation and serum thromboxane levels in aspirin-treated patients with prior myocardial infarction.

    Science.gov (United States)

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

    2012-07-01

    The antiplatelet effect of aspirin displays considerable inter-individual variability. We investigated the antiplatelet effect of aspirin in patients with coronary artery disease on aspirin mono-therapy with and without prior myocardial infarction (MI). Further, we investigated whether the effect of aspirin differed between patients with and without aspirin use at the time of MI onset. We performed a study on 231 patients, including 171 with prior MI. Among patients with only one prior MI (116 patients), 59 patients were on aspirin at the time of MI onset. All patients received 75 mg aspirin as mono-therapy. Platelet aggregation was assessed by multiple electrode aggregometry (Multiplate) and VerifyNow, and platelet activation was evaluated by soluble P-selectin. Furthermore, we measured serum thromboxane B2. MI patients had higher median platelet aggregation levels than patients without prior MI when evaluated by Multiplate (parachidonic acidaspirin before MI onset had significantly higher median aggregation levels compared with MI patients not on aspirin when evaluated by Multiplate (pcollagen=0.02) and VerifyNow (paspirin dose and optimal compliance. Serum thromboxane B2 levels were higher in MI patients than in patients without prior MI. Finally, patients on aspirin before MI onset had higher aggregation levels compared with patients not on aspirin.

  17. 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

  18. 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.

  19. Acidic-alkaline ferulic acid esterase from Chaetomium thermophilum var. dissitum: Molecular cloning and characterization of recombinant enzyme expressed in Pichia pastoris

    DEFF Research Database (Denmark)

    Dotsenko, Gleb; Tong, Xiaoxue; Pilgaard, Bo

    2016-01-01

    A novel ferulic acid esterase encoding gene CtFae, was successfully cloned from a highly esterase active strain of the thermophile ascomycetous fungus Chaetomium thermophilum var. dissitum; the gene was heterologously expressed in Pichia pastoris KM71H. The recombinant enzyme (CtFae) was purified...

  20. 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.

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

    OpenAIRE

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

    2015-01-01

    Overexpression of efflux transporters, in human cells, is a mechanism of resistance to drug and also to chemotherapy. We found that multidrug resistance protein-4 (MRP4) overexpression has a role in reducing aspirin action in patients after bypass surgery and, very recently, we found that aspirin enhances platelet MRP4 levels through peroxisome proliferator activated receptor-α (PPARα). In the present paper, we verified whether exposure of human embryonic kidney-293 cells (Hek-293) to aspirin...

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

    OpenAIRE

    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 ...

  3. Phylogeny, classification and metagenomic bioprospecting of microbial acetyl xylan esterases.

    Science.gov (United States)

    Adesioye, Fiyinfoluwa A; Makhalanyane, Thulani P; Biely, Peter; Cowan, Don A

    2016-11-01

    Acetyl xylan esterases (AcXEs), also termed xylan deacetylases, are broad specificity Carbohydrate-Active Enzymes (CAZymes) that hydrolyse ester bonds to liberate acetic acid from acetylated hemicellulose (typically polymeric xylan and xylooligosaccharides). They belong to eight families within the Carbohydrate Esterase (CE) class of the CAZy database. AcXE classification is largely based on sequence-dependent phylogenetic relationships, supported in some instances with substrate specificity data. However, some sequence-based predictions of AcXE-encoding gene identity have proved to be functionally incorrect. Such ambiguities can lead to mis-assignment of genes and enzymes during sequence data-mining, reinforcing the necessity for the experimental confirmation of the functional properties of putative AcXE-encoding gene products. Although one-third of all characterized CEs within CAZy families 1-7 and 16 are AcXEs, there is a need to expand the sequence database in order to strengthen the link between AcXE gene sequence and specificity. Currently, most AcXEs are derived from a limited range of (mostly microbial) sources and have been identified via culture-based bioprospecting methods, restricting current knowledge of AcXEs to data from relatively few microbial species. More recently, the successful identification of AcXEs via genome and metagenome mining has emphasised the huge potential of culture-independent bioprospecting strategies. We note, however, that the functional metagenomics approach is still hampered by screening bottlenecks. The most relevant recent reviews of AcXEs have focused primarily on the biochemical and functional properties of these enzymes. In this review, we focus on AcXE phylogeny, classification and the future of metagenomic bioprospecting for novel AcXEs. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Genome-wide analysis of esterase-like genes in the striped rice stem borer, Chilo suppressalis.

    Science.gov (United States)

    Wang, Baoju; Wang, Ying; Zhang, Yang; Han, Ping; Li, Fei; Han, Zhaojun

    2015-06-01

    The striped rice stem borer, Chilo suppressalis, a destructive pest of rice, has developed high levels of resistance to certain insecticides. Esterases are reported to be involved in insecticide resistance in several insects. Therefore, this study systematically analyzed esterase-like genes in C. suppressalis. Fifty-one esterase-like genes were identified in the draft genomic sequences of the species, and 20 cDNA sequences were derived which encoded full- or nearly full-length proteins. The putative esterase proteins derived from these full-length genes are overall highly diversified. However, key residues that are functionally important including the serine residue in the active site are conserved in 18 out of the 20 proteins. Phylogenetic analysis revealed that most of these genes have homologues in other lepidoptera insects. Genes CsuEst6, CsuEst10, CsuEst11, and CsuEst51 were induced by the insecticide triazophos, and genes CsuEst9, CsuEst11, CsuEst14, and CsuEst51 were induced by the insecticide chlorantraniliprole. Our results provide a foundation for future studies of insecticide resistance in C. suppressalis and for comparative research with esterase genes from other insect species.

  5. 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 ...

  6. 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 ...

  7. Dampak Hipoksia Sistemik terhadap Malondialdehida, Glial Fibrillary Acidic Protein dan Aktivitas Asetilkolin Esterase Otak Tikus

    Directory of Open Access Journals (Sweden)

    Andriani Andriani

    2016-09-01

    Full Text Available Hipoksia sistemik menyebabkan berkurangnya oksigen dan energi di otak sehingga memicupenglepasan neurotransmiter asetilkolin, meningkatkan radikal bebas dan glial fibrillary acidic protein (GFAPyang berfungsi menjaga kekuatan membran. Tujuan penelitian untuk melihat gambaran adaptasi otak padahipoksia sistemik terhadap fungsi asetilkolin esterase, kerusakan membran sel neuron dan astrosit. Penelitiandilakukan di Laboratorium Biokimia & Biologi Molekuler FK Universitas Indonesia, pada tahun 2013.Penelitian ekperimental ini menggunakan hewan coba tikus spraque dawley yang diinduksi hipoksia sistemikyang diambil jaringan otak bagian korteks dan plasma tikus. Kelompok tikus terdiri atas kelompok kontrol,kelompok perlakuan induksi hipoksia hari ke-1, 3 hari, 5 hari dan hari ke-7. Parameter yang diukur adalahkadar malondialdehida (MDA otak dan plasma, aktivitas spesifik enzim AChE jaringan otak serta kadar GFAPjaringan otak. Hasil menunjukkan bahwa hipoksia sistemik tidak meningkatkankadar MDA otak dan plasma.Induksi hipoksia sistemik meningkatkan aktivitas spesifik enzim AChE dan kadar GFAP jaringan otak secarabermakna. Pada plasma tidak terjadi peningkatan kadar GFAP. Hipoksia sistemik selama hari ke-7 belummenyebabkan kerusakan oksidatif, namun memperlihatkan peningkatan aktivitas AChe dan adaptasi astrositmelalui peningkatan GFAP. Kata kunci: hipoksia, astrosit, glial fibrillary acidic protein, malondialdehida, asetilkolin esterase   Systemic Hypoxia Effect on Rat Brain Malondialdehyde, Glial FibrillaryAcidic Protein, and Acetylcholine Esterase Activity Abstract Sistemic hypoxia causes lack of oxygen and energy in brain that trigger the release of acetylcholine,free radical and Glial fibrillary acidic protein (GFAP, a specific protein in astrocyte cells that act to strenghtenastrocite membrane. The aim of the research was to evaluate the damages of brain in systemic hypoxiathrough activity of acetylcholine esterase, neuron and astrocyte membran

  8. Est10: A Novel Alkaline Esterase Isolated from Bovine Rumen Belonging to the New Family XV of Lipolytic Enzymes.

    Directory of Open Access Journals (Sweden)

    María Cecilia Rodríguez

    Full Text Available A metagenomic fosmid library from bovine rumen was used to identify clones with lipolytic activity. One positive clone was isolated. The gene responsible for the observed phenotype was identified by in vitro transposon mutagenesis and sequencing and was named est10. The 367 amino acids sequence harbors a signal peptide, the conserved secondary structure arrangement of alpha/beta hydrolases, and a GHSQG pentapeptide which is characteristic of esterases and lipases. Homology based 3D-modelling confirmed the conserved spatial orientation of the serine in a nucleophilic elbow. By sequence comparison, Est10 is related to hydrolases that are grouped into the non-specific Pfam family DUF3089 and to other characterized esterases that were recently classified into the new family XV of lipolytic enzymes. Est10 was heterologously expressed in Escherichia coli as a His-tagged fusion protein, purified and biochemically characterized. Est10 showed maximum activity towards C4 aliphatic chains and undetectable activity towards C10 and longer chains which prompted its classification as an esterase. However, it was able to efficiently catalyze the hydrolysis of aryl esters such as methyl phenylacetate and phenyl acetate. The optimum pH of this enzyme is 9.0, which is uncommon for esterases, and it exhibits an optimal temperature at 40 °C. The activity of Est10 was inhibited by metal ions, detergents, chelating agents and additives. We have characterized an alkaline esterase produced by a still unidentified bacterium belonging to a recently proposed new family of esterases.

  9. 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.

  10. Histochemical studies on genetical control of hormonal enzyme inducibility in the mouse. IV: Cellular localization of androgen sensitive nonspecific esterase in the epididymis

    DEFF Research Database (Denmark)

    Kirkeby, S; Blecher, S R

    1981-01-01

    Nonspecific esterase of mouse epididymis has previously been studied histochemically, using alpha naphthyl-acetate and 5-bromoindoxyl acetate techniques, as well as certain inhibitors. Epithelial cell types of the epididymis have been characterized, and certain esterase isozymes in a particular c...... to normal. This method can now be applied to the study of epididymides of genetically sex-reversed chromosomal female, to analyze genetic control of X-chromosomal activation....

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

    Directory of Open Access Journals (Sweden)

    Paola Patrignani

    2012-12-01

    Full Text Available Recent findings have shown that aspirin, taken for several years, reduces the long-term risk of some cancers, particularly colorectal cancer. The result that aspirin benefit is detectable at daily low-doses (at least 75mg, the same used for the prevention of cardiovascular disease, positions the antiplatelet action of aspirin at the center of its antitumor efficacy. At low-doses given every 24 h, aspirin is acting by a complete and persistent inhibition of cyclooxygenase (COX-1 in platelets (in the pre-systemic circulation while causing a limited and rapidly reversible inhibitory effect on COX-2 and/or COX-1 expressed in nucleated cells. Aspirin has a short half-life in human circulation (approximately 20 min; nucleated cells have the ability to resynthesize the acetylated COX-isozymes within a few hours, while platelets do not. COX-independent mechanisms of aspirin, such as the inhibition of Wnt/ b-catenin and NF-kB signaling and the acetylation of extra-COX proteins, have been suggested to play a role in its chemo-preventive effects, but their relevance remains to be demonstrated in vivo at clinical doses. In conclusion, the results of clinical pharmacology and the analysis of randomized and epidemiological studies suggest that colorectal cancer and atherothrombosis share a common mechanism of disease, i.e. enhanced platelet activation in response to injury at distinct sites.

  12. 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.

  13. 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....

  14. 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.

  15. 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

  16. 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.

  17. 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...

  18. Biochemical characterization of an enantioselective esterase from Brevundimonas sp. LY-2.

    Science.gov (United States)

    Zhang, Jing; Zhao, Mengjun; Yu, Die; Yin, Jingang; Zhang, Hao; Huang, Xing

    2017-06-19

    Lactofen, a member of the diphenylether herbicides, has high activity and is commonly used to control broadleaf weeds. As a post-emergent herbicide, it is directly released to the environment, and easily caused the pollution. This herbicide is degraded in soil mainly by microbial activity, but the functional enzyme involved in the biodegradation of lactofen is still not clear now. A novel esterase gene lacH, involved in the degradation of lactofen, was cloned from the strain Brevundimonas sp. LY-2. The gene contained an open reading frame of 921 bp, and a putative signal peptide at the N-terminal was identified with the most likely cleavage site between Ala 28 and Ala 29. The encoded protein, LacH, could catalyze the hydrolysis of lactofen to form acifluorfen. Phylogenetic analysis showed that LacH belong to family V of bacterial lipolytic enzymes. Biochemical characterization analysis showed that LacH was a neutral esterase with an optimal pH of 7.0 and an optimal temperature of 40 °C toward lactofen. Besides, the activity of LacH was strongly inhibited by Hg 2+ and Zn 2+ . LacH preferred short chain p-nitrophenyl esters (C 2 -C 6 ), exhibited maximum activity toward p-nitrophenyl acetate. Furthermore, the enantioselectivity of LacH during lactofen hydrolysis was also studied, and the results show that R-(-)-lactofen was degraded faster than S-(+)-lactofen, indicating the occurrence of enantioselectivity in the enzymatic reaction. Our studies characterized a novel esterase involved in the biodegradation of diphenylether herbicide lactofen. The esterase showed enantioselectivity during lactofen degradation, which revealed the occurrence of enzyme-mediated enantioselective degradation of chiral herbicides.

  19. A chlorogenic acid esterase with a unique substrate specificity from Ustilago maydis.

    Science.gov (United States)

    Nieter, Annabel; Haase-Aschoff, Paul; Kelle, Sebastian; Linke, Diana; Krings, Ulrich; Popper, Lutz; Berger, Ralf G

    2015-03-01

    An extracellular chlorogenic acid esterase from Ustilago maydis (UmChlE) was purified to homogeneity by using three separation steps, including anion-exchange chromatography on a Q Sepharose FF column, preparative isoelectric focusing (IEF), and, finally, a combination of affinity chromatography and hydrophobic interaction chromatography on polyamide. SDS-PAGE analysis suggested a monomeric protein of ∼71 kDa. The purified enzyme showed maximal activity at pH 7.5 and at 37°C and was active over a wide pH range (3.5 to 9.5). Previously described chlorogenic acid esterases exhibited a comparable affinity for chlorogenic acid, but the enzyme from Ustilago was also active on typical feruloyl esterase substrates. Kinetic constants for chlorogenic acid, methyl p-coumarate, methyl caffeate, and methyl ferulate were as follows: Km values of 19.6 μM, 64.1 μM, 72.5 μM, and 101.8 μM, respectively, and kcat/Km values of 25.83 mM(-1) s(-1), 7.63 mM(-1) s(-1), 3.83 mM(-1) s(-1) and 3.75 mM(-1) s(-1), respectively. UmChlE released ferulic, p-coumaric, and caffeic acids from natural substrates such as destarched wheat bran (DSWB) and coffee pulp (CP), confirming activity on complex plant biomass. The full-length gene encoding UmChlE consisted of 1,758 bp, corresponding to a protein of 585 amino acids, and was functionally produced in Pichia pastoris GS115. Sequence alignments with annotated chlorogenic acid and feruloyl esterases underlined the uniqueness of this enzyme. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. Switching Catalysis from Hydrolysis to Perhydrolysis in Pseudomonas fluorescens Esterase

    Energy Technology Data Exchange (ETDEWEB)

    Yin, D.; Bernhardt, P; Morley, K; Jiang, Y; Cheeseman, J; Purpero, V; Schrag, J; Kazlauskas, R

    2010-01-01

    Many serine hydrolases catalyze perhydrolysis, the reversible formation of peracids from carboxylic acids and hydrogen peroxide. Recently, we showed that a single amino acid substitution in the alcohol binding pocket, L29P, in Pseudomonas fluorescens (SIK WI) aryl esterase (PFE) increased the specificity constant of PFE for peracetic acid formation >100-fold [Bernhardt et al. (2005) Angew. Chem., Int. Ed. 44, 2742]. In this paper, we extend this work to address the three following questions. First, what is the molecular basis of the increase in perhydrolysis activity? We previously proposed that the L29P substitution creates a hydrogen bond between the enzyme and hydrogen peroxide in the transition state. Here we report two X-ray structures of L29P PFE that support this proposal. Both structures show a main chain carbonyl oxygen closer to the active site serine as expected. One structure further shows acetate in the active site in an orientation consistent with reaction by an acyl-enzyme mechanism. We also detected an acyl-enzyme intermediate in the hydrolysis of {var_epsilon}-caprolactone by mass spectrometry. Second, can we further increase perhydrolysis activity? We discovered that the reverse reaction, hydrolysis of peracetic acid to acetic acid and hydrogen peroxide, occurs at nearly the diffusion limited rate. Since the reverse reaction cannot increase further, neither can the forward reaction. Consistent with this prediction, two variants with additional amino acid substitutions showed 2-fold higher k{sub cat}, but K{sub m} also increased so the specificity constant, k{sub cat}/K{sub m}, remained similar. Third, how does the L29P substitution change the esterase activity? Ester hydrolysis decreased for most esters (75-fold for ethyl acetate) but not for methyl esters. In contrast, L29P PFE catalyzed hydrolysis of {var_epsilon}-caprolactone five times more efficiently than wild-type PFE. Molecular modeling suggests that moving the carbonyl group closer to the

  1. Active-control trials: how would a new agent compare with placebo? A method illustrated with clopidogrel, aspirin, and placebo

    NARCIS (Netherlands)

    Fisher, L. D.; Gent, M.; Büller, H. R.

    2001-01-01

    In an active-control trial with a new treatment and a comparator that has placebo-controlled trials, how might the effect of the new therapy versus placebo be estimated? For many diseases it is not ethically justified to use a placebo-control trial, yet in the United States regulatory efficacy is

  2. Novel Cold-Adapted Esterase MHlip from an Antarctic Soil Metagenome

    Directory of Open Access Journals (Sweden)

    Moreno Galleni

    2013-01-01

    Full Text Available An Antarctic soil metagenomic library was screened for lipolytic enzymes and allowed for the isolation of a new cytosolic esterase from the a/b hydrolase family 6, named MHlip. This enzyme is related to hypothetical genes coding esterases, aryl-esterases and peroxydases, among others. MHlip was produced, purified and its activity was determined. The substrate profile of MHlip reveals a high specificity for short p-nitrophenyl-esters. The apparent optimal activity of MHlip was measured for p-nitrophenyl-acetate, at 33 °C, in the pH range of 6–9. The MHlip thermal unfolding was investigated by spectrophotometric methods, highlighting a transition (Tm at 50 °C. The biochemical characterization of this enzyme showed its adaptation to cold temperatures, even when it did not present evident signatures associated with cold-adapted proteins. Thus, MHlip adaptation to cold probably results from many discrete structural modifications, allowing the protein to remain active at low temperatures. Functional metagenomics is a powerful approach to isolate new enzymes with tailored biophysical properties (e.g., cold adaptation. In addition, beside the ever growing amount of sequenced DNA, the functional characterization of new catalysts derived from environment is still required, especially for poorly characterized protein families like α/b hydrolases.

  3. 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

  4. PRODUCTION AND CHARACTERIZATION OF AN ALKALOTHERMOSTABLE, ORGANIC SOLVENT TOLERANT AND SURFACTANT TOLERANT ESTERASE PRODUCED BY A THERMOPHILIC BACTERIUM GEOBACILLUS SP. AGP-04, ISOLATED FROM BAKRESHWAR HOT SPRING, INDIA

    Directory of Open Access Journals (Sweden)

    Amit Ghati

    2013-10-01

    Full Text Available A thermophilic bacteria, Geobacillus sp. AGP-04, isolated from Surya Kund hot spring, Bakreshwar, West Bengal, India was studied in terms of capability of tributyrin hydrolysis and characterization of its thermostable esterase activity using p-nitrophenyl butyrate (PNPB as substrate. The extracellular crude preparation was characterized in terms of pH and temperature optima and stability, organic solvent tolerance capacity and stability, substrate specificity, surfactant tolerance capacity, kinetic parameters and activation/inhibition behavior towards some metal ions and chemicals. Tributyrin agar assay exhibited that Geobacillus sp. AGP-04 secretes an extracellular esterase. The Vmax and Km values of the esterase were found to be 5099 U/Land 103.5µM, respectively in the presence of PNPB as substrate. The optimum temperature and pH, for Geobacillus sp. AGP-04 esterase was 60oC and 8.0, respectively. Although the enzyme activity was not significantly altered by incubating crude extract solution at 20-70oC for 1 hour, the enzyme activity was fully lost at 90oC for same incubation period. The pH stability profile showed that original crude esterase activity is stable at a broad range (pH 5.0-10.0. Moreover, the enzyme was highly organic solvent and surfactant tolerant. The effect of some chemical on crude esterase activity indicated that Geobacillus sp. AGP-04 produce an esterase which contains a serine residue in active site and for its activity -SH groups are essential. Besides, enzyme production was highly induced if fermentation medium contain polysaccharides and oil as carbon source.

  5. Esterases of Varroa destructor (Acari: Varroidae), parasitic mite of the honeybee.

    Science.gov (United States)

    Dmitryjuk, Małgorzata; Żołtowska, Krystyna; Frączek, Regina; Lipiński, Zbigniew

    2014-04-01

    Varroa destructor is an ectoparasite that causes serious damage to the population of the honeybee. Increasing resistance of the parasite to acaricides is related, among others, to metabolic adaptations of its esterases to facilitate decomposition of the chemicals used. Esterases are a large heterogeneous group of enzymes that metabolize a number of endogenous and exogenous substrates with ester binding. The aim of the present study was to determine the activity of esterases in the body extracts (BE) and excretion/secretion products (E/SP) of the mite. The enzymes contained in the E/SP should originate mainly from the salivary glands and the alimentary system and they may play a particularly important role in the first line of defence of the mite against acaricides. Activity of cholinesterases (ChEs) [acetylcholinesterase (AChE) and butyrylcholinesterase], carboxylesterases (CEs) and phosphatases [alkaline phosphatase (AP) and acid phosphatase (AcP)] was investigated. The activity of all the enzymes except AChE was higher in the E/SP than in the BE. ChEs from the BE and from the E/SP reacted differently on eserine, a ChE inhibitor. Eserine inhibited both enzymes from the BE, increased decomposition of acetylcholine, but did not influence hydrolysis of butyrylcholine by the E/SP. Activity of the CEs from the BE in relation to the esters of carboxylic acids can be presented in the following series: C10 > C12 > C14 > C8 > C2 > C4 = C16, while activity of the CEs from the E/SP was: C4 > C8 > C2 > C14 > C10 > C12 > C16. The inhibitor of CEs, triphenyl phosphate, reduced the activity of esterases C2–C8 and C14–C16; however, it acted in the opposite way to CEs C10 and C12. The activity of both phosphatases was higher in the E/SP than in the BE (AcP about twofold and AP about 2.6-fold); the activities of AP and AcP in the same material were similar. Given the role of esterases in resistance to pesticides, further studies are necessary to obtain complete biochemical

  6. 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 ...

  7. Acetylcholine esterase inhibitors and melanin synthesis inhibitors from Salvia officinalis.

    Science.gov (United States)

    Sallam, Amal; Mira, Amira; Ashour, Ahmed; Shimizu, Kuniyoshi

    2016-09-15

    Salvia officinalis is a traditionally used herb with a wide range of medicinal applications. Many phytoconstituents have been isolated from S. officinalis, mainly phenolic diterpenes, which possess many biological activities. This study aimed to evaluate the ability of the phenolic diterpenes of S. officinalis to inhibit acetylcholine esterase (AChE) as well as their ability to inhibit melanin biosynthesis in B16 melanoma cells. The phenolic diterpenes isolated from the aerial parts of S. officinalis were tested for their effect on melanin biosynthesis in B16 melanoma cell lines. They were also tested for their ability to inhibit AChE using Ellman's method. Moreover, a molecular docking experiment was used to investigate the binding affinity of the isolated phenolic diterpenes to the amino acid residues at the active sites of AChE. Seven phenolic diterpenes-sageone, 12-methylcarnosol, carnosol, 7b-methoxyrosmanol, 7a-methoxyrosmanol, isorosmanol and epirosmanol-were isolated from the methanolic extract of the aerial parts of S. officinalis. Isorosmanol showed a melanin-inhibiting activity as potent as that of arbutin. Compounds 7a-methoxyrosmanol and isorosmanol inhibited AChE activity by 50% and 65%, respectively, at a concentration of 500 µM. The results suggest that isorosmanol is a promising natural compound for further studies on development of new medications which might be useful in ageing disorders such as the declining of cognitive functions and hyperpigmentation. Copyright © 2016 Elsevier GmbH. All rights reserved.

  8. Aspirin inhibits the SHH/GLI1 signaling pathway and sensitizes malignant glioma cells to temozolomide therapy.

    Science.gov (United States)

    Ming, Jianguang; Sun, Bo; Li, Ziwei; Lin, Lin; Meng, Xiangqi; Han, Bo; Wang, Ruijia; Wu, Pengfei; Li, Jianlong; Cai, Jinquan; Jiang, Chuanlu

    2017-04-01

    Aberrant activation of sonic hedgehog (SHH)/glioma-associated oncogene homolog 1 (GLI1) pathway plays an important role in the tumorigenicity of malignant glioma cells and resistance to temozolomide (TMZ). Here we investigated the aspirin's antineoplastic molecular route by targeting SHH/GLI1 pathway and examined the feasibility of aspirin combined with TMZ therapy. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) revealed that the activity of the SHH/GLI1 pathway was strongly inhibited by aspirin. Aspirin acted as the glioma growth-inhibitory and pro-apoptosis roles by inhibiting the SHH/GLI1 pathway and reprogramming the epithelial to mesenchymal transition (EMT). The immunofluorescence assay showed aspirin could prevent the nuclear translocation of GLI1 to inhibit its transcriptional regulation. The stable lentiviral overexpression of GLI1 reversed the DNA double strand breaks (DSBs) caused by the GANT61 and TMZ. Furthermore, aspirin combined with TMZ enhanced chemosensitivity and GLI1-induced chemoprotection was partly blocked by aspirin in vitro and in vivo . Collectively, aspirin has a therapeutic potential for SHH/GLI1 targeted therapy against glioma cells. Acquired activation of GLI1 protects glioma cells against TMZ therapy. Impairment of DNA DSBs repair activity might be involved in the route of aspirin-induced chemosensitivity. Combined aspirin with TMZ may be a promising strategy against malignant glioma.

  9. Biochemical Characterization of a Family 15 Carbohydrate Esterase from a Bacterial Marine Arctic Metagenome.

    Directory of Open Access Journals (Sweden)

    Concetta De Santi

    Full Text Available The glucuronoyl esterase enzymes of wood-degrading fungi (Carbohydrate Esterase family 15; CE15 form part of the hemicellulolytic and cellulolytic enzyme systems that break down plant biomass, and have possible applications in biotechnology. Homologous enzymes are predicted in the genomes of several bacteria, however these have been much less studied than their fungal counterparts. Here we describe the recombinant production and biochemical characterization of a bacterial CE15 enzyme denoted MZ0003, which was identified by in silico screening of a prokaryotic metagenome library derived from marine Arctic sediment. MZ0003 has high similarity to several uncharacterized gene products of polysaccharide-degrading bacterial species, and phylogenetic analysis indicates a deep evolutionary split between these CE15s and fungal homologs.MZ0003 appears to differ from previously-studied CE15s in some aspects. Some glucuronoyl esterase activity could be measured by qualitative thin-layer chromatography which confirms its assignment as a CE15, however MZ0003 can also hydrolyze a range of other esters, including p-nitrophenyl acetate, which is not acted upon by some fungal homologs. The structure of MZ0003 also appears to differ as it is predicted to have several large loop regions that are absent in previously studied CE15s, and a combination of homology-based modelling and site-directed mutagenesis indicate its catalytic residues deviate from the conserved Ser-His-Glu triad of many fungal CE15s. Taken together, these results indicate that potentially unexplored diversity exists among bacterial CE15s, and this may be accessed by investigation of the microbial metagenome. The combination of low activity on typical glucuronoyl esterase substrates, and the lack of glucuronic acid esters in the marine environment suggest that the physiological substrate of MZ0003 and its homologs is likely to be different from that of related fungal enzymes.

  10. Novel feruloyl esterase from Lactobacillus fermentum NRRL B-1932 and analysis of the recombinant enzyme produced in Escherichia coli.

    Science.gov (United States)

    Using agar plates containing ethyl ferulate as the sole carbon source, 33 Lactobacillus strains were screened for feruloyl esterase (FE) activity. Among a dozen species showing a clearing zone on the opaque plate containing ethyl ferulate, Lactobacillus fermentum NRRL B-1932 demonstrated the stronge...

  11. Oriented covalent immobilization of esterase BioH on hydrophilic-modified Fe3O4 nanoparticles.

    Science.gov (United States)

    Li, Rongrong; Jiang, Ling; Ye, Lidan; Lu, Jie; Yu, Hongwei

    2014-01-01

    The esterase BioH from Escherichia coli was covalently immobilized onto the surface of the functional magnetic nanosupport in an oriented manner. The surface of the Fe3O4 nanosupport was modified with acyl azide groups or both acyl azide groups and hydroxyl groups. The protein loading of the support was increased from 55 to 99 mg/g by an improvement in hydrophilicity, and the activity retention of the immobilized esterase on the nanosupport was improved by 40% after hydrophilic modification (30% and 70% of the free BioH, respectively). For the BioH immobilized on the hydrophilic-modified nanosupport, the recovery activity remained 80% of the original activity after 10 times of recycling. The catalytic kinetics and thermo-/pH-stability of the immobilized esterase BioH were also determined and compared with those of the free enzyme. The comparatively high activity retention, improved thermo-/pH-stability, and good reusability of the immobilized enzyme indicate that oriented covalent immobilization is an efficient method for immobilizing esterase BioH. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

  12. Novel ferulate esterase from Gram-positive lactic acid bacteria and analyses of the recombinant enzyme produced in E. coli

    Science.gov (United States)

    Using a plate containing ethyl ferulate as sole carbon source, various bacteria cultures were screened for ferulate esterase (FAE). Among a dozen of species showing positive FAE, one Lactobacillus fermentum strain NRRL 1932 demonstrated the strongest activity. Using a published sequence of ferulate ...

  13. Expression of the juvenile hormone esterase gene in the Colorado potato beetle, Leptinotarsa decemlineata : Photoperiodic and juvenile hormone analog response

    NARCIS (Netherlands)

    Vermunt, A.M.W.; Koopmanschap, A.B.; Vlak, J.M.; Kort, de C.A.D.

    1999-01-01

    Metamorphosis and reproduction in insects are controlled by juvenile hormone (JH). One of the factors, which regulate the JH titer in the hemolymph, is the activity of juvenile hormone esterase (JHE). JHE from the Colorado potato beetle, Leptinotarsa decemlineata, consists of two 57kDa subunits. In

  14. UP-REGULATION OF ANTITHROMBOTIC ECTONUCLEOTIDASES BY ASPIRIN IN HUMAN ENDOTHELIAL-CELLS IN-VITRO

    NARCIS (Netherlands)

    CHEUNG, PK; VISSER, J; BAKKER, WW

    1994-01-01

    Ecto ATP-diphosphohydrolase (apyrase) activity of human endothelial cells following aspirin treatment has been studied in-vitro. It was shown by HPLC analysis of supernatant samples that pre-incubation of the cultures with aspirin resulted in a significantly increased turnover of supplemented ATP

  15. Aspirin Prevents Colorectal Cancer by Normalizing EGFR Expression.

    Science.gov (United States)

    Li, Haitao; Zhu, Feng; Boardman, Lisa A; Wang, Lei; Oi, Naomi; Liu, Kangdong; Li, Xiang; Fu, Yang; Limburg, Paul J; Bode, Ann M; Dong, Zigang

    2015-05-01

    Aspirin intake reduces the risk of colorectal cancer (CRC), but the molecular underpinnings remain elusive. Epidermal growth factor receptor (EGFR), which is overexpressed in about 80% of CRC cases, is implicated in the etiology of CRC. Here, we investigated whether aspirin can prevent CRC by normalizing EGFR expression. Immunohistochemistry staining was performed on paraffin-embedded tissue sections from normal colon mucosa, adenomatous polyps from FAP patients who were classified as regular aspirin users or nonusers. The interplay between cyclooxygenase-2 (COX-2) and EGFR was studied in primary intestinal epithelial cells isolated from Apc(Min) mice, immortalized normal human colon epithelial cells (HCEC) as well as murine embryonic fibroblasts (MEFs). Immunohistochemistry staining results established that EGFR overexpression is an early event in colorectal tumorigenesis, which can be greatly attenuated by regular use of aspirin. Importantly, EGFR and COX-2 were co-overexpressed and co-localized with each other in FAP patients. Further mechanistic studies revealed that COX-2 overexpression triggers the activation of the c-Jun-dependent transcription factor, activator protein-1 (AP-1), which binds to the Egfr promoter. Binding facilitates the cellular accumulation of EGFR and lowers the threshold required for pre-neoplastic cells to undergo transformation. Aspirin might exert its chemopreventive activity against CRC, at least partially, by normalizing EGFR expression in gastrointestinal precancerous lesions.

  16. Aspirin inhibits ErbB2 to induce apoptosis in cervical cancer cells.

    Science.gov (United States)

    Xiang, Shuanglin; Sun, Zhenhua; He, Qiongzhi; Yan, Feng; Wang, Yijun; Zhang, Jian

    2010-06-01

    The use of aspirin is associated with a lower risk of many cancer types. However, there are few reports about cervical cancer. The proto-oncogene ErbB2 is overexpressed in cervical cancer, and considered as a therapeutic target. In the present study, we investigated whether aspirin had therapeutic value in cervical cancer and examined the effects of aspirin on the amplification and expression of ErbB2. To investigate the effects of aspirin on apoptosis and proliferation, we tested apoptosis by Hoechst 33258 staining and Annexin V-FITC/PI method; MTT assay and colony formation assay were used to detect proliferation. Induction of apoptosis and inhibition of proliferation were observed in HeLa cells incubated with aspirin. Western blot and immunocytochemical staining showed that aspirin induced a dose- and time-dependent reduction of ErbB2 expression that was due to proteosome-mediated degradation of this protein. To further investigate the underlying mechanism by which aspirin exerts its apoptosis effects, we studied the ErbB2 downstream cell survival signaling pathways and the expression of anti-apoptosis gene Bcl-2. We found that aspirin inhibited the activation of extracellular signal-regulated kinase (ERK) and AKT. The inhibition of Bcl-2 expression was also observed. These data reveal that aspirin significantly induces apoptosis and inhibits proliferation, which maybe via inhibiting ErbB2 downstream cell survival signaling pathways. Taken together, our article describes a novel mechanism of action for anti-tumor activity of aspirin and implicates aspirin as a novel agent for cervical cancer.

  17. Generation of transgenic wheat (Triticum aestivum L.) accumulating heterologous endo-xylanase or ferulic acid esterase in the endosperm

    Energy Technology Data Exchange (ETDEWEB)

    Harholt, Jesper; Bach, Inga C; Lind-Bouquin, Solveig; Nunan, Kylie J.; Madrid, Susan M.; Brinch-Pedersen, Henrik; Holm, Preben B.; Scheller, Henrik V.

    2009-12-08

    Endo-xylanase (from Bacillus subtilis) or ferulic acid esterase (from Aspergillus niger) were expressed in wheat under the control of the endosperm specific 1DX5 glutenin promoter. Constructs both with and without the endoplasmic reticulum retention signal KDEL were used. Transgenic plants were recovered in all four cases but no qualitative differences could be observed whether KDEL was added or not. Endo-xylanase activity in transgenic grains was increased between two and three fold relative to wild type. The grains were shriveled and had a 25-33% decrease in mass. Extensive analysis of the cell walls showed a 10-15% increase in arabinose to xylose ratio, a 50% increase in the proportion of water extractable arabinoxylan, and a shift in the MW of the water extractable arabinoxylan from being mainly larger than 85 kD to being between 2 kD and 85 kD. Ferulic acid esterase expressing grains were also shriveled and the seed weight was decreased by 20-50%. No ferulic acid esterase activity could be detected in wild type grains whereas ferulic acid esterase activity was detected in transgenic lines. The grain cell walls had 15-40% increase in water unextractable arabinoxylan and a decrease in monomeric ferulic acid between 13 and 34%. In all the plants the observed changes are consistent with a plant response that serves to minimize the effect of the heterologously expressed enzymes by increasing arabinoxylan biosynthesis and cross-linking.

  18. 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.

  19. Combined effects of aspirin and vitamin D3 on two OSCC cell lines: a preliminary study.

    Science.gov (United States)

    Xiao, Ting-Ting; Li, Xian; Feng, Jia-Li; Li, Yong

    2018-01-18

    We evaluated the potential effects of aspirin combined with vitamin D3 on cell proliferation and apoptosis in oral cancer cells. Compared to the untreated control or individual drug, the combinations of aspirin and vitamin D3 significantly decreased the rates of cell proliferation by CCK-8 assay, and caused higher rates of cell apoptosis in both CAL-27 and SCC-15 cells by Annexin V-FITC apoptosis assay and flow cytometry. Remarkably, the combined treatment with aspirin and vitamin D3 significantly suppressed the expression of Bcl-2 protein and p-Erk1/2 protein, examined by western blot analysis. Our study demonstrates that aspirin and vitamin D3 have biological activity against two human OSCC cell lines and their activity is synergistic or additive when two drugs used in combination with therapeutic concentrations. The combination of aspirin and vitamin D3 may be an effective approach for inducing cell death in OSCC.

  20. Aspirin-triggered lipoxin A4 attenuates LPS-induced pro-inflammatory responses by inhibiting activation of NF-κB and MAPKs in BV-2 microglial cells

    Directory of Open Access Journals (Sweden)

    Yuan Shi-Ying

    2011-08-01

    Full Text Available Abstract Background Microglial activation plays an important role in neurodegenerative diseases through production of nitric oxide (NO and several pro-inflammatory cytokines. Lipoxins (LXs and aspirin-triggered LXs (ATLs are considered to act as 'braking signals' in inflammation. In the present study, we investigated the effect of aspirin-triggered LXA4 (ATL on infiammatory responses induced by lipopolysaccharide (LPS in murine microglial BV-2 cells. Methods BV-2 cells were treated with ATL prior to LPS exposure, and the effects of such treatment production of nitric oxide (NO, inducible nitric oxide synthase (iNOS, interleukin-1β (IL-1β and tumour necrosis factor-α (TNF-α were analysed by Griess reaction, ELISA, western blotting and quantitative RT-PCR. Moreover, we investigated the effects of ATL on LPS-induced nuclear factor-κB (NF-κB activation, phosphorylation of mitogen-activated protein kinases (MAPKs and activator protein-1 (AP-1 activation. Results ATL inhibited LPS-induced production of NO, IL-1β and TNF-α in a concentration-dependent manner. mRNA expressions for iNOS, IL-1β and TNF-α in response to LPS were also decreased by ATL. These effects were inhibited by Boc-2 (a LXA4 receptor antagonist. ATL significantly reduced nuclear translocation of NF-κB p65, degradation of the inhibitor IκB-α, and phosphorylation of extracellular signal-regulated kinase (ERK and p38 MAPK in BV-2 cells activated with LPS. Furthermore, the DNA binding activity of NF-κB and AP-1 was blocked by ATL. Conclusions This study indicates that ATL inhibits NO and pro-inflammatory cytokine production at least in part via NF-κB, ERK, p38 MAPK and AP-1 signaling pathways in LPS-activated microglia. Therefore, ATL may have therapeutic potential for various neurodegenerative diseases.

  1. Aspirin induces Beclin-1-dependent autophagy of human hepatocellular carcinoma cell.

    Science.gov (United States)

    Huang, Zhenjun; Fang, Weilun; Liu, Weihua; Wang, Li; Liu, Bin; Liu, Shiming; Liu, Shaojun

    2018-01-31

    Aspirin not only reduces the incidence of hepatocellular carcinoma (HCC) but also plays a synergistic role with chemotherapy for HCC treatment. However, the underlying mechanisms remain incompletely elucidated. Given that autophagy triggers cancer cell death, the present study examined the autophagic effect of aspirin on HCC cells. Results showed that aspirin increased LC3II/LC3I ratio, decreased p62 expression, and enhanced autophagic flux (autophagosome and autolysosome puncta) in Hep3B, HepG2, or SMMC-7721 cells, reflecting the autophagy of HCC cells. The autophagic effects of aspirin depended on Beclin-1 expression. Aspirin disrupted the interaction between Bcl-2 and Beclin-1. In addition to activating the AMP-activated protein kinase, c-Jun N-terminal kinase, and Glycogen synthase kinase-3 pathways, aspirin inhibited the mammalian-target-of rapamycin-S6K1/4E-BP1 signaling. Aspirin induced autophagy of HCC cell. This study contributes to understanding the chemoprotective and inhibitory effects of aspirin on HCC development. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Deposition and aggregation of aspirin molecules on a phospholipid bilayer pattern.

    Science.gov (United States)

    Mao, Guangzhao; Chen, Dongzhong; Handa, Hitesh; Dong, Wenfei; Kurth, Dirk G; Möhwald, Helmuth

    2005-01-18

    Aspirin and 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) are deposited from their alcoholic mixed solution onto highly oriented pyrolytic graphite (HOPG) by spin coating. The film structure and morphology are characterized by atomic force microscopy (AFM). The barely soluble DMPE forms a highly oriented stripe phase as a result of its one-dimensional epitaxy with the HOPG lattice. The bilayer stripe pattern exposes the cross section of the lipid bilayer lamellae and enables the direct visualization of the molecular interactions of drug or biological molecules with either the hydrophobic or the hydrophilic part of the phospholipid bilayer. The bilayer pattern affects the aspirin molecular deposition and aggregation. AFM shows that the aspirin molecules prefer to deposit and aggregate along the aliphatic interior part of the bilayer pattern, giving rise to parallel dimer rods in registry with the underlying pattern. The nonpolar interactions between aspirin and the phospholipid bilayer are consistent with the lipophilic nature of aspirin. The bilayer pattern not only stabilizes the rodlike aggregate structure of aspirin at low aspirin concentration but also inhibits crystallization of aspirin at high aspirin concentration. Molecular models show that the width of the DMPE aliphatic chain interior can accommodate no more than two aspirin dimers. The bilayer confinement may prevent aspirin from reaching its critical nucleus size. This study illustrates a general method to induce a metastable or amorphous form of an active pharmaceutical ingredient (API) by chemical confinement under high undercooling conditions. Metastable and amorphous solids often display better solubility and bioavailability than the stable crystalline form of the API.

  3. 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...

  4. 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 ...

  5. 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/ ...

  6. 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.

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

    Science.gov (United States)

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

    2010-02-01

    Nifurtimox and benznidazole are the only active drugs against Trypanosoma cruzi; however, they have limited efficacy and severe side effects. During primoinfection, T. cruzi infected macrophages mount an antiparasitic response, which the parasite evades through an increase of tumor growth factor beta and PGE(2) activation as well as decreased iNOS activity. Thus, prostaglandin synthesis inhibition with aspirin might increase macrophage antiparasitic activity and increase nifurtimox and benznidazole effect. Aspirin alone demonstrated a low effect upon macrophage antiparasitic activity. However, isobolographic analysis of the combined effects of aspirin, nifurtimox and benznidazole indicated a synergistic effect on T. cruzi infection of RAW cells, with combinatory indexes of 0.71 and 0.61, respectively. The observed effect of aspirin upon T. cruzi infection was not related with the PGE(2) synthesis inhibition. Nevertheless, NO() levels were restored by aspirin in T. cruzi-infected RAW cells, contributing to macrophage antiparasitic activity improvement. Thus, the synergy of aspirin with nifurtimox and benznidazole is due to the capability of aspirin to increase antiparasitic activity of macrophages. Copyright 2009 Elsevier Inc. All rights reserved.

  8. 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.

  9. 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.

  10. 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.

  11. 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,

  12. Molecular cloning, and characterization of a modular acetyl xylan esterase from the edible straw mushroom Volvariella volvacea.

    Science.gov (United States)

    Ding, Shaojun; Cao, Jie; Zhou, Rui; Zheng, Fei

    2007-09-01

    A new Volvariella volvacea gene encoding an acetyl xylan esterase (designated as Vvaxe1) was cloned and expressed in Pichia pastoris. The cDNA contained an ORF of 1047 bp encoding 349 amino acids with a calculated mass of 39 990 Da. VvAXE1 is a modular enzyme consisting of an N-terminal signal peptide, a catalytic domain, and a cellulose-binding domain. The amino acid sequence of the enzyme exhibited a high degree of similarity to cinnamoyl esterase B from Penicillium funiculosum, and acetyl xylan esterases from Aspergillus oryzae, Penicillium purpurogenum, and Aspergillus ficuum. Recombinant acetyl xylan esterase released acetate from several acetylated substrates including beta-d-xylose tetraacetate and acetylated xylan. No activity was detectable on p-nitrophenyl acetate. Enzyme-catalyzed hydrolysis of 4-methylumbelliferyl acetate was maximal at pH 8.0 and 60 degrees C, and reciprocal plots revealed an apparent K(m) value of 307.7 microM and a V(max) value of 24 733 IU micromol(-1) protein. ReAXE1 also exhibited a capacity to bind to Avicel and H(3)PO(4) acid-swollen cellulose.

  13. Juvenile hormone (JH esterase of the mosquito Culex quinquefasciatus is not a target of the JH analog insecticide methoprene.

    Directory of Open Access Journals (Sweden)

    Shizuo G Kamita

    Full Text Available Juvenile hormones (JHs are essential sesquiterpenes that control insect development and reproduction. JH analog (JHA insecticides such as methoprene are compounds that mimic the structure and/or biological activity of JH. In this study we obtained a full-length cDNA, cqjhe, from the southern house mosquito Culex quinquefasciatus that encodes CqJHE, an esterase that selectively metabolizes JH. Unlike other recombinant esterases that have been identified from dipteran insects, CqJHE hydrolyzed JH with specificity constant (k(cat/K(M ratio and V(max values that are common among JH esterases (JHEs. CqJHE showed picomolar sensitivity to OTFP, a JHE-selective inhibitor, but more than 1000-fold lower sensitivity to DFP, a general esterase inhibitor. To our surprise, CqJHE did not metabolize the isopropyl ester of methoprene even when 25 pmol of methoprene was incubated with an amount of CqJHE that was sufficient to hydrolyze 7,200 pmol of JH to JH acid under the same assay conditions. In competition assays in which both JH and methoprene were available to CqJHE, methoprene did not show any inhibitory effects on the JH hydrolysis rate even when methoprene was present in the assay at a 10-fold higher concentration relative to JH. Our findings indicated that JHE is not a molecular target of methoprene. Our findings also do not support the hypothesis that methoprene functions in part by inhibiting the action of JHE.

  14. 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.

  15. 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.

  16. Biochemical Characterization and Relative Expression Levels of Multiple Carbohydrate Esterases of the Xylanolytic Rumen Bacterium Prevotella ruminicola 23 Grown on an Ester-Enriched Substrate ▿ †

    Science.gov (United States)

    Kabel, Mirjam A.; Yeoman, Carl J.; Han, Yejun; Dodd, Dylan; Abbas, Charles A.; de Bont, Jan A. M.; Morrison, Mark; Cann, Isaac K. O.; Mackie, Roderick I.

    2011-01-01

    We measured expression and used biochemical characterization of multiple carbohydrate esterases by the xylanolytic rumen bacterium Prevotella ruminicola 23 grown on an ester-enriched substrate to gain insight into the carbohydrate esterase activities of this hemicellulolytic rumen bacterium. The P. ruminicola 23 genome contains 16 genes predicted to encode carbohydrate esterase activity, and based on microarray data, four of these were upregulated >2-fold at the transcriptional level during growth on an ester-enriched oligosaccharide (XOSFA,Ac) from corn relative to a nonesterified fraction of corn oligosaccharides (AXOS). Four of the 16 esterases (Xyn10D-Fae1A, Axe1-6A, AxeA1, and Axe7A), including the two most highly induced esterases (Xyn10D-Fae1A and Axe1-6A), were heterologously expressed in Escherichia coli, purified, and biochemically characterized. All four enzymes showed the highest activity at physiologically relevant pH (6 to 7) and temperature (30 to 40°C) ranges. The P. ruminicola 23 Xyn10D-Fae1A (a carbohydrate esterase [CE] family 1 enzyme) released ferulic acid from methylferulate, wheat bran, corn fiber, and XOSFA,Ac, a corn fiber-derived substrate enriched in O-acetyl and ferulic acid esters, but exhibited negligible activity on sugar acetates. As expected, the P. ruminicola Axe1-6A enzyme, which was predicted to possess two distinct esterase family domains (CE1 and CE6), released ferulic acid from the same substrates as Xyn10D-Fae1 and was also able to cleave O-acetyl ester bonds from various acetylated oligosaccharides (AcXOS). The P. ruminicola 23 AxeA1, which is not assigned to a CE family, and Axe7A (CE7) were found to be acetyl esterases that had activity toward a broad range of mostly nonpolymeric acetylated substrates along with AcXOS. All enzymes were inhibited by the proximal location of other side groups like 4-O-methylglucuronic acid, ferulic acid, or acetyl groups. The unique diversity of carbohydrate esterases in P. ruminicola 23

  17. Expanding the feruloyl esterase gene family of Aspergillus niger by characterization of a feruloyl esterase, FaeC.

    Science.gov (United States)

    Dilokpimol, Adiphol; Mäkelä, Miia R; Mansouri, Sadegh; Belova, Olga; Waterstraat, Martin; Bunzel, Mirko; de Vries, Ronald P; Hildén, Kristiina S

    2017-07-25

    A feruloyl esterase (FAE) from Aspergillus niger N402, FaeC was heterologously produced in Pichia pastoris X-33 in a yield of 10mg/L. FaeC was most active at pH 7.0 and 50°C, and showed broad substrate specificity and catalyzed the hydrolysis of methyl 3,4-dimethoxycinnamate, ethyl ferulate, methyl ferulate, methyl p-coumarate, ethyl coumarate, methyl sinapate, and methyl caffeate. The enzyme released both ferulic acid and p-coumaric acid from wheat arabinoxylan and sugar beet pectin (up to 3mg/g polysaccharide), and acted synergistically with a commercial xylanase increasing the release of ferulic acid up to six-fold. The expression of faeC increased over time in the presence of feruloylated polysaccharides. Cinnamic, syringic, caffeic, vanillic and ferulic acid induced the expression of faeC. Overall expression of faeC was very low in all tested conditions, compared to two other A. niger FAE encoding genes, faeA and faeB. Our data showed that the fae genes responded differently towards the feruloylated polysaccharides and tested monomeric phenolic compounds suggesting that the corresponding FAE isoenzymes may target different substrates in a complementary manner. This may increase the efficiency of the degradation of diverse plant biomass. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. 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).

  19. 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.

  20. 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 ...

  1. Fitness differences due to allelic variation at Esterase-4 locus in ...

    Indian Academy of Sciences (India)

    KAVITA KRISHNAMOORTI

    2017-08-31

    Aug 31, 2017 ... Abstract. Esterases are known to play essential role in metabolism, reproductive physiology and behaviour of Drosophila. Esterases are highly polymorphic enzymes in Drosophila, but the polymorphism of these enzymes is not well studied in Drosophila ananassae. Recent studies on esterase ...

  2. Fitness differences due to allelic variation at Esterase-4 locus in ...

    Indian Academy of Sciences (India)

    Keywords. esterases; null allele; reproductive fitness; natural selection; Drosophila ananassae. Abstract. Esterases are known to play essential role inmetabolism, reproductive physiology and behaviour of Drosophila. Esterases are highly polymorphic enzymes in Drosophila, but the polymorphism of these enzymes is not ...

  3. 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...

  4. 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.

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

    Science.gov (United States)

    Grove, Erik Lerkevang

    2012-09-01

    of aspirin were evaluated in healthy individuals and patients with coronary artery disease. Pharmaco-specific metabolites were measured in urine and serum to investigate the pharmacodynamic effect of aspirin and to enable the comparison with the more global tests of platelet function. Based on repeated duplicate measurements, we evaluated the reproducibility of each test. We found that reproducibility of the classical reference method was not impressive and that the newer, so-called point-of-care tests differed markedly on reproducibility. With coefficients of variation of about 3%, the VerifyNow Aspirin test was clearly the most reproducible test - even after correction of the official scale, which begins at about 350 aspirin reaction units and, therefore, results in artificially low coefficients of variation. Among the platelet function tests investigated, Multiplate was most sensitive for aspirin treatment. In study 2 we performed the hitherto largest study of newly released, immature platelets as a marker of platelet turnover. The study population included healthy individuals, patients with stable coronary artery disease, and patients with acute coronary syndromes. The main finding was an increased fraction of immature platelets in patients with ST-segment myocardial infarction, indicating an increased platelet turnover. Smoking and type 2 diabetes were identified as independent determinants of platelet turnover. In study 3 we explored the relationship between platelet turnover and the antiplatelet effect of aspirin in patients with stable coronary artery disease. The study results support the hypothesis that an increased platelet turnover reduces the antiplatelet effect of aspirin. The main findings were: 1) platelet turnover correlated with platelet aggregation measured by Multiplate and with sP-selectin, a marker of platelet activation. 2) Patients with diabetes mellitus type 2 had reduced antiplatelet effect of aspirin compared with patients without diabetes

  6. In vitro effects of aspirin and paracetamol on human erythrocyte ...

    African Journals Online (AJOL)

    The activity of glutathione-S-transferase of human erythrocytes was monitored spectrophotometically in the presence and absence of two analgesics (aspirin and paracetamol). Five different concentrations (1.0, 3.0, 5.0, 7.0, 9.0 and 10.0 mg/ml) of each analgesic were used which covers the reported therapeutic and toxic ...

  7. Pharmacological action of choline and aspirin coadministration on acute inflammatory pain.

    Science.gov (United States)

    Yong-Ping, Shi; Jin-Da, Wang; Ru-Huan, Wang; Xiang-Di, Zhao; Hai-Tao, Yu; Hai, Wang

    2011-09-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain but undesirable side effects limit their clinical usefulness. Choline is a α7 nicotinic receptor agonist that has antinociceptive effects in a variety of pain models. Drug combination is a strategy in the management of pain to reduce side effects. The aim of the study was to evaluate the nature of the interaction between choline and aspirin in two distinct inflammatory pain models. The analgesic mechanism of choline was also investigated. In the writhing test, intravenous administration of choline or aspirin showed dose-dependent antinociceptive activity, and isobolographic analysis revealed a synergistic nature of the interaction between choline and aspirin. More importantly, coadministration choline with aspirin could significantly shorten the antinociceptive latency of aspirin and prolong the antinociceptive duration of aspirin in the writhing test. In the carrageenan test, single administration of choline or aspirin significantly attenuated carrageenan-induced thermal hyperalgesia in a dose-dependent relationship. Coadministration of non-analgesic doses of aspirin with choline significantly suppressed the thermal hyperalgesia, with a longer duration efficacy. Furthermore, we found that α7 nicotinic, muscarinic, and opioid-receptors are involved in the antinociceptive effect of choline in the writhing test and the antinociceptive effect produced by systemically administered choline may be via a peripheral mechanism. In conclusion, coadministration of choline and aspirin holds promise for development as a safe analgesic drug combination for inflammatory pain, with a higher potency and longer duration than either aspirin or choline alone. Copyright © 2011 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

  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. 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.

  10. Cellular function of neuropathy target esterase in lysophosphatidylcholine action.

    Science.gov (United States)

    Vose, Sarah C; Fujioka, Kazutoshi; Gulevich, Alex G; Lin, Amy Y; Holland, Nina T; Casida, John E

    2008-11-01

    Neuropathy target esterase (NTE) plays critical roles in embryonic development and maintenance of peripheral axons. It is a secondary target of some organophosphorus toxicants including analogs of insecticides and chemical warfare agents. Although the mechanistic role of NTE in vivo is poorly defined, it is known to hydrolyze lysophosphatidylcholine (LPC) in vitro and may protect cell membranes from cytotoxic accumulation of LPC. To determine the cellular function of NTE, Neuro-2a and COS-7 cells were transfected with a full-length human NTE-containing plasmid yielding recombinant NTE (rNTE). We find the same inhibitor sensitivity and specificity profiles for rNTE assayed with LPC or phenyl valerate (a standard NTE substrate) and that this correlation extends to the LPC hydrolases of human brain, lymphocytes and erythrocytes. All of these LPC hydrolases are therefore very similar to each other in respect to a conserved inhibitor binding site conformation. NTE is expressed in brain and lymphocytes and contributes to LPC hydrolase activities in these tissues. The enzyme or enzymes responsible for erythrocyte LPC hydrolase activity remain to be identified. We also show that rNTE protects Neuro-2a and COS-7 cells from exogenous LPC cytotoxicity. Expression of rNTE in Neuro-2a cells alters their phospholipid balance (analyzed by liquid chromatography-mass spectrometry with single ion monitoring) by lowering LPC-16:0 and LPC-18:0 and elevating glycerophosphocholine without a change in phosphatidylcholine-16:0/18:1 or 16:0/18:2. NTE therefore serves an important function in LPC homeostasis and action.

  11. 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

  12. New cholesterol esterase inhibitors based on rhodanine and thiazolidinedione scaffolds

    DEFF Research Database (Denmark)

    Heng, Sabrina; Tieu, William; Hautmann, Stephanie

    2011-01-01

    We present a new class of inhibitors of pancreatic cholesterol esterase (CEase) based on 'priviledged' 5-benzylidenerhodanine and 5-benzylidene-2,4-thiazolidinedione structural scaffolds. The lead structures (5-benzylidenerhodanine 4a and 5-benzylidene-2,4-thiazolidinedione 4b) were identified...

  13. Analysis on the correlation between serum esterase polymorphism ...

    African Journals Online (AJOL)

    张德杨

    2013-02-01

    Feb 1, 2013 ... The polymorphism of serum esterase (Es) of Henan Yuxi fat-tailed sheep was detected through polyacrylamide gel electrophoresis ... strain selection in early stage. As the most common index of genetic marker in blood .... exerted indistinctive impact on body size index and other indexes (P>0.05) except for ...

  14. Esterase, total protein and seed storage protein diversity in Okra ...

    African Journals Online (AJOL)

    Twenty-two accessions of okra (Abelmoschus esculentus), maintained at the Plant Genetic Resources Centre, Bunso, Ghana, were assayed for diversity in esterases, and total and storage proteins. A total of 34 reproducible and easily scorable bands were exposed with the number of bands per accession ranging from one ...

  15. Assessment Of Leukocyte Esterase Dipstick Test In Diagnosis Of ...

    African Journals Online (AJOL)

    This is a prospective study of urinary tract infection in 65 children (38 males and 27 females, M: F ratio 1: 0.7). Urine samples were evaluated by culture, microscopy and leukocyte esterase dipstick test. Positive urine culture, with significant bacteriuria was found in 19(29.2%). Urine microscopy for leukocyturia identified ...

  16. Molecular cloning and characterization of a novel pyrethroid-hydrolyzing esterase originating from the Metagenome

    Directory of Open Access Journals (Sweden)

    Liu Yu

    2008-12-01

    Full Text Available Abstract Background Pyrethroids and pyrethrins are widely used insecticides. Extensive applications not only result in pest resistance to these insecticides, but also may lead to environmental issues and human exposure. Numerous studies have shown that very high exposure to pyrethroids might cause potential problems to man and aquatic organisms. Therefore, it is important to develop a rapid and efficient disposal process to eliminate or minimize contamination of surface water, groundwater and agricultural products by pyrethroid insecticides. Bioremediation is considered to be a reliable and cost-effective technique for pesticides abatement and a major factor determining the fate of pyrethroid pesticides in the environment, and suitable esterase is expected to be useful for potential application for detoxification of pyrethroid residues. Soil is a complex environment considered as one of the main reservoirs of microbial diversity on the planet. However, most of the microorganisms in nature are inaccessible as they are uncultivable in the laboratory. Metagenomic approaches provide a powerful tool for accessing novel valuable genetic resources (novel enzymes and developing various biotechnological applications. Results The pyrethroid pesticides residues on foods and the environmental contamination are a public safety concern. Pretreatment with pyrethroid-hydrolyzing esterase has the potential to alleviate the conditions. To this end, a pyrethroid-hydrolyzing esterase gene was successfully cloned using metagenomic DNA combined with activity-based functional screening from soil, sequence analysis of the DNA responsible for the pye3 gene revealed an open reading frame of 819 bp encoding for a protein of 272 amino acid residues. Extensive multiple sequence alignments of the deduced amino acid of Pye3 with the most homologous carboxylesterases revealed moderate identity (45–49%. The recombinant Pye3 was heterologously expressed in E. coli BL21(DE3

  17. 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.

  18. Protein Phosphatase Methyl-Esterase PME-1 Protects Protein Phosphatase 2A from Ubiquitin/Proteasome Degradation.

    Directory of Open Access Journals (Sweden)

    Ryotaro Yabe

    Full Text Available Protein phosphatase 2A (PP2A is a conserved essential enzyme that is implicated as a tumor suppressor based on its central role in phosphorylation-dependent signaling pathways. Protein phosphatase methyl esterase (PME-1 catalyzes specifically the demethylation of the C-terminal Leu309 residue of PP2A catalytic subunit (PP2Ac. It has been shown that PME-1 affects the activity of PP2A by demethylating PP2Ac, but also by directly binding to the phosphatase active site, suggesting loss of PME-1 in cells would enhance PP2A activity. However, here we show that PME-1 knockout mouse embryonic fibroblasts (MEFs exhibit lower PP2A activity than wild type MEFs. Loss of PME-1 enhanced poly-ubiquitination of PP2Ac and shortened the half-life of PP2Ac protein resulting in reduced PP2Ac levels. Chemical inhibition of PME-1 and rescue experiments with wild type and mutated PME-1 revealed methyl-esterase activity was necessary to maintain PP2Ac protein levels. Our data demonstrate that PME-1 methyl-esterase activity protects PP2Ac from ubiquitin/proteasome degradation.

  19. Esterase polymorphism marking cultivars of Manihot esculenta, Crantz

    Directory of Open Access Journals (Sweden)

    Adriana Gazoli Resende

    2004-07-01

    Full Text Available Esterase isozymes were used to detected substrate-preference polymorphism in twenty cultivars of Manihot esculenta, and to show cultivar-specific variation of this species. A relatively complex extraction solution of proteins from leaves was needed to show a larger number of esterase isozymes. Similarity between cultivars from six groups ranged from 51 to 96%. The cultivars identified by the same name seemed to be biochemically different regarding esterase isozymes. Esterase isozyme electrophoretic patterns could, therefore, be used to discriminate the cultivars identified by the same name, and to monitor the vegetative propagation of cultivars maintained in the germplasm collection. In breeding strategies, isoesterase analysis could be used to avoid intercrossing between the similar genotypes.Isoenzimas esterases foram usadas no presente estudo, para detectar polimorfismos específicos para diferentes substratos em vinte cultivares de Manihot esculenta, e para mostrar variações específicas de cultivares nesta espécie. Os diferentes cultivares de M. esculenta tem sido mantidos na coleção de germoplasma do Departamento de Agronomia da Universidade Estadual de Maringá (Maringá, PR, e foram provenientes de cultivares tradicionais coletados nas regiões sudoeste e noroeste do Estado. Foi necessário a utilização de uma solução de extração de proteínas relativamente mais complexa, para evidenciar um maior número de isoenzimas esterases. A similaridade entre os cultivares variou de 51 a 96%. Cultivares identificados pelo mesmo nome parecem ser bioquimicamente diferentes para as isoenzimas esterases. Os padrões eletroforéticos das isoesterases podem, portanto, serem usados para discriminar os cultivares que são identificados pelo mesmo nome, e para monitorar a propagação vegetativa dos cultivares mantidos na coleção de germoplasma. A análise das isoesterases pode também ser usada para evitar cruzamentos entre genótipos mais

  20. Production and partial characterization of alkaline feruloyl esterases by Fusarium oxysporum during submerged batch cultivation

    DEFF Research Database (Denmark)

    Topakas, E.; Christakopoulos, Paul

    2004-01-01

    Production of feruloyl esterases (FAEs) by Fusarium oxysporum was enhanced by optimization of initial pH of the culture medium, the type and concentration of nitrogen and carbon source. Submerged batch cultivation in a laboratory bioreactor (17 1) produced activity at 82 nkat g(-1) dry substrate...... (corn cobs) which compared favorably to those reported for the other microorganisms. Use of de-esterified corn cobs as carbon source decreased FAE production by 5.5-fold compared to untreated corn cobs even though ferulic acid (FA) was added to the concentration found in alkali-extracts of corn cobs...

  1. 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.

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

    Science.gov (United States)

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

    2012-03-15

    The balance between phase-I carcinogen-activating and phase-II detoxifying xenobiotic metabolizing enzymes is critical to determining an individual's risk for cancer. We evaluated the effect of Hydrogen sulfide-releasing aspirin (HS-ASA) on xenobiotic metabolizing enzymes in HT-29 human colon and Hepa 1c1c7 mouse liver adenocarcinoma cells and in Wistar rats. HS-ASA inhibited the growth of HT-29 and Hepa 1c1c7 cells, with an IC(50) of 3.2 ± 0.3 μM and 4.2 ± 0.4 μM, respectively. The IC(50) for ASA in both cell lines was greater than 5000 μM at 24h. In these cell lines, HS-ASA caused a dose-dependent increase in activity and expression of the phase-II enzymes glutathione S-transferase (GST) and NAD(P)H:quinoneoxireductase (NQO1). It also caused an increase in UDP-glucuronosyltransferase (UGT) expression. The levels of CYP 1A1 a phase-I enzyme was increased by HS-ASA in both cell lines. Pretreatment of cells with NaF, an esterase inhibitor, abrogated the HS-ASA-mediated increases in NQO1 enzyme activity. HS-ASA increased the protein levels of the transcription factor Nrf2, which is a regulator of the phase-II enzymes. In vivo, HS-ASA at 100mg/kg/day had no effect on rat's weights; it induced a 3.4-fold and 1.4-fold increase in hepatic GST and NQO1 enzyme activities, respectively. GST and NQO1 protein levels were also increased. In contrast to that in cultured cells, CYP 1A1 protein levels were not altered in vivo. Therefore, HS-ASA induces phase-II enzymes, at least in part, through the action of H(2)S and by modulating Nrf2; these effects may be part of its mechanism of action against carcinogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Organophosphate insecticides and acaricides antagonise bifenazate toxicity through esterase inhibition in Tetranychus urticae.

    Science.gov (United States)

    Van Leeuwen, Thomas; Van Pottelberge, Steven; Nauen, Ralf; Tirry, Luc

    2007-12-01

    Bifenazate is a carbazate acaricide known for its potency, particularly against tetranychid mite species such as the two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae). It was recently shown that the compound needs to be activated by an S,S,S-tributyl-phosphorotrithioate (DEF)-sensitive mechanism in spider mites to display full acaricidal efficacy. The ability of well-known organophosphates and carbamates to inhibit the activation of bifenazate and thus compromise its acaricidal potential was tested. Esterase activity determined in vivo after pre-exposure of mites with organophosphates and carbamates revealed--depending on the compound--varying esterase inhibition nicely correlated with the ability of the individual compound to antagonise bifenazate action on mites. The findings illustrate that organophosphates and carbamates interfere with bifenazate efficacy, most probably by inhibiting carboxylesterases responsible for the activation of the pro-drug. As a result of the strong antagonism, mixtures of bifenazate with carbamates or organophosphates should not be used under field conditions. Moreover, there exists a real threat in repeatedly applying organophosphates and bifenazate. The present study again illustrates how important mode of action information is for the proper planning of resistance management strategies. Copyright (c) 2007 Society of Chemical Industry.

  4. Characterisation of esterases as potential biomarkers of pesticide exposure in the lugworm Arenicola marina (Annelida: Polychaeta)

    Energy Technology Data Exchange (ETDEWEB)

    Hannam, Marie L. [Ecotoxicology and Stress Biology Research Centre, School of Biological Sciences, University of Plymouth, Drake Circus, Plymouth, Devon, PL4 8AA (United Kingdom)], E-mail: marie.hannam@plymouth.ac.uk; Hagger, Josephine A.; Jones, Malcolm B.; Galloway, Tamara S. [Ecotoxicology and Stress Biology Research Centre, School of Biological Sciences, University of Plymouth, Drake Circus, Plymouth, Devon, PL4 8AA (United Kingdom)

    2008-03-15

    Here, we identify and characterise cholinesterase (ChE) and carboxylesterase (CbE) activities in the body tissues of the sediment dwelling worm Arenicola marina. Exposure to the organophosphorus pesticide azamethiphos yielded an in vitro IC{sub 50} of 5 {mu}g l{sup -1} for propionylcholinesterase (PChE). PChE was significantly inhibited in vivo after a 10 day exposure to 100 {mu}g l{sup -1} azamethiphos, equivalent to the recommended aquatic application rate (ANOVA; F = 2.75, P = 0.033). To determine sensitivity to environmental conditions, A. marina were exposed for 10 days to field collected sediments. PChE activity was significantly lower in worms exposed to sediments from an estuary classified to be at high risk from point source pollution by the UK Environment Agency (ANOVA; F = 15.33, P < 0.001). Whilst causality cannot be directly attributed from these latter exposures, they provide an important illustration of the potential utility of esterase activity as a biomarker of environmental quality in this ecologically relevant sentinel species. - This paper provides a preliminary characterisation of esterase enzyme activities in the tissues and body fluids of the sediment dwelling worm Arenicola marina and explores their potential use as biomarkers of organophosphorus pesticide exposure in the marine environment.

  5. Synergistic interaction between choline and aspirin against acute inflammation induced by carrageenan and lipopolysaccharide.

    Science.gov (United States)

    Pan, Zhi-Yuan; Wang, Hai

    2014-05-01

    The simultaneous use of drugs with different mechanisms of anti-inflammatory action is a strategy for achieving effective control of inflammation while minimizing dose-related side effects. Choline was described to potentiate the antinociceptive action of aspirin at small doses in several inflammatory pain models. However, these findings are only limited to alleviating pain, more associated data are required to confirm the effectiveness of the combined choline and aspirin therapy against inflammatory disorders. Moreover, no report is available regarding the mechanism responsible for their synergism. Here, we first investigated the anti-inflammatory activity and pharmacological mechanisms of co-administration of choline and aspirin in 2 commonly studied inflammation models, carrageenan-induced paw edema and lipopolysaccharide (LPS)-induced sepsis in mice. Isobolographic analysis revealed that combined choline and aspirin administration exhibited a strong synergistic interaction in reducing carrageenan-mediated edema, and the estimated combination index values at 50%, 75%, and 90% effective dose (ED50, ED75, and ED90) were 0.25, 0.32, and 0.44. Drug co-administration also afforded synergistic protection against LPS-induced sepsis and mortality, since aspirin or choline alone was inadequate to improve survival. The effects of choline-aspirin co-administration were blocked by methyllycaconitine, suggesting that activation of alpha 7 nicotinic acetylcholine receptor participates in the interaction between choline and aspirin. Furthermore, co-administration of choline and aspirin was more likely to inhibit the production of pro-inflammatory mediators induced by LPS. Our results indicated that combined choline and aspirin therapy represented a significant synergistic interaction in attenuating acute inflammatory response. This preclinical relevant evidence provides a promising approach to treat inflammation-based diseases such as arthritis and sepsis. Copyright © 2014

  6. 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 ...

  7. 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 ...

  8. Isolation and characterization of a heavy metal-resistant, thermophilic esterase from a Red Sea Brine Pool

    KAUST Repository

    Mohamed, Yasmine M.

    2013-11-28

    The Red Sea Atlantis II brine pool is an extreme environment that displays multiple harsh conditions such as high temperature, high salinity and high concentrations of multiple, toxic heavy metals. The survival of microbes in such an environment by utilizing resistant enzymes makes them an excellent source of extremophilic enzymes. We constructed a fosmid metagenomic library using DNA isolated from the deepest and most secluded layer of this pool. We report the isolation and biochemical characterization of an unusual esterase: EstATII. EstATII is thermophilic (optimum temperature, 65 C), halotolerant (maintains its activity in up to 4.5â€...M NaCl) and maintains at least 60% of its activity in the presence of a wide spectrum of heavy metals. The combination of biochemical characteristics of the Red Sea Atlantis II brine pool esterase, i.e., halotolerance, thermophilicity and resistance to heavy metals, makes it a potentially useful biocatalyst.

  9. 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...

  10. 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 ...

  11. 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 ...

  12. Crystal structure of human esterase D: a potential genetic marker of retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Dong; Li, Yang; Song, Gaojie; Zhang, David; Shaw, Neil; Liu, Zhi-Jie; (Chinese Aca. Sci.)

    2009-07-10

    Retinoblastoma (RB), a carcinoma of the retina, is caused by mutations in the long arm of chromosome 13, band 13q14. The esterase D (ESD) gene maps at a similar location as the RB gene locus and therefore serves as a potential marker for the prognosis of retinoblastoma. Because very little is known about the structure and function of ESD, we determined the 3-dimensional structure of the enzyme at 1.5 {angstrom} resolution using X-ray crystallography. ESD shows a single domain with an {alpha}/{beta}-hydrolase fold. A number of insertions are observed in the canonical {alpha}/{beta}-hydrolase fold. The active site is located in a positively charged, shallow cleft on the surface lined by a number of aromatic residues. Superimposition studies helped identify the typical catalytic triad residues -- Ser-153, His264, and Asp230 -- involved in catalysis. Mutagenesis of any of the catalytic triad residues to alanine abolished the enzyme activity. Backbone amides of Leu54 and Met150 are involved in the formation of the oxyanion hole. Interestingly, a M150A mutation increased the enzyme activity by 62%. The structure of human ESD determined in this study will aid the elucidation of the physiological role of the enzyme in the human body and will assist in the early diagnosis of retinoblastoma. Wu, D., Li, Y., Song, G., Zhang, D., Shaw, N., Liu, Z. J. Crystal structure of human esterase D: a potential genetic marker of retinoblastoma.

  13. [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.

  14. Aspirin for Prevention of Preeclampsia in Lupus Pregnancy

    Directory of Open Access Journals (Sweden)

    Amelie M. Schramm

    2014-01-01

    Full Text Available Preeclampsia, the onset of hypertension and proteinuria during pregnancy, is a common medical disorder with high maternal and fetal mortality and morbidity. The underlying pathology remains poorly understood and includes inflammation, endothelial dysfunction, and an unbalanced thromboxane A2/prostacyclin ratio. For women with systemic lupus erythematosus (SLE, particularly those with preexisting renal disease or with active lupus, the risk of developing preeclampsia is up to 14% higher than it is among healthy individuals. The mechanism is still unknown and the data for preventing preeclampsia in lupus pregnancies are rare. Modulating the impaired thromboxane A2/prostacyclin ratio by administration of low-dose aspirin appears to be the current best option for the prevention of preeclampsia. After providing an overview of the pathogenesis of preeclampsia, preeclampsia in lupus pregnancies, and previous trials for prevention of preeclampsia with aspirin treatment, we recommend low-dose aspirin administration for all lupus patients starting prior to 16 weeks of gestation. Patients with SLE and antiphospholipid syndrome should receive treatment with heparin and low-dose aspirin during pregnancy.

  15. 12-[(5-iodo-4-azido-2-hydroxybenzoyl)amino]dodecanoic acid: biological recognition by cholesterol esterase and acyl-CoA:cholesterol O-acyltransferase.

    Science.gov (United States)

    Kinnunen, P M; Klopf, F H; Bastiani, C A; Gelfman, C M; Lange, L G

    1990-02-13

    Potential probes of protein cholesterol and fatty acid binding sites, namely, 12-[(5-iodo-4-azido-2-hydroxybenzoyl)amino]dodecanoate (IFA) and its coenzyme A (IFA:CoA) and cholesteryl (IFA:CEA) esters, were synthesized. These radioactive, photoreactive lipid analogues were recognized as substrates and inhibitors of acyl-CoA:cholesterol O-acyltransferase (ACAT) and cholesterol esterase, neutral lipid binding enzymes which are key elements in the regulation of cellular cholesterol metabolism. In the dark, IFA reversibly inhibited cholesteryl [14C]oleate hydrolysis by purified bovine pancreatic cholesterol esterase with an apparent Ki of 150 microM. Cholesterol esterase inhibition by IFA became irreversible after photolysis with UV light and oleic acid (1 mM) provided 50% protection against inactivation. Incubation of homogeneous bovine pancreatic cholesterol esterase with IFA:CEA resulted in its hydrolysis to IFA and cholesterol, indicating recognition of IFA:CEA as a substrate by cholesterol esterase. The coenzyme A ester, IFA:CoA, was a reversible inhibitor of microsomal ACAT activity under dark conditions (apparent Ki = 20 microM), and photolysis resulted in irreversible inhibition of enzyme activity with 87% efficiency. IFA:CoA was also recognized as a substrate by both liver and aortic microsomal ACATs, with resultant synthesis of 125IFA:CEA. IFA and its derivatives, IFA:CEA and IFA:CoA, are thus inhibitors and substrates for cholesterol esterase and ACAT. Biological recognition of these photoaffinity lipid analogues will facilitate the identification and structural analysis of hitherto uncharacterized protein lipid binding sites.

  16. Oxidative stress-related mechanisms affecting response to aspirin in diabetes mellitus.

    Science.gov (United States)

    Santilli, Francesca; Lapenna, Domenico; La Barba, Sara; Davì, Giovanni

    2015-03-01

    Type 2 diabetes mellitus (T2DM) is a major cardiovascular risk factor. Persistent platelet activation plays a key role in atherothrombosis in T2DM. However, current antiplatelet treatments appear less effective in T2DM patients vs nondiabetics at similar risk. A large body of evidence supports the contention that oxidative stress, which characterizes DM, may be responsible, at least in part, for less-than-expected response to aspirin, with multiple mechanisms acting at several levels. This review discusses the pathophysiological mechanisms related to oxidative stress and contributing to suboptimal aspirin action or responsiveness. These include: (1) mechanisms counteracting the antiplatelet effect of aspirin, such as reduced platelet sensitivity to the antiaggregating effects of NO, due to high-glucose-mediated oxidative stress; (2) mechanisms interfering with COX acetylation especially at the platelet level, e.g., lipid hydroperoxide-dependent impaired acetylating effects of aspirin; (3) mechanisms favoring platelet priming (lipid hydroperoxides) or activation (F2-isoprostanes, acting as partial agonists of thromboxane receptor), or aldose-reductase pathway-mediated oxidative stress, leading to enhanced platelet thromboxane A2 generation or thromboxane receptor activation; (4) mechanisms favoring platelet recruitment, such as aspirin-induced platelet isoprostane formation; (5) modulation of megakaryocyte generation and thrombopoiesis by oxidative HO-1 inhibition; and (6) aspirin-iron interactions, eventually resulting in impaired pharmacological activity of aspirin, lipoperoxide burden, and enhanced generation of hydroxyl radicals capable of promoting protein kinase C activation and platelet aggregation. Acknowledgment of oxidative stress as a major contributor, not only of vascular complications, but also of suboptimal response to antiplatelet agents in T2DM, may open the way to designing and testing novel antithrombotic strategies, specifically targeting

  17. Cytoprotective effects of essential oil of Pinus halepensis L. against aspirin-induced toxicity in IEC-6 cells.

    Science.gov (United States)

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

    2017-12-01

    Essential oils from Pinus species have been reported to have various therapeutic properties. This study was undertaken to identify the chemical composition and cytoprotective effects of the essential oil of Pinus halepensis L. against aspirin-induced damage in cells in vitro. The cytoprotection of the oil against toxicity of aspirin on the small intestine epithelial cells IEC-6 was tested. The obtained results have shown that 35 different compounds were identified. Aspirin induced a decrease in cell viability, and exhibited significant damage to their morphology and an increase in superoxide dismutase (SOD) and catalase (CAT) activities. However, the co-treatment of aspirin with the essential oil of Pinus induced a significant increase in cell viability and a decrease in SOD and CAT activities. Overall, these finding suggest that the essential oil of Pinus halepensis L. has potent cytoprotective effect against aspirin-induced toxicity in IEC-6 cells.

  18. B-type esterases in the snail Xeropicta derbentina: An enzymological analysis to evaluate their use as biomarkers of pesticide exposure

    Energy Technology Data Exchange (ETDEWEB)

    Laguerre, Christel [Universite d' Avignon et des Pays de Vaucluse, UMR 406 UAPV/INRA, F-84914 Avignon (France); INRA, Laboratoire de Toxicologie Environnementale, UMR 406 UAPV/INRA, F-84914 Avignon (France); Sanchez-Hernandez, Juan C. [Laboratory of Ecotoxicology, Faculty of Environmental Science, University of Castilla-La Mancha, Avda. Carlos III s/n, 45071 Toledo (Spain); Koehler, Heinz R. [Animal Physiological Ecology, University of Tuebingen, Konrad-Adenauer-Strasse 20, D-72072 Tuebingen (Germany); Triebskorn, Rita [Animal Physiological Ecology, University of Tuebingen, Konrad-Adenauer-Strasse 20, D-72072 Tuebingen (Germany); Steinbeis-Transfer Center for Ecotoxicology and Ecophysiology, Blumenstrasse 13, D-72108 Rottenburg (Germany); Capowiez, Yvan [INRA, Unite PSH, F- 84914 Avignon (France); Rault, Magali [Universite d' Avignon et des Pays de Vaucluse, UMR 406 UAPV/INRA, F-84914 Avignon (France); INRA, Laboratoire de Toxicologie Environnementale, UMR 406 UAPV/INRA, F-84914 Avignon (France); Mazzia, Christophe [Universite d' Avignon et des Pays de Vaucluse, UMR 406 UAPV/INRA, F-84914 Avignon (France); INRA, Laboratoire de Toxicologie Environnementale, UMR 406 UAPV/INRA, F-84914 Avignon (France)], E-mail: mazzia@avignon.inra.fr

    2009-01-15

    The study was prompted to characterize the B-type esterase activities in the terrestrial snail Xeropicta derbentina and to evaluate its sensitivity to organophosphorus and carbamate pesticides. Specific cholinesterase and carboxylesterase activities were mainly obtained with acetylthiocholine (K{sub m} = 77.2 mM; V{sub max} = 38.2 mU/mg protein) and 1-naphthyl acetate (K{sub m} = 222 mM, V{sub max} = 1095 mU/mg protein) substrates, respectively. Acetylcholinesterase activity was concentration-dependently inhibited by chlorpyrifos-oxon, dichlorvos, carbaryl and carbofuran (IC50 = 1.35 x 10{sup -5}-3.80 x 10{sup -8} M). The organophosphate-inhibited acetylcholinesterase activity was reactivated in the presence of pyridine-2-aldoxime methochloride. Carboxylesterase activity was inhibited by organophosphorus insecticides (IC50 = 1.20 x 10{sup -5}-2.98 x 10{sup -8} M) but not by carbamates. B-esterase-specific differences in the inhibition by organophosphates and carbamates are discussed with respect to the buffering capacity of the carboxylesterase to reduce pesticide toxicity. These results suggest that B-type esterases in X. derbentina are suitable biomarkers of pesticide exposure and that this snail could be used as sentinel species in field monitoring of Mediterranean climate regions. - Characterization of the B-type esterases in the terrestrial snail Xeropicta derbentina in order to evaluate pesticide exposure.

  19. An essential role of caffeoyl shikimate esterase in monolignol biosynthesis in Medicago truncatula.

    Science.gov (United States)

    Ha, Chan Man; Escamilla-Trevino, Luis; Yarce, Juan Carlos Serrani; Kim, Hoon; Ralph, John; Chen, Fang; Dixon, Richard A

    2016-06-01

    Biochemical and genetic analyses have previously identified caffeoyl shikimate esterase (CSE) as an enzyme in the monolignol biosynthesis pathway in Arabidopsis thaliana, although the generality of this finding has been questioned. Here we show the presence of CSE genes and associated enzyme activity in barrel medic (Medicago truncatula, dicot, Leguminosae), poplar (Populus deltoides, dicot, Salicaceae), and switchgrass (Panicum virgatum, monocot, Poaceae). Loss of function of CSE in transposon insertion lines of M. truncatula results in severe dwarfing, altered development, reduction in lignin content, and preferential accumulation of hydroxyphenyl units in lignin, indicating that the CSE enzyme is critical for normal lignification in this species. However, the model grass Brachypodium distachyon and corn (Zea mays) do not possess orthologs of the currently characterized CSE genes, and crude protein extracts from stems of these species exhibit only a weak esterase activity with caffeoyl shikimate. Our results suggest that the reaction catalyzed by CSE may not be essential for lignification in all plant species. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  20. Cocaine benzoyl thioester: synthesis, kinetics of base hydrolysis, and application to the assay of cocaine esterases.

    Science.gov (United States)

    Cashman, J R; Berkman, C E; Underiner, G; Kolly, C A; Hunter, A D

    1998-08-01

    The synthesis and characterization of diastereomers of cocaine benzoyl thioester is described. Allococaine benzoyl thioester and allopseudococaine benzoyl thioester were synthesized by the conjugate addition of p-methoxytolyl thiol to ecgonine methyl ester followed by debenzylation and benzoylation. The absolute structure of the hydrochloride salt of the major ecgonine p-methoxytolyl sulfide formed was determined by single-crystal diffraction analysis and used to establish the addition geometry. When placed in aqueous solution, the cocaine benzoyl thioester diastereomers hydrolyzed to give thioecgonine methyl ester. The rate of cocaine benzoyl thioester hydrolysis was carefully investigated spectrophotometrically by using the Ellman reagent. At neutral pH, the hydrolysis of the diastereomers was found to proceed at detectable rates. Upon increasing pH, the rate of hydrolysis of cocaine benzoyl thioester diastereomers was increased and the reaction was catalyzed by basic buffer species. In addition to defining the kinetics of hydrolysis in aqueous solution, cocaine benzoyl thioester was utilized as a highly efficient method to monitor the activity of cholinesterases and pig liver esterase. Use of cocaine benzoyl thioester represents a rapid and sensitive way to screen for cocaine esterase activity.

  1. Directed evolution of an esterase: screening of enzyme libraries based on pH-indicators and a growth assay.

    Science.gov (United States)

    Bornscheuer, U T; Altenbuchner, J; Meyer, H H

    1999-10-01

    In order to resolve a sterically hindered 3-hydroxy ethyl ester, which was not accepted as substrate by 20 wild-type hydrolases, a directed evolution of an esterase from Pseudomonas fluorescens (PFE) was performed. Mutations were introduced using the mutator strain Epicurian coli XL1-Red. Enzyme libraries derived from seven mutation cycles were assayed on minimal media agar plates supplemented with pH indicators (neutral red and crystal violet), thus allowing the identification of active esterase variants by the formation of a red color caused by a pH decrease due to the released acid. A further selection criteria was introduced by using the corresponding glycerol estar, because release of the carbon source glycerol facilitates growth on minimal media. By this strategy, one double mutant (A209D and L181V) of PFE was identified, which hydrolyzed the 3-hydroxy ethyl ester in a stereoselective manner (25% ee for the remaining ester, E approximate to 5).

  2. 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.

  3. Overexpression of esterase D in kidney from trisomy 13 fetuses

    Energy Technology Data Exchange (ETDEWEB)

    Loughna, S.; Moore, G. (Institute of Obstetrics and Gynaecology, London (United Kingdom)); Gau, G.; Blunt, S. (Cytogenetics Lab., London (United Kingdom)); Nicolaides, K. (King' s College School of Medicine and Dentistry, London (United Kingdom))

    1993-10-01

    Human trisomy 13 (Patau syndrome) occurs in approximately 1 in 5,000 live births. It is compatible with life, but prolonged survival is rare. Anomalies often involve the urogenital, cardiac, craniofacial, and central nervous systems. It is possible that these abnormalities may be due to the overexpression of developmentally important genes on chromosome 13. The expression of esterase D (localized to chromosome 13q14.11) has been investigated in both muscle and kidney from trisomy 13 fetuses and has been compared with normal age- and sex-matched fetal tissues, by using northern analysis. More than a twofold increase in expression of esterase D was found in the kidney of two trisomy 13 fetuses, with normal levels in a third. Overexpression was not seen in the muscle tissues from these fetuses. 34 refs., 3 figs., 2 tabs.

  4. Leucocyte esterase in the rapid diagnosis of paediatric septic arthritis.

    LENUS (Irish Health Repository)

    Kelly, E G

    2013-02-01

    Septic arthritis may affect any age group but is more common in the paediatric population. Infection is generally bacterial in nature. Prompt diagnosis is crucial, as delayed treatment is associated with lifelong joint dysfunction. A clinical history and application of Kocher\\'s criteria may indicate that there is a septic arthritis. However, definitive diagnosis is made on culture of septic synovial fluid. The culture process can take over 24h for the initial culture to yield bacterial colonies. Leucocyte esterase is released by leucocytes at the site of an infection. We hypothesise that leucocyte esterase can be utilized in the rapid diagnosis of septic arthritis and shorten the time to decisive treatment whilst simultaneously decreasing unnecessary treatment of non-septic joints.

  5. Overexpression of esterase D in kidney from trisomy 13 fetuses.

    Science.gov (United States)

    Loughna, S; Bennett, P; Gau, G; Nicolaides, K; Blunt, S; Moore, G

    1993-01-01

    Human trisomy 13 (Patau syndrome) occurs in approximately 1 in 5,000 live births. It is compatible with life, but prolonged survival is rare. Anomalies often involve the urogenital, cardiac, craniofacial, and central nervous systems. It is possible that these abnormalities may be due to the overexpression of developmentally important genes on chromosome 13. The expression of esterase D (localized to chromosome 13q14.11) has been investigated in both muscle and kidney from trisomy 13 fetuses and has been compared with normal age- and sex-matched fetal tissues, by using northern analysis. More than a twofold increase in expression of esterase D was found in the kidney of two trisomy 13 fetuses, with normal levels in a third. Overexpression was not seen in the muscle tissues from these fetuses. Images Figure 1 Figure 2 Figure 3 PMID:8213811

  6. 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.

  7. An eleven amino acid residue deletion expands the substrate specificity of acetyl xylan esterase II (AXE II) from Penicillium purpurogenum

    Science.gov (United States)

    Colombres, Marcela; Garate, José A.; Lagos, Carlos F.; Araya-Secchi, Raúl; Norambuena, Patricia; Quiroz, Soledad; Larrondo, Luis; Pérez-Acle, Tomas; Eyzaguirre, Jaime

    2008-01-01

    The soft-rot fungus Penicillium purpurogenum secretes to the culture medium a variety of enzymes related to xylan biodegradation, among them three acetyl xylan esterases (AXE I, II and III). AXE II has 207 amino acids; it belongs to family 5 of the carbohydrate esterases and its structure has been determined by X-ray crystallography at 0.9 Å resolution (PDB 1G66). The enzyme possesses the α/β hydrolase fold and the catalytic triad typical of serine esterases (Ser90, His187 and Asp175). AXE II can hydrolyze esters of a large variety of alcohols, but it is restricted to short chain fatty acids. An analysis of its three-dimensional structure shows that a loop that covers the active site may be responsible for this strict specificity. Cutinase, an enzyme that hydrolyzes esters of long chain fatty acids and shows a structure similar to AXE II, lacks this loop. In order to generate an AXE II with this broader specificity, the preparation of a mutant lacking residues involving this loop (Gly104 to Ala114) was proposed. A set of molecular simulation experiments based on a comparative model of the mutant enzyme predicted a stable structure. Using site-directed mutagenesis, the loop's residues have been eliminated from the AXE II cDNA. The mutant protein has been expressed in Aspergillus nidulans A722 and Pichia pastoris, and it is active towards a range of fatty acid esters of up to at least 14 carbons. The availability of an esterase with broader specificity may have biotechnological applications for the synthesis of sugar esters.

  8. Aspirin augments the expression of Adenomatous Polyposis Coli protein by suppression of IKKβ

    Energy Technology Data Exchange (ETDEWEB)

    Ashida, Noboru, E-mail: nashida@kuhp.kyoto-u.ac.jp [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan); Kishihata, Masako [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan); Tien, Dat Nguyen [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan); Department of Biomolecular Engineering, Kyoto Institute of Technology, Kyoto (Japan); Kamei, Kaeko [Department of Biomolecular Engineering, Kyoto Institute of Technology, Kyoto (Japan); Kimura, Takeshi [Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Yokode, Masayuki [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan)

    2014-04-04

    Highlights: • Clinical studies revealed aspirin inhibits cancer, but the mechanism is not known. • Adenomatous Polyposis Coli (APC) is a well-known tumor-suppressing gene. • We found aspirin up-regulates the protein of APC. • Aspirin suppressed the expression of IKKβ, an essential kinase in NFκB activation. • The deletion of IKKβ significantly increases the expression of APC protein. - Abstract: Aspirin has been widely used as analgesic, antipyretic and anti-inflammatory medicine for long. In addition to these traditional effects, clinical studies suggest that aspirin can protect against cancer, but its mechanism has not been explored. To unveil it, we identified the proteins up- or down-regulated after incubation with aspirin by using proteomics analysis with Nano-flow LC/MALDI-TOF system. Interestingly, the analysis identified the protein of Adenomatous Polyposis Coli (APC) as one of the most up-regulated protein. APC regulates cell proliferation or angiogenesis, and is widely known as a tumor-suppressing gene which can cause colorectal cancer when it is mutated. Western blots confirmed this result, and real-time PCR indicated it is transcriptionally regulated. We further tried to elucidate the molecular mechanism with focusing on IKKβ. IKKβ is the essential kinase in activation of nuclear factor-kappa B (NF-κB), major transcriptional factors that regulate genes responsible for inflammation or immune response. Previous reports indicated that aspirin specifically inhibits IKKβ activity, and constitutively active form of IKKβ accelerates APC loss. We found that aspirin suppressed the expression of IKKβ, and the deletion of IKKβ by siRNA increases the expression of APC in HEK294 cells. Finally, we observed similar effects of aspirin in human umbilical vein endothelial cells. Taken together, these results reveal that aspirin up-regulates the expression of APC via the suppression of IKKβ. This can be a mechanism how aspirin prevents cancer at

  9. 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...

  10. Dependency of the hydrogen bonding capacity of the solvent anion on the thermal stability of feruloyl esterases in ionic liquid systems

    DEFF Research Database (Denmark)

    Zeuner, Birgitte; Ståhlberg, Tim; Nguyen van Buu, Olivier

    2011-01-01

    Three feruloyl esterases, EC 3.1.1.73, (FAEs), namely FAE A from Aspergillus niger (AnFaeA), FAE C from Aspergillus nidulans (AndFaeC), and the FAE activity in a commercial b-glucanase mixture from Humicola insolens (Ultraflo L) were tested for their ability to catalyse esterification of sinapic ...

  11. Aspirin Inhibits Platelet-Derived Sphingosine-1-Phosphate Induced Endothelial Cell Migration.

    Science.gov (United States)

    Polzin, Amin; Knoop, Betül; Böhm, Andreas; Dannenberg, Lisa; Zurek, Mark; Zeus, Tobias; Kelm, Malte; Levkau, Bodo; Rauch, Bernhard H

    2018-01-01

    Aspirin plays a crucial role in the prevention of cardiovascular diseases. We previously described that aspirin has effects beyond inhibition of platelet aggregation, as it inhibited thrombin-mediated release of sphingosine-1-phosphate (S1P) from human platelets. S1P is a bioactive lipid with important functions on inflammation and apoptosis. In endothelial cells (EC), S1P is a key regulator of cell migration. In this study, we aimed to analyze the effects of aspirin on platelet-induced EC migration. Human umbilical EC migration was measured by Boyden chamber assay. EC migration was induced by platelet supernatants of thrombin receptor-activating peptide-1 (AP1) stimulated platelets. To investigate the S1P receptor subtype that promotes EC migration, specific inhibitors of S1P receptor subtypes were applied. S1P induced EC migration in a concentration-dependent manner. EC migration induced by AP1-stimulated platelet supernatants was reduced by aspirin. S1P1 receptor inhibition almost completely abolished EC migration induced by activated platelets. The inhibition of S1P2 or S1P3 receptor had no effect. Aspirin inhibits EC migration induced by activated platelets that is in part due to S1P and mediated by the endothelial S1P1 receptor. The clinical significance of this novel mechanism of aspirin action has to be investigated in future studies. © 2017 S. Karger AG, Basel.

  12. Preparation and Properties of Novel Dentin Adhesives with Esterase Resistance.

    Science.gov (United States)

    Park, Jong-Gu; Ye, Qiang; Topp, Elizabeth M; Kostoryz, Elisabet L; Wang, Yong; Kieweg, Sarah L; Spencer, Paulette

    2008-03-15

    A new methacrylate monomer, trimethylolpropane mono allyl ether dimethacrylate (TMPEDMA), was synthesized and evaluated. This branched methacrylate was designed to increase esterase-resistance when incorporated into conventional HEMA (2-hydroxyethyl methacrylate)/BisGMA (2,2-bis[4(2-hydroxy-3-methacryloyloxy-propyloxy)-phenyl] propane) dental adhesives. The new adhesives, HEMA/BisGMA/TMPEDMA in a 45/30/25 (w/w) ratio were formulated with H(2)O at 0 (A0T) and 8 wt % water (A8T) and compared with control adhesives (HEMA/BisGMA, 45/55 (w/w), at 0 (A0) and 8 wt % (A8) water). Camphoroquinone (CQ), 2-(dimethylamino) ethyl methacrylate and diphenyliodonium hexafluorophosphate were used as photoinitiators. The new adhesives showed a degree of conversion comparable with the control and improved modulus and glass transition temperature (T(g)). Exposure of photopolymerized discs to porcine liver esterase for up to eight days showed that the net cumulative methacrylic acid (MAA) release in adhesives formulated with the new monomer and 8% water (A8T: 182 μg/mL) was dramatically (P adhesives made with the new monomer and cured in water to simulate wet bonding are more resistant to esterase than conventional HEMA/BisGMA adhesive.

  13. Catalytic Promiscuity of Ancestral Esterases and Hydroxynitrile Lyases.

    Science.gov (United States)

    Devamani, Titu; Rauwerdink, Alissa M; Lunzer, Mark; Jones, Bryan J; Mooney, Joanna L; Tan, Maxilmilien Alaric O; Zhang, Zhi-Jun; Xu, Jian-He; Dean, Antony M; Kazlauskas, Romas J

    2016-01-27

    Catalytic promiscuity is a useful, but accidental, enzyme property, so finding catalytically promiscuous enzymes in nature is inefficient. Some ancestral enzymes were branch points in the evolution of new enzymes and are hypothesized to have been promiscuous. To test the hypothesis that ancestral enzymes were more promiscuous than their modern descendants, we reconstructed ancestral enzymes at four branch points in the divergence hydroxynitrile lyases (HNL's) from esterases ∼ 100 million years ago. Both enzyme types are α/β-hydrolase-fold enzymes and have the same catalytic triad, but differ in reaction type and mechanism. Esterases catalyze hydrolysis via an acyl enzyme intermediate, while lyases catalyze an elimination without an intermediate. Screening ancestral enzymes and their modern descendants with six esterase substrates and six lyase substrates found higher catalytic promiscuity among the ancestral enzymes (P promiscuous and catalyzed both hydrolysis and lyase reactions with many substrates. A broader screen tested mechanistically related reactions that were not selected for by evolution: decarboxylation, Michael addition, γ-lactam hydrolysis and 1,5-diketone hydrolysis. The ancestral enzymes were more promiscuous than their modern descendants (P = 0.04). Thus, these reconstructed ancestral enzymes are catalytically promiscuous, but HNL1 is especially so.

  14. 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.

  15. Could empirical low-dose-aspirin administration during IVF cycle affect both the oocytes and embryos quality via COX 1-2 activity inhibition?

    Science.gov (United States)

    Gizzo, Salvatore; Capuzzo, Denise; Zicchina, Cecilia; Di Gangi, Stefania; Coronella, Maria Lia; Andrisani, Alessandra; Gangemi, Michele; Nardelli, Giovanni Battista

    2014-03-01

    To compare qualitative and quantitative ovarian response in idiopathic infertile women treated with low-dose-aspirin (LDA) during in-vitro-fertilization (IVF) cycles (pl) versus untreated ones. We conducted an observational-cohort-study on normo-responders patients aged between 25 and 45,years referred to Assisted-Reproductive Unit --University of Padua--in order to evaluate the ovarian response effects (both qualitative and quantitative) after LDA administration. In detail we aim to assess if LDA administration could improve ovarian response, reducing the gonadotropin administration, and if its administration could increase the amount of follicles greater than 16 mm at pick-up, the amount and quality of oocytes retrieved, the amount and quality of embryos, the chance to achieve a pregnancy and to carry it on. One hundred six LDA-treated patients (Group-A) and 100 not-treated ones (Group-B) were homogeneous for age and BMI. The Group-A, compared to Group-B, showed higher gonadotropin request, higher number of ovarian follicles at pick-up, more follicles bigger than 16 mm in diameter and more retrieved oocytes (despite higher number of immature and at germinal vesicle stage oocytes) but lower quality of obtained embryos. The comparison between two Groups in term of retrieved oocytes /number of follicles, mature oocytes/retrieved oocytes, fertilized oocytes/mature oocytes and good embryos quality/mature oocytes showed a strongly advantageous ratio for Group-B. For each considered outcome, we found a dose-related effect. It is mandatory to define which patients could benefit from LDA administration and the adequate timing to administer it since the empirical administration could negatively affect both oocyte and embryo quality during IVF cycles.

  16. 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 ...

  17. A Disease Marker for Aspirin-Induced Chronic Urticaria

    Science.gov (United States)

    Hsieh, Chia-Wei; Lee, Jeen-Wei; Liao, En-Chih; Tsai, Jaw-Ji

    2014-01-01

    There are currently no diagnostic methods in vitro for aspirin-induced chronic urticaria (AICU) except for the provocation test in vivo. To identify disease markers for AICU, we investigated the single nucleotide polymorphism (SNP) of the promoter loci of high-affinity IgE receptor (FcεRIα) and CD203c expression level in Chinese patients with AICU. We studied two genotypic and allelic frequencies of rs2427827 (–344C/T) and rs2251746 (–66T/C) gene polymorphisms of FcεRIα in 20 patients with AICU, 52 subjects with airway hypersensitivity without aspirin intolerance, and 50 controls in a Chinese population. The results showed that the frequencies of two SNPs (–344C>T, –66C>T) were similar to the normal controls. The allele frequency of –344CC was significantly higher in the patients with AICU compared to those with airway sensitivity (p = 0.019). We also studied both histamine release and CD203c expression on KU812 cells to assess aspirin-induced basophil activation. We found that the activity of basophil activation of AICU was significantly higher in the patients with AICU compared to those with airway hypersensitivity without aspirin intolerance. The mean fluorescence intensity of the CD203c expression were 122.5 ± 5.2 vs. 103.3 ± 3.3 respectively, (p T) is less likely to develop AICU and the basophil activation activity in the sera by measuring CD203c expression can be applicable to confirm the diagnosis of AICU. PMID:25029546

  18. The inhibitory effect of simvastatin and aspirin on histamine responsiveness in human vascular endothelial cells.

    Science.gov (United States)

    Absi, Mais; Bruce, Jason I; Ward, Donald T

    2014-04-01

    Statins and aspirin deliver well-established cardiovascular benefits resulting in their increased use as combined polypills to decrease risk of stroke and heart disease. However, the direct endothelial effect of combined statin/aspirin cotreatment remains unclear. Histamine is an inflammatory mediator that increases vascular permeability, and so we examined the effect of treating human umbilical vein endothelial cells (HUVECs) for 24 h with 1 μM simvastatin and 100 μM aspirin on histamine responsiveness. Subsequent histamine (1 μM) challenge increased intracellular calcium (Ca(2+)i) concentration, an effect that was significantly inhibited by combined simvastatin/aspirin pretreatment but not when then the compounds were given separately, even at 10-fold higher concentrations. In contrast, the Ca(2+)i mobilization response to ATP challenge (10 μM) was not inhibited by combined simvastatin/aspirin pretreatment. The H1 receptor antagonist pyrilamine significantly inhibited both histamine-induced Ca(2+)i mobilization and extracellular signal-regulated kinase (ERK) activation, whereas ranitidine (H2 receptor antagonist) was without effect. However, combined simvastatin/aspirin pretreatment failed to decrease H1 receptor protein expression ruling out receptor downregulation as the mechanism of action. Histamine-induced ERK activation was also inhibited by atorvastatin pretreatment, while simvastatin further inhibited histamine-induced vascular endothelial cadherin phosphorylation as well as altered HUVEC morphology and inhibited actin polymerization. Therefore, in addition to the known therapeutic benefits of statins and aspirin, here we provide initial cellular evidence that combined statin/aspirin treatment inhibits histamine responsiveness in HUVECs.

  19. Esterase profile in a pyrethroid-resistant Brazilian strain of the cattle tick Boophilus microplus (Acari, Ixodidae

    Directory of Open Access Journals (Sweden)

    Milla Alves Baffi

    2005-12-01

    Full Text Available The cattle tick Boophilus microplus causes great damage in livestock and is considered one of the most important tropical ectoparasites. The traditional method of control is based on the intensive use of pesticides, however the indiscriminate use of these compounds over the years has led to the selection of resistant ticks. Hydrolases, particularly esterases (EST, have been reported to be associated with acaricide resistance in B. microplus. We compared the esterase profile of susceptible and cypermethrin-resistant strains of adult B. microplus and a pyrethroid susceptible reference strain (the Mozzo strain using polyacrylamide gel electrophoresis and specific staining. The electrophoretic profiles of protein extracts revealed the presence of four regions with esterase activity in the cypermethrin-resistant strain and three of these regions in the susceptible strains. The bands were numbered EST-1 to EST-4 in sequence (starting from the anode according to their decrease in negative charge. The EST-1A and EST-1B enzymes were detected only in the resistant strain. The inhibition studies with eserine sulfate, copper sulfate, p- p-chloromercuribenzoate (pCMB, malathion and phenylmethylsulfonyl fluoride (PMSF indicated that the EST-1A and EST-1B enzymes belong to the acetylcholinesterase class and are probably associated with resistance to acaricides in this Brazilian resistant strain of B. microplus.

  20. Esterase and peroxidase isoforms in different stages of morphogenesis in Fritillaria meleagris L. in bulb-scale culture.

    Science.gov (United States)

    Petrić, Marija; Subotić, Angelina; Jevremović, Slađana; Trifunović-Momčilov, Milana; Tadić, Vojin; Grujić, Marica; Vujčić, Zoran

    2015-12-01

    Morphogenesis in vitro is a complex and still poorly defined process. We investigated esterase and peroxidase isoforms detected in bulb scale, during Fritillaria meleagris morphogenesis. Bulbs were grown either at 4 °C or on a medium with an increased concentration of sucrose (4.5%) for 30 days. After these pre-treatments, the bulb scales were further grown on nutrient media that contained different concentrations of 2,4-dichlorophenoxyacetic acid (2,4-D) and kinetin (KIN) or thidiazuron (TDZ). Regeneration of somatic embryos and bulblets occurred at the same explant. The highest numbers of somatic embryos and bulblets were regenerated on the medium containing 2,4-D and KIN (1mg/L each), while morphogenesis was most successful at a TDZ concentration between 0.5 and 1mg/L. Monitoring of esterases and peroxidases was performed by growing bulb scales on a medium enriched with 2,4-D and KIN or TDZ (1mg/L), and the number and activity of isoforms were followed every 7 days for 4 weeks. In control explants, six isoforms of esterase were observed. Three isoforms of peroxidase were not detected in the control bulb scale, which has not begun its morphogenesis process. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  1. INTERRELATION BETWEEN 3-HYDROXY-1,4-BENZODIAZEPINE-2-ONE ESTERS STRUCTURE ON THEIR HYDROLYSIS BY CARBOXYL ESTERASE

    Directory of Open Access Journals (Sweden)

    E. A. Shesterenko

    2013-04-01

    Full Text Available The synthesis of new series of 7-bromo-5-aryl-1,2-dihydro-3H-1,4-benzdiazepine-2-one derivatives, containing in the tree position phthalimidoacyl and hexylacyl fragments was accomplished. The structure of new compounds was proved by mass-spectrometry and PMRspectroscopy methods. For the first time, hydrolysis of the earlier synthesized 3-hydroxy-7-bromo-5-aryl-1,2-dihydro-3H-1,4-benzdiazepine-2-one esters, potential anxiolytic and hypnotic means, catalyzed by carboxyl esterase in composition of pig liver microsomal fraction was studied. The quantitative inhibition of pig liver microsomal fraction esterase activity in the presence of carboxyl esterase selective inhibitor di-(pnitrophenyl-phosphate was shown. The nonlinear dependence both of hydrolysis degree with acyl moiety length in 3-acyloxy-7-bromo-5-aryl-1,2-dihydro-3H-1,4-benzdiazepine-2-ones and decreased substrate transformation degree after substituent introduction in the first position of molecule was established. For the derivatives with phthalimidoacyl and hexylacyl-mo ie ties in the molecule 3 position it was shown, that increasing of CH2-groups number in this substituents and incorporation of chlorine atom in o-position of phenyl ring bring to increasing of hydrolysis degree.

  2. Est16, a New Esterase Isolated from a Metagenomic Library of a Microbial Consortium Specializing in Diesel Oil Degradation.

    Directory of Open Access Journals (Sweden)

    Mariana Rangel Pereira

    Full Text Available Lipolytic enzymes have attracted attention from a global market because they show enormous biotechnological potential for applications such as detergent production, leather processing, cosmetics production, and use in perfumes and biodiesel. Due to the intense demand for biocatalysts, a metagenomic approach provides methods of identifying new enzymes. In this study, an esterase designated as Est16 was selected from 4224 clones of a fosmid metagenomic library, revealing an 87% amino acid identity with an esterase/lipase (accession number ADM63076.1 from an uncultured bacterium. Phylogenetic studies showed that the enzyme belongs to family V of bacterial lipolytic enzymes and has sequence and structural similarities with an aryl-esterase from Pseudomonas fluorescens and a patented Anti-Kazlauskas lipase (patent number US20050153404. The protein was expressed and purified as a highly soluble, thermally stable enzyme that showed a preference for basic pH. Est16 exhibited activity toward a wide range of substrates and the highest catalytic efficiency against p-nitrophenyl butyrate and p-nitrophenyl valerate. Est16 also showed tolerance to the presence of organic solvents, detergents and metals. Based on molecular modeling, we showed that the large alpha-beta domain is conserved in the patented enzymes but not the substrate pocket. Here, it was demonstrated that a metagenomic approach is suitable for discovering the lipolytic enzyme diversity and that Est16 has the biotechnological potential for use in industrial processes.

  3. 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.

  4. Preoperative aspirin administration improves oxygenation in patients undergoing coronary artery bypass grafting.

    Science.gov (United States)

    Gerrah, Rabin; Elami, Amir; Stamler, Alon; Smirnov, Asya; Stoeger, Zeev

    2005-05-01

    Release of thromboxane (Tx) A(2) by platelets may be one of multiple factors that are responsible for lung injury after cardiopulmonary bypass, leading to pulmonary vasoconstriction and impaired oxygenation. In experimental models, the inhibition of Tx receptor or its production improved lung function. The use of aspirin, which is used widely in the treatment of ischemic heart disease because of its antiplatelet activity, is usually discontinued a week before the patient undergoes the operation to restore normal platelet hemostatic function. The purpose of this study was to determine the relationship between the time of cessation of aspirin before coronary artery bypass surgery, and postoperative oxygenation and bleeding. A prospective clinical study comparing the effect of aspirin on postoperative oxygenation in patients who had been treated or had not been treated with aspirin. Tx levels in the pericardial fluid, oxygenation, and bleeding were compared between the two groups. Thirty-two patients with coronary artery disease who were undergoing coronary artery bypass grafting. Fourteen of these patients received aspirin until the day of the operation, whereas 18 patients stopped receiving aspirin at least 1 week before undergoing the operation. Mean (+/- SD) Tx levels in the pericardial fluid were significantly lower in the aspirin group (117 +/- 47 pg/mL) compared to those in the control group (1,306 +/- 2,048 pg/mL; p = 0.02). The duration of ventilation after the operation was significantly longer in the nonaspirin group (9.6 +/- 5.6 h vs 3.8 +/- 1.4 h, respectively; p = 0.0004). Po(2) reached a higher level while patients breathed 100% O(2) in the aspirin group (235 +/- 54 mm Hg vs 176 +/- 27 mm Hg, respectively; p = 0.001). The mean amount of bleeding during the first 24 h after surgery was increased in the aspirin group (710 +/- 202 mL) compared with the nonaspirin group (539 +/- 143 mL; p = 0.01), but these patients did not require more transfusions. The

  5. Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS.

    Science.gov (United States)

    Hamid, U; Krasnodembskaya, A; Fitzgerald, M; Shyamsundar, M; Kissenpfennig, A; Scott, C; Lefrancais, E; Looney, M R; Verghis, R; Scott, J; Simpson, A J; McNamee, J; McAuley, D F; O'Kane, C M

    2017-11-01

    Platelets play an active role in the pathogenesis of acute respiratory distress syndrome (ARDS). Animal and observational studies have shown aspirin's antiplatelet and immunomodulatory effects may be beneficial in ARDS. To test the hypothesis that aspirin reduces inflammation in clinically relevant human models that recapitulate pathophysiological mechanisms implicated in the development of ARDS. Healthy volunteers were randomised to receive placebo or aspirin 75  or 1200 mg (1:1:1) for seven days prior to lipopolysaccharide (LPS) inhalation, in a double-blind, placebo-controlled, allocation-concealed study. Bronchoalveolar lavage (BAL) was performed 6 hours after inhaling 50 µg of LPS. The primary outcome measure was BAL IL-8. Secondary outcome measures included markers of alveolar inflammation (BAL neutrophils, cytokines, neutrophil proteases), alveolar epithelial cell injury, systemic inflammation (neutrophils and plasma C-reactive protein (CRP)) and platelet activation (thromboxane B2, TXB2). Human lungs, perfused and ventilated ex vivo (EVLP) were randomised to placebo or 24 mg aspirin and injured with LPS. BAL was carried out 4 hours later. Inflammation was assessed by BAL differential cell counts and histological changes. In the healthy volunteer (n=33) model, data for the aspirin groups were combined. Aspirin did not reduce BAL IL-8. However, aspirin reduced pulmonary neutrophilia and tissue damaging neutrophil proteases (Matrix Metalloproteinase (MMP)-8/-9), reduced BAL concentrations of tumour necrosis factor α and reduced systemic and pulmonary TXB2. There was no difference between high-dose and low-dose aspirin. In the EVLP model, aspirin reduced BAL neutrophilia and alveolar injury as measured by histological damage. These are the first prospective human data indicating that aspirin inhibits pulmonary neutrophilic inflammation, at both low and high doses. Further clinical studies are indicated to assess the role of aspirin in the

  6. Esterase isozymes in a solitary bee, Megachile rotundata (Fab.): characterization, developmental multiplicity, and adult variability.

    Science.gov (United States)

    Frohlich, D R; Brindley, W A; Burris, T E; Youssef, N N

    1990-08-01

    This study describes the biochemical characterization and genetic variation of cytosolic esterases in the alfalfa leafcutting bee, Megachile rotundata (Fab.). Esterase isozymes were separated by nondenaturing polyacrylamide gel electrophoresis and isoelectric focusing and characterized by inhibition with eserine sulfate, EDTA, paraoxon, and p-hydroxymercuribenzoate. Based on inhibition patterns and substrate specificity, there are major differences between adults and immature forms and more subtle differences between male and female adults. M. rotundata esterases are largely organophosphate sensitive and the two major adult allozymes were highly variable within the population examined. Differences in esterase expression between life stages with respect to niche and the occurrence of diploid males are discussed.

  7. 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.

  8. Amelioration of Aspirin Induced Oxidative Impairment and Apoptotic Cell Death by a Novel Antioxidant Protein Molecule Isolated from the Herb Phyllanthus niruri

    Science.gov (United States)

    Bhattacharyya, Sudip; Ghosh, Shatadal; Sil, Parames C.

    2014-01-01

    Aspirin has been used for a long time as an analgesic and anti-pyretic drug. Limitations of its use, however, remain for the gastro-intestinal side effects and erosions. Although the role of aspirin on gastro-intestinal injury has been extensively studied, the molecular mechanisms underlying aspirin-induced liver and spleen pathophysiology are poorly defined. The present study has been conducted to investigate whether phyllanthus niruri protein (PNP) possesses any protective role against aspirin mediated liver and spleen tissue toxicity, and if so, what signaling pathways it utilizes to convey its protective action. Aspirin administration in mice enhanced serum marker (ALP) levels, reactive oxygen species (ROS) generation, reduced antioxidant power and altered oxidative stress related biochemical parameters in liver and spleen tissues. Moreover, we observed that aspirin intoxication activated both the extrinsic and intrinsic apoptotic pathways, as well as down regulated NF-κB activation and the phosphorylation of p38 and JNK MAPKs. Histological assessments and TUNEL assay also supported that aspirin induced tissue damages are apoptotic in nature. PNP treatment after aspirin exposure effectively neutralizes all these abnormalities via the activation of survival PI3k/Akt pathways. Combining all results suggest that PNP could be a potential protective agent to protect liver and spleen from the detrimental effects of aspirin. PMID:24586486

  9. Esterase and glutathione S-transferase levels associated with synthetic pyrethroid resistance in Hyalomma anatolicum and Rhipicephalus microplus ticks from Punjab, India.

    Science.gov (United States)

    Nandi, Abhijit; Jyoti; Singh, Harkirat; Singh, Nirbhay Kumar

    2015-05-01

    Larval packet test was used for assessment of resistance status against cypermethrin and deltamethrin in Hyalomma anatolicum and Rhipicephalus microplus from various districts of Punjab (India). Among the various field isolates of H. anatolicum susceptible status was recorded against cypermethrin in all isolates, whereas against deltamethrin resistance status (level I-III) was recorded. In R. microplus lower resistance levels (I-II) were recorded against cypermethrin in comparison to deltamethrin (level I-IV). Quantitative analysis of general esterase activity revealed a range of 4.21 ± 0.46 to 6.05 ± 0.55 and 2.23 ± 0.23 to 2.66 ± 0.24 µmol/min/mg protein for α- and β-esterase activity, respectively, in different field isolates of H. anatolicum and the increase in comparison to susceptible was not significant (P > 0.05). In contrast to H. anatolicum, the α- and β-esterase activity in all field isolates (except Jalandhar) of R. microplus was higher (range of 3.89 ± 0.26 to 10.85 ± 0.47 and 1.75 ± 0.08 to 5.87 ± 0.29 µmol/min/mg protein, respectively) (P < 0.001). The glutathione-S-transferase (GST) activity in field isolates of H. anatolicum and R. microplus was in the range of 0.01 ± 0.001 to 0.03 ± 0.001 and 0.02 ± 0.0003 to 0.03 ± 0.001 mM/mg/min. The enzyme ratios (α-and β-esterase and GST) and RR95 against deltamethrin of H. anatolicum isolates were correlated (P < 0.05), whereas in R. microplus only α-and β-esterase and RR50 against deltamethrin were correlated (P < 0.05).

  10. 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

  11. 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.

  12. Effect of aspirin on chromosome aberration and DNA damage induced by X-rays in mice

    Science.gov (United States)

    Niikawa, M.; Chuuriki, K.; Shibuya, K.; Seo, M.; Nagase, H.

    In order to reveal the anticlastogenic potency of aspirin, we evaluated the suppressive ability of aspirin on chromosome aberrations induced by X-ray. Aspirin at doses of 0.5, 5 and 50 mg/kg was administrated intraperitoneally or orally at 0.5 h after or before the X-ray irradiation. The anticlastogenic activity of aspirin on chromosome aberrations induced by X-ray was determined in the mouse micronucleus test and alkaline single cell gel electrophoresis (SCG) assay in vivo. The frequency by polychromatic erythrocytes with micronuclei (MNPCEs) was decreased by about 19-61% at 0.5 h after and about 23-62% at 0.5 h before the X-ray irradiation. DNA damage by X-ray was significantly decreased by oral administration of aspirin at 0.5 h after or before the X-ray irradiation for the SCG assay. We consider aspirin can be used as preventive agents against exposure of X-ray.

  13. Identification and Characterization of a Novel Salt-Tolerant Esterase from the Deep-Sea Sediment of the South China Sea.

    Science.gov (United States)

    Zhang, Yi; Hao, Jie; Zhang, Yan-Qi; Chen, Xiu-Lan; Xie, Bin-Bin; Shi, Mei; Zhou, Bai-Cheng; Zhang, Yu-Zhong; Li, Ping-Yi

    2017-01-01

    Marine esterases play an important role in marine organic carbon degradation and cycling. Halotolerant esterases from the sea may have good potentials in industrial processes requiring high salts. Although a large number of marine esterases have been characterized, reports on halotolerant esterases are only a few. Here, a fosmid library containing 7,200 clones was constructed from a deep-sea sediment sample from the South China Sea. A gene H8 encoding an esterase was identified from this library by functional screening and expressed in Escherichia coli . Phylogenetic analysis showed that H8 is a new member of family V of bacterial lipolytic enzymes. H8 could effectively hydrolyze short-chain monoesters (C4-C10), with the highest activity toward p -nitrophenyl hexanoate. The optimal temperature and pH for H8 activity were 35°C and pH 10.0, respectively. H8 had high salt tolerance, remaining stable in 4.5 M NaCl, which suggests that H8 is well adapted to the marine saline environment and that H8 may have industrial potentials. Unlike reported halophilic/halotolerant enzymes with high acidic/basic residue ratios and low pI values, H8 contains a large number of basic residues, leading to its high basic/acidic residue ratio and high predicted pI (9.09). Moreover, more than 10 homologous sequences with similar basic/acidic residue ratios and predicted pI values were found in database, suggesting that H8 and its homologs represent a new group of halotolerant esterases. We also investigated the role of basic residues in H8 halotolerance by site-directed mutation. Mutation of Arg195, Arg203 or Arg236 to acidic Glu significantly decreased the activity and/or stability of H8 under high salts, suggesting that these basic residues play a role in the salt tolerance of H8. These results shed light on marine bacterial esterases and halotolerant enzymes.

  14. A novel phospholipase A2/esterase from hyperthermophilic archaeon Aeropyrum pernix K1.

    Science.gov (United States)

    Wang, Baijing; Lu, Dongmei; Gao, Renjun; Yang, Zhen; Cao, Shugui; Feng, Yan

    2004-06-01

    An open reading frame of the hyperthermophilic archaeon Aeropyrum pernix K1 APE2325, which composed of 474 bases, was cloned and expressed in Escherichia coli BL21 (DE3) Codon Plus-RIL. The recombinant protein was purified by Ni-chelation affinity chromatography. It showed a single band with a molecular mass of 18kDa in SDS-PAGE. The purified enzyme exhibited both phospholipase A(2) and esterase activities with the optimal catalytic temperature at 90 degrees C. The enzyme activity was Ca(2+)-independent. Kinetic analysis revealed its Km, k cat, and Vm for the p-nitrophenyl propionate substrate were 103microM, 39s(-1), and 249micromol/min/mg, respectively. The recombinant protein was thermostable and its half-life at 100 degrees C was about 1h.

  15. C1-esterase inhibitor blocks T lymphocyte proliferation and cytotoxic T lymphocyte generation in vitro

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Bregenholt, S; Nording, J A

    1998-01-01

    We have previously shown that activated C1s complement and activated T cells cleave beta2-microglobulin (beta2m) in vitro leading to the formation of desLys58 beta2m. This process can specifically be inhibited by C1-esterase inhibitor (C1-inh). Furthermore we showed that exogenously added desLys58...... beta2m in nanomolar amounts to a one-way allogenic mixed lymphocyte culture (MLC) increased the endogenous production of IL-2 and the generation of allo-specific cytotoxic T lymphocytes. C1-inh was purified from fresh human plasma and added to human or murine MLC and mitogen-stimulated lymphocyte...... cultures grown in the presence of complement-inactivated serum. Read-outs were cell proliferation, lymphokine production and development of T cell-mediated cytotoxicity. We found that addition of C1-inh to MLC and mitogen-exposed murine and human lymphocyte cultures inhibited proliferation, the development...

  16. 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...

  17. An acidic feruloyl esterase from the mushroom Lactarius hatsudake: A potential animal feed supplement.

    Science.gov (United States)

    Wang, Li; Li, Zhuang; Zhu, Mengjuan; Meng, Li; Wang, Hexiang; Ng, Tzi Bun

    2016-12-01

    An acidic feruloyl esterase (lhFAE) from Lactarius hatsudake was purified to homogeneity, resulting in a high specific activity of 10.3U/mg toward methyl ferulate as substrate, which was 33.2-fold higher than that of the crude enzyme. lhFAE was a monomeric protein with a molecular mass of 55kDa. All three internal amino acid sequences exhibited 100% identity with the Laccaria bicolor carbohydrate esterase family 9 protein. The enzyme demonstrated high activity toward methyl ferulate (MFA) at an optimum pH of 4.0 and an optimum temperature at 30°C, and under these conditions, the Km and Vmax were 0.54mM and 13.84Umg-1, respectively. The purified FAE exhibited preference for methyl caffeate over methyl ferulate, and was least active on methyl p-coumarate. Interestingly, above 80% of the enzyme activity was preserved in the presence of metal ions at 5.0mM concentration, which indicated that lhFAE was highly metal-tolerant. lhFAE was able to release ferulic acid from de-starched wheat bran (DSWB) both in the absence and presence of xylanase, and 70.2% (of the total amount of) ferulic acid (FA) was released by the synergistic action of xylanase. The result showed that lhFAE has good acid and metal ion stability, and is suitable to be used as an animal feed supplement. Copyright © 2016. Published by Elsevier B.V.

  18. Physicochemical impact studies of gamma rays on "aspirin" analgesics drug and its metal complexes in solid form: Synthesis, spectroscopic and biological assessment of Ca(II), Mg(II), Sr(II) and Ba(II) aspirinate complexes

    Science.gov (United States)

    Refat, Moamen S.; Sharshar, T.; Elsabawy, Khaled M.; Heiba, Zein K.

    2013-09-01

    Metal aspirinate complexes, M2(Asp)4, where M is Mg(II), Ca(II), Sr(II) or Ba(II) are formed by refluxed of aspirin (Asp) with divalent non-transition metal ions of group (II) and characterized by elemental analysis and spectroscopic measurements (infrared, electronic, 1H NMR, Raman, X-ray powder diffraction and scanning electron microscopy). Elemental analysis of the chelates suggests the stoichiometry is 1:2 (metal:ligand). Infrared spectra of the complexes agree with the coordination to the central metal atom through three donation sites of two oxygen atoms of bridge bidentate carboxylate group and oxygen atom of sbnd Cdbnd O of acetyl group. Infrared spectra coupled with the results of elemental analyzes suggested a distorted octahedral structure for the M(II) aspirinate complexes. Gamma irradiation was tested as a method for stabilization of aspirin as well as their complexes. The effect of gamma irradiation, with dose of 80 Gy, on the properties of aspirinate complexes was studied. The aspirinate chelates have been screened for their in vitro antibacterial activity against four bacteria, gram-positive (Bacillus subtilis and Staphylococcus aureus) and gram-negative (Escherichia coli and Pseudomonas aeruginosa) and two strains of fungus (Aspergillus flavus and Candida albicans). The metal chelates were shown to possess more antibacterial activity than the free aspirin chelate.

  19. Preparation and Properties of Novel Dentin Adhesives with Esterase Resistance

    OpenAIRE

    Park, Jong-Gu; Ye, Qiang; Topp, Elizabeth M.; Kostoryz, Elisabet L.; Wang, Yong; Kieweg, Sarah L; Spencer, Paulette

    2007-01-01

    A new methacrylate monomer, trimethylolpropane mono allyl ether dimethacrylate (TMPEDMA), was synthesized and evaluated. This branched methacrylate was designed to increase esterase-resistance when incorporated into conventional HEMA (2-hydroxyethyl methacrylate)/BisGMA (2,2-bis[4(2-hydroxy-3-methacryloyloxy-propyloxy)-phenyl] propane) dental adhesives. The new adhesives, HEMA/BisGMA/TMPEDMA in a 45/30/25 (w/w) ratio were formulated with H2O at 0 (A0T) and 8 wt % water (A8T) and compared with...

  20. Degradation products of the artificial azo dye, Allura red, inhibit esterase activity of carbonic anhydrase II: A basic in vitro study on the food safety of the colorant in terms of enzyme inhibition.

    Science.gov (United States)

    Esmaeili, Sajjad; Ashrafi-Kooshk, Mohammad Reza; Khaledian, Koestan; Adibi, Hadi; Rouhani, Shohre; Khodarahmi, Reza

    2016-12-15

    Allura red is a widely used food colorant, but there is debate on its potential security risk. In the present study, we found that degradation products of the dye were more potent agents with higher carbonic anhydrase inhibitory action than the parent dye. The mechanism by which the compounds inhibit the enzyme activity has been determined as competitive mode. In addition, the enzyme binding properties of the compounds were investigated employing different spectroscopic techniques and molecular docking. The analyses of fluorescence quenching data revealed the existence of the same binding site for the compounds on the enzyme molecule. The thermodynamic parameters of ligand binding were not similar, which indicates that different interactions are responsible in binding of the parent dye and degradation products to the enzyme. It appears that enzyme inhibition should be considered, more seriously, as a new opened dimension in food safety. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Extracellular esterases of phylloplane yeast Pseudozyma antarctica induce defect on cuticle layer structure and water-holding ability of plant leaves.

    Science.gov (United States)

    Ueda, Hirokazu; Mitsuhara, Ichiro; Tabata, Jun; Kugimiya, Soichi; Watanabe, Takashi; Suzuki, Ken; Yoshida, Shigenobu; Kitamoto, Hiroko

    2015-08-01

    Aerial plant surface (phylloplane) is a primary key habitat for many microorganisms but is generally recognized as limited in nutrient resources. Pseudozyma antarctica, a nonpathogenic yeast, is commonly isolated from plant surfaces and characterized as an esterase producer with fatty acid assimilation ability. In order to elucidate the biological functions of these esterases, culture filtrate with high esterase activity (crude enzyme) of P. antarctica was applied onto leaves of tomato and Arabidopsis. These leaves showed a wilty phenotype, which is typically associated with water deficiency. Furthermore, we confirmed that crude enzyme-treated detached leaves clearly lost their water-holding ability. In treated leaves of both plants, genes associated to abscisic acid (ABA; a plant stress hormone responding osmotic stress) were activated and accumulation of ABA was confirmed in tomato plants. Microscopic observation of treated leaf surfaces revealed that cuticle layer covering the aerial epidermis of leaves became thinner. A gas chromatography-mass spectrometry (GC-MS) analysis exhibited that fatty acids with 16 and 18 carbon chains were released in larger amounts from treated leaf surfaces, indicating that the crude enzyme has ability to degrade lipid components of cuticle layer. Among the three esterases detected in the crude enzyme, lipase A, lipase B, and P. antarctica esterase (PaE), an in vitro enzyme assay using para-nitrophenyl palmitate as substrate demonstrated that PaE was the most responsible for the degradation. These results suggest that PaE has a potential role in the extraction of fatty acids from plant surfaces, making them available for the growth of phylloplane yeasts.

  2. Esterases in striated muscle from mice with the Chediak-Higashi syndrome

    DEFF Research Database (Denmark)

    Kirkeby, S; Moe, D

    1981-01-01

    In this paper a localized strong reaction for non-specific esterase forming cylindric structures is described within skeletal muscle fibres from the beige mouse. It seems from zymograms and protein electrophoresis that this esterase is membrane bound, highly reactive and present in rather small a...

  3. 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.

  4. Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction: enhanced inhibitory effects of combination therapy.

    Science.gov (United States)

    Moshfegh, K; Redondo, M; Julmy, F; Wuillemin, W A; Gebauer, M U; Haeberli, A; Meyer, B J

    2000-09-01

    We sought to compare the inhibitory effects of the combination of two doses of aspirin plus clopidogrel with either drug alone on platelet aggregation and activation. Enhanced platelet inhibitory effects of clopidogrel by aspirin on platelet aggregation and activation are suggested by experimental studies but have not been shown in humans. The effects of clopidogrel 75 mg or aspirin 100 (300) mg on platelet aggregation and activation by flow cytometry after stimulation with various agonists were determined in 30 patients with a past history of myocardial infarction. Clopidogrel alone or in combination with aspirin markedly inhibited adenosine diphosphate (ADP)-mediated platelet aggregation compared with monotherapy with aspirin (24.6 +/- 3.3% or 26.6 +/- 2.7% vs. 44.7 +/- 2.9%; p after stimulation with ADP or thrombin (p after activation with low dose thrombin (p after stimulation with collagen and thrombin compared with monotherapies. Thus, this dual antiplatelet treatment strategy deserves further evaluation in clinical trials for secondary prevention of acute myocardial infarction or unstable angina.

  5. Chronic Use of Aspirin and Total White Matter Lesion Volume: Results from the Women's Health Initiative Memory Study of Magnetic Resonance Imaging Study.

    Science.gov (United States)

    Holcombe, Andrea; Ammann, Eric; Espeland, Mark A; Kelley, Brendan J; Manson, JoAnn E; Wallace, Robert; Robinson, Jennifer

    2017-10-01

    To investigate the relationship between aspirin and subclinical cerebrovascular heath, we evaluated the effect of chronic aspirin use on white matter lesions (WML) volume among women. Chronic aspirin use was assessed in 1365 women who participated in the Women's Health Initiative Memory Study of Magnetic Resonance Imaging. Differences in WML volumes between aspirin users and nonusers were assessed with linear mixed models. A number of secondary analyses were performed, including lobe-specific analyses, subgroup analyses based on participants' overall risk of cerebrovascular disease, and a dose-response relationship analysis. The mean age of the women at magnetic resonance imaging examination was 77.6 years. Sixty-one percent of participants were chronic aspirin users. After adjusting for demographic variables and comorbidities, chronic aspirin use was nonsignificantly associated with 4.8% (95% CI: -6.8%, 17.9%) larger WML volumes. These null findings were confirmed in secondary and sensitivity analyses, including an active comparator evaluation where aspirin users were compared to users of nonaspirin nonsteroidal anti-inflammatory drugs or acetaminophen. There was a nonsignificant difference in WML volumes between aspirin users and nonusers. Further, our results suggest that chronic aspirin use may not have a clinically significant effect on WML volumes in women. Published by Elsevier Inc.

  6. 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 ...

  7. 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 ...

  8. Organophosphate acetylcholine esterase inhibitor poisoning from a home-made shampoo.

    Science.gov (United States)

    Sadaka, Yair; Broides, Arnon; Tzion, Raffi Lev; Lifshitz, Matitiahu

    2011-07-01

    Organophosphate acetylcholine esterase inhibitor poisoning is a major health problem in children. We report an unusual cause of organophosphate acetylcholine esterase inhibitor poisoning. Two children were admitted to the pediatric intensive care unit due to organophosphate acetylcholine esterase inhibitor poisoning after exposure from a home-made shampoo that was used for the treatment of head lice. Owing to no obvious source of poisoning, the diagnosis of organophosphate acetylcholine esterase inhibitor poisoning in one of these patients was delayed. Both patients had an uneventful recovery. Organophosphate acetylcholine esterase inhibitor poisoning from home-made shampoo is possible. In cases where the mode of poisoning is unclear, direct questioning about the use of home-made shampoo is warranted, in these cases the skin and particularly the scalp should be rinsed thoroughly as soon as possible.

  9. [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.

  10. NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid has enhanced chemo-preventive properties compared to aspirin, is gastrointestinal safe with all the classic therapeutic indications

    Science.gov (United States)

    Kodela, Ravinder; Chattopadhyay, Mitali; Velázquez-Martínez, Carlos A.; Kashfi, Khosrow

    2015-01-01

    Aspirin is chemopreventive; however, side effects preclude its long-term use. NOSH-aspirin (NBS-1120), a novel hybrid that releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, antipyretic, anti-platelet, and chemopreventive properties of aspirin and NBS-1120 administered orally to rats at equimolar doses. Gastrointestinal safety: 6h post-administration, the number and size of hemorrhagic lesions in stomachs were counted; tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Chemoprevention: Nude mice were gavaged daily for 25 days with vehicle, aspirin or NBS-1120. After one week, each mouse was inoculated subcutaneously in the right flank with HT-29 human colon cancer cells. Both agents reduced PGE2 levels in stomach tissue; however, NBS-1120 did not cause any stomach ulcers, whereas aspirin caused significant bleeding. Lipid peroxidation induced by aspirin was higher than that exerted by NBS-1120. SOD activity was significantly inhibited by aspirin but increased by NBS-1120. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Aspirin increased plasma TNFα more than NBS-1120-treated animals. NBS-1120 was better than aspirin as a chemopreventive agent; it dose-dependently inhibited tumor growth and tumor mass. PMID:26394025

  11. Resistance to aspirin is increased by ST-elevation myocardial infarction and correlates with adenosine diphosphate levels

    Directory of Open Access Journals (Sweden)

    Öhlin Hans

    2005-07-01

    Full Text Available Abstract Background To be fully activated platelets are dependent on two positive feedback loops; the formation of thromboxane A2 by cyclooxygenase in the platelets and the release of ADP. We wanted to evaluate the effect of aspirin on platelet function in patients with acute coronary syndromes and we hypothesized that increased levels of ADP in patients with acute coronary syndromes could contribute to aspirin resistance. Methods Platelet activity in 135 patients admitted for chest pain was assessed with PFA-100. An epinephrine-collagen cartridge (EPI-COLL was used for the detection of aspirin resistance together with an ADP-collagen cartridge (ADP-COLL. ADP was measured with hplc from antecubital vein samples. Three subgroups were compared: chest pain with no sign of cardiac disease (NCD, NonST-elevation myocardial infarction (NSTEMI and STEMI. Results Platelet activation was increased for the STEMI group compared NCD. Aspirin resistance defined as Conclusion Platelets are activated and aspirin resistance is more frequent in STEMI, probably due to a general activation of platelets. ADP levels are increased in STEMI and correlates with platelet activation. Increased levels of ADP could be one reason for increased platelet activity and aspirin resistance.

  12. Air pressure pulsation solid state fermentation of feruloyl esterase by Aspergillus niger.

    Science.gov (United States)

    Zeng, W; Chen, H Z

    2009-02-01

    Air pressure pulsation solid state fermentation (APP-SSF) was applied to produce feruloyl esterase (FAE) by Aspergillus niger. With the optimization of some variables by orthogonal design, the optimal condition obtained was 0.2 MPa (gauge pressure) of high pressure intensity, 30 min of low pressure duration and 20s of high pressure duration. Based on the optimized condition, the APP-SSF achieved the reasonable enzyme yield of 881 mU/g at 48 h, which was 58% more than that by static solid state fermentation (static SSF) at 72 h. By comparison of two fermentation methods in temperature, O(2) and CO(2) concentration, and respiration intensity, it was concluded that APP-SSF enhanced heat and mass transfer of fermentation system and strengthened the metabolism of microorganisms. The APP-SSF had a greatly positive effect on FAE production by A. niger, by enhancing mass and heat transfer and activating growth and metabolism.

  13. Reduction of 4-ethylphenol production in red wines using HCDC+ yeasts and cinnamyl esterases.

    Science.gov (United States)

    Morata, A; Vejarano, R; Ridolfi, G; Benito, S; Palomero, F; Uthurry, C; Tesfaye, W; González, C; Suárez-Lepe, J A

    2013-02-05

    Hydroxycinnamate decarboxylase (HCDC) activity has been evaluated in several commercial yeast strains. The combined effect of using cinnamyl esterases (CE) and HCDC+ Saccharomyces cerevisiae strains has been studied in the formation of vinylphenolic pyranoanthocyanins (VPAs) during fermentation, analysing the kind and concentration of pigments formed according to the yeast strain used. Wines fermented with yeasts HCDC+ were contaminated with Dekkera bruxellensis and afterwards analysed to evaluate the formation of ethylphenols (EPs). The musts treated with CE and later fermented with HCDC+ yeast strains showed lower contents of 4-ethylphenol than those fermented with HCDC- strains. This reduction in the EP content is due to the transformation of hydroxycinnamic acids in stable VPAs pigments. The associated use of CEs and HCDC+ Saccharomyces strains is a natural strategy to reduce the formation of EPs in wines contaminated by Dekkera/Brettanomyces. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. C1-esterase inhibitor deficiency and elective caesarean section.

    Science.gov (United States)

    Griffiths, R J; O'Sullivan, G

    2005-07-01

    C1-esterase inhibitor deficiency is a rare disorder of the complement system characterised by episodes of cutaneous and mucosal oedema. Life-threatening airway oedema can follow airway instrumentation or minor trauma. We describe the successful management of a 37-year-old primiparous woman with inherited C1-esterase inhibitor deficiency who was admitted at 38 weeks' gestation for elective caesarean section. Whilst undergoing general anaesthesia 18 months previously she had experienced facial and pharyngeal oedema despite prophylaxis (one unit of fresh frozen plasma). On this occasion she underwent elective caesarean section following intrathecal anaesthesia with 0.5% hyperbaric bupivacaine 2 mL and diamorphine 300 microg. Cardiovascular stability was ensured using glycopyrolate and intravenous Hartmann's solution 2 L; a live female infant was delivered successfully. There were no peri- or postoperative complications. Regional anaesthesia is the safest method for providing surgical anaesthesia in the obstetric patient. We believe elective caesarean section under regional anaesthesia should be considered if there are predicted difficulties with vaginal delivery.

  15. 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.

  16. 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

  17. Diagnosing bacterial peritonitis made easy by use of leukocyte esterase dipsticks.

    Science.gov (United States)

    Chugh, Kiran; Agrawal, Yuthika; Goyal, Vipin; Khatri, Vinod; Kumar, Pradeep

    2015-01-01

    Spontaneous bacterial peritonitis (SBP) requires rapid diagnosis for the initiation of antibiotics. Its diagnosis is usually based on manual examination of ascitic fluid (AF) having long reporting time. AF infection is diagnosed when the fluid polymorphonuclear leukocyte (PMNL) concentration ≥250 cells/mm(3). Aim was to evaluate the diagnostic utility of leukocyte esterase (LE) reagent strip for rapid diagnosis of SBP in patients who underwent abdominal paracentesis and to calculate the sensitivity, specificity, positive, and negative predictive values. The study was carried out on 103 patients with ascites. Cell count of AF as determined by colorimetric scale of Multistix 10 SG reagent strip was compared with counting chamber method (PMNL count ≥250 cells/mm(3) was considered positive). Of the 103 patients SBP was diagnosed in 20 patients, 83 patients were negative for SBP by manual cell count. The sensitivity and specificity of the LE test for detecting neutrocytic SBP taking grade 2 as cut off were 95% and 96.4% respectively, with a positive predictive value of 86.4% and a negative predictive value of 98.8%. Diagnostic accuracy of LE test was 96.1%. There was a good correlation between the reagent strip result and PMNL count. The LE strip test is based on the esterase activity of activated granulocytes which reacts with an ester-releasing hydroxyphenylpyrrole causing a colour change in the azo dye of reagent strip. It is a very sensitive and specific method for the prompt detection of elevated PMNL count, and represents a convenient, inexpensive, simple, and bedside method for diagnosis of SBP. A negative LE test result excludes SBP with a high degree of certainty.

  18. Cyclooxygenase-independent neuroprotective effects of aspirin against dopamine quinone-induced neurotoxicity.

    Science.gov (United States)

    Asanuma, Masato; Miyazaki, Ikuko; Kikkawa, Yuri; Kimoto, Naotaka; Takeshima, Mika; Murakami, Shinki; Miyoshi, Ko

    2012-09-01

    Prostaglandin H synthase exerts not only cyclooxygenase activity but also peroxidase activity. The latter activity of the enzyme is thought to couple with oxidation of dopamine to dopamine quinone. Therefore, it has been proposed that cyclooxygenase inhibitors could suppress dopamine quinone formation. In the present study, we examined effects of various cyclooxygenase inhibitors against excess methyl L-3,4-dihydroxyphenylalanine (L-DOPA)-induced quinoprotein (protein-bound quinone) formation and neurotoxicity using dopaminergic CATH.a cells. The treatment with aspirin inhibited excess methyl L-DOPA-induced quinoprotein formation and cell death. However, acetaminophen did not show protective effects, and indomethacin and meloxicam rather aggravated these methyl L-DOPA-induced changes. Aspirin and indomethacin did not affect the level of glutathione that exerts quenching dopamine quinone in dopaminergic cells. In contrast with inhibiting effects of higher dose in the previous reports, relatively lower dose of aspirin that affected methyl L-DOPA-induced quinoprotein formation and cell death failed to prevent cyclooxygenase-induced dopamine chrome generation in cell-free system. Furthermore, aspirin but not acetaminophen or meloxicam showed direct dopamine quinone-scavenging effects in dopamine-semiquinone generating systems. The present results suggest that cyclooxygenase shows little contribution to dopamine oxidation in dopaminergic cells and that protective effects of aspirin against methyl L-DOPA-induced dopamine quinone neurotoxicity are based on its cyclooxygenase-independent property.

  19. 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

  20. 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.

  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. Polypeptide having acetyl xylan esterase activity and uses thereof

    Energy Technology Data Exchange (ETDEWEB)

    Schoonneveld-Bergmans, Margot Elisabeth Francoise; Heijne, Wilbert Herman Marie; Los, Alrik Pieter

    2015-10-20

    The invention relates to a polypeptide comprising the amino acid sequence set out in SEQ ID NO: 2 or an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 1, or a variant polypeptide or variant polynucleotide thereof, wherein the variant polypeptide has at least 82% sequence identity with the sequence set out in SEQ ID NO: 2 or the variant polynucleotide encodes a polypeptide that has at least 82% sequence identity with the sequence set out in SEQ ID NO: 2. The invention features the full length coding sequence of the novel gene as well as the amino acid sequence of the full-length functional polypeptide and functional equivalents of the gene or the amino acid sequence. The invention also relates to methods for using the polypeptide in industrial processes. Also included in the invention are cells transformed with a polynucleotide according to the invention suitable for producing these proteins.

  3. A novel esterase gene cloned from a metagenomic library from neritic sediments of the South China Sea

    Science.gov (United States)

    2011-01-01

    Background Marine microbes are a large and diverse group, which are exposed to a wide variety of pressure, temperature, salinity, nutrient availability and other environmental conditions. They provide a huge potential source of novel enzymes with unique properties that may be useful in industry and biotechnology. To explore the lipolytic genetic resources in the South China Sea, 23 sediment samples were collected in the depth South China Sea sediments assemblage in plasmid vector containing about 194 Mb of community DNA was prepared. Screening of a part of the unamplified library resulted in isolation of 15 unique lipolytic clones with the ability to hydrolyze tributyrin. A positive recombinant clone (pNLE1), containing a novel esterase (Est_p1), was successfully expressed in E. coli and purified. In a series of assays, Est_p1 displayed maximal activity at pH 8.57, 40°C, with ρ-Nitrophenyl butyrate (C4) as substrate. Compared to other metagenomic esterases, Est_p1 played a notable role in specificity for substrate C4 (kcat/Km value 11,500 S-1m M-1) and showed no inhibited by phenylmethylsulfonyl fluoride, suggested that the substrate binding pocket was suitable for substrate C4 and the serine active-site residue was buried at the bottom of substrate binding pocket which sheltered by a lid structure. Conclusions Esterase, which specificity towards short chain fatty acids, especially butanoic acid, is commercially available as potent flavoring tools. According the outstanding activity and specificity for substrate C4, Est_p1 has potential application in flavor industries requiring hydrolysis of short chain esters. PMID:22067554

  4. A novel esterase gene cloned from a metagenomic library from neritic sediments of the South China Sea

    Directory of Open Access Journals (Sweden)

    Peng Qing

    2011-11-01

    Full Text Available Abstract Background Marine microbes are a large and diverse group, which are exposed to a wide variety of pressure, temperature, salinity, nutrient availability and other environmental conditions. They provide a huge potential source of novel enzymes with unique properties that may be useful in industry and biotechnology. To explore the lipolytic genetic resources in the South China Sea, 23 sediment samples were collected in the depth Results A metagenomic library of South China Sea sediments assemblage in plasmid vector containing about 194 Mb of community DNA was prepared. Screening of a part of the unamplified library resulted in isolation of 15 unique lipolytic clones with the ability to hydrolyze tributyrin. A positive recombinant clone (pNLE1, containing a novel esterase (Est_p1, was successfully expressed in E. coli and purified. In a series of assays, Est_p1 displayed maximal activity at pH 8.57, 40°C, with ρ-Nitrophenyl butyrate (C4 as substrate. Compared to other metagenomic esterases, Est_p1 played a notable role in specificity for substrate C4 (kcat/Km value 11,500 S-1m M-1 and showed no inhibited by phenylmethylsulfonyl fluoride, suggested that the substrate binding pocket was suitable for substrate C4 and the serine active-site residue was buried at the bottom of substrate binding pocket which sheltered by a lid structure. Conclusions Esterase, which specificity towards short chain fatty acids, especially butanoic acid, is commercially available as potent flavoring tools. According the outstanding activity and specificity for substrate C4, Est_p1 has potential application in flavor industries requiring hydrolysis of short chain esters.

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

    Science.gov (United States)

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

    2015-01-01

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

  6. In Silico Modeling of the Antiplatelet Pharmacodynamics of Low-dose Aspirin in Health and Disease.

    Science.gov (United States)

    Giaretta, A; Rocca, B; Di Camillo, B; Toffolo, G M; Patrono, C

    2017-11-01

    The influence of platelet turnover on cyclooxygenase (COX-1) inhibition by low-dose aspirin remains largely uncharacterized due to limited feasibility of studying aspirin pharmacodynamics in bone marrow precursors. We developed an in silico compartmental model describing the aspirin effects on COX-1 activity in a population of megakaryocytes (MK) and in peripheral platelets. Model parameters were inferred from the literature and calibrated using measurements of serum thromboxane B2 (sTXB2 ), as proxy of COX-1 activity in peripheral platelets, in 17 healthy subjects and 24 patients with essential thrombocythemia (ET). The model reproduced well the average time-course of sTXB2 inhibition in healthy (accuracy = 10.4%), the reduced inhibition of sTXB2 observed in ET, and the effect of different dosing regimens. In conclusion, the in silico model accurately describes COX-1 inactivation by low-dose aspirin in MK and platelets in different clinical settings, and might help personalize aspirin regimens in conditions of altered megakaryopoiesis. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  7. 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 outcome event was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever happened first. Treatment was open, but auditing of outcome events was blinded. Primary analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN73824458) and with (NCT00161070). Mean follow-up was 3.5 years (SD 2.0). Median aspirin dose was 75 mg in both treatment groups (range 30-325); extended-release dipyridamole was used by 83% (n=1131) of patients on the combination regimen. Primary outcome events arose in 173 (13%) patients on aspirin and dipyridamole and in 216 (16%) on aspirin alone (hazard ratio 0.80, 95% CI 0.66-0.98; absolute risk reduction 1.0% per year, 95% CI 0.1-1.8). Addition of the ESPRIT data to the meta-analysis of previous trials resulted in an overall risk ratio for the composite of vascular death, stroke, or myocardial infarction of 0.82 (95% CI 0.74-0.91). Patients on aspirin and dipyridamole discontinued trial medication more often than those on aspirin alone (470 vs 184), mainly because of headache. The ESPRIT results, combined with the results of previous trials, provide sufficient evidence to prefer the combination regimen of aspirin plus dipyridamole over aspirin alone as antithrombotic therapy after cerebral ischaemia of arterial origin.

  8. Inhibition, recovery and oxime-induced reactivation of muscle esterases following chlorpyrifos exposure in the earthworm Lumbricus terrestris

    Energy Technology Data Exchange (ETDEWEB)

    Collange, B. [Universite d' Avignon et des Pays de Vaucluse, UMR 406 Abeilles et Environnement, Site AGROPARC, F-84914, Avignon Cede 09 (France); Wheelock, C.E. [Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 171 77, Stockholm (Sweden); Rault, M.; Mazzia, C. [Universite d' Avignon et des Pays de Vaucluse, UMR 406 Abeilles et Environnement, Site AGROPARC, F-84914, Avignon Cede 09 (France); Capowiez, Y. [INRA, Unite PSH, Site AGROPARC, F-84914 Avignon Cedex 09 (France); Sanchez-Hernandez, J.C., E-mail: juancarlos.sanchez@uclm.e [Laboratory of Ecotoxicology, Faculty of Environmental Science, University of Castilla-La Mancha, Avda. Carlos III s/n, 45071, Toledo (Spain)

    2010-06-15

    Assessment of wildlife exposure to organophosphorus (OP) pesticides generally involves the measurement of cholinesterase (ChE) inhibition, and complementary biomarkers (or related endpoints) are rarely included. Herein, we investigated the time course inhibition and recovery of ChE and carboxylesterase (CE) activities in the earthworm Lumbricus terrestris exposed to chlorpyrifos, and the ability of oximes to reactivate the phosphorylated ChE activity. Results indicated that these esterase activities are a suitable multibiomarker scheme for monitoring OP exposure due to their high sensitivity to OP inhibition and slow recovery to full activity levels following pesticide exposure. Moreover, oximes reactivated the inhibited ChE activity of the earthworms exposed to 12 and 48 mg kg{sup -1} chlorpyrifos during the first week following pesticide exposure. This methodology is useful for providing evidence for OP-mediated ChE inhibition in individuals with a short history of OP exposure (<=1 week); resulting a valuable approach for assessing multiple OP exposure episodes in the field. - Esterase inhibition combined with oxime reactivation methods is a suitable approach for monitoring organophosphate contamination

  9. Identification of a bacterial pectin acetyl esterase in Erwinia chrysanthemi 3937.

    Science.gov (United States)

    Shevchik, V E; Hugouvieux-Cotte-Pattat, N

    1997-06-01

    Erwinia chrysanthemi causes soft-rot diseases of various plants by enzymatic degradation of the pectin in plant cell walls. The structural complexity of pectin requires the combined action of several pectinases for its efficient breakdown. Three types of pectinases have so far been identified in E. chrysanthemi: two pectin methyl esterases (PemA, PemB), a polygalacturonase (PehX), and eight pectate lyases (PelA, PelB, PelC, PelD, PelE, PelL, PelZ, PelX). We report in this paper the analysis of a novel enzyme, the pectin acetyl esterase encoded by the paeY gene. No bacterial form of pectin acetyl esterases has been described previously, while plant tissues and some pectinolytic fungi were found to produce similar enzymes. The paeY gene is present in a cluster of five pectinase-encoding genes, pelA-pelE-pelD-paeY-pemA. The paeY open reading frame is 1650 bases long and encodes a 551-residue precursor protein of 60704Da, including a 25-amino-acid signal peptide. PaeY shares one region of homology with a rhamnogalacturonan acetyl esterase of Aspergillus aculeatus. To characterize the enzyme, the paeY gene was overexpressed and its protein product was purified. PaeY releases acetate from sugar-beet pectin and from various synthetic substrates. Moreover, the enzyme was shown to act in synergy with other pectinases. The de-esterification rate by PaeY increased after previous demethylation of the pectins by PemA and after depolymerization of the pectin by pectate lyases. In addition, the degradation of sugar-beet pectin by pectate lyases is favoured after the removal of methyl and acetyl groups by PemA and PaeY, respectively. The paeY gene was first identified on the basis of its regulation, which shares several characteristics with that of other pectinases. Analysis of the paeY transcription, using gene fusions, revealed that it is induced by pectic catabolic products and is affected by growth phase, oxygen limitation and catabolite repression. Regulation of pae

  10. 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.

  11. B-type esterases in the snail Xeropicta derbentina: an enzymological analysis to evaluate their use as biomarkers of pesticide exposure.

    Science.gov (United States)

    Laguerre, Christel; Sanchez-Hernandez, Juan C; Köhler, Heinz R; Triebskorn, Rita; Capowiez, Yvan; Rault, Magali; Mazzia, Christophe

    2009-01-01

    The study was prompted to characterize the B-type esterase activities in the terrestrial snail Xeropicta derbentina and to evaluate its sensitivity to organophosphorus and carbamate pesticides. Specific cholinesterase and carboxylesterase activities were mainly obtained with acetylthiocholine (K(m)=77.2 mM; V(max)=38.2 mU/mg protein) and 1-naphthyl acetate (K(m)=222 mM, V(max)=1095 mU/mg protein) substrates, respectively. Acetylcholinesterase activity was concentration-dependently inhibited by chlorpyrifos-oxon, dichlorvos, carbaryl and carbofuran (IC50=1.35x10(-5)-3.80x10(-8) M). The organophosphate-inhibited acetylcholinesterase activity was reactivated in the presence of pyridine-2-aldoxime methochloride. Carboxylesterase activity was inhibited by organophosphorus insecticides (IC50=1.20x10(-5)-2.98x10(-8) M) but not by carbamates. B-esterase-specific differences in the inhibition by organophosphates and carbamates are discussed with respect to the buffering capacity of the carboxylesterase to reduce pesticide toxicity. These results suggest that B-type esterases in X. derbentina are suitable biomarkers of pesticide exposure and that this snail could be used as sentinel species in field monitoring of Mediterranean climate regions.

  12. The role of Ca2+ and Mg2+ in the cytotoxic T lymphocyte reaction and in the secretion of N alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester-serine esterase by human T cell clones

    NARCIS (Netherlands)

    Blanchard, D.; Aubry, J. P.; de Vries, J. E.; Spits, H.

    1989-01-01

    Human T cell clones contain enzymes that can cleave the substrate N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester (BLT). All CTL clones tested in this study secreted BLT-serine esterase activity, whereas only one of three tested non-cytolytic T cell clones secreted this enzymatic activity upon

  13. Comparative effect of clopidogrel plus aspirin and aspirin monotherapy on hematological parameters using propensity score matching

    Directory of Open Access Journals (Sweden)

    Hayasaka M

    2013-02-01

    Full Text Available Masatoshi Hayasaka,1 Yasuo Takahashi,2 Yayoi Nishida,2 Yoshikazu Yoshida,1 Shinji Hidaka,3 Satoshi Asai41Department of Pharmacy, Nihon University Itabashi Hospital, Tokyo, 2Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, Nihon University School of Medicine, Tokyo, 3Laboratory of Pharmaceutical Regulatory Science, Department of Pharmacy, School of Pharmacy, Nihon University, Chiba, 4Division of Pharmacology, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, JapanBackground: Clopidogrel and aspirin are antiplatelet agents that are recommended to reduce the risk of recurrent stroke and other cardiovascular events. Dual antiplatelet therapy with clopidogrel and aspirin has been shown to increase the risk of hemorrhage, but the effects of the drugs on laboratory parameters have not been well studied in real-world clinical settings. Therefore, we evaluated and compared the effects of combination therapy with clopidogrel plus aspirin and aspirin monotherapy on laboratory parameters.Methods: We used data from the Nihon University School of Medicine Clinical Data Warehouse obtained between November 2004 and May 2011 to identify cohorts of new users (n = 130 of clopidogrel (75 mg/day plus aspirin (100 mg/day and a propensity score matched sample of new users (n = 130 of aspirin alone (100 mg/day. We used a multivariate regression model to compare serum levels of creatinine, aspartate aminotransferase, and alanine aminotransferase, as well as hematological parameters including hemoglobin level, hematocrit, and white blood cell, red blood cell, and platelet counts up to 2 months after the start of administration of the study drugs.Results: There were no significant differences for any characteristics and baseline laboratory parameters between users of clopidogrel plus aspirin and users of aspirin alone. Reductions in white blood cell and red blood cell counts, hemoglobin levels, and

  14. Thieno[2,3-b]pyridine derivatives are potent anti-platelet drugs, inhibiting platelet activation, aggregation and showing synergy with aspirin.

    Science.gov (United States)

    Binsaleh, Naif K; Wigley, Catherine A; Whitehead, Kathryn A; van Rensburg, Michelle; Reynisson, Johannes; Pilkington, Lisa I; Barker, David; Jones, Sarah; Dempsey-Hibbert, Nina C

    2018-01-01

    Drugs which inhibit platelet function are commonly used to prevent blood clot formation in patients with Acute Coronary Syndromes (ACS) or those at risk of stroke. The thieno[3,2-c]pyridine class of therapeutic agents, of which clopidogrel is the most commonly used, target the P2Y12 receptor, and are often used in combination with acetylsalicylic acid (ASA). Six thieno[2,3-b]pyridine were assessed for in vitro anti-platelet activity; all derivatives showed effects on both platelet activation and aggregation, and showed synergy with ASA. Some compounds demonstrated greater activity when compared to clopidogrel. These compounds, therefore, represent potential novel P2Y12 inhibitors for improved treatment for patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Aspirin and Reye's syndrome — do parents know?

    OpenAIRE

    Hall, R. W.

    1987-01-01

    Amid growing concern over the association between aspirin and Reye's syndrome, the Aspirin Foundation has recently mounted a publicity campaign advising against the use of aspirin in children. Of 50 parents questioned at a children's ward of a district general hospital, 46 (92%) had heard of the publicity, 38 via the television. The number of parents who would give aspirin to their child had dropped significantly from 45 before the campaign to five after it (P

  16. Aspirin and Reye's syndrome — do parents know?

    Science.gov (United States)

    Hall, R.W.

    1987-01-01

    Amid growing concern over the association between aspirin and Reye's syndrome, the Aspirin Foundation has recently mounted a publicity campaign advising against the use of aspirin in children. Of 50 parents questioned at a children's ward of a district general hospital, 46 (92%) had heard of the publicity, 38 via the television. The number of parents who would give aspirin to their child had dropped significantly from 45 before the campaign to five after it (PReye's syndrome as the reason. PMID:3505289

  17. Protective effects of essential oil of Citrus limon against aspirin-induced toxicity in IEC-6 cells.

    Science.gov (United States)

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

    2017-05-01

    Aspirin, one of the widely used nonsteroidal anti-inflammatory drugs, is the most highly consumed pharmaceutical product in the world. However, it has several side effects in cells. This study was designed to investigate the antioxidative activity and cytoprotective effects of essential oil of Citrus limon (EOC) extracted from leaves against aspirin-induced damages in the rat small intestine epithelial cells (IEC-6). Biochemical indicators were used to assess cytotoxicity and oxidative damages caused by aspirin treatment on IEC-6. Our results showed that the chemical characterization of EOC identified 25 compounds representing 98.19% of the total oil. The major compounds from this oil were z-citral (53.21%), neryl acetate (13.06%), geranyl acetate (10.33%), and limonene (4.23%). Aspirin induced a decrease in cell viability as well as an increase in superoxide dismutase (SOD) and catalase (CAT) activities. Contrariwise, the co-exposure of cells to aspirin and EOC alleviated every above syndrome by an increase in cell survival and decrease in SOD and CAT activities. In conclusion, the essential oil of C. limon has a potent cytoprotective effect against aspirin-induced toxicity in IEC-6 cells.

  18. Beneficial effect of aspirin on renal function post-cardiopulmonary bypass.

    Science.gov (United States)

    Gerrah, Rabin; Izhar, Uzi

    2003-12-01

    Urine thromboxane, plasma creatinine, and creatinine clearance were determined perioperatively in 20 patients undergoing coronary bypass surgery. Ten patients took aspirin until the day of surgery, and 10 discontinued aspirin at least one week before surgery. A significant increase in urine thromboxane following establishment of cardiopulmonary bypass was observed only in the control group. Plasma creatinine increased in the control group on the 1st postoperative day (from 81.9 +/- 13.2 to 97.6 +/- 13.2 micromol.L(-1), p = 0.02) and decreased next day to the preoperative level (82.7 +/- 9 micromol.L(-1), p = 0.03). In the aspirin group, creatinine remained unchanged on the 1st postoperative day (89.4 +/- 14.2 vs. 87.2 +/- 7.7 micromol.L(-1), p = 0.6), and increased significantly on the 2nd day (101.4 +/- 8.5 micromol.L(-1), p = 0.01). The aspirin group had higher creatinine levels (p < 0.0001) and lower creatinine clearance (60.2 +/- 16.5 vs. 82 +/- 25.7 mL.min(-1), p < 0.0001) than the control group on the 2nd postoperative day. A significant positive correlation was seen between urine thromboxane and creatinine on day 2 in both groups (r = 0.6). Aspirin administrated before coronary surgery may have a beneficial effect on renal function, probably mediated by its antiplatelet activity and thromboxane inhibition.

  19. 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.

  20. Effect of Glucose or Fat Challenge on Aspirin Resistance in Diabetes

    Directory of Open Access Journals (Sweden)

    Hussein N. Yassine

    2010-01-01

    Full Text Available Aspirin has lower antiplatelet activity in diabetic patients. Our aim is to study the roles of acute hyperglycemia and hyperlipidemia on aspirin function in diabetic subjects with and without cardiovascular disease. Using urine thromboxane (pg/mg creatinine and VerifyNow (Aspirin Resistance Measures-ARU, we investigated diabetic subjects during a 2-hour glucose challenge (n=49 or a 4-hour fat challenge (n=11. All subjects were currently taking aspirin (81 or 325 mg. After fat ingestion, urine thromboxane increased in all subjects (Mean ± SE before: after (1209 ± 336: 1552 ±371, P=.01, while we noted a trend increase in VerifyNow measures (408±8: 431±18, P=.1. The response to glucose ingestion was variable. Diabetic subjects with cardiac disease and dyslipidemia increased thromboxane (1693±364: 2799 ± 513, P<.05 and VerifyNow (457.6 ± 22.3: 527.1 ± 25.8, P<.05 measures after glucose. We conclude that saturated fat ingestion increases in vivo thromboxane production despite aspirin therapy.

  1. Aspirin, platelets, and cancer: The point of view of the internist.

    Science.gov (United States)

    Santilli, F; Boccatonda, A; Davì, G

    2016-10-01

    Growing evidence suggests the beneficial effect of aspirin against some types of cancer, particularly of the gastrointestinal tract, and it has been provided for an effect both in cancer prevention as well as in survival improvement of cancer patients. Aspirin benefits increase with duration of treatment, especially after 10years of treatment. The inhibition of platelet activation at sites of gastrointestinal mucosal lesions could be the primary mechanism of action of low-dose aspirin. Indeed, the formation of tumor cell-induced platelet aggregates may favor immune evasion, by releasing angiogenic and growth factors, and also by promoting cancer cell dissemination. Moreover, platelets may contribute to aberrant COX-2 expression in colon carcinoma cells, thereby contributing to downregulation of oncosuppressor genes and upregulation of oncogenes, such as cyclin B1. Platelet adhesion to cancer cells leads also to an increased expression of genes involved in the EMT, such as the EMT-inducing transcription factors ZEB1 and TWIST1 and the mesenchymal marker vimentin. The aspirin-mediated inactivation of platelets may restore antitumor reactivity by blocking the release of paracrine lipid and protein mediators that induce COX-2 expression in adjacent nucleated cells at sites of mucosal injury. Thus, recent findings suggest interesting perspectives on "old" aspirin and NSAID treatment and/or "new" specific drugs to target the "evil" interactions between platelets and cancer for chemoprevention. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

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

  3. 21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c) NAS/NRC...

  4. A critical appraisal of the phenomenon of aspirin resistance

    DEFF Research Database (Denmark)

    Svenstrup Poulsen, Tina; Risom Kristensen, Søren; Atar, Dan

    2005-01-01

    Aspirin is the mainstay antiplatelet treatment in patients with high risk of cardiovascular atherothrombotic events, and its beneficial effect is documented in several clinical trials. Nevertheless, the effectiveness of aspirin has been questioned by the emergence of the concept of 'aspirin...

  5. PIXE analysis of trace metals in aspirin-treated rats

    Energy Technology Data Exchange (ETDEWEB)

    Van Rinsvelt, H.A.; Sater, R.; Hurd, R.W.; Andres, J.M.

    1985-01-01

    Aspirin is known to complex metals, yet its effect on trace metals of the body remains poorly characterized. Chronic aspirin treatment of rats for one week produced significant alterations of serum iron, zinc, and selenium, and liver selenium and copper. Implications of metal complexation on the mechanism of action of aspirin and the association with Reye's Syndrome are discussed.

  6. PIXE analysis of trace metals in aspirin-treated rats

    Science.gov (United States)

    Van Rinsvelt, H. A.; Sater, R.; Hurd, R. W.; Andres, J. M.

    1985-05-01

    Aspirin is known to complex metals, yet its effect on trace metals of the body remains poorly characterized. Chronic aspirin treatment of rats for one week produced significant alterations of serum iron, zinc, and selenium, and liver selenium and copper. Implications of metal complexation on the mechanism of action of aspirin and the association with Reye's Syndrome are discussed.

  7. Outcomes after complete endoscopic sinus surgery and aspirin desensitization in aspirin-exacerbated respiratory disease.

    Science.gov (United States)

    Adappa, Nithin D; Ranasinghe, Viran J; Trope, Michal; Brooks, Steven G; Glicksman, Jordan T; Parasher, Arjun K; Palmer, James N; Bosso, John V

    2018-01-01

    In this study we assessed patient outcomes after complete endoscopic sinus surgery (ESS) and aspirin desensitization for patients with aspirin-exacerbated respiratory disease (AERD). A retrospective chart review was conducted for patients with aspirin challenge-proven AERD who underwent complete ESS followed by aspirin desensitization. Outcomes assessed included need for revision surgery and quality-of-life measures using the 22-item Sino-Nasal Outcomes Test (SNOT-22). Data were collected preoperatively, postoperatively prior to desensitization, and then at intervals post-desensitization through 30 months after aspirin desensitization. A longitudinal linear mixed-effects model was used for data analysis. Thirty-four patients met the inclusion criteria for this study. Thirty-two patients successfully completed aspirin desensitization and were subsequently followed for 30 months after desensitization. Two patients were unable to complete desensitization. Five patients discontinued aspirin maintenance therapy due to gastrointestinal and respiratory side effects. Within the follow-up period, there were only 3 (9.4%) revision sinus surgeries. Notably, 1 of these revision cases occurred in a patient who had discontinued aspirin maintenance therapy. After surgical treatment and prior to desensitization patients had significant reductions in SNOT-22 scores. Our results demonstrate that total SNOT-22 scores remained statistically unchanged from immediate post-desensitization throughout the 30-month follow-up period. Complete sinus surgery followed by timely aspirin desensitization and maintenance therapy is an effective combination in the long-term management of sinus disease in patients with AERD. © 2017 ARS-AAOA, LLC.

  8. Inhibition of Pancreatic Intraepithelial Neoplasia Progression to Carcinoma by Nitric Oxide-Releasing Aspirin in p48Cre/+-LSL-KrasG12D/+ Mice

    Directory of Open Access Journals (Sweden)

    Chinthalapally V. Rao

    2012-09-01

    Full Text Available Nitric oxide-releasing aspirin (NO-aspirin represents a novel class of promising chemopreventive agents. Unlike conventional nonsteroidal anti-inflammatory drugs, NO-aspirin seems to be free of adverse effects while retaining the beneficial activities of its parent compound. The effect of NO-aspirin on pancreatic carcinogenesis was investigated by assessing the development of precursor pancreatic lesions and adenocarcinomas in KrasG12D/+ transgenic mice that recapitulate human pancreatic cancer progression. Six-week-old male p48Cre/+-LSL-KrasG12D/+ transgenic mice (20 per group were fed diets containing 0, 1000, or 2000 ppm NO-aspirin. The development of pancreatic tumors was monitored by positron emission tomography imaging. All mice were killed at the age of 41 weeks and assessed for pancreatic intraepithelial neoplasia (PanIN and pancreatic ductal adenocarcinoma (PDAC and for molecular changes in the tumors. Our results reveal that NO-aspirin at 1000 and 2000 ppm significantly suppressed pancreatic tumor weights, PDAC incidence, and carcinoma in situ (PanIN-3 lesions. The degree of inhibition of PanIN-3 and carcinoma was more pronounced with NO-aspirin at 1000 ppm (58.8% and 48%, respectively than with 2000 ppm (47% and 20%, respectively. NO-aspirin at 1000 ppm significantly inhibited the spread of carcinoma in the pancreas (∼97%; P < .0001. Decreased expression of cyclooxygenase (COX; with ∼42% inhibition of total COX activity, inducible nitric oxide synthase, proliferating cell nuclear antigen, Bcl-2, cyclin D1, and β-catenin was observed, with induction of p21, p38, and p53 in the pancreas of NO-aspirin-treated mice. These results suggest that low-dose NO-aspirin possesses inhibitory activity against pancreatic carcinogenesis by modulating multiple molecular targets.

  9. Esterase-D and chromosome patterns in Central Amazon piranha (Serrasalmus rhombeus Linnaeus, 1766 from Lake Catalão

    Directory of Open Access Journals (Sweden)

    Aylton Saturnino Teixeira

    2006-01-01

    Full Text Available This study presents additional genetic data on piranha (Serrasalmus rhombeus Linnaeus, 1766 complex previously diagnosed due to the presence of distinct cytotypes 2n = 58 and 2n = 60. Three esterase-D enzyme loci (Est-D1, Est-D2 and Est-D3 were examined and complemented with chromosomal data from 66 piranha specimens collected from Lake Catalão. For all specimens the Est-D1 and Est-D2 loci were monomorphic. In contrast, the Est-D3 locus was polymorphic with genotypes and alleles being differentially distributed in the previously described cytotypes and served as the basis for detecting a new cytotype (2n = 60 B. In cytotype 2n = 58 the Est-D3 locus was also polymorphic and presented Mendelian allelic segregation with four genotypes (Est-D3(11, Est-D3(12, Est-D3(22 and Est-D3(33 out of six theoretically possible genotypes, presumably encoded by alleles Est-D3¹ (frequency = 0.237, EsT-D3² (0.710 and Est-D3³ (0.053. A Chi-squared (chi2 test for Hardy-Weinberg equilibrium was applied to the Est-D3 locus and revealed a genetic unbalance in cytotype 2n = 58, indicating the probable existence in the surveyed area of different stocks for that karyotypic structure. A silent null allele (Est-D3(0 with a high frequency (0.959 occurred exclusively in the 2n = 60 cytotype. On the other hand, the new cytotype 2n = 60 B described here for the first time was monomorphic for the presumably fixed Est-D3³ allele. The data as a whole should contribute to the better understanding the rhombeus complex taxonomic status definition in the Central Amazon.

  10. Do Aspirin and Other Antiplatelet Drugs Reduce the Mortality in Critically Ill Patients?

    Directory of Open Access Journals (Sweden)

    Wolfgang Lösche

    2012-01-01

    Full Text Available Platelet activation has been implicated in microvascular thrombosis and organ failure in critically ill patients. In the first part the present paper summarises important data on the role of platelets in systemic inflammation and sepsis as well as on the beneficial effects of antiplatelet drugs in animal models of sepsis. In the second part the data of retrospective and prospective observational clinical studies on the effect of aspirin and other antiplatelet drugs in critically ill patients are reviewed. All of these studies have shown that aspirin and other antiplatelet drugs may reduce organ failure and mortality in these patients, even in case of high bleeding risk. From the data reviewed here interventional prospective trials are needed to test whether aspirin and other antiplatelet drugs might offer a novel therapeutic option to prevent organ failure in critically ill patients.

  11. Aspirin ameliorates cerebral infarction through regulation of TLR4/NF‑κB‑mediated endoplasmic reticulum stress in mouse model.

    Science.gov (United States)

    Wang, Xin; Shen, Bin; Sun, Dezhou; Cui, Xiangyu

    2018-01-01

    Cerebral infarction is a cerebrovascular disease caused by local brain ischemic necrosis or softening, which is associated with diabetes, obesity, hypertension and rheumatic heart arrhythmia. Previous studies have indicated that aspirin is a potential oral anticoagulant in the treatment of cerebral ischemic stroke. However, the potential mechanism mediated by aspirin in cerebral infarction therapy is not well understood. The present study analyzed the therapeutic effects of aspirin on cerebral infarction and investigated the underlying molecular mechanism of aspirin‑ameliorated benefits for thrombolysis. The results demonstrated that aspirin inhibited inflammation and apoptosis of cerebrovascular endothelial cells in a mouse model of cerebral infarction. Aspirin treatment suppressed toll‑like receptor (TLR)4 and nuclear factor (NF)‑κB expression in cerebrovascular endothelial cells. Endoplasmic reticulum (ER) stress was suppressed by aspirin treatment through the downregulation of protein kinase R‑like endoplasmic reticulum kinase, eukaryotic translation initiation factor 2 subunit 1 and C/EBP homologous protein expression levels in cerebrovascular endothelial cells. It was identified that knockdown of TLR4 inhibited aspirin‑mediated downregulation of NF‑κB signaling pathway and ER stress in cerebrovascular endothelial cells. Expression levels of adenosine diphosphate plasminogen activator inhibitors, von Willebrand factor and thromboxane were downregulated in cerebrovascular endothelial cells and in serum in experimental mice. The results demonstrated that aspirin was beneficial forthrombolysis by decreasing thrombin‑activatable fibrinolysis inhibitor and plasminogen activator inhibitor‑1 expression in a mouse model of cerebral infarction. These results suggested that aspirin may improve cerebral infarction by downregulating TLR4/NF‑κB‑mediated ER stress in a mouse model.

  12. Pectin Esterase in Relation to Leaf Abscission in Coleus and Phaseolus1

    Science.gov (United States)

    Lamotte, Clifford E.; Gochnauer, Carl; Lamotte, Lynn R.; Mathur, J. Raj; Davies, Leslie L. R.

    1969-01-01

    Pectin esterase (PE) activities in abscission zones, other portions of leaves, and adjacent stem tissues were compared in attached leaves and abscissing petioles (previously debladed) of Coleus blumei Benth. and Phaseolus vulgaris L., cv. Canadian Wonder. Earlier findings of Osborne in bean were confirmed and changes in PE activity in coleus were shown to resemble those in bean in some respects. In both plants PE was lower in the distal portion of abscission zones of abscissing petioles than in that portion of attached leaves but this difference was not as large or as consistently clear-cut in coleus as in bean. The general level of PE activity was an order of magnitude lower and changes associated with abscission were smaller in coleus than in bean. Auxin treatment of debladed petioles of coleus prevented abscission and resulted in small increases in PE activity in abscission zones and most of the other regions sampled. The largest increase was observed in the stem tissue adjacent to the attached leaf opposite the debladed, auxin treated one. The activity of coleus PE was highest in the pH range from 7.3 to 7.6. The pH of distal tissue from abscission zones of abscissing petioles was 5.8. This was 0.7 pH units lower than that of proximal tissue from the same zones. PE from both coleus and bean appears to be denatured by freezing and/or thawing. PMID:16657029

  13. Pectin esterase in relation to leaf abscission in coleus and Phaseolus

    Energy Technology Data Exchange (ETDEWEB)

    LaMotte, C.E.; Gochnauer, C.; LaMotte, L.R.; Mathur, J.R.; Davies, L.L.R.

    1969-01-01

    Pectin esterase (PE) activities in abscission zones, other portions of leaves, and adjacent stem tissues were compared in attached leaves and abscissing petioles (previously debladed) of Coleus blumei Benth. and Phaseolus vulgaris L., cv. Canadian Wonder. Changes in PE activity in coleus were shown to resemble those in bean in some respects. In both plants PE was lower in the distal portion of abscission zones of abscissing petioles than in that portion of attached leaves but this difference was not as large or as consistently clear-cut in coleus as in bean. The general level of PE activity was an order of magnitude lower and changes associated with abscission were smaller in coleus than in bean. Auxin treatment of debladed petioles of coleus prevented abscission and resulted in small increases in PE activity in abscission zones and most of the other regions sampled. The largest increase was observed in the stem tissue adjacent to the attached leaf opposite the debladed, auxin treated one. The activity of coleus PE was highest in the pH range from 7.3 to 7.6. The pH of distal tissue from abscission zones of abscissing petioles was 5.8. This was 0.7 pH units lower than that of proximal tissue from the same zones. PE from both coleus and bean appears to be denatured by freezing and/or thawing. 26 references, 3 figures, 2 tables.

  14. 21 CFR 173.140 - Esterase-lipase derived from Mucor miehei.

    Science.gov (United States)

    2010-04-01

    ... which completely removes the organism Mucor miehei var. Cooney et Emerson from the esterase-lipase. (d... milk products as defined in § 170.(3)(n)(31) of this chapter. Use of this food ingredient is limited to...

  15. Physicochemical characterization and tissue distribution of esterases in two salamandridae species (Mertensiella luschani and Salamandra salamandra).

    Science.gov (United States)

    Tzannetatou-Polymeni, R; Haritos, A A

    1989-01-01

    1. Tissue- and species-specificity of the electrophoretic patterns of the multiple molecular forms of esterases were observed in the urodele amphibians Mertensiella luschani luschani, M.l. helverseni and Salamandra salamandra. All esterases--distributed into two electrophoretic mobility areas in gonads, muscles and brain and into four areas in liver, stomach and intestine--were characterized as carboxylesterases. 2. M. l. luschani and S. salamandra liver esterases were electrofocused into nine and eleven major bands with pIs ranging from 4.60 to 5.65 and from 4.40 to 6.20, respectively. 3. Two size groups of esterases were observed in liver extracts of the above three subspecies by Sephadex G-200 gel filtration. The mean values of their apparent molecular weights were 70,000 and 230,000 respectively.

  16. Enzymatic Synthesis of Hydroxycinnamic Acid Glycerol Esters Using Type A Feruloyl Esterase from Aspergillus niger

    National Research Council Canada - National Science Library

    TSUCHIYAMA, Moriyasu; SAKAMOTO, Tatsuji; TANIMORI, Shinji; MURATA, Shuichi; KAWASAKI, Haruhiko

    2007-01-01

    We found that hydroxycinnamic acid (HA) glycerol esters such as 1-sinapoyl glycerol and 1-p-coumaroyl glycerol can be synthesized through a direct esterification reaction using a type A feruloyl esterase from Aspergillus niger...

  17. Esterases A5-B5 in organophosphate-resistant Culex pipiens from Italy.

    Science.gov (United States)

    Severini, C; Romi, R; Marinucci, M; Guillemaud, T; Raymond, M

    1997-04-01

    Culex pipiens mosquitos from Lignano city, Udine province, northeast Italy, were found to carry over-produced non-specific esterases A1, A2-B2 and A4-B4 or A5-B5, detected by starch gel electrophoresis, giving multiple resistance to organophosphorus insecticides. In order to differentiate between A4-B4 and A5-B5 esterases, the latter known only from Cyprus whereas the former is widespread in Italy and elsewhere, restriction fragment length polymorphism (RFLP) analysis was performed at the esterase B locus. Both B4 and B5 haplotypes were found. This is the first record of A5-B5 esterase-mediated resistance in continental Europe.

  18. Comparison of fungal carbohydrate esterases of family CE16 on artificial and natural substrates

    OpenAIRE

    Puchart, Vladimir; Agger, Jane W.; Berrin, Jean-Guy; Varnai, Aniko; Westereng, Bjorge; Biely, Peter

    2016-01-01

    The enzymatic conversion of acetylated hardwood glucuronoxylan to functional food oligomers, biochemicals or fermentable monomers requires besides glycoside hydrolases enzymes liberating acetic acid esterifying position 2 and/or 3 in xylopyranosyl (Xylp) residues. The 3-0-acetyl group at internal Xylp residues substituted by MeGlcA is the only acetyl group of hardwood acetylglucuronoxylan and its fragments not attacked by acetylxylan esterases of carbohydrate esterase (CE) families 1, 4, 5 an...

  19. 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.

  20. Oral aspirin for treating venous leg ulcers.

    Science.gov (United States)

    de Oliveira Carvalho, Paulo Eduardo; Magolbo, Natiara G; De Aquino, Rebeca F; Weller, Carolina D

    2016-02-18

    Venous leg ulcers (VLUs) or varicose ulcers are the final stage of chronic venous insufficiency (CVI), and are the most common type of leg ulcer. The development of VLUs on ankles and lower legs can occur spontaneously or after minor trauma. The ulcers are often painful and exudative, healing is often protracted and recurrence is common. This cycle of healing and recurrence has a considerable impact on the health and quality of life of individuals, and healthcare and socioeconomic costs. VLUs are a common and costly problem worldwide; prevalence is estimated to be between 1.65% to 1.74% in the western world and is more common in adults aged 65 years and older. The main treatment for a VLU is a firm compression bandage. Compression assists by reducing venous hypertension, enhancing venous return and reducing peripheral oedema. However, studies show that it only has moderate effects on healing, with up to 50% of VLUs unhealed after two years of compression. Non-adherence may be the principal cause of these poor results, but presence of inflammation in people with CVI may be another factor, so a treatment that suppresses inflammation (healing ulcers more quickly) and reduces the frequency of ulcer recurrence (thereby prolonging time between recurrent episodes) would be an invaluable intervention to complement compression treatments. Oral aspirin may have a significant impact on VLU clinical practice worldwide. Evidence for the effectiveness of aspirin on ulcer healing and recurrence in high quality RCTs is currently lacking. To assess the benefits and harms of oral aspirin on the healing and recurrence of venous leg ulcers. In May 2015 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. Additional searches were made in trial registers and reference lists of relevant publications for

  1. Application of two newly identified and characterized feruloyl esterases from Streptomyces sp. in the enzymatic production of ferulic acid from agricultural biomass.

    Directory of Open Access Journals (Sweden)

    Misugi Uraji

    Full Text Available Ferulic acid (FA, a component of hemicellulose in plant cell walls, is a phenolic acid with several potential applications based on its antioxidant properties. Recent studies have shown that feruloyl esterase (FAE is a key bacterial enzyme involved in FA production from agricultural biomass. In this study, we screened a library of 43 esterases from Streptomyces species and identified two enzymes, R18 and R43, that have FAE activity toward ethyl ferulate. In addition, we characterized their enzyme properties in detail. R18 and R43 showed esterase activity toward other hydroxycinnamic acid esters as well, such as methyl p-coumarate, methyl caffeate, and methyl sinapinate. The amino acid sequences of R18 and R43 were neither similar to each other, nor to other FAEs. We found that R18 and R43 individually showed the ability to produce FA from corn bran; however, combination with other Streptomyces enzymes, namely xylanase and α-l-arabinofuranosidase, increased FA production from biomass such as corn bran, defatted rice bran, and wheat bran. These results suggest that R18 and R43 are effective FAEs for the enzymatic production of FA from biomass.

  2. Does low-dose aspirin improve pregnancy rate in IVF/ICSI? A randomized double-blind placebo controlled trial.

    Science.gov (United States)

    Dirckx, K; Cabri, P; Merien, A; Galajdova, L; Gerris, J; Dhont, M; De Sutter, P

    2009-04-01

    It has been suggested in the literature that low-dose aspirin leads to an increased number of oocytes in IVF/ICSI as well as a higher pregnancy rate. The aim of the present study was to investigate the effect of daily administration of low-dose aspirin, compared with placebo, on pregnancy rate in IVF and ICSI. This study was a prospective, randomized, double-blind placebo controlled trial, performed in the fertility centre of the University Hospital of Ghent. Concealed allocation by computerized randomization was done by the central pharmacy of the hospital. Daily oral administration of aspirin 100 mg or placebo started before stimulation and was continued until confirmation of pregnancy by detection of fetal heart activity on ultrasound. The primary outcome measure assessed in this trial was clinical pregnancy rate per cycle. Two hundred and one couples were included in this study, 193 women (aspirin group n = 97, placebo group n = 96) started treatment and 181 underwent an embryo transfer. There were 31 clinical pregnancies (31/97 or 32%) in the aspirin group versus 30 (30/96 or 31%; P = 0.916; OR 1.033; 95% CI 0.565-1.890) in the placebo group. This randomized controlled trial could not show a significant difference in clinical pregnancy rate between the aspirin and the placebo group in a first or second IVF/ICSI cycle. Given the lack of evidence for a beneficial effect of low-dose aspirin, it appears that low-dose aspirin should not be prescribed routinely in IVF/ICSI treatment. ClinicalTrials.gov Identifier: NCT00644085.

  3. 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.

  4. Rivaroxaban with or without aspirin in stable cardiovascular disease

    DEFF Research Database (Denmark)

    Eikelboom, John W; Connolly, Stuart J; Bosch, Jackie

    2017-01-01

    BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive...... rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after...... a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P

  5. Nitric oxide-releasing aspirin but not conventional aspirin improves healing of experimental colitis

    Science.gov (United States)

    Zwolinska-Wcislo, Malgorzata; Brzozowski, Tomasz; Ptak-Belowska, Agata; Targosz, Aneta; Urbanczyk, Katarzyna; Kwiecien, Slawomir; Sliwowski, Zbigniew

    2011-01-01

    AIM: To determine the effect of non-selective cyclooxygenase (COX) inhibitors, selective COX-2 inhibitors and nitric oxide (NO)-releasing aspirin in the healing of ulcerative colitis. METHODS: Rats with 2,4,6 trinitrobenzenesulfon-ic acid (TNBS)-induced colitis received intragastric (ig) treatment with vehicle, aspirin (ASA) (a non-selective COX inhibitor), celecoxib (a selective COX-2 inhibitor) or NO-releasing ASA for a period of ten days. The area of colonic lesions, colonic blood flow (CBF), myeloperoxidase (MPO) activity and expression of proinflammatory markers COX-2, inducible form of nitric oxide synthase (iNOS), IL-1β and tumor necrosis factor (TNF)-α were assessed. The effects of glyceryl trinitrate (GTN), a NO donor, and 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-​tetramethyl-1H-imidazolyl-1-oxy-3-oxide, onopotassium salt (carboxy-PTIO), a NO scavenger, administered without and with ASA or NO-ASA, and the involvement of capsaicin-sensitive afferent nerves in the mechanism of healing the experimental colitis was also determined. RESULTS: Rats with colitis developed macroscopic and microscopic colonic lesions accompanied by a significant decrease in the CBF, a significant rise in colonic weight, MPO activity and plasma IL-1β and TNF-α levels. These effects were aggravated by ASA and 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560), but not celecoxib and counteracted by concurrent treatment with a synthetic prostaglandin E2 (PGE2) analog. Treatment with NO-ASA dose-dependently accelerated colonic healing followed by a rise in plasma NOx content and CBF, suppression of MPO and downregulation of COX-2, iNOS, IL-1β and TNF-α mRNAs. Treatment with GTN, the NO donor, significantly inhibited the ASA-induced colonic lesions and increased CBF, while carboxy-PTIO or capsaicin-denervation counteracted the NO-ASA-induced improvement of colonic healing and the accompanying increase in the CBF. These effects were restored by co

  6. 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

    2014-12-02

    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. Retrospective. 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. 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 history of atrial fibrillation, valvular heart disease or coagulopathy. Therefore, 1884 patients were included in our final analysis. Patients were categorised into two groups based on whether clopidogrel or 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. 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. 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. 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.

  7. 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.

  8. Reverse effect of aspirin: is the prothrombotic effect after aspirin discontinuation mediated by cyclooxygenase 2 inhibition?

    Science.gov (United States)

    Doutremepuich, Christian; Aguejouf, Omar; Eizayaga, Francisco X; Desplat, Vanessa

    2007-01-01

    While aspirin is the drug most often used to prevent cardiovascular complications, its discontinuation induces an increased risk of acute coronary syndrome and ischemic stroke in some patients. We hypothesized that infinitesimal concentrations of aspirin could persist in plasma after its discontinuation, thereby inducing a prothrombotic effect that could be due to a modification in the mechanism of action of aspirin via the cyclooxygenase 1 (COX-1) and COX-2 pathways. We studied the effects of ultra-low-dose aspirin (ULDA) as well as those of sc-560 and ns-398, specific COX-1 and COX-2 inhibitors, on induced hemorrhagic time and in a model of laser-induced thrombosis in rats. In the laser-induced thrombosis model, ULDA treatment increased the number of emboli and the duration of embolization, thereby confirming its prothrombotic effect described in previous publications. This effect was also observed in rats pretreated with sc-560 but not in those pretreated with ns-398. We demonstrated that ULDA induced a prothrombotic effect in the rats studied. This strongly suggests that a very small amount of aspirin could remain in the patient's blood after aspirin therapy, leading to cardiovascular complications. This effect may be mediated by the COX-2 pathway. Copyright 2008 S. Karger AG, Basel.

  9. Baseline Characteristics of Participants in the ASPREE (ASPirin in Reducing Events in the Elderly) Study.

    Science.gov (United States)

    McNeil, John J; Woods, Robyn L; Nelson, Mark R; Murray, Anne M; Reid, Christopher M; Kirpach, Brenda; Storey, Elsdon; Shah, Raj C; Wolfe, Rory S; Tonkin, Andrew M; Newman, Anne B; Williamson, Jeff D; Lockery, Jessica E; Margolis, Karen L; Ernst, Michael E; Abhayaratna, Walter P; Stocks, Nigel; Fitzgerald, Sharyn M; Trevaks, Ruth E; Orchard, Suzanne G; Beilin, Lawrence J; Donnan, Geoffrey A; Gibbs, Peter; Johnston, Colin I; Grimm, Richard H

    2017-10-12

    There are no primary prevention trials of aspirin with relevant geriatric outcomes in elderly people. ASPirin in Reducing Events in the Elderly (ASPREE) is a placebo-controlled trial of low-dose aspirin that will determine whether 5 years of daily 100-mg enteric-coated aspirin extends disability-free and dementia-free life in a healthy elderly population and whether these benefits outweigh the risks. Set in primary care, this randomized double-blind placebo-controlled trial has a composite primary endpoint of death, incident dementia or persistent physical disability. Participants aged 70+ years (non-minorities) or 65+ years (U.S. minorities) were free of cardiovascular disease, dementia, or physical disability and without a contraindication to, or indication for, aspirin. Baseline data include physical and lifestyle, personal and family medical history, hemoglobin, fasting glucose, creatinine, lipid panel, urinary albumin:creatinine ratio, cognition (3MS, HVLT-R, COWAT, SDMT), mood (CES-D-10), physical function (gait speed, grip strength), Katz activities of daily living and quality of life (SF-12). Recruitment ended in December 2014 with 16,703 Australian and 2,411 U.S. participants, a median age of 74 (range 65-98) years and 56% women. Approximately 55% of the U.S. cohort were from minority groups; 9% of the total cohort. Proportions with hypertension, overweight, and chronic kidney disease were similar to age-matched populations from both countries although lower percentages had diabetes, dyslipidemia, and osteoarthritis. Findings from ASPREE will be generalizable to a healthier older population in both countries and will assess whether the broad benefits of daily low-dose aspirin in prolonging independent life outweigh the risks.

  10. Highly efficient electro-oxidation catalyst under ultra-low voltage for degradation of aspirin.

    Science.gov (United States)

    Kang, Xiaolei; Sun, Wei; Cao, Limei; Yang, Ji

    2017-11-01

    A novel cryptomelane-Ir (cry-Ir) electrode is prepared for Ir to enter into the cryptomelane (named as cry-Mn) structure and used for aspirin degradation. This catalyst can efficiently reduce the Ir usage from 85 to 34%. Also, the onset potential of cry-Ir is about 1.40 V and the over potential is about 0.34 V at 10 mA cm -2 , indicating that cry-Ir has an excellent oxygen evolution reaction (OER) activity to produce oxidizing species and can decrease electrolytic voltage during the electro-oxidation process. So, the electrical efficiency per log order (EE/O) for cry-Ir electrode is only 5% of PbO 2 electrode, which is the best electrode for organic degradation. Also, cry-Ir has large tunnel size which favors insertion of aspirin molecule into cry-Ir structure and enhances the contact between reactive intermediates and the contaminant. Using cry-Ir as anode, 100% aspirin removal and 55% chemical oxygen demand (COD) removal could be obtained at 4 V. We also compare cry-Ir electrode with IrO 2 and find that IrO 2 anode can only eliminate 20% aspirin under the same condition. As a result, cry-Ir is a promising anode material for organic pollutant degradation. Graphical abstract Aspirin removal after 4h under different voltages. Aspirin removal on IrO 2 /Ti-f and cry-Ir/Ti-f after 4h.

  11. [The Role of Aspirin in Preeclampsia Prevention: State of the Art].

    Science.gov (United States)

    Campos, Ana

    2015-01-01

    The role of acetyl salicylic acid (ASA or aspirin) in preeclampsia prevention and in other complications has been subject to studies and controversies for the last 30 years. The first research results concerning the role of placenta in preeclampsia have been published by the end of seventies and they showed an increase in the platelet activity and a prostaglandin synthesis disturbance, as a consequence of a deficient placentation. In the last twenty years of the XX century important studies were published on the aspirinprophylactic role in preeclampsia risk reduction. To analyze published studies about Aspirin use for preeclampsia prevention and about the more adequate dosage to be administered, Medline was used for searching the most relevant prospective research papers on this subject in order to evaluate current evidence about the use of aspirin in this context. Relevant citations were extracted from Embase, PubMed and the Cochrane Central Register of Controlled Trials. We divided the studies in two groups; one with aspirine administration before 16 weeks and the other having a larger use, between the first and the third trimester. The first group of studies, with a lesser number of cases but an earlier time of administration until 16 weeks, concluded that a positive role of aspirine was possible in reducing severity of preeclampsia; the second group with a larger number of cases but less restricted conditions and timing of administration, had controversial results, with reduced positive actions of the drug. Meta-analysis of these published studies concluded that favorable results were associated to stricter criteria and ideal timing for startingthe drug. As we do not have other pharmacologic alternatives, low dosage of Aspirin between 80-150 mg a day in the first trimester and until 16 weeks, at evening time, is a possible choice in cases of risk, and is still contributing for an early preeclampsia risk reduction.

  12. Inappropriate combination of warfarin and aspirin.

    Science.gov (United States)

    Turan, Burak; Demir, Hakan; Mutlu, Ayhan; Daşlı, Tolga; Erkol, Ayhan; Erden, İsmail

    2016-03-01

    A combination of warfarin and aspirin is associated with increased bleeding compared with warfarin monotherapy. The aim of the study was to investigate the incidence and appropriateness of the combination of warfarin and aspirin in patients with atrial fibrillation (AF) or mechanical heart valve (MHV). This cross-sectional study included consecutive patients with AF or MHV on chronic warfarin therapy (>3 months) without acute coronary syndrome or have not undergone a revascularization procedure in the preceding year. Medical history, concomitant diseases, and treatment data were acquired through patient interviews and from hospital records. Three hundred and sixty patients (213 with AF, 147 with MHV) were included. In those with AF, a significantly higher warfarin-aspirin combination was observed with concomitant vascular disease (38.8% vs. 14.6%), diabetes (36.6% vs. 16.3%), statin therapy (40% vs. 16.9%), left ventricular systolic dysfunction (33.3% vs. 17.5%) (paspirin combination were concomitant vascular disease, diabetes, and (younger) age in patients with AF and were concomitant AF and male sex in patients with MHV. Interestingly, the incidence of combination therapy was found to increase with a higher HAS-BLED score in both patients with AF and MHV (paspirin was found to be prescribed to patients with AF mainly for the prevention of cardiovascular events, for which warfarin monotherapy usually suffices. On the other hand, co-treatment with aspirin appeared to be underused in patients with MHV.

  13. [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.

  14. Aspirin augments hyaluronidase induced adhesion inhibition ...

    African Journals Online (AJOL)

    Postoperative adhesions occur after virtually all abdomino-pelvic surgery and are the leading cause of intestinal obstruction and other gynaecologic problems. We used an animal model to test the efficacy of combined administration of aspirin and hyaluronidase on adhesion formation. Adhesions were induced using ...

  15. Van der Waals Interactions in Aspirin

    Science.gov (United States)

    Reilly, Anthony; Tkatchenko, Alexandre

    2015-03-01

    The ability of molecules to yield multiple solid forms, or polymorphs, has significance for diverse applications ranging from drug design and food chemistry to nonlinear optics and hydrogen storage. In particular, aspirin has been used and studied for over a century, but has only recently been shown to have an additional polymorphic form, known as form II. Since the two observed solid forms of aspirin are degenerate in terms of lattice energy, kinetic effects have been suggested to determine the metastability of the less abundant form II. Here, first-principles calculations provide an alternative explanation based on free-energy differences at room temperature. The explicit consideration of many-body van der Waals interactions in the free energy demonstrates that the stability of the most abundant form of aspirin is due to a subtle coupling between collective electronic fluctuations and quantized lattice vibrations. In addition, a systematic analysis of the elastic properties of the two forms of aspirin rules out mechanical instability of form II as making it metastable.

  16. 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.

  17. 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

  18. Heterologous production and characterization of a chlorogenic acid esterase from Ustilago maydis with a potential use in baking.

    Science.gov (United States)

    Nieter, Annabel; Kelle, Sebastian; Takenberg, Meike; Linke, Diana; Bunzel, Mirko; Popper, Lutz; Berger, Ralf G

    2016-10-15

    Ustilago maydis, an edible mushroom growing on maize (Zea mays), is consumed as the food delicacy huitlacoche in Mexico. A chlorogenic acid esterase from this basidiomycete was expressed in good yields cultivating the heterologous host Pichia pastoris on the 5L bioreactor scale (reUmChlE; 45.9UL(-1)). In contrast to previously described chlorogenic acid esterases, the reUmChlE was also active towards feruloylated saccharides. The enzyme preferred substrates with the ferulic acid esterified to the O-5 position of arabinose residues, typical of graminaceous monocots, over the O-2 position of arabinose or the O-6 position of galactose residues. Determination of kcat/Km showed that the reUmChlE hydrolyzed chlorogenic acid 18-fold more efficiently than methyl ferulate, p-coumarate or caffeate. Phenolic acids were released by reUmChlE from natural substrates, such as destarched wheat bran, sugar beet pectin and coffee pulp. Treatment of wheat dough using reUmChlE resulted in a noticeable softening indicating a potential application of the enzyme in bakery and confectionery. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. [Cloning of feruloyl esterase gene from Aspergillus niger h408 and high-efficient expression in Pichia pastoris].

    Science.gov (United States)

    Zhou, Yanyan; Liu, Xinli; Chen, Jing; Hu, Hongyu; Hou, Yunhua

    2014-08-04

    To achieve the high-efficiency expression of feruloyl estrase gene (AnfaeA) from Aspergillus niger h408 in Pichia pastoris and characterize the recombinant feruloyl esterase (FAE). Using gene splicing by overlap extension (SOE), we cloned AnfaeA gene from A. niger h408 and subcloned into T vector for sequencing analysis. The expression vector pPIC9K-Anfae was constructed by the ligation of the Anfae A gene into the shuttle vector pPIC9K. The plasmid pPIC9K-Anfae was linearized and then electrotransformed into P. pastoris GS115. The recombinant strain with high level of FAE activity was obtained through plate screening. Effects of pH and temperature on recombinant FAE were determined by ultraviolet (UV) methods. We have successfully cloned and high-efficiently expressed the AnfaeA gene (GenBank: KF911349) from A. niger h408 in P. pastoris GS115. The sequencing result showed that the length of Anfae A was 783bp. The gene contained an Open Reading Frame encoding 260 amino acids and was similar to feruloyl esterase A from A. niger by homology analysis. The deduced amino acids contained a typical active lid and catalytic triad of lipase. The SDS-PAGE result indicated that molecular weight of the recombinant FAE was about 30 kDa and the activity of the recombinant enzyme was 24.72 U/mL. The specific activity of the recombinant FAE was 40.84 U/mg. Compared with A. niger h408, the recombinant enzyme activity increased about to 1100 times. The optimal temperature and pH for recombinant FAE was 50 degrees C and 5.0, respectively. Recombinant FAE showed nearly 80% of its maximal activity at 60 degrees C and was active in the pH range 4.0-9.0. The high-efficient expression of AnfaeA gene in P. pastoris provided a prerequisite for achieving industrial application in feed and paper-making industry. In addition, the results established the experimental basis for further improvement of recombinant feruloyl esterase by directed evolution.

  20. Mycobacteriophage Lysin B is a novel mycolylarabinogalactan esterase

    Energy Technology Data Exchange (ETDEWEB)

    Payne, K.; Sun, Q.; Sacchettini, J.; Hatfull, G.F.; (Pitt)

    2010-08-27

    Mycobacteriophages encounter a unique problem among phages of Gram-positive bacteria, in that lysis must not only degrade the peptidoglycan layer but also circumvent a mycolic acid-rich outer membrane covalently attached to the arabinogalactan-peptidoglycan complex. Mycobacteriophages accomplish this by producing two lysis enzymes, Lysin A (LysA) that hydrolyses peptidoglycan, and Lysin B (LysB), a novel mycolylarabinogalactan esterase, that cleaves the mycolylarabinogalactan bond to release free mycolic acids. The D29 LysB structure shows an {alpha}/{beta} hydrolase organization with a catalytic triad common to cutinases, but which contains an additional four-helix domain implicated in the binding of lipid substrates. Whereas LysA is essential for mycobacterial lysis, a Giles {Delta}lysB mutant mycobacteriophage is viable, but defective in the normal timing, progression and completion of host cell lysis. We propose that LysB facilitates lysis by compromising the integrity of the mycobacterial outer membrane linkage to the arabinogalactan-peptidoglycan layer.

  1. Structural analysis of thermostabilizing mutations of cocaine esterase

    Energy Technology Data Exchange (ETDEWEB)

    Narasimhan, Diwahar; Nance, Mark R.; Gao, Daquan; Ko, Mei-Chuan; Macdonald, Joanne; Tamburi, Patricia; Yoon, Dan; Landry, Donald M.; Woods, James H.; Zhan, Chang-Guo; Tesmer, John J.G.; Sunahara, Roger K. (Michigan); (Columbia); (Kentucky)

    2010-09-03

    Cocaine is considered to be the most addictive of all substances of abuse and mediates its effects by inhibiting monoamine transporters, primarily the dopamine transporters. There are currently no small molecules that can be used to combat its toxic and addictive properties, in part because of the difficulty of developing compounds that inhibit cocaine binding without having intrinsic effects on dopamine transport. Most of the effective cocaine inhibitors also display addictive properties. We have recently reported the use of cocaine esterase (CocE) to accelerate the removal of systemic cocaine and to prevent cocaine-induced lethality. However, wild-type CocE is relatively unstable at physiological temperatures ({tau}{sub 1/2} {approx} 13 min at 37 C), presenting challenges for its development as a viable therapeutic agent. We applied computational approaches to predict mutations to stabilize CocE and showed that several of these have increased stability both in vitro and in vivo, with the most efficacious mutant (T172R/G173Q) extending half-life up to 370 min. Here we present novel X-ray crystallographic data on these mutants that provide a plausible model for the observed enhanced stability. We also more extensively characterize the previously reported variants and report on a new stabilizing mutant, L169K. The improved stability of these engineered CocE enzymes will have a profound influence on the use of this protein to combat cocaine-induced toxicity and addiction in humans.

  2. Platelet hyperfunction is decreased by additional aspirin loading in patients presenting with myocardial infarction on daily aspirin therapy.

    Science.gov (United States)

    Fuchs, Ingrid; Spiel, Alexander O; Frossard, Martin; Derhaschnig, Ulla; Riedmüller, Eva; Jilma, Bernd

    2010-06-01

    Currently 162-325 mg aspirin is recommended for the treatment of acute coronary syndrome. We tested the effect of an additional loading dose of 250 mg aspirin at the onset of acute coronary syndrome in patients who were already on chronic therapy with 100 mg aspirin. This was a prospective trial in patients presenting with symptoms suggestive of acute coronary syndrome that included a randomized, double-blind, placebo-controlled trial subgroup. An emergency department in a tertiary care center. Consecutive patients with symptoms suggestive of acute coronary syndrome were enrolled, including a cohort already on chronic aspirin therapy. Patients received an intravenous infusion of 250 mg aspirin. Platelet function was measured with a platelet function analyzer in 234 patients before and after aspirin infusion. Aspirin infusion prolonged collagen epinephrine closure times in almost all patients. Aspirin infusion further lowered thromboxane B(2) levels in patients with acute coronary syndrome who were on chronic aspirin therapy before admission. Concomitantly, collagen epinephrine closure times increased by 22% from 223 secs (95% confidence interval, 192-255 secs) before to 273 secs (95% confidence interval, 252-294 secs) after aspirin infusion (p myocardial infarction on daily aspirin therapy (53%) displayed platelet hyperfunction (collagen epinephrine closure times aspirin infusion further decreased platelet function in these patients with ST-elevation myocardial infarction (30% prolongation of collagen epinephrine closure times; p myocardial infarction still displayed platelet hyperfunction (p = .02). Aspirin loading in the emergency room further reduced thromboxane B(2) levels and further inhibited platelet function in many patients with acute coronary syndrome already on 100 mg aspirin.

  3. Multiple episodes of aspirin overdose in an individual patient: a case report.

    Science.gov (United States)

    Ghosh, Debasish; Williams, Kenneth M; Graham, Garry G; Nair, Priya; Buscher, Hergen; Day, Richard O

    2014-11-19

    Aspirin overdose, though now infrequently encountered, nevertheless continues to contribute to significant morbidity and mortality. The patient described in this case report intentionally ingested overdoses of aspirin on repeated occasions. The case provided an unusual and possibly one-of-a-kind opportunity to focus on the variability in the time course of plasma salicylate concentrations with current treatment modalities of aspirin overdose in an individual patient. A 75-year-old Caucasian man who weighed 45 kg and had an extensive history of various drug overdoses and stage 3 chronic kidney disease presented to a tertiary university hospital on three occasions within 2 months after successive overdoses of aspirin. During his third admission, he overdosed with aspirin, while on the ward recovering from the previous aspirin overdose. The overdoses were categorized as "potentially lethal" on two occasions and as "serious" in the other two, based on the alleged dose of aspirin ingested (over 500 mg/kg in the first two overdoses, and 320 mg/kg and 498 mg/kg in the other two, respectively). However, as assessed by the observed salicylate concentrations, the ingestions would more appropriately have been categorized as being of "moderate" severity for the first and second overdose and "mild" severity for each of the others. This categorization was more consistent with the clinical severity of his admissions. A single dose of activated charcoal was administered only after the second overdose. On each occasion, he was given intravenous fluid with the aim of achieving euvolemia. Urinary alkalization was not attempted during the first admission, which was associated with the longest apparent elimination half-life of salicylate (30 hours). A plasma potassium concentration of approximately 4 mmol/L appeared to be needed for adequate urinary alkalization. In a patient with impaired renal function, intravenous fluid and urinary alkalization are the mainstays of treatment of

  4. HIGHLY METHYL ESTERIFIED SEEDS is a pectin methyl esterase involved in embryo development.

    Science.gov (United States)

    Levesque-Tremblay, Gabriel; Müller, Kerstin; Mansfield, Shawn D; Haughn, George W

    2015-03-01

    Homogalacturonan pectin domains are synthesized in a highly methyl-esterified form that later can be differentially demethyl esterified by pectin methyl esterase (PME) to strengthen or loosen plant cell walls that contain pectin, including seed coat mucilage, a specialized secondary cell wall of seed coat epidermal cells. As a means to identify the active PMEs in seed coat mucilage, we identified seven PMEs expressed during seed coat development. One of these, HIGHLY METHYL ESTERIFIED SEEDS (HMS), is abundant during mucilage secretion, peaking at 7 d postanthesis in both the seed coat and the embryo. We have determined that this gene is required for normal levels of PME activity and homogalacturonan methyl esterification in the seed. The hms-1 mutant displays altered embryo morphology and mucilage extrusion, both of which are a consequence of defects in embryo development. A significant decrease in the size of cells in the embryo suggests that the changes in embryo morphology are a consequence of lack of cell expansion. Progeny from a cross between hms-1 and the previously characterized PME inhibitor5 overexpression line suggest that HMS acts independently from other cell wall-modifying enzymes in the embryo. We propose that HMS is required for cell wall loosening in the embryo to facilitate cell expansion during the accumulation of storage reserves and that its role in the seed coat is masked by redundancy. © 2015 American Society of Plant Biologists. All Rights Reserved.

  5. Potential human cholesterol esterase inhibitor design: benefits from the molecular dynamics simulations and pharmacophore modeling studies.

    Science.gov (United States)

    John, Shalini; Thangapandian, Sundarapandian; Lee, Keun Woo

    2012-01-01

    Human pancreatic cholesterol esterase (hCEase) is one of the lipases found to involve in the digestion of large and broad spectrum of substrates including triglycerides, phospholipids, cholesteryl esters, etc. The presence of bile salts is found to be very important for the activation of hCEase. Molecular dynamic simulations were performed for the apoform and bile salt complexed form of hCEase using the co-ordinates of two bile salts from bovine CEase. The stability of the systems throughout the simulation time was checked and two representative structures from the highly populated regions were selected using cluster analysis. These two representative structures were used in pharmacophore model generation. The generated pharmacophore models were validated and used in database screening. The screened hits were refined for their drug-like properties based on Lipinski's rule of five and ADMET properties. The drug-like compounds were further refined by molecular docking simulation using GOLD program based on the GOLD fitness score, mode of binding, and molecular interactions with the active site amino acids. Finally, three hits of novel scaffolds were selected as potential leads to be used in novel and potent hCEase inhibitor design. The stability of binding modes and molecular interactions of these final hits were re-assured by molecular dynamics simulations.

  6. Duration of increased bleeding tendency after cessation of aspirin therapy.

    LENUS (Irish Health Repository)

    Cahill, Ronan A

    2012-02-03

    BACKGROUND: Aspirin has a significant effect on hemostasis, so it is often recommended that patients taking aspirin discontinue treatment before elective surgery. While off aspirin, these patients may be at risk of thrombosis. The optimum period of time that aspirin should be withheld is controversial. The aim of this study was to establish the duration of the antihemostatic effect of prolonged aspirin therapy. STUDY DESIGN: In a prospective study, 51 healthy volunteers were randomly assigned into 3 groups, each receiving an identical tablet for 14 days. One group received a placebo tablet; individuals in the other two groups received either 75 mg or 300 mg of aspirin once a day. Template bleeding times and specific platelet function testing (using the PFA-100; Dade Behring) were carried out on subjects before therapy and again after its completion until they returned to baseline. RESULTS: Thirty-eight volunteers complied sufficiently with the protocol to provide useful results. All bleeding times normalized within 96 hours and all platelet function tests within 144 hours after stopping aspirin. There was no demonstrable hemostatic defect in any volunteer persisting by or beyond the sixth day after treatment cessation. There was no apparent difference in duration of effect between those taking either 75 mg or 300 mg of aspirin. CONCLUSIONS: This study uses sensitive measures of platelet function to demonstrate the duration of increased bleeding tendency after withdrawal of aspirin therapy. It supports discontinuation of aspirin therapy 5 days before elective surgery (with the operation being performed on the sixth day).

  7. The role of aspirin in childhood tuberculous meningitis.

    Science.gov (United States)

    Schoeman, Johan F; Janse van Rensburg, Anita; Laubscher, Jacoba A; Springer, Priscilla

    2011-08-01

    Arterial stroke is the main cause of poor outcome in childhood tuberculous meningitis. Aspirin has an antithrombotic action at low dose and anti-ischemic and anti-inflammatory properties, which are dose-related. The aim of the study was to explore the possible benefits of aspirin in children with tuberculous meningitis. A total of 146 consecutive children with a diagnosis of probable tuberculous meningitis were studied. Patients were randomized into 3 groups: (1) placebo group, (2) low-dose aspirin group, and (3) high-dose aspirin group. Twenty-nine additional patients who received aspirin before admission were excluded from the randomized study, but continued on low-dose aspirin. Aspirin, irrespective of dose, did not show any significant benefit regarding morbidity (hemiparesis and developmental outcome) and mortality. Aspirin was well tolerated, but 1 death was probably related to aspirin. The fact that the outcome of the high-dose aspirin group compared favorably with the other treatment groups despite younger age and more severe neurological involvement at baseline needs further investigation.

  8. Mechanism of action of novel NO-releasing furoxan derivatives of aspirin in human platelets.

    Science.gov (United States)

    Turnbull, Catriona M; Cena, Clara; Fruttero, Roberta; Gasco, Alberto; Rossi, Adriano G; Megson, Ian L

    2006-06-01

    Incorporation of a nitric oxide (NO)-releasing moiety in aspirin can overcome its gastric side effects. We investigated the NO-release patterns and antiplatelet effects of novel furoxan derivatives of aspirin (B8 and B7) in comparison to existing antiplatelet agents. Cyclooxygenase (COX) activity was investigated in purified enzyme using an electron paramagnetic resonance-based technique. Concentration-response curves for antiplatelet agents +/- the soluble guanylate cyclase inhibitor, ODQ (50 microM) were generated in platelet-rich plasma (PRP) and washed platelets (WP) activated with collagen using turbidometric aggregometry. NO was detected using an isolated NO electrode. The furoxan derivatives of aspirin (B8, B7) and their NO-free furazan equivalents (B16, B15; all 100 microM) significantly inhibited COX activity (P aspirin-independent, cGMP-dependent inhibition of collagen-induced platelet aggregation in WP. B8 was more potent than B7 (PRP IC(50) = 0.62 +/- 0.1 microM for B8; 400 +/- 89 microM for B7; P aspirin hybrids was undetectable in buffer alone, but was accelerated in the presence of either plasma or plasma components, albumin (4%), glutathione (GSH; 3 microM) and ascorbate (50 microM), the effects of which were additive for B7 but not B8. NO generation from furoxans was greatly enhanced by platelet extract, an effect that could largely be explained by the synergistic effect of intracellular concentrations of GSH (3 mM) and ascorbate (1 mM). We conclude that the decomposition of furoxan-aspirin hybrids to generate biologically active NO is catalysed by endogenous agents which may instil a potential for primarily intracellular delivery of NO. The blunting of the aspirin effects of furoxan hybrids is likely to be due to loss of the acetyl moiety in plasma; the observed antiplatelet effects are thereby primarily mediated via NO release. Compounds of this class might represent a novel means of inhibiting platelet aggregation by a combination of NO

  9. 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.

  10. Aspirin overutilization for the primary prevention of cardiovascular disease

    Directory of Open Access Journals (Sweden)

    VanWormer JJ

    2014-12-01

    Full Text Available Jeffrey J VanWormer,1 Aaron W Miller,2 Shereif H Rezkalla3 1Center for Clinical Epidemiology and Population Health, 2Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, WI, USA; 3Department of Cardiology, Marshfield Clinic, Marshfield, WI, USA Background: Aspirin is commonly used for the primary prevention of cardiovascular disease (CVD in the US. Previous research has observed significant levels of inappropriate aspirin use for primary CVD prevention in some European populations, but the degree to which aspirin is overutilized in the US remains unknown. This study examined the association between regular aspirin use and demographic/clinical factors in a population-based sample of adults without a clinical indication for aspirin for primary prevention.Methods: A cross-sectional analysis was performed using 2010–2012 data from individuals aged 30–79 years in the Marshfield Epidemiologic Study Area (WI, USA. Regular aspirin users included those who took aspirin at least every other day.Results: There were 16,922 individuals who were not clinically indicated for aspirin therapy for primary CVD prevention. Of these, 19% were regular aspirin users. In the final adjusted model, participants who were older, male, lived in northern Wisconsin, had more frequent medical visits, and had greater body mass index had significantly higher odds of regular aspirin use (P<0.001 for all. Race/ethnicity, health insurance, smoking, blood pressure, and lipid levels had negligible influence on aspirin use. A sensitivity analysis found a significant interaction between age and number of medical visits, indicating progressively more aspirin use in older age groups who visited their provider frequently.Conclusion: There was evidence of aspirin overutilization in this US population without CVD. Older age and more frequent provider visits were the strongest predictors of inappropriate aspirin use. Obesity was the only significant

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-02-11

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

  12. Aspirin Has Antitumor Effects via Expression of Calpain Gene in Cervical Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sang Koo Lee

    2008-01-01

    Full Text Available Aspirin and other nonsteroidal anti-inflammatory drugs show efficacy in the prevention of cancers. It is known that they can inhibit cyclooxygenases, and some studies have shown that they can induce apoptosis. Our objective in this study was to investigate the mechanism by which aspirin exerts its apoptosis effects in human cervical cancer HeLa cells. The effect of aspirin on the gene expression was studied by differential mRNA display RT-PCR. Among the isolated genes, mu-type calpain gene was upregulated by aspirin treatment. To examine whether calpain mediates the antitumor effects, HeLa cells were stably transfected with the mammalian expression vector pCR3.1 containing mu-type calpain cDNA (pCRCAL/HeLa, and tumor formations were measured in nude mice. When tumor burden was measured by day 49, HeLa cells and pCR/HeLa cells (vector control produced tumors of 2126 mm3 and 1638 mm3, respectively, while pCRCAL/HeLa cells produced markedly smaller tumor of 434 mm3 in volume. The caspase-3 activity was markedly elevated in pCRCAL/HeLa cells. The increased activity levels of caspase-3 in pCRCAL/HeLa cells, in parallel with the decreased tumor formation, suggest a correlation between caspase-3 activity and calpain protein. Therefore, we conclude that aspirin-induced calpain mediates an antitumor effect via caspase-3 in cervical cancer cells.

  13. State of the Art: Medical treatment of aspirin exacerbated respiratory disease (AERD).

    Science.gov (United States)

    Ta, Von; Simon, Ronald

    2015-01-01

    Aspirin exacerbated respiratory disease (AERD) is characterized as adult onset asthma, nasal polyps, chronic rhinosinusitis, and hypersensitivity to a cyclooxygenase-1 (COX-1) inhibitor, viz aspirin or nonsteroidal antiinflammatory drugs (NSAIDs). The method for diagnosing AERD is with aspirin challenge, and treatment includes aspirin desensitization followed by continued daily aspirin. Although oral challenge has been the mainstay in the United States, lysyl-aspirin has been validated as a diagnostic tool for aspirin-sensitive asthma and will be discussed further in this article. The challenges with aspirin therapy surrounding endoscopy and perioperative aspirin therapy will be discussed. Additionally, daily aspirin therapy is not for everyone. Aspirin is relatively contraindicated in those with a history of gastrointestinal bleed and an absolute contraindication in pregnancy. Aspirin desensitization and subsequent treatment has been shown to be highly effective for AERD.

  14. Comparison of increased aspirin dose versus combined aspirin plus clopidogrel therapy in patients with diabetes mellitus and coronary heart disease and impaired antiplatelet response to low-dose aspirin.

    Science.gov (United States)

    Duzenli, Mehmet Akif; Ozdemir, Kurtulus; Aygul, Nazif; Soylu, Ahmet; Tokac, Mehmet

    2008-08-15

    The effects of therapy with aspirin 300 mg/day and with combined aspirin 100 mg/day plus clopidogrel 75 mg/day on platelet function were compared in patients with diabetes mellitus and coronary artery disease and impaired antiplatelet responses to aspirin 100 mg/day. The study population consisted of 151 outpatients with type II diabetes mellitus and coronary artery disease who were taking aspirin 100 mg/day. Of the 151 patients, a subgroup of subjects with impaired aspirin response were selected on the basis of the results of platelet aggregometry. Nonresponsiveness to aspirin was defined as mean aggregation > or =69% with 3 micromol/L adenosine diphosphate and mean aggregation > or =70% with 2 micromol/L collagen. Aspirin semiresponders were defined as meeting 1 but not both of these criteria. Nonresponders and semiresponders were randomized equally to aspirin 300 mg/day and aspirin 100 mg/day plus clopidogrel 75 mg/day, and aggregation tests were repeated after 2 weeks. Sixty of the 151 patients with diabetes (40%) were found to respond to aspirin inadequately. Platelet aggregation induced by adenosine diphosphate and collagen decreased significantly after aspirin 300 mg/day or combined therapy. Combined treatment was found to have a stronger inhibitory effect on platelet aggregation induced by adenosine diphosphate than aspirin 300 mg/day (p = 0.002). Impaired aspirin response was resolved by increasing the aspirin dose or adding clopidogrel to aspirin (p <0.0001 for each). However, desired platelet inhibition was achieved in significantly more patients by combined treatment than by aspirin 300 mg/day (p <0.05). In conclusion, aspirin 100 mg/day does not inhibit platelet function adequately in a significant number of patients with diabetes mellitus and coronary artery disease. Increasing the aspirin dose to 300 mg/day or adding clopidogrel to aspirin can provide adequate platelet inhibition in a significant number of those patients with impaired responses to

  15. Synthesis of fatty acid sterol esters using cholesterol esterase from Trichoderma sp. AS59.

    Science.gov (United States)

    Morinaga, Naoya; Maeda, Atsushi; Mizuno, Takayuki; Bunya, Masanori; Sugihara, Shigeo; Sugihara, Akio

    2011-05-06

    We recently reported the characterization of novel cholesterol esterase (EC. 3.1.1.13) from Trichoderma sp. and preliminary work on sterol ester synthesis. In the present study, we further examined the enzyme ability to synthesize cholesterol esters from cholesterol and free fatty acids of various chain lengths, and compared the fatty acid specificity in synthesis with that in hydrolysis. The enzyme catalyzed the synthesis of medium- and long-chain fatty acid cholesterol esters, but failed to synthesize short-chain fatty acid esters. The fatty acid specificities in the synthesis and hydrolysis of cholesterol esters were entirely different from each other. Unlike other lipolytic enzymes, the enzyme was largely independent of water content in the synthesis of cholesterol oleate, and it achieved near-complete esterification in the presence of an equimolar excess of oleic acid. Of additional interest is the finding that the addition of n-hexane markedly enhanced the esterification activities on all the medium- and long-chain saturated fatty acids used. Based on these findings, we attempted to synthesize stigmasterol stearate as a food additive to lower cholesterol levels in blood plasma, and found that the enzyme catalyzed effective synthesis of the ester without the need of dehydration during the reaction, indicating the potential utility of the enzyme in the food industry. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Feruloyl esterases from Schizophyllum commune to treat food industry side-streams.

    Science.gov (United States)

    Nieter, Annabel; Kelle, Sebastian; Linke, Diana; Berger, Ralf G

    2016-11-01

    Agro-industrial side-streams are abundant and renewable resources of hydroxycinnamic acids with potential applications as antioxidants and preservatives in the food, health, cosmetic, and pharmaceutical industries. Feruloyl esterases (FAEs) from Schizophyllum commune were functionally expressed in Pichia pastoris with extracellular activities of 6000UL(-1). The recombinant enzymes, ScFaeD1 and ScFaeD2, released ferulic acid from destarched wheat bran and sugar beet pectin. Overnight incubation of coffee pulp released caffeic (>60%), ferulic (>80%) and p-coumaric acid (100%) indicating applicability for the valorization of food processing wastes and enhanced biomass degradation. Based on substrate specificity profiling and the release of diferulates from destarched wheat bran, the recombinant FAEs were characterized as type D FAEs. ScFaeD1 and ScFaeD2 preferably hydrolyzed feruloylated saccharides with ferulic acid esterified to the O-5 position of arabinose residues and showed an unprecedented ability to hydrolyze benzoic acid esters. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Function of bacteriophage G7C esterase tailspike in host cell adsorption.

    Science.gov (United States)

    Prokhorov, Nikolai S; Riccio, Cristian; Zdorovenko, Evelina L; Shneider, Mikhail M; Browning, Christopher; Knirel, Yuriy A; Leiman, Petr G; Letarov, Andrey V

    2017-08-01

    Bacteriophages recognize and bind to their hosts with the help of receptor-binding proteins (RBPs) that emanate from the phage particle in the form of fibers or tailspikes. RBPs show a great variability in their shapes, sizes, and location on the particle. Some RBPs are known to depolymerize surface polysaccharides of the host while others show no enzymatic activity. Here we report that both RBPs of podovirus G7C - tailspikes gp63.1 and gp66 - are essential for infection of its natural host bacterium E. coli 4s that populates the equine intestinal tract. We characterize the structure and function of gp63.1 and show that unlike any previously described RPB, gp63.1 deacetylates surface polysaccharides of E. coli 4s leaving the backbone of the polysaccharide intact. We demonstrate that gp63.1 and gp66 form a stable complex, in which the N-terminal part of gp66 serves as an attachment site for gp63.1 and anchors the gp63.1-gp66 complex to the G7C tail. The esterase domain of gp63.1 as well as domains mediating the gp63.1-gp66 interaction is widespread among all three families of tailed bacteriophages. © 2017 John Wiley & Sons Ltd.

  18. The role of low levels of juvenile hormone Esterase in the metamorphosis of Manduca sexta

    Directory of Open Access Journals (Sweden)

    M.H. Browder

    2001-10-01

    Full Text Available The activity of juvenile hormone esterase (JHE in feeding fifth instar larvae of Manduca sexta increases gradually with larval weight and rises to a peak after larvae pass the critical weight when juvenile hormone secretion ceases. Starvation of larvae of Manduca sexta (L. that had exceeded the critical weight inhibited peak levels of JHE, but did not delay entry into the wandering stage when larvae leave the plant in search of a pupation site. This suggests that peak levels of JHE may not be essential for the normal timing of metamorphosis. Starved larvae pupated normally, indicating the peak of JHE was not necessary for a morphologically normal pupation. Treatments of larvae with the selective JHE inhibitor O-ethyl-S-phenyl phosphoramidothiolate (EPPAT that began immediately after larvae achieved the critical weight (6.0 to 6.5 grams for our strain of Manduca delayed entry into the wandering stage. By contrast, EPPAT treatment of larvae at weights above 8.0g had no effect on the subsequent timing of the onset of wandering. Therefore, although the normal timing of the onset of wandering does not require peak levels of JHE, it requires low to moderate levels of JHE to be present until larvae reach a weight of about 8.0g.

  19. Separating esterase targets of organophosphorus compounds in the brain by preparative chromatography.

    Science.gov (United States)

    Mangas, I; Vilanova, E; Benabent, M; Estévez, J

    2014-02-10

    Low level exposure to organophosphorus esters (OPs) may cause long-term neurological effects and affect specific cognition domains in experimental animals and humans. Action on known targets cannot explain most of these effects by. Soluble carboxylesterases (EC 3.1.1.1) of chicken brain have been kinetically discriminated using paraoxon, mipafox and phenylmethyl sulfonylfluoride as inhibitors and phenyl valerate as a substrate. Three different enzymatic components were discriminated and called Eα, Eβ and Eγ. In this work, a fractionation procedure with various steps was developed using protein native separation methods by preparative HPLC. Gel permeation chromatography followed by ion exchange chromatography allowed enriched fractions with different kinetic behaviors. The soluble chicken brain fraction was fractionated, while total esterase activity, proteins and enzymatic components Eα, Eβ and Eγ were monitored in each subfraction. After the analysis, 13 fractions were pooled and conserved. Preincubation of the soluble chicken brain fraction of with the organophosphorus mipafox gave rise to a major change in the ion exchange chromatography profile, but not in the molecular exchanged chromatography profile, which suggest that mipafox permanently modifies the ionic properties of numerous proteins. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Subunit Stabilization and Polyethylene Glycolation of Cocaine Esterase Improves In Vivo Residence Time

    Energy Technology Data Exchange (ETDEWEB)

    Narasimhan, Diwahar; Collins, Gregory T.; Nance, Mark R.; Nichols, Joseph; Edwald, Elin; Chan, Jimmy; Ko, Mei-Chuan; Woods, James H.; Tesmer, John J.G.; Sunahara, Roger K. (Michigan)

    2012-03-15

    No small-molecule therapeutic is available to treat cocaine addiction, but enzyme-based therapy to accelerate cocaine hydrolysis in serum has gained momentum. Bacterial cocaine esterase (CocE) is the fastest known native enzyme that hydrolyzes cocaine. However, its lability at 37 C has limited its therapeutic potential. Cross-linking subunits through disulfide bridging is commonly used to stabilize multimeric enzymes. Herein we use structural methods to guide the introduction of two cysteine residues within dimer interface of CocE to facilitate intermolecular disulfide bond formation. The disulfide-crosslinked enzyme displays improved thermostability, particularly when combined with previously described mutations that enhance stability (T172R-G173Q). The newly modified enzyme yielded an extremely stable form of CocE (CCRQ-CocE) that retained greater than 90% of its activity after 41 days at 37 C, representing an improvement of more than 4700-fold over the wild-type enzyme. CCRQ-CocE could also be modified by polyethylene glycol (PEG) polymers, which improved its in vivo residence time from 24 to 72 h, as measured by a cocaine lethality assay, by self-administration in rodents, and by measurement of inhibition of cocaine-induced cardiovascular effects in rhesus monkeys. PEG-CCRQ elicited negligible immune response in rodents. Subunit stabilization and PEGylation has thus produced a potential protein therapeutic with markedly higher stability both in vitro and in vivo.

  1. The role of aspirin in the prevention of cardiovascular disease.

    Science.gov (United States)

    Ittaman, Sunitha V; VanWormer, Jeffrey J; Rezkalla, Shereif H

    2014-12-01

    Aspirin therapy is well-accepted as an agent for the secondary prevention of cardiovascular events and current guidelines also define a role for aspirin in primary prevention. In this review, we describe the seminal trials of aspirin use in the context of current guidelines, discuss factors that may influence the effectiveness of aspirin therapy for cardiovascular disease prevention, and briefly examine patterns of use. The body of evidence supports a role for aspirin in both secondary and primary prevention of cardiovascular events in selected population groups, but practice patterns may be suboptimal. As a simple and inexpensive prophylactic measure for cardiovascular disease, aspirin use should be carefully considered in all at-risk adult patients, and further measures, including patient education, are necessary to ensure its proper use. © 2013 Marshfield Clinic.

  2. The Role of Aspirin in the Prevention of Cardiovascular Disease

    Science.gov (United States)

    Ittaman, Sunitha V.; VanWormer, Jeffrey J.; Rezkalla, Shereif H.

    2014-01-01

    Aspirin therapy is well-accepted as an agent for the secondary prevention of cardiovascular events and current guidelines also define a role for aspirin in primary prevention. In this review, we describe the seminal trials of aspirin use in the context of current guidelines, discuss factors that may influence the effectiveness of aspirin therapy for cardiovascular disease prevention, and briefly examine patterns of use. The body of evidence supports a role for aspirin in both secondary and primary prevention of cardiovascular events in selected population groups, but practice patterns may be suboptimal. As a simple and inexpensive prophylactic measure for cardiovascular disease, aspirin use should be carefully considered in all at-risk adult patients, and further measures, including patient education, are necessary to ensure its proper use. PMID:24573704

  3. SH groups in the alpha-naphthyl acetate esterase in the thyroid of the guinea-pig. A histochemical study

    DEFF Research Database (Denmark)

    Kirkeby, S

    1976-01-01

    The alpha-naphthyl acetate esterase in both group I and group II thyroid cells is shown to contain SH groups since there is a decline in activity in both cell groups when certain sulfhydryl reagents [DTNB; 5,5'-Dithiobis-(2-nitrobenzoic acid)-AgNO3-Mersalyl-PCMB (parachloro mercuribenzoate) + urea......] are added to the incubation media. Thus the inhibition is by far the greatest in group I cells, which also show the greatest activity after incubation in conventional media, when long fixation and storage times are used. In all cases the inhibiting effect was complete or almost completely reversed...... if cysteine was added to the incubation media in equivalent concentrations to the SH blocker. There were great differences among the sulfhydryl reagents used in their ability to bring about enzyme inhibition. The alkylating agents NEM (N-ethylmaleimide) and iodoacetamide had no or little effect while PCMB...

  4. Aspirin resistance: Prevalence and clinical outcome in Egypt

    OpenAIRE

    Ahmed Salah; Mohammed El-Desuky; Amal Rizk; Amr El-Hadidy

    2015-01-01

    Introduction: The antiplatelet drug aspirin is considered as a cornerstone in medical treatment of patients with CV or cerebrovascular diseases. Despite its use, a significant number of patients had recurrent adverse ischemic events. Inter-individual variability of platelet aggregation in response to aspirin may be an explanation for some of these events. Multiple trials have linked aspirin resistance to these adverse events. Objectives: The aim of this study was to estimate the prevalence...

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

    Science.gov (United States)

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

  6. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease.

    Science.gov (United States)

    Eikelboom, John W; Connolly, Stuart J; Bosch, Jackie; Dagenais, Gilles R; Hart, Robert G; Shestakovska, Olga; Diaz, Rafael; Alings, Marco; Lonn, Eva M; Anand, Sonia S; Widimsky, Petr; Hori, Masatsugu; Avezum, Alvaro; Piegas, Leopoldo S; Branch, Kelley R H; Probstfield, Jeffrey; Bhatt, Deepak L; Zhu, Jun; Liang, Yan; Maggioni, Aldo P; Lopez-Jaramillo, Patricio; O'Donnell, Martin; Kakkar, Ajay K; Fox, Keith A A; Parkhomenko, Alexander N; Ertl, Georg; Störk, Stefan; Keltai, Matyas; Ryden, Lars; Pogosova, Nana; Dans, Antonio L; Lanas, Fernando; Commerford, Patrick J; Torp-Pedersen, Christian; Guzik, Tomek J; Verhamme, Peter B; Vinereanu, Dragos; Kim, Jae-Hyung; Tonkin, Andrew M; Lewis, Basil S; Felix, Camilo; Yusoff, Khalid; Steg, P Gabriel; Metsarinne, Kaj P; Cook Bruns, Nancy; Misselwitz, Frank; Chen, Edmond; Leong, Darryl; Yusuf, Salim

    2017-10-05

    We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; Paspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; Paspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).

  7. Improving the Gastrointestinal Tolerability of Aspirin in Older People

    OpenAIRE

    Newton, Julia L.

    2006-01-01

    Interventions to reduce mortality and disability in older people are vital. Aspirin is cheap and effective and known to prevent cardiovascular and cerebrovascular disease, many cancers, and Alzheimer dementia. The widespread use of aspirin in older people is limited by its gastrointestinal side effects. Understanding age-related changes in gastrointestinal physiology that could put older people at risk of the side effects of aspirin may direct strategies to improve tolerance and hence lead to...

  8. 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

  9. Aspirin inhibits interleukin 1-induced prostaglandin H synthase expression in cultured endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, K.K.; Sanduja, R.; Tsai, A.L.; Ferhanoglu, B.; Loose-Mitchell, D.S. (Univ. of Texas Medical School, Houston (United States))

    1991-03-15

    Prostaglandin H (PGH) synthase is a key enzyme in the biosynthesis of prostaglandins, thromboxane, and prostacyclin. In cultured human umbilical vein endothelial cells, interleukin 1 (IL-1) is known to induce the synthesis of this enzyme, thereby raising the level of PGH synthase protein severalfold over the basal level. Pretreatment with aspirin at low concentrations inhibited more than 60% of the enzyme mass and also the cyclooxygenase activity in IL-1-induced cells with only minimal effects on the basal level of the synthase enzyme in cells without IL-1. Sodium salicylate exhibited a similar inhibitory action whereas indomethacin had no apparent effect. Similarly low levels of aspirin inhibited the increased L-({sup 35}S)methionine incorporation into PGH synthase that was induced by IL0-1 and also suppressed expression of the 2.7-kilobase PGH synthase mRNA. These results suggest that in cultured endothelial cells a potent inhibition of eicosanoid biosynthetic capacity can be effected by aspirin or salicylate at the level of PGH synthase gene expression. The aspirin effect may well be due to degradation of salicylate.

  10. Positional preferences of acetyl esterases from different CE families towards acetylated 4-O-methyl glucuronic acid-substituted xylo-oligosaccharides

    NARCIS (Netherlands)

    Neumüller, K.G.; Carvalho de Souza, A.; Rijn, van J.H.J.; Streekstra, H.; Gruppen, H.; Schols, H.A.

    2015-01-01

    Background Acetylation of the xylan backbone restricts the hydrolysis of plant poly- and oligosaccharides by hemicellulolytic enzyme preparations to constituent monosaccharides. The positional preferences and deacetylation efficiencies of acetyl esterases from seven different carbohydrate esterase

  11. Aspirin for primary prevention of cardiov