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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. Serum cholesterol concentration associated with aspirin esterase activity in older people: preliminary data

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    Kazuhiko Kotani, Russell Caccavello, Ricardo Hermo, Toshiyuki Yamada, Nobuyuki Taniguchi, Alejandro Gugliucci

    2010-01-01

    Full Text Available OBJECTIVE: Metabolism of aspirin (acetylsalicylic acid, commonly used in older people for the prevention of cardiovascular disease, is important to the effectiveness of this drug. Whereas part of aspirin hydrolysis occurs in blood, there is a paucity of information in regards to circulating aspirin esterase activity in various physiological and pathological conditions. High aspirin esterase activity, corresponding to faster aspirin hydrolysis (thus aspirin non-responsiveness, may occur in cardiovascular disease-prone states. The objective of this study was to investigate the effects of cardio-metabolic variables such as cholesterol on serum aspirin esterase activity in older people who participated in an intervention study on physical activity. METHODS: A total of 18 non-medicated subjects (7 men/11 women, mean age 67.8 years, body mass index = 23.4 ± 3.3 kg/m2, who completed a 3-month interventional program for a mild-to-moderate increase in physical activity, were analyzed. The body mass index, plasma glucose, serum total cholesterol and aspirin esterase activity were measured in the pre- and post-interventional phases of the study. RESULTS: During the interventional period, the changes in aspirin esterase activity correlated significantly and positively with those of total cholesterol concentrations (r = 0.542, P = 0.020; β = 0.609, P = 0.035 in a multiple linear regression analysis after adjusting for all the measured variables. CONCLUSION: The results suggest that cholesterol metabolism alterations may be associated with aspirin metabolism in older people.

  3. 绿原酸及其同分异构体对人血浆阿司匹林酯酶活性的影响%Effects of chlorogenic acid and its isomers on the activity of aspirin esterase in human plasma

    Institute of Scientific and Technical Information of China (English)

    戴国梁; 马世堂; 居文政; 程小桂; 谢丽艳; 徐洁; 谈恒山

    2013-01-01

    目的 探究绿原酸及其同分异构体对人血浆阿司匹林酯酶活性的影响.方法 以高效液相色谱法测定阿司匹林酯酶体外培养体系中水杨酸(SA)和阿司匹林(ASA)的浓度,以CSA/(CASA+CSA)反映阿司匹林酯酶的活性.通过空白对照组和添加单体成分的实验组间阿司匹林酯酶活性的变化来分析各成分对阿司匹林酯酶活性的影响.结果 实验组与空白对照组之间差异没有显著性.结论 在本实验浓度下,绿原酸及其同分异构体对酯酶影响不明显,为临床同时使用阿司匹林与含有该类化合物的中药或中药制剂提供理论依据.%Aim To investigate the effects of chloro-genic acid and its isomers on the activity of aspirin es-terase in human plasma. Methods The concentrations of aspirin ( ASA ) and its metabolite salicylic acid ( SA ) in the culture in vitro were determined by HPLC。 The ratio of CSA/( CASA + CSA ) was used as the activity of aspirin esterase. The effects of chlorogenic acid and its isomers on aspirin esterase were evaluated by comparing the activities of aspirin esterase in human plasma between blank control and experimental group. Results The results suggested that there were no sig-nificant differences between the blank control and experimental group. Conclusions Chlorogenic acid and its isomers had no significant effect on the activity of aspirin esterase at the experimental concentrations. As a few herbs and herbal preparations contained experimental compounds, the conclusion provides practical information for clinical practice for herbs ( or herbal preparations ) and aspirin used concurrently.

  4. 丹参水溶性成分对人血浆阿司匹林酯酶活性的影响%Effects of the water-soluble constituents in Radix Salviae Miltiorrhizae on aspirin esterase in human plasma

    Institute of Scientific and Technical Information of China (English)

    徐瑞军; 于宗琴; 李军; 张鉴

    2011-01-01

    目的:探究丹参水溶性成分对阿司匹林酯酶活性的影响.方法:以高效液相色谱法测定阿司匹林酯酶体外代谢系统中阿司匹林(ASA)和水杨酸(SA)的浓度,以CsA/(CAsA+ CsA)反应阿司匹林酯酶的活性.通过空白对照组和添加丹参水溶性成分的实验组间阿司匹林酯酶活性的变化来评价丹参水溶性成分对人血浆阿司匹林酯酶活性的影响.结果:实验用量的丹参素钠使阿司匹林酯酶活性提高(P<0.05),对阿司匹林酯酶有一定的诱导作用.其他水溶性成分对阿司匹林酯酶的活性影响不大(P>0.05).结论:丹参素钠会影响阿司匹林的代谢,临床合用时应注意相互作用,本研究对临床合理应用两药具有一定的指导意义.%OBJECTIVE To study the effects of water-soluble constituents in Radix Salviae Miltiorrhizae on the aspirin ester-ase in human plasma. METHODS The concentrations of aspirin and it's metabolite (salicylic acid) in the culture in vitro were determined by RP- HPLC. The concetrations ratio of Csa/(Casa + CSa) was used to represent the activity of aspirin esterase. The impact of water-soluble constituents on aspirin esterase in human plasma was evaluated by comparing aspirin esterase activities between control group and experimental group. RESULTS Tanshinol sodium improved aspirin esterase activity (P0. 05). CONCLUSION Tanshinol sodium affects the metabolic rate of aspirin esterase, so their interaction should be paid attention when clinical combination which should guide the use of both drugs rationally in clinical trials.

  5. Cholesterol esterase activity of human intestinal mucosa

    International Nuclear Information System (INIS)

    It has been suggested that cholesterol absorption in humans is dependent on bile acid pool composition and that expansion of the cholic acid pool size is followed by an increase of the absorption values. Similar observations were reported in rats. In the present study, therefore, the authors investigated some general properties of human intestinal cholesterol esterase, with particular emphasis on the effect of bile acids on this enzymatic activity. Twenty-nine segments of small intestine were taken during operations; the enzymatic activity was studied by using mucosal homogenate as a source of enzyme and oleic acid, cholesterol, and 14C-labeled cholesterol as substrates. The time-activity relationship was linear within the first two hours; optimal pH for esterification ranged between 5 and 6.2. There was little difference between the esterifying activity of the jejunal and ileal mucosa. Esterification of cholesterol was observed with all the investigated fatty acids but was maximal with oleic acid. Bile acids did not affect cholesterol esterase activity when present in the incubation mixture at 0.1 and 1.0 mM; the enzymatic activity, however, was significantly inhibited when bile acids were added at 20 mM. In conclusion, this study has shown that the human intestinal mucosa possesses a cholesterol esterase activity; at variance with the rat, however, the human enzyme does not seem to be stimulated by trihydroxy bile acids

  6. CALCIUM ENHANCES ANTIINFLAMMATORY ACTIVITY OF ASPIRIN

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    Choksi Krishna

    2011-03-01

    Full Text Available The objective of present study is to evaluate the effects of calcium carbonate and calcium gluconate on acute and subacute inflammation and to study their possible interactions with Aspirin. Calcium carbonate (10 mg/kg and calcium gluconate (5 mg/kg were administered individually and also co-administered along with sub therapeutic dose Aspirin (50mg/kg to study their interaction. The inflammation was induced by carrageenan or a foreign body. Both calcium carbonate and calcium gluconate could not show significant anti-inflammatory activity on their own in acute as well as subacute inflammation models. Aspirin at sub-anti-inflammatory dose (50mg/Kg when co-administered along with calcium salts produced the significant anti-inflammatory response which was comparable to anti-inflammatory response of aspirin at therapeutic dose (200mg/Kg. Also co-adminostration minimized the gastro-toxicity of aspirin.

  7. Comparative study of human intestinal and hepatic esterases as related to enzymatic properties and hydrolizing activity for ester-type drugs.

    Science.gov (United States)

    Inoue, M; Morikawa, M; Tsuboi, M; Ito, Y; Sugiura, M

    1980-08-01

    In attempts to determine the exact role of intestinal esterase in the body, we purified esterases from human intestinal mucosa and liver, and compared the enzymatic properties and substrate specificities with those of purified esterases. Esterase from human liver was purified 58-fold, by treatment with butanol, DE-52 and DEAE Sephadex A-50 column chromatographies, Sephadex G-200 gel filtration, and isoelectric focusing. The purified preparation showed a single band by polyacylamide gel electrophoresis. The molecular weights of intestinal and hepatic esterases were determined to be 53,000-55,000 and 180,000, respectively, by gel filtration on Sephadex G-200. The activity of the purified intestinal and hepatic esterases was strongly inhibited by diethyl-p-nitrophenyl phosphate and diisopropyl fluorophosphate, and was not inhibited by eserine sulfate and p-chloromercuribenzoate. Moreover, the purified esterases hydrolyzed ester-type drugs such as aspirin, clofibrate, indanyl carbenicillin and procaine. Hepatic esterase had properties similar to those of intestinal esterase with respect to the sensitivity to organophosphate and the substrate specificity. However, the two purified esterases differed in properties such as molecular weight, isoelectric point, thermostability and optimal pH. PMID:7206363

  8. Pectin methyl esterase activity in apple and orange pulps

    International Nuclear Information System (INIS)

    The results of pectin methyl esterase activity from apple, orange pulp and orange peel depending of ph and temperature are discussed. It's shown that the methyl esterase activity form apple and orange pulps higher in range of temperatures from +37...+60digC. The analysis of dependence of its activity from ph has shown that in both case the enzyme activity increase with increase of ph

  9. Activity of pectin methyl esterase during blanching of peaches

    NARCIS (Netherlands)

    Tijskens, L.M.M.; Rodis, P.S.; Hertog, M.L.A.T.M.; Proxenia, N.; Dijk, van C.

    1999-01-01

    The activity of pectin methyl esterase (PE) in peaches during blanching treatments was modelled and analyzed. It was postulated that the enzyme exists in two configurations, one bound and one soluble. The bound configuration can be converted into the soluble configuration. These two configurations h

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

    Science.gov (United States)

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

    2015-01-01

    Salicylic acid (SA) and its derivatives have been used for millennia to reduce pain, fever and inflammation. In addition, prophylactic use of acetylsalicylic acid, commonly known as aspirin, reduces the risk of heart attack, stroke and certain cancers. Because aspirin is rapidly de-acetylated by esterases in human plasma, much of aspirin's bioactivity can be attributed to its primary metabolite, SA. Here we demonstrate that human high mobility group box 1 (HMGB1) is a novel SA-binding protein. SA-binding sites on HMGB1 were identified in the HMG-box domains by nuclear magnetic resonance (NMR) spectroscopic studies and confirmed by mutational analysis. Extracellular HMGB1 is a damage-associated molecular pattern molecule (DAMP), with multiple redox states. SA suppresses both the chemoattractant activity of fully reduced HMGB1 and the increased expression of proinflammatory cytokine genes and cyclooxygenase 2 (COX-2) induced by disulfide HMGB1. Natural and synthetic SA derivatives with greater potency for inhibition of HMGB1 were identified, providing proof-of-concept that new molecules with high efficacy against sterile inflammation are attainable. An HMGB1 protein mutated in one of the SA-binding sites identified by NMR chemical shift perturbation studies retained chemoattractant activity, but lost binding of and inhibition by SA and its derivatives, thereby firmly establishing that SA binding to HMGB1 directly suppresses its proinflammatory activities. Identification of HMGB1 as a pharmacological target of SA/aspirin provides new insights into the mechanisms of action of one of the world's longest and most used natural and synthetic drugs. It may also provide an explanation for the protective effects of low-dose aspirin usage. PMID:26101955

  11. CALCIUM ENHANCES ANTIINFLAMMATORY ACTIVITY OF ASPIRIN

    OpenAIRE

    Choksi Krishna; Shenoy Ashoka M; A. R. Shabharaya; Lala Minaxi

    2011-01-01

    The objective of present study is to evaluate the effects of calcium carbonate and calcium gluconate on acute and subacute inflammation and to study their possible interactions with Aspirin. Calcium carbonate (10 mg/kg) and calcium gluconate (5 mg/kg) were administered individually and also co-administered along with sub therapeutic dose Aspirin (50mg/kg) to study their interaction. The inflammation was induced by carrageenan or a foreign body. Both calcium carbonate and calcium gluconate cou...

  12. Inhibition of Pectin Methyl Esterase Activity By Green Tea Catechins

    OpenAIRE

    Sagi, Irit; Lewis, Kristin; Tworowski, Dmitry; Shahar, Chen; Selzer, Tzvia

    2008-01-01

    Pectin methyl esterases (PMEs) and their endogenous inhibitors are involved in the regulation of many processes in plant physiology, ranging from tissue growth and fruit ripening to parasitic plant haustorial formation and host invasion. Thus, control of PME activity is critical for enhancing our understanding of plant physiological processes and regulation. Here we report on the identification of epigallocatechin gallate (EGCG), a green tea component, as a natural inhibitor for pectin ...

  13. Aspirin metabolism and efficacy in postoperative dental pain.

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    Seymour, R A; Williams, F M; Ward, A; Rawlins, M D

    1984-01-01

    Aspirin 1200 mg was compared with placebo in a randomised, double-blind, crossover study in 15 patients with postoperative pain after removal of impacted lower third molars. Over a 5 h investigation period, patients reported significantly less pain (P less than 0.01) after treatment with aspirin, than after treatment with placebo. Peak concentrations of aspirin occurred at 15 min after dosage. Significant negative correlations were observed between plasma aspirin esterase activity and both AUC aspirin (r = -0.904, P less than 0.001) and AUC analgesia (r = -0.91, P less than 0.001). Similarly, a significant correlation was observed between AUC aspirin and AUC analgesia (r = 0.96, P less than 0.001). Evidence from this study would suggest that an individual's pain relief in postoperative dental pain is determined by the rate of aspirin hydrolysis to salicylate. PMID:6378231

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

    International Nuclear Information System (INIS)

    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.)

  15. Assessment of erythrocyte acetylcholine esterase activities in painters

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    Khan Mohd

    2009-01-01

    Full Text Available Thirty-five male painters in the age group of 20-50 years occupationally engaged in domestic and commercial painting for 5-12 years having blood lead levels (BLL ≤40 µg/dl were subjected to the determination of acetyl choline esterase (AChE levels both in plasma and red blood cell (RBC lysate. BLL were determined using a graphite furnace atomic absorption spectrometer. The results showed that BLL were 7.7 times higher in the painters as compared with that of the control group. Significant decreases in RBC and plasma AChE were observed in the exposed group in comparison with controls. RBC and plasma AChE showed a decrease of 18.4% and 18%, respectively, in the exposed group. The findings also indicated a significant negative correlation of both RBC and plasma AChE activities with BLL. The marked reduction observed in both RBC and plasma AChE activity may account for disruption of cholinergic function and result in neurotoxicity among the painters.

  16. The search of the target of promotion: Phenylbenzoate esterase activities in hen peripheral nerve

    International Nuclear Information System (INIS)

    Certain esterase inhibitors, such as carbamates, phosphinates and sulfonyl halides, do not cause neuropathy as some organophosphates, but they may exacerbate chemical or traumatic insults to axons. This phenomenon is called promotion of axonopathies. Given the biochemical and toxicological characteristics of these compounds, the hypothesis was made that the target of promotion is a phenyl valerate (PV) esterase similar to neuropathy target esterase (NTE), the target of organophosphate induced delayed polyneuropathy. However, attempts to identify a PV esterase in hen peripheral nerve have been, so far, unsuccessful. We tested several esters, other than PV, as substrates of esterases from crude homogenate of the hen peripheral nerve. The ideal substrate should be poorly hydrolysed by NTE but extensively by enzyme(s) that are insensitive to non-promoters, such as mipafox, and sensitive to promoters, such as phenyl methane sulfonyl fluoride (PMSF). When phenyl benzoate (PB) was used as substrate, about 65% of total activity was resistant to the non-promoter mipafox (up to 0.5 mM, 20 min, pH 8.0), that inhibits NTE and other esterases. More than 90% of this resistant activity was sensitive to the classical promoter PMSF (1 mM, 20 min, pH 8.0) with an IC50 of about 0.08 mM (20 min, pH 8.0). On the contrary, the non-promoter p-toluene sulfonyl fluoride caused only about 10% inhibition at 0.5 mM. Several esterase inhibitors including, paraoxon, phenyl benzyl carbamate, di-n-butyl dichlorovinyl phosphate and di-isopropyl fluorophosphate, were tested both in vitro and in vivo for inhibition of this PB activity. Mipafox-resistant PMSF-sensitive PB esterase activity(ies) was inhibited by promoters but not by non promoters and neuropathic compounds

  17. Pharmacokinetics of aspirin and salicylate in relation to inhibition of arachidonate cyclooxygenase and antiinflammatory activity.

    OpenAIRE

    Higgs, G. A.; Salmon, J. A.; Henderson, B; Vane, J R

    1987-01-01

    Among the nonsteroid antiinflammatory drugs there is generally a close correlation between the potency of their inhibition of arachidonate cyclooxygenase, and thus prostaglandin production, and their antiinflammatory activity. One anomaly in this generalization is that whereas aspirin and salicylate are equipotent as antiinflammatory agents, salicylate is less active than aspirin in inhibiting prostaglandin production in vitro. Using rats, we have now measured the concentrations of aspirin an...

  18. Cigarette smoking inhibits the anti-platelet activity of aspirin in patients with coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    LI Wei-ju; ZHANG Hong-yin; MIAO Cheng-long; TANG Ri-bo; DU Xin; SHI Ji-hui; MA Chang-sheng

    2011-01-01

    Objective Tobacco smoking results in increased platelet aggregability, which suggests that low-dose aspirin used in common clinical practice may not effectively inhibit platelet activity in smokers with coronary heart disease (CHD). This review was performed to assess the effect of aspirin on platelet aggregation in patients with CHD.Data sources We performed an electronic literature search of MEDLINE (starting from the beginning to March 15, 2009)using the term "smoking" or "tobacco" paired with the following: "platelet", "aspirin" or "coronary heart disease".Study selection We looked for review articles regarding the effect of tobacco smoking on platelet activity and on the anti-platelet efficacy of aspirin in healthy people and patients with CHD. The search was limited in "core clinical journal".In total, 1321 relevant articles were retrieved, and 36 articles were ultimately cited.Results Tobacco smoking results in increased platelet aggregability, which can be inhibited by low-dose aspirin in the healthy population. However, in patients with CHD, the increased platelet aggregability can not be effectively inhibited by the same low-dose of aspirin. A recent study indicated that clopidogrel or an increased dose of aspirin can effectively inhibit the increased platelet aggregability induced by tobacco smoking in patients with CHD.Conclusions It is important for patients with CHD to quit smoking. For the current smoker, it may be necessary to take larger doses of aspirin than normal or take an adenosine diphosphate receptor inhibitor along with aspirin to effectively inhibit the increased platelet activity.

  19. Characterization of a novel cold active and salt tolerant esterase from Zunongwangia profunda.

    Science.gov (United States)

    Rahman, Mohammad Asadur; Culsum, Umma; Tang, Wenhao; Zhang, Shao Wei; Wu, Gaobing; Liu, Ziduo

    2016-04-01

    A novel cold active esterase, EstLiu was cloned from the marine bacterium Zunongwangia profunda, overexpressed in E. coli BL21 (DE3) and purified by glutathione-S transferase (GST) affinity chromatography. The mature esterase EstLiu sequence encodes a protein of 273 amino acids residues, with a predicted molecular weight of 30KDa and containing the classical pentapeptidase motif from position 156 to 160 with the catalytic triad Ser158-Asp211-His243. Although, EstLiu showed 64% similarity with the hypothetical esterase from Chryseobacterium sp. StRB126 (WP_045498424), phylogenetic analysis showed it had no similarity with any of the established family of lipases/esterases, suggesting that it could be considered as a new family. The purified enzyme showed broad substrate specificity with the highest hydrolytic activity against p-nitrophenyl butyrate (C4). EstLiu showed remarkable activity (75%) at 0°Cand the optimal activity at pH 8.0 and 30°C with good thermostability and quickened inactivation above 60°C. EstLiu retained 81, 103, 67 and 78% of its original activity at 50% (v/v) in ethanol, isopropanol, DMSO and ethylene glycol, respectively. In the presence of Tween 20, Tween 80 and Triton X-100, EstLiu showed 88, 100 and 117% of relative activity. It is also co-factor independent. The high activity at low temperature and desirable stability in organic solvents and salts of this novel family esterase represents a good evidence of novel biocatalyst. Overall, this novel enzyme showed better activity than previously reported esterases in extreme reaction conditions and could promote the reaction in both aqueous and non-aqueous conditions, indicating its great potential for industrial applications. PMID:26920474

  20. Aspirin and atenolol enhance metformin activity against breast cancer by targeting both neoplastic and microenvironment cells.

    Science.gov (United States)

    Talarico, Giovanna; Orecchioni, Stefania; Dallaglio, Katiuscia; Reggiani, Francesca; Mancuso, Patrizia; Calleri, Angelica; Gregato, Giuliana; Labanca, Valentina; Rossi, Teresa; Noonan, Douglas M; Albini, Adriana; Bertolini, Francesco

    2016-01-01

    Metformin can induce breast cancer (BC) cell apoptosis and reduce BC local and metastatic growth in preclinical models. Since Metformin is frequently used along with Aspirin or beta-blockers, we investigated the effect of Metformin, Aspirin and the beta-blocker Atenolol in several BC models. In vitro, Aspirin synergized with Metformin in inducing apoptosis of triple negative and endocrine-sensitive BC cells, and in activating AMPK in BC and in white adipose tissue (WAT) progenitors known to cooperate to BC progression. Both Aspirin and Atenolol added to the inhibitory effect of Metformin against complex I of the respiratory chain. In both immune-deficient and immune-competent preclinical models, Atenolol increased Metformin activity against angiogenesis, local and metastatic growth of HER2+ and triple negative BC. Aspirin increased the activity of Metformin only in immune-competent HER2+ BC models. Both Aspirin and Atenolol, when added to Metformin, significantly reduced the endothelial cell component of tumor vessels, whereas pericytes were reduced by the addition of Atenolol but not by the addition of Aspirin. Our data indicate that the addition of Aspirin or of Atenolol to Metformin might be beneficial for BC control, and that this activity is likely due to effects on both BC and microenvironment cells. PMID:26728433

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

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    G M Gururaja

    2015-01-01

    Full Text Available Background: 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. Objective: 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. Materials and Methods: 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. Results and Discussion: 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.Conclusion: 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.

  2. 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...... group I cells. EDTA and Mn2+, on the other hand, activated the esterase activity in group II cells....

  3. A unique CE16 acetyl esterase from Podospora anserina active on polymeric xylan.

    Science.gov (United States)

    Puchart, Vladimír; Berrin, Jean-Guy; Haon, Mireille; Biely, Peter

    2015-12-01

    The genome of the coprophilous fungus Podospora anserina displays an impressive array of genes encoding hemicellulolytic enzymes. In this study, we focused on a putative carbohydrate esterase (CE) from family 16 (CE16) that bears a carbohydrate-binding module from family CBM1. The protein was heterologously expressed in Pichia pastoris and purified to electrophoretic homogeneity. The P. anserina CE16 enzyme (PaCE16A) exhibited different catalytic properties than so far known CE16 esterases represented by the Trichoderma reesei CE16 acetyl esterase (TrCE16). A common property of both CE16 esterases is their exodeacetylase activity, i.e., deesterification at positions 3 and 4 of monomeric xylosides and the nonreducing end xylopyranosyl (Xylp) residue of oligomeric homologues. However, the PaCE16A showed lower positional specificity than TrCE16 and efficiently deacetylated also position 2. The major difference observed between PaCE16A and TrCE16 was found on polymeric substrate, acetylglucuronoxylan. While TrCE16 does not attack internal acetyl groups, PaCE16A deacetylated singly and doubly acetylated Xylp residues in the polymer to such an extent that it resulted in the polymer precipitation. Similarly as typical acetylxylan esterases belonging to CE1, CE4, CE5, and CE6 families, PaCE16A did not attack 3-O-acetyl group of xylopyranosyl residues carrying 4-O-methyl-D-glucuronic acid at position 2. PaCE16A thus represents a CE16 member displaying unique catalytic properties, which are intermediate between the TrCE16 exodeacetylase and acetylxylan esterases designed to deacetylate polymeric substrate. The catalytic versatility of PaCE16A makes the enzyme an important candidate for biotechnological applications. PMID:26329850

  4. Total esterase activity in human saliva: Validation of an automated assay, characterization and behaviour after physical stress.

    Science.gov (United States)

    Tecles, Fernando; Tvarijonaviciute, Asta; De Torre, Carlos; Carrillo, José M; Rubio, Mónica; García, Montserrat; Cugat, Ramón; Cerón, José J

    2016-07-01

    Although saliva has esterase activity, this activity has not been characterized or studied in individuals subjected to physical stress. The aim of this report was to develop and validate an automated spectrophotometric assay for total esterase activity measurement in human saliva, as well as to study the contribution of different enzymes on this activity and its behaviour under physical stress in healthy subjects. The assay used 4-nitrophenyl acetate as substrate and was precise, accurate and provided low limits of detection and quantification. Inhibition with diisopropylfluorophosphate showed that cholinesterase, carboxylesterase and cholesterol esterase contributions not represented more than 20% of total esterase. Addition of standards of lipase and albumin to saliva samples showed that both proteins significantly contributed to esterase activity only when equal or higher than 11.6 IU/L and 250 μg/mL, respectively. Western blot analyses showed absence of paraoxonase-1 and high amount of carbonic anhydrase-VI. The high affinity of purified carbonic anhydrase-VI for the substrate supported a major contribution of this enzyme. Total esterase activity and alpha-amylase was measured in saliva samples from 12 healthy male students before and after participation in an indoor football match. The activity significantly increased after match and positively correlated with salivary alpha-amylase. This method could be used as a biomarker of physical stress in humans, with carbonic anhydrase-VI being the esterase that contributed more to the activity of the assay. PMID:27045801

  5. Gene cloning and characterization of a novel esterase from activated sludge metagenome

    Directory of Open Access Journals (Sweden)

    Liu Zhi-Pei

    2009-12-01

    Full Text Available Abstract A metagenomic library was prepared using pCC2FOS vector containing about 3.0 Gbp of community DNA from the microbial assemblage of activated sludge. Screening of a part of the un-amplified library resulted in the finding of 1 unique lipolytic clone capable of hydrolyzing tributyrin, in which an esterase gene was identified. This esterase/lipase gene consists of 834 bp and encodes a polypeptide (designated EstAS of 277 amino acid residuals with a molecular mass of 31 kDa. Sequence analysis indicated that it showed 33% and 31% amino acid identity to esterase/lipase from Gemmata obscuriglobus UQM 2246 (ZP_02733109 and Yarrowia lipolytica CLIB122 (XP_504639, respectively; and several conserved regions were identified, including the putative active site, HSMGG, a catalytic triad (Ser92, His125 and Asp216 and a LHYFRG conserved motif. The EstAS was overexpressed, purified and shown to hydrolyse p-nitrophenyl (NP esters of fatty acids with short chain lengths (≤ C8. This EstAS had optimal temperature and pH at 35°C and 9.0, respectively, by hydrolysis of p-NP hexanoate. It also exhibited the same level of stability over wide temperature and pH ranges and in the presence of metal ions or detergents. The high level of stability of esterase EstAS with its unique substrate specificities make itself highly useful for biotechnological applications.

  6. Inhibition of monocyte esterase activity by organophosphate insecticides.

    Science.gov (United States)

    Lee, M J; Waters, H C

    1977-11-01

    Organophosphate insecticides, such as Vapona, Naled, and Rabon, are highly potent inhibitors of an enzyme found in human monocytes. The enzyme, a specific monocyte esterase, could be inhibited by Vapona in blood samples via airborne contamination at levels easily achieved from commercial slow-release insecticide strips. Fifty percent inhibition (I50)--as measured on the Hemalog D (Technicon Corp.)--occurred at solution concentrations of 0.22, 1.5, and 2.6 X 10(-6) g/liter for Vapona, Rabon, and Naled, respectively. Parathion (a thiophosphate) and Baygon (a carbamate) were less potent, with I50 values of 3.7 X 10(-5) and 1.5 X 10(-4) g/liter, respectively. Dursban (another thiophosphate) and Carbaryl (a carbamate) showed only marginal inhibition. Eserine, malathion, nicotine and pyrethrum had no inhibitory effect up to 0.5 g/liter. The occurrence of this effect in vivo has not yet been shown, nor is it clear what the implications of such an effect would be. The inhibition of this enzyme by airborne contaminants, however, may interfere with the proper functioning of the Hemalog D. PMID:907842

  7. Comparative evaluation of antipyretic activity of ibuprofen and aspirin in children with pyrexia of varied aetiology.

    Science.gov (United States)

    Kandoth, P W; Joshi, M K; Joshi, V R; Satoskar, R S

    1984-01-01

    The antipyretic activity of ibuprofen and aspirin was compared in sixteen children with pyrexia due to upper respiratory tract infection and in twelve with fever due to other causes. All 28 children received ibuprofen (7 mg/kg of body-weight) and aspirin (15 mg/kg of body-weight) in a single dose on 2 consecutive days in a crossover manner. Rectal temperature was recorded prior to and at regular intervals up to 8 hours after drug administration. Analysis of the results indicate that ibuprofen and aspirin effectively lower temperature and the two drugs are comparable in their antipyretic activity. In conclusion, significant antipyretic activity, good tolerance profile and availability in syrup form make ibuprofen a useful substitute for aspirin in children with fever. PMID:6500169

  8. Promiscuous enantioselective (−)-γ-lactamase activity in the Pseudomonas fluorescens esterase I

    OpenAIRE

    Torres, Leticia L.; Schließmann, Anna; Schmidt, Marlen; Silva-Martín, Noella; Hermoso, Juan A.; Berenguer, José; Bornscheuer, Uwe T.; Hidalgo, Aurelio

    2012-01-01

    A promiscuous but very enantioselective (−)-γ-lactamase activity in the kinetic resolution of the Vince lactam (2-azabicyclo[2.2.1]hept-5-en-3-one) was detected in the Pseudomonas fluorescens esterase I (PFEI). The lactamase activity was increased 200-fold by the introduction of a point mutation and resulted as enantioselective as the Microbacterium sp. enzyme used industrially in this resolution. The structural and mechanistic determinants for the catalytic promiscuity and enantioselectivity...

  9. Screening, Nucleotide Sequence, and Biochemical Characterization of an Esterase from Pseudomonas fluorescens with High Activity towards Lactones

    OpenAIRE

    Khalameyzer, V.; Fischer, I; Bornscheuer, U. T.; Altenbuchner, J

    1999-01-01

    A genomic library of Pseudomonas fluorescens DSM 50106 in a λRESIII phage vector was screened in Escherichia coli K-12 for esterase activity by using α-naphthyl acetate and Fast Blue RR. A 3.2-kb DNA fragment was subcloned from an esterase-positive clone and completely sequenced. Esterase EstF1 was encoded by a 999-bp open reading frame (ORF) and exhibited significant amino acid sequence identity with members of the serine hydrolase family. The deduced amino acid sequences of two other C-term...

  10. Organophosphorous biocides reduce tenacity and cellular viability but not esterase activities in a non-target prosobranch (limpet)

    International Nuclear Information System (INIS)

    Detecting impacts of organophosphorus biocides (OP) is facilitated by analysing “biomarkers” – biological responses to environmental insults. Understanding is hampered by studying biomarkers in isolation at different levels of biological response and limited work on ecologically-important species. We tested the relevance of esterases as biomarkers of OP-exposure in limpets (Patella vulgata), abundant prosobranchs that structure the assemblages on rocky shores through their grazing. We characterized esterases in haemolymph and tissue, and quantified their dose-dependent inhibition by chlorfenvinphos (0.1–3.0 mM) in vitro. To determine whether esterases are useful biomarkers we exposed limpets to chlorfenvinphos (0–10 μg L−1). Despite reduced tenacity (ability to stick to a surface) and haemocyte-viability, esterases remained unaffected. Tenacity was reduced by >50% at 5 μg L−1 and by 95% at 10 μg L−1, whilst haemocyte-viability was more sensitive with >40% reductions at concentrations of 0.5 μg L−1 and above. We discuss results in relation to linking sub-lethal and ecological impacts at contaminated sites. - Highlights: • We investigated if esterases are useful biomarkers of chlorfenvinphos-exposure. • Esterases in tissues of limpets (Patella vulgata) were characterized. • The dose-dependent inhibition of esterases by chlorfenvinphos was shown in vitro. • In vivo, tenacity and haemocyte-viability were reduced, but not esterase activities. - Organophosphorous biocides reduce tenacity and cellular viability but not esterase activities in the limpet, Patella vulgata

  11. Biochemical studies on a versatile esterase that is most catalytically active with polyaromatic esters

    OpenAIRE

    Martínez-Martínez, Mónica; Lores, Iván; Peña-García, Carlina; Bargiela, Rafael; Reyes-Duarte, Dolores; Guazzaroni, María-Eugenia; Peláez, Ana Isabel; Sánchez, Jesús; Ferrer, Manuel

    2014-01-01

    Herein, we applied a community genomic approach using a naphthalene-enriched community (CN1) to isolate a versatile esterase (CN1E1) from the α/β-hydrolase family. The protein shares low-to-medium identity (≤ 57%) with known esterase/lipase-like proteins. The enzyme is most active at 25–30°C and pH 8.5; it retains approximately 55% of its activity at 4°C and less than 8% at ≥ 55°C, which indicates that it is a cold-adapted enzyme. CN1E1 has a distinct substrate preference compared with other ...

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

    OpenAIRE

    Lomolino G; Lante A

    2012-01-01

    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 t...

  13. Environmental Factors Modulating the Stability and Enzymatic Activity of the Petrotoga mobilis Esterase (PmEst.

    Directory of Open Access Journals (Sweden)

    Jose L S Lopes

    Full Text Available Enzymes isolated from thermophilic organisms found in oil reservoirs can find applications in many fields, including the oleochemical, pharmaceutical, bioenergy, and food/dairy industries. In this study, in silico identification and recombinant production of an esterase from the extremophile bacteria Petrotoga mobilis (designated PmEst were performed. Then biochemical, bioinformatics and structural characterizations were undertaken using a combination of synchrotron radiation circular dichroism (SRCD and fluorescence spectroscopies to correlate PmEst stability and hydrolytic activity on different substrates. The enzyme presented a high Michaelis-Menten constant (KM 0.16 mM and optimum activity at ~55°C for p-nitrophenyl butyrate. The secondary structure of PmEst was preserved at acid pH, but not under alkaline conditions. PmEst was unfolded at high concentrations of urea or guanidine through apparently different mechanisms. The esterase activity of PmEst was preserved in the presence of ethanol or propanol and its melting temperature increased ~8°C in the presence of these organic solvents. PmEst is a mesophilic esterase with substrate preference towards short-to medium-length acyl chains. The SRCD data of PmEst is in agreement with the prediction of an α/β protein, which leads us to assume that it displays a typical fold of esterases from this family. The increased enzyme stability in organic solvents may enable novel applications for its use in synthetic biology. Taken together, our results demonstrate features of the PmEst enzyme that indicate it may be suitable for applications in industrial processes, particularly, when the use of polar organic solvents is required.

  14. 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; Olsson, Lisbeth

    2015-01-01

    The catalytic residues in carbohydrate esterase enzyme families constitute a highly conserved triad: serine, histidine and aspartic acid. This catalytic triad is generally located in a very sharp turn of the protein backbone structure, called the nucleophilic elbow and identified by the consensus...... sequence GXSXG. An esterase from Sorangium cellulosum Soce56 that contains five nucleophilic elbows was cloned and expressed in Escherichia coli and the function of each nucleophilic elbowed site was characterized. In order to elucidate the function of each nucleophilic elbow, site directed mutagenesis 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...

  15. Novel Redox-Dependent Esterase Activity (EC 3.1.1.2) for DJ-1: Implications for Parkinson's Disease.

    Science.gov (United States)

    Vázquez-Mayorga, Emmanuel; Díaz-Sánchez, Ángel G; Dagda, Ruben K; Domínguez-Solís, Carlos A; Dagda, Raul Y; Coronado-Ramírez, Cynthia K; Martínez-Martínez, Alejandro

    2016-01-01

    Mutations the in human DJ-1 (hDJ-1) gene are associated with early-onset autosomal recessive forms of Parkinson's disease (PD). hDJ-1/parkinsonism associated deglycase (PARK7) is a cytoprotective multi-functional protein that contains a conserved cysteine-protease domain. Given that cysteine-proteases can act on both amide and ester substrates, we surmised that hDJ-1 possessed cysteine-mediated esterase activity. To test this hypothesis, hDJ-1 was overexpressed, purified and tested for activity towards 4-nitrophenyl acetate (pNPA) as µmol of pNPA hydrolyzed/min/mg·protein (U/mg protein). hDJ-1 showed maximum reaction velocity esterase activity (Vmax = 235.10 ± 12.00 U/mg protein), with a sigmoidal fit (S0.5 = 0.55 ± 0.040 mM) and apparent positive cooperativity (Hill coefficient of 2.05 ± 0.28). A PD-associated mutant of DJ-1 (M26I) lacked activity. Unlike its protease activity which is inactivated by reactive oxygen species (ROS), esterase activity of hDJ-1 is enhanced upon exposure to low concentrations of hydrogen peroxide (100 µM) suggesting that its activity is resistant to oxidative stress. Esterase activity of DJ-1 requires oxidation of catalytic cysteines, as chemically protecting cysteines blocked its activity whereas an oxido-mimetic mutant of DJ-1 (C106D) exhibited robust esterase activity. Molecular docking studies suggest that C106 and L126 within its catalytic site interact with esterase substrates. Overall, our data show that hDJ-1 contains intrinsic redox-sensitive esterase activity that is abolished in a PD-associated mutant form of the hDJ-1 protein. PMID:27556455

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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...

  18. Aspirin augments carotid-cardiac baroreflex sensitivity during muscle mechanoreflex and metaboreflex activation in humans.

    Science.gov (United States)

    Drew, Rachel C; Muller, Matthew D; Blaha, Cheryl A; Mast, Jessica L; Herr, Michael D; Stocker, Sean D; Sinoway, Lawrence I

    2013-10-15

    Muscle mechanoreflex activation decreases the sensitivity of carotid baroreflex (CBR)-heart rate (HR) control during local metabolite accumulation in humans. However, the contribution of thromboxane A2 (TXA2) toward this response is unknown. Therefore, the effect of inhibiting TXA2 production via low-dose aspirin on CBR-HR sensitivity during muscle mechanoreflex and metaboreflex activation in humans was examined. Twelve young subjects performed two trials during two visits, preceded by 7 days' low-dose aspirin (81 mg) or placebo. One trial involved 3-min passive calf stretch (mechanoreflex) during 7.5-min limb circulatory occlusion (CO). In another trial, CO was preceded by 1.5 min of 70% maximal voluntary contraction isometric calf exercise to accumulate metabolites during CO and stretch (mechanoreflex and metaboreflex). HR (ECG) and mean arterial pressure (Finometer) were recorded. CBR function was assessed using rapid neck pressures ranging from +40 to -80 mmHg. Aspirin significantly decreased baseline thromboxane B2 production by 84 ± 4% (P aspirin, stretch with metabolite accumulation significantly augmented maximal gain (GMAX) and operating point gain (GOP) of CBR-HR (GMAX; -0.71 ± 0.14 vs. -0.37 ± 0.08 and GOP; -0.69 ± 0.13 vs. -0.35 ± 0.12 beats·min(-1)·mmHg(-1) for aspirin and placebo, respectively; P aspirin and placebo during stretch with metabolite accumulation. In conclusion, these findings suggest that low-dose aspirin augments CBR-HR sensitivity during concurrent muscle mechanoreflex and metaboreflex activation in humans. This increased sensitivity appears linked to reduced TXA2 production, which likely plays a role in metabolite sensitization of muscle mechanoreceptors. PMID:23970529

  19. 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.

  20. 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

    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...

  1. In Vivo Platelet Activation and Aspirin Responsiveness in Type 1 Diabetes.

    Science.gov (United States)

    Zaccardi, Francesco; Rizzi, Alessandro; Petrucci, Giovanna; Ciaffardini, Flavia; Tanese, Luigi; Pagliaccia, Francesca; Cavalca, Viviana; Ciminello, Angela; Habib, Aida; Squellerio, Isabella; Rizzo, Paola; Tremoli, Elena; Rocca, Bianca; Pitocco, Dario; Patrono, Carlo

    2016-02-01

    Platelet activation is persistently enhanced, and its inhibition by low-dose aspirin is impaired in type 2 diabetes mellitus. We investigated in vivo thromboxane (TX) and prostacyclin (PGI2) biosynthesis and their determinants, as well as aspirin responsiveness, in young adult subjects with type 1 diabetes mellitus (T1DM) without overt cardiovascular disease and stable glycemic control. The biosynthesis of TXA2 was persistently increased in subjects with T1DM versus matched healthy subjects, with females showing higher urinary TX metabolite (TXM) excretion than male subjects with T1DM. Microalbuminuria and urinary 8-iso-PGF2α, an index of in vivo oxidative stress, independently predicted TXM excretion in T1DM. No homeostatic increase in PGI2 biosynthesis was detected. Platelet COX-1 suppression by low-dose aspirin and the kinetics of its recovery after drug withdrawal were similar in patients and control subjects and were unaffected by glucose variability. We conclude that patients with T1DM and stable glycemic control display enhanced platelet activation correlating with female sex and microvascular and oxidative damages. Moreover, aspirin responsiveness is unimpaired in T1DM, suggesting that the metabolic disturbance per se is unrelated to altered pharmacodynamics. The efficacy and safety of low-dose aspirin in T1DM warrant further clinical investigation. PMID:26470782

  2. Arginine-esterase activity of kallikrein in the sera of whole-body irradiated rats and guinea-pigs

    International Nuclear Information System (INIS)

    In whole-body irradiated rats (800 R=LDsub(50/30)) and guinea pigs (300 R=LDsub(50/30)) changes were investigated in the arginine esterase activity of kallikrein in native serum as well as in serum exposed to contact with a clay suspension. From the values obtained the activity of prekallikrein was calculated. While in the rat serum significant changes in the arginine esterase activity of kallikrein were found, in the guinea pig serum the kallikrein activity did not change markedly. The activity of prekallikrein immediately after irradiation assumes a similar course in both types of laboratory animals while during later intervals a reverse pattern was observed. (author)

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

    OpenAIRE

    Abolfazl HAJIBEMANI; Mirzaei, Abdolah; Sharifiyazdi, Hassan; Rowshan Ghasrodashti, Abbas

    2016-01-01

    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/ml) 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 mi...

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

    OpenAIRE

    Abolfazl HAJIBEMANI; Mirzaei, Abdolah; Sharifiyazdi, Hassan; Rowshan Ghasrodashti, Abbas

    2016-01-01

    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 mi...

  5. The activity of non-specific esterase in the thyroid epithelial cells of the guinea pig as influenced by various inhibitors and activators. A histochemical study

    DEFF Research Database (Denmark)

    Kirkeby, S

    1976-01-01

    The action of various inhibitors and activators upon esterase activity in the thyroid epithelial cells is demonstrated. The agents used were triorthocresylphosphate (TOCP), parachloromercuribenzoate (PCMB), Arsanillic acid, p-nitrophenyl dimethyl carbamate and bis p-nitrophenyl phosphate. TOCP was...

  6. Use of esterase activities for the detection of chemical neurotoxic agents.

    Science.gov (United States)

    Manco, Giuseppe; Nucci, Roberto; Febbraio, Ferdinando

    2009-01-01

    The quest for a quick and easy detection of the neurotoxin levels in the environment has fostered the search for systems alternative to currently employed analytical methods such as spectrophotometer, gas-liquid chromatography, thin-layer chromatography, and more recently mass spectrometry. These drawbacks lead to intense research efforts to develop biosensor devices for the determination of these compounds. In this review, we present an overview of the actual development of research in neurotoxin detection by using enzymatic biosensors based on esterase activity, in particular cholinesterases, and carboxylesterases. Detection by enzymatic activity could be carried out measuring the hydrolysis products or the residual enzymatic activity after inhibition, using a transducer system that makes possible the correlation between the determined activity and the analyte concentration. Several transducer systems were adopted for the neurotoxins identification using esterases, including electrochemical, optical, conductimetric and piezoelectric procedures. The differences in the used transducer determine the final sensitivity and specificity of the biosensor. Moreover, a brief description of immobilization procedure, that is an important step in the biosensor development and could affect the final characteristic of biosensor (sensibility, stability, response time and reproducibility), was accomplished. Final considerations on advantages and problems, related to actual development of these technologies, and its prospective were discussed. PMID:19508179

  7. Organophosphates and monocyte esterase deficiency.

    OpenAIRE

    1995-01-01

    AIMS--To examine the possibility that monocyte esterase deficiency (MED) could be caused by exposure to organophosphates. METHODS--Pseudocholinesterase, paraoxonase and arylesterase activities were measured in the serum and acetylcholinesterase activity was measured in the red cells of a group of monocyte esterase deficient subjects and compared with the enzyme activities of a control group of monocyte esterase positive subjects. RESULTS--No significant difference was found between the enzyme...

  8. 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 ...

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

    Directory of Open Access Journals (Sweden)

    Yuan Li

    2016-01-01

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

  10. 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......-free extracts obtained 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 and wheat brans. Hydrolysis by intestinal esterase(s) is very likely the major route for release of antioxidant hydroxycinnamic acids in vivo. Udgivelsesdato: 2001-Nov...

  11. Aliphatic esters as targets of esterase activity in the parsnip webworm (Depressaria pastinacella).

    Science.gov (United States)

    Zangerl, Arthur R; Liao, Ling-Hsiu; Jogesh, Tania; Berenbaum, May R

    2012-02-01

    As a specialist on the reproductive structures of Pastinaca sativa and species in the related genus Heracleum, the parsnip webworm (Depressaria pastinacella) routinely encounters a distinctive suite of phytochemicals in hostplant tissues. Little is known, however, about the detoxification mechanisms upon which this species relies to metabolize these compounds. In this study, larval guts containing hostplant tissues were homogenized, and metabolism was determined by incubating reactions with and without NADPH and analyzing for substrate disappearance and product appearance by gas chromatography-mass spectrometry. Using this approach, we found indications of carboxylesterase activity, in the form of appropriate alcohol metabolites for three aliphatic esters in hostplant tissues-octyl acetate, octyl butyrate, and hexyl butyrate. Involvement of webworm esterases in hostplant detoxification subsequently was confirmed with metabolism assays with pure compounds. This study is the first to implicate esterases in lepidopteran larval midgut metabolism of aliphatic esters, ubiquitous constituents of flowers and fruits. In addition, this method confirmed that webworms detoxify furanocoumarins and myristicin in their hostplants via cytochrome P450-mediated metabolism, and demonstrated that these enzymes also metabolize the coumarin osthol and the fatty acid derivative palmitolactone. PMID:22350520

  12. Effect of gamma irradiation on the insect development and esterase activity in the confused flour beetle, tribolium confusum (Duval.)

    International Nuclear Information System (INIS)

    Three day-old adults of the confused flour beetle, tribolium confusum were irradiated with gamma doses (10-40 Gray) to investigate the effects of irradiation on the F1 development and on the activity of esterase enzyme in F1 adult males and females. The total numbers of the F1 larvae, pupae and adults were decreased with increasing the irradiation dose. Esterase pattern of the adults was affected by the higher doses of irradiation. The mutagenic effect of these doses is represented by the disappearance of the electrophoretic patterns of some beetles.4 Figs., 1 Tab

  13. Comparative antiplatelet activity of COX1 NSAIDS versus aspirin, encompassing regimen simplification and gastroprotection: a call for a controlled study

    Directory of Open Access Journals (Sweden)

    B. Rothschild

    2011-09-01

    Full Text Available The cardioprotective/platelet inhibitory role of non-steroidal antiinflammatory drugs (NSAIDs has been controversial, perhaps in contrast to the accepted prophylactic role of aspirin (114. That cardioprotective effect is attributed to the platelet aggregation inhibitory effects of aspirin and COX 1 active NSAIDS (10, 11, 13 and can be studied without requirement for massive numbers of patients. Such cardioprotection, however, has its own risks. Significant gastrointestinal toxicity is still present with the 75-81 mg aspirin dose and appears no less than that found with the higher doses once routinely utilized in treatment of arthritis (2, 8, 9. One study even reported that 4% of patients receiving aspirin had moderate to severe bleeding (14. The challenge with aspirin is that even with a 75 mg dose, the frequency of severe gastrointestinal hemorrhage is double that of placebo (2, 8, 9 and not different from that observed with COX 1 NSAIDs, in the abse

  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. The psychrophilic bacterium Pseudoalteromonas halosplanktis TAC125 possesses a gene coding for a cold-adapted feruloyl esterase activity that shares homology with esterase enzymes from gamma-proteobacteria and yeast.

    Science.gov (United States)

    Aurilia, Vincenzo; Parracino, Antonietta; Saviano, Michele; Rossi, Mose'; D'Auria, Sabato

    2007-08-01

    The complete genome of the psychrophilic bacteria Pseudoalteromonas haloplanktis TAC 125, recently published, owns a gene coding for a putative esterase activity corresponding to the ORF PSHAa1385, also classified in the Carbohydrate Active Enzymes database (CAZY) belonging to family 1 of carbohydrate esterase proteins. This ORF is 843 bp in length and codes for a protein of 280 amino acid residues. In this study we characterized and cloned the PSHAa1385 gene in Escherichia coli. We also characterized the recombinant protein by biochemical and biophysical methodologies. The PSHAa1385 gene sequence showed a significant homology with several carboxyl-esterase and acetyl-esterase genes from gamma-proteobacteria genera and yeast. The recombinant protein exhibited a significant activity towards pNP-acetate, alpha-and beta-naphthyl acetate as generic substrates, and 4-methylumbelliferyl p-trimethylammonio cinnamate chloride (MUTMAC) as a specific substrate, indicating that the protein exhibits a feruloyl esterase activity that it is displayed by similar enzymes present in other organisms. Finally, a three-dimensional model of the protein was built and the amino acid residues involved in the catalytic function of the protein were identified. PMID:17543477

  16. An Esterase with Superior Activity and Enantioselectivity towards 1,2-O-Isopropylideneglycerol Esters Obtained by Protein Design

    NARCIS (Netherlands)

    Godinho, Luis F.; Reis, C.R.; van Merkerk, Ronald; Poelarends, Gerrit J.; Quax, Wim J.

    2012-01-01

    The Escherichia coli esterase YbfF displays high activity towards 1,2-O-isopropylideneglycerol (IPG) butyrate and IPG caprylate, and prefers the R-enantiomer of these substrates, producing the S-enantiomer of the IPG product in excess. To improve the potential of the enzyme for the kinetic resolutio

  17. Evaluation of the nitrite and leukocyte esterase activity tests for the diagnosis of acute symptomatic urinary tract infection in men.

    NARCIS (Netherlands)

    Koeijers, J.J.; Kessels, A.G.H.; Nys, S.; Bartelds, A.; Donker, G.; Stobberingh, E.; Verbon, A.

    2007-01-01

    For 422 male patients with symptoms indicative of a urinary tract infection, nitrite and leukocyte esterase activity dipstick test results were compared with results of culture of urine samples. The positive predictive value of a positive nitrite test result was 96%. Addition of results of the leuko

  18. Aspirin inhibits vascular plasminogen activator activity in vivo. Studies utilizing a new assay to quantify plasminogen activator activity.

    OpenAIRE

    Levin, R I; Harpel, P C; Weil, D; T. S. Chang; Rifkin, D. B.

    1984-01-01

    Vascular or tissue-type plasminogen activator (TPA) is a key enzyme in physiologic fibrinolysis. To study the role of prostaglandins in modulating the synthesis and release of TPA in vivo, we prospectively studied the effect of aspirin (650 mg/d X 2) on TPA activity in 13 human subjects before and after 10 min of forearm venous occlusion. TPA activity was quantified by a newly developed enzyme-linked immunosorbent assay that both measures and differentiates between TPA and urokinase (UK)-like...

  19. Spatial distribution and esterase activity in populations of Aedes (Stegomyia aegypti (Linnaeus (Diptera: Culicidae resistant to temephos

    Directory of Open Access Journals (Sweden)

    Wanessa Porto Tito Gambarra

    2013-04-01

    Full Text Available INTRODUCTION: The need for studies that describe the resistance patterns in populations of Aedes aegypti (Linnaeus in function of their region of origin justified this research, which aimed to characterize the resistance to temephos and to obtain information on esterase activity in populations of Aedes aegypti collected in municipalities of the State of Paraíba. METHODS: Resistance to temephos was evaluated and characterized from the diagnostic dose of 0.352mg i.a./L and multiple concentrations that caused mortalities between 5% and 99%. Electrophoresis of isoenzymes was used to verify the patterns of esterase activity among populations of the vector. RESULTS: All populations of Aedes aegypti were resistant to temephos, presenting a resistance rate (RR greater than 20. The greatest lethal dose 50% of the sample (CL50 was found for the municipality of Lagoa Seca, approximately forty-one times the value of CL50 for the Rockefeller population. The populations characterized as resistant showed two to six regions of α and β-esterase, called EST-1 to EST-6, while the susceptible population was only seen in one region of activity. CONCLUSIONS: Aedes aegypti is widely distributed and shows a high degree of resistance to temephos in all municipalities studied. In all cases, esterases are involved in the metabolism and, consequently, in the resistance to temephos.

  20. Spatial distribution and esterase activity in populations of Aedes (Stegomyia aegypti (Linnaeus (Diptera: Culicidae resistant to temephos

    Directory of Open Access Journals (Sweden)

    Wanessa Porto Tito Gambarra

    2013-09-01

    Full Text Available INTRODUCTION: The need for studies that describe the resistance patterns in populations of Aedes aegypti (Linnaeus in function of their region of origin justified this research, which aimed to characterize the resistance to temephos and to obtain information on esterase activity in populations of Aedes aegypti collected in municipalities of the State of Paraíba. METHODS: Resistance to temephos was evaluated and characterized from the diagnostic dose of 0.352mg i.a./L and multiple concentrations that caused mortalities between 5% and 99%. Electrophoresis of isoenzymes was used to verify the patterns of esterase activity among populations of the vector. RESULTS: All populations of Aedes aegypti were resistant to temephos, presenting a resistance rate (RR greater than 20. The greatest lethal dose 50% of the sample (CL50 was found for the municipality of Lagoa Seca, approximately forty-one times the value of CL50 for the Rockefeller population. The populations characterized as resistant showed two to six regions of α and β-esterase, called EST-1 to EST-6, while the susceptible population was only seen in one region of activity. CONCLUSIONS: Aedes aegypti is widely distributed and shows a high degree of resistance to temephos in all municipalities studied. In all cases, esterases are involved in the metabolism and, consequently, in the resistance to temephos.

  1. 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.

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

    OpenAIRE

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

    2015-01-01

    Introduction 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...

  3. Solution behavior and activity of a halophilic esterase under high salt concentration.

    Directory of Open Access Journals (Sweden)

    Lang Rao

    Full Text Available BACKGROUND: Halophiles are extremophiles that thrive in environments with very high concentrations of salt. Although the salt reliance and physiology of these extremophiles have been widely investigated, the molecular working mechanisms of their enzymes under salty conditions have been little explored. METHODOLOGY/PRINCIPAL FINDINGS: A halophilic esterolytic enzyme LipC derived from archeaon Haloarcula marismortui was overexpressed from Escherichia coli BL21. The purified enzyme showed a range of hydrolytic activity towards the substrates of p-nitrophenyl esters with different alkyl chains (n = 2-16, with the highest activity being observed for p-nitrophenyl acetate, consistent with the basic character of an esterase. The optimal esterase activities were found to be at pH 9.5 and [NaCl] = 3.4 M or [KCl] = 3.0 M and at around 45 degrees C. Interestingly, the hydrolysis activity showed a clear reversibility against changes in salt concentration. At the ambient temperature of 22 degrees C, enzyme systems working under the optimal salt concentrations were very stable against time. Increase in temperature increased the activity but reduced its stability. Circular dichroism (CD, dynamic light scattering (DLS and small angle neutron scattering (SANS were deployed to determine the physical states of LipC in solution. As the salt concentration increased, DLS revealed substantial increase in aggregate sizes, but CD measurements revealed the maximal retention of the alpha-helical structure at the salt concentration matching the optimal activity. These observations were supported by SANS analysis that revealed the highest proportion of unimers and dimers around the optimal salt concentration, although the coexistent larger aggregates showed a trend of increasing size with salt concentration, consistent with the DLS data. CONCLUSIONS/SIGNIFICANCE: The solution alpha-helical structure and activity relation also matched the highest proportion of enzyme unimers

  4. Comparative antiplatelet activity of COX1 NSAIDS versus aspirin, encompassing regimen simplification and gastroprotection: a call for a controlled study

    OpenAIRE

    B. Rothschild

    2011-01-01

    The cardioprotective/platelet inhibitory role of non-steroidal antiinflammatory drugs (NSAIDs) has been controversial, perhaps in contrast to the accepted prophylactic role of aspirin (114). That cardioprotective effect is attributed to the platelet aggregation inhibitory effects of aspirin and COX 1 active NSAIDS (10, 11, 13) and can be studied without requirement for massive numbers of patients. Such cardioprotection, however, has its own risks. Significant gastrointestinal toxicity is stil...

  5. Cloning, expression and characterization of a novel cold-active and organic solvent-tolerant esterase from Monascus ruber M7.

    Science.gov (United States)

    Guo, Hailun; Zhang, Yan; Shao, Yanchun; Chen, Wanping; Chen, Fusheng; Li, Mu

    2016-07-01

    Cold active esterases are a class of important biocatalysts that exhibit high activity at low temperatures. In this study, a search for putative cold-active esterase encoding genes from Monascus ruber M7 was performed. A cold-active esterase, named Lip10, was isolated, cloned, purified, and characterized. Amino acid sequence analysis reveals that Lip10 contained a conserved sequence motif Gly(173)-Xaa-Ser(175)-Xaa-Gly(177) that is also present in the majority of esterases and lipases. Phylogenetic analysis indicated that Lip10 was a novel microbial esterase. The lip10 gene was cloned and heterologously expressed in Escherichia coli BL21(DE3), resulting in the expression of an active and soluble protein that constituted 40 % of the total cell protein content. Lip10 maintained almost 50 % of its maximal activity at 4-10 °C, with optimal activity at 40 °C. Furthermore, Lip10 retained 184-216 % of its original activity, after incubation in 50 % (v/v) hydrophobic organic solvents for 24 h. The enzyme also exhibited high activity under alkaline conditions and good tolerance to metal ions in the reaction mixture. These results indicate that Lip10 may have potential uses in chemical synthesis and food processing industrial applications as an esterase. PMID:27209523

  6. 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.)

  7. 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.

  8. Activity and dynamics of an enzyme, pig liver esterase, in near-anhydrous conditions

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, Murielle [ORNL; Kurkal-Siebert, V [University of Heidelberg; Dunn, Rachel V. [University of Manchester, UK; Tehei, M [University of Waikato, New Zealand; Finney, J.L. [University College, London; Smith, Jeremy C [ORNL; Daniel, R. M. [University of Waikato, New Zealand

    2010-10-01

    Water is widely assumed to be essential for life, although the exact molecular basis of this requirement is unclear. Water facilitates protein motions, and although enzyme activity has been demonstrated at low hydrations in organic solvents, such nonaqueous solvents may allow the necessary motions for catalysis. To examine enzyme function in the absence of solvation and bypass diffusional constraints we have tested the ability of an enzyme, pig liver esterase, to catalyze alcoholysis as an anhydrous powder, in a reaction system of defined water content and where the substrates and products are gaseous. At hydrations of 3 ( 2) molecules of water per molecule of enzyme, activity is several orders-of-magnitude greater than nonenzymatic catalysis. Neutron spectroscopy indicates that the fast ( nanosecond) global anharmonic dynamics of the anhydrous functional enzyme are suppressed. This indicates that neither hydration water nor fast anharmonic dynamics are required for catalysis by this enzyme, implying that one of the biological requirements of water may lie with its role as a diffusion medium rather than any of its more specific properties.

  9. Potato tuber pectin structure is influenced by pectin methyl esterase activity and impacts on cooked potato texture

    OpenAIRE

    Ross, Heather A.; Wright, Kathryn M.; McDougall, Gordon J.; Roberts, Alison G.; Chapman, Sean N.; Morris, Wayne L.; Hancock, Robert D; Stewart, Derek; Tucker, Gregory A; James, Euan K.; Taylor, Mark A

    2010-01-01

    Although cooked potato tuber texture is an important trait that influences consumer preference, a detailed understanding of tuber textural properties at the molecular level is lacking. Previous work has identified tuber pectin methyl esterase activity (PME) as a potential factor impacting on textural properties. In this study, tuber PME isoform and gene expression profiles have been determined in potato germplasm with differing textural properties as assessed using an amended wedge fracture m...

  10. Spatial distribution and esterase activity in populations of Aedes (Stegomyia) aegypti (Linnaeus) (Diptera: Culicidae) resistant to temephos

    OpenAIRE

    Wanessa Porto Tito Gambarra; Walter Fabrício Silva Martins; Maurício Lilioso de Lucena Filho; Ingredy Meneses Cavalcanti de Albuquerque; Otávia Karla dos Santos Apolinário; Eduardo Barbosa Beserra

    2013-01-01

    INTRODUCTION: The need for studies that describe the resistance patterns in populations of Aedes aegypti (Linnaeus) in function of their region of origin justified this research, which aimed to characterize the resistance to temephos and to obtain information on esterase activity in populations of Aedes aegypti collected in municipalities of the State of Paraíba. METHODS: Resistance to temephos was evaluated and characterized from the diagnostic dose of 0.352mg i.a...

  11. 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 purification. The enzyme with retained peptide demonstrated 2 to 4-fold higher activity against methyl caffeate and methyl p-coumarate, with specific activities of 477.6 and 174.4 U mg(-1) respectively, than the equivalent activities of the benchmark FAE from Aspergillus niger A and B. ActOFaeI retained activity over a broad pH range with a maximum at 9 but >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. PMID:26497017

  12. 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.

  13. 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.

  14. Immobilization of cholesterol esterase in mesoporous silica materials and its hydrolytic activity toward diethyl phthalate

    Energy Technology Data Exchange (ETDEWEB)

    Orita, Toru, E-mail: nqj45366@nifty.com [Division of Chemistry for Materials, Graduate School of Engineering, Mie University, 1577 Kurimamachiya-cho, Tsu, Mie 514-8570 (Japan); Taiyo Kagaku Co. Ltd., 800 Yamada-cho, Yokkaichi, Mie 512-1111 (Japan); Tomita, Masahiro [Division of Chemistry for Materials, Graduate School of Engineering, Mie University, 1577 Kurimamachiya-cho, Tsu, Mie 514-8570 (Japan); Saito, Takao; Nishida, Nasakazu; Kato, Katsuya [National Institute of Advanced Industrial Science and Technology, 2266-78 Anagahora, Moriyamaku, Nagoya, Aichi 463-8560 (Japan)

    2012-05-01

    Cholesterol esterase (CE, cholesteryl ester hydrolase, EC 3.1.1.13) from porcine pancreas (molecular weight 400-500 kDa) exhibits hydrolytic activity toward various toxic organic phthalate esters. CE was confined in the nanospace (diameter 3-30 nm) of five types of mesoporous silica (MPS) that differ in structural properties such as pore diameter, pore volume, and particle morphology. These structural properties were characterized by transmission electron microscopy, small-angle X-ray diffraction, N{sub 2} adsorption-desorption experiments, solid-state {sup 13}C nuclear magnetic resonance (NMR), and solid-state {sup 29}Si NMR. Catalytic activities of immobilized and free CE were evaluated by the hydrolysis of diethyl phthalate in phosphate buffer solutions containing an organic cosolvent. Optimal activity recovery was achieved when CE was immobilized in n-decane-functionalized MPS, which had a large pore size (22.5 nm). The immobilization also protected against effects of temperature within the range 30 Degree-Sign C-60 Degree-Sign C; CE immobilized in n-decyl-functionalized MPS exhibited better thermal stability than in non-functionalized MPS or free CE. Moreover, it retained approximately 60% of its catalytic activity even after six catalytic cycles. - Highlights: Black-Right-Pointing-Pointer The highest activity of immobilized CE was shown in MPS with a pore size of 22.5 nm. Black-Right-Pointing-Pointer Catalytic efficiency improved when MPS was functionalized by n-decyl substitution. Black-Right-Pointing-Pointer Immobilized CE exhibited good thermal stability and reusability. Black-Right-Pointing-Pointer Organic co-solvent and the substrate structures affected enzyme activities.

  15. Immobilization of cholesterol esterase in mesoporous silica materials and its hydrolytic activity toward diethyl phthalate

    International Nuclear Information System (INIS)

    Cholesterol esterase (CE, cholesteryl ester hydrolase, EC 3.1.1.13) from porcine pancreas (molecular weight 400–500 kDa) exhibits hydrolytic activity toward various toxic organic phthalate esters. CE was confined in the nanospace (diameter 3–30 nm) of five types of mesoporous silica (MPS) that differ in structural properties such as pore diameter, pore volume, and particle morphology. These structural properties were characterized by transmission electron microscopy, small-angle X-ray diffraction, N2 adsorption–desorption experiments, solid-state 13C nuclear magnetic resonance (NMR), and solid-state 29Si NMR. Catalytic activities of immobilized and free CE were evaluated by the hydrolysis of diethyl phthalate in phosphate buffer solutions containing an organic cosolvent. Optimal activity recovery was achieved when CE was immobilized in n-decane-functionalized MPS, which had a large pore size (22.5 nm). The immobilization also protected against effects of temperature within the range 30 °C–60 °C; CE immobilized in n-decyl-functionalized MPS exhibited better thermal stability than in non-functionalized MPS or free CE. Moreover, it retained approximately 60% of its catalytic activity even after six catalytic cycles. - Highlights: ► The highest activity of immobilized CE was shown in MPS with a pore size of 22.5 nm. ► Catalytic efficiency improved when MPS was functionalized by n-decyl substitution. ► Immobilized CE exhibited good thermal stability and reusability. ► Organic co-solvent and the substrate structures affected enzyme activities.

  16. [Application of basophil activation test in diagnosing aspirin hypersensitivity].

    Science.gov (United States)

    Gawinowska, Marika; Specjalski, Krzysztof; Chełmińska, Marta; Łata, Jakub; Zieliński, Maciej

    2015-01-01

    In the face of increasing prevalence of hypersensitivity reactions, introduction of effective, reliable and safe methods plays a crucial role in their diagnosing. Among the currently available laboratory (in vitro) methods is basophil activation test (BAT). It is a flow- cytometry based assay that allows to identificate in the blood sample basophils and additionally to asses the degree of cell activation after exposure to an antigen. The most common superficial identification markers are CD63 and CD203c, which increase in number after activation. Basophil actvation test can be applied to confirm diagnosis of allergy to Hymenoptera venoms, food, pollens and hypersensitivity to drugs. The aim of present paper is to present theoretical methods of this test as well as its pros and cons. We focus also on presentation of clinical case where BAT seemed to be a necessary addition to a routine diagnostic pathway. We present a case of identification of the culprit drug which caused an anaphylactic reaction. PMID:25577537

  17. Healthy older humans exhibit augmented carotid-cardiac baroreflex sensitivity with aspirin during muscle mechanoreflex and metaboreflex activation.

    Science.gov (United States)

    Drew, Rachel C; Blaha, Cheryl A; Herr, Michael D; Stocker, Sean D; Sinoway, Lawrence I

    2015-10-01

    Low-dose aspirin inhibits thromboxane production and augments the sensitivity of carotid baroreflex (CBR) control of heart rate (HR) during concurrent muscle mechanoreflex and metaboreflex activation in healthy young humans. However, it is unknown how aging affects this response. Therefore, the effect of low-dose aspirin on carotid-cardiac baroreflex sensitivity during muscle mechanoreflex with and without metaboreflex activation in healthy older humans was examined. Twelve older subjects (6 men and 6 women, mean age: 62 ± 1 yr) performed two trials during two visits preceded by 7 days of low-dose aspirin (81 mg) or placebo. One trial involved 3 min of passive calf stretch (mechanoreflex) during 7.5 min of limb circulatory occlusion (CO). In another trial, CO was preceded by 1.5 min of 70% maximal voluntary contraction isometric calf exercise (mechanoreflex and metaboreflex). HR (ECG) and mean arterial blood pressure (MAP; Finometer) were recorded. CBR function was assessed using rapid neck pressure application (+40 to -80 mmHg). Aspirin significantly decreased baseline thromboxane B2 production by 83 ± 4% (P aspirin, CBR-HR maximal gain and operating point gain were significantly higher during stretch with metabolite accumulation compared with placebo (maximal gain: -0.23 ± 0.03 vs. -0.14 ± 0.02 and operating point gain: -0.11 ± 0.03 vs. -0.04 ± 0.01 beats·min(-1)·mmHg(-1) for aspirin and placebo, respectively, P aspirin augments CBR-HR sensitivity during concurrent muscle mechanoreflex and metaboreflex activation in healthy older humans. This increased sensitivity appears linked to reduced thromboxane sensitization of muscle mechanoreceptors, which consequently improves CBR-HR control. PMID:26371168

  18. Novel Redox-Dependent Esterase Activity (EC 3.1.1.2 for DJ-1: Implications for Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Emmanuel Vázquez-Mayorga

    2016-08-01

    Full Text Available Mutations the in human DJ-1 (hDJ-1 gene are associated with early-onset autosomal recessive forms of Parkinson’s disease (PD. hDJ-1/parkinsonism associated deglycase (PARK7 is a cytoprotective multi-functional protein that contains a conserved cysteine-protease domain. Given that cysteine-proteases can act on both amide and ester substrates, we surmised that hDJ-1 possessed cysteine-mediated esterase activity. To test this hypothesis, hDJ-1 was overexpressed, purified and tested for activity towards 4-nitrophenyl acetate (pNPA as µmol of pNPA hydrolyzed/min/mg·protein (U/mg protein. hDJ-1 showed maximum reaction velocity esterase activity (Vmax = 235.10 ± 12.00 U/mg protein, with a sigmoidal fit (S0.5 = 0.55 ± 0.040 mM and apparent positive cooperativity (Hill coefficient of 2.05 ± 0.28. A PD-associated mutant of DJ-1 (M26I lacked activity. Unlike its protease activity which is inactivated by reactive oxygen species (ROS, esterase activity of hDJ-1 is enhanced upon exposure to low concentrations of hydrogen peroxide (<10 µM and plateaus at elevated concentrations (>100 µM suggesting that its activity is resistant to oxidative stress. Esterase activity of DJ-1 requires oxidation of catalytic cysteines, as chemically protecting cysteines blocked its activity whereas an oxido-mimetic mutant of DJ-1 (C106D exhibited robust esterase activity. Molecular docking studies suggest that C106 and L126 within its catalytic site interact with esterase substrates. Overall, our data show that hDJ-1 contains intrinsic redox-sensitive esterase activity that is abolished in a PD-associated mutant form of the hDJ-1 protein.

  19. Novel Redox-Dependent Esterase Activity (EC 3.1.1.2) for DJ-1: Implications for Parkinson’s Disease

    Science.gov (United States)

    Vázquez-Mayorga, Emmanuel; Díaz-Sánchez, Ángel G.; Dagda, Ruben K.; Domínguez-Solís, Carlos A.; Dagda, Raul Y.; Coronado-Ramírez, Cynthia K.; Martínez-Martínez, Alejandro

    2016-01-01

    Mutations the in human DJ-1 (hDJ-1) gene are associated with early-onset autosomal recessive forms of Parkinson’s disease (PD). hDJ-1/parkinsonism associated deglycase (PARK7) is a cytoprotective multi-functional protein that contains a conserved cysteine-protease domain. Given that cysteine-proteases can act on both amide and ester substrates, we surmised that hDJ-1 possessed cysteine-mediated esterase activity. To test this hypothesis, hDJ-1 was overexpressed, purified and tested for activity towards 4-nitrophenyl acetate (pNPA) as µmol of pNPA hydrolyzed/min/mg·protein (U/mg protein). hDJ-1 showed maximum reaction velocity esterase activity (Vmax = 235.10 ± 12.00 U/mg protein), with a sigmoidal fit (S0.5 = 0.55 ± 0.040 mM) and apparent positive cooperativity (Hill coefficient of 2.05 ± 0.28). A PD-associated mutant of DJ-1 (M26I) lacked activity. Unlike its protease activity which is inactivated by reactive oxygen species (ROS), esterase activity of hDJ-1 is enhanced upon exposure to low concentrations of hydrogen peroxide (100 µM) suggesting that its activity is resistant to oxidative stress. Esterase activity of DJ-1 requires oxidation of catalytic cysteines, as chemically protecting cysteines blocked its activity whereas an oxido-mimetic mutant of DJ-1 (C106D) exhibited robust esterase activity. Molecular docking studies suggest that C106 and L126 within its catalytic site interact with esterase substrates. Overall, our data show that hDJ-1 contains intrinsic redox-sensitive esterase activity that is abolished in a PD-associated mutant form of the hDJ-1 protein. PMID:27556455

  20. Variations in elastaselike esterase activities in human leucocytes during cell maturation.

    Science.gov (United States)

    Feinstein, G; Janoff, A

    1976-05-01

    Granules of human peripheral blood leucocytes contain four well-characterized elastase isozymes and one or two slow-moving elastaselike esterases (SE) which have not been as well characterized. SE are capable of hydrolyzing typical elastase synthetic sybstrates such as N-acetyl-dl-alanine-alpha-naphthyl ester (Ac-DL-Ala-1-ONap) and N-t-butyloxycarbonyl-L-alanine-p-nitrophenyl ester (Boc-Ala-ONp), but unlike the highly basic elastase isozymes, SE barely migrate into 13% acrylamide gels during cationic electrophoresis at pH 4.3. Hydrolysis of Ac-DL-Ala-1-ONap by SE requires the presence of Triton in the gel, and hydrolysis of Boc-Ala-ONp by the same enzyme(s) is also enhanced in the presence of the detergent. Triton is not required for these activities, in the case of the elastase isozymes. Diisopropylfluorophosphate (Dip-F) inactivates both SE and the elastase isozymes, whereas Ac-(Ala)2-Pro-AlaCH2Cl (a powerful inactivator of the leucocyte elastase isozymes at 10-4 M concentration) does not inactivate SE at the same concentration. Immunochemical studies revealed antigenic cross-reaction between the rapidly migrating leucocyte elastase isozymes and SE. Two preparations of leucocyte granules from nonleukemic bone marrow cells showed no activity of the rapidly migrating elastase isozymes, but did contain SE activity. SE may be a precursor or zymogen form of the elastase isozymes, present in immature cells and partly retained through later stages of development. PMID:1265076

  1. Leukocyte Esterase Activity in Vaginal Fluid of Pregnant and Non-Pregnant Women With Vaginitis/Vaginosis and in Controls

    Directory of Open Access Journals (Sweden)

    Per-Anders Mårdh

    2003-01-01

    Full Text Available Objectives: To determine the leukocyte esterase (LE activity in vaginal lavage fluid of women with acute and recurrent vulvovaginal candidosis (VVC and RVVC respectively, bacterial vaginosis (BV, and in pregnant and non-pregnant women without evidence of the three conditions. Also to compare the result of LE tests in women consulting at different weeks in the cycle and trimesters of pregnancy.The LE activity was correlated to vaginal pH, number of inflammatory cells in stained vaginal smears, type of predominating vaginal bacteria and presence of yeast morphotypes.

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

    Science.gov (United States)

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

    2013-10-01

    Different aspirin dosing regimens have been suggested to impact outcomes when used in combination with adenosine diphosphate (ADP) P2Y12 receptor antagonists. Prior investigations have shown that not only aspirin, but also potent ADP P2Y12 receptor blockade can inhibit thromboxane A2-mediated platelet activation. The impact of aspirin dosing on ADP mediated platelet activities is unknown and represents the aim of this in vitro pilot pharmacodynamic (PD) investigation. Twenty-six patients with stable coronary artery disease on aspirin 81 mg/day and P2Y12 naïve were enrolled. PD assessments were performed at baseline, while patients were on 81 mg/day aspirin and after switching to 325 mg/day for 7 ± 2 days with and without escalating concentrations (vehicle, 1, 3, and 10 μM) of prasugrel's active metabolite (P-AM). PD assays included flow cytometric assessment of VASP to define the platelet reactivity index (PRI) and the Multiplate Analyzer (MEA) using multiple agonists [ADP, ADP + prostaglandin (PGE1), arachidonic acid (AA), and collagen]. Escalating P-AM concentrations showed incremental platelet P2Y12 inhibition measured by VASP-PRI (paspirin dosing regimen at any P-AM concentration (vehicle: p=0.899; 1 μM: p=0.888; 3 μM: p=0.524; 10 μM: p=0.548). Similar findings were observed in purinergic markers assessed by MEA (ADP and ADP+PGE1). P-AM addition significantly reduced AA and collagen induced platelet aggregation (paspirin dose. In conclusion, aspirin dosing does not appear to affect PD measures of ADP-mediated platelet reactivity irrespective of the degree of P2Y12 receptor blockade. P2Y12 receptor blockade modulates platelet reactivity mediated by alternative activators. PMID:23884248

  3. Aspirin decreases systemic exposure to clopidogrel through modulation of P-glycoprotein but does not alter its antithrombotic activity.

    Science.gov (United States)

    Oh, J; Shin, D; Lim, K S; Lee, S; Jung, K-H; Chu, K; Hong, K S; Shin, K-H; Cho, J-Y; Yoon, S H; Ji, S C; Yu, K-S; Lee, H; Jang, I-J

    2014-06-01

    Decreased oral clopidogrel absorption caused by induction of intestinal permeability glycoprotein (P-gp) expression after aspirin administration was observed in rats. This study evaluated the effect of aspirin coadministration on the pharmacokinetics/pharmacodynamics of clopidogrel in humans. A single 75-mg dose of clopidogrel was orally administered before and after 2 and 4 weeks of once-daily 100-mg aspirin administration in 18 healthy volunteers who were recruited based on CYP2C19 and PON1 genotypes. Plasma concentrations of clopidogrel and its active metabolite, H4, and relative platelet inhibition (RPI) were determined. The P-gp microRNA miR-27a increased by up to 7.67-fold (P = 0.004) and the clopidogrel area under the concentration-time curve (AUC) decreased by 14% (P > 0.05), but the AUC of H4 remained unchanged and RPI increased by up to 15% (P = 0.002) after aspirin administration. These findings indicate low-dose aspirin coadministration may decrease clopidogrel bioavailability but does not decrease its efficacy. PMID:24566733

  4. 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.

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

    International Nuclear Information System (INIS)

    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

  6. Toxicity of dimlore and its effect on acetylcholine esterase (ache) activity in chilo partellus (swinhoe)

    International Nuclear Information System (INIS)

    Dimlore (662 EC), a mixture of chlorpyriphos and dimethoate insecticide, was tested against the larvae of Chilo partellus (Swinhoe). Administration of 10 ml of 0.1%, Dimlore per insect resulted in the inhibition of Acetyl choline esterase (AchE) by 57.22% as compared to the control. The topical application of same dose of different concentrations of Dimlore resulted in significant dose dependant mortality after 24h and 48th of treatment. (author)

  7. 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.

  8. Glucuronoyl esterases are active on the polymeric substrate methyl esterified glucuronoxylan.

    Science.gov (United States)

    Biely, Peter; Malovíková, Anna; Uhliariková, Iveta; Li, Xin-Liang; Wong, Dominic W S

    2015-08-19

    Alkali extracted beechwood glucuronoxylan methyl ester prepared by esterification of 4-O-methyl-D-glucuronic acid side residues by methanol was found to serve as substrate of microbial glucuronoyl esterases from Ruminococcus flavefaciens, Schizophyllum commune and Trichoderma reesei. The enzymatic deesterification was monitored by (1)H NMR spectroscopy and evaluated on the basis of the decrease of the signal of the ester methyl group and increase of the signal of methanol. The results show for the first time the action of enzymes on polymeric substrate, which imitates more closely the natural substrate in plant cell walls than the low molecular mass artificial substrates used up to present. PMID:26216754

  9. Effects of aspirin on number,activity and inducible nitric oxide synthase of endothelial progenitor cells from peripheral blood

    Institute of Scientific and Technical Information of China (English)

    Tu-gang CHEN; Jun-zhu CHEN; Xu-dong XIE

    2006-01-01

    Aim:To investigate whether aspirin has an influence on endothelial progenitor cells (EPC).Methods:Total mononuclear cells (MNC) were isolated from peripheral blood by Ficoll density gradient centrifugation,then cells were plated on fibronectin-coated culture dishes.After 7 d of culture,attached cells were stimulated with aspirin (to achieve final concentrations of 1,2,5,and 10 mmol/L) for 3,6,12,and 24 h.EPC were characterized as adherent cells that were double positive for 1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine low density lipoprotein (DiLDL) uptake and lectin binding by direct fluorescent staining.EPC proliferation and migration were assayed using a 3- (4,5-dimethyl-2 thiazoyl) -2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and a modified Boyden chamber assay.respectively.An EPC adhesion assay was performed by replating the EPC on fibronectin-coated dishes,and then adherent cells were counted.In vitro vasculogenesis activity was assayed by using an in vitro vasculogenesis kit. Inducible nitric oxide synthase (iNOS) was assayed by Westem blotting.Results:Incubation of isolated human MNC with aspirin decreased the number of EPC.Aspirin also decreased the proliferative,migratory,adhesive,and in vitro Vasculogenesis capacity of EPC,and also their iNOS levels in a concentration-and time-dependent manner.Conclusion:Aspirin decreases (1) the number of EPC; (2) the proliferative,migratory,adhesive and in vitro vasculogenesis capacities of EPC;and (3) iNOS levels in EPC.

  10. 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

    OpenAIRE

    Russo, Isabella; Viretto, Michela; Barale, Cristina; Mattiello, Luigi; Doronzo, Gabriella; Pagliarino, Andrea; Cavalot, Franco; Trovati, Mariella; Anfossi, Giovanni

    2012-01-01

    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...

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

    OpenAIRE

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

    2015-01-01

    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...

  12. 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.

  13. 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. PMID:26991291

  14. Flexibility and Stability Trade-Off in Active Site of Cold-Adapted Pseudomonas mandelii Esterase EstK.

    Science.gov (United States)

    Truongvan, Ngoc; Jang, Sei-Heon; Lee, ChangWoo

    2016-06-28

    Cold-adapted enzymes exhibit enhanced conformational flexibility, especially in their active sites, as compared with their warmer-temperature counterparts. However, the mechanism by which cold-adapted enzymes maintain their active site stability is largely unknown. In this study, we investigated the role of conserved D308-Y309 residues located in the same loop as the catalytic H307 residue in the cold-adapted esterase EstK from Pseudomonas mandelii. Mutation of D308 and/or Y309 to Ala or deletion resulted in increased conformational flexibility. Particularly, the D308A or Y309A mutant showed enhanced substrate affinity and catalytic rate, as compared with wild-type EstK, via enlargement of the active site. However, all mutant EstK enzymes exhibited reduced thermal stability. The effect of mutation was greater for D308 than Y309. These results indicate that D308 is not preferable for substrate selection and catalytic activity, whereas hydrogen bond formation involving D308 is critical for active site stabilization. Taken together, conformation of the EstK active site is constrained via flexibility-stability trade-off for enzyme catalysis and thermal stability. Our study provides further insights into active site stabilization of cold-adapted enzymes. PMID:27259687

  15. Effects of juvenile hormone (JH) analog insecticides on larval development and JH esterase activity in two spodopterans.

    Science.gov (United States)

    El-Sheikh, El-Sayed A; Kamita, Shizuo G; Hammock, Bruce D

    2016-03-01

    Juvenile hormone analog (JHA) insecticides are biological and structural mimics of JH, a key insect developmental hormone. Toxic and anti-developmental effects of the JHA insecticides methoprene, fenoxycarb, and pyriproxyfen were investigated on the larval and pupal stages of Spodoptera littoralis and Spodoptera frugiperda. Bioassays showed that fenoxycarb has the highest toxicity and fastest speed of kill in 2nd instar S. littoralis. All three JHAs affected the development of 6th instar (i.e., final instar) and pupal S. frugiperda. JH esterase (JHE) is a critical enzyme that helps to regulate JH levels during insect development. JHE activity in the last instar S. littoralis and S. frugiperda was 11 and 23nmolmin(-1)ml(-1) hemolymph, respectively. Methoprene and pyriproxyfen showed poor inhibition of JHE activity from these insects, whereas fenoxycarb showed stronger inhibition. The inhibitory activity of fenoxycarb, however, was more than 1000-fold lower than that of OTFP, a highly potent inhibitor of JHEs. Surprisingly, topical application of methoprene, fenoxycarb or pyriproxyfen on 6th instars of S. littoralis and S. frugiperda prevented the dramatic reduction in JHE activity that was found in control insects. Our findings suggest that JHAs may function as JH agonists that play a disruptive role or a hormonal replacement role in S. littoralis and S. frugiperda. PMID:26969437

  16. Aspirin and heart disease

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000092.htm Aspirin and heart disease To use the sharing features ... say if you are pregnant or breastfeeding. Taking Aspirin Take your aspirin with food and water. This ...

  17. 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.

  18. Ferulic acid release and 4-vinylguaiacol formation during brewing and fermentation: indications for feruloyl esterase activity in Saccharomyces cerevisiae.

    Science.gov (United States)

    Coghe, Stefan; Benoot, Koen; Delvaux, Filip; Vanderhaegen, Bart; Delvaux, Freddy R

    2004-02-11

    The release of ferulic acid and the subsequent thermal or enzymatic decarboxylation to 4-vinylguaiacol are inherent to the beer production process. Phenolic, medicinal, or clove-like flavors originating from 4-vinylguaiacol frequently occur in beer made with wheat or wheat malt. To evaluate the release of ferulic acid and the transformation to 4-vinylguaiacol, beer was brewed with different proportions of barley malt, wheat, and wheat malt. Ferulic acid as well as 4-vinylguaiacol levels were determined by HPLC at several stages of the beer production process. During brewing, ferulic acid was released at the initial mashing phase, whereas moderate levels of 4-vinylguaiacol were formed by wort boiling. Higher levels of the phenolic flavor compound were produced during fermentations with brewery yeast strains of the Pof(+) phenotype. In beer made with barley malt, ferulic acid was mainly released during the brewing process. Conversely, 60-90% of ferulic acid in wheat or wheat malt beer was hydrolyzed during fermentation, causing higher 4-vinylguaiacol levels in these beers. As cereal enzymes are most likely inactivated during wort boiling, the additional release of ferulic acid during fermentation suggests the activity of feruloyl esterases produced by brewer's yeast. PMID:14759156

  19. 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.)

    Institute of Scientific and Technical Information of China (English)

    Wanigasekera Daya Ratnasooriya

    2015-01-01

    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 ofCamellia sinensis L. Methods: Black tea brew (BTB) was made according to International Organization for Standardization 3103 specifications and concentrations ofBTB tested were 37.5, 75.0, 150.0, 300.0 and 600.0µg/mL for antilipase and anti-cholesterol esterase assays and 0.25, 0.50 and 1.00µg/mL for cholesterol micellization inhibitory assay. Results:The results showed thatBTB of Sri Lankan low grown orthodox Orange Pekoe grade black tea has marked and dose-dependent (r2 = 0.95) cholesterol micellization inhibitory activityin vitro comparable to epigallocatechin gallate, the reference drug used. In contrast, BTB had only mild but dose-dependent (r2= 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 ofBTB of Sri Lankan low grown orthodox Orange Pekoe grade tea as a beverage may be a useful strategy in the management of hyperlipidaemia.

  20. CHOLESTEROL ESTERASE ENZYME INHIBITORY AND ANTIOXIDANT ACTIVITIES OF LEAVES OF CAMELLIA SINENSIS (L. KUNTZE. USING IN VITRO MODELS

    Directory of Open Access Journals (Sweden)

    Pradeep Kumar et al.

    2011-11-01

    Full Text Available The present study was to evaluate the in vitro cholesterol esterase enzyme inhibitory and in vitro antioxidant activity of the methanol extract of the leaves of Camellia sinensis (L.. Phytochemical screening of the extract shows the presence of flavonoids, phenolics and terpenoids. The extract shows ability to inhibit the enzyme with IC50 (82.46±0.74µg/ml where as that of standard, Orlistat (24.15±0.59µg/ml. Antioxidant and free radical scavenging activity were also assessed by using the methods, IC50 values for Nitric oxide radical scavenging activity (396.83±0.83µg/ml, whereas for standard curcumin (260.38±0.66µg/ml, hydroxyl radical scavenging activity (47.04±2.26µg/ml and for quercetin (70.99±1.31µg/ml. Moreover, the extract was found to scavenge the superoxide with 50% inhibition at 308.17±23.25µg/ml and standard ascorbic acid at 225.08±2.44µg/ml, IC50 for ferrous chelating ability assay (44.12±4.63µg/ml and of ascorbic acid (47.25±.89µg/ml. Total content of flavonoids present in 1mg of extract was 19.8±0.11 µg quercetin equivalents/mg. Results indicated that the extract shows potential bioactive compounds which might have a beneficial impact on diseases related to cholesterol synthesis and showed potential antioxidant and free radical scavenging activities.

  1. Aspirin for the next generation

    OpenAIRE

    Henderson, Nick; Smith, Tom

    2013-01-01

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

  2. Neuroprotection by Aspirin and Sodium Salicylate Through Blockade of NF-kappaB Activation

    Science.gov (United States)

    Grilli, Mariagrazia; Pizzi, Marina; Memo, Maurizio; Spano, Pierfranco

    1996-11-01

    Aspirin (acetylsalicylic acid) is a commonly prescribed drug with a wide pharmacological spectrum. At concentrations compatible with amounts in plasma during chronic anti-inflammatory therapy, acetylsalicylic acid and its metabolite sodium salicylate were found to be protective against neurotoxicity elicited by the excitatory amino acid glutamate in rat primary neuronal cultures and hippocampal slices. The site of action of the drugs appeared to be downstream of glutamate receptors and to involve specific inhibition of glutamate-mediated induction of nuclear factor kappa B. These results may contribute to the emerging theme of anti-inflammatory drugs and neurodegeneration.

  3. Mucosal adaptation to aspirin induced gastric damage in humans. Studies on blood flow, gastric mucosal growth, and neutrophil activation.

    OpenAIRE

    Konturek, J W; Dembinski, A; Stoll, R.; Domschke, W; Konturek, S. J.

    1994-01-01

    The gastropathy associated with the ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin is a common side effect of this class of drugs, but the precise mechanisms by which they cause mucosal damage have not been fully explained. During continued use of an injurious substance, such as aspirin, the extent of gastric mucosal damage decreases and this phenomenon is named gastric adaptation. To assess the extent of mucosal damage by aspirin and subsequent adaptation the eff...

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

    Institute of Scientific and Technical Information of China (English)

    Maushmi Shailesh Kumar; Sukanya Gopalkrishnan

    2014-01-01

    Objective: To test three marine sponges Halichondria glabrata Keller, 1891; Spirastrellapachyspira (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.

  5. 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.

  6. A novel cold active esterase derived from Colombian high Andean forest soil metagenome.

    Science.gov (United States)

    Jiménez, Diego Javier; Montaña, José Salvador; Alvarez, Diana; Baena, Sandra

    2012-01-01

    In order to search new lipolytic enzymes and conduct bioprospecting of microbial communities from high Andean forest soil, a metagenomic library of approximately 20,000 clones was constructed in Escherichia coli using plasmid p-Bluescript II SK+. The library covered 80 Mb of the metagenomic DNA mainly from Proteobacteria, Actinobacteria and Acidobacteria. Two clones with lipolytic activity in tributyrin as a substrate were recovered. Clone BAA3G2 (pSK-estGX1) was selected and the entire 4.6 Kb insert sequence was determined. The sequence had a GC content of 70.6% and could be derived from an undescribed Actinobacteria genome. One open reading frame encoded a polypeptide of 210 amino acids (gene estGX1) with a molecular mass of 22.4 kDa that contained the pentapeptide G-P-S-G-G near the N-terminus essential for lipase activity and the putative catalytic triad was identified, also a putative ribosomal binding site located 18 bp upstream the estGX1 ATG start codon was identified. The phylogenetic analysis suggested that the protein belonged to a new lipase family. The secreted enzyme showed a preference for short length fatty acids, with specific activity against p-nitrophenyl-butyrate (0.142 U/mg of total protein), it was cold active with relative activity of 30% at 10°C and moderately thermo active with relative activity of 80% at 50°C and had a pH optimum of 8.0 at 40°C. PMID:22806812

  7. 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.

    solvents that favour synthesis over hydrolysis, i.e. systems with low water content such as organic solvents or ionic liquids (ILs). The esterification of sinapic acid with glycerol catalysed by FAE A from Aspergillus niger (AnFaeA) in a series of ILs containing 15% (v/v) buffer showed that An......FaeA stability – and hence activity – was highly dependent on the anion nature: AnFaeA was stable and active for more than 2 hours in [PF6]--based ILs, but rapidly lost activity in [BF4]--based systems. This effect can be explained in terms of hydrogen bonding capacity of the two anions: As predicted by the......], but this is the first report on FAE stability in ILs [2]. COSMO-RS, which is now widely used for solvent screening in the complex IL systems [3], may be a valuable tool for fast enzyme stability predictions and/or solvent screening in the future....

  8. Does high serum uric acid level cause aspirin resistance?

    Science.gov (United States)

    Yildiz, Bekir S; Ozkan, Emel; Esin, Fatma; Alihanoglu, Yusuf I; Ozkan, Hayrettin; Bilgin, Murat; Kilic, Ismail D; Ergin, Ahmet; Kaftan, Havane A; Evrengul, Harun

    2016-06-01

    In patients with coronary artery disease (CAD), though aspirin inhibits platelet activation and reduces atherothrombotic complications, it does not always sufficiently inhibit platelet function, thereby causing a clinical situation known as aspirin resistance. As hyperuricemia activates platelet turnover, aspirin resistance may be specifically induced by increased serum uric acid (SUA) levels. In this study, we thus investigated the association between SUA level and aspirin resistance in patients with CAD. We analyzed 245 consecutive patients with stable angina pectoris (SAP) who in coronary angiography showed more than 50% occlusion in a major coronary artery. According to aspirin resistance, two groups were formed: the aspirin resistance group (Group 1) and the aspirin-sensitive group (Group 2). Compared with those of Group 2, patients with aspirin resistance exhibited significantly higher white blood cell counts, neutrophil counts, neutrophil-to-lymphocyte ratios, SUA levels, high-sensitivity C-reactive protein levels, and fasting blood glucose levels. After multivariate analysis, a high level of SUA emerged as an independent predictor of aspirin resistance. The receiver-operating characteristic analysis provided a cutoff value of 6.45 mg/dl for SUA to predict aspirin resistance with 79% sensitivity and 65% specificity. Hyperuricemia may cause aspirin resistance in patients with CAD and high SUA levels may indicate aspirin-resistant patients. Such levels should thus recommend avoiding heart attack and stroke by adjusting aspirin dosage. PMID:26656902

  9. Ultra-sensitive conductometric detection of pesticides based on inhibition of esterase activity in Arthrospira platensis

    International Nuclear Information System (INIS)

    Enzymatic conductometric biosensor, using immobilized Arthrospira platensis cells on gold interdigitated electrodes, for the detection of pesticides in water, was elaborated. Cholinesterase activity (AChE) was inhibited by pesticides and a variation of the local conductivity was measured after addition of the substrate acetylthiocholine chloride (AChCl). The Michaelis–Menten constant (Km) was evaluated to be 1.8 mM through a calibration curve of AChCl. Inhibition of AChE was observed with paraoxon-methyl, parathion-methyl, triazine and diuron with a detection limit of 10−18 M, 10−20 M, 10−20 M and 10−12 M, respectively and the half maximal inhibitory concentration (IC50) was determined at 10−16 M, 10−20 M, 10−18 M and 10−06 M, respectively. An important decrease of response time τ90% was recorded for AChE response towards AChCl after 30 min cell exposure to pesticides. Scanning electron microscopy images revealed a degradation of the cell surface in presence of pesticides at 10−06 M. -- Highlights: •Conductometric measurements of AChE activity of Arthrospira platensis. •Enhancement of sensitivity of detection using gold nanoparticles. •Determination of Michaelis–Menten constant Km (1.8 mM). •Study of inhibition of AChE of Spirulina by pesticides. •Determination of IC50 for each pesticide. -- We develop a biosensor, based on microalgae, devoted for toxicity measurements in water for environmental control

  10. Aspirin, Butalbital, and Caffeine

    Science.gov (United States)

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

  11. Aspirin and NSAIDS

    Science.gov (United States)

    ... Digestive Health Topic / Aspirin and NSAIDS Aspirin and NSAIDS Basics Resources Overview What should I know about Non-Steroidal Anti-Inflammatory Drugs (NSAIDS)? The second major cause for ulcers is irritation ...

  12. Non-specific esterases in partly mineralized bovine enamel

    DEFF Research Database (Denmark)

    Moe, D; Kirkeby, S

    1990-01-01

    esterases were shown to be present in the enamel matrix. The enzymes showed highest activity at pH 6.5-7.5. In sections a strong reaction was observed in the secretory ameloblasts. The esterases may be proteolytic enzymes that participate in the degradation of the matrix proteins....

  13. 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. Assu...... 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....

  14. The Wood Rot Ascomycete Xylaria polymorpha Produces a Novel GH78 Glycoside Hydrolase That Exhibits α-l-Rhamnosidase and Feruloyl Esterase Activities and Releases Hydroxycinnamic Acids from Lignocelluloses

    OpenAIRE

    Nghi, Do Huu; Bittner, Britta; Kellner, Harald; Jehmlich, Nico; Ullrich, René; Pecyna, Marek J.; Nousiainen, Paula; Sipilä, Jussi; Huong, Le Mai; Hofrichter, Martin; Liers, Christiane

    2012-01-01

    Soft rot (type II) fungi belonging to the family Xylariaceae are known to substantially degrade hardwood by means of their poorly understood lignocellulolytic system, which comprises various hydrolases, including feruloyl esterases and laccase. In the present study, several members of the Xylariaceae were found to exhibit high feruloyl esterase activity during growth on lignocellulosic materials such as wheat straw (up to 1,675 mU g−1) or beech wood (up to 80 mU g−1). Following the ester-clea...

  15. 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.

  16. 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.

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

    OpenAIRE

    Yuan Shi-Ying; Zhou Jie-Ping; Liu Ren-Gang; Zheng Jin; Li Long-Yan; Wu Yan; Wang Yan-Ping; Shang You; Yao Shang-Long

    2011-01-01

    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 ...

  18. 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

  19. 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.

  20. 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

  1. Biochemical characterization and structural analysis of a new cold-active and salt-tolerant esterase from the marine bacterium Thalassospira sp.

    Science.gov (United States)

    De Santi, Concetta; Leiros, Hanna-Kirsti S; Di Scala, Alessia; de Pascale, Donatella; Altermark, Bjørn; Willassen, Nils-Peder

    2016-05-01

    A gene encoding an esterase, ThaEst2349, was identified in the marine psychrophilic bacterium Thalassospira sp. GB04J01. The gene was cloned and overexpressed in E. coli as a His-tagged fusion protein. The recombinant enzyme showed optimal activity at 45 °C and the thermal stability displayed a retention of 75 % relative activity at 40 °C after 2 h. The optimal pH was 8.5 but the enzyme kept more than 75 % of its maximal activity between pH 8.0 and 9.5. ThaEst2349 also showed remarkable tolerance towards high concentrations of salt and it was active against short-chain p-nitrophenyl esters, displaying optimal activity with the acetate. The enzyme was tested for tolerance of organic solvents and the results are suggesting that it could function as an interesting candidate for biotechnological applications. The crystal structure of ThaEst2349 was determined to 1.69 Å revealing an asymmetric unit containing two chains, which also is the biological unit. The structure has a characteristic cap domain and a catalytic triad comprising Ser158, His285 and Asp255. To explain the cold-active nature of the enzyme, we compared it against thermophilic counterparts. Our hypothesis is that a high methionine content, less hydrogen bonds and less ion pairs render the enzyme more flexible at low temperatures. PMID:27016194

  2. The structure of a novel thermophilic esterase from the Planctomycetes species, Thermogutta terrifontis reveals an open active site due to a minimal ‘cap’ domain.

    Directory of Open Access Journals (Sweden)

    Jennifer Ann Littlechild

    2015-11-01

    Full Text Available A carboxyl esterase (TtEst2 has been identified in a novel thermophilic bacterium, Thermogutta terrifontis from the phylum Planctomycetes and has been cloned and over-expressed in Escherichia coli. The enzyme has been characterised biochemically and shown to have activity towards small p-nitrophenyl (pNP carboxylic esters with optimal activity for pNP-acetate. The enzyme shows moderate thermostability retaining 75% activity after incubation for 30 minutes at 70°C. The crystal structures have been determined for the native TtEst2 and its complexes with the carboxylic acid products propionate, butyrate and valerate. TtEst2 differs from most enzymes of the α/β-hydrolase family 3 as it lacks the majority of the ‘cap’ domain and its active site cavity is exposed to the solvent. The bound ligands have allowed the identification of the carboxyl pocket in the enzyme active site. Comparison of TtEst2 with structurally related enzymes has given insight into how differences in their substrate preference can be rationalised based upon the properties of their active site pockets.

  3. 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. PMID:27561771

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

    Directory of Open Access Journals (Sweden)

    Zhou L

    2015-08-01

    Full Text Available Lin Zhou,1,2,* Xingmei Duan,1,2,* Shi Zeng,1 Ke Men,1 Xueyan Zhang,1 Li Yang,1 Xiang Li1 1State Key Laboratory of Biotherapy, Cancer Center and Department of Urology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Sichuan Food and Drug Safety Monitoring and Review of Certification, Adverse Reaction Monitoring Center, Drug Abuse Monitoring Center, Chengdu, People’s Republic of China *These authors contributed equally to this work Abstract: Natural product curcumin (Cur and H2S-releasing prodrug SH-aspirin (SH-ASA are potential anticancer agents with diverse mechanisms, but their clinical application prospects are restricted by hydrophobicity and limited efficiency. In this work, we coencapsulated SH-ASA and Cur into methoxy poly(ethylene glycol-poly (lactide-coglycolide (mPEG-PLGA nanoparticles through a modified oil-in-water single-emulsion solvent evaporation process. The prepared SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles had a mean particle size of 122.3±6.8 nm and were monodispersed (polydispersity index =0.179±0.016 in water, with high drug-loading capacity and stability. Intriguingly, by treating with SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles, obvious synergistic anticancer effects on ES-2 and SKOV3 human ovarian carcinoma cells were observed in vitro, and activation of the mitochondrial apoptosis pathway was indicated. Our results demonstrated that SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles could have potential clinical advantages for the treatment of ovarian cancer. Keywords: drug delivery, cancer therapy, ovarian cancer, synergistic effect

  5. Attenuation of gastric mucosal inflammation induced by aspirin through activation of A2A adenosine receptor in rats

    Institute of Scientific and Technical Information of China (English)

    Masaru Odashima; Reina Ohba; Sumio Watanabe; Joel Linden; Michiro Otaka; Mario Jin; Koga Komatsu; Isao Wada; Youhei Horikawa; Tamotsu Matsuhashi; Natsumi Hatakeyama; Jinko Oyake

    2006-01-01

    AIM: To determine whether a specific adenosine A2A receptor agonist (ATL-146e) can ameliorate aspirin-induced gastric mucosal lesions in rats, and reduce neutrophil accumulation and production of pro-inflammatory cytokines.METHODS: Gastric lesions were produced by oral gavage of aspirin (200 mg/kg) and HCl (0.15 mol/L,8.0 mL/kg). 4-{3-[6-Amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-cyclohexanecarboxylic acid methyl ester (ATL-146e,2.5-5 μg/kg, IP) was injected 30 min before the administration of aspirin. Tissue myeloperoxidase (MPO) concentration in gastric mucosa was measured as an index of neutrophil infiltration. Gastric mucosal concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined by ELISA. Also, we examined the effect of ATL-146e on tissue prostaglandin E2 (PGE2) production and gastric secretion.RESULTS: Intragastric administration of aspirin induced multiple hemorrhagic erosions in rat gastric mucosa. The total length of gastric erosions (ulcer index) in control rats was 29.8±7.75 mm and was reduced to 3.8±1.42 mm after pretreatment with 5.0 g/kg ATL-146e (P< 0.01).The gastric contents of MPO and pro-inflammatory cytokines were all increased after the administration of aspirin and reduced to nearly normal levels by ATL-146e.Gastric mucosal PGE2 concentration was not affected by intraperitoneal injection of ATL-146e.CONCLUSION: The specific adenosine A2A receptor agohist, ATL-146e, has potent anti-ulcer effects presumably mediated by its anti-inflammatory properties.

  6. Immobilization of a novel cold active esterase onto Fe3O4∼cellulose nano-composite enhances catalytic properties.

    Science.gov (United States)

    Rahman, Mohammad Asadur; Culsum, Umma; Kumar, Ashok; Gao, Haofeng; Hu, Nan

    2016-06-01

    A novel esterase, EstH was cloned, purified and characterized from the marine bacterium Zunongwangia sp. The purified EstH showed optimum activity at 30°C and pH 8.5 with ∼50% of original activity at 0°C. EstH was stable in high salt conditions (0-4.5M NaCl). To improve the characteristics and explore the possibilities for application, a new immobilization matrix, Fe3O4∼cellulose nano-composite, was prepared and was characterized by Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscope (SEM). Interestingly the optimal temperature of immobilized EstH elevated to 35°C. Compared to its free form, immobilized EstH showed better temperature stability (48.5% compared to 22.40% at 50°C after 30min), prolonged half-life (32h compared to 18h), higher storage stability (∼71% activity compared to ∼40% after 50days of storage), improved pH tolerance (∼73% activity at pH 4 and 10), and, more importantly, reusability (∼50% activity after 8 repetitive cycles of usage). Enzyme kinetics showed an increase in the Vmax (from 35.76 to 51.14μM/min) and Kcat (from 365s(-1) to 520s(-1)) after immobilization. The superior catalytic properties of immobilized EstH suggest its great potential in biotechnology and industrial processes. PMID:26976070

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

    Science.gov (United States)

    Russo, Matias; Fabersani, Emanuel; Abeijón-Mukdsi, María C; Ross, Romina; Fontana, Cecilia; Benítez-Páez, Alfonso; Gauffin-Cano, Paola; Medina, Roxana B

    2016-01-01

    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. PMID:27399766

  8. Directed evolution of a thermostable esterase

    OpenAIRE

    Giver, Lori; Gershenson, Anne; Freskgard, Per-Ola; Arnold, Frances H

    1998-01-01

    We have used in vitro evolution to probe the relationship between stability and activity in a mesophilic esterase. Previous studies of these properties in homologous enzymes evolved for function at different temperatures have suggested that stability at high temperatures is incompatible with high catalytic activity at low temperatures through mutually exclusive demands on enzyme flexibility. Six generations of random mutagenesis, recombination, and screening stabilized Bacillus subtilis p-nit...

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

    OpenAIRE

    Pettit, Lauren K; Varsanyi, Christopher; Tadros, James; Vassiliou, Evros

    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 ...

  10. Xylella fastidiosa esterase rather than hydroxynitrile lyase.

    Science.gov (United States)

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

    2015-03-01

    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. PMID:25684099

  11. Pharmacological and anti-oxidant evaluation of Aspirin, nimodipine and its combination for anti-Parkinson′s activity in MPTP induced rat model

    Directory of Open Access Journals (Sweden)

    Nilesh S Ambhore

    2014-01-01

    Full Text Available Background: Mitochondrial damage and oxidative stress plays important role in Parkinson′s disease (PD. Mitochondria are very crucial part in the cell and have many cellular functions including the generation of ATP and intracellular calcium (Ca 2+ homeostasis. Mitochondria also contribute in the formation of reactive oxygen species (ROS and activating the programmed cell death response, apoptosis. Usually ROS is eliminated by antioxidants present in body, but in case of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP induction all the antioxidants become ineffective. Aim: The present study investigated the effects of the non selective cyclooxygenase (COX inhibitor aspirin and L-type calcium channel inhibitor nimodipine in the prevention of motor impairments and observed anti-oxidant effects in rats after induction of early phase of Parkinson′s disease by using neurotoxin MPTP. Materials and Methods: The PD was induced in animals by single injection of MPTP. After 48 hrs of induction animals were treated with aspirin and nimodipine for 60 days, then behavioral, biochemical and antioxidant parameters were evaluated to examine the effectiveness of treatment. Statistical analysis was carried out by using one-way ANOVA followed by Bonferroni multiple comparisons test. Results: The treatment with combination (Aspirin 50mg/kg, Nimodipine 30mg/kg showed significant (P < 0.001 increase in brain dopamine level, improves the complex I activity and also ameliorate the amount of antioxidant enzymes like superoxide dismutase (SOD, glutathione reductase (GSH, catalase (CAT and decrease in lipid peroxidation. Conclusions : These results strongly suggest that combination shows a good neuroprotective effect compared to single treatment on motor, biochemical and antioxidant parameters in early phase of Parkinson′s disease.

  12. Antiulcer activity of water soaked Glycine max L. grains in aspirin induced model of gastric ulcer in Wistar rats

    Directory of Open Access Journals (Sweden)

    Dushyant Kumar

    2013-01-01

    Full Text Available Introduction: Glycine max L. with Drakshasava, widely used by traditional healers as a formulation for the treatment of peptic ulcer in rural northern Karnataka in India, appears to be effective as assessed by patients and in our previously published research work of traditionally used formulation. Aim: The present study was undertaken to evaluate the safety and efficacy of the overnight water soaked G. max grains. This is one of the components of traditional formulation. The study, approved by Institutional Animal Ethics Committee was carried out in male Wistar rats after assessing its toxicity in mice. Materials and Methods: Four groups of rats (n = 6 in each group were treated with aspirin 200 mg/kg oral. In addition to aspirin control group received normal saline, standard group received 20 mg/kg omeprazole and 3 rd and 4 th group received G. max 250 and 500 mg/kg, respectively. All treatments were administered orally every 24 h for 7 days. After 24 hours fasting, on the 8 th day stomach contents were aspirated under anesthesia to estimate free and total acidity. Stomachs were opened along the greater curvature to calculate ulcer index and subjected to histopathology studies. Statistics: The results were analyzed by one-way analysis of variance followed-by Dunnett′s post hoc test. P ≤0.05 was considered as significant. Results: The severity of aspirin induced ulceration was found significantly (P < 0.05 decreased in test groups compared with the control group. Free and total acidity was significantly reduced in 500 mg/kg treated group, compared with the control group and was inferior to omeprazole treated group. Conclusion: The grain of G. max was found to be effective against aspirin induced ulcers.

  13. A Method for Fast Assessment of OP/CB Exposure in the Japanese Quail (Coturnix coturnix japonica Using Combined Esterases Enzyme Activity as Biomarkers

    Directory of Open Access Journals (Sweden)

    Kasim Sakran Abass

    2014-01-01

    Full Text Available The aims of this study were to investigate the presence of different esterase activities in plasma and liver for Japanese quail and to combine determination of both carboxylesterase and cholinesterase as biochemical biomarker in order to identify the effects of carbamate and organophosphate compounds exposure. Carboxylesterase exhibits larger sensitivity to carbamate and organophosphate compounds than to cholinesterase and is present at higher levels. This permitted nature and distribution of carboxylesterase or cholinesterase to be measured. One predominant toxicological form of enzyme level constant in its patterns of motivation and inhibition with cholinesterase was identified in plasma with an apparent Michaelis constant for butyrylthiocholine iodide of 0.394 mM. Carboxylesterase activity in liver was considered by its preferential hydrolysis of the S-phenyl thioacetate. A concentration dependent decrease of carboxylesterase and cholinesterase has demonstrated during in vitro incubation of malathion, parathion, and trichlorfon in the range 0.125–2 mM, while with methomyl was in the range 0.25–4 mM. When quail (n=15 was exposed orally for 48 h to concentrations of carbamate or organophosphate compounds of 3–200 mg/kg, the percentage inhibition of cholinesterase was in each case larger than that of carboxylesterase and reached statistical significance (P<0.05 at lower concentrations.

  14. Phospho-Aspirin (MDC-22) Prevents Pancreatic Carcinogenesis in Mice.

    Science.gov (United States)

    Mattheolabakis, George; Papayannis, Ioannis; Yang, Jennifer; Vaeth, Brandon M; Wang, Ruixue; Bandovic, Jela; Ouyang, Nengtai; Rigas, Basil; Mackenzie, Gerardo G

    2016-07-01

    Pancreatic cancer is a deadly disease with a dismal 5-year survival rate of <6%. The currently limited treatment options for pancreatic cancer underscore the need for novel chemopreventive and therapeutic agents. Accumulating evidence indicates that aspirin use is associated with a decreased risk of pancreatic cancer. However, the anticancer properties of aspirin are restricted by its gastrointestinal toxicity and its limited efficacy. Therefore, we developed phospho-aspirin (MDC-22), a novel derivative of aspirin, and evaluated its chemopreventive efficacy in preclinical models of pancreatic cancer. Phospho-aspirin inhibited the growth of human pancreatic cancer cell lines 8- to 12-fold more potently than aspirin; based on the 24-hour IC50 values. In a Panc-1 xenograft model, phospho-aspirin, at a dose of 100 mg/kg/d 5 times per week for 30 days, reduced tumor growth by 78% (P < 0.01 vs. vehicle control). Furthermore, phospho-aspirin prevented pancreatitis-accelerated acinar-to-ductal metaplasia in mice with activated Kras. In p48-Cre;Kras(G12D) mice, cerulein treatment (6 hourly injections two times per week for 3 weeks) led to a significant increase in ductal metaplasia, replacing the majority of the exocrine compartment. Administration of phospho-aspirin 100 mg/kg/day five times per week for 21 days (starting on the first day of cerulein injection) inhibited the acinar-to-ductal metaplasia, reducing it by 87% (P < 0.01, vs. cerulein-treated control). Phospho-aspirin appeared to be safe, with the animals showing no signs of toxicity during treatment. Mechanistically, phospho-aspirin inhibited EGFR activation in pancreatic cancer, an effect consistently observed in pancreatic cancer cells, primary acinar explants and in vivo In conclusion, our findings indicate that phospho-aspirin has strong anticancer efficacy in preclinical models of pancreatic cancer, warranting its further evaluation. Cancer Prev Res; 9(7); 624-34. ©2016 AACR. PMID:27138793

  15. Genetic Determinants of On-Aspirin Platelet Reactivity: Focus on the Influence of PEAR1

    OpenAIRE

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

    2014-01-01

    Background 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. Aim 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...

  16. Repellent Activity of Extracts of Wild Rice Species against Panonychus citri and Aphis citricola in Associated with Esterase Isoenzyme in Insests

    Institute of Scientific and Technical Information of China (English)

    WAN Shu-qing; LIU Xiang-fa; FENG Guo-zhong; PAN Da-jian

    2006-01-01

    Six species of wild rice with different ecophenotypes including Oryza grandiglumis (E6-1, E6-3 / 6-4), O. minuta (E13-9,E13-13), O. officinalis (E15-8, E15-13), O. punctata (E16-1, E16-3, E1 6-13), O. granulata (E7-4), and O. latifolia (101392, E9-1, E9-10)were extracted with methnol and the repellent activity of the extracts against the two insects Aphis citricola and Panonychus citri were studied. The extracts of O. officinalis E15-8 showed higher repellent rate to the two insects than those of the other species. The repellent rates of the extracts of E15-8 to P. citriand A. citricola were 83.26% and 87.86% at 5×104 μg/mL in 24 h and 87.95% and 82.43% in 48 h, respectively. The extracts of O. officinalis E15-8 had the effect of inhibition to the esterase of the two insects.

  17. 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

    Science.gov (United States)

    Ranjbar, Samira; Shokoohinia, Yalda; Ghobadi, Sirous; Gholamzadeh, Saeed; Moradi, Nastaran; Ashrafi-Kooshk, Mohammad Reza; Aghaei, Abbas

    2013-01-01

    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. PMID:24319355

  18. 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 ...

  19. Isozymic variations in specific and nonspecific esterase and its thermostability in silkworm, Bombyx mori L.

    Science.gov (United States)

    Patnaik, Bharat Bhusan; Biswas, Tapati Datta; Nayak, Sandeepta Kumar; Saha, A K; Majumdar, M K

    2012-09-01

    Esterase isozymic variations were documented in the haemolymph of developed multivoltine and bivoltine silkworm breeds during unfavorable seed crop seasons of May - September using á- and â- napthylacetate separately to identify specific and nonspecific esterase having thermotolerant potentiality. Variations existed in the isozyme pattern with three bands (Est-2, 3 and 4) in pure Nistari race and other developed multivoltine and bivoltine breeds. Est-2 and Est-3 were non-specific esterases as they were observed when both á- and â-napthylacetate was used as substrates separately. Est-4 band was observed only with á-napthylacetate as substrate and was therefore confirmed to be specific á-esterase band in the haemolymph of silkworm, Bombyx mori L. Zymograms showed that the non-specific esterase band (Est-3) with R1 of 0.43 and specific á-esterase band (Est-4) with R(f) of 0.32 predominately withstood a temperature of 70 +/- 2 degrees C for a duration of 10 min and were confirmed as thermostable esterases in haemolymph of silkworm, Bombyx mori L. This also categorized the presence of thermostable esterases in developed multivoltine and bivoltine breeds of silkworm, even though the qualitative activity was more in the former than the latter. The qualitative presence of thermostable esterases and their activity could be adopted as an indicative biochemical marker in relation to thermotolerance in silkworm. PMID:23734447

  20. Temperature-sensitive molecularly imprinted microgels with esterase activity%具酯酶活性的温敏型分子印迹微凝胶

    Institute of Scientific and Technical Information of China (English)

    王红飞; 杨浩; 张黎明

    2011-01-01

    Temperature-sensitive molecularly imprinted microgels (MIGs) exhibiting esterase activity were prepared by a reverse emulsion method using dialdehyde dextran-histidine conjugate (PAD-His) as the functional macromonomer and p-nitrophenyl phosphate (NPP) as the stable transition state analogue (TSA) as well as Co2+ as the coordination center. The catalytic activity of MIGs was greatly influenced by the template amount, and could be modulated by temperature. The hydrolysis kinetics ofp-nitrophenyl acetate (NPA) in the presence of MIGs could be described by the Michaelis-Menten equation. The Michaelis-Menten constant and maximium velocity were found to be 2.2×105 mol/L and 2.04×108 mol/h,respectively. In addition, the MIGs were found to have a high catalytic selectivity to NPA.%以双醛葡聚糖-组氨酸偶连物(PAD-His)为功能大单体、过渡态类似物p-硝基苯磷酸酯(NPP)为模板分子、Co2+为中心离子,采用油包水反相乳液法首次制得具有酯酶活性的温敏型分子印迹微凝胶(MIGs).催化水解实验表明,MIGs催化活性受模板分子用量的影响,并可通过温度进行有效调控.MIGs催化p-硝基乙酸苯酯(NPA)水解反应行为可用Michaelis-Menten方程进行描述,其最大催化水解反应速率和Michaelis-Menten常数分别为2.04×10-8 mol/h和2.2×10-5 mol/L,且具有较好的催化选择性.

  1. 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. PMID:26201059

  2. Molecular targets of aspirin and cancer prevention.

    Science.gov (United States)

    Alfonso, L; Ai, G; Spitale, R C; Bhat, G J

    2014-07-01

    Salicylates from plant sources have been used for centuries by different cultures to treat a variety of ailments such as inflammation, fever and pain. A chemical derivative of salicylic acid, aspirin, was synthesised and mass produced by the end of the 19th century and is one of the most widely used drugs in the world. Its cardioprotective properties are well established; however, recent evidence shows that it can also act as a chemopreventive agent. Its antithrombotic and anti-inflammatory actions occur through the inhibition of cyclooxygenases. The precise mechanisms leading to its anticancer effects are not clearly established, although multiple mechanisms affecting enzyme activity, transcription factors, cellular signalling and mitochondrial functions have been proposed. This review presents a brief account of the major COX-dependent and independent pathways described in connection with aspirin's anticancer effects. Aspirin's unique ability to acetylate biomolecules besides COX has not been thoroughly investigated nor have all the targets of its primary metabolite, salicylic acid been identified. Recent reports on the ability of aspirin to acetylate multiple cellular proteins warrant a comprehensive study to investigate the role of this posttranslational modification in its anticancer effects. In this review, we also raise the intriguing possibility that aspirin may interact and acetylate cellular molecules such as RNA, and metabolites such as CoA, leading to a change in their function. Research in this area will provide a greater understanding of the mechanisms of action of this drug. PMID:24874482

  3. Individual variability in esterase activity and CYP1A levels in Chinook salmon (Oncorhynchus tshawytscha) exposed to esfenvalerate and chlorpyrifos

    OpenAIRE

    Wheelock, Craig E; Eder, Kai J.; Werner, Inge; Huang, Huazhang; Jones, Paul D.; Brammell, Benjamin F.; Elskus, Adria A.; Hammock, Bruce D.

    2005-01-01

    Acetylcholinesterase (AChE) activity has traditionally been monitored as a biomarker of organophosphate (OP) and/or carbamate exposure. However, AChE activity may not be the most sensitive endpoint for these agrochemicals, because OPs can cause adverse physiological effects at concentrations that do not affect AChE activity. Carboxylesterases are a related family of enzymes that have higher affinity than AChE for some OPs and carbamates and may be more sensitive indicators of environmental ex...

  4. EFFECT OF EDTA ON GASTRIC MUCOSAL LESION INDUCED BY ASPIRIN

    Directory of Open Access Journals (Sweden)

    M.A FESHARAKI M.A

    2002-06-01

    Full Text Available Introduction. Gastric ulcer is a multifactorial disease, which its pathophysioligy has not been clear yet. The aim of this study was to obtain the prophylactic effects of EDTA on Aspirin induced gastric mucosal lesions. Methods. In fasted male rats the effect of a single oral dose of the EDTA was evaluated in the following test systems: combination of 1 ml EDTA 1.5% + 300 mg/kg aspirin and 1 ml EDTA 1.5%, 2.5%, 5% and 7.5% 30 minutes before 300 mg/kg aspirin. Then the gastric mucosal lesions were assessed microscopically and marcroscopically. Results. EDTA at different doses reduced macroscopic and microscpic gastric mucosal lesion induced by aspirin. Discussion. Combination therapy of EDTA and aspirin has distinct advantages regard to both low gastrointestinal toxicity and restored therapeutic activity.

  5. On-line anti-acetylcholine esterase activity of extracts of oxystelma esculentum, aerva javanica and zanthoxylum armatum

    International Nuclear Information System (INIS)

    Alzheimer's disease (AD), a disease of brain, resulting in memory impairment and the loss of thinking. The main reason of Alzheimer's disease is firmly associated with some impairment in cholinergic transmission. This impairment may be improved by diminishing the breakdown of acetylcholine at the synaptic site in the brain by inhibiting acetylcholinesterase (AChE). In this work, extracts of three different plants Oxystelma esculentum (OEM), Aerva javanica (AJM) and Zanthoxylum armatum (ZAA) have been screened for their anti-AchE activity. Results of the study demonstrate that of the studied extracts, ZAA (IC/sub 50/ 55.5 micro g/ml) acquired stronger anti-AChE activity. While OEM with IC/sub 50/ 107.2 micro g/ml showed moderate and ZAE and AJM showed weaker action (IC/sub 50/ 182.5 and 275.2 micro g/ml). Galanthamine was used as a positive control (IC/sub 50/ 1.47 micro g/ml). (author)

  6. [Milestones of cardivascular pharmacotherapy: salicylates and aspirin].

    Science.gov (United States)

    Jerie, P

    2006-01-01

    The analgesic and antipyretic effect of the bark of willow has been known in Egypt and Greece for canturies. The modem era of salicylates starts with a letter sent 1758 by Reverend Edward Stone to The Royal Society in London. He described "an account of the success of the bark of willow in the cure of agues". His report. erroneously attributed to Edmond Stone. was published five years later. The active ingredient of willow bark. "salicine". was first isolated 1828 by Joseph Buchner, then by Henri Leroux, and also prepared from the oil of wintergreen (Gaultheria) and meadowsweet (Spirea ulmaria) by J. W. Lowig 1833. and called "Spirsäure", which was already pure acetylsalicylic acid. It was also synthetised 1853 by Ch. Gerhardt and finally 1897 in Bayer's laboratoires by Felix Hoffman, who also demonstrated its antiinflammatory efficacy. After two years of clinical trials with low doses, Bayer's management decided to start the productions and launched Aspirin as an analgetic worldwide in summer 1899. The first ASPIRIN ERA bagun. A completely new epoch started when J. N. Vane and Priscilla Piner demonstrated 1971 that the main mechanism of action of aspirin-like drugs is the inhibition of prostaglandin synthesis. In later studies the potency to inhibit platelet aggregation with small doses of aspirin (30-125 mg) was demonstrated. The Physicians'Health Study 1988 confirmed this effect: aspirin significantly reduced the risk of both, fatal and non-fatal myocardial infarction. and is now used in primary and secondary prevention of atherosclerosis. However the idea was not new: The use of salicylates and aspirin was throughly discussed more than 50 years ago: Paul C. Gibson published 1949 a well-documented case report on efficacy of aspirin in patients with angina, and Kl. Weber and P. Klein in Prague used Gibson's mixture successfully for patients with acute myocardial infarction (1951). Recently, the efficacy and security, the interactions and side-effects of low

  7. Mechanism of action of Neisseria gonorrhoeae O-acetylpeptidoglycan esterase, an SGNH serine esterase.

    Science.gov (United States)

    Pfeffer, John M; Weadge, Joel T; Clarke, Anthony J

    2013-01-25

    O-Acetylpeptidoglycan esterase from Neisseria gonorrhoeae functions to release O-acetyl groups from the C-6 position of muramoyl residues in O-acetylated peptidoglycan, thereby permitting the continued metabolism of this essential cell wall heteropolymer. It has been demonstrated to be a serine esterase with sequence similarity to the family CE-3 carbohydrate esterases of the CAZy classification system. In the absence of a three-dimensional structure for any Ape, further knowledge of its structure and function relationship is dependent on modeling and kinetic studies. In this study, we predicted Neisseria gonorrhoeae Ape1a to be an SGNH hydrolase with an adopted α/β-hydrolase fold containing a central twisted four-stranded parallel β-sheet flanked by six α-helices with the putative catalytic triad, Asp-366, His-369, and Ser-80 appropriately aligned within a pocket. The role of eight invariant and highly conserved residues localized to the active site was investigated by site-directed replacements coupled with kinetic characterization and binding studies of the resultant engineered enzymes. Based on these data and theoretical considerations, Gly-236 and Asn-268 were identified as participating at the oxyanion hole to stabilize the tetrahedral species in the reaction mechanism, whereas Gly-78, Asp-79, His-81, Asn-235, Thr-267, and Val-368 are proposed to position appropriately the catalytic residues and participate in substrate binding. PMID:23209280

  8. 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.

  9. 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?

    International Nuclear Information System (INIS)

    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

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    Satya Pathi

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

  12. 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. PMID:26491233

  13. Aspirin Often Wrongly Prescribed for Atrial Fibrillation

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159459.html Aspirin Often Wrongly Prescribed for Atrial Fibrillation Blood thinners -- not aspirin -- dramatically cut the risk of stroke, researchers say ...

  14. Macrophage activation by a vanadyl-aspirin complex is dependent on L-type calcium channel and the generation of nitric oxide

    International Nuclear Information System (INIS)

    Bone homeostasis is the result of a tight balance between bone resorption and bone formation where macrophage activation is believed to contribute to bone resorption. We have previously shown that a vanadyl(IV)-aspirin complex (VOAspi) regulates cell proliferation and differentiation of osteoblasts in culture. In this study, we assessed VOAspi and VO effects and their possible mechanism of action on a mouse macrophage cell line RAW 264.7. Both vanadium compounds inhibited cell proliferation in a dose-dependent manner. Nifedipine completely reversed the VOAspi-induced macrophage cytotoxicity, while it could not block the effect of VO. VOAspi also stimulated nitric oxide (NO) production, the oxidation of dihydrorhodamine 123 (DHR-123) and enhanced the expression of both constitutive and inducible isoforms of nitric oxide syntases (NOS). All these effects were abolished by nifedipine. Althogether our finding give evidence that VOAspi-induced macrophage cytotoxicity is dependent on L-type calcium channel and the generation of NO though the induction of eNOS and iNOS. Contrary, the parent compound VO exerted a cytotoxic effect by mechanisms independent of a calcium entry and the NO/NOS activation

  15. Trace element impurity determination in aspirin tablets by INAA

    International Nuclear Information System (INIS)

    Instrumental neutron activation analysis (INAA) was applied to assess trace element concentrations in six samples of aspirin tablets acquired in Sao Paulo city, Brazil. Concentrations of the elements Br, Ca, Co, Cr, Fe, K, La, Na, Sc and Zn were determined. Comparisons were made between the results obtained with published data for aspirins from foreign countries. Certified reference materials, INCT-MPH-2 Mixed Polish Herbs were analyzed for quality control of the analytical results. (author)

  16. Drug/drug interaction of common NSAIDs with antiplatelet effect of aspirin in human platelets.

    Science.gov (United States)

    Saxena, Aaruni; Balaramnavar, Vishal M; Hohlfeld, Thomas; Saxena, Anil K

    2013-12-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with the anti-platelet activity of aspirin at the level of the platelet cyclooxygenase-1 (COX-1) enzyme. In order to examine the interference of common NSAIDs with the anti-platelet activity of aspirin the human platelet rich plasma from voluntary donors was used for arachidonic acid-induced aggregation and determination of thromboxane synthesis. Further, docking studies were used to explain the molecular basis of the NSAID/aspirin interaction. The experimental results showed that celecoxib, dipyrone (active metabolite), ibuprofen, flufenamic acid, naproxen, nimesulide, oxaprozin, and piroxicam significantly interfere with the anti-platelet activity of aspirin, while diclofenac, ketorolac and acetaminophen do not. Docking studies suggested that NSAIDs forming hydrogen bonds with Ser530, Arg120, Tyr385 and other amino acids of the COX-1 hydrophobic channel interfere with antiplatelet activity of aspirin while non interfering NSAIDs do not form relevant hydrogen bond interactions within the aspirin binding site. In conclusion, docking analysis of NSAID interactions at the COX-1 active site appears useful to predict their interference with the anti-platelet activity of aspirin. The results, demonstrate that some NSAIDs do not interfere with the antiplatelet action of aspirin while many others do and provide a basis for understanding the observed differences among individual non-aspirin NSAIDs. PMID:24075938

  17. RELATIONSHIP OF NEUROPATHY TARGET ESTERASE INHIBITION TO NEUROPATHOLOGY AND ATAXIA IN HENS GIVEN ORGANOPHOSPHORUS ESTERS

    Science.gov (United States)

    Adult WhiteLeghorn hens were acutely exposed to 3 dosages of the following organophosphorus esters: mipafox, tri-ortho-tolyl phosphate (TOTP), penyl saligenin phosphate, diisppropylophosphoro-fluoridate (DFP), malathion and dichlorvos. europathy target esterase (NTE) activity was...

  18. 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 <0.0001) with corresponding increases in thromboxane B2 (5...

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

    Science.gov (United States)

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

    2016-05-01

    Aspirin's ability to inhibit cell proliferation and induce apoptosis in cancer cell lines is considered to be an important mechanism for its anti-cancer effects. We previously demonstrated that aspirin acetylated the tumor suppressor protein p53 at lysine 382 in MDA-MB-231 human breast cancer cells. Here, we extended these observations to human colon cancer cells, HCT 116 harboring wild type p53, and HT-29 containing mutant p53. We demonstrate that aspirin induced acetylation of p53 in both cell lines in a concentration-dependent manner. Aspirin-acetylated p53 was localized to the nucleus. In both cell lines, aspirin induced p21(CIP1). Aspirin also acetylated recombinant p53 (rp53) in vitro suggesting that it occurs through a non-enzymatic chemical reaction. Mass spectrometry analysis and immunoblotting identified 10 acetylated lysines on rp53, and molecular modeling showed that all lysines targeted by aspirin are surface exposed. Five of these lysines are localized to the DNA-binding domain, four to the nuclear localization signal domain, and one to the C-terminal regulatory domain. Our results suggest that aspirin's anti-cancer effect may involve acetylation and activation of wild type and mutant p53 and induction of target gene expression. This is the first report attempting to characterize p53 acetylation sites targeted by aspirin. PMID:26596838

  20. Effects of Rosiglitazone and High Fat Diet on Lipase/Esterase Expression in Adipose Tissue

    OpenAIRE

    Shen, Wen‐Jun; Patel, Shailja; Yu, Zaixin; Jue, Dyron; Kraemer, Fredric B.

    2006-01-01

    A number of intracellular lipase/esterase have been reported in adipose tissue either by functional assays of activity or through proteomic analysis. In the current work, we have studied the relative expression level of 12 members of the lipase/esterase family that are found in white adipose tissue. We found that the relative mRNA levels of ATGL and HSL are the most abundant, being 2–3 fold greater than TGH or ADPN; whereas other intracellular neutral lipase/esterases were expressed at substa...

  1. 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.

  2. Aspirin Resistance: A Clinical Review Focused on the Most Common Cause, Noncompliance

    OpenAIRE

    Schwartz, Kenneth A.

    2011-01-01

    Aspirin is an inexpensive, readily available medication that reduces the risk of subsequent vascular disease by about 25% in patients with known occlusive vascular disease. Aspirin’s beneficial effect is mediated via inhibition of arachidonic acid (AA) activation of platelets and is detected by demonstrating a decrease in platelet function and/or a decrease in prostaglandin metabolites. Patients who are assumed to be taking their aspirin, but who do not demonstrate an aspirin effect are label...

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

    OpenAIRE

    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...

  4. 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.

  5. Tolerabilidad de Aspirina Aspirin tolerability

    Directory of Open Access Journals (Sweden)

    M. R. Moreno-Brea

    2005-09-01

    ácter atero-trombótico. El síndrome de Reye es un cuadro de rara presentación, pero de graves consecuencias, que contraindica el uso de Aspirina en niños o adolescentes con fiebre o ciertas infecciones virales. Dada la extensa utilización de Aspirina, puede ser considerado un fármaco bien tolerado en general, cuyas reacciones adversas más graves deben ser objeto de una especial farmacovigilancia, prestando especial atención a la población de mayor riesgo. Esta situación aconseja, asimismo, la puesta en marcha de programas de educación sanitaria sobre el uso de los analgésicos. En todo caso, Aspirina sigue siendo un fármaco de referencia con una importante potencialidad terapéutica derivada de los beneficios inherentes a su uso.The acetylsalicylic acid (ASA is a widely used drug worldwide, both as prescription and over-the-counter products, and both as the only active drug or associated to other drugs in fixed doses. It is used either occasionally for the management of acute symptomatic conditions, or continuously in prophylactic anti-thrombotic regimes. Its profile of adverse reactions and potential interactions with other drugs makes it very important to have a well-tolerated and safe substance. Both things are particularly relevant when the population exposed to this drug has reached a certain age, since its specific features may increase its susceptibility to side effects and complications. Aspirin shares the general profile of adverse reactions of the NSAIs and it is considered as its prototype. When acutely administered, the incidence of side effects, most of them light, are the same as with other analgesics. Gastrointestinal effects are the most frequent of all and several risk factors have been identify for the development of severe gastrointestinal complications. These risk factors must be considered along with the need to take prophylactic measures in order to reduce the morbi-mortality. In recent years, special attention has been devoted to

  6. Influenza C virus esterase: analysis of catalytic site, inhibition, and possible function

    International Nuclear Information System (INIS)

    The active site serine of the acetylesterase of influenza C virus was localized to amino acid 71 of the hemagglutinin-esterase protein by affinity labeling with 3H-labeled diisopropylfluorophosphate. This serine and the adjacent amino acids (Phe-Gly-Asp-Ser) are part of a consensus sequence motif found in serine hydrolases. Since comparative analysis failed to reveal esterase sequence similarities with other serine hydrolases, the authors suggest that this viral enzyme is a serine hydrolase constituting a new family of serine esterases. Furthermore, they found that the influenza C virus esterase was inhibited by isocoumarin derivatives, with 3,4-dichloroisocoumarin being the most potent inhibitor. Addition of this compound prevented elution of influenza C virus from erythrocytes and inhibited virus infectivity, possibly through inhibition of virus entry into cells

  7. 3 Benzyl-6-chloropyrone: a suicide inhibitor of cholesterol esterase

    International Nuclear Information System (INIS)

    Cholesterol, absorbed from the intestine, appears in lymph as the ester. Cholesterol esterase is essential for this process, since depletion of the enzyme blocks and repletion restores, absorption. Selective inhibitors of cholesterol esterase may thus prove useful in reducing cholesterol uptake. A series of potential suicide substrates were synthesized which, following cleavage by the enzyme, would attack the putative nucleophile in the active site. One of these, 3-benzyl-6-chloropyrone (3BCP), inhibited both synthesis and hydrolysis of 14C-cholesteryl oleate with an I50 of approximately 150 μM. The inactivation was time-dependent and characteristic of a suicide mechanism. The α pyrone structure (lactone analog) is cleaved by a serine-hydroxyl in the active site. This generates an enoyl chloride which inactivates the imidazole believed to play a part in the catalytic function of the enzyme. Inhibition by 3BCP is selective for cholesterol esterase. The activity of pancreatic lipase as not affected by concentrations up to 1 mM

  8. 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 ...

  9. 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.

  10. 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,

  11. Differential Sex Response to Aspirin in Decreasing Aneurysm Rupture in Humans and Mice.

    Science.gov (United States)

    Chalouhi, Nohra; Starke, Robert M; Correa, Tatiana; Jabbour, Pascal M; Zanaty, Mario; Brown, Robert D; Torner, James C; Hasan, David M

    2016-08-01

    We previously found that aspirin decreases the risk of cerebral aneurysm rupture in humans. We aim to assess whether a sex differential exists in the response of human cerebral aneurysms to aspirin and confirm these observations in a mouse model of cerebral aneurysm. A nested case-control analysis from the International Study of Unruptured Intracranial Aneurysms was performed to assess whether a sex differential exists in the response of human cerebral aneurysms to aspirin. A series of experiments were subsequently performed in a mouse model of cerebral aneurysms. Aneurysms were induced with hypertension and elastase injection into mice basal cisterns. We found that aspirin decreased the risk of aneurysm rupture more significantly in men than in women in the International Study of Unruptured Intracranial Aneurysms. In mice, aspirin and cyclooxygenase-2 inhibitor did not affect cerebral aneurysm formation but significantly decreased the incidence of rupture. The incidence of rupture was significantly lower in male versus female mice on aspirin. Gene expression analysis from cerebral arteries showed higher 15-hydroxyprostaglandin dehydrogenase levels in male mice. The rate of cerebral aneurysm rupture was similar in male mice receiving aspirin and 15-hydroxyprostaglandin dehydrogenase inhibitor compared with females receiving aspirin and 15-hydroxyprostaglandin dehydrogenase agonist, signaling a reversal of the sex-differential response to aspirin. Aspirin decreases aneurysm rupture in human and mice, in part through cyclooxygenase-2 pathways. Evidence from animal and human studies suggests a consistent differential effect by sex. 15-Hydroxyprostaglandin dehydrogenase activation in females reduces the incidence of rupture and eliminates the sex-differential response to aspirin. PMID:27296993

  12. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

  14. Technetium-aspirin molecule complexes

    International Nuclear Information System (INIS)

    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)

  15. Enhanced biosurfactant production through cloning of three genes and role of esterase in biosurfactant release

    Directory of Open Access Journals (Sweden)

    Khanna Sunil

    2011-06-01

    Full Text Available Abstract Background Biosurfactants have been reported to utilize a number of immiscible substrates and thereby facilitate the biodegradation of panoply of polyaromatic hydrocarbons. Olive oil is one such carbon source which has been explored by many researchers. However, studying the concomitant production of biosurfactant and esterase enzyme in the presence of olive oil in the Bacillus species and its recombinants is a relatively novel approach. Results Bacillus species isolated from endosulfan sprayed cashew plantation soil was cultivated on a number of hydrophobic substrates. Olive oil was found to be the best inducer of biosurfactant activity. The protein associated with the release of the biosurfactant was found to be an esterase. There was a twofold increase in the biosurfactant and esterase activities after the successful cloning of the biosurfactant genes from Bacillus subtilis SK320 into E.coli. Multiple sequence alignment showed regions of similarity and conserved sequences between biosurfactant and esterase genes, further confirming the symbiotic correlation between the two. Biosurfactants produced by Bacillus subtilis SK320 and recombinant strains BioS a, BioS b, BioS c were found to be effective emulsifiers, reducing the surface tension of water from 72 dynes/cm to as low as 30.7 dynes/cm. Conclusion The attributes of enhanced biosurfactant and esterase production by hyper-producing recombinant strains have many utilities from industrial viewpoint. This study for the first time has shown a possible association between biosurfactant production and esterase activity in any Bacillus species. Biosurfactant-esterase complex has been found to have powerful emulsification properties, which shows promising bioremediation, hydrocarbon biodegradation and pharmaceutical applications.

  16. 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 ...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    1997-05-01

    In this pilot study, aimed at exploring the feasibility of a large-scale trial of low-dose aspirin in polycythaemia vera (PV), 112 PV patients (42 females, 70 males. aged 17-80 years) were selected for not having a clear indication for, or contraindication to, aspirin treatment and randomized to receive oral aspirin (40 mg/d) or placebo. Follow-up duration was 16 +/- 6 months. Measurements of thromboxane A2 production during whole blood clotting demonstrated complete inhibition of platelet cyclooxygenase activity in patients receiving aspirin. Aspirin administration was not associated with any bleeding complication. Within the limitations of the small sample size, this study indicates that a biochemically effective regimen of antiplatelet therapy is well tolerated in patients with polycythaemia vera and that a large-scale placebo-controlled trial is feasible. PMID:9163613

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Aspirin protected against endothelial damage induced by LDL:role of endogenous NO synthase inhibitors in rats

    Institute of Scientific and Technical Information of China (English)

    Sheng DENG; Pan-yue DENG; Jun-lin JIANG; Feng YE; Jing YU; Tian-lun YANG; Han-wu DENG; Yuan-jian LI

    2004-01-01

    AIM: To study the protective effect of aspirin on damages of the endothelium induced by low-density lipoprotein (LDL), and whether the protective effect of aspirin is related to reduction of nitric oxide synthase inhibitor level.METHODS: Vascular endothelial injury was induced by a single injection of native LDL (4 mg/kg) in rats. Vasodilator responses to acetylcholine (Ach) in the isolated aortic rings were determined, and serum concentrations of asymmetric dimethylarginine (ADMA), malondialdehyde (MDA), tumour necrosis factor-α(TNF-α), and the activity of dimethylaminohydrolase (DDAH) were measured. RESULTS: A single injection of LDL (4 mg/kg)significantly decreased vasodilator responses to Ach, increased the serum level of ADMA, MDA, and TNF-α, and decreased DDAH activity. Aspirin (30 or 100 mg/kg) markedly reduced the inhibition of vasodilator responses to Ach by LDL, and the protective effect of aspirin at the lower dose was greater compared with high-dose aspirin group. Aspirin inhibited the increased level of MDA and TNF-α induced by LDL. Aspirin at the dose of 30 mg/kg,but not at higher dose (100 mg/kg), significantly reduced the concentration of ADMA and increased the activity of DDAH. CONCLUSION: Aspirin at the lower dose (30 mg/kg) protects the endothelium against damages elicited by LDL in vivo, and the protective effect of aspirin on endothelium is related to reduction of ADMA concentration by increasing DDAH activity.

  1. Effects of copper-aspirin complex on platelet-neutrophil interactions

    Institute of Scientific and Technical Information of China (English)

    Zhi-qiang SHEN; Peng CHEN; Ling LI; Peng CHEN; Wei-ping LIU

    2004-01-01

    AIM: To investigate the effects of copper-aspirin complex on rat thrombosis and the interaction between platelets and neutrophils. METHODS: The model of electrically stimulated carotid artery thrombosis in Sprague Dawley rats was used; the effects of copper-aspirin complex on rat platelet-neutrophil adhesion and platelet aggregation stimulated by activated neutrophils were observed by rosette assay and Born's method, respectively. RESULTS:Intragastric copper-aspirin complex (5, 7, and 10 mg/kg) dose-dependently prolonged the occlusion time; it significantly decreased the rosette number formed between thrombin-activated platelets and neutrophils; the 50 % of inhibitory concentration (IC50) was (54.6±4.3) μmol/L. Copper-aspirin complex markedly inhibited rat platelet aggregation induced by either cell free supernatant of activated neutrophils or by activated neutrophil suspension.The values of IC50 were (224.5±16.2) μmol/L and (820.5±21.4) μmol/L, whereas aspirin had no influence.CONCLUSION: Copper-aspirin complex inhibited platelet-neutrophil interactions through a different property from aspirin and resulted in a more potent antithrombotic activity.

  2. 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. PMID:26369647

  3. 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

  4. Esterase isozyme polymorphism, specific and nonspecific esterase, syngenic lines development and natural occurrence of a thermostable esterase in the tropical silkworm Bombyx mori L.

    Science.gov (United States)

    Chattopadhyay, G K; Sengupta, A K; Verma, A K; Sen, S K; Saratchandra, B

    2001-11-01

    Esterase isozyme polymorphism was documented for digestive juice and haemolymph of the tropical multivoltine silkworm, Bombyx mori L., breed CB5 (GP) and its syngenic lines (CB5Lm(e)-1, CB5Lm-2 and CB5Lm-5) using alpha- and beta-naphthylacetate separately as nonspecific substrates (Ogita, Z., Kasai, T., 1965. Genetico-biochemical analysis of specific esterases in Musca domestica. Jpn. J. Genet. 40, 173-184). Polymorphism existed in the isozyme pattern of alpha-esterase with two or three bands in digestive juice and three to five bands in haemolymph. No polymorphism was observed in beta-esterase isozyme pattern having four bands in digestive juice and two bands in haemolymph. During the course of esterase isozyme studies, the presence of some specific alpha-esterase bands (Est-1, 4 and 5) in haemolymph and beta-esterase bands (Est-1, 2 and 3) in digestive juice were observed. But both alpha- and beta-esterase bands Est-3 and 4 in digestive juice and Est-2 and 3 in haemolymph were found to be nonspecific. Nonspecific beta-esterase band (Est-3) in haemolymph of CB5 (GP) and its syngenic lines withstood a temperature up to 80+/-1 degrees C for 10 min. No thermostable band was observed in the isozyme zymogram of alpha-esterase in digestive juice and haemolymph or beta-esterase in digestive juice. Overall, this study discusses the presence of esterase heterogeneity in the CB5 (GP) genepool, syngenic lines development, occurrence of specific alpha- and beta-esterase bands in digestive juice and haemolymph and thermostable beta-esterase band Est-3 in haemolymph in tropical silkworm Bombyx mori L. PMID:11583932

  5. Characterization of two metagenome-derived esterases that reactivate chloramphenicol by counteracting chloramphenicol acetyltransferase.

    Science.gov (United States)

    Tao, Weixin; Lee, Myung Hwan; Yoon, Mi-Young; Kim, Jin-Cheol; Malhotra, Shweta; Wu, Jing; Hwang, Eul Chul; Lee, Seon-Woo

    2011-12-01

    Function-driven metagenomic analysis is a powerful approach to screening for novel biocatalysts. In this study, we investigated lipolytic enzymes selected from an alluvial soil metagenomic library, and identified two novel esterases, EstDL26 and EstDL136. EstDL26 and EstDL136 reactivated chloramphenicol from its acetyl derivates by counteracting the chloramphenicol acetyltransferase (CAT) activity in Escherichia coli. These two enzymes showed only 27% identity in amino acid sequence to each other; however both preferentially hydrolyzed short-chain p-nitrophenyl esters (lipase (HSL), and since chloramphenicol acetate esterase (CAE) activity was detected from two other soil esterases in the HSL family, this suggests a distribution of CAE among the soil microorganisms. The isolation and characterization of EstDL26 and EstDL136 in this study may be helpful in understanding the diversity of CAE enzymes and their potential role in releasing active chloramphenicol in the producing bacteria. PMID:22210605

  6. 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...

  7. Effect of low-dose aspirin during pregnancy on fibrinolytic variables before and after parturition

    OpenAIRE

    Bremer, Henk; Rotmans, Nel; Brommer, E.J.Ph.; Wallenburg, Henk

    1995-01-01

    textabstractOBJECTIVE: We assessed the effects of a daily oral dose of 60 to 80 mg of aspirin from 12 weeks gestation until delivery on fibrinolytic variables before and after parturition. STUDY DESIGN: In a prospective controlled study labor was electively induced in 24 patients, eight receiving low-dose aspirin and 16 controls. Levels were determined in maternal and cord plasma of tissue-type plasminogen activator antigen and activity, plasminogen activator inhibitor-1 antigen, plasminogen ...

  8. Biochemical characterization of a first fungal esterase from Rhizomucor miehei showing high efficiency of ester synthesis.

    Directory of Open Access Journals (Sweden)

    Yu Liu

    Full Text Available BACKGROUND: Esterases with excellent merits suitable for commercial use in ester production field are still insufficient. The aim of this research is to advance our understanding by seeking for more unusual esterases and revealing their characterizations for ester synthesis. METHODOLOGY/PRINCIPAL FINDINGS: A novel esterase-encoding gene from Rhizomucor miehei (RmEstA was cloned and expressed in Escherichia coli. Sequence analysis revealed a 975-bp ORF encoding a 324-amino-acid polypeptide belonging to the hormone-sensitive lipase (HSL family IV and showing highest similarity (44% to the Paenibacillus mucilaginosus esterase/lipase. Recombinant RmEstA was purified to homogeneity: it was 34 kDa by SDS-PAGE and showed optimal pH and temperature of 6.5 and 45°C, respectively. The enzyme was stable to 50°C, under a broad pH range (5.0-10.6. RmEstA exhibited broad substrate specificity toward p-nitrophenol esters and short-acyl-chain triglycerols, with highest activities (1,480 U mg(-1 and 228 U mg(-1 for p-nitrophenyl hexanoate and tributyrin, respectively. RmEstA efficiently synthesized butyl butyrate (92% conversion yield when immobilized on AOT-based organogel. CONCLUSION: RmEstA has great potential for industrial applications. RmEstA is the first reported esterase from Rhizomucor miehei.

  9. The classification of esterases: an important gene family involved in insecticide resistance - A review

    Directory of Open Access Journals (Sweden)

    Isabela Reis Montella

    2012-06-01

    Full Text Available The use of chemical insecticides continues to play a major role in the control of disease vector populations, which is leading to the global dissemination of insecticide resistance. A greater capacity to detoxify insecticides, due to an increase in the expression or activity of three major enzyme families, also known as metabolic resistance, is one major resistance mechanisms. The esterase family of enzymes hydrolyse ester bonds, which are present in a wide range of insecticides; therefore, these enzymes may be involved in resistance to the main chemicals employed in control programs. Historically, insecticide resistance has driven research on insect esterases and schemes for their classification. Currently, several different nomenclatures are used to describe the esterases of distinct species and a universal standard classification does not exist. The esterase gene family appears to be rapidly evolving and each insect species has a unique complement of detoxification genes with only a few orthologues across species. The examples listed in this review cover different aspects of their biochemical nature. However, they do not appear to contribute to reliably distinguish among the different resistance mechanisms. Presently, the phylogenetic criterion appears to be the best one for esterase classification. Joint genomic, biochemical and microarray studies will help unravel the classification of this complex gene family.

  10. New Thermophilic and Thermostable Esterase with Sequence Similarity to the Hormone-Sensitive Lipase Family, Cloned from a Metagenomic Library

    OpenAIRE

    Rhee, Jin-Kyu; Ahn, Dae-Gyun; Kim, Yeon-Gu; Oh, Jong-Won

    2005-01-01

    A gene coding for a thermostable esterase was isolated by functional screening of Escherichia coli cells that had been transformed with fosmid environmental DNA libraries constructed with metagenomes from thermal environmental samples. The gene conferring esterase activity on E. coli grown on tributyrin agar was composed of 936 bp, corresponding to 311 amino acid residues with a molecular mass of 34 kDa. The enzyme showed significant amino acid similarity (64%) to the enzyme from a hypertherm...

  11. 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...

  12. Gastrointestinal symptoms in low-dose aspirin users: a comparison between plain and buffered aspirin

    OpenAIRE

    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; van Oijen, M.G.H.

    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 volunteers, but at lower cardiovascular doses no beneficial effects were observed. Aim To compare the prevalence of self-reported gastrointestinal symptoms between low-dose plain aspirin and ECC. Methods A...

  13. Talk with Your Doctor about Taking Aspirin Every Day

    Science.gov (United States)

    ... En español Talk with Your Doctor about Taking Aspirin Every Day Browse Sections The Basics Overview Benefits ... and Risks What are the benefits of taking aspirin daily? Aspirin can reduce your risk of heart ...

  14. A regimen for low-dose aspirin?

    OpenAIRE

    Hanley, S. P.; Bevan, J.; Cockbill, S. R.; Heptinstall, S

    1982-01-01

    The effects of different regimens of 40 mg aspirin on platelet thromboxane A2 synthesis and vascular prostacyclin synthesis were determined in patients who were undergoing elective surgery for removal of varicose veins. Aspirin 40 mg taken at intervals of 48 hours consistently reduced platelet thromboxane A2 synthesis to a level at which it failed to support platelet aggregation and the associated release reaction. This effect lasted for at least 36 hours. In contrast, aspirin 40 mg every 72 ...

  15. Aspirin and tension-type headache

    OpenAIRE

    Farinelli, I.; Martelletti, P.

    2007-01-01

    Acetylsalicylic acid (ASA, Aspirin) is among the most used drugs worldwide. At present, Aspirin represents a quite versatile drug employed in the control of pain symptomatologies and in situations such as prevention of both ischaemic stroke and cardiovascular events. Aspirin causes inhibition of prostaglandin (PG) synthesis by inactivation of the cyclooxygenase (COX) enzyme. ASA constitutes the focus of new researches explaining more widely Aspirin’s control of inflammation. The induction of ...

  16. Extraction systems for isolating esterases having interfacial adsorption

    Directory of Open Access Journals (Sweden)

    Alberto del Monte Martínez

    2009-06-01

    Full Text Available Resumen: En el presente trabajo se optimizaron las condiciones de extracción de esterasas con actividad en interfaces, a partir de la anémona marina Stichodactyla helianthus y del camarón peneido Litopenaeus vannamei. Las esterasas interfaciales, cuya presencia en estas especies había sido informada previamente, presentan características funcionales que las hacen muy atractivas para su empleo industrial. Los homogenados de los animales se trataron con los detergentes Tritón X-100, Tween 20 y Tween 80 en dos concentraciones cada uno: la Concentración Micelar Crítica (CMC y la mitad de ésta. Además se empleó NaCl 0,5 mol/L y n-butanol a las proporciones 5, 10 y 20%. Cada variante fue comparada con el método tradicional de extracción con agua destilada, que fue tomado como control. Los mejores resultados se obtuvieron empleando n-butanol al 20%, para recuperar las actividades esterasa y fosfolipasa, y al 10%, en el aislamiento de la actividad lipasa. La efectividad de este solvente en el aislamiento de estas enzimas con afinidad por las interfaces lípido/agua, pudiera estar dada por su capacidad para romper los agregados entre estas moléculas y causar la desorción de las mismas a los restos de membrana y tejidos presentes en la preparación.Palabras clave: activación interfacial, esterasas interfaciales, lipasas, Stichodactyla helianthus, Litopenaeus vannamei.interfacial activation, interfacial esterase, lipase, Stichodactyla helianthus, Litopenaeus vannamei.Abstract: Interfacial esterases present great functional versatility, making them very attractive molecules for industrial applications. The conditions for extracting interfacial esterases previously detected in the sea anemone Stichodactyla helianthus and the shrimp Litopenaeus vannamei were optimised in this work. Animal homogenates were treated with Triton X-100, Tween 20 and Tween 80 detergents at two different concentrations: critical micellar concentration (CMC and half

  17. Polyacrylamide Gel Electrophoretic Band Pattern of Esterase in the Pupae of Bactrocera papavae and Bactrocera carambolae (Diptera: Tephritidae

    Directory of Open Access Journals (Sweden)

    M. Hasanuzzaman

    2012-11-01

    Full Text Available The study was undertaken to compare the electrophoretic banding patterns of esterase isozyme between the pupae of Bactrocera papayae and Bactrocera carambolae (Diptera: Tephritidae by using polyacrylamide gel. These two Bactrocera species are the major agricultural pests, especially fruits and vegetables. One esterase band, EST-1 was detected and the relative mobility value was 0.15 which was close to the cathode. The EST-1 band was present in the pupae of both Bactrocera species. There was no difference in the esterase patterns of both species. The thickness and activation of the band varied slightly. So, the results prove that the pupae of the two Bactrocera species have almost similar esterase band pattern in the same polyacrylamide gel.

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

    Science.gov (United States)

    Landolfi, R; Patrono, C

    1996-09-01

    The role of aspirin in the antithrombotic strategy of patients with polycythemia vera (PV) and essential thrombocythemia (ET) is highly controversial. Long considered unsafe on the basis of a single clinical trial testing very high doses in PV patients, aspirin is being increasingly used at lower dosage. The rationale for the use of aspirin in patients with PV and ET is provided by the efficacy of this agent in the treatment of microcirculatory disturbances of thrombocythemic states associated with myeloproliferative disorders and by recent evidence that asymptomatic PV and ET patients have persistently increased thromboxane (TX) A2-biosynthesis. This increase, which most likely reflects enhanced platelet activation in vivo, is independent of the platelet mass and blood viscosity and largely supressed by a short term low-dose aspirin regimen (50 mg/day for 7 days). Since enhanced TXA2 biosynthesis may play a role in transducing the increased thrombotic risk associated with PV and ET, long-term low-dose aspirin administration has been proposed as a possible antithombotic strategy in these subjects. The safety of this treatment in PV patients has been recently reassessed by the Gruppo Italiano per lo Studio della Policitemia Vera (GISP) which has followed for over one year 112 patients randomized to receive 40 mg/day aspirin or placebo. In the same study, serum TXB2 measurements provided evidence that the low-dose aspirin regimen tested was fully effective in inhibiting platelet cyclooxygenase activity. On this basis, a large scale trial aimed at assessing the antithrombotic efficacy of this approach is currently being organized. In patients with ET both the minimal aspirin dose required for complete inhibition of platelet cyclooxygenase and the safety of long-term aspirin administration need to be established prior to extensive clinical evaluation of this strategy. PMID:8951777

  19. 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.

  20. Esterases immobilized on aminosilane modified magnetic nanoparticles as a catalyst for biotransformation reactions.

    Science.gov (United States)

    Alex, Deepthy; Mathew, Abraham; Sukumaran, Rajeev K

    2014-09-01

    Magnetite nanoparticles were prepared by reacting ferrous and ferric salts in presence of aqueous ammonia. The magnetic nanoparticles (MNPs) were amino functionalized by treating with 3-aminopropyl triethoxy silane (APTES) and was coupled with glutaraldehyde. A novel solvent tolerant esterase from Pseudozyma sp. NII 08165 was immobilized on the MNPs through covalent bonding to the glutaraldehyde. The magnetite nanoparticles had a size range of 10-100 nm, confirmed by DLS. Lipases immobilized on MNPs were evaluated for biotransformation reactions including synthesis of ethyl acetate and transesterification of vegetable oil for producing biodiesel. The MNP immobilized esterase had prolonged shelf life and there was no loss in enzyme activity. PMID:24968816

  1. Aspirin and clopidogrel resistance: possible mechanisms and clinical relevance. Part II: Potential causes and laboratory tests.

    Science.gov (United States)

    Vadász, Dávid; Sztriha, László K; Sas, Katalin; Vécsei, László

    2013-01-30

    Recent meta-analyses have indicated that patients with vascular disease demonstrated by laboratory tests to be aspirin or clopidogrel-resistant are at an increased risk of major vascular events. The suggested mechanisms of aspirin resistance include genetic polymorphism, alternative pathways of platelet activation, aspirin-insensitive thromboxane biosynthesis, drug interactions, or a low aspirin dose. Clopidogrel resistance is likely to develop as a result of a decreased bioavailability of the active metabolite, due to genetic variation or concomitant drug treatment. Additional work is required to improve and validate laboratory tests of platelet function, so that they may become useful tools for selection of the most appropriate antiplatelet therapy for an individual patient. Improvements in antiplatelet treatment strategies in the future should lead to a reduction in premature vascular events. PMID:23607225

  2. An evaluation of different doses of soluble aspirin and aspirin tablets in postoperative dental pain.

    Science.gov (United States)

    Holland, I S; Seymour, R A; Ward-Booth, R P; Ord, R A; Lim, K L; Hoare, R C

    1988-01-01

    1. The efficacy of three different single doses (600, 900 and 1200 mg of soluble aspirin and aspirin tablets) was determined in a randomized placebo-controlled parallel study in 140 patients (70 females) with postoperative pain after removal of impacted third molars. 2. Patients treated with soluble aspirin 600 mg, 900 mg, 1200 mg and aspirin tablet 1200 mg reported significantly less pain (P less than 0.01) throughout the investigation period than those treated with placebo. 3. Overall pain scores after treatment with aspirin tablets 600 and 900 mg did not differ significantly from those after treatment with placebo (P greater than 0.05). 4. On a comparative dose basis, soluble aspirin was significantly more potent (P less than 0.05) than aspirin tablets. PMID:3190996

  3. 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. PMID:27439201

  4. 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...

  5. Suppression of inducible cyclooxygenase 2 gene transcription by aspirin and sodium salicylate

    OpenAIRE

    Xu, Xiao-Ming; Sansores-Garcia, Leticia; Chen, Xian-Ming; Matijevic-Aleksic, Nevenka; Du, Min; Kenneth K. Wu

    1999-01-01

    The pharmacological action of salicylate cannot be explained by its inhibition of cyclooxygenase (COX) activity. In this report, the effects of aspirin and sodium salicylate on COX-2 expressions in human umbilical vein endothelial cells and foreskin fibroblasts were evaluated. Aspirin and sodium salicylate at therapeutic concentrations equipotently blocked COX-2 mRNA and protein levels induced by interleukin-1β and phorbol 12-myristate 13-acetate. The suppressing effect was more pronounced in...

  6. Psychotropic effects of aspirin, acetylsalicylate cobalt and acetylsalicylate zinc at various doses

    OpenAIRE

    Tatyana V. Yakovchyuk; Oksana V. Katiushyna; Ivan I. Koreniuk; Denis R. Khusainov; Tatyana V. Gamma

    2012-01-01

    For the first time it is shown that psychotropic action of acetylsalicylates at various doses is manifested as a nonmonotonic dependence having its peaks at therapeutic and ultra-low dose zones. It is discovered that development of effects of aspirin resembles that of acetylsalicylate zinc. Acetylsalicylate cobalt at extremely low doses zone showed the highest antidepressant activity, demonstrating toxicity at high doses. Generally, it is revealed that the use of aspirin and its salts at high...

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

    DEFF Research Database (Denmark)

    Topakas, E.; Kalogeris, E.; Kekos, D.; Macris, B.J.; Christakopoulos, Paul

    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...

  8. Non-specific esterases and esterproteases in masticatory muscles from the muscular dystrophic mouse

    DEFF Research Database (Denmark)

    Kirkeby, S; Moe, D; Vilmann, H

    1989-01-01

    With the aid of histochemical and electrophoretic techniques activities for esterase and esterprotease were investigated in the digastric and masseter muscles from normal and dystrophic mice. The substrates used were alpha-naphthyl acetate and N-acetyl-L-alanine alpha-naphthyl ester. According to...

  9. 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

  10. Effects of prednisone, aspirin, and acetaminophen on an in vivo biologic response to interferon in humans.

    Science.gov (United States)

    Witter, F R; Woods, A S; Griffin, M D; Smith, C R; Nadler, P; Lietman, P S

    1988-08-01

    In healthy volunteers receiving a single intramuscular dose of 18 X 10(6) U interferon alone or after 24 hours of an 8-day course of prednisone (40 mg/day), aspirin (650 mg every 4 hours), or acetaminophen (650 mg every 4 hours), the magnitude of the biologic response to interferon was quantified by measuring the time course of the induction of 2'-5'-oligoadenylate synthetase and resistance to vesicular stomatitis virus infection in human peripheral blood mononuclear cells. Prednisone decreased the AUC of 2'-5'-oligoadenylate synthetase activity (p less than 0.05), whereas administration of aspirin or acetaminophen did not affect this biologic response. No measurable effect was seen during administration of prednisone, aspirin, or acetaminophen on the duration or intensity of vesicular stomatitis virus yield reduction. The side effects seen with interferon administration at the dose tested were not altered in a clinically meaningful manner by prednisone, aspirin, or acetaminophen. PMID:2456175

  11. 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.

  12. Uncovering divergent evolution of α/β-hydrolases: a surprising residue substitution needed to convert Hevea brasiliensis hydroxynitrile lyase into an esterase.

    Science.gov (United States)

    Nedrud, David M; Lin, Hui; Lopez, Gilsinia; Padhi, Santosh K; Legatt, Graig A; Kaz-Lauskas, Romas J

    2014-11-01

    Hevea brasiliensis hydroxynitrile lyase (HbHNL) and salicylic acid binding protein 2 (SABP2, an esterase) share 45% amino acid sequence identity, the same protein fold, and even the same catalytic triad of Ser-His-Asp. However, they catalyze different reactions: cleavage of hydroxynitriles and hydrolysis of esters, respectively. To understand how other active site differences in the two enzymes enable the same catalytic triad to catalyze different reactions, we substituted amino acid residues in HbHNL with the corresponding residues from SABP2, expecting hydroxynitrile lyase activity to decrease and esterase activity to increase. Previous mechanistic studies and x-ray crystallography suggested that esterase activity requires removal of an active site lysine and threonine from the hydroxynitrile lyase. The Thr11Gly Lys236Gly substitutions in HbHNL reduced hydroxynitrile lyase activity for cleavage of mandelonitrile 100-fold, but increased esterase activity only threefold to kcat ~ 0.1 min(-1) for hydrolysis of p-nitrophenyl acetate. Adding a third substitution - Glu79His - increased esterase activity more than tenfold to kcat ~ 1.6 min(-1). The specificity constant (kcat/KM) for this triple substitution variant versus wild type HbHNL shifted more than one million-fold from hydroxynitrile lyase activity (acetone cyanohydrin substrate) to esterase activity (p-nitrophenyl acetate substrate). The contribution of Glu79His to esterase activity was surprising since esterases and lipases contain many different amino acids at this position, including glutamate. Saturation mutagenesis at position 79 showed that 13 of 19 possible amino acid substitutions increased esterase activity, suggesting that removal of glutamate, not addition of histidine, increased esterase activity. Molecular modeling indicates that Glu79 disrupts esterase activity in HbHNL when its negatively charged side chain distorts the orientation of the catalytic histidine. Naturally occurring glutamate at the

  13. SOX7 is involved in aspirin-mediated growth inhibition of human colorectal cancer cells

    Institute of Scientific and Technical Information of China (English)

    Xin Zhou; Shu-Yan Huang; Jing-Xin Feng; Yan-Yan Gao; Li Zhao; Jun Lu; Bai-Qu Huang; Yu Zhang

    2011-01-01

    AIM: To confirm the role of sex-determining region Y-box 7 (Sox7) in aspirin-mediated growth inhibition of COX-independent human colorectal cancer cells.METHODS: The cell survival percentage was examined by MTT (Moto-nuclear cell direc cytotoxicity) assay.SOX7 expression was assessed by using reverse transcription-polymerase chain reaction and Western blotting. SB203580 was used to inhibit the p38MAPK signal pathway. SOX7 promoter activity was detected by Luciferase reporter assay.RESULTS: SOX7 was upregulated by aspirin and was involved in aspirin-mediated growth inhibition of SW480 human colorectal cancer cells. The p38MAPK pathway played a role in aspirin-induced SOX7 expression, during which the AP1 transcription factors c-Jun and c-Fos upregulated SOX7 promoter activities.RESULTS: SOX7 is upregulated by aspirin and is involved in aspirin-mediated growth inhibition of human colorectal cancer SW480 cells.

  14. New insights into the mechanisms of action of aspirin and its use in the prevention and treatment of arterial and venous thromboembolism

    OpenAIRE

    Mekaj, Agon

    2015-01-01

    Ymer H Mekaj,1,2 Fetije T Daci,2 Agon Y Mekaj3 1Institute of Pathophysiology, Faculty of Medicine, University of Prishtina, 2Department of Hemostasis and Thrombosis, National Blood Transfusion Center of Kosovo, 3Clinic of Neurosurgery, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo Abstract: The antithrombotic action of aspirin has long been recognized. Aspirin inhibits platelet function through irreversible inhibition of cyclooxygenase (COX) activity. Until recently, aspirin...

  15. Association of esterases with insecticide resistance in Culex quinquefasciatus (Diptera: Culicidae).

    Science.gov (United States)

    Gordon, Jennifer R; Ottea, James

    2012-06-01

    The southern house mosquito, Culex quinquefasciatus Say, is a competent vector of human disease and an important target of mosquito abatement programs. However, these management programs have been compromised by development of insecticide resistance. In the current study, susceptibilities to naled and resmethrin, two adulticides used in mosquito abatement, were monitored using a topical and contact bioassay, respectively, in five field- collected populations of C. quinquefasciatus (MARC, HOOD1, HOOD2, MINLOVE, and THIB). Frequencies of resistance, measured as survival after treatment with discriminating concentrations (i.e., sufficient to kill > 90% of a reference susceptible strain) were high (88.0-96.8%) in all field collections treated with naled, but were variable (3.3-94.2%) with resmethrin. In addition, esterase activities in mosquitoes from these collections were quantified using alpha-naphthyl acetate and ranged from 1.08 to 3.39 micromol alpha-naphthol produced min(-1) mg prot(-1). Heightened activities were associated with decreased insecticide susceptibility in HOOD1, THIB, and MINLOVE but not HOOD2. Esterases were visualized using native polyacrylamide gel electrophoresis, and intra- and interstrain differences in banding patterns were detected. In addition, esterases from MINLOVE mosquitoes were more numerous and intensely staining when compared with those from a laboratory-susceptible strain. Finally, naled synergized the toxicity of resmethrin in populations with decreased insecticide susceptibility and increased esterase activity by 2.5-(MINLOVE) to three-fold (THIB). Results from this study will allow management strategies for populations of C. quinquefasciatus to be optimized, and provide a foundation for further studies exploring use of esterase inhibitors as synergists of pyrethroid toxicity. PMID:22812138

  16. Aspirin and cancer: has aspirin been overlooked as an adjuvant therapy?

    OpenAIRE

    Langley, R E; Burdett, S.; Tierney, J F; Cafferty, F; Parmar, M K B; Venning, G

    2011-01-01

    Aspirin inhibits the enzyme cyclooxygenase (Cox), and there is a significant body of epidemiological evidence demonstrating that regular aspirin use is associated with a decreased incidence of developing cancer. Interest focussed on selective Cox-2 inhibitors both as cancer prevention agents and as therapeutic agents in patients with proven malignancy until concerns were raised about their toxicity profile. Aspirin has several additional mechanisms of action that may contribute to its anti-ca...

  17. 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.

  18. Amelioration of aspirin induced oxidative impairment and apoptotic cell death by a novel antioxidant protein molecule isolated from the herb Phyllanthus niruri.

    Directory of Open Access Journals (Sweden)

    Sudip Bhattacharyya

    Full Text Available 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.

  19. Aspirin

    Science.gov (United States)

    ... if you have or have ever had asthma, frequent stuffed or runny nose, or nasal polyps (growths on the linings of the nose). If you have these conditions, there is a risk that you will have ... ulcers, anemia, bleeding problems such as hemophilia, or kidney or liver ...

  20. Aspirin

    Science.gov (United States)

    ... LIBRARY Hello, Guest! My alerts Sign In Join Facebook Twitter Home About this Journal Editorial Board General Statistics Circulation Cover Doodle → Blip the Doodle Go Red For Women's Issue Information for Advertisers Author Reprints Commercial Reprints Customer Service and Ordering ...

  1. 阿司匹林和氯吡格雷对体外血小板黏附内皮细胞基质活性的影响及其机制研究%Ettects ot Aspirin and Clopidogrel on the Adhesion Activity ot Platelet to Endothelial Cell Matrix in Vitro and Its Mechanism

    Institute of Scientific and Technical Information of China (English)

    朱晋坤; 毛华; 尹扬光; 董文; 杜峰; 鲁玉明; 熊宗华; 邓梦扬

    2015-01-01

    200μl 血小板黏附内皮细胞基质活性分别低于对照组、阿司匹林组和氯吡格雷组(P ﹤0.05)。蛋白质免疫印迹法显示,阿司匹林和氯吡格雷均能抑制由 ox - LDL 引起的 TM 表达的减少。ox - LDL 能明显诱导血管内皮细胞 LOX -1表达,阿司匹林能明显抑制由 ox - LDL 引起的 LOX -1和 IL -6的表达;而氯吡格雷则能明显抑制内皮细胞 CD40的表达。结论阿司匹林和氯吡格雷均能从上调 TM 和抑制炎性因子两方面降低血小板对内皮细胞基质的黏附作用。但两者联合更能抑制由 ox - LDL引起的炎性因子的表达,降低血小板对内皮细胞基质的黏附。%Objective To study the effects of aspirin and clopidogrel on the adhesion activity of platelet to endothelial cell matrix in vitro and its mechanism, and to find the reasons why combination use of two drugs is better than monotherapy. Methods A total of 42 healthy female SD rats were bought from the animal centre of Third Military Medical University. By using random number table method,SD rats were divided into aspirin group(8 rats),clopidogrel group(8 rats),aspirin and clopidogrel(combination)group(8 rats),control group(8 rats),the other 10 rats were used for primary isolation and culture of cells. The isolated and cultured primary rat vascular endothelial cells were treated with ox - LDL to establish damaged vascular endothelial cell model. 100 mg/ kg aspirin,10 mg/ kg clopidogrel,combination of 100 mg/ kg aspirin and 10 mg/ kg clopidogrel,and 200 μl castor oil were used respectively to prepare endothelial cell matrix plate. 3 days before the separation and preparation of platelet from plasma,rats in aspirin group were fed with 100 mg·kg - 1 ·d - 1 aspirin,rats in clopidogrel group were fed with 10 mg·kg - 1 ·d - 1 clopidogrel,rats in aspirin and clopidogrel group were fed with 100 mg·kg - 1 ·d - 1 aspirin and 10 mg·kg - 1 ·d - 1 clopidogrel,rats in control group were fed with

  2. 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.

  3. Regular aspirin use and lung cancer risk

    Directory of Open Access Journals (Sweden)

    Cummings K

    2002-11-01

    Full Text Available Abstract Background Although a large number of epidemiological studies have examined the role of aspirin in the chemoprevention of colon cancer and other solid tumors, there is a limited body of research focusing on the association between aspirin and lung cancer risk. Methods We conducted a hospital-based case-control study to evaluate the role of regular aspirin use in lung cancer etiology. Study participants included 868 cases with primary, incident lung cancer and 935 hospital controls with non-neoplastic conditions who completed a comprehensive epidemiological questionnaire. Participants were classified as regular aspirin users if they had taken the drug at least once a week for at least one year. Results Results indicated that lung cancer risk was significantly lower for aspirin users compared to non-users (adjusted OR = 0.57; 95% CI 0.41–0.78. Although there was no clear evidence of a dose-response relationship, we observed risk reductions associated with greater frequency of use. Similarly, prolonged duration of use and increasing tablet years (tablets per day × years of use was associated with reduced lung cancer risk. Risk reductions were observed in both sexes, but significant dose response relationships were only seen among male participants. When the analyses were restricted to former and current smokers, participants with the lowest cigarette exposure tended to benefit most from the potential chemopreventive effect of aspirin. After stratification by histology, regular aspirin use was significantly associated with reduced risk of small cell lung cancer and non-small cell lung cancer. Conclusions Overall, results from this hospital-based case-control study suggest that regular aspirin use may be associated with reduced risk of lung cancer.

  4. Toxic action of organophosphorus compounds and esterase inhibition in houseflies

    NARCIS (Netherlands)

    Asperen, K. van

    1960-01-01

    The paper deals with investigations on the inhibition in vivo of the cholin-esterase and the aliesterase in houseflies poisoned by treatment with organophosphorus insecticides. The kinetics of the inhibition of esterases by DDVP, paraoxon and diazoxon in the presence and in the absence of substrate

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

    Science.gov (United States)

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

    2013-01-01

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

  6. Heterologous Expression of Two Ferulic Acid Esterases from Penicillium funiculosum

    Science.gov (United States)

    Knoshaug, Eric P.; Selig, Michael J.; Baker, John O.; Decker, Stephen R.; Himmel, Michael E.; Adney, William S.

    Two recombinant ferulic acid esterases from Penicillium funiculosum produced in Aspergillus awamori were evaluated for their ability to improve the digestibility of pretreated corn stover. The genes, faeA and faeB, were cloned from P. funiculosum and expressed in A. awamori using their native signal sequences. Both enzymes contain a catalytic domain connected to a family 1 carbohydrate-binding module by a threonine-rich linker peptide. Interestingly, the carbohydrate binding-module is N-terminal in FaeA and C-terminal in FaeB. The enzymes were purified to homogeneity using column chromatography, and their thermal stability was characterized by differential scanning microcalorimetry. We evaluated both enzymes for their potential to enhance the cellulolytic activity of purified Trichoderma reesei Cel7A on pretreated corn stover.

  7. Endotoxin-induced pulmonary dysfunction is prevented by C1-esterase inhibitor.

    OpenAIRE

    R. Guerrero; Velasco, F; M. Rodriguez; Lopez, A; Rojas, R; Alvarez, M A; Villalba, R.; V. Rubio; Torres, A.; del Castillo, D

    1993-01-01

    In septic shock, hypotension, disseminated intravascular coagulation, and neutrophil activation are related to the activation of the blood coagulation contact system. This study evaluates in dogs the effect of the C1-esterase inhibitor (C1-INH), a main inhibitor of the blood coagulation contact system, on the cardiovascular and respiratory dysfunction associated with endotoxic shock. Two groups were included: controls, which received Escherichia coli endotoxin, and a C1-INH group in which C1-...

  8. 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.

  9. 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.

  10. A New Strategy for Fluorogenic Esterase Probes Displaying Low Levels of Non-specific Hydrolysis.

    Science.gov (United States)

    Kim, Sungwoo; Kim, Hyunjin; Choi, Yongdoo; Kim, Youngmi

    2015-06-26

    A new design for fluorescence probes of esterase activity that features a carboxylate-side pro-fluorophore is demonstrated with boron dipyrromethene (BODIPY)-based probes 1 a and 1 b. Because the design relies on the enzyme-catalyzed hydrolysis of an ester group that is not electronically activated, these probes exhibit a stability to background hydrolysis that is far superior to classical alcohol-side profluorophore-based probes, large signal-to-noise ratios, reduced sensitivity to pH variations, and high enzymatic reactivity. The utility of probe 1 a was established with a real-time fluorescence imaging experiment of endogenous esterase activity that does not require washing of the extracellular medium. PMID:26033618

  11. Insights into and relative effect of chitosan-krill oil, chitosan-H-aspirin, chitosan-H-krill oil-nystatin and chitosan-H-krill oil-aspirin-nystatin on dentin bond strength and functional drug delivery capacity: In-vitro studies

    OpenAIRE

    Victoria Tamara Perchyonok; Shengmiao Zhang; Grobler, Sias R; Oberholzer, Theunis G.; Ward Massey

    2014-01-01

    Background: Restorative materials in the new era aim to be "bio-active" and long-lasting. The purpose of this study was to design and to evaluate a novel chitosan hydrogels containing krill oil (antioxidant containing material), nystatin (antifungal), aspirin (pain relieve medication and free radical scavengers) and combinations thereof (chitosan-H-krill oil, chitosan-H-krill oil-nystatin and chitosan-H-aspirin, chitosan-H-aspirin-nystatin, chitosan-H-krill oil-aspirin and chitosan-H-krill oi...

  12. 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

  13. Evaluation of ketorolac, aspirin, and an acetaminophen-codeine combination in postoperative oral surgery pain.

    Science.gov (United States)

    Forbes, J A; Butterworth, G A; Burchfield, W H; Beaver, W T

    1990-01-01

    One-hundred twenty-eight outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive oral doses of ketorolac tromethamine 10 mg, aspirin 650 mg, a combination of acetaminophen 600 mg plus codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. All active medications were significantly superior to placebo. The acetaminophen-codeine combination was significantly superior to aspirin for peak analgesia. Ketorolac was significantly superior to aspirin for every measure of total and peak analgesia, and significantly superior to acetaminophen-codeine for measures of total effect. The analgesic effect of ketorolac was significant by hour 1 and persisted for 6 hours. Repeat-dose data also suggested that ketorolac 10 mg was superior to aspirin 650 mg and acetaminophen-codeine on the day of surgery. Differences among the active medications were trivial for the postoperative days 1-6 analyses. The frequency of adverse effects was over 4 times greater for acetaminophen-codeine than for ketorolac or aspirin. PMID:2082317

  14. Time of taking aspirin can have an effect on the frequency of occurrence of stroke

    Institute of Scientific and Technical Information of China (English)

    Ildiko Csoboth; Anita Matyus; Krisztina Gabara; Imre Boncz

    2009-01-01

    @@ To the Editor: We read the article by Ke et al1 with great interest, in which they investigated the usage of aspirin for the secondary prevention of ischemic stroke. The incidence of ischemic stroke and transient ischemic attack assessed by onset of clinical symptoms exhibits a marked circadian variation with a peak period during the morning. Stroke usually occurs unexpectedly or more frequently in the morning hours, between 7-12 a.m. In this morning period there is a higher aggregability of thrombocytes. Patients usually take aspirin in the morning for prevention as the treatment regimen is one tablet per day to be swallowed without chewing at least 30 minutes before breakfast (Figure). The highest plasma level of the drug occurs after the morning peak-incidence of the thromboembolic event, suggesting lower prophylactic effect of aspirin. Taking aspirin in the morning has its highest protective effect during the day, when normal physical activity exerts a protective action. Furthermore, this method of daily aspirin administration has its lowest protective value against cardio- and cerebrovascular events during the night and early rooming, when the lack of physical activity further augment the cascade of haemorheological events favoring platelet aggregation and subsequent ischemia.2-5

  15. 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. PMID:25947914

  16. Caffeine and Aspirin Protecting Albino Rats A gainst Biochemical and Histological Disorders Induced by Whole Body Gamma Irradiation

    International Nuclear Information System (INIS)

    Caffeine is an alkaloid (purine derivative) that contains flavonoids, where as aspirin, natural component of mammalian tissue ( acetylsalicylic acid) is one of the most commonly used non steroidal anti - inflammatory , and it is a necessary factor in the utilization of long - chain fatty acids to produce energy. Furthermore, it has been shown to protect cells from per oxidative stress. Th e objective of the present study is to evaluate the efficacy of caffeine (1,3,7 - trimethyl xanthine) 80 mg/kg b.wt. a nd aspirin ( acetylsalicylic acid) in the amelioration of the physiological and histological changes in stomach and intestine of rats exposed to gamma irradiation . Male albino rats were divided into 8 groups. 1 - Control group: rats not subject to any treatment, 2 - Caffeine group: rats received caffeine ( 80 ml/Kg body weight )via intraperitoneal injection for 21 days, 3 - Aspirin group: rats received aspirin (150 mg / kg body) via intraperitoneal injection for 21 days , 4 - Caffeine + Aspirin group: rats received caffeine a nd aspirin treatment, 5 - Radiation groups: rats were whole body gamma irradiated at 8 Gy , 6 - Caffeine + Radiation group: rats received caffeine for 21 days before whole body gamma irradiation at 8 Gy, 7 - Aspirin + Radiation group: rats received aspirin during 21 days before w hole body gamma irradiation , 8 - Caffeine + Aspirin + Radiation group: rats received caffeine parallel to aspirin for 21 days before whole body gamma irradiation. Animals were sacrificed 24 hrs post irradiation. The results demonstrated that rats exposed to whole body gamma irradiation showed a significant increase in alanine amino transferase (AL ) , aspartate amino transferase ( AST), and alkaline phosphatase (ALP) activities, and a significant decrease in total protein indicating liver injury. A significant increase in urea, creatinine, Na+,and K+ were recorded indicating kidney damage. Alteration of liver and kidney functions was accompanied by a significant

  17. Aspirin, cyclooxygenase inhibition and colorectal cancer

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  18. Hormone-sensitive lipase is a cholesterol esterase of the intestinal mucosa.

    Science.gov (United States)

    Grober, Jacques; Lucas, Stéphanie; Sörhede-Winzell, Maria; Zaghini, Isabelle; Mairal, Aline; Contreras, Juan-Antonio; Besnard, Philippe; Holm, Cecilia; Langin, Dominique

    2003-02-21

    The identity of the enzymes responsible for lipase and cholesterol esterase activities in the small intestinal mucosa is not known. Because hormone-sensitive lipase (HSL) catalyzes the hydrolysis of acylglycerols and cholesteryl esters, we sought to determine whether HSL could be involved. HSL mRNA and protein were detected in all segments of the small intestine by Northern and Western blot analyses, respectively. Immunocytochemistry experiments revealed that HSL was expressed in the differentiated enterocytes of the villi and was absent in the undifferentiated cells of the crypt. Diacylglycerol lipase and cholesterol esterase activities were found in the different segments. Analysis of gut from HSL-null mice showed that diacylglycerol lipase activity was unchanged in the duodenum and reduced in jejunum. Neutral cholesterol esterase activity was totally abolished in duodenum, jejunum, and ileum of HSL-null mice. Analysis of HSL mRNA structure showed two types of transcripts expressed in equal amounts with alternative 5'-ends transcribed from two exons. This work demonstrates that HSL is expressed in the mucosa of the small intestine. The results also reveal that the enzyme participates in acylglycerol hydrolysis in jejunal enterocytes and cholesteryl ester hydrolysis throughout the small intestine. PMID:12482847

  19. Novel ferulic acid esterases from Bifidobacterium sp. produced on selected synthetic and natural carbon sources

    Directory of Open Access Journals (Sweden)

    Dominik Szwajgier

    2010-09-01

    Full Text Available Background. Ferulic acid esterases (or feruloyl esterases, a common group of hydrolases are very well distributed in the plant kongdom. The fungal feruloyl esterases were very extensively studied whereas probiotic lactic acid bacteria as the source of this enzyme were generally omitted. Free phenolic acids – strong antioxidants can be released from the dietary fiber by the action of intestinal lactic acid bacteria. The aim of this study was to examine the three probiotic Bifidobacterium strains to produce extracellular FAE on different synthetic and natural carbon sources. Material and methods. Studies were carried out using Bifidibacteriumstrains (B. animalis Bi30, B. catenulatum KD 14 and B. longum KN 29. The strains were cultivated using minimal growth media containing selected natural and synthetic carbon sources: German wheat bran, rye bran, barley spent grain, isolated larchwood arabinogalactan, apple pectin, corn pectin, methyl esters of phenolic acids. The production of extracellular feruloyl esterase was estimated using the post cultivation supernatants and methyl ferulate. The concentration of ferulic acid released from the ester was determined using HPLC with DAD detection. Results. The most efficient bacterial strain for FAE production was B. animalis cultivated in the presence of methyl p-coumarate and methyl ferulate as the main carbon sources (14.95 nmol·ml-1·min-1 and 4.38 nmol·ml-1·min-1, respectively. In the case of each FAE, the highest activity was obtained at 37oC (pH 6.3 in Theorell/Steinhagen buffer (B. animalis Bi30 or in Tris/HCl buffer (B. catenulatum KD14 and B. longum KN29. Taking under consideration all results, it should be noticed that the highest feruloyl esterase activities were obtained using synthetic methyl esters of phenolic acids. Conclusions. The presented resultsbroaden the knowledgeabout the production of the feruloyl esterase by probiotic bacteria. Although the enzyme is only accessory during

  20. 12-[(5-Iodo-4-azido-2-hydroxybenzoyl)amino]dodecanoic acid: Biological recognition by cholesterol esterase and acyl-CoA:cholesterol O-acyltransferase

    International Nuclear Information System (INIS)

    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 μM. Cholesterol esterase inhibition by IFA became irreversible after photolysis with UV light and oleic acid 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, 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

  1. Aspirin and colorectal cancer: Back to the Future

    OpenAIRE

    Tougeron, David; Sha, Dan; Manthravadi, Sashidhar; Sinicrope, Frank A

    2013-01-01

    Abundant epidemiological evidence indicates that regular and long term use of aspirin is associated with a significant reduction in the incidence of colorectal cancer (CRC). The long duration of aspirin needed to prevent CRC is believed to be due to inhibition of precursor lesions known as adenomas, whose recurrence is inhibited by aspirin in randomized trials. Aspirin intake has also been associated with a statistically significant improvement in patient survival after curative resection of ...

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

    OpenAIRE

    Kacprzak, Dorota; Pawliczak, Rafał

    2015-01-01

    Aspirin-induced asthma (AIA) is a distinct clinical syndrome characterized by severe asthma exacerbations after ingestion of aspirin or other non-steroidal anti-inflammatory drugs. The exact pathomechanism of AIA remains unknown, though ongoing research has shed some light. Recently, more and more attention has been focused on the role of aspirin in the induction of oxidative stress, especially in cancer cell systems. However, it has not excluded the similar action of aspirin in other inflamm...

  3. Exocellular esterase and emulsan release from the cell surface of Acinetobacter calcoaceticus.

    OpenAIRE

    Shabtai, Y; Gutnick, D. L.

    1985-01-01

    An esterase activity has been found, both in the cell-free growth medium and on the cell surface of the hydrocarbon-degrading Acinetobacter calcoaceticus RAG-1. The enzyme catalyzed the hydrolysis of acetyl and other acyl groups from triglycerides and aryl and alkyl esters. Emulsan, the extracellular heteropolysaccharide bioemulsifier produced by strain RAG-1, was also a substrate for the enzyme. Gel filtration showed that the cell-free enzyme was released from the cell surface either emulsan...

  4. Synthesis of [11C]N-methyl tetrahydroaminoacridine, a potent acetylcholine esterase inhibitor

    International Nuclear Information System (INIS)

    Tetrahydroaminoacridine (THA) is a potent central acting acetylcholine esterase (AChE) inhibitor which might be used as therapeutic agent in the treatment of Alzheimer's disease (AZD). In order to study the AChE activity in the brain by PET, the authors selected N-methyl THA, a potent AChE inhibitor, as a potential radioligand. In this paper, they report the synthesis and labelling of N-methyl THA with [11C]methyl iodide

  5. Separation and characterization of the acid lipase and neutral esterases from human liver.

    OpenAIRE

    Warner, T G; Dambach, L M; Shin, J H; O'Brien, J S

    1980-01-01

    Electrophoresis of human liver homogenates followed by reaction with 4-methylumbelliferyl palmitate reveals the presence of two major electrophoretic forms with esterase (lipase) activity toward this substrate. The two enzymes were isolated and partially purified based on their solubility differences and their relative affinities for the lectin column concanavalin A-Sepharose 4B. Lipase A was particulate with an acidic pH optimum (5.2) and could be solubilized with the non-ionic surfactant Tr...

  6. 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.

  7. 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)...

  8. The association of Hsp90 expression induced by aspirin with anti-stress damage in chicken myocardial cells

    OpenAIRE

    Zhang, Xiao-Hui; Zhu, Huai-sen; Qian, Zhuang; Tang, Shu; Wu, Di; Kemper, Nicole; Hartung, Joerg; Bao, En-dong

    2016-01-01

    The protective effect of aspirin during exposure to heat stress in broiler chickens was investigated. We assayed pathological damage, expression and distribution of Hsp90 protein and hsp90 mRNA expression in chicken heart tissues after oral administration of aspirin following exposure to high temperature for varying times. Heat stress induced increases in plasma aspartate aminotransferase, creatine kinase and lactate dehydrogenase activities while causing severe heart damage, which was charac...

  9. Prevention of ethanol and aspirin-induced gastric mucosal lesions by paracetamol and salicylate in rats: role of endogenous prostaglandins.

    OpenAIRE

    Konturek, S. J.; Brzozowski, T; Piastucki, I; Radecki, T

    1982-01-01

    Paracetamol or sodium salicylate given intragastrically 30 minutes before the administration of absolute ethanol or acidified aspirin dose-dependently reduced the formation of mucosal lesions. The generation of gastric mucosal prostaglandin-like activity increased with ethanol and was completely suppressed by acidified aspirin. Paracetamol or sodium salicylate given alone increased the generation of mucosal prostaglandin-like material. Indomethacin, the prostaglandin synthesis inhibitor, supp...

  10. 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.

  11. 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

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

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    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.

  13. Hydrolysis of synthetic polyesters by Clostridium botulinum esterases.

    Science.gov (United States)

    Perz, Veronika; Baumschlager, Armin; Bleymaier, Klaus; Zitzenbacher, Sabine; Hromic, Altijana; Steinkellner, Georg; Pairitsch, Andris; Łyskowski, Andrzej; Gruber, Karl; Sinkel, Carsten; Küper, Ulf; Ribitsch, Doris; Guebitz, Georg M

    2016-05-01

    Two novel esterases from the anaerobe Clostridium botulinum ATCC 3502 (Cbotu_EstA and Cbotu_EstB) were expressed in Escherichia coli BL21-Gold(DE3) and were found to hydrolyze the polyester poly(butylene adipate-co-butylene terephthalate) (PBAT). The active site residues (triad Ser, Asp, His) are present in both enzymes at the same location only with some amino acid variations near the active site at the surrounding of aspartate. Yet, Cbotu_EstA showed higher kcat values on para-nitrophenyl butyrate and para-nitrophenyl acetate and was considerably more active (sixfold) on PBAT. The entrance to the active site of the modeled Cbotu_EstB appears more narrowed compared to the crystal structure of Cbotu_EstA and the N-terminus is shorter which could explain its lower activity on PBAT. The Cbotu_EstA crystal structure consists of two regions that may act as movable cap domains and a zinc metal binding site. Biotechnol. Bioeng. 2016;113: 1024-1034. © 2015 Wiley Periodicals, Inc. PMID:26524601

  14. Theoretical studies of interaction models of human acetylcholine esterase with different inhibitors

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Alzheimer’s disease(AD) is a progressive neurodegenerative disorder and one of the most common causes of dementia in the elderly.Acetylcholine esterase inhibitors(AChEI) are the main drugs used in the treatment of AD.In this work,docking studies have been performed in order to understand the interaction between a number of inhibitors(tacrine,rivastigmine,huperzine A,TV-3326(ladostigil),donepezil and anseculin) and acetylcholine esterase(AChE).The calculated binding affinities between inhibitors and AChE increase in the order tacrineactivity expressed in terms of the half maximal inhibitory concentration(the IC50 value).Of the above inhibitors,anseculin is the most useful drug for the treatment of dementia.

  15. Esterase mediated resistance in deltamethrin resistant reference tick colony of Rhipicephalus (Boophilus) microplus.

    Science.gov (United States)

    Gupta, Snehil; Ajith Kumar, K G; Sharma, Anil Kumar; Nagar, Gaurav; Kumar, Sachin; Saravanan, B C; Ravikumar, Gandham; Ghosh, Srikant

    2016-06-01

    Monitoring of acaricide resistance is considered as one of the important facets of integrated tick management. In an attempt of development of resistance monitoring indicators, in the present study two reference tick lines of Rhipicephalus (Boophilus) microplus maintained in the Entomology laboratory, Indian Veterinary Research Institute (IVRI), Izatnagar, India, were studied to determine the possible contributing factors involved in development of resistance to deltamethrin. Electrophoretic profiling of esterase enzymes detected high activities of EST-1 in reference resistant tick colony designated as IVRI-IV whereas it was not detectable in reference susceptible IVRI-I line of R. (B.) microplus. Esterases were further characterized as carboxylesterase or acetylcholinesterase based on inhibitor study using PMSF, eserine sulphate, malathion, TPP and copper sulphate. It was concluded that an acetylcholinesterase, EST-1, possibly plays an important role for development of deltamethrin resistance in IVRI-IV colony of R. (B.) microplus. PMID:26979585

  16. 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 ...

  17. 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...

  18. Cloning, expression and characterization of a novel esterase from a South China Sea sediment metagenome

    Science.gov (United States)

    Zhang, Hao; Li, Fuchao; Chen, Huaxin; Zhao, Jin; Yan, Jinfei; Jiang, Peng; Li, Ronggui; Zhu, Baoli

    2015-07-01

    Lipolytic enzymes, including esterases and lipases, represent a group of hydrolases that catalyze the cleavage and formation of ester bonds. A novel esterase gene, scsEst01, was cloned from a South China Sea sediment metagenome. The scsEst01 gene consisted of 921 bp encoding 307 amino acid residues. The predicted amino acid sequence shared less than 90% identity with other lipolytic enzymes in the NCBI nonredundant protein database. ScsEst01 was successfully co-expressed in Escherichia coli BL21 (DE3) with chaperones (dnaK-dnaJ-grpE) to prevent the formation of inclusion bodies. The recombinant protein was purified on an immobilized metal ion affinity column containing chelating Sepharose charged with Ni2+. The enzyme was characterized using p -nitrophenol butyrate as a substrate. ScsEst01 had the highest lipolytic activity at 35°C and pH 8.0, indicative of a meso-thermophilic alkaline esterase. ScsEst01 was thermostable at 20°C. The lipolytic activity of scsEst01 was strongly increased by Fe2+, Mn2+ and 1% Tween 80 or Tween 20.

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

    Science.gov (United States)

    De Santi, Concetta; Willassen, Nils Peder

    2016-01-01

    Background 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. Results 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. PMID:27433797

  20. 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.

  1. 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.

  2. 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.

  3. Recovery of prostacyclin synthesis by rabbit aortic endothelium and other tissues after inhibition by aspirin.

    OpenAIRE

    Frazer, C. E.; Ritter, J M

    1987-01-01

    The effect of aspirin on prostacyclin (PGI2) and thromboxane B2 (TXB2) synthesis was studied in rabbits. Tissues were removed from animals killed at intervals after injection of aspirin, and incubated with Hanks' solution. PGI2 synthesis was monitored by radioimmunoassay of its hydrolysis product, 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha). TXB2 production in clotted blood, also measured by radioimmunoassay, was determined as an index of platelet cyclo-oxygenase activity. 6-oxo-PGF1 alph...

  4. 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.

  5. Aspirin and esophageal squamous cell carcinoma: bedside to bench

    Institute of Scientific and Technical Information of China (English)

    Li Peng; Cheng Rui; Zhang Shutian

    2014-01-01

    Objective To review the advances of studies on clinical results of aspirin's chemopreventive effect against esophageal squamous cell carcinoma (ESCC) and evidences for mechanisms of the antitumoural effects of aspirin in experimental research.Data sources A comprehensive search of the PubMed literatures without restriction on the publication date was carried out using keywords such as aspirin and esophageal cancer.Study selection Articles associated with aspirin and esophageal cancer are analyzed.Results This review focuses on the current evidence for use of aspirin as a chemopreventive agent in ESCC.Aspirin is the most widely used among all nonsteroidal anti-inflammatory drugs (NSAIDs),which is cheap and acceptable to patients.Several observational results provide the further investigation of prevention and therapy of aspirin or similar drugs in esophageal cancer.Data from case control studies,cohort studies and randomized controlled trials (RCTs) also give some support of a beneficial role of aspirin on ESCC.Experimental data suggest that aspirin may prevent carcinogenesis of ESCC by favorably affecting proliferation,apoptosis,or other as yet unidentified growth-regulating processes.But the mechanism by which aspirin influence on esophageal squamous cell carcinoma needs further investigation.Conclusion A wealth of evidences ranging from clinical data to experimental results are building to suggest that aspirin has significant effects in reducing both the incidence and mortality of ESCC.

  6. 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.

  7. Identification of petrogenic produced water components as acetylcholine esterase inhibitors.

    Science.gov (United States)

    Froment, Jean; Langford, Katherine; Tollefsen, Knut Erik; Bråte, Inger Lise N; Brooks, Steven J; Thomas, Kevin V

    2016-08-01

    Effect-directed analysis (EDA) was applied to identify acetylcholine esterase (AChE) inhibitors in produced water. Common produced water components from oil production activities, such as polycyclic aromatic hydrocarbons (PAHs), alkylphenols, and naphthenic acids were tested for AChE inhibition using a simple mixture of PAHs and naphthenic acids. Produced water samples collected from two offshore platforms in the Norwegian sector of the North Sea were extracted by solid phase extraction and fractionated by open-column liquid solid chromatography and high-performance liquid chromatography (HPLC) before being tested using a high-throughput and automated AChE assay. The HPLC fractions causing the strongest AChE inhibition were analysed by gas chromatography coupled to a high-resolution time-of-flight mass spectrometry (GC-HR-ToF-MS). Butylated hydroxytoluene and 4-phenyl-1,2-dihydronaphthalene were identified as two produced water components capable of inhibiting AChE at low concentrations. In order to assess the potential presence of such compounds discharged into aquatic ecosystems, AChE activity in fish tissues was measured. Saithe (Pollachius virens) caught near two offshore platforms showed lower enzymatic activity than those collected from a reference location. Target analysis of saithe did not detected the presence of these two putative AChE inhibitors and suggest that additional compounds such as PAHs, naphthenic acids and yet un-identified compounds may also contribute to the purported AChE inhibition observed in saithe. PMID:27176761

  8. Eco-friendly surface modification on polyester fabrics by esterase treatment

    International Nuclear Information System (INIS)

    Graphical abstract: - Highlights: • We used a simple and easy way to measure the enzyme activity. • We studied the mechanism by characterizing the chemical changes in the surface of fabric. • We studied the advantages in surface wettability, fiber integrity and mechanical performance of cutinase treated fabrics. • Cutinase pretreated fibers exhibited much improved fabric wicking and better fiber integrity comparing to alkali treated ones. • Cutinase pretreatment technology promotes energy conservation and emission reduction. - Abstract: Currently, traditional alkali deweighting technology is widely used to improve the hydrophilicity of polyester fabrics. However, the wastewater and heavy chemicals in the effluent cause enormous damage to the environment. Esterase treatment, which is feasible in mild conditions with high selectivity, can provide a clean and efficient way for polyester modification. Under the optimum conditions, the polyester fabric hydrolysis process of esterase had a linear kinetics. X-ray photoelectron spectrometry (XPS) results showed that hydroxyl and carboxyl groups were produced only on the surface of modified fiber without changing the chemical composition of the bulk. These fibers exhibited much improved fabric wicking, as well as greatly improved oily stain removal performance. Compared to the harsh alkali hydrolysis, the enzyme treatment led to smaller weight loss and better fiber integrity. The esterase treatment technology is promising to produce higher-quality polyester textiles with an environmental friendly approach

  9. Extração de esterase de fígado suíno (PLE) Pig liver esterase (PLE) extraction

    OpenAIRE

    Henrique Celso Trevisan; João Batista de Medeiros; Helen Cristina Fávero Lisboa

    2006-01-01

    A simple, fast and low-cost methodology was optimized, seeking preparation of a crude pig liver esterase (PLE) concentrate. Basically, the method consisted of the following steps: liver homogenization, acetone washing, enzyme extraction and purification/concentration. Starting from 1 kg of fresh liver more than 200 kU of PLE suspension were obtained after 8 hours, at an estimated cost of US$0.21/kU. The PLE concentrate thus obtained was stable, showing 96-100% of the initial activity after 7 ...

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

    Science.gov (United States)

    Chen, Grace; Zhang, Wencan; Serenko, Michael

    2015-06-01

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

  11. Aspirin treatment of the low-dose-endotoxin-treated pregnant rat : Pathophysiologic and immunohistologic aspects

    NARCIS (Netherlands)

    Faas, MM; Schuiling, GA; Baller, JFW; Valkhof, N; Bakker, WW

    1997-01-01

    In the present study, we evaluated the effect of low-dose aspirin (acetylsalicylic acid (ASA); 1.0 mg/kg daily) on blood pressure, albumin excretion, glomerular fibrinogen deposits, and glomerular (basement) membrane-bound adenosine diphosphatase (ecto-ADPase) activity, as well as on glomerular infl

  12. 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).

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

    Science.gov (United States)

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

    2011-06-01

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

  14. Juvenile Hormone (JH) Esterase of the Mosquito Culex quinquefasciatus Is Not a Target of the JH Analog Insecticide Methoprene

    Science.gov (United States)

    Kamita, Shizuo G.; Samra, Aman I.; Liu, Jun-Yan; Cornel, Anthony J.; Hammock, Bruce D.

    2011-01-01

    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 (kcat/KM ratio) and Vmax 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. PMID:22174797

  15. 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.

  16. Studies on the Purification and Characterization of Soybean Esterase,and Its Sensitivity to Organophosphate and Carbamate Pesticides

    Institute of Scientific and Technical Information of China (English)

    LI Jian-ke; ZHOU Yan-li; WEN Yan-xia; WANG Jian-hua; HU Qiu-hui

    2009-01-01

    Soybean esterase,a cholinesterase-like enzyme,was purified by differential centrifugation firstly,then,ammonium sulfate precipitation,dialysis,and finally,DEAE-cellulose-32 ion-exchange chromatography after extracting it from soybean seeds with phosphate buffer(0.3 mol L-1,pH 7.0).The extract recovery rate of the purified enzyme was 8.18% and purification fold was 91.58.The soybean esterase appeared as two bands on the denaturing SDS-PAGE with molecular weights of 24 and 37.2 kDa,respectively,which proved that it is a dimer protein consisting of two subunits.The result of nondenaturing PAGE revealed that the soybean esterase is a single band with cholinesterase-like activity using α-naphthyl acetate as the substrate and fast blue B salt as coloring agent.The esterase showed very high sensitivity to 18 kinds of organophosphate pesticides and 6 kinds of carbamate pesticides with the lowest detective limits of 0.03125-0.0625 and 0.03 125-0.25 mg kg-1,respectively,and can meet the demands of MRL specified by the most countries.

  17. 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. PMID:26695776

  18. 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

  19. Cloning and characterization of a novel thermostable esterase from Bacillus gelatini KACC 12197.

    Science.gov (United States)

    Kim, Jinyeong; Deng, Lili; Hong, Eunsoo; Ryu, Yeonwoo

    2015-12-01

    A novel gene encoding a thermostable esterase (designated as Est-gela) was isolated from the moderate thermophile Bacillus gelatini KACC 12197. The open reading frame of this gene (1170 bp) encodes 389 amino acid residues, and the molecular weight of Est-gela is approximately 42 kDa. The protein sequence of Est-gela shows similarity with β-lactamases and esterases (⩽ 43%). Est-gela contains the Ser-X-X-Lys conserved sequence (Ser58-Met59-Thr60-Lys61) and belongs to family VIII of esterases. We overexpressed Est-gela in Escherichia coli XL1-blue and purified this protein using a His tag. Est-gela showed a strong enzymatic activity toward p-nitrophenyl esters with short acyl chains (⩽ C4) and the strongest activity toward p-nitrophenyl butyrate. Est-gela showed an enhanced enzymatic activity at 65-75 °C and retained more than 90% of the activity after incubation at 65 °C for 180 min. These results indicated that Est-gela was thermostable. In addition, Est-gela showed the maximal activity at pH 10. We also evaluated the effects of surfactants and organic solvents. Surfactants were more effective at improving the enzymatic activity than were organic solvents. Finally, Est-gela hydrolyzed (R,S)-ketoprofen ethyl ester (Kcat/Km = 5.0 ± 0.2 s(-1) mM(-1), mean ± standard error) with enantioselectivity toward (S)-ketoprofen ethyl ester rather than (R)-ketoprofen ethyl ester. PMID:26276473

  20. Characterization of EST3: a metagenome-derived esterase with suitable properties for biotechnological applications.

    Science.gov (United States)

    Maester, Thaís Carvalho; Pereira, Mariana Rangel; Machado Sierra, E G; Balan, Andrea; de Macedo Lemos, Eliana Gertrudes

    2016-07-01

    Metagenomic libraries from diverse environments have been extensive sources of many lipases and esterases; nevertheless, most of these enzymes remain biochemically uncharacterized. We previously built a metagenomic fosmid library from a microbial consortium specialized for diesel oil degradation and tested it for lipolytic activity. In the present study, we identified the PL14.H10 clone that was subcloned and sequenced, which enabled the identification of the EST3 protein. This enzyme exhibited 74 % amino acid identity with the uncharacterized alpha/beta hydrolase from Parvibaculum lavamentivorans [GenBank: WP012110575.1] and was classified into lipolytic enzyme family IV. Biochemical characterization revealed that EST3 presents high activity in a wide range of temperature with highest activity from 41 to 45 °C. Also, this thermostable esterase acts from mild acidic to alkaline conditions with an optimum pH of 6.0. The enzyme exhibited activity against p-nitrophenyl esters of different chain lengths and highest catalytic efficiency against p-nitrophenyl caprylate. The activity of the protein was increased in the presence of 0.5 mM of Mn(+2), Li(+), EDTA, and 1 % of CTAB and exhibited half of the activity in the presence of 10 % methanol and ethanol. Moreover, the homology model of EST3 was built and compared to other esterases, revealing a substrate channel that should fit a wide range of substrates. Taken together, the data presented in this work reveal the unique and interesting characteristics of EST3 that might be explored for further use in biotechnological applications. PMID:26915995

  1. Interaction of monosulfonate tetraphenyl porphyrin (H 2TPPS 1) with plant-esterase: Determination of the binding mechanism by spectroscopic methods

    Science.gov (United States)

    Yang, Limin; Huo, Danqun; Hou, Changjun; Yang, Mei; Fa, Huanbao; Luo, Xiaogang

    2011-05-01

    The interaction of monosulfonate tetraphenyl porphyrin (H 2TPPS 1) with plant-esterase was investigated using fluorescence and UV-vis absorption spectroscopy. Fluorescence quenching, from which the binding parameters were evaluated, revealed that the quenching of the esterase by H 2TPPS 1 resulted from the formation of a dye-esterase complex. According to the modified Stern-Volmer equation, the effective quenching constants ( Ka) between H 2TPPS 1 and plant-esterase at four different temperatures (297 K, 300 K, 303 K, and 306 K) were obtained to be 14.132 × 10 5, 5.734 × 10 5, 2.907 × 10 5, and 2.291 × 10 5 M -1, respectively. The thermodynamic parameters, enthalpy change (Δ H) and entropy change (Δ S) for the reaction were calculated to be -181.67 kJ M -1 and -0.49 kJ M -1 K -1, indicating that van der Waals force and hydrogen bonds were the dominant intermolecular force in stabilizing the complex. Site marker competitive experiments showed that the binding of H 2TPPS 1 to plant-esterase primarily took place in the active site. The binding distance ( r) was obtained to be 5.99 nm according to Förster theory of non-radioactive energy transfer. The conformation of plant-esterase was investigated by synchronous fluorescence and UV-vis absorption spectroscopy, and the results confirmed some micro-environmental and conformational changes of plant-esterase molecules.

  2. Formulation and evaluation of novel aspirin nanoparticles loaded suppositories

    Institute of Scientific and Technical Information of China (English)

    Ravi Sankar V.; Dhachinamoorthi D.; Chandra Shekar K.B.

    2013-01-01

    The main objective of the present work is to design aspirin nanoparticles loaded suppositories which will reduce the side effects caused by aspirin suppositories.Aspirin nanoparticles were prepared initially based on ionic-gelation mechanism and lyophilized.The prepared nanoparticles were evaluated,and the results confirmed that Fa9 formulation was the best with greater drug entrapment efficiency.Aspirin suppositories were prepared in order to investigate the best base composition.The prepared suppositories were evaluated and FS1,FS3,FS4,FS8,FS11,and FS12 were proved to be the best base compositions based on dissolution performed.The lyophilized aspirin nanoparticles of Fa9 were used to prepare aspirin nanoparticles loaded suppositories.The in vitro results revealed that Fas 11 was the best formulation.

  3. A vasculo-protective circuit centered on lipoxin A4 and aspirin-triggered 15-epi-lipoxin A4 operative in murine microcirculation

    OpenAIRE

    Brancaleone, Vincenzo; Gobbetti, Thomas; Cenac, Nicolas; Le Faouder, Pauline; Colom, Bartomeu; Flower, Roderick J.; Vergnolle, Nathalie; Nourshargh, Sussan; Perretti, Mauro

    2013-01-01

    Fpr2/3 activation controls platelet/neutrophil aggregates to afford LXA4 synthesis, thus inhibiting vascular inflammation on reperfusion.Aspirin can jumpstart this circuit by triggering 15-epi-lipoxin synthesis.

  4. Production of extracellular ferulic acid esterases by Lactobacillus strains using natural and synthetic carbon sources

    OpenAIRE

    Dominik Szwajgier; Anna Jakubczyk

    2011-01-01

    Background. Ferulic acid esterases (FAE, EC 3.1.1.73), also known as feruloyl esterases, cinnamic acid esterases or cinnamoyl esterases, belong to a common group of hydrolases distributed in the plant kingdom. Especially the fungal enzymes were very well characterised in the past whereas the enzyme was rarely found in the lactic acid bacteria (LAB) strains. It is well known that strong antioxidants free phenolic acids can be released from the dietary fiber by the action of intestinal microflo...

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

    Science.gov (United States)

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

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

    Science.gov (United States)

    ... the-Counter Medicines Safe Daily Use of Aspirin Aspirin for Reducing Your Risk of Heart Attack and ... any pharmacy, grocery or convenience store and buy aspirin without a prescription. The Drug Facts label on ...

  7. Aspirin as Primary Prevention of Acute Coronary Heart Disease Events

    OpenAIRE

    Glasser, Stephen P.; Hovater, Martha; Brown, Todd M.; Howard, George; Safford, Monika M.

    2014-01-01

    Background/Objective Aspirin for primary prophylaxis is controversial. This study evaluated associations between prophylactic aspirin use and incident acute coronary heart disease (CHD) events. Methods and Results The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study was accessed for aspirin use examining black and white hazards for incident CHD, for men and women, each adjusting incrementally for sampling, sociodemographics, and CHD risk factors. Stratified models exami...

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

    OpenAIRE

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

    1988-01-01

    In a series of experiments to investigate interactions between industrial solvents and common medications the interaction between m-xylene and aspirin was studied. As both these substances are metabolised and excreted as glycine conjugates there would possibly be competition for this conjugation pathway. Five male volunteers were exposed on separate occasions to m-xylene by inhalation (100 ppm), aspirin (1500 mg) by mouth, and m-xylene and aspirin together under controlled conditions in an ex...

  9. Two cases of oral aspirin overdose.

    Science.gov (United States)

    Kato, Hideaki; Yoshimoto, Kanji; Ikegaya, Hiroshi

    2010-07-01

    A 30-year-old woman and a 27-year-old man were found in a parked car after the man had telephoned his father to tell him of their suicide attempt. In spite of emergent hospitalization and intensive care, the woman died. Due to the possibility of his assisting her suicide, medicolegal autopsy and toxicological analysis were performed. On forensic autopsy, no external injuries or pathological findings were detected. The man recovered after 5 days of hospitalization. In spite of a negative toxicological screening test, the police investigation revealed that they may have taken 120 tablets (330 mg/tablet; 39,600 mg total dose) of aspirin (acetylsalicylic acid) orally; therefore, we analyzed the concentrations of acetylsalicylic acid and two kinds of metabolite in specimens obtained at autopsy and on emergent hospitalization using high performance liquid chromatography. Acetylsalicylic acid and/or the two metabolites were found in the woman's specimens. These substances were also present in the man's specimens. It is still unclear why the man survived in spite of what appeared to be a fatal aspirin overdose. It was very straightforward to diagnose aspirin poisoning in these cases; however, we have to be aware of poisoning by drugs which are not included in simple drug screening examinations. PMID:20569957

  10. 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.

  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 Promotes Oligodendroglial Differentiation Through Inhibition of Wnt Signaling Pathway.

    Science.gov (United States)

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

    2016-07-01

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

  13. Gastroprotective Effect of Rubia cordifolia Linn. on Aspirin Plus Pylorus-Ligated Ulcer

    OpenAIRE

    S. S. Bhujbal; Dinesh Kumar; R S Deoda

    2011-01-01

    The present study was designed to investigate the effect of Rubia cordifolia (Rubiaceae) against experimentally induced gastric ulcer and compare activity with its fractions by employing aspirin plus pylorus-ligated ulcer screening model in Wistar rats. Total acidity, volume of gastric acid secretion, total acid output, and pepsin activity show significant reduction, when compared with the control group. The present study confirmed that chloroform fraction showed the significant activity at l...

  14. Production of extracellular ferulic acid esterases by Lactobacillus strains using natural and synthetic carbon sources

    Directory of Open Access Journals (Sweden)

    Dominik Szwajgier

    2011-09-01

    Full Text Available Background. Ferulic acid esterases (FAE, EC 3.1.1.73, also known as feruloyl esterases, cinnamic acid esterases or cinnamoyl esterases, belong to a common group of hydrolases distributed in the plant kingdom. Especially the fungal enzymes were very well characterised in the past whereas the enzyme was rarely found in the lactic acid bacteria (LAB strains. It is well known that strong antioxidants free phenolic acids can be released from the dietary fiber by the action of intestinal microflora composed among others also of Lactobacillus strains. The aim of this study was to examine four Lactobacillus strains (L. acidophilus K1, L. rhamnosus E/N, PEN, OXYfor the ability to produce extracellular FAE on different synthetic and natural carbon sources. Material and methods. The LAB strains were grown in the minimal growth media using German wheat bran, rye bran, brewers’ spent grain, isolated larchwood arabinogalactan, apple pectin, corn pectin, methyl ferulate, methyl p-coumarate, methyl syringate or methyl vanillate as the sole carbon source. FAE activity was determined using the post-cultivation supernatants, methyl ferulate and HPLC with UV detection. Results. The highest FAE activity was obtained with L. acidophilus K1 and methyl ferulate (max. 23.34 ±0.05 activity units and methyl p-coumarate (max. 14.96 ±0.47 activity units as carbon sources. L. rhamnosus E/N, OXY and PEN exhibited the limited ability to produce FAE with cinnamic acids methyl esters. Methyl syringate and methyl vanillate (MS and MV were insufficient carbon sources for FAE production. Brewers’ spent grain was the most suitable substrate for FAE production by L. acidophilus K1 (max. 2.64 ±0.06 activity units and L. rhamnosus E/N, OXY and PEN. FAE was also successfully induced by natural substrates rye bran, corn pectin (L. acidophilus K1, German wheat bran and larchwood arabinogalactan (E/N, PEN or German wheat bran and corn pectin (OXY. Conclusions. This study proved the

  15. Aspirin inhibits interleukin 1-induced prostaglandin H synthase expression in cultured endothelial cells

    International Nuclear Information System (INIS)

    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-[35S]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

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

    Science.gov (United States)

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

    2016-08-01

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

  17. 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.

  18. Biphasic effect of aspirin on apoptosis of bovine vascular endothelial cells and its molecular mechanism

    Institute of Scientific and Technical Information of China (English)

    Qing-quan CHEN; Wen-lan LIU; Xun GUO; Yuan-jian LI; Zhao-gui GUO

    2007-01-01

    Aim: To investigate the effect of aspirin on the apoptosis of cultured bovine aortic endothelial cells (BAEC) and the signal pathways involved in this process.Methods: BAEC were cultured and passaged in Dulbecco's modified Eagle's medium culture medium. Morphologic changes and quantification of apoptotic cells were determined using fluorescence microscope after staining the cells with Hoechst 33258. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method. DNA fragmentation was visualized by agarose gel electrophoresis. Phospho-p38 mitogen-activated protein kinase(MAPK) expression was detected by Western blotting. Results: Aspirin at low concentrations from 1×10-10 mol/L to 1×10-8 mol/L decreased the apoptosis and p38 MAPK phosphorylation induced by H2O2 in BAEC, while high doses of aspi-fin (1×10-7-1×10-4 mol/L) induced typical apoptotic changes in BAEC and stimu-lated the expression of phospho-p38 MAPK in a concentration-dependent manner.SB203580, a specific p38 MAPK inhibitor, blocked such effects. Conclusion:Aspirin exhibits a biphasic effect on the apoptosis in BAEC, reducing apoptosis at low concentration and inducing apoptosis at high concentration, p38 MAPK may be an important signal molecule mediating the effects of aspirin.

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

    Science.gov (United States)

    Yang, H; Pellegrini, L; Napolitano, A; Giorgi, C; Jube, S; Preti, A; Jennings, C J; De Marchis, F; Flores, E G; Larson, D; Pagano, I; Tanji, M; Powers, A; Kanodia, S; Gaudino, G; Pastorino, S; Pass, H I; Pinton, P; Bianchi, M E; Carbone, M

    2015-01-01

    High-mobility group box 1 (HMGB1) is an inflammatory molecule that has a critical role in the initiation and progression of malignant mesothelioma (MM). Aspirin (acetylsalicylic acid, ASA) is the most widely used nonsteroidal anti-inflammatory drug that reduces the incidence, metastatic potential and mortality of many inflammation-induced cancers. We hypothesized that ASA may exert anticancer properties in MM by abrogating the carcinogenic effects of HMGB1. Using HMGB1-secreting and -non-secreting human MM cell lines, we determined whether aspirin inhibited the hallmarks of HMGB1-induced MM cell growth in vitro and in vivo. Our data demonstrated that ASA and its metabolite, salicylic acid (SA), inhibit motility, migration, invasion and anchorage-independent colony formation of MM cells via a novel HMGB1-mediated mechanism. ASA/SA, at serum concentrations comparable to those achieved in humans taking therapeutic doses of aspirin, and BoxA, a specific inhibitor of HMGB1, markedly reduced MM growth in xenograft mice and significantly improved survival of treated animals. The effects of ASA and BoxA were cyclooxygenase-2 independent and were not additive, consistent with both acting via inhibition of HMGB1 activity. Our findings provide a rationale for the well documented, yet poorly understood antitumorigenic activity of aspirin, which we show proceeds via HMGB1 inhibition. Moreover, the use of BoxA appears to allow a more efficient HMGB1 targeting while eluding the known gastrointestinal side effects of ASA. Our findings are directly relevant to MM. Given the emerging importance of HMGB1 and its tumor-promoting functions in many cancer types, and of aspirin in cancer prevention and therapy, our investigation is poised to provide broadly applicable information. PMID:26068794

  20. 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

  1. 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....... Production of FAE does not therefore, require FA, however, production is diminished by the removal of esterified FA from the growth substrate. Optimal FAE activity was observed at pH 7 and 50 degreesC with 68 and 55% activity at pH 8 and pH 9, respectively. The esterase was fully stable at pH 5-8 and up to...... 40 degreesC and retained 72 and 40% of its activity after 6 h at pH 9 and pH 10, respectively. After separation by isoelectric focusing electrophoresis, a zymogram indicated one major FAE activity exhibiting pI value of 10.5....

  2. Purification and characterization of a pregastric esterase from a hygienized kid rennet paste.

    Science.gov (United States)

    Calvo, M V; Fontecha, J

    2004-05-01

    Rennet pastes obtained by maceration of gastric tissues from suckling kids are used traditionally to produce some artisanal cheeses in Spain. Besides milk-clotting function, rennet pastes provide proteolytic activity and lipolytic system, essentially pregastric, necessary in the development of piquant flavor typical of these cheeses. A simple and reproducible procedure allows us to obtain a standardized rennet paste that posses the desired activity and is of good microbiological quality. Concomitantly, a kid pregastric esterase (KPGE) was purified to homogeneity. The purification procedure was based on an aqueous extract of hygienized rennet paste (HRP), which was chromatographed on DEAE-Sepharose Fast Flow then adsorbed on phenyl superose followed by a re-chromatography on the same column. The final enzymatic preparation, where the overall activity recovery was 3%, showed a molecular mass of 53 kDa. The highest activity was determined on p-nitrophenyl butyrate, but marked hydrolysis was also detected on beta-naphthyl caprylate. In contrast, low activity on tributyrin (substrate under emulsion form) was detected, thus confirming the esterase character of purified enzyme. PMID:15290959

  3. Cellular function of neuropathy target esterase in lysophosphatidylcholine action

    International Nuclear Information System (INIS)

    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

  4. Cloning, expression and characterization of a novel cold‑adapted GDSL family esterase from Photobacterium sp. strain J15.

    Science.gov (United States)

    Shakiba, Mehrnoush Hadaddzadeh; Ali, Mohd Shukuri Mohamad; Rahman, Raja Noor Zaliha Raja Abd; Salleh, Abu Bakar; Leow, Thean Chor

    2016-01-01

    The gene encoding for a novel cold-adapted enzyme from family II of bacterial classification (GDSL family) was cloned from the genomic DNA of Photobacterium sp. strain J15 in an Escherichia coli system, yielding a recombinant 36 kDa J15 GDSL esterase which was purified in two steps with a final yield and purification of 38.6 and 15.3 respectively. Characterization of the biochemical properties showed the J15 GDSL esterase had maximum activity at 20 °C and pH 8.0, was stable at 10 °C for 3 h and retained 50 % of its activity after a 6 h incubation at 10 °C. The enzyme was activated by Tween-20, -60 and Triton-X100 and inhibited by 1 mM Sodium dodecyl sulphate (SDS), while β-mercaptoethanol and Dithiothreitol (DTT) enhanced activity by 4.3 and 5.4 fold respectively. These results showed the J15 GDSL esterase was a novel cold-adapted enzyme from family II of lipolytic enzymes. A structural model constructed using autotransporter EstA from Pseudomonas aeruginosa as a template revealed the presence of a typical catalytic triad consisting of a serine, aspartate, and histidine which was verified with site directed mutagenesis on active serine. PMID:26475626

  5. Esterases as biomarkers in Nereis (Hediste) diversicolor exposed to temephos and Bacillus thuringiensis var. israelensis used for mosquito control in coastal wetlands of Morbihan (Brittany, France).

    Science.gov (United States)

    Fourcy, D; Jumel, A; Heydorff, M; Lagadic, L

    2002-01-01

    Since 1998, a biomonitoring programme has been implemented to assess the potential impact of chemical mosquito control on macroinvertebrates of the coastal wetlands of Morbihan (Brittany, France). Acetylcholinesterase and carboxylesterases were used as biomarkers to assess the effects of Abate 500e (a.i. temephos) and Vectobac 12 AS (a.i. endotoxins of Bacillus thuringiensis var. israelensis, Bti) in Nereis (Hediste) diversicolor. Esterase inhibition revealed a marked impact of temephos, suggesting preferential contamination of the worms through the food. In Bti-exposed N. diversicolor, random variations of esterase activities were observed, that could not be attributed to the larvicide. However, esterases only reflected indirect physiological effects of Bti, and further investigations are needed to identify biomarkers more specific of Bti endotoxins. PMID:12408646

  6. Effect of Bark Extract and Gum Exudate of Commiphora Caudata on Aspirin Induced Ulcer in Rats

    OpenAIRE

    R Nanthakumar; Ambrose S Stephen; E Sriram; Babu, G.; K Chitra; C Uma maheswara Reddy

    2009-01-01

    Commiphora caudata is used in Indian folk medicine as an antiulcerogenic agent. Despite of its promising use, there has been no scientific report present regarding its antiulcer activity. Therefore, this study was designed to evaluate the antiulcer activity of bark extract and gum exudate of commiphora caudata on aspirin induced ulcer in rats. Acute toxicity study was performed and 200 mg/kg was selected as an effective dose. Four groups of Albino Swiss rats were included in this study. Aspir...

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

    International Nuclear Information System (INIS)

    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 IC50 of 5 μg l-1 for propionylcholinesterase (PChE). PChE was significantly inhibited in vivo after a 10 day exposure to 100 μg l-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

  8. Aspirin and clonidine in non-cardiac surgery

    DEFF Research Database (Denmark)

    Garg, Amit; Kurz, Andrea; Sessler, Daniel I;

    2014-01-01

    INTRODUCTION: Perioperative Ischaemic Evaluation-2 (POISE-2) is an international 2×2 factorial randomised controlled trial of low-dose aspirin versus placebo and low-dose clonidine versus placebo in patients who undergo non-cardiac surgery. Perioperative aspirin (and possibly clonidine) may reduc...

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

    Science.gov (United States)

    Morgan, Gareth

    2014-01-01

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

  10. 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.

  11. 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

  12. Effects of piperonyl butoxide on the toxicity of the organophosphate temephos and the role of esterases in the insecticide resistance of Aedes aegypti

    OpenAIRE

    Boscolli Barbosa Pereira; Jean Ezequiel Limongi; Edimar Olegário de Campos Júnior; Denis Prudencio Luiz; Warwick Estevam Kerr

    2014-01-01

    Introduction The effects of piperonyl butoxide (PBO) on the toxicity of the organophosphate temephos (TE) and the role of esterases in the resistance of Aedes aegypti to this insecticide were evaluated. Methods A. aegypti L4 larvae susceptible and resistant to TE were pre-treated with PBO solutions in acetone at concentrations of 0.125, 0.25, 0.5, 1, and 2% for 24h and subsequently exposed to a diagnostic concentration of 0.02mg/L aqueous TE solution. The esterase activity of the larvae ext...

  13. Everted Intestinal Sacs As In vitro Model For Assessing Absorptivity Of L Histidine Under The Effect Of Aspirine And Gum Acacia In Male Rats

    Directory of Open Access Journals (Sweden)

    Mahmoud Rabeh Mahmoud

    2004-09-01

    Full Text Available The purpose of this study was to characterize intestinal permeability changes over a range of physiologically relevant intestinal injury. The experiments were performed in 80 rats subdivided into four groups as aspirin (400 mg/kg b.w., gum Acacia ( 1g./day and aspirin with gum Acacia groups for 21 days compared with control group. Relative reabsorption of L-Histidine was greater(p<0.001 in the aspirin in 10 min of incubation compared with that of the control rats. In aspirin in combination with gum Acacia, the relative reabsorption were significantly (p<0.001 decrease in 10, 20 and 30 min. of incubation compared with that of the control rats. Moreover, the relative reabsorption of L-histidine was significantly (p<0.01 reduced by the aspirin at 45 min of time of the incubation buffer compared with that of the control. However, gum acacia treatment was increased at 10 min (p<0.01 ,30 min (p<0.01 and 45 min (p<0.001 respectively compared with that of the control rats. Relative reabsorption of L-histidine record a nonsignificant increase of aspirin at 20 min and 30 min of incubation compared with that of the control. Gum and aspirin with gum at 20min and 45min of incubation resulted an increase and decrease in relative reabsorption of L-histidine respectively compared with that of the control. Aspirin and aspirin in combination with gum acacia treatment increased body, intestinal weights and mucosal total protein significantly with percent changes ranged from 8% to 40% compared with that of the control. On the other hand, gum treatment decreased body, intestinal weights and mucosal total protein significantly with percent changes ranged from 8% to 35% compared with that of the control. These results demonstrated that L-histidine is actively taken up by a gum Acacia system in intestinal everted sac mechanism of rat with energy supplied by glucose and Na+in incubation buffer. Moreover, aspirin system had an inhibitory effect on L-histidine uptake in

  14. The association of Hsp90 expression induced by aspirin with anti-stress damage in chicken myocardial cells.

    Science.gov (United States)

    Zhang, Xiao-Hui; Zhu, Huai-Sen; Qian, Zhuang; Tang, Shu; Wu, Di; Kemper, Nicole; Hartung, Joerg; Bao, En-Dong

    2016-03-01

    The protective effect of aspirin during exposure to heat stress in broiler chickens was investigated. We assayed pathological damage, expression and distribution of Hsp90 protein and hsp90 mRNA expression in chicken heart tissues after oral administration of aspirin following exposure to high temperature for varying times. Heat stress induced increases in plasma aspartate aminotransferase, creatine kinase and lactate dehydrogenase activities while causing severe heart damage, which was characterized by granular and vacuolar degeneration, nuclear shrinkage and even myocardium fragmentation in cardiac muscle fibers. After aspirin administration, myocardial cells showed fewer pathological lesions than broilers treated with heat alone. A high positive Hsp90 signal was always detected in the nuclei of myocardial cells from broilers treated with aspirin, while in myocardial cells treated with heat alone, Hsp90 in the nuclei decreased, as did that in the cytoplasm. Aspirin induced rapid and significant synthesis of Hsp90 before and at the initial phase of heat stress, and significant expression of hsp90 mRNA was stimulated throughout the experiment when compared with cells exposed to heat stress alone. Thus, specific pre-induction of Hsp90 in cardiovascular tissue was useful for resisting heat stress damage because it produced stable damage-related enzymes and fewer pathologic changes. PMID:27051338

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

    Science.gov (United States)

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

    2015-07-01

    We have recently shown that dipyrone (metamizole), a non-opioid analgesic, can nullify aspirin (acetylsalicylic acid; ASA) antiplatelet effects in patients with coronary artery disease (CAD). In this study, we analysed the aspirin and dipyrone drug-drug interaction in order to identify strategies to prevent the dipyrone induced inhibition of asprin antiplatelet effects. Platelet function was measured by arachidonic acid-induced light-transmission aggregometry, thromboxane (TX) B2- formation by immunoassay. Dipyrone metabolite plasma levels were determined by high-performance-liquid-chromatography (HPLC). In seven healthy individuals, in vitro ASA (30 µM/ 100 µM/ 300 µM/ 1,000 µM) and dipyrone (10 µM) coincubation revealed, that the aspirin and dipyrone interaction can be overcome by increasing doses of aspirin. In 36 aspirin and dipyrone comedicated CAD patients, addition of ASA (30 µM/ 100 µM) in vitro inhibited, but did not completely overcome the dipyrone induced reduction of aspirin antiplatelet effects. Notably, the inhibition of thromboxane formation in aspirin and dipyrone comedicated CAD patients coincided with dipyrone plasma levels. In a cross-over designed study in four healthy individuals, we were able to prove that inhibition of aspirin (100 mg/ day) effects by dipyrone (750 mg/ day) was reversible. Furthermore, aspirin (100 mg/ day) medication prior to dipyrone (750 mg/ day) intake prevented the inhibition of antiplatelet effects by dipyrone in 12 healthy individuals. In conclusion, aspirin medication prior to dipyrone intake preserves antiplatelet effects, circumventing the pharmacodynamic drug-drug interaction at the level of cyclooxygenase-1. PMID:25789542

  16. 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.

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

    International Nuclear Information System (INIS)

    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 (Km = 77.2 mM; Vmax = 38.2 mU/mg protein) and 1-naphthyl acetate (Km = 222 mM, Vmax = 1095 mU/mg protein) substrates, respectively. Acetylcholinesterase activity was concentration-dependently inhibited by chlorpyrifos-oxon, dichlorvos, carbaryl and carbofuran (IC50 = 1.35 x 10-5-3.80 x 10-8 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 10-5-2.98 x 10-8 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

  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. A new family of carbohydrate esterases is represented by a GDSL hydrolase/acetylxylan esterase from Geobacillus stearothermophilus.

    Science.gov (United States)

    Alalouf, Onit; Balazs, Yael; Volkinshtein, Margarita; Grimpel, Yael; Shoham, Gil; Shoham, Yuval

    2011-12-01

    Acetylxylan esterases hydrolyze the ester linkages of acetyl groups at positions 2 and/or 3 of the xylose moieties in xylan and play an important role in enhancing the accessibility of xylanases to the xylan backbone. The hemicellulolytic system of the thermophilic bacterium Geobacillus stearothermophilus T-6 comprises a putative acetylxylan esterase gene, axe2. The gene product belongs to the GDSL hydrolase family and does not share sequence homology with any of the carbohydrate esterases in the CAZy Database. The axe2 gene is induced by xylose, and the purified gene product completely deacetylates xylobiose peracetate (fully acetylated) and hydrolyzes the synthetic substrates 2-naphthyl acetate, 4-nitrophenyl acetate, 4-methylumbelliferyl acetate, and phenyl acetate. The pH profiles for k(cat) and k(cat)/K(m) suggest the existence of two ionizable groups affecting the binding of the substrate to the enzyme. Using NMR spectroscopy, the regioselectivity of Axe2 was directly determined with the aid of one-dimensional selective total correlation spectroscopy. Methyl 2,3,4-tri-O-acetyl-β-d-xylopyranoside was rapidly deacetylated at position 2 or at positions 3 and 4 to give either diacetyl or monoacetyl intermediates, respectively; methyl 2,3,4,6-tetra-O-acetyl-β-d-glucopyranoside was initially deacetylated at position 6. In both cases, the complete hydrolysis of the intermediates occurred at a much slower rate, suggesting that the preferred substrate is the peracetate sugar form. Site-directed mutagenesis of Ser-15, His-194, and Asp-191 resulted in complete inactivation of the enzyme, consistent with their role as the catalytic triad. Overall, our results show that Axe2 is a serine acetylxylan esterase representing a new carbohydrate esterase family. PMID:21994937

  20. Aspirin Plays Dual Role in Helping Heart

    Institute of Scientific and Technical Information of China (English)

    余玲梅

    2002-01-01

    贵刊多次介绍“百年老药”aspirin(阿斯匹林,解热镇痛药,又称“乙酰水杨酸”)的神奇作用,我读了贵刊的介绍后,也开始服用aspirin,收到了意想不到的效果。现在,我上网时,对aspirin的报道特别留心。今日又在网上读到此文,特地加注后,发你们。文中有两个单词:interleukin-1(IL-1)/endothelialfunction,查阅了许多词典,仍不得其解。好在紧接其后的同谓语对这两个词作了解释。前者的以意思是:a blood of chemical associated with inflammation(一种炎 症有关的血液化学物质);后者是:the ability of the blood vessels to expand(血管扩张的能力)这两个词与新发现的aspirin两个功能有关,一是,能增加抗炎症作用,二是令血管得以扩张。】

  1. Glutaraldehyde Cross-Linking of Immobilized Thermophilic Esterase on Hydrophobic Macroporous Resin for Application in Poly(ε-caprolactone Synthesis

    Directory of Open Access Journals (Sweden)

    Min Wang

    2014-07-01

    Full Text Available The immobilized thermophilic esterase from Archaeoglobus fulgidus was successfully constructed through the glutaraldehyde-mediated covalent coupling after its physical adsorption on a hydrophobic macroporous resin, Sepabeads EC-OD. Through 0.05% glutaraldehyde treatment, the prevention of enzyme leaching and the maintenance of catalytic activity could be simultaneously realized. Using the enzymatic ring-opening polymerization of ε-caprolactone as a model, effects of organic solvents and reaction temperature on the monomer conversion and product molecular weight were systematically investigated. After the optimization of reaction conditions, products were obtained with 100% monomer conversion and Mn values lower than 1010 g/mol. Furthermore, the cross‑linked immobilized thermophilic esterase exhibited an excellent operational stability, with monomer conversion values exceeding 90% over the course of 12 batch reactions, still more than 80% after 16 batch reactions.

  2. Effect of Bark Extract and Gum Exudate of Commiphora Caudata on Aspirin Induced Ulcer in Rats

    Directory of Open Access Journals (Sweden)

    R Nanthakumar

    2009-01-01

    Full Text Available Commiphora caudata is used in Indian folk medicine as an antiulcerogenic agent. Despite of its promising use, there has been no scientific report present regarding its antiulcer activity. Therefore, this study was designed to evaluate the antiulcer activity of bark extract and gum exudate of commiphora caudata on aspirin induced ulcer in rats. Acute toxicity study was performed and 200 mg/kg was selected as an effective dose. Four groups of Albino Swiss rats were included in this study. Aspirin suspended in 0.5 % carboxymethyl cellulose (CMC was given orally to group 1 rats as a negative control group. Group 2 and group 3 animals received methanolic extract and gum exudate of commiphora caudata respectively. Sucralfate was given orally to group 4 animals as a positive control. The methanolic extract of commiphora caudata has been found to reduce total acidity as much as by sucralfate. However, it has not changed the fluid secretion. The gum preparation not only reduced the total acidity but also considerably reduce the gastric fluid secretion. In case of ulcer score sucralfate, methanolic extract and the gum have produced the low ulcer score compared to aspirin. Increased gastric mucosal protective mechanism by bark extract and gum exudate is probably due to the presence of some active principles present in the plant. However, further investigations are required to elucidate their exact mechanism of anti-ulcer activity.

  3. New insights into the anti-inflammatory actions of aspirin- induction of nitric oxide through the generation of epi-lipoxins

    Directory of Open Access Journals (Sweden)

    Derek W Gilroy

    2005-03-01

    Full Text Available Aspirin has always remained an enigmatic drug. Not only does it present with new benefits for treating an ever-expanding list of apparently unrelated diseases at an astounding rate but also because aspirin enhances our understanding of the nature of these diseases processe. Originally, the beneficial effects of aspirin were shown to stem from its inhibition of cyclooxygenase-derived prostaglandins, fatty acid metabolites that modulate host defense. However, in addition to inhibiting cyclooxygenase activity aspirin can also inhibit pro-inflammatory signaling pathways, gene expression and other factors distinct from eicosanoid biosynthesis that drive inflammation as well as enhance the synthesis of endogenous protective anti-inflammatory factors. Its true mechanism of action in anti-inflammation remains unclear. Here the data from a series of recent experiments proposing that one of aspirin's predominant roles in inflammation is the induction of nitric oxide, which potently inhibits leukocyte/endothelium interaction during acute inflammation, will be discussed. It will be argued that this nitric oxide-inducing effects are exclusive to aspirin due to its unique ability, among the family of traditional anti-inflammatory drugs, to acetylate the active site of inducible cyclooxygenase and generate a family of lipid mediators called the epi-lipoxins that are increasingly being shown to have profound roles in a range of host defense responses.

  4. 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 ...

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

    OpenAIRE

    Yoshihiro Suzuki; Toshio Inoue; Chisei Ra

    2010-01-01

    Aspirin (acetylsalicylic acid) is a well-known nonsteroidal anti-inflammatory drug (NSAID) that has long been used as an anti-pyretic and analgesic drug. Recently, much attention has been paid to the chemopreventive and apoptosis-inducing effects of NSAIDs in cancer cells. These effects have been thought to be primarily attributed to the inhibition of cyclooxygenase activity and prostaglandin synthesis. However, recent studies have demonstrated unequivocally that certain NSAIDs, including asp...

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

    OpenAIRE

    Wolfgang Lösche; Janina Boettel; Björn Kabisch; Johannes Winning; Claus, Ralf A.; Michael Bauer

    2011-01-01

    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 ...

  7. Comparison of Activities of Amylase, Esterase, Acid Phosphatase in Ginseng Radix et Rhizoma from Different Origins and Different Growth Periods%不同产地、不同年限人参中淀粉酶、酯酶、酸性磷酸酯酶的活力比较

    Institute of Scientific and Technical Information of China (English)

    邢楠楠; 赵雨; 刘宏; 张惠; 李红艳

    2011-01-01

    目的 对不同产地、不同生长年限人参进行淀粉酶(AMY)、酯酶(Est)和酸性磷酸酯酶(ACP)活力比较.方法 用中性缓冲溶液提取总蛋白,应用3,5-二硝基水杨酸比色法测定AMY活力;乙酸-α-萘酯比色法测定Est活力;对硝基酚比色法测定ACP活力.结果 不同产地人参AMY、Est、ACP活力均存在很大差异.取不同产地、相同生长年限酶活力平均值进行不同年限的酶活力比较,可知4年与5年生人参3种水解酶活力均无明显差异.结论 AMY、Est、ACP活力可以作为评价人参质量的内在指标之一.%OBJECTIVE To compare activities of Ginseng Radix et Rhizoma amylase(AMY), esterase (Est) and acid phosphatase (ACP) from different origins and different growth periods. METHODS Total protein was extracted using a neutral buffer solution. Determination of AMY activity applied 3,5-dinitrosalicylic acid colorimetry. Determination of Est activity was using acetic acid-α-naphthyl ester colorimetry. Determination of ACP activity was using p-nitrophenol colorimetry. RESULTS There was a significant difference in activities of AMY, Est and ACP in Ginseng Radix et Rhizoma from different origins. Take the average value for enzyme activity in Ginseng Radix et Rhizoma of different origin and the same growth period, purpose was to compare the enzyme activity at different ages. We can know that activities of three kinds of enzyme hydrolysis were not significantly different in Ginseng Radix et Rhizoma from 4 years old and 5 years old. CONCLUSION Activities of AMY, Est,ACP can be used as one of the intrinsic indicators to assess the quality of Ginseng Radix et Rhizoma.

  8. Sex hormones alter the effect of aspirin on bleeding

    Directory of Open Access Journals (Sweden)

    Muhammad Tariq Aftab

    2013-10-01

    Full Text Available Background: Interaction of aspirin and sex hormones was investigated through bleeding time. Methods: Bleeding time in 32 males and 105 unmarried females with previous 6 normal menstrual cycles and all aged between 18 to 21 years was found by Duke’s method before and after 2 hours of aspirin administration. Phase of menstrual cycle of each female was determined by present menstrual history. Results: Bleeding time in 32 male was 69.33± 4.94 seconds and in 105 female was 73.03±1.89 seconds which were not statistically different (P>0.05.This time was increased to 107.66±4.76 seconds in males and 113.65±3.73 seconds in females after aspirin administration which were statistically different (P0.05 difference after aspirin administration with a greater effect in Follicular phase probably due to estradiol. Conclusion: Males respond to aspirin more as compared to females which is likely the effect of the drug and testosterone interaction. Similarly females in the follicular phase respond to aspirin more as compared to females in the luteal phase which may be a result of interaction of estrogen and aspirin. [Int J Basic Clin Pharmacol 2013; 2(5.000: 537-540

  9. Purine Pathway Implicated in Mechanism of Resistance to Aspirin Therapy: Pharmacometabolomics-Informed-Pharmacogenomics

    OpenAIRE

    Yerges-Armstrong, Laura M; Ellero-Simatos, Sandrine; Georgiades, Anastasia; Zhu, Hongjie; Lewis, Joshua; Horenstein, Richard B; Beitelshees, Amber L; Dane, Adrie; Reijmers, Theo; Hankemeier, Thomas; Fiehn, Oliver; Shuldiner, Alan R.; Kaddurah-Daouk, Rima; ,

    2013-01-01

    Though aspirin is a well-established antiplatelet agent, the mechanisms of aspirin resistance remain poorly understood. Metabolomics allows for measurement of hundreds of small molecules in biological samples enabling detailed mapping of pathways involved in drug response. We defined the metabolic signature of aspirin exposure in subjects from the Heredity and Phenotype Intervention (HAPI) Heart Study. Many metabolites, including known aspirin catabolites, changed upon exposure to aspirin and...

  10. Effects of piperonyl butoxide on the toxicity of the organophosphate temephos and the role of esterases in the insecticide resistance of Aedes aegypti

    Directory of Open Access Journals (Sweden)

    Boscolli Barbosa Pereira

    2014-10-01

    Full Text Available Introduction The effects of piperonyl butoxide (PBO on the toxicity of the organophosphate temephos (TE and the role of esterases in the resistance of Aedes aegypti to this insecticide were evaluated. Methods A. aegypti L4 larvae susceptible and resistant to TE were pre-treated with PBO solutions in acetone at concentrations of 0.125, 0.25, 0.5, 1, and 2% for 24h and subsequently exposed to a diagnostic concentration of 0.02mg/L aqueous TE solution. The esterase activity of the larvae extracts pre-treated with varying PBO concentrations and exposed to TE for three time periods was determined. Results At concentrations of 0.25, 0.5, 1, and 2%, PBO showed a significant synergistic effect with TE toxicity. High levels of esterase activity were associated with the survival of A. aegypti L4 larvae exposed to TE only. Conclusions The results of the biochemical assays suggest that PBO has a significant inhibitory effect on the total esterase activity in A. aegypti larvae.

  11. Update on the Management of Aspirin-Exacerbated Respiratory Disease.

    Science.gov (United States)

    Buchheit, Kathleen M; Laidlaw, Tanya M

    2016-07-01

    Aspirin-exacerbated respiratory disease (AERD) is an adult-onset upper and lower airway disease consisting of eosinophilic nasal polyps, asthma, and respiratory reactions to cyclooxygenase 1 (COX-1) inhibitors. Management includes guideline-based treatment of asthma and sinus disease, avoidance of COX-1 inhibitors, and for some patients aspirin desensitization followed by high-dose aspirin therapy. Despite this, many patients have inadequately controlled symptoms and require multiple sinus surgeries. In this review, we discuss the current standard approaches to the management of AERD, and we introduce several therapeutics under development that may hold promise for the treatment of AERD. PMID:27126722

  12. 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...... resistance' (AR). This phenomenon, although lacking a precise definition, covers the fact that some patients do not exhibit the expected platelet inhibition by use of various techniques for measuring platelet function. In this critical review, we evaluate the methods used for measuring AR. We will discuss...

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

    Science.gov (United States)

    Steinke, John W; Wilson, Jeff M

    2016-01-01

    Asthma and chronic rhinosinusitis are heterogeneous airway diseases of the lower and upper airways, respectively. Molecular and cellular studies indicate that these diseases can be categorized into unique endotypes, which have therapeutic implications. One such endotype is aspirin-exacerbated respiratory disease (AERD), which encompasses the triad of asthma, aspirin (or nonsteroidal anti-inflammatory drug) hypersensitivity, and nasal polyposis. AERD has unique pathophysiological features that distinguish it from aspirin-tolerant asthma and other forms of chronic rhinosinusitis. This review details molecular and cellular features of AERD and highlights current and future therapies that are based on these insights. PMID:27022293

  14. EFFECT OF EDTA ON GASTRIC MUCOSAL LESION INDUCED BY ASPIRIN

    OpenAIRE

    M.A FESHARAKI M.A; A SHARAITI KAMALABADI; R MOKHTARI

    2002-01-01

    Introduction. Gastric ulcer is a multifactorial disease, which its pathophysioligy has not been clear yet. The aim of this study was to obtain the prophylactic effects of EDTA on Aspirin induced gastric mucosal lesions. Methods. In fasted male rats the effect of a single oral dose of the EDTA was evaluated in the following test systems: combination of 1 ml EDTA 1.5% + 300 mg/kg aspirin and 1 ml EDTA 1.5%, 2.5%, 5% and 7.5% 30 minutes before 300 mg/kg aspirin. Then the gastric mucosal les...

  15. Aspirin Breaks the Crosstalk between 3T3-L1 Adipocytes and 4T1 Breast Cancer Cells by Regulating Cytokine Production.

    Directory of Open Access Journals (Sweden)

    Chia-Chien Hsieh

    Full Text Available Breast cancer is one of the most common cancers in women worldwide. The obesity process is normally accompanied by chronic, low-grade inflammation. Infiltration by inflammatory cytokines and immune cells provides a favorable microenvironment for tumor growth, migration, and metastasis. Epidemiological evidence has shown that aspirin is an effective agent against several types of cancer. The aim of this study is to investigate the anti-inflammatory and anti-cancer effects of aspirin on 3T3-L1 adipocytes, 4T1 murine breast cancer cells, and their crosstalk. The results showed that aspirin treatment inhibited differentiation and lipid accumulation by 3T3-L1 preadipocytes, and decreased the secretion of the inflammatory adipokine MCP-1 after stimulation with tumor necrosis factor (TNF-α or conditioned medium from RAW264.7 cells. In 4T1 cells, treatment with aspirin decreased cell viability and migration, possibly by suppressing MCP-1 and VEGF secretion. Subsequently, culture of 4T1 cells in 3T3-L1 adipocyte-conditioned medium (Ad-CM and co-culture of 3T3-L1 and 4T1 cells using a transwell plate were performed to clarify the relationship between these two cell lines. Aspirin exerted its inhibitory effects in the transwell co-culture system, as well as the conditioned-medium model. Aspirin treatment significantly inhibited the proliferation of 4T1 cells, and decreased the production of MCP-1 and PAI-1 in both the Ad-CM model and co-culture system. Aspirin inhibited inflammatory MCP-1 adipokine production by 3T3-L1 adipocytes and the cell growth and migration of 4T1 cells. It also broke the crosstalk between these two cell lines, possibly contributing to its chemopreventive properties in breast cancer. This is the first report that aspirin's chemopreventive activity supports the potential application in auxiliary therapy against obesity-related breast cancer development.

  16. 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.

  17. 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.

  18. Aspirin reduces hypertriglyceridemia by lowering VLDL-triglyceride production in mice fed a high-fat diet.

    NARCIS (Netherlands)

    Diepen, J.A. van; Vroegrijk, I.O.; Berbee, J.F.; Shoelson, S.E.; Romijn, J.A.; Havekes, L.M.; Rensen, P.C.; Voshol, P.J.

    2011-01-01

    Systemic inflammation is strongly involved in the pathophysiology of the metabolic syndrome, a cluster of metabolic risk factors that includes hypertriglyceridemia. Aspirin treatment lowers inflammation via inhibition of NF-kappaB activity but also reduces hypertriglyceridemia in humans. The aim of

  19. Aspirin reduces hypertriglyceridemia by lowering VLDL-triglyceride production in mice fed a high-fat diet

    NARCIS (Netherlands)

    Diepen, J.A. van; Vroegrijk, I.O.C.M.; Berbée, J.F.P.; Shoelson, S.E.; Romijn, J.A.; Havekes, L.M.; Rensen, P.C.N.; Voshol, P.J.

    2011-01-01

    Systemic inflammation is strongly involved in the pathophysiology of the metabolic syndrome, a cluster of metabolic risk factors that includes hypertriglyceridemia. Aspirin treatment lowers inflammation via inhibition of NF-?B activity but also reduces hypertriglyceridemia in humans. The aim of this

  20. Analysis of esterase isozyme and SSR for mutagenic progenies induced by space mutation in mustard

    International Nuclear Information System (INIS)

    Seeds of five mustard (Brassica juncea Coss) varieties were carried into outer space by 'Shijian No.8' satellite. After five years' consecutive planting and selection, ten relatively stable mutant lines were obtained, which had significant variation in agronomic and economic characters. The mutant lines and their original varieties without space mutation treatment as control were studied by esterase isozyme and SSR analyses. Electrophoresis analysis of esterase isozymes indicated that there were differences between mutant lines and their controls in enzyme types and enzyme activity. Different mustard varieties had different enzymographs, and so did the mutants induced by space mutation, which shows different sensitivity among different mustard varieties. The SSR analysis showed that large differences were found in the SSR loci between mutant lines and their original variety, the variation frequency was between 9.52% and 57.14% with an average frequency of 26.19% for all the mutant lines. Among the mutant SSR loci, about 56.36% showed changes in band number and 43.64% in molecular weight. These results indicated that the ten mutant lines had large genetic difference in phenotype, genomic sequence and gene expression, and the outer space mutation would be an effective method to develop new mustard germplasm and variety. (authors)

  1. 3-d structure-based amino acid sequence alignment of esterases, lipases and related proteins

    Energy Technology Data Exchange (ETDEWEB)

    Gentry, M.K.; Doctor, B.P.; Cygler, M.; Schrag, J.D.; Sussman, J.L.

    1993-05-13

    Acetylcholinesterase and butyrylcholinesterase, enzymes with potential as pretreatment drugs for organophosphate toxicity, are members of a larger family of homologous proteins that includes carboxylesterases, cholesterol esterases, lipases, and several nonhydrolytic proteins. A computer-generated alignment of 18 of the proteins, the acetylcholinesases, butyrylcholinesterases, carboxylesterases, some esterases, and the nonenzymatic proteins has been previously presented. More recently, the three-dimensional structures of two enzymes enzymes in this group, acetylcholinesterase from Torpedo californica and lipase from Geotrichum candidum, have been determined. Based on the x-ray structures and the superposition of these two enzymes, it was possible to obtain an improved amino acid sequence alignment of 32 members of this family of proteins. Examination of this alignment reveals that 24 amino acids are invariant in all of the hydrolytic proteins, and an additional 49 are well conserved. Conserved amino acids include those of the active site, the disulfide bridges, the salt bridges, in the core of the proteins, and at the edges of secondary structural elements. Comparison of the three-dimensional structures makes it possible to find a well-defined structural basis for the conservation of many of these amino acids.

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

    OpenAIRE

    Loughna, S; P. Bennett; Gau, G; K. Nicolaides; 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 a...

  3. 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.

  4. Insecticidal properties of genetically engineered baculoviruses expressing an insect juvenile hormone esterase gene.

    OpenAIRE

    Eldridge, R; O'Reilly, D R; Hammock, B D; Miller, L K

    1992-01-01

    Exploring the possibility of enhancing the properties of baculoviruses as biological control agents of insect pests, we tested the effect of expressing an insect gene (jhe) encoding juvenile hormone esterase. Juvenile hormone esterase inactivates juvenile hormone, which regulates the outcome of an insect molt. A cDNA encoding the juvenile hormone esterase of Heliothis virescens was inserted into the genome of Autographa californica nuclear polyhedrosis virus such that the gene was expressed u...

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

    OpenAIRE

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

    2011-01-01

    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 ester...

  6. Novel ferulic acid esterases from Bifidobacterium sp. produced on selected synthetic and natural carbon sources

    OpenAIRE

    Dominik Szwajgier; Anna Dmowska

    2010-01-01

    Background. Ferulic acid esterases (or feruloyl esterases), a common group of hydrolases are very well distributed in the plant kongdom. The fungal feruloyl esterases were very extensively studied whereas probiotic lactic acid bacteria as the source of this enzyme were generally omitted. Free phenolic acids – strong antioxidants can be released from the dietary fiber by the action of intestinal lactic acid bacteria. The aim of this study was to examine the three probiotic Bifi...

  7. Inhibition of pancreatic cholesterol esterase reduces cholesterol absorption in the hamster

    OpenAIRE

    Heidrich, John E.; Contos, Linda M; Hunsaker, Lucy A; Deck, Lorraine M.; Vander Jagt, David L.

    2004-01-01

    Background Pancreatic cholesterol esterase has three proposed functions in the intestine: 1) to control the bioavailability of cholesterol from dietary cholesterol esters; 2) to contribute to incorporation of cholesterol into mixed micelles; and 3) to aid in transport of free cholesterol to the enterocyte. Inhibitors of cholesterol esterase are anticipated to limit the absorption of dietary cholesterol. Results The selective and potent cholesterol esterase inhibitor 6-chloro-3-(1-ethyl-2-cycl...

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

    Directory of Open Access Journals (Sweden)

    Yoshihiro Suzuki

    2010-05-01

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

  9. The Lp_3561 and Lp_3562 Enzymes Support a Functional Divergence Process in the Lipase/Esterase Toolkit from Lactobacillus plantarum

    Science.gov (United States)

    Esteban-Torres, María; Reverón, Inés; Santamaría, Laura; Mancheño, José M.; de las Rivas, Blanca; Muñoz, Rosario

    2016-01-01

    Lactobacillus plantarum species is a good source of esterases since both lipolytic and esterase activities have been described for strains of this species. No fundamental biochemical difference exists among esterases and lipases since both share a common catalytic mechanism. L. plantarum WCFS1 possesses a protein, Lp_3561, which is 44% identical to a previously described lipase, Lp_3562. In contrast to Lp_3562, Lp_3561 was unable to degrade esters possessing a chain length higher than C4 and the triglyceride tributyrin. As in other L. plantarum esterases, the electrostatic potential surface around the active site in Lp_3561 is predicted to be basic, whereas it is essentially neutral in the Lp_3562 lipase. The fact that the genes encoding both proteins were located contiguously in the L. plantarum WCFS1 genome, suggests that they originated by tandem duplication, and therefore are paralogs as new functions have arisen during evolution. The presence of the contiguous lp_3561 and lp_3562 genes was studied among L. plantarum strains. They are located in a 8,903 bp DNA fragment that encodes proteins involved in the catabolism of sialic acid and are predicted to increase bacterial adaptability under certain growth conditions. PMID:27486450

  10. Production of Feruloyl Esterase from Aspergillus niger by Solid-State Fermentation on Different Carbon Sources

    Directory of Open Access Journals (Sweden)

    Shiyi Ou

    2011-01-01

    Full Text Available A mixture of wheat bran with maize bran as a carbon source and addition of (NH4SO4 as nitrogen source was found to significantly increase production of feruloyl esterase (FAE enzyme compared with wheat bran as a sole carbon and nitrogen source. The optimal conditions in conical flasks were carbon source (30 g to water 1 : 1, maize bran to wheat bran 1 : 2, (NH4SO4 1.2 g and MgSO4 70 mg. Under these conditions, FAE activity was 7.68 mU/g. The FAE activity on the mixed carbon sources showed, high activity against the plant cell walls contained in the cultures.

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

    Directory of Open Access Journals (Sweden)

    Steinke JW

    2016-03-01

    Full Text Available John W Steinke, Jeff M Wilson Asthma and Allergic Disease Center, Carter Immunology Center, Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA Abstract: Asthma and chronic rhinosinusitis are heterogeneous airway diseases of the lower and upper airways, respectively. Molecular and cellular studies indicate that these diseases can be categorized into unique endotypes, which have therapeutic implications. One such endotype is aspirin-exacerbated respiratory disease (AERD, which encompasses the triad of asthma, aspirin (or nonsteroidal anti-inflammatory drug hypersensitivity, and nasal polyposis. AERD has unique pathophysiological features that distinguish it from aspirin-tolerant asthma and other forms of chronic rhinosinusitis. This review details molecular and cellular features of AERD and highlights current and future therapies that are based on these insights. Keywords: leukotriene, cyclooxygenase, prostaglandin, aspirin-exacerbated respiratory disease, arachidonic acid

  12. Using the Platelet Function Analyzer-100 for monitoring aspirin therapy

    DEFF Research Database (Denmark)

    Poulsen, Tina Svenstrup; Mickley, Hans; Korsholm, Lars;

    2007-01-01

    INTRODUCTION: The aim of the study was to evaluate the test characteristics of the Platelet Function Analyzer-100 (PFA-100) in patients treated with aspirin. METHODS AND RESULTS: The study consisted of two sub-studies. In study 1, 10 patients with ischemic heart disease (IHD) and 10 controls had...... platelet function assessed by optical platelet aggregation and the PFA-100 method in two 5-week periods. Patients with IHD were treated with aspirin 150 mg/day (first 5-week period), and 300 mg/day (second 5-week period), whereas the controls only received aspirin (150 mg/day) during the second 5-week...... period. From the results of study 1, we found that a cut-off value for the PFA-100 collagen/epinephrine cartridge <165 s identified patients not taking aspirin (sensitivity 0.91, specificity 1.00). A good agreement between the PFA-100 method and optical platelet aggregation was found. Within...

  13. Aspirin as a chemoprevention agent for colorectal cancer.

    LENUS (Irish Health Repository)

    Lee, Chun Seng

    2012-11-01

    Colorectal cancer (CRC) is one of the leading causes of mortality in the western world. It is widely accepted that neoplasms such as colonic polyps are precursors to CRC formation; with the polyp-adenoma-carcinoma sequences well described in medical literature [1, 2]. It has been shown that Aspirin and other non-steroid anti-inflammatory drugs (NSAID) have a negative effect on polyp and cancer formation. This review aims to describe some of the mechanism behind the chemoprotective properties of aspirin; COX 2 inhibition, regulation of proliferation and apoptosis and effects on the immune system and also the current evidence that supports its use as a chemoprevention agent against CRC. We will also aim to explore the side effects with the use of aspirin and the pitfalls of using aspirin routinely for primary prophylaxis against CRC.

  14. Talk with Your Doctor about Taking Aspirin Every Day

    Science.gov (United States)

    ... Print This Topic En español Talk with Your Doctor about Taking Aspirin Every Day Browse Sections The ... sections Take Action! Take Action: Talk with Your Doctor Take these steps to protect your health if ...

  15. A new esterase EstD2 isolated from plant rhizosphere soil metagenome.

    Science.gov (United States)

    Lee, Myung Hwan; Hong, Kyung Sik; Malhotra, Shweta; Park, Ji-Hye; Hwang, Eul Chul; Choi, Hong Kyu; Kim, Young Sup; Tao, Weixin; Lee, Seon-Woo

    2010-11-01

    Soil metagenome constitutes a reservoir for discovering novel enzymes from the unculturable microbial diversity. From three plant rhizosphere metagenomic libraries comprising a total of 142,900 members of recombinant plasmids, we obtained 14 recombinant fosmids that exhibited lipolytic activity. A selected recombinant plasmid, pFLP-2, which showed maximum lipolytic activity, was further analyzed. DNA sequence analysis of the subclone in pUC119, pELP-2, revealed an open reading frame of 1,191 bp encoding a 397-amino-acid protein. Purified EstD2 exhibited maximum enzymatic activity towards p-nitrophenyl butyrate, indicating that it is an esterase. Purified EstD2 showed optimal activity at 35 °C and at pH 8.0. The K(m) and K(cat) values were determined to be 79.4 μM and 120.5/s, respectively. The esterase exhibited an increase in enzymatic activity in the presence of 15% butanol and 15% methanol. Phylogenetic analysis revealed that the lipolytic protein EstD2 may be a member of a novel family of lipolytic enzymes. Several hypothetical protein homologs of EstD2 were found in the database. A hypothetical protein from Phenylobacterium zucineum HLK1, a close homolog of EstD2, displayed lipolytic activity when the corresponding gene was expressed in Escherichia coli. Our results suggest that the other hypothetical protein homologs of EstD2 might also be members of this novel family. PMID:20683720

  16. An Efficient Microscale Procedure for the Synthesis of Aspirin

    Science.gov (United States)

    Pandita, Sangeeta; Goyal, Samta

    1998-06-01

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

  17. Genetic Mechanisms in Aspirin-Exacerbated Respiratory Disease

    OpenAIRE

    Nami Shrestha Palikhe; Seung-Hyun Kim; Hyun Jung Jin; Eui-Kyung Hwang; Young Hee Nam; Hae-Sim Park

    2011-01-01

    Aspirin-exacerbated respiratory disease (AERD) refers to the development of bronchoconstriction in asthmatics following the exposure to aspirin or other nonsteroidal anti-inflammatory drugs. The key pathogenic mechanisms associated with AERD are the overproduction of cysteinyl leukotrienes (CysLTs) and increased CysLTR1 expression in the airway mucosa and decreased lipoxin and PGE2 synthesis. Genetic studies have suggested a role for variability of genes in disease susceptibility and the resp...

  18. Aspirin overutilization for the primary prevention of cardiovascular disease

    OpenAIRE

    VanWormer JJ; Miller AW; Rezkalla SH

    2014-01-01

    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 i...

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

    OpenAIRE

    Ellero-Simatos, S; Lewis, JP; Georgiades, A; Yerges-Armstrong, LM; Beitelshees, AL; Horenstein, RB; Dane, A.; Harms, AC; Ramaker, R; Vreeken, RJ; Perry, CG; Zhu, H.; Sanchez, CL; Kühn, C.; ORTEL, TL

    2014-01-01

    While aspirin is generally effective for prevention of cardiovascular disease, considerable variation in drug response exists, resulting in some individuals displaying high on-treatment platelet reactivity. We used pharmacometabolomics to define pathways implicated in variation of response to treatment. We profiled serum samples from healthy subjects pre- and postaspirin (14 days, 81 mg/day) using mass spectrometry. We established a strong signature of aspirin exposure independent ...

  20. Small bowel injury in low-dose aspirin users.

    Science.gov (United States)

    Endo, Hiroki; Sakai, Eiji; Kato, Takayuki; Umezawa, Shotaro; Higurashi, Takuma; Ohkubo, Hidenori; Nakajima, Atsushi

    2015-04-01

    The use of low-dose aspirin (LDA) is well known to be associated with an increased risk of serious upper gastrointestinal complications, such as peptic ulceration and bleeding. Until recently, attention was mainly focused on aspirin-induced damage of the stomach and duodenum. However, recently, there has been growing interest among gastroenterologists on the adverse effects of aspirin on the small bowel, especially as new endoscopic techniques, such as capsule endoscopy (CE) and balloon-assisted endoscopy, have become available for the evaluation of small bowel lesions. Preliminary CE studies conducted in healthy subjects have shown that short-term administration of LDA can induce mild mucosal inflammation of the small bowel. Furthermore, chronic use of LDA results in a variety of lesions in the small bowel, including multiple petechiae, loss of villi, erosions, and round, irregular, or punched-out ulcers. Some patients develop circumferential ulcers with stricture. In addition, to reduce the incidence of gastrointestinal lesions in LDA users, it is important for clinicians to confirm the differences in the gastrointestinal toxicity between different types of aspirin formulations in clinical use. Some studies suggest that enteric-coated aspirin may be more injurious to the small bowel mucosa than buffered aspirin. The ideal treatment for small bowel injury in patients taking LDA would be withdrawal of aspirin, however, LDA is used as an antiplatelet agent in the majority of patients, and its withdrawal could increase the risk of cardiovascular/cerebrovascular morbidity and mortality. Thus, novel means for the treatment of aspirin-induced enteropathy are urgently needed. PMID:25501289

  1. Gastroprotective Effect of Rubia cordifolia Linn. on Aspirin Plus Pylorus-Ligated Ulcer

    Directory of Open Access Journals (Sweden)

    R. S. Deoda

    2011-01-01

    Full Text Available The present study was designed to investigate the effect of Rubia cordifolia (Rubiaceae against experimentally induced gastric ulcer and compare activity with its fractions by employing aspirin plus pylorus-ligated ulcer screening model in Wistar rats. Total acidity, volume of gastric acid secretion, total acid output, and pepsin activity show significant reduction, when compared with the control group. The present study confirmed that chloroform fraction showed the significant activity at lower doses compared to parent extract. The mechanism can be attributed to decrease in gastric acid secretary activity along with strengthening of mucosal defensive mechanism by prostaglandin synthesis and antioxidant potential.

  2. 'Aspirin resistance' or treatment non-compliance: Which is to blame for cardiovascular complications?

    Directory of Open Access Journals (Sweden)

    Shantsila Eduard

    2008-08-01

    Full Text Available Abstract Aspirin is one of the 'cornerstone' drugs in our current management of cardiovascular disorders. However, despite the prescription of aspirin recurrent vascular events still occur in 10–20% of patients. These, data together with the observations of diminished antiaggregatory response to aspirin in some subjects have provided the basis of the current debate on the existence of so-called "aspirin resistance". Unfortunately, many of the tests employed to define 'aspirin resistance' lack sufficient sensitivity, specificity, and reproducibility. The prevalence of 'aspirin resistance' as defined by each test varies widely, and furthermore, the value of a single point estimate measure of aspirin resistance is questionable. The rate of 'aspirin resistance' is law if patients observed to ingest aspirin, with large proportion of patients to be pseudo-'aspirin resistant', due to non-compliance. What are the implications for clinical practice? Possible non-adherence to aspirin prescription should also be carefully considered before changing to higher aspirin doses, other antiplatelet drugs (e.g. clopidogrel or even combination antiplatelet drug therapy. Given the multifactorial nature of atherothrombotic disease, it is not surprising that only about 25% of all cardiovascular complications can usually be prevented by any single medication. We would advocate against routine testing of platelet sensitivity to aspirin (as an attempt to look for 'aspirin resistance' but rather, to highlight the importance of clinicians and public attention to the problem of treatment non-compliance.

  3. Prevalence of and risk factors for aspirin resistance in elderly patients with coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    Xian-Feng Liu; Jian Cao; Li Fan; Lin Liu; Jian Li; Guo-Liang Hu; Yi-Xin Hu; Xiao-Li Li

    2013-01-01

    Objective To assess the prevalence of and related risk factors for aspirin resistance in elderly patients with coronary artery disease (CAD). Methods Two hundred and forty-six elderly patients (75.9 ± 7.4 years) with CAD who received daily aspirin therapy (≥ 75 mg) over one month were recruited. The effect of aspirin was assessed using light transmission aggregometry (LTA) and thrombelastography platelet mapping assay (TEG). Aspirin resistance was defined as ≥ 20% arachidonic acid (AA)-induced aggregation and ≥ 70% adenosine diphosphate (ADP)-induced aggregation in the LTA assay. An aspirin semi-responder was defined as meeting one (but not both) of the criteria described above. Based on the results of TEG, aspirin resistance was defined as ≥ 50% aggregation induced by AA. Results As determined by LTA, 23 (9.3%) of the elderly CAD patients were resistant to aspirin therapy; 91 (37.0%) were semi-responders. As determined by TEG, 61 patients (24.8%) were aspirin resistant. Of the 61 patients who were aspirin resistant by TEG, 19 were aspirin resistant according to LTA results. Twenty-four of 91 semi-responders by LTA were aspirin resistant by TEG. Multivariate logistic risk factor for aspirin resistance as determined by TEG. Conclusions A significant number of elderly patients with CAD are resistant to aspirin therapy. Fasting blood glucose level is closely associated with aspirin resistance in elderly CAD patients.

  4. Aspirin resistance as cardiovascular risk after kidney transplantation

    Science.gov (United States)

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

    2014-05-01

    International surveys have shown that the leading cause of death after kidney transplantation has cardiovascular origin with a prevalence of 35-40%. As a preventive strategy these patients receive aspirin (ASA) therapy, even though their rate of aspirin resistance is still unknown. In our study, platelet aggregation measurements were performed between 2009 and 2012 investigating the laboratory effect of low-dose aspirin (100 mg) treatment using a CARAT TX4 optical aggregometer. ASA therapy was considered clinically effective in case of low ( i.e., below 40%) epinephrine-induced (10 μM) platelet aggregation index. Rate of aspirin resistance, morbidity and mortality data of kidney transplanted patients (n = 255, mean age: 49 ± 12 years) were compared to a patient population with cardio- and cerebrovascular diseases (n = 346, mean age: 52.6 ± 11 years). Rate of aspirin resistance was significantly higher in the renal transplantation group (RT) compared to the positive control group (PC) (35.9% vs. 25.6%, p aspirin resistance contributes to the high cardiovascular mortality after kidney transplantation.

  5. Role of Aspirin and Dexamethasone against Experimentally Induced Depression in Rats.

    Science.gov (United States)

    Bhatt, Shailendra; Shukla, Priyanka; Raval, Jibril; Goswami, Sunita

    2016-07-01

    A large number of current studies indicate that inflammatory mediators may contribute to depression in experimental models as well as in human beings. Nevertheless, the subject, whether anti-inflammatory treatments can prevent depression still remains controversial. In the present study, a chronic mild stress (CMS) model of male Sprague Dawley rats was used to investigate the role of anti-inflammatory drugs in the treatment of depression. All the animals in different groups, except the normal control group, were exposed to CMS procedure for 28 days and concurrently treated with aspirin (10 mg/kg, p.o.), dexamethasone (1 mg/kg p.o.) and amitriptyline (10 mg/kg p.o., reference standard), respectively. Amitriptyline was also used in combination with aspirin and dexamethasone to inspect any synergistic effects. Tests performed towards the end of the study included sucrose preference test, behavioural tests like forced swim test, elevated plus-maze, light/dark box, locomotor activity and biochemical estimations like serum cortisol and brain neurotransmitters. Disease control group (CMS-treated) produced significant depressive behaviour in rats. The animals treated with aspirin showed increased sucrose preference, decreased immobility time in forced swim test, decreased serum cortisol and increased brain serotonin levels signifying antidepressant action. In contrast, there was aggravation of depressive behaviour in rats treated with dexamethasone. Together, these findings suggest that aspirin can serve as a potential antidepressant both individually and as adjunctive agent in the treatment of depression. Inhibition of the inflammatory mediators during stress procedures or any other potential physiological and biochemical mechanisms may be involved in its antidepressant effect. PMID:26645736

  6. Radiochromium (chromium-51) evaluation of gastrointestinal blood loss associated with placebo, aspirin, and nabumetone

    Energy Technology Data Exchange (ETDEWEB)

    Lussier, A.; LeBel, E.

    1987-10-30

    Gastrointestinal blood loss is one of the most serious clinical events induced by drugs. To date, almost no nonsteroidal anti-inflammatory drug has been shown to be devoid of that side effect in a strictly controlled study. The objective of this study was to assess quantitatively, by use of radioactive chromium (chromium-51)-labeled red blood cells, gastrointestinal blood loss associated with nabumetone (1000 mg daily), aspirin (3.6 g daily), and placebo. A total of 37 normal subjects, divided among the three treatment groups and a fourth group that received no treatment, were assessed clinically and quantitatively for gastrointestinal blood loss over a period of 28 days of active treatment. The results with chromium-51, analyzed on a logarithmic scale, revealed no statistically significant differences between the nabumetone, placebo, and control groups. Gastrointestinal blood loss in the aspirin group, however, was elevated when compared with all other groups at a high level of statistical significance (p less than 0.001). It is concluded that, under conditions in which aspirin causes substantial gastrointestinal microbleeding, nabumetone is not significantly different from placebo.

  7. Low-Dose Aspirin-Associated Upper and Mid Gastrointestinal Tract Damage and Gene Polymorphism.

    Science.gov (United States)

    Shiotani, Akiko; Fujita, Yoshihiko; Nishio, Kazuto

    2015-01-01

    The risk of gastrointestinal (GI) bleeding is increased in association with the use of low-dose aspirin (LDA). There are few studies of the association between genetic polymorphisms and the risks of aspirin-induced ulcer or its complications. Individuals with two single nucleotide polymorphisms (SNPs) of cyclooxygenase-1 (COX-1), A-842G and C50T, exhibit increased sensitivity to aspirin and lower prostaglandin synthesis capacity but the polymorphism lacked statistical significance in relation to an association with bleeding peptic ulcer. In our previous Japanese study, SLCO1B1 521TT genotype and the SLCO1B1 *1b haplotype were significantly associated with the risk of peptic ulcer and ulcer bleeding in patients taking LDA, especially in the patients with angiotensin converting enzyme inhibitor (ACEI), angiotensin type 1 receptor blocker (ARB), or statin co-treatment. Protonpump inhibitors (PPIs) are recommended for patients who require antiplatelet therapy and have a history of upper GI bleeding. The interaction between PPIs and consequent impaired effectiveness of clopidogrel has caused concern regarding the effect of genetic polymorphisms of the CYP2C19 which mediates conversion of clopidogrel to its active metabolite. The later recent genome-wide analysis of SNPs indicated the association of several SNPs with small bowel bleeding in Japanese patients taking LDA. The data are still lacking and further prospective studies are needed to identify the specific gene polymorphisms as risk or protective factors for GI bleeding associated with LDA. PMID:26369686

  8. Comparison of Two Therapeutic Protocols : Heparin with Aspirin VS Prednisolone with Aspirin, in Patients with Recurrent Miscarriages

    Directory of Open Access Journals (Sweden)

    S. Rabiee, M.D.

    2007-01-01

    Full Text Available AbstractBackground and Purpose: The most common complication of pregnancy is abortion. The etiology of recurrent pregnancy loss is not completely known. There are few therapeutics and diagnostic strategies in recurrent abortion. The aim of this study was to compare the use of heparin with aspirin vs prednisolone with aspirin in patients with recurrent pregnancy loss (RPL.Materials and Methods: This randomized clinical trial study comprised of 50 patients with RPL referred to Fatemieh Hospital, Hamadan. These patients were selected when β-HCG test was positive and were divided into two groups (n=25 for each group. Patients in the first group received subcutaneous heparin (5000 U twice a day and oral microcoated aspirin (80 mg once a day up to 20th week of pregnancy. Ultrasonography was repeated 3 times for these patients. Ca tablet was administrated in order to prevent osteoporosis. Antiphospholipid and anticardiolipin antibodies were checked for all patients. Neonates were visited by a neonatologist and followed up for one month. Finally, the data were analyzed by t-test and Fisher’s exact test.Results: The mean age of prednisolone with aspirin group were 31.83.3 years while, it was 30.73.2 years in heparin with aspirin group and, this difference was not significant (P>0.05. The mean pregnancy loss number was 2.81.1 while 2.41 in prednisolone with aspirin and heparin with aspirin groups respectively, which was not statistically significant (P>0.05. Anticardiolipin antibody was positive in 4 (8% patients, and antiphospholipid antibody was also positive in 4(8% patients. Pregnancy loss with heparin+aspirin was significantly higher than prednisolone+aspirin (P<0.05. There was not any case of complications in two groups.Conclusion: The results of this study showed that prednisolone with aspirin are more effective than heparin with aspirin in the management of recurrent pregnancy loss and are preferred to use in these patients.

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

    DEFF Research Database (Denmark)

    Topakas, E.; Christakopoulos, Paul

    (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....... Production of FAE does not therefore, require FA, however, production is diminished by the removal of esterified FA from the growth substrate. Optimal FAE activity was observed at pH 7 and 50 degreesC with 68 and 55% activity at pH 8 and pH 9, respectively. The esterase was fully stable at pH 5-8 and up to...

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

    Science.gov (United States)

    ... Medicines Safe Daily Use of Aspirin Before Using Aspirin to Lower Your Risk of Heart Attack or ... care provider can determine whether regular use of aspirin will help to prevent a heart attack or ...

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

    OpenAIRE

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

    1991-01-01

    1. Gastric damage induced by low-dose aspirin and the protective effect of enteric-coating was assessed in healthy volunteers in a double-blind placebo-controlled cross-over trial using Latin square design. Each was administered placebo, plain aspirin 300 mg daily, plain aspirin 600 mg four times daily, enteric-coated aspirin 300 mg daily, or enteric-coated aspirin 600 mg four times daily for 5 days. Gastric damage was assessed endoscopically, and gastric mucosal bleeding measured. 2. Aspirin...

  12. Insights into and relative effect of chitosan-krill oil, chitosan-H-aspirin, chitosan-H-krill oil-nystatin and chitosan-H-krill oil-aspirin-nystatin on dentin bond strength and functional drug delivery capacity: In-vitro studies

    Directory of Open Access Journals (Sweden)

    Victoria Tamara Perchyonok

    2014-01-01

    Full Text Available Background: Restorative materials in the new era aim to be "bio-active" and long-lasting. The purpose of this study was to design and to evaluate a novel chitosan hydrogels containing krill oil (antioxidant containing material, nystatin (antifungal, aspirin (pain relieve medication and free radical scavengers and combinations thereof (chitosan-H-krill oil, chitosan-H-krill oil-nystatin and chitosan-H-aspirin, chitosan-H-aspirin-nystatin, chitosan-H-krill oil-aspirin and chitosan-H-krill oil-aspirin-nystatin as functional additive prototypes for further development of "dual function restorative materials," and secondly to determine their effect on the dentin bond strength of a composite. Materials and Methods: The above-mentioned hydrogels were prepared by dispersion the corresponding component in glycerol and acetic acid with the addition of chitosan gelling agent. The surface morphology (scanning electron microscope (SEM, release behaviors (physiological pH and also in acidic conditions, stability of the therapeutic agent-antioxidant-chitosan and the effect of the hydrogels on the shear bond strength of dentin were also evaluated. Results: The release of nystatin and aspirin confer the added benefit of synergistic action of a functional therapeutic delivery when comparing the newly designed chitosan-based hydrogel restorative materials to the commercially available products alone. Neither the release of nystatin and aspirin nor the antioxidant stability was affected by storage over a 6 month period. The hydrogel formulations have a uniform distribution of drug content, homogenous texture and yellow color (SEM study. All chitosan dentin treated hydrogels gave significantly (P<0.05; non-parametric ANOVA test higher shear bond values (P<0.05 than dentin treated or not treated with phosphoric acid. Conclusion: The added benefits of the chitosan treated hydrogels involved positive influence on the nystatin and aspirin release as well as increased

  13. 15-epi-lipoxin A4-mediated induction of nitric oxide explains how aspirin inhibits acute inflammation.

    OpenAIRE

    Paul-Clark, M. J.; Cao, T; Moradi-Bidhendi, N.; Cooper, D; Gilroy, D. W.

    2004-01-01

    The established model for the mechanism of action of aspirin is the inhibition of prostaglandin synthesis. However, this has never fully explained aspirin\\'s repertoire of antiinflammatory properties. We found in acute pleuritis that aspirin, but not salicylate, indomethacin, or piroxicam, increased plasma nitric oxide (NO), which correlated with a reduction in inflammation. Inhibiting aspirin-elicited NO pharmacologically in this model nullified the antiinflammatory effects of aspirin. Moreo...

  14. Competing intermolecular interactions of artemisinin-type agents and aspirin with membrane phospholipids: Combined model mass spectrometry and quantum-chemical study

    International Nuclear Information System (INIS)

    Highlights: • Competitive binding of artemisinin agents and aspirin with phospholipids is shown. • Complexation between the antimalarial drugs and aspirin molecules is also found. • Energetically favorable structures of the model complexes are identified by DFT. • Membranotropic activity of the studied drugs can be modified under joint usage. - Abstract: Study of intermolecular interactions of antimalarial artemisinin-type drugs and aspirin with membrane phospholipids is important in term of elucidation of the drugs activity modification under their joint usage. Combined experimental and computational study of the interaction of dihydroartemisinin, α-artemether, and artesunate with aspirin (ASP) and dipalmitoylphosphatidylcholine (DPPC) is performed by electrospray ionization (ESI) mass spectrometry and by DFT B3LYP/aug-cc-pVDZ methods. The results of the ESI investigation of systems containing artemisinin-type agent, ASP and DPPC, reveal a competition between the antimalarial agents and ASP for binding with DPPC molecules. The complexation between the antimalarial drugs and ASP is also found. Observed phenomena suggest that membranotropic activity of artemisin-type agents and aspirin is modified under their combined usage. To elucidate structure-energy characteristics of the non-covalent complexes studied the model DFT calculations are performed for dihydroartemisinin · ASP complex and complexes of the each drug with phosphatidylcholine head of DPPC in neutral and cationized forms

  15. Competing intermolecular interactions of artemisinin-type agents and aspirin with membrane phospholipids: Combined model mass spectrometry and quantum-chemical study

    Energy Technology Data Exchange (ETDEWEB)

    Pashynska, Vlada, E-mail: vlada@vl.kharkov.ua [B.Verkin Institute for Low Temperature Physics and Engineering of the National Academy of Sciences of Ukraine, Lenin Ave., 47, 61103 Kharkov (Ukraine); Stepanian, Stepan [B.Verkin Institute for Low Temperature Physics and Engineering of the National Academy of Sciences of Ukraine, Lenin Ave., 47, 61103 Kharkov (Ukraine); Gömöry, Agnes; Vekey, Karoly [Institute of Organic Chemistry of Research Centre for Natural Sciences of the Hungarian Academy of Sciences, Magyar tudosok korutja, 2, Budapest H-1117 (Hungary); Adamowicz, Ludwik [University of Arizona, Department of Chemistry and Biochemistry, Tucson, AZ 85721 (United States)

    2015-07-09

    Highlights: • Competitive binding of artemisinin agents and aspirin with phospholipids is shown. • Complexation between the antimalarial drugs and aspirin molecules is also found. • Energetically favorable structures of the model complexes are identified by DFT. • Membranotropic activity of the studied drugs can be modified under joint usage. - Abstract: Study of intermolecular interactions of antimalarial artemisinin-type drugs and aspirin with membrane phospholipids is important in term of elucidation of the drugs activity modification under their joint usage. Combined experimental and computational study of the interaction of dihydroartemisinin, α-artemether, and artesunate with aspirin (ASP) and dipalmitoylphosphatidylcholine (DPPC) is performed by electrospray ionization (ESI) mass spectrometry and by DFT B3LYP/aug-cc-pVDZ methods. The results of the ESI investigation of systems containing artemisinin-type agent, ASP and DPPC, reveal a competition between the antimalarial agents and ASP for binding with DPPC molecules. The complexation between the antimalarial drugs and ASP is also found. Observed phenomena suggest that membranotropic activity of artemisin-type agents and aspirin is modified under their combined usage. To elucidate structure-energy characteristics of the non-covalent complexes studied the model DFT calculations are performed for dihydroartemisinin · ASP complex and complexes of the each drug with phosphatidylcholine head of DPPC in neutral and cationized forms.

  16. 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. PMID:27451209

  17. Comparison of aspirin and indobufen in healthy volunteers.

    Science.gov (United States)

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

    2016-01-01

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

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

    OpenAIRE

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

    2015-01-01

    We recently reported the synthesis of NOSH-aspirin, a novel hybrid that releases both nitric oxide (NO) and hydrogen sulfide (H2S). In NOSH-aspirin, the two moieties that release NO and H2S are covalently linked at the 1, 2 positions of acetyl salicylic acid, i.e. ortho-NOSH-aspirin (o-NOSH-aspirin). In the present study, we compared the effects of the positional isomers of NOSH-ASA (o-NOSH-aspirin, m-NOSH-aspirin and p-NOSH-aspirin) to that of aspirin on growth of HT-29 and HCT 15 colon canc...

  19. Prevalence of daily or near daily aspirin use by US adults with diabetes: A cross-sectional study using a multi-year national database

    Directory of Open Access Journals (Sweden)

    Michael T. Swanoski

    2012-06-01

    Full Text Available Introduction: For persons with diabetes, cardiovascular disease is the major cause of morbidity and mortality that is reflected in a two-to- four times greater risk for both heart disease and stroke when compared to adults without diabetes. Although not without controversy, diabetes and cardiovascular disease (CVD management guidelines in the US recommend the use of once-daily aspirin. This epidemiological study was undertaken to fill the knowledge gap regarding the prevalence of daily or near daily aspirin use for US age-appropriate adults with diabetes. Methods: Using bivariate and multivariate techniques, a cross-sectional analysis of an amalgamated database using 2005, 2007, and 2009 Behavioral Risk Factor Surveillance Survey data was performed. The dependent variable for this analysis was daily or near daily aspirin use. The population of interest was US adults, men >= 45 - 79 and women >= 55 - 79 years of age. Results: Overall the prevalence of daily or near daily aspirin use by age-appropriate US adults with diabetes was 62.5%; it was 41.0% for similar non-diabetic adults. Logistic regression analysis yielded that age-appropriate adults, of both genders, with diabetes taking daily or near daily aspirin were more likely to be: physically active, male, live in rural locales, not have a health care provider, have deferred medical care because of cost, have an elevated BMI, a smoker, and have hypertension. Conclusion: It was determined that the age-appropriate use of aspirin in the US adult population with diabetes is underutilized. The role of the pharmacist through- out the continuum of care is one way to improve appropriate aspirin use in patients with diabetes.

  20. SYNTHESIS AND EVALUATION OF MUTUAL PRODRUG OF ASPIRIN AND CHLORZOXAZONE

    Directory of Open Access Journals (Sweden)

    Sandeep Walsangikar

    2013-04-01

    Full Text Available Aspirin chlorzoxazone ester linked mutual prodrug was synthesized with the aim of improving the therapeutic index through prevention of gastrointestinal irritation and bleeding. The structure of the synthesized ester prodrug was confirmed by IR and 1H NMR spectroscopy and their purity was established by elemental analysis, HPLC and TLC. The release of ASP as well as CZX, from the ester prodrug was studied. A validated analytical HPLC method for the estimation of the ASP, and the prodrug was developed. The kinetics of ester hydrolysis was studied in four different non-enzymatic buffer solutions, at pH 3, 4, 5 and 7.4 as well as in experimental plasma. Study of skeletal muscle relaxant and anti-inflammatory properties in comparison with the reference compounds has shown that both skeletal muscle relaxant and anti-inflammatory activities were present at the same doses of the investigated compounds. The ester was found to be less irritating to gastric mucosal membrane than the parent drugs. These results suggest that the synthesized prodrug is characterized by better therapeutic index than the parent drugs.

  1. Regular use of aspirin and prostate cancer risk (United States).

    Science.gov (United States)

    Menezes, Ravi J; Swede, Helen; Niles, Robert; Moysich, Kirsten B

    2006-04-01

    It has been hypothesized that aspirin and other nonsteroidal anti-inflammatory drugs can decrease the risk of developing prostate and other cancers, although observational studies have not been very conclusive. The current study examined the effects of regular aspirin use on prostate cancer risk in 1,029 patients with primary, incident cancer of the prostate and 1,029 hospital controls frequency-matched to cases by 5-year age group and period of questionnaire completion. Patients who reported use of aspirin for at least once a week for at least 6 months were classified as regular users, with others classified as non-users. Results indicate that regular aspirin use may not be associated with decreased prostate cancer risk [odds ratio (OR) 1.05, 95% confidence interval (CI) 0.89-1.25], frequency of use (OR for at least seven/week 0.91, 95% CI 0.73-1.13), duration of use (OR for at least 10 years of use 1.17 95% CI 0.93-1.46) or tablet years (defined as tablets per day x years of use). A similar lack of association was observed when analyses were performed examining stage of the cancer. These data suggest that aspirin use may not be associated with reduced risk of prostate cancer. PMID:16489532

  2. Design of aspirin formulation for rapid pain relief

    Directory of Open Access Journals (Sweden)

    Suman P. Mohanan

    2011-04-01

    Full Text Available Objective: Aspirin has always had excellent pain relief benefits. To reduce the gastric problems in the present study we had made an attempt to make aspirin fast dissolving tablets. Methods: Aspirin fast dissolving tablets were developed by direct compression method using Indion 254, Indion 214 and croscarmellose as superdisintegrants. Microcrystalline cellulose was used as diluent, and mannitol, as sweetening agent. The tablets were evaluated for weight variation, mechanical strength, in vitro disintegration time, wetting time and drug release characteristics. Results: Hardness and friability data indicated good mechanical strength of tablets. The results of in vitro disintegration time indicated that formulation FD3 (containing 5 mg Indion 254 as superdisintegrant was found to be suitable tablets as it showed rapid disintegration within 8 to 32 seconds. Dissolution study revealed the release rate of aspirin fast dissolving tablet and these was compared with that of marketed tablet formulation of aspirin. Conclusion: It was concluded that superdisintegrants addition technique is a useful method for preparing fast dissolving tablets by direct compression method and present study revealed that Indion 254 could produce good superdisintegrating property. [J Exp Integr Med 2011; 1(2.000: 131-134

  3. Investigating the Effect of Aspirin on Mercury Toxicity

    Directory of Open Access Journals (Sweden)

    Fatih Polat

    2013-01-01

    Full Text Available The effect of aspirin on the toxicology of mercury was investigated by using fish. The variations between blood parameters of the fish, which were made exposed directly to mercury solutions prepared at certain concentrations (500 μg/L, 250 μg/L, 125 μg/L, 62.5 μg/L, and 31.25 μg/L, and blood parameters of the fish, which were made exposed to mercury at the same concentrations after they had been interacting with aspirin, were investigated. At the end of the study, increases in blood parameters were observed depending on the increases in mercury concentration. Statistically significant variations were observed in blood parameters of the fish, which were made exposed to mercury at the same concentrations after they had been interacting with aspirin, compared to blood parameters of the fish, which were made exposed directly to mercury (. It was found that aspirin has caused significant increases in especially the levels of serum aspartate aminotransferase and alanine aminotranspherase and significant decreases in cortisol and glucose levels among to blood parameters. It was concluded that aspirin alters the toxic effect of mercury.

  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. Overexpression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma.

    OpenAIRE

    Cowburn, A. S.; Sladek, K; Soja, J; L. Adamek; Nizankowska, E; Szczeklik, A.; Lam, B K; Penrose, J F; Austen, F K; Holgate, S T; Sampson, A P

    1998-01-01

    Aspirin causes bronchoconstriction in aspirin-intolerant asthma (AIA) patients by triggering cysteinyl-leukotriene (cys-LT) production, probably by removing PGE2-dependent inhibition. To investigate why aspirin does not cause bronchoconstriction in all individuals, we immunostained enzymes of the leukotriene and prostanoid pathways in bronchial biopsies from AIA patients, aspirin-tolerant asthma (ATA) patients, and normal (N) subjects. Counts of cells expressing the terminal enzyme for cys-LT...

  6. Safety of 12 core transrectal ultrasound guided prostate biopsy in patients on aspirin

    OpenAIRE

    Pawan Vasudeva; Niraj Kumar; Anup Kumar; Harbinder Singh; Gaurav Kumar

    2015-01-01

    ABSTRACT Objective: To prospectively assess safety outcome of TRUS guided prostate biopsy in patients taking low dose aspirin. Materials and methods: Consecutive patients, who were planned for 12 core TRUS guided prostate biopsy and satisfied eligibility criteria, were included in the study and divided into two Groups: Group A: patients on aspirin during biopsy, Group B: patients not on aspirin during biopsy, including patients in whom aspirin was stopped prior to the biopsy. Parameters inclu...

  7. Protective Effects of Ginger against Aspirin-Induced Gastric Ulcers in Rats

    OpenAIRE

    Wang, Zhongzhi; HASEGAWA, JUNICHI; Wang, Xinhui; Matsuda, Akiko; Tokuda, Takahiro; Miura, Norimasa; Watanabe, Tatsuo

    2011-01-01

    We investigated the mechanism underlying the protective effects of ginger against gastric damage induced by aspirin in rats. Gastric mucosal lesions were produced by orally administering 200 mg/kg aspirin suspended in 1% carboxymethylcellulose solution to pyloric-ligated male Wistar rats. Ginger powder (200 mg/kg) markedly reduced the aspirin-induced gastric hemorrhagic ulcer area. The total acidity of gastric juice was not significantly influenced by aspirin or ginger. Ginger powder did not ...

  8. Influencia de la aspirina sobre el sangrado al sondaje Influence of aspirin on the bleeding on probing

    Directory of Open Access Journals (Sweden)

    C.M. Ardila Medina

    2011-08-01

    Full Text Available La presencia de sangrado es un signo de inflamación en los tejidos gingivales y periodontales. Aun cuando el sangrado puede ser causado por eventos inflamatorios hiperémicos, otras variables como una función defectuosa de las plaquetas también pueden ocasionar hemorragia. El uso de la aspirina comúnmente ocasiona disfunción adquirida de las plaquetas. Las indicaciones de la aspirina incluyen la reducción del riesgo de varias enfermedades cerebrovasculares y cardiovasculares debido a su actividad antitrombolítica. La aspirina en bajas concentraciones inhibe preferencialmente la síntesis de tromboxanos responsable en la agregación de plaquetas. De esta forma, la aspirina tiene el potencial de alterar la aparición de sangrado valorado por algunos índices empleados en la evaluación clínica periodontal.The presence of bleeding is a sign of inflammation in gingival and periodontal tissues. Although bleeding can be caused by hyperemic inflammatory events, other variables such as defective platelet function can also cause bleeding. The acquired platelet dysfunction is most commonly caused by the use of aspirin. The indication of aspirin include risk reduction for various cerebrovascular and cardiovascular diseases, these benefits derive from aspirin's anti-thromobolytic activity. Aspirin at low concentrations preferentially inhibits the synthesis of thromboxanes responsible for the aggregation of platelets. Thus, aspirin has the potential to alter the appearance of bleeding on some indices used in clinical periodontal evaluation.

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

    Directory of Open Access Journals (Sweden)

    Haider Raza

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

  10. 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

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

    International Nuclear Information System (INIS)

    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-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

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

    NARCIS (Netherlands)

    V.E. Valkhoff (Vera)

    2012-01-01

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

  13. Comparison of hyperuricemia in type 2 diabetics on low dose aspirin and not on low dose aspirin

    International Nuclear Information System (INIS)

    Objective: To compare the frequency of hyperuricemia in type 2 diabetes patients who are taking low dose aspirin with those patients who are not taking low dose aspirin. Study design: Quasi experimental study. Place and duration of study: This study was carried out at Military Hospital Rawalpindi for a period of two years (June 2006-May 2008). Patients and Methods: Sixty diabetic patients were selected who were taking low dose aspirin comparing group A and sixty diabetic patients who were not taking aspirin were placed in group B. These patients were selected from the OPD through non probability convenience sampling. All these patients were being followed up in medical outpatient quite regularly on fort-nightly basis. Data had been collected through a carefully designed questionnaire. Results: In group A, 90% of the patients had uric acid less than 445 micro mol/l and 10% of the patients had uric acid more than 445micro mol/l. Whereas in group B 100% of the patients had uric acid less than 445umol/l, there was a statistically significant difference between the two groups (p< 0.05). Conclusion: Aspirin in low doses cause hyperuricemia and regular monitoring of uric acid is mandatory to prevent its adverse effects. (author)

  14. Use of low-dose aspirin and non-aspirin nonsteroidal anti-inflammatory drugs and risk of glioma

    DEFF Research Database (Denmark)

    Gaist, David; García-Rodríguez, L A; Sørensen, H T;

    2013-01-01

    Background:Few studies have examined the association between use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and risk of glioma and the results have been equivocal. We therefore investigated the influence of NSAID use on glioma risk in a nationwide setting.Methods:We used...... exposure to low-dose aspirin or non-aspirin (NA) NSAIDs into ever use or long-term use, defined as continuous use for 5 years. Conditional logistic regression was used to compute odds ratios (ORs), with 95% confidence intervals (CIs), for glioma associated with NSAID use, adjusted for potential...... confounders.Results:A total of 2688 glioma cases and 18 848 population controls were included in the study. Ever use of low-dose aspirin (OR=0.90; 95% CI: 0.77-1.04) or NA-NSAIDs (OR=1.05; 95% CI: 0.96-1.14) was not associated with glioma risk. Compared with never use, long-term use of low-dose aspirin or of...

  15. 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.

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

    Science.gov (United States)

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

    2015-02-01

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

  17. Aspirin use for primary prevention in elderly patients.

    Science.gov (United States)

    Terrosu, Pierfranco

    2016-01-01

    The net clinical benefit of aspirin in primary prevention is uncertain as the reduction in occlusive events needs to be balanced against the increase in gastro-intestinal and cerebral bleedings. The meta-analysis of ATT (Anti Thrombotic Trialists) Collaboration in 2009 showed that aspirin therapy in primary prevention was associated with 12% reduction in cardio-vascular events, due mainly to a reduction in non-fatal myocardial infarction (0.18% vs 0.23% per year, pheart attack and stroke. As a consequence, it is important consider both likelihoods of benefits as well as harm within the lifespan and functioning of the person. The older people who most likely benefit from aspirin in primary prevention are those at higher cardio-vascular risk, with preserved functional abilities, low comorbidity, low risk of bleeding and a prolonged life expectancy. PMID:27374042

  18. Aspirin for the primary prevention of cardiovascular events.

    Science.gov (United States)

    Colwell, John A

    2006-01-01

    There is significant evidence that low-dose aspirin is effective in preventing the first myocardial infarction in men and ischemic stroke in women. There is also an increased risk for major gastrointestinal tract hemorrhage and a suggestive, but nonsignificant, increase in the risk for hemorrhagic stroke. If there is a history of ulcer disease or upper-gastrointestinal tract bleeding, Helicobacter pylori should be eradicated (if present) and a proton pump inhibitor used with aspirin therapy. In conclusion, the benefits of low-dose aspirin (75-162 mg/day) in the prevention of myocardial infarction in men and thrombotic stroke in women generally outweigh the risks of serious bleeding in adults with a coronary heart disease risk >1% per year or >1% in 10 years. PMID:17066145

  19. Aspirin Increases the Solubility of Cholesterol in Lipid Membranes

    Science.gov (United States)

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

    2014-03-01

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

  20. Functionalized bimodal mesoporous silicas as carriers for controlled aspirin delivery

    Science.gov (United States)

    Gao, Lin; Sun, Jihong; Li, Yuzhen

    2011-08-01

    The bimodal mesoporous silica modified with 3-aminopropyltriethoxysilane was performed as the aspirin carrier. The samples' structure, drug loading and release profiles were characterized with X-ray diffraction, scanning electron microscopy, N 2 adsorption and desorption, Fourier transform infrared spectroscopy, TG analysis, elemental analysis and UV-spectrophotometer. For further exploring the effects of the bimodal mesopores on the drug delivery behavior, the unimodal mesoporous material MCM-41 was also modified as the aspirin carrier. Meantime, Korsmeyer-Peppas equation ft= ktn was employed to analyze the dissolution data in details. It is indicated that the bimodal mesopores are beneficial for unrestricted drug molecules diffusing and therefore lead to a higher loading and faster releasing than that of MCM-41. The results show that the aspirin delivery properties are influenced considerably by the mesoporous matrix, whereas the large pore of bimodal mesoporous silica is the key point for the improved controlled-release properties.

  1. Prostaglandin receptor EP3 mediates growth inhibitory effect of aspirin through androgen receptor and contributes to castration resistance in prostate cancer cells.

    Science.gov (United States)

    Kashiwagi, Eiji; Shiota, Masaki; Yokomizo, Akira; Itsumi, Momoe; Inokuchi, Junichi; Uchiumi, Takeshi; Naito, Seiji

    2013-06-01

    Although numerous epidemiological studies show aspirin to reduce risk of prostate cancer, the mechanism of this effect is unclear. Here, we first confirmed that aspirin downregulated androgen receptor (AR) and prostate-specific antigen in prostate cancer cells. We also found that aspirin upregulated prostaglandin receptor subtype EP3 but not EP2 or EP4. The EP3 antagonist L798106 and EP3 knockdown increased AR expression and cell proliferation, whereas the EP3 agonist sulprostone decreased them, indicating that EP3 affects AR expression. Additionally, EP3 (PTGER3) transcript levels were significantly decreased in human prostate cancer tissues compared with those in normal human prostate tissues, suggesting that EP3 is important to prostate carcinogenesis. Decreased EP3 expression was also seen in castration-resistant subtype CxR cells compared with parental LNCaP cells. Finally, we found that aspirin and EP3 modulators affected prostate cancer cell growth. Taken together, aspirin suppressed LNCaP cell proliferation via EP3 signaling activation; EP3 downregulation contributed to prostate carcinogenesis and to progression from androgen-dependent prostate cancer to castration-resistant prostate cancer by regulating AR expression. In conclusion, cyclooxygenases and EP3 may represent attractive therapeutic molecular targets in androgen-dependent prostate cancer. PMID:23493387

  2. Cloning, recombinant expression and biochemical characterisation of novel esterases from Bacillus sp. associated with the marine sponge Aplysina aerophoba.

    Science.gov (United States)

    Karpushova, A; Brümmer, F; Barth, S; Lange, S; Schmid, R D

    2005-04-01

    Two novel esterases (EstB1 and EstB2) were isolated from a genomic library of Bacillus sp. associated with the marine sponge Aplysina aerophoba. EstB1 shows low identity (26-44%) with the published hydrolases of the genus Bacillus, whereas EstB2 shows high identity (73-74%) with the carboxylesterases from B. cereus and B. anthracis. Both esterases were efficiently expressed in Escherichia coli under the control of T7 promoter using the vector pET-22b(+). Recombinant EstB1 was purified in a single step to electrophoretic homogeneity by IMAC. A method for the refolding of inclusion bodies formed by the recombinant EstB2 was established to obtain active enzyme. Substrate specificity of the two enzymes towards p-nitrophenyl and methyl esters and the respective kinetic parameters K(m) and V(max) were determined. The temperature optima of EstB1 and EstB2 were determined to be in the range of 30-50 degrees C and 20-35 degrees C, respectively. The pH optima were found to be in the range of 6.5-7.5 and 6.5-8.0, respectively. Both enzymes showed the highest stability in up to 50% (v/v) DMSO followed by methanol, ethanol and 2-propanol. The influence of high NaCl and KCl concentrations was tested. The inhibition effect of 10-50 mM Zn(2+) and 50 mM Mg(2+) and Ca(2+) ions was observed for both esterases. One to five millimolar PMSF deactivated the enzymes, whereas beta-mercaptoethanol, DTT and EDTA had no effect on the enzymes activity. PMID:15614567

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

    International Nuclear Information System (INIS)

    Aspirin (acetyl salicylic acid, ASA) is a common drug used for its analgesic and antipyretic effects. Recent studies show that ASA not only blocks cyclooxygenase, but also inhibits NADPH oxidase and resultant reactive oxygen species (ROS) generation, a pathway that underlies pathogenesis of several ailments, including hypertension and tissue remodeling after injury. In these disease states, angiotensin II (Ang II) activates NADPH oxidase via its type 1 receptor (AT1R) and leads to fibroblast growth and collagen synthesis. In this study, we examined if ASA would inhibit NADPH oxidase activation, upregulation of AT1R transcription, and subsequent collagen generation in mouse cardiac fibroblasts challenged with Ang II. Mouse heart fibroblasts were isolated and treated with Ang II with or without ASA. As expected, Ang II induced AT1R expression, and stimulated cardiac fibroblast growth and collagen synthesis. The AT1R blocker losartan attenuated these effects of Ang II. Similarly to losartan, ASA, and its SA moiety suppressed Ang II-mediated AT1R transcription and fibroblast proliferation as well as expression of collagens and MMPs. ASA also suppressed the expression of NADPH oxidase subunits (p22phox, p47phox, p67phox, NOX2 and NOX4) and ROS generation. ASA did not affect total NF-κB p65, but inhibited its phosphorylation and activation. These observations suggest that ASA inhibits Ang II-induced NADPH oxidase expression, NF-κB activation and AT1R transcription in cardiac fibroblasts, and fibroblast proliferation and collagen expression. The critical role of NADPH oxidase activity in stimulation of AT1R transcription became apparent in experiments where ASA also inhibited AT1R transcription in cardiac fibroblasts challenged with H2O2. Since SA had similar effect as ASA on AT1R expression, we suggest that ASA's effect is mediated by its SA moiety. -- Highlights: ► Aspirin in therapeutic concentrations decreases mouse cardiac fibroblast growth and collagen formation

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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xianwei, E-mail: XWang2@UAMS.edu; Lu, Jingjun; Khaidakov, Magomed; Mitra, Sona; Ding, Zufeng; Raina, Sameer; Goyal, Tanu; Mehta, Jawahar L., E-mail: MehtaJL@UAMS.edu

    2012-03-15

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

  5. 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

  6. Novel Pro-resolving Aspirin-Triggered DHA Pathway

    OpenAIRE

    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

    Endogenous mechanisms in the resolution of acute inflammation are of interest since excessive inflammation underlies many pathologies. We report a new 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)]. The complete stereochemistry of AT-(NPD1/PD1) proved to be 10R,17R-dihydroxydocosa- 4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid. The chirality of hydroxyl groups a...

  7. Investigating the Effect of Aspirin on Mercury Toxicity

    OpenAIRE

    Fatih Polat; Tarık Dal

    2013-01-01

    The effect of aspirin on the toxicology of mercury was investigated by using fish. The variations between blood parameters of the fish, which were made exposed directly to mercury solutions prepared at certain concentrations (500 μg/L, 250 μg/L, 125 μg/L, 62.5 μg/L, and 31.25 μg/L), and blood parameters of the fish, which were made exposed to mercury at the same concentrations after they had been interacting with aspirin, were investigated. At the end of the study, increases in blood paramet...

  8. Aspirin inhibits interleukin 1-induced prostaglandin H synthase expression in cultured endothelial cells.

    OpenAIRE

    Wu, K. K.; Sanduja, R; Tsai, A. L.; Ferhanoglu, B.; Loose-Mitchell, D S

    1991-01-01

    Prostaglandin H (PGH) synthase (EC 1.14.99.1) 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 (0.1-1 micrograms/ml) inhibited more than 60% of the enzyme mass and also the cyclooxygenase activity in IL-1-i...

  9. Methods for field detection of resistance to temephos in simuliids. Larval esterase level and topical application of the insecticide to adults

    OpenAIRE

    Carlos Fernando S. de Andrade; Armando Castello Branco Junior

    1990-01-01

    Two practical field methods for indirect detection of simuliid populations resistant to temephos are proposed. The first is based on high esterase activity in resistant larvae and involves adaptations of a filter paper test in which faintly stained spots indicate susceptible populations and strongly stained ones reveal populations resistant to temephos. The second is based on the resistance to the larvicide when adults are topically exposed, and involves the use of diagnostic doses obtained b...

  10. Uncovering divergent evolution of α/β-hydrolases: a surprising residue substitution needed to convert Hevea brasiliensis hydroxynitrile lyase into an esterase

    OpenAIRE

    Nedrud, David M.; Lin, Hui; Lopez, Gilsinia; Padhi, Santosh K.; Legatt, Graig A.; Kaz-lauskas, Romas J.

    2014-01-01

    Hevea brasiliensis hydroxynitrile lyase (HbHNL) and salicylic acid binding protein 2 (SABP2, an esterase) share 45% amino acid sequence identity, the same protein fold, and even the same catalytic triad of Ser-His-Asp. However, they catalyze different reactions: cleavage of hydroxynitriles and hydrolysis of esters, respectively. To understand how other active site differences in the two enzymes enable the same catalytic triad to catalyze different reactions, we substituted amino acid residues...

  11. Determination of organophosphorus pesticide residues in vegetables by an enzyme inhibition method using α-naphthyl acetate esterase extracted from wheat flour*

    OpenAIRE

    WANG, JUN-LIANG; Xia, Qing; Zhang, An-Ping; Hu, Xiao-Yan; Lin, Chun-mian

    2012-01-01

    The widespread use of organophosphorus pesticides (OPs) poses a great threat to human health and has made the detection of OP residues in food an important task, especially in view of the fact that easy and rapid detection methods are needed. Because OPs have inhibitory effects on the activity of α-naphthyl acetate esterase (ANAE) in plants, in this work we evaluated the possibility of detecting OPs in vegetables with ANAE extracted from commercial flour. The limits of detection (LODs) obtain...

  12. Biochemical Properties of Two Cinnamoyl Esterases Purified from a Lactobacillus johnsonii Strain Isolated from Stool Samples of Diabetes-Resistant Rats▿

    OpenAIRE

    Lai, Kin Kwan; Lorca, Graciela L.; Gonzalez, Claudio F.

    2009-01-01

    Cinnamic acids (i.e., ferulic and caffeic acids) that are esterified to the vegetable cell walls should be enzymatically released to be absorbed in a mammal's intestines. A low dosage of ferulic acid in rodent diets stimulates insulin production and alleviates symptoms caused by diabetes (M. Sri Balasubashini, R. Rukkumani, and V. P. Menon, Acta Diabetol. 40:118-122, 2003). Several lactic acid bacteria are able to display ferulic acid esterase (FAE) activity, suggesting that their probiotic a...

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  14. Heterologous expression of a fungal sterol esterase/lipase in different hosts: Effect on solubility, glycosylation and production.

    Science.gov (United States)

    Vaquero, María Eugenia; Barriuso, Jorge; Medrano, Francisco Javier; Prieto, Alicia; Martínez, María Jesús

    2015-12-01

    Ophiostoma piceae secretes a versatile sterol-esterase (OPE) that shows high efficiency in both hydrolysis and synthesis of triglycerides and sterol esters. This enzyme produces aggregates in aqueous solutions, but the recombinant protein, expressed in Komagataella (synonym Pichia) pastoris, showed higher catalytic efficiency because of its higher solubility. This fact owes to a modification in the N-terminal sequence of the protein expressed in Pichia pastoris, which incorporated 4-8 additional amino acids, affecting its aggregation behavior. In this study we present a newly engineered P. pastoris strain with improved protein production. We also produced the recombinant protein in the yeast Saccharomyces cerevisiae and in the prokaryotic host Escherichia coli, corroborating that the presence of these N-terminal extra amino acids affected the protein's solubility. The OPE produced in the new P. pastoris strain presented the same physicochemical properties than the old one. An inactive form of the enzyme was produced by the bacterium, but the recombinant esterase from both yeasts was active even after its enzymatic deglycosylation, suggesting that the presence of N-linked carbohydrates in the mature protein is not essential for enzyme activity. Although the yield in S. cerevisiae was lower than that obtained in P. pastoris, this work demonstrates the importance of the choice of the heterologous host for successful production of soluble and active recombinant protein. In addition, S. cerevisiae constitutes a good engineering platform for improving the properties of this biocatalyst. PMID:25939548

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

    International Nuclear Information System (INIS)

    Highlights: ► NOSH–aspirin is the first dual acting NO and H2S releasing hybrid. ► Its IC50 for cell growth inhibition is in the low nano-molar range. ► Structure–activity studies show that the sum of the parts does not equal the whole. ► NOSH–aspirin reduced tumor growth by 85% in mice bearing a colon cancer xenograft. -- Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) are prototypical anti-cancer agents. However, their long-term use is associated with adverse gastrointestinal effects. Recognition that endogenous gaseous mediators, nitric oxide (NO) and hydrogen sulfide (H2S) can increase mucosal defense mechanisms has led to the development of NO- and H2S-releasing NSAIDs with increased safety profiles. Here we report on a new hybrid, NOSH–aspirin, which is an NO- and H2S-releasing agent. NOSH–aspirin inhibited HT-29 colon cancer growth with IC50s of 45.5 ± 2.5, 19.7 ± 3.3, and 7.7 ± 2.2 nM at 24, 48, and 72 h, respectively. This is the first NSAID based agent with such high degree of potency. NOSH–aspirin inhibited cell proliferation, induced apoptosis, and caused G0/G1 cell cycle block. Reconstitution and structure–activity studies representing a fairly close approximation to the intact molecule showed that NOSH–aspirin was 9000-fold more potent than the sum of its parts towards growth inhibition. NOSH–aspirin inhibited ovine COX-1 more than ovine COX-2. NOSH–ASA treatment of mice bearing a human colon cancer xenograft caused a reduction in volume of 85%. Taken together, these results demonstrate that NOSH–aspirin has strong anti-cancer potential and merits further evaluation.

  16. A cold-adapted, solvent and salt tolerant esterase from marine bacterium Psychrobacter pacificensis.

    Science.gov (United States)

    Wu, Gaobing; Zhang, Xiangnan; Wei, Lu; Wu, Guojie; Kumar, Ashok; Mao, Tao; Liu, Ziduo

    2015-11-01

    Lipolytic enzymes with unique physico-chemical characteristics are gaining more attention for their immense industrial importance. In this study, a novel lipolytic enzyme (Est11) was cloned from the genomic library of a marine bacterium Psychrobacter pacificensis. The enzyme was expressed in Escherichia coli and purified to homogeneity with molecular mass of 32.9kDa. The recombinant Est11 was able to hydrolyze short chain esters (C2-C8) and displayed an optimum activity against butyrate ester (C4). The optimal temperature and pH were 25°C and 7.5, respectively. Est11 retained more than 70% of its original activity at 10°C, suggesting that it was a cold-active esterase. The enzyme was highly active and stable at high concentration of NaCl (5M). Further, incubation with ethanol, isopropanol, propanediol, DMSO, acetonitrile, and glycerol rendered remarkable positive effects on Est11 activity. Typically, even at the concentration of 30% (v/v), ethanol, DMSO, and propanediol increased Est11 activity by 1.3, 2.0, and 2.4-folds, respectively. This new robust enzyme with remarkable properties like cold-adaptability, exceptional tolerance to salt and organic solvents provides us a promising candidate to meet the needs of some harsh industrial processes. PMID:26231332

  17. Soluble CD40 Ligand in Aspirin-Treated Patients Undergoing Cardiac Catheterization.

    Directory of Open Access Journals (Sweden)

    Thomas Gremmel

    Full Text Available Plasma soluble CD40 ligand (sCD40L is mainly generated by cleavage of CD40L from the surface of activated platelets, and therefore considered a platelet activation marker. Although the predictive value of sCD40L for ischemic events has been demonstrated in patients with acute coronary syndromes (ACS, studies on the association of sCD40L with cardiovascular outcomes in lower risk populations yielded heterogeneous results. We therefore sought to investigate factors influencing sCD40L levels, and the predictive value of sCD40L for long-term ischemic events in unselected, aspirin-treated patients undergoing cardiac catheterization. sCD40L was determined by a commercially available enzyme-linked immunosorbent assay in 682 consecutive patients undergoing cardiac catheterization. Two-year follow-up data were obtained from 562 patients. Dual antiplatelet therapy with aspirin and clopidogrel was associated with significantly lower levels of sCD40L and lower platelet surface expressions of P-selectin and activated GPIIb/IIIa compared to aspirin monotherapy (all p≤0.01. Hypertension was linked to lower plasma concentrations of sCD40L, whereas female sex, increasing high-sensitivity C-reactive protein, and hematocrit were associated with higher sCD40L concentrations (all p<0.05. sCD40L levels were similar in patients without and with the primary endpoint in the overall study population (p = 0.4. Likewise, sCD40L levels did not differ significantly between patients without and with the secondary endpoints (both p≥0.4. Similar results were obtained when only patients with angiographically-proven coronary artery disease (n = 459, stent implantation (n = 205 or ACS (n = 125 were analyzed. The adjustment for differences in patient characteristics by multivariate regression analyses did not change the results. ROC curve analyses did not reveal cut-off values for sCD40L for the prediction of the primary or secondary endpoints. In conclusion, plasma sCD40L

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

    International Nuclear Information System (INIS)

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

  19. In vivo prostacyclin biosynthesis and effects of different aspirin regimens in patients with essential thrombocythaemia.

    Science.gov (United States)

    Cavalca, V; Rocca, B; Squellerio, I; Dragani, A; Veglia, F; Pagliaccia, F; Porro, B; Barbieri, S S; Tremoli, E; Patrono, C

    2014-07-01

    Essential thrombocythaemia (ET) is characterised by enhanced platelet generation and thrombosis. Once daily (od) aspirin incompletely inhibits platelet thromboxane (TX)A2 production in ET. A twice daily (bid) dosing is necessary to fully inhibit TXA2. Whether this dosing regimen affects in vivo prostacyclin (PGI2) biosynthesis is unknown. PGI2 biosynthesis was characterised in 50 ET patients on enteric-coated (EC) aspirin 100 mg od, by measuring its urinary metabolite, 2,3-dinor-6-keto-PGF1α (PGI-M). Moreover, in a crossover study 22 patients poorly responsive to standard aspirin based on serum TXB2 levels (≥4 ng/ml) were randomised to different seven-day aspirin regimens: EC aspirin 100 mg od, 100 mg bid, 200 mg od, or plain aspirin 100 mg od. PGI-M measured 24 hours after the last aspirin intake (EC, 100 mg od) was similar in patients and healthy subjects both on (n=10) and off (n=30) aspirin. PGI-M was unrelated to in vivo TXA2 biosynthesis, and not affected by EC aspirin 100 mg bid or 200 mg od as compared to EC 100 mg od. PGI2 biosynthesis in aspirin-treated ET patients appears unrelated to TXA2 biosynthesis, and not affected by an improved aspirin regimen, demonstrating its vascular safety for future trials. PMID:24671522

  20. Endothelial dysfunction in young healthy men is associated with aspirin resistance.

    Science.gov (United States)

    Doroszko, Adrian; Szahidewicz-Krupska, Ewa; Janus, Agnieszka; Jakubowski, Maciej; Turek, Aleksandra; Ilnicka, Paulina; Szuba, Andrzej; Mazur, Grzegorz; Derkacz, Arkadiusz

    2015-01-01

    The aim of this study was to investigate the relation between endothelial dysfunction and aspirin response in a young healthy population (102 men aged 18-40). Initial concentrations of the NO pathway metabolites (ADMA, l-arginine, SDMA), cardiovascular risk markers, oxidative stress markers (MDA, thiol index), sICAM1, sVCAM1, PAI-1, sE-selectin, sP-selectin, VEGF, thromboxane B2, 6-keto-PGF1α and arachidonate-induced platelet aggregation (to separate aspirin resistant from sensitive group) were measured. Flow-mediated-vasodilation (FMD) was measured before and after intravenous infusion of 16.0 g of l-arginine. Measurements were repeated following aspirin administration (75 mg/24 h) for 4 days. Both groups were homogenous regarding demographic and biochemical characteristics reflecting cardiovascular risk. Aspirin resistant subjects were characterized by lower baseline FMD and higher FMD following aspirin and l-arginine treatment, as compared to aspirin sensitive control. MDA and nitrotyrosine were greater, whereas thiol index was lower in aspirin resistant men. The sICAM1, sVCAM1, PAI-1, sE-selectin, sP-selectin and VEGF levels were similar in the analyzed groups. Thromboxane in aspirin resistant subjects was greater both at baseline and following aspirin therapy. However, a significant decrease following aspirin treatment was present in both groups. Aspirin resistance in young men is associated with endothelial dysfunction, which could be due to oxidative stress resulting from lipid peroxidation. PMID:25697550

  1. Monitoring the hydrolyzation of aspirin during the dissolution testing for aspirin delayed-release tablets with a fiber-optic dissolution system

    Institute of Scientific and Technical Information of China (English)

    Yan Wang; Ping-Ping Xu; Xin-Xia Li; Kun Nie; Ming-Fu Tuo; Bin Kong; Jian Chen

    2012-01-01

    The purpose of this study was to investigate the hydrolyzation of aspirin during the process of dissolution testing for aspirin delayed-release tablets. Hydrolysis product of salicylic acid can result in adverse effects and affect the determination of dissolution rate assaying. In this study, the technique of differential spectra was employed, which made it possible to monitor the dissolution testing in situ. The results showed that the hydrolyzation of aspirin made the percentage of salicylic acid exceed the limit of free salicylic acid (4.0), and the hydrolyzation may affect the quality detection of aspirin delayed-release tablets.

  2. Aspirin-Exacerbated Diseases: Advances in Asthma with Nasal Polyposis, Urticaria, Angioedema, and Anaphylaxis.

    Science.gov (United States)

    Stevens, Whitney; Buchheit, Kathleen; Cahill, Katherine N

    2015-12-01

    Aspirin-exacerbated diseases are important examples of drug hypersensitivities and include aspirin-exacerbated respiratory disease (AERD), aspirin- or non-steroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema, and aspirin- or NSAID-induced anaphylaxis. While each disease subtype may be distinguished by unique clinical features, the underlying mechanisms that contribute to these phenotypes are not fully understood. However, the inhibition of the cyclooxygenase-1 enzyme is thought to play a significant role. Additionally, eosinophils, mast cells, and their products, prostaglandins and leukotrienes, have been identified in the pathogenesis of AERD. Current diagnostic and treatment strategies for aspirin-exacerbated diseases remain limited, and continued research focusing on each of the unique hypersensitivity reactions to aspirin is essential. This will not only advance the understanding of these disease processes, but also lead to the subsequent development of novel therapeutics that patients who suffer from aspirin-induced reactions desperately need. PMID:26475526

  3. Synthesis and Chemical and Biological Comparison of Nitroxyl and Nitric Oxide Releasing Diazeniumdiolate-based Aspirin Derivatives

    OpenAIRE

    Basudhar, Debashree; Bharadwaj, Gaurav; Cheng, Robert Y.; Jain, Sarthak; Shi, Sa; Heinecke, Julie L.; Holland, Ryan J.; Ridnour, Lisa A.; Caceres, Viviane de M.; Spadari-Bratfisch, Regina C.; Paolocci, Nazareno; Velázquez-Martínez, Carlos A.; Wink, David A.; Miranda, Katrina M.

    2013-01-01

    Structural modifications of non-steroidal anti-inflammatory drugs (NSAIDs) have successfully reduced the side effect of gastrointestinal ulceration without affecting anti-inflammatory activity, but may increase risk of myocardial infarction with chronic use. That nitroxyl (HNO) reduces platelet aggregation, preconditions against myocardial infarction and enhances contractility led us to synthesize a diazeniumdiolate-based HNO releasing aspirin and to compare it to an NO-releasing analogue. He...

  4. Assessment of the Prophylactic Role of Aspirin and/or Clopidogrel on Experimentally Induced Acute Myocardial Infarction in Hypercholesterolemic Rats

    OpenAIRE

    Mohamed, Adham R.; Wessam F. El-Hadidy; Mannaa, Hazem F.

    2014-01-01

    Introduction Hyperlipidemia is a risk factor for cardiovascular diseases such as acute infarction. Inflammation and platelet activation are critical phenomena in acute myocardial infarction (AMI). Aim The aim of the study was to assess potential protective effects of aspirin and/or clopidogrel on AMI in hypercholesterolemic rats. Methods Forty adult male Wistar rats were divided into five groups (eight rats in each). Group I included normal healthy rats. The other 32 rats were subjected to in...

  5. Why we should not skip aspirin in cardiovascular prevention.

    Science.gov (United States)

    Schrör, K

    2016-01-01

    Since more than 20 years, aspirin is an approved and established first-line antiplatelet medication in cardiovascular prevention. This is partially due to ist unique mode of action which is not shared with any other antiplatelet agent as well by the reliability of its pharmacological efficacy: inhibition of platelet COX-1 and subsequent thromboxane formation in almost every patient. Aspirin acts synergistic with ADP-antagonists in dual antiplatelet therapy of acute coronary syndromes (ACS) and percutaneous coronary interventions (PCI) and is also approved for long-term secondary prevention. Patients with atrial fibrillation are an exception and benefit more from anticoagulants. After the introduction of the new oral anticoagulants (NOACs), i.e. direct inhibitors of factor Xa or thrombin formation, there is a renewed discussion about the role of antiplatelet agents, specifically if additional dual antiplatelet treatment is still necessary for an optimum clinical effect or whether one component, such as aspirin might be skipped in favor of other classes of oral antiplatelet agents, such as ADP-antagonists. The available data are insufficient to recommend this because of a low number of studies and a still uncertain benefit/risk (bleeding) ratio. More research on aspirin as a chemopreventive appears also to be necessary and is going on, in particular in individuals at high-risk for vascular thrombotic diseases (diabetics, preeclampsia, venous thromboembolism). PMID:25891122

  6. Perioperative aspirin and clonidine and risk of acute kidney injury

    DEFF Research Database (Denmark)

    Garg, Amit X; Kurz, Andrea; Sessler, Daniel I;

    2014-01-01

    IMPORTANCE: Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain and ...

  7. Aspirin induced fixed drug eruptions: a case report

    Directory of Open Access Journals (Sweden)

    Rama R. Bhosale

    2013-04-01

    Full Text Available Fixed drug eruptions are common cutaneous adverse drug reactions, commonly caused by anticonvulsants, antibiotics and analgesics. Here, we report a case of a 27-year-old male of fixed drug eruptions due to Aspirin which was used in treatment of headache. [Int J Basic Clin Pharmacol 2013; 2(2.000: 220-221

  8. SYNTHESIS OF BIOCOMPATIBLE ACRYLIC POLYMERS HAVING ASPIRIN-MOIETIES

    Institute of Scientific and Technical Information of China (English)

    LI Fumian; GU Zhongwei; FENG Xinde(S. T. Voong)

    1983-01-01

    Several new monomers, β-(acetylsalicylyloxy)ethyl methacrylate, β-(acetylsalicylyloxy)propyl methacrylate, β-(acetylsalicylyloxy)ethyl acrylate, β-hydroxy-γ-(acetylsalicylyloxy)propyl methacrylate, β-hydroxy-γ-(acetylsalicylyloxy)propyl acrylate have been synthesized from aspirin with corresponding hydroxyalkyl or glycidyl acrylates, and then polymerized by free radical initiator.

  9. The neuroprotection of Aspirin on Cerebral Ischemia-Reperfusion rats

    Institute of Scientific and Technical Information of China (English)

    QiuLi-ying; YuJuan; ChenChong-hong; ZhouYu

    2004-01-01

    AIM: Aspirin (aeetylsalicylic acid, ASA as a nonsteroidal anti-inflammatory drug not only has well-established efficacy in anti-thromboxane, but also has direct neuroprotective effect. In this study, we design to investigate its neuroprotective effect on focal cerebral ischemia-reperfusion injury (CIRI rats, and its effect on ATP level from occluded brain tis-

  10. Aspirin in Cardiovascular and Cerebrovascular Events: Does Market Failure Matter?

    Directory of Open Access Journals (Sweden)

    Roger L. Mendoza

    2011-01-01

    Full Text Available Problem statement: Two interrelated questions were raised for investigation in this study: (1 why may government intervene in an otherwise private transaction between physician and patient and between drug manufacturer and buyer? (2 Does government intervention make a difference in what these transacting parties would otherwise have decided or chosen in its absence? Approach: An internet literature search was performed, using query term combinations, to identify aspirin-related studies. The search yielded 51 juried publications that met our predetermined criteria for inclusion and thematic analysis. Results: Some variance exists within the surveyed literature concerning government intervention in aspirin prophylaxis for cardiovascular and cerebrovascular events, particularly heart attacks, strokes and cardiovascular death. This study identified 4 instances of market failure that offer some of the strongest theoretical and practical considerations for public policy intervention in aspirin’s pharmacological information. However, there is also indication that the sense of increased protection arising from safety regulations could stimulate risky behavior that nullifies their net protective effects or benefits. Conclusion: It is not clear either from the surveyed literature or existing economic theory if, ceteris paribus, mandatory safety information is necessary to alter or modify the marginal propensity of a physician to recommend and a patient to purchase, aspirin. The study suggested the need for policy reinforcements to any safety information regulation, if market failures are to be effectively addressed and risk compensating behavior reduced.

  11. The role of aspirin in colorectal cancer chemoprevention.

    Science.gov (United States)

    Singh Ranger, Gurpreet

    2016-08-01

    Considerable interest has emerged over the last decade regarding the role of aspirin in prevention of colorectal cancer. This disease is one of the commonest cancers in the Western World, therefore, the existence of a simple "everyday" agent, which could have the ability to prevent the disease, represents an invaluable opportunity clinicians may be able to exploit. Evidence from case-control and cohort studies, and recent updates of randomised controlled trials have been very encouraging-indicating benefit from long term use of aspirin at low dose. Possible mechanisms of chemoprevention include inhibition of the cyclooxygenase (COX) pathway, or COX-independent mechanisms, for example, the PIK3CA pathway, or therapy-induced senescence of cancer cells. The most serious side effect of prolonged aspirin treatment is haemorrhage, especially from the GI tract. This is likely to be less of a problem with chemoprevention at lower doses. One also needs to consider the impact if aspirin resistance, an increasingly recognised clinical entity. PMID:27289249

  12. Estrogenic and esterase-inhibiting potency in rainwater in relation to pesticide concentrations, sampling season and location

    International Nuclear Information System (INIS)

    Estrogenic potency of rainwater correlated well with organochlorine concentrations, but could not be attributed to specific pesticides. - In a year-round monitoring program (1998), pesticide composition and toxic potency of the mix of pollutants present in rainwater were measured. The goal of the study was to relate atmospheric deposition of toxic potency and pesticide composition to each other and to sampling period and local agricultural activity. Rainwater was collected in 26 consecutive periods of 14 days in a background location (BACK) and in two locations representative for different agricultural practices, i.e. intensive greenhouse horticulture (HORT) and flower bulb culture (BULB). Samples were chemically analyzed for carbamate (CARB), organophosphate (OP) and organochlorine (OC) pesticides and metabolites. Esterase inhibiting potency of rainwater extracts was measured in a specially developed bio-assay with honeybee esterases and was expressed as an equivalent concentration of the model inhibitor dichlorvos. Estrogenic potency of the extracts was measured in the ER-CALUX reporter gene assay and was expressed as an equivalent concentration of estradiol. Multivariate principal component analysis (PCA) techniques proved to be valuable tools to analyze the numerous pesticide concentrations in relation to toxic potency, sampling location, and sampling season. Pesticide composition in rainwater depended much more on sampling season than on sampling location, but differences between SPRING and SUMMER were mainly attributed to local differences in agricultural practice. On average, the esterase inhibiting potency exceeded the maximum permissible concentration set for dichlorvos in The Netherlands, and was significantly higher in HORT than in BACK and BULB. Esterase inhibition correlated significantly with OP and CARB concentrations, as expected given the working mechanism of these insecticides. The estrogenic potency incidentally exceeded NOEC levels reported for

  13. The utilization status of aspirin for the secondary prevention of ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    KE Xian-jun; YU Yong-fei; GUO Zhen-li; XU Kang; HAl Hong; ZHANG Ai-he; JIANG Hong; PENG Hong

    2009-01-01

    Background The present study was aimed to investigate the usage of aspirin for the secondary prevention of ischemic stroke, evaluate the correlated factors, and analyze the reasons for not taking and irregularly taking aspirin. Methods The patients in this group were all stroke survivors who have formerly been diagnosed with a cerebral infarction or transient ischemic attack (TIA) in our hospital. We investigated their use of aspirin over a three-year periodfollowing their hospitalization. According to the patients' aspirin usage, they were divided into treatment and non-treatment groups. In addition, the reasons for not taking or irregularly taking aspirin were analyzed in the two groups. Results A total of 1240 patients were studied, including 367 (29.60%) in the treatment group and 873 (70.40%) cases in the non-treatment group. In addition, 201 (16.20%) cases in the treatment group had been regularly taking aspirin (50-325 mg of aspirin daily) for 1 to 3 years or longer. The results demonstrated that the main reasons for not taking aspirin in this study were related to patients' concems regarding the side effects of taking aspirin (46.45%), as well as the doctors' inadequacy in informing their patients to take aspirin (38.71%). The major reasons for patients to irregularly take aspirin were that the doctors did not notify the length of aspirin usage to their patients (41.57%), and that doctors did not prescribe aspirin upon the patients' follow-up visit (26.51%). Conclusion The most effective way to increase patient's compliance for aspirin consumption is to promote the guidelines for stroke treatment and to relay these advances in stroke therapy to the patient.

  14. Probing role of key residues in the divergent evolution of Yarrowia lipolytica lipase 2 and Aspergillus niger eruloyl esterase A.

    Science.gov (United States)

    Wang, Guilong; Liu, Zimin; Xu, Li; Zhang, Houjin; Yan, Yunjun

    2015-09-01

    Yarrowia lipolytica lipase 2 (YLLip2) and Aspergillus niger feruloyl esterase A (AnFaeA) are enzymes of similar structures but with different functions. They are both classified into the same homologous family in Lipase Engineering Database (LED). The major difference between the two enzymes is that YLLip2 exhibits interfacial activity while AnFaeA does not. In order to better understand the interfacial activation mechanisms of YLLip2, structure guided site-directed mutagenesis were performed, mutants were constructed, kinetics parameters and lipase properties were detected. Mutant enzymes showed enhanced catalytic efficiency towards p-nitrophenyl butyrin (pNPB) but their catalytic efficiency decreased towards p-nitrophenyl palmitate (pNPP), their catalysis behavior was more close to feruloyl esterase. Moreover, the mutant enzymes exhibited enhanced thermostability compared with their wild type. These results indicate that I100 and F129 are probably cut-off point of divergent functions between the two enzymes during evolution. PMID:26302844

  15. Aspirin insensitive thrombophilia: Transcript profiling of blood identifies platelet abnormalities and HLA restriction

    Science.gov (United States)

    Fallahi, Payam; Katz, Richard; Toma, Ian; Li, Ranyang; Reiner, Jonathan; VanHouten, Kiersten; Carpio, Larry; Marshall, Lorraine; Lian, Yi; Bupp, Sujata; Fu, Sidney W.; Rickles, Frederick; Leitenberg, David; Lai, Yinglei; Weksler, Babette B.; Rebling, Frederik; Yang, Zhaoqing; McCaffrey, Timothy A.

    2016-01-01

    Aspirin is the most widely used antiplatelet agent because it is safe, efficient, and inexpensive. However, a significant subset of patients does not exhibit a full inhibition of platelet aggregation, termed ‘aspirin resistance’ (AR). Several major studies have observed that AR patients have a 4-fold increased risk of myocardial infarction (MI), stroke, and other thrombotic events. Arachidonic acid-stimulated whole blood aggregation was tested in 132 adults at risk for ischemic events, and identified an inadequate response to aspirin therapy in 9 patients (6.8%). Expression profiling of blood RNA by microarray was used to generate new hypotheses about the etiology of AR. Among the differentially expressed genes, there were decreases in several known platelet transcripts, including clusterin (CLU), glycoproteins IIb/IIIa (ITGA2B/3), lipocalin (LCN2), lactoferrin (LTF), and the thrombopoetin receptor (MPL), but with increased mRNA for the T-cell Th1 chemokine CXCL10. There was a strong association of AR with expression of HLA-DRB4 and HLA-DQA1. Similar HLA changes have been linked to autoimmune disorders, particularly antiphospholipid syndrome (APS), in which autoantibodies to phospholipid/protein complexes can trigger platelet activation. Consistent with APS, AR patients exhibited a 30% reduction in platelet counts. Follow-up testing for autoimmune antibodies observed only borderline titers in AR patients. Overall, these results suggest that AR may be related to changes in platelet gene expression creating a hyperreactive platelet, despite antiplatelet therapy. Future studies will focus on determining the protein levels of these differential transcripts in platelets, and the possible involvement of HLA restriction as a contributing factor. PMID:23454623

  16. Common and Distant Structural Characteristics of Feruloyl Esterase Families from Aspergillus oryzae

    DEFF Research Database (Denmark)

    Udatha, D. B. R. K. Gupta; Mapelli, Valeria; Panagiotou, Gianni;

    2012-01-01

    Background: Feruloyl esterases (FAEs) are important biomass degrading accessory enzymes due to their capability of cleaving the ester links between hemicellulose and pectin to aromatic compounds of lignin, thus enhancing the accessibility of plant tissues to cellulolytic and hemicellulolytic enzy...

  17. Purification and Characterization of a Feruloyl Esterase from the Intestinal Bacterium Lactobacillus acidophilus

    OpenAIRE

    Wang, Xiaokun; Geng, Xin; Egashira, Yukari; Sanada, Hiroo

    2004-01-01

    Dietary ferulic acid (FA), a significant antioxidant substance, is currently the subject of extensive research. FA in cereals exists mainly as feruloylated sugar ester. To release FA from food matrices, it is necessary to cleave ester cross-linking by feruloyl esterase (FAE) (hydroxycinnamoyl esterase; EC 3.1.1.73). In the present study, the FAE from a human typical intestinal bacterium, Lactobacillus acidophilus, was isolated, purified, and characterized for the first time. The enzyme was pu...

  18. Hydrolases as Catalysts for Green Chemistry and Industrial Applications - Esterase, Lipase and Phytase

    OpenAIRE

    Gaber, Yasser

    2012-01-01

    The use of enzymes in industrial applications has been recognised for providing clean processes with minimal impact on the environment. This thesis presents studies on engineering of enzymes and enzyme-based processes in the light of green chemistry and environmental sustainability, and focuses on three hydrolases: esterase, lipase and phytase. The use of esterase has been investigated to provide an alternative clean route for the synthesis of a chiral pharmaceutical compound, ...

  19. Recombinant sterol esterase from Ophiostoma piceae: an improved biocatalyst expressed in Pichia pastoris

    Directory of Open Access Journals (Sweden)

    Cedillo Víctor

    2012-06-01

    Full Text Available Abstract Background The ascomycete Ophiostoma piceae produces a sterol esterase (OPE with high affinity towards p-nitrophenol, glycerol and sterol esters. Its hydrolytic activity on natural mixtures of triglycerides and sterol esters has been proposed for pitch biocontrol in paper industry since these compounds produce important economic losses during paper pulp manufacture. Results Recently, this enzyme has been heterologously expressed in the methylotrophic yeast Pichia pastoris, and the hydrolytic activity of the recombinant protein (OPE* studied. After the initial screening of different clones expressing the enzyme, only one was selected for showing the highest production rate. Different culture conditions were tested to improve the expression of the recombinant enzyme. Complex media were better than minimal media for production, but in any case the levels of enzymatic activity were higher (7-fold in the best case than those obtained from O. piceae. The purified enzyme had a molecular mass of 76 kDa, higher than that reported for the native enzyme under SDS-PAGE (60 kDa. Steady-state kinetic characterization of the recombinant protein showed improved catalytic efficiency for this enzyme as compared to the native one, for all the assayed substrates (p-nitrophenol, glycerol, and cholesterol esters. Different causes for this were studied, as the increased glycosylation degree of the recombinant enzyme, their secondary structures or the oxidation of methionine residues. However, none of these could explain the improvements found in the recombinant protein. N-terminal sequencing of OPE* showed that two populations of this enzyme were expressed, having either 6 or 8 amino acid residues more than the native one. This fact affected the aggregation behaviour of the recombinant protein, as was corroborated by analytical ultracentrifugation, thus improving the catalytic efficiency of this enzyme. Conclusion P. pastoris resulted to be an optimum

  20. Aspirin inhibits the proliferation of tobacco-related esophageal squamous carcinomas cell lines through cyclooxygenase 2 pathway

    Institute of Scientific and Technical Information of China (English)

    ZHOU Qiao-Zhi; LIU Hai-bo; DING Xin-chun; LI Peng; ZHANG Shu-tian; YU Zhong-lin

    2007-01-01

    Background Cigarette smoking has been verified as the risk factor of esophageal squamous cell carcinoma(ESCC).Overexpression of cyclooxygenase 2(COX-2)is shown in ESCC.The objective of this study was to investigate the effects of cigarette smoking ethanol extract(EE)on the proliferation of the human ESCC cell Iines,and to explore the correlation between the proliferation rate of human ESCC cell lines and the expression pattern of COX-2.Whether aspirin can inhibit the proliferation of the ESCC cell lines pretreated with EE.and regulate the mRNA expression levels of COX-2 are also examined.Methods Two human ESCC cell Iines were selected.EC109 was poorly differentiated and EC9706 was highly differentiated.EC109 and EC9706 were treated with EE and aspirin for different time course.The cell growth of ESCC was measured by MTT reduction assay and the expression of COX-2 was measured by RT-PCR and Western blot analysis.Results EE promoted the proliferation of EC109 and EC9706 in dose- and time-dependent manners.In the concentration range (10-100 μg/ml for EE)and in the time range(24-72 hours)after addition of EE,the cell proliferation was prominent in an up-scaled manner respectively.Aspirin could inhibit the proliferation of cell lines EC109 and EC9706.pretreated with EE for 5 hours,in a dose-dependent manner.In the concentration range (0.5-8.0 mmol/L for aspirin),the cell growth inhibition was prominent in an up-scaled manner accordingly (P<0.05).The effect of EE on cell proliferation was correlated with the up-regulation of COX-2 gene.However,the cell growth inhibition of aspirin was correlated with the down-regulation of COX-2 gene.Conclusions EE can stimulate the proliferation of human ESCC cell lines EC109 and EC9706,most likely through up-regulating the expression of COX-2.Aspirin can inhibit the proliferation of ESCC cell lines induced by EE,which suggests it may be advantageous in the chemoprevention and therapy of human tobacco-related ESCC.And its effect is

  1. Patients with previous definite stent thrombosis have a larger fraction of immature platelets and a reduced antiplatelet effect of aspirin

    DEFF Research Database (Denmark)

    Würtz, Morten; Grove, Erik; Wulff, Lise Nielsen; Kaltoft, Anne; Hansen, Hans-Henrik Tilsted; Jensen, Lisette Okkels; Hvas, Anne-Mette; Kristensen, Steen Dalby

    when assessed by multiple electrode aggregometry induced by collagen (pcitrated blood = 0.003; phirudinized blood < 0.0001) and by arachidonic acid (pcitrated blood = 0.16; phirudinized blood = 0.04), respectively. Similarly, platelet aggregation assessed by VerifyNow was higher in ST cases (p = 0...... were treated with aspirin 75 mg once daily. Platelet function was assessed by multiple electrode aggregometry in citrated and hirudinized blood and by VerifyNow Aspirin Assay (Accumetrics, San Diego, California). Flow cytometric determination of the immature platelet fraction was performed to evaluate...... platelet turnover. Platelet activation was evaluated by soluble serum P-selectin. Compliance was confirmed by serum thromboxane B2. Results All patients were fully compliant, which was confirmed by suppressed levels of serum thromboxane B2. Platelet aggregation was increased in patients with previous ST...

  2. Extended Anticoagulant and Aspirin Treatment for the Secondary Prevention of Thromboembolic Disease: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Paul E Marik

    Full Text Available Patients who have had an unprovoked deep venous thrombosis (DVT or pulmonary embolus (PE are at a high risk for recurrent venous thromboembolism (VTE. Extended "life-long" anticoagulation has been recommended in these patients. However, the risk benefit ratio of this approach is controversial and the role of the direct oral anticoagulants (DOACs and aspirin is unclear. Furthermore, in some patients with a "weak provoking factor" there is clinical equipoise regarding continuation or cessation of anticoagulant therapy after treatment of the acute VTE event.A systematic review and meta-analysis to determine the risks (major bleeding and benefits (recurrent VTE and mortality of extended anticoagulation with vitamin k antagonists (VKA, DOACs and aspirin in patients with an unprovoked VTE and in those patients with clinical equipoise regarding continuation or cessation of anticoagulant therapy. In addition, we sought to determine the risk of recurrent VTE events once extended anti-thrombotic therapy was discontinued.MEDLINE, Cochrane Register of Controlled Trials, citation review of relevant primary and review articles.Randomized placebo-controlled trials (RCTs that compared the risk of recurrent VTE in patients with an unprovoked DVT or PE who had been treated for at least 3 months with a VKA or a DOAC and were then randomized to receive an oral anti-thrombotic agent or placebo for at least 6 additional months. We included studies that included patients in whom clinical equipoise existed regarding the continuation or cessation of anticoagulant therapy.Independent extraction of articles by both authors using predefined data fields, including study quality indicators. Data were abstracted on study size, study setting, initial event (DVT or PE, percentage of patients where the initial VTE event was unprovoked, the number of recurrent VTE events, major bleeds and mortality during the period of extended anticoagulation in the active treatment and placebo

  3. Poor awareness of preventing aspirin-induced gastrointestinal injury with combined protective medications

    Institute of Scientific and Technical Information of China (English)

    Ling-Ling Zhu; Ling-Cheng Xu; Yan Chen; Quan Zhou; Su Zeng

    2012-01-01

    AIM:To investigate prescribing pattern in low-dose aspirin users and physician awareness of preventing aspirin-induced gastrointestinal (GI) injury with combined protective medications.METHODS:A retrospective drug utilization study was conducted in the 2nd Affiliated Hospital,School of Medicine,Zhejiang University.The hospital has 2300 beds and 2.5 million outpatient visits annually.Data mining was performed on all aspirin prescriptions for outpatients and emergency patients admitted in 2011.Concomitant use of proton-pump inhibitors (PPIs),histamine 2-receptor antagonists (H2RA) and mucoprotective drugs (MPs) were analyzed.A defined daily dose (DDD) methodology was applied to each MP.A further investigation was performed in aspirin users on combination use of GI injurious medicines [non-steoid anti-inflammatory drugs (NSAIDs),corticosteroids and clopidogrel and warfarin] or intestinal protective drugs (misoprostol,rebamipide,teprenone and gefarnate).Data of major bleeding episodes were derived from medical records and adverse drug reaction monitoring records.The annual incidence of major GI bleeding due to low-dose aspirin was estimated for outpatients.RESULTS:Prescriptions for aspirin users receiving PPIs,H2RA and MPs (n =1039) accounted for only 3.46%of total aspirin prescriptions (n =30 015).The ratios of coadministration of aspirin/PPI,aspirin/H2RA,aspirin/MP and aspirin/PPI/MP to the total aspirin prescriptions were 2.82%,0.12%,0.40% and 0.12%,respectively.No statistically significant difference was observed in age between patients not receiving any GI protective medications and patients receiving PPIs,H2RA or MPs.The combined medication of aspirin and PPI was used more frequently than that of aspirin and MPs (2.82% vs 0.40%,P < 0.05) and aspirin/H2RA (2.82% vs 0.12%,P < 0.05).The values of DDDs of MPs in descending order were as follows:gefarnate,hydrotalcite > teprenone > sucralfate oral suspension > L-glutamine and sodium

  4. Using a simple HPLC approach to identify the enzymatic products of UTL-5g, a small molecule TNF-α inhibitor, from porcine esterase and from rabbit esterase

    OpenAIRE

    Swartz, Kenneth; ZHANG, YIGUAN; Valeriote, Frederick; Chen, Ben; SHAW, JIAJIU

    2013-01-01

    UTL-5g is a novel small-molecule chemoprotector that lowers hepatotoxicity, nephrotoxicity, and myelotoxicity induced by cisplatin through TNF-α inhibition among other factors. As a prelude to investigating the metabolites of UTL-5g, we set out to identify the enzymatic products of UTL-5g under the treatment of both porcine liver esterase (PLE) and rabbit liver esterase (RLE). First, a number of mixtures made by UTL-5g and PLE were incubated at 25 °C. At predetermined time points, individual ...

  5. Cytotoxic action of triterpene glycosides from sea cucumbers from the genus Cucumaria on mouse spleen lymphocytes. Inhibition of nonspecific esterase.

    Science.gov (United States)

    Aminin, Dmitry L; Silchenko, Alexandra S; Avilov, Sergey A; Stepanov, Vadim G; Kalinin, Vladimir I

    2009-06-01

    Four triterpene glycosides from sea cucumbers belonging to the genus Cucumaria, okhotoside A(1)-1 (1), cucumarioside A(0)-1 (2), frondoside A (3) and cucumarioside A(2)-2 (4) inhibit the activity of nonspecific esterase of mouse spleen lymphocytes. The dependence of the inhibitory activity of the glycosides on their structure is similar to that for hemolytic activity. The absence of inhibitory activity for the preparation Cumaside, which is a complex of cucumarioside A(2)-2 and related compounds with cholesterol, shows a cholesterol-dependent character of the inhibitory action of the glycosides. The effective inhibitory concentrations of frondoside A and cucumarioside A(2)-2 are significantly higher than the immunomodulatory doses of these glycosides. PMID:19634320

  6. 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. PMID:27173527

  7. Glucuronoyl Esterase Screening and Characterization Assays Utilizing Commercially Available Benzyl Glucuronic Acid Ester

    Directory of Open Access Journals (Sweden)

    Hampus Sunner

    2015-09-01

    Full Text Available Research on glucuronoyl esterases (GEs has been hampered by the lack of enzyme assays based on easily obtainable substrates. While benzyl d-glucuronic acid ester (BnGlcA is a commercially available substrate that can be used for GE assays, several considerations regarding substrate instability, limited solubility and low apparent affinities should be made. In this work we discuss the factors that are important when using BnGlcA for assaying GE activity and show how these can be applied when designing BnGlcA-based GE assays for different applications: a thin-layer chromatography assay for qualitative activity detection, a coupled-enzyme spectrophotometric assay that can be used for high-throughput screening or general activity determinations and a HPLC-based detection method allowing kinetic determinations. The three-level experimental procedure not merely facilitates routine, fast and simple biochemical characterizations but it can also give rise to the discovery of different GEs through an extensive screening of heterologous Genomic and Metagenomic expression libraries.

  8. Characterisation of esterase genes in the genomes of Streptomyces coelicolor A3(2) and Streptomyces avermitilis

    OpenAIRE

    Soror, Sameh

    2007-01-01

    Esterases and lipases are widely used as industrial enzymes and for the synthesis of chiral drugs. Because of their rich secondary metabolism, Streptomyces species offer a relatively untapped source of interesting esterases and lipases. S. coelicolor and S. avermitilis contain 51 genes annotated as esterases and/or lipases. In this study I have cloned 14 different genes encoding for lipolytic enzymes from S. coelicolor (11 genes) and S. avermitilis (four genes). Some of these genes were over-...

  9. Inter-conversion of catalytic abilities in a bifunctional carboxyl/feruloyl-esterase from earthworm gut metagenome.

    Science.gov (United States)

    Vieites, José María; Ghazi, Azam; Beloqui, Ana; Polaina, Julio; Andreu, José M; Golyshina, Olga V; Nechitaylo, Taras Y; Waliczek, Agnes; Yakimov, Michail M; Golyshin, Peter N; Ferrer, Manuel

    2010-01-01

    Carboxyl esterases (CE) exhibit various reaction specificities despite of their overall structural similarity. In present study we have exploited functional metagenomics, saturation mutagenesis and experimental protein evolution to explore residues that have a significant role in substrate discrimination. We used an enzyme, designated 3A6, derived from the earthworm gut metagenome that exhibits CE and feruloyl esterase (FAE) activities with p-nitrophenyl and cinnamate esters, respectively, with a [(k(cat)/K(m))](CE)/[(k(cat)/K(m))](FAE) factor of 17. Modelling-guided saturation mutagenesis at specific hotspots (Lys(281), Asp(282), Asn(316) and Lys(317)) situated close to the catalytic core (Ser(143)/Asp(273)/His(305)) and a deletion of a 34-AA-long peptide fragment yielded mutants with the highest CE activity, while cinnamate ester bond hydrolysis was effectively abolished. Although, single to triple mutants with both improved activities (up to 180-fold in k(cat)/K(m) values) and enzymes with inverted specificity ((k(cat)/K(m))(CE)/(k(cat)/K(m))(FAE) ratio of ∼0.4) were identified, no CE inactive variant was found. Screening of a large error-prone PCR-generated library yielded by far less mutants for substrate discrimination. We also found that no significant changes in CE activation energy occurs after any mutation (7.3 to -5.6 J mol(-1)), whereas a direct correlation between loss/gain of FAE function and activation energies (from 33.05 to -13.7 J mol(-1)) was found. Results suggest that the FAE activity in 3A6 may have evolved via introduction of a limited number of 'hot spot' mutations in a common CE ancestor, which may retain the original hydrolytic activity due to lower restrictive energy barriers but conveys a dynamic energetically favourable switch of a second hydrolytic reaction. PMID:21255305

  10. Risk and preventive factors of low-dose aspirin-induced gastroduodenal injuries: a comprehensive review.

    Science.gov (United States)

    Shiotani, Akiko; Manabe, Noriaki; Kamada, Tomoari; Fujimura, Yoshinori; Sakakibara, Takashi; Haruma, Ken

    2012-04-01

    The risk of peptic ulcer complications, particularly bleeding, is increased in association with the use of low-dose aspirin (LDA). Risk factors for upper gastrointestinal (GI) ulcer or bleeding among LDA users include a history of prior GI events, older age, chronic renal failure, combined antithrombotic therapy and nonsteroidal anti-inflammatory drugs (NSAIDs). Helicobacter pylori and aspirin seem to be independent risk factors for peptic ulcer and bleeding. The studies report conflicting findings about the effect of H. pylori infection on NSAID-related ulcers, and proton-pump inhibitors (PPIs) seem to be superior to eradication only to prevent recurrent ulcer bleeding with LDA. Previous studies indicate that hypoacidity related to corpus atrophy, as well as taking PPIs and co-treatment with angiotensin type 1 receptor blockers (ARBs) and statins seem to reduce peptic ulcer among LDA users. In addition, the interleukin-1β (IL-1β)-511 T allele and angiotensinogen (AGT)-20 CC, which work as the high-producer allele of IL-1β and AGT, are significantly associated with ulcer or ulcer bleeding. The SLCO1B1*1b haplotype, which has the highest transport activity, may diminish the preventive effect of statins or ARBs. The data are still lacking and further prospective studies are needed to identify the specific risk or protective factors for upper GI ulcer and its complications associated with LDA. PMID:22486865

  11. Expression and characterization of a new esterase with GCSAG motif from a permafrost metagenomic library.

    Science.gov (United States)

    Petrovskaya, Lada E; Novototskaya-Vlasova, Ksenia A; Spirina, Elena V; Durdenko, Ekaterina V; Lomakina, Galina Yu; Zavialova, Maria G; Nikolaev, Evgeny N; Rivkina, Elizaveta M

    2016-05-01

    As a result of construction and screening of a metagenomic library prepared from a permafrost-derived microcosm, we have isolated a novel gene coding for a putative lipolytic enzyme that belongs to the hormone-sensitive lipase family. It encodes a polypeptide of 343 amino acid residues whose amino acid sequence displays maximum likelihood with uncharacterized proteins from Sphingomonas species. A putative catalytic serine residue of PMGL2 resides in a new variant of a recently discovered GTSAG sequence in which a Thr residue is replaced by a Cys residue (GCSAG). The recombinant PMGL2 was produced in Escherichia coli cells and purified by Ni-affinity chromatography. The resulting protein preferably utilizes short-chain p-nitrophenyl esters (C4 and C8) and therefore is an esterase. It possesses maximum activity at 45°C in slightly alkaline conditions and has limited thermostability at higher temperatures. Activity of PMGL2 is stimulated in the presence of 0.25-1.5 M NaCl indicating the good salt tolerance of the new enzyme. Mass spectrometric analysis demonstrated that N-terminal methionine in PMGL2 is processed and cysteine residues do not form a disulfide bond. The results of the study demonstrate the significance of the permafrost environment as a unique genetic reservoir and its potential for metagenomic exploration. PMID:26929439

  12. Characteristics of pancreatic cholesterol esterase binding to and uptake by rat intestinal cells

    International Nuclear Information System (INIS)

    In the intestinal lumen cholesterol esterase derived from pancreatic juice catalyzes the hydrolysis of cholesteryl esters (CE). The characteristics of Ce'ase binding to and uptake by rat intestinal cells were determined. CE'ase purified from rat pancreas with a specific activity 2 fold higher and a yield 5 fold greater than that previously attainable was judged as homogeneous on the basis of SDS-PAGE and sedimentation equilibrium centrifugation. Intestinal cell types and membranes were isolated and judged as pure on the basis of marker enzyme analyses. The enzyme was radiolabeled with [125-I] to a specific radioactivity of 55 Ci/mmole with retention of biological activity, gross molecular size, secondary structure, and immunological properties. [125-I] CE'ase bound preferentially to mature absorptive cells from proximal intestine and their brush border membranes. A specific, low affinity binding phenomenon was demonstrated with the following characteristics: linearity with increasing ligand concentration (non-saturability) or cell concentration, time and temperature dependency, and irreversibility. Native CE'ase, at a 500 fold molar excess did not displace bound [125-I] CE'ase

  13. Salicylic acid: a link between aspirin, diet and the prevention of colorectal cancer.

    Science.gov (United States)

    Paterson, J R; Lawrence, J R

    2001-08-01

    Aspirin was introduced into clinical practice more than 100 years ago. This unique drug belongs to a family of compounds called the salicylates, the simplest of which is salicylic acid, the principal metabolite of aspirin. Salicylic acid is responsible for the anti-inflammatory action of aspirin, and may cause the reduced risk of colorectal cancer observed in those who take aspirin. Yet salicylic acid and other salicylates occur naturally in fruits and plants, while diets rich in these are believed to reduce the risk of colorectal cancer. Serum salicylic acid concentrations are greater in vegetarians than non-vegetarians, and there is overlap between concentrations in vegetarians and those taking low-dose aspirin. We propose that the cancer-preventive action of aspirin is due to its principal metabolite, salicylic acid, and that dietary salicylates can have the same effect. It is also possible that natural salicylates contribute to the other recognized benefits of a healthy diet. PMID:11493722

  14. Risk analysis for aspirin and postoperative intracranial hemorrhage - report of 3 cases

    Institute of Scientific and Technical Information of China (English)

    YU Shu-qing; WANG Ji-sheng; JI Nan; LIU Wei; QIAN Ke

    2009-01-01

    @@ Aspirin has been widely used clinically since 1899.For patients with cerebral ischemia and implanted intravascular stents, aspirin has been used routinely for prevention of intracranial hemorrhage and for anticoagulation treatment. However, many multi-center,large sample, controlled studies have shown that aspirin may actually increase the risk of spontaneous cerebral hemorrhage, and that aspirin was an independent predictor of death shortly after cerebral hemorrhage. Here we report a case series, between July 1 2006 and January 1 2008, of 3 patients who experienced postoperative intracranial hemorrhage after receiving regular aspirin treatment before surgery in the Center of Neurosurgery,Beijing Tiantan Hospital, Capital Medical University.Two of them died. There were 86 patients in all receiving regular aspirin treatment before surgery in the same period. The incidence of intracranial hemorrhage in this group is 3.49%.

  15. Aspirin vs Heparin for the Prevention of Preeclampsia.

    Science.gov (United States)

    Katsi, Vasiliki; Kanellopoulou, Theoni; Makris, Thomas; Nihoyannopoulos, Petros; Nomikou, Efrosyni; Tousoulis, Dimitrios

    2016-07-01

    Preeclampsia is a hypertensive disorder of pregnancy that remains a significant cause of maternal morbidity and mortality worldwide. Preeclampsia can be resolved by delivery, and most of the proposed preventive treatment approaches are based on processes involved in placental development in early pregnancy. Yet, none of these has been established in clinical practice. Low-dose aspirin is the most promising candidate, nevertheless; while some individual randomized controlled trials showed minimal or no statistically significant benefit, recent metanalyses showed that early initiation before 16 weeks of gestation is associated with prevention of early-onset preeclampsia and reduction in prevalence of perinatal death or morbidity of pregnant women. Heparin could be an alternative antithrombotic and anti-inflammatory median to prevent preeclampsia either alone or in combination with aspirin; however, results are conflicting concerning efficacy. PMID:27251704

  16. 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.

  17. Carboxylesterase1/Esterase-x regulates chylomicron production in mice.

    Directory of Open Access Journals (Sweden)

    Ariel D Quiroga

    Full Text Available Elevated postprandial plasma triacylglycerol (TG concentrations are commonly associated with obesity and the risk of cardiovascular disease. Dietary fat contributes to this condition through the production of chylomicrons. Carboxylesterases have been mainly studied for their role in drug metabolism, but recently they have been shown to participate in lipid metabolism; however, their role in intestinal lipid metabolism is unknown. Carboxylesterase1/esterase-x (Ces1/Es-x deficient mice become obese, hyperlipidemic and develop hepatic steatosis even on standard chow diet. Here, we aimed to explore the role of Ces1/Es-x in intestinal lipid metabolism. Six-month old wild-type and Ces1/Es-x deficient mice were maintained on chow diet and intestinal lipid metabolism and plasma chylomicron clearance were analyzed. Along the intestine Ces1/Es-x protein is expressed only in proximal jejunum. Ablation of Ces1/Es-x expression results in postprandial hyperlipidemia due to increased secretion of chylomicrons. The secreted chylomicrons have aberrant protein composition, which results in their reduced clearance. In conclusion, Ces1/Es-x participates in the regulation of chylomicron assembly and secretion. Ces1/Es-x might act as a lipid sensor in enterocytes regulating chylomicron secretion rate. Ces1/Es-x might represent an attractive pharmacological target for the treatment of lipid abnormalities associated with obesity, insulin resistance and fatty liver disease.

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

    OpenAIRE

    P. Marson; Pasero, G

    2011-01-01

    The discovery of aspirin, an antipyretic, anti-inflammatory and analgesic drug, undoubtedly represents a milestone in the history of medical therapy. Since ancient times the derivatives of willow (Salix alba) were used to treat a variety of fevers and pain syndromes, although the first report dates back to 1763 when the English Reverend Edward Stone described the effect of an extract of the bark willow in treating malaria. In the XIX century many apothecaries and chemists, including the Itali...

  19. Aspirin in Cardiovascular and Cerebrovascular Events: Does Market Failure Matter?

    OpenAIRE

    Roger Lee Mendoza

    2010-01-01

    Problem statement: Against the backdrop of the 2009 scientific studies qualifying the cardiovascular and cerebrovascular benefits of aspirin, two interrelated questions are raised for investigation in this study. First, why may the government intervene in an otherwise private transaction between physician and patient and between drug manufacturer and buyer, when it involves contentious pharmacological information? Second, does government intervention make a difference in what these transactin...

  20. Aspirin in Cardiovascular and Cerebrovascular Events: Does Market Failure Matter?

    Directory of Open Access Journals (Sweden)

    Roger Lee Mendoza

    2010-01-01

    Full Text Available Problem statement: Against the backdrop of the 2009 scientific studies qualifying the cardiovascular and cerebrovascular benefits of aspirin, two interrelated questions are raised for investigation in this study. First, why may the government intervene in an otherwise private transaction between physician and patient and between drug manufacturer and buyer, when it involves contentious pharmacological information? Second, does government intervention make a difference in what these transacting parties would otherwise have chosen to do in its absence? Approach: An Internet literature search was performed, using query term combinations, to identify relevant aspirin studies. The search yielded 61 juried publications that met our predetermined criteria for inclusion and thematic analysis. Results: Variance exists within the mix of economic and non-economic literature on aspirin information regulation. The study identified 4 instances of market failure that offer some of the most compelling theoretical and practical considerations for public policy intervention in the context of the 2009 findings. However, there is also indication that the sense of increased protection arising from safety regulations could stimulate risky behavior that nullifies their net protective effects or benefits. Conclusion: It is not clear either from the surveyed literature or existing economic theory if, ceteris paribus, regulated information alters or modifies the marginal propensity of a physician to recommend, and a patient to consume, aspirin to prevent cardiovascular and cerebrovascular events, particularly heart attacks, strokes and vascular death. The study suggests the need for policy reinforcements to safety information, if market failures are to be efficiently addressed and risk compensating behavior reduced.

  1. Aspirin treatment exacerbates oral infections by Trypanosoma cruzi.

    Science.gov (United States)

    Cossentini, Luana Aparecida; Da Silva, Rosiane Valeriano; Yamada-Ogatta, Sueli Fumie; Yamauchi, Lucy Megumi; De Almeida Araújo, Eduardo José; Pinge-Filho, Phileno

    2016-05-01

    Oral transmission of the protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas disease, has been documented in Latin American countries. The reported cases of infection were due to the ingestion of contaminated fresh fruit, juices, or sugar cane juice. There have been few studies on the physiopathology of the disease in oral transmission cases. Gastritis is a common ailment that can be caused by poor dietary habits, intake of alcohol or other gastric irritants, bacterial infection, or by the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs). This study investigated in a mouse model whether gastric mucosal injury, induced by aspirin, would affect the course of disease in animals infected with T. cruzi by the oral route. The CL14 and G strains of T. cruzi, both of low infectivity, were used. To this end, groups of BALB/c mice were treated during 5 days with aspirin (100 mg kg(-1)) before oral infection with T. cruzi metacyclic forms (4 × 10(5) or 5 × 10(7) parasites/mouse). Histological analysis and determination of nitric oxide and TNF-α were performed in gastric samples obtained 5 days after infection. Parasitemia was monitored from the thirteenth day after infection. The results indicate that aspirin treatment of mice injured their gastric mucosa and facilitated invasion by both CL14 and G strains of T. cruzi. Strain CL14 caused more severe infection compared to the G strain, as larger numbers of amastigote nests were found in the stomach and parasitemia levels were higher. Our study is novel in that it shows that gastric mucosal damage caused by aspirin, a commonly used NSAID, facilitates T. cruzi infection by the oral route. PMID:26826555

  2. Anti-thrombotic effects of a nitric oxide-releasing, gastric-sparing aspirin derivative.

    OpenAIRE

    Wallace, J. L.; McKnight, W; del Soldato, P; Baydoun, A. R.; Cirino, G

    1995-01-01

    Effects of a nitroxybutylester derivative of aspirin (NCX 4215) on platelet aggregation and prostanoid synthesis were compared to the effects of aspirin. NCX 4215 was approximately seven times more potent than aspirin as an inhibitor of thrombin-induced human platelet aggregation in vitro, but did not inhibit platelet thromboxane synthesis or gastric prostaglandin synthesis. NCX 4215 released nitric oxide when incubated in the presence of platelets and increased platelet levels of cGMP within...

  3. Selective Cumulative Inhibition of Platelet Thromboxane Production by Low-dose Aspirin in Healthy Subjects

    OpenAIRE

    Patrignani, Paola; Filabozzi, Paola; Patrono, Carlo

    1982-01-01

    Acetylation of platelet cyclooxygenase by oral aspirin is dose dependent and cumulative with repeated administration. However, no single dose of aspirin has been found to be completely selective of platelet thromboxane (TX) synthesis inhibition in man. We determined the dose dependence, cumulative nature and selectivity of aspirin effects on platelet TXB2 and renal prostaglandin (PG) and prostacyclin (PGI2) production. We measured, by radioimmunoassay, serum TXB2 levels after whole blood clot...

  4. New Perspectives on Aspirin and the Endogenous Control of Acute Inflammatory Resolution

    OpenAIRE

    Thea Morris; Melanie Stables; Gilroy, Derek W.

    2006-01-01

    Aspirin is unique among the nonsteroidal anti-inflammatory drugs in that it has both anti-inflammatory as well as cardio-protective properties. The cardio-protective properties arise form its judicious inhibition of platelet-derived thromboxane A2 over prostacyclin, while its anti-inflammatory effects of aspirin stem from its well-established inhibition of prostaglandin (PG) synthesis within inflamed tissues. Thus aspirin and the other NSAIDs have popularised the notion of inhibiting PG biosy...

  5. Aspirin induces nitric oxide release from vascular endothelium: a novel mechanism of action

    OpenAIRE

    Taubert, D.; Berkels, R; Grosser, N.; Schröder, H; Gründemann, D; Schömig, E

    2004-01-01

    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.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.Luminal NO release was monitored in real time on dissected porcine coron...

  6. Low-Dose Aspirin for Prevention of Cardiovascular Disease in Patients with Chronic Kidney Disease

    OpenAIRE

    Kim, Ae Jin; Lim, Hye Jin; Ro, Han; Ko, Kwang-Pil; Han, Song Yi; Chang, Jae Hyun; Lee, Hyun Hee; Chung, Wookyung; Jung, Ji Yong

    2014-01-01

    Background Chronic kidney disease (CKD) is a major risk factor for the development of cardiovascular disease (CVD). Previous trials have investigated the effects of low-dose aspirin on CVD prevention in patients with diabetes; however, patients with CKD were not examined. The role of aspirin in diabetics is controversial, and the available literature is contradictory. Therefore, we studied whether low-dose aspirin would be beneficial for patients with CKD, a group that is at high risk for CVD...

  7. Estimates of benefits and harms of prophylactic use of aspirin in the general population

    OpenAIRE

    Cuzick, J; Thorat, M. A.; Bosetti, C; Brown, P H; Burn, J.; Cook, N. R.; Ford, L. G.; Jacobs, E. J.; Jankowski, J.A.; La Vecchia, C.; Law, M.; Meyskens, F.; Rothwell, P.M.; Senn, H. J.; Umar, A.

    2014-01-01

    Background: Accumulating evidence supports an effect of aspirin in reducing overall cancer incidence and mortality in the general population. We reviewed current data and assessed the benefits and harms of prophylactic use of aspirin in the general population. Methods: The effect of aspirin for site-specific cancer incidence and mortality, cardiovascular events was collated from the most recent systematic reviews. Studies identified through systematic Medline search provided data regarding ha...

  8. Profile and prevalence of aspirin resistance in patients with metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    Zhaoping Liu; Yang Yu; Yuanjie Mao; Xinhua Wang; Jianzhong Wang; Yong Huo

    2008-01-01

    Objective Aspirin has been used extensively in primary and secondary prevention of cardiovascular disease,particularly for subjects at high risk such as metabolic syndrome.However,the responsiveness to aspirin treatment may vary among individuals.The present study was conducted to investigate the profile and prevalence of aspirin resistance in patients with metabolic syndrome.Methods In 221 consecutive patients,platelet aggregation induced by arachidonic acid (0.5mg/ml) was assessed after 10 days of aspirin treatment (200mg/d).Aspirin resistance was defined as mean optical platelet aggregation =20%.Results Aspirin resistance occurred in 39 patients (17.6%).Serum fibrinogen level was higher in patients with than in those without aspirin resistance (2.6_+0.4g/l vs 2.4±0.4g/L,P=0.017).The 2 groups,aspirin resistance group and no aspirin resistance group,did not differ significantly,with regard to gender,age,body mass index,waist-hip ratio,blood pressure level,serum cholesterol level and history of myocardial or cerebral infarction.Multivariate logistic regression analysis revealed that only serum fibrinogen level entered the model (odds ratio 2.973,p=0.023).Subgroup analysis further showed that aspirin resistance occurred more in male patients with myocardial infarction (50% vs14.5%,P=0.02) and in female patients with diastolic blood pressure=85mmHg (34% vs 15.5%,P=0.043).But after multifactor logistic regression,in women blood pressure=85mmHg was not a predictor any more.Conclusions In patients with metabolic syndrome,aspirin resistance is not uncommon,especially for men with history of myocardial infarction.Patients with aspirin resistance have an increased serum fibrinogen level.(J Geriatr Cardio12008;5:7-10)

  9. Aspirin versus warfarin in atrial fibrillation: decision analysis may help patients' choice.

    LENUS (Irish Health Repository)

    Romero-Ortuno, Roman

    2012-03-01

    the primary prevention of ischaemic stroke in chronic non-valvular atrial fibrillation (AF) typically involves consideration of aspirin or warfarin. CHA(2)DS(2)-VASc estimates annual stroke rates for untreated AF patients, which are reduced by 60% with warfarin and by 20% with aspirin. HAS-BLED estimates annual rates of major bleeding on warfarin. The latter risk with aspirin is 0.5-1.2% per year.

  10. Effect of allopurinol, sulphasalazine, and vitamin C on aspirin induced gastroduodenal injury in human volunteers.

    OpenAIRE

    McAlindon, M E; Muller, A F; Filipowicz, B; Hawkey, C J

    1996-01-01

    BACKGROUND--The mechanisms of aspirin induced gastroduodenal injury are not fully understood. Aspirin induces the release of reactive oxygen metabolites in animal models, which may contribute to mucosal injury. AIMS--To investigate the effects of aspirin administered with placebo or antioxidants on gastric mucosal reactive oxygen metabolite release and gastroduodenal injury in human volunteers. SUBJECTS--Fourteen healthy volunteers participated in the study (seven male; mean age 27 years, ran...

  11. Critical appraisal of a fixed combination of esomeprazole and low dose aspirin in risk reduction

    OpenAIRE

    Vachhani, Ravi; Bouhaidar, Doumit; Zfass, Alvin; Sandhu, Bimaljit; Nawras, Ali

    2010-01-01

    Low dose aspirin (≤325 mg) is routinely used for primary and secondary prophylaxis of cardiovascular and cerebrovascular events. The use of low dose aspirin is associated with two- to four-fold greater risk of symptomatic or complicated peptic ulcers. Risk factors associated with low dose aspirin induced gastrointestinal toxicity includes prior history of ulcer or upper gastrointestinal (GI) bleeding, concomitant use of other nonsteroidal anti-inflammatory drugs, corticosteroid or warfarin, d...

  12. Interactions of aspirin and other potential etiologic factors in an animal model of Reye syndrome.

    OpenAIRE

    Deshmukh, D.R.; Maassab, H. F.; Mason, M.

    1982-01-01

    Recent studies of Reye syndrome (RS) patients have suggested aspirin treatment as a possible factor in the etiology of this often fatal childhood disorder. the relationship of aspirin treatment to other factors that have been strongly implicated (influenza, ammonia toxicity) cannot be examined directly in patients because aspirin treatment is usually initiated by family members in the prodromal period before RS is diagnosed. In this report we describe the use of an animal model for RS in exam...

  13. Cancers prevented in Australia in 2010 through the consumption of aspirin

    OpenAIRE

    Wilson, Louise F.; Green, Adele C.; Kendall, Bradley J; Jordan, Susan J.; Nagle, Christina M; Bain, Christopher J; Neale, Rachel E; Whiteman, David C

    2015-01-01

    Objectives To estimate the proportion and number of cancers in Australia in 2010 that may have been prevented from occurring due to daily use of aspirin in the population. Methods We calculated the Prevented Fraction (PF) of colorectal and oesophageal cancers using standard formulae. The PF is the proportion of the hypothetical total load of cancer in the population that was prevented by exposure to aspirin. The formula incorporates estimates of the prevalence of aspirin use in Australian adu...

  14. Association of regular aspirin use and breast cancer risk.

    Science.gov (United States)

    Swede, Helen; Mirand, Amy L; Menezes, Ravi J; Moysich, Kirsten B

    2005-01-01

    Of the limited number of epidemiological investigations on aspirin (and other nonsteroidal anti-inflammatory drugs) and breast cancer, the majority observe a protective role, yet only a few report dose-response effects for frequency or duration of use. We studied aspirin use among 1,478 breast cancer patients diagnosed from 1982 to 1998, and 3,383 cancer-free hospital controls at the Roswell Park Cancer Institute. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Compared to never use,both regular (> or =1 tablet per week for > or =1 year) and occasional use were inversely associated with breast cancer (adjusted OR = 0.84, 95% CI 0.64-0.97; adjusted OR = 0.80, 95% CI 0.67-0.96, respectively). Among regular users, an inverse trend was found for number of tablets consumed per week (1, 2-6, or > or =7) with corresponding ORs of 0.95, 0.80, and 0.74 (P(trend) = 0.01). Daily use spanning 10 or more years was associated with a more pronounced reduction in risk (P(trend) = 0.005). Our findings corroborate the growing body of observational evidence that regular aspirin use may be associated with reduced risk of breast cancer. PMID:15802928

  15. Phytoremediation of aspirin and tetracycline by Brassica juncea.

    Science.gov (United States)

    Gahlawat, Sonal; Gauba, Pammi

    2016-09-01

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

  16. Slow release delivery of rioprostil by an osmotic pump inhibits the formation of acute aspirin-induced gastric lesions in dogs and accelerates the healing of chronic lesions without incidence of side effects.

    Science.gov (United States)

    Katz, L B; Shriver, D A

    1989-10-01

    Rioprostil, a primary alcohol prostaglandin E1 analog, inhibits gastric acid secretion and prevents gastric lesions induced by a variety of irritants in experimental animals. Because rioprostil is relatively short-acting, it would be of significant benefit clinically if its duration of action could be extended to allow once daily dosing. This investigation demonstrates that when administered via an osmotically driven pump (Osmet, Alza Corp.), rioprostil prevents the acute effects of aspirin on the gastric mucosa of dogs, accelerates the healing of aspirin-induced gastric lesions, and heals preexisting aspirin-induced gastric lesions during chronic administration of aspiring. The potency of rioprostil against acute gastric lesion formation was greatest when delivered from a 24-hr release pump (ED50 = 0.77 micrograms/kg/24 hr) and was 37 times greater than when administered as a single oral bolus. In addition, this activity occurred at doses which had little or no gastric antisecretory activity in betazole-stimulated Heidenhain pouch dogs. When delivered from a 24-hr pump, rioprostil (100 micrograms/kg/24 hr) healed preexisting aspirin-induced gastric lesions within 8 days after removal of aspirin, or after 15 days during continued daily aspirin administration. Additional studies determined that administration of rioprostil at doses of 720, 1440, or 2160 micrograms/kg/24 hr (935-2805 times the gastroprotective ED50 in 24 hr pumps) was well tolerated, with only slight, transient increases in body temperature, softening of the stools, and mild sedation at the highest dose. Administration of rioprostil daily for 5 days at 960 micrograms/kg/24 hr from 24-hr release pumps was also well tolerated by all dogs with no evidence of any accumulation of effect of rioprostil. In summary, administration of rioprostil via an osmotic pump increases its potency and duration of action against the gastric lesion-inducing effect of aspirin, and maintains a wide ratio of safety. PMID

  17. Phospho-aspirin (MDC-22) inhibits breast cancer in preclinical animal models: an effect mediated by EGFR inhibition, p53 acetylation and oxidative stress

    International Nuclear Information System (INIS)

    The anticancer properties of aspirin are restricted by its gastrointestinal toxicity and its limited efficacy. Therefore, we synthesized phospho-aspirin (PA-2; MDC-22), a novel derivative of aspirin, and evaluated its chemotherapeutic and chemopreventive efficacy in preclinical models of triple negative breast cancer (TNBC). Efficacy of PA-2 was evaluated in human breast cancer cells in vitro, and in orthotopic and subcutaneous TNBC xenografts in nude mice. Mechanistic studies were also carried out to elucidate the mechanism of action of PA-2. PA-2 inhibited the growth of TNBC cells in vitro more potently than aspirin. Treatment of established subcutaneous TNBC xenografts (MDA-MB-231 and BT-20) with PA-2 induced a strong growth inhibitory effect, resulting in tumor stasis (79% and 90% inhibition, respectively). PA-2, but not aspirin, significantly prevented the development of orthotopic MDA-MB-231 xenografts (62% inhibition). Mechanistically, PA-2: 1) inhibited the activation of epidermal growth factor receptor (EGFR) and suppressed its downstream signaling cascades, including PI3K/AKT/mTOR and STAT3; 2) induced acetylation of p53 at multiple lysine residues and enhanced its DNA binding activity, leading to cell cycle arrest; and 3) induced oxidative stress by suppressing the thioredoxin system, consequently inhibiting the activation of the redox sensitive transcription factor NF-κB. These molecular alterations were observed in vitro and in vivo, demonstrating their relevance to the anticancer effect of PA-2. Our findings demonstrate that PA-2 possesses potent chemotherapeutic efficacy against TNBC, and is also effective in its chemoprevention, warranting further evaluation as an anticancer agent

  18. Membrane Permeable Esterase–Activated Fluorescent Imaging Probe

    OpenAIRE

    Kim, Youngmi; Choi, Yongdoo; Weissleder, Ralph; Tung, Ching-Hsuan

    2007-01-01

    An esterase-triggered probe 2 derived from a cyanine-based pH sensitive dye was developed for cell labeling. Permeation of probe 2 into cells and subsequent hydrolytic activation by cellular esterases result in a bright fluorescent intracellular signal.

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

    Science.gov (United States)

    Czernichow, Pierre; Merle, Véronique

    2004-04-01

    Low-dose aspirin (myocardial infarction or ischemic stroke. Six to 12% of the general population is exposed to low-dose aspirin. The most frequently studied digestive complications are bleeding peptic ulcers, whose risk is increased twofold by low-dose aspirin treatment, and non-complicated peptic ulcers. History of bleeding or non-complicated peptic ulcer, alcohol intake, concomitant treatment with NSAID or calcic inhibitors are demonstrated risk factors of bleeding ulcer associated with low-dose aspirin. The role of enteric coating, of low-dose aspirin dose, of delay since low-dose aspirin treatment onset, and of Helicobacter pylori infection, remains controversial. Antisecretory drugs (H2 inhibitors, proton pump inhibitors), and nitroglycerin are associated with a decreased risk of bleeding ulcer. The protective effect of COX-2 inhibitors on the risk of bleeding ulcer is suppressed by concomitant treatment with low-dose aspirin. The risk of no- complicated peptic ulcer was increased by low-dose aspirin intake by a factor 2.9 in one study. Low-dose aspirin dose, infection by Helicobacter pylori, NSAID intake, and absence of enteric coating, are possible risk factors for non-complicated peptic ulcer. No association was retrieved with alcohol intake and peptic ulcer history. PMID:15366673

  20. Effect of aspirin on DNA damage induced by MMC in Drosophila.

    Science.gov (United States)

    Niikawa, Miki; Nagase, Hisamitsu

    2007-06-01

    In our previous paper, we found that aspirin suppressed the genotoxicity of mitomycin C (MMC) in a somatic mutation and recombination test (SMART) in Drosophila melanogaster. In order to reveal the mechanism of antigenotoxicity of aspirin, we evaluated the protective effects of aspirin against the genotoxicity of MMC with the DNA repair test in Drosophila melanogaster. Three types of treatment of aspirin were performed as co-, post- and pre-treatment. Aspirin co-treatment suppressed effectively the genotoxicity of MMC in a dose-dependent manner and the sex ratio at a dose of aspirin 10mg/bottle elevated from 0.01 (without aspirin) to 0.65 at sc z(1) w(+(TE)) mei-9(a) mei-41(D5)/-C(1)DX, y f [mei-9 mei-41, Rec(-) male.Rec(+) female] consists of DNA repair-deficient (Rec(-)) males and -proficient (Rec(+)) females. The antigenotoxic effect of aspirin on [mei-41, Rec(-) male.Rec(+) female] was similar to that on [mei-9, Rec(-) male.Rec(+) female]. But post- and pre-treatment by aspirin did not affect the genotoxicity of MMC on [mei-9 mei-41, Rec(-) male.Rec(+) female]. PMID:17336029

  1. Aspirin as a risk factor for hemorrhage in patients with head injuries.

    Science.gov (United States)

    Reymond, M A; Marbet, G; Radü, E W; Gratzl, O

    1992-01-01

    The role of aspirin as a risk factor in the occurrence of intracranial bleeding following head injury was investigated. Chronic subdural hematoma appears to be a suitable model for the evaluation of risk factors in the development of hemorrhage. The most common risk factors found in our study were, apart from age, chronic alcohol abuse (28%), consumption of cumarin-derivates (21%), aspirin (13%), and heparin (5%). A patient undergoing aspirin treatment must be considered at risk of development of chronic subdural hematoma. Aspirin should not be prescribed to patients with post-traumatic headaches. PMID:1584433

  2. The effects of aspirin plus cisplatin on SGC7901/CDDP cells in vitro.

    Science.gov (United States)

    Dong, Hanzhang; Liu, Gaogao; Jiang, Biao; Guo, Jiubing; Tao, Guoquan; Yiu, Wei; Zhou, Jingsong; Li, Guoxin

    2014-05-01

    The purpose of this study was to determine the effect of aspirin plus cisplatin (CDDP) in the chemotherapy of gastric cancer. We cultured SGC7901/CDDP cells by long-term exposure of SGC7901 cells to small doses of CDDP in vitro. The cells were treated with aspirin, CDDP or aspirin plus CDDP for 24 h and cell growth was assessed by the MTT assay, the apoptotic rate by flow cytometry, the survivin mRNA expression by RT-PCR and the survivin protein expression by western blotting. The results revealed that the cell growth in the aspirin plus CDDP group was significantly inhibited. The apoptotic rate in the aspirin plus CDDP was significantly higher compared to that in the other groups. The survivin mRNA and protein expression were also significantly reduced in the aspirin plus CDDP group. Our data suggest that the combination of aspirin and CDDP exhibited a higher degree of toxicity against SGC7901/CDDP cells compared to that of aspirin or CDDP alone. Thus, the combination of aspirin plus CDDP may reduce the expression of survivin and induce the apoptosis of SGC7901/CDDP cells. PMID:24748972

  3. Carboxylic Esterase and Its Associations With Long-term Effects of Organophosphorus Pesticides

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To examine a) the effect of organophosphorus pesticide exposure on activity of carboxylic esterases, namely butyrylcholinesterase (BChE), carboxylesterase (CarbE) and paraoxonase (PonE); and b) the association of polymorphisms of BChE and PonE with individual genetic susceptibility to organophosphorus pesticide exposure. Methods A cross-sectional study was conducted in 75 workers exposed to organophosphorus pesticides and 100 non-exposed controls. The serum activity of these enzymes was measured. Variant forms of BCHE-K, PON-192, and PON-55 were detected. A symptom score was developed as a proxy measure of clinical outcomes. Results Activities of both BChE and CarbE were lower in exposed exposed workers with BCHE-K genotype UU (61 cases), genotype UK (12 cases) and genotype KK (2 cases) was 105.05, 84.42 activity in the exposed workers with PON-192 genotype BB (37), genotype AB (27) and genotype AA (11) was 116.8, 91.2, and 9.20. The symptom score was the highest in individuals with abnormal homozygote for each of the three gene loci. Conclusions Long-term exposure to organophosphorus pesticides can inhibit BChE and CarbE activity, but exerts no inhibitory effect on PonE activity. Different genotypes of BCHE-K, PON-192, and PON-55 may be related to the severity of adverse health effects of organophosphorus pesticide exposure. Implications of potentially higher susceptibility of workers with mutant homozygotes should be evaluated to reduce health risks.

  4. Low dose aspirin therapy and renal function in elderly patients

    Directory of Open Access Journals (Sweden)

    Akinwusi PO

    2013-01-01

    Full Text Available Patience Olayinka Akinwusi,1,2 Rotimi Oluyombo,2 Paul Sunday Ogunro,3 Adetunji Oladeni Adeniji,4 Oluyomi Olusola Okunola,5 Olugbenga Edward Ayodele21Department of Medicine, Osun State University, Osogbo, Osun State, Nigeria; 2Department of Medicine, LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria; 3Department of Chemical Pathology, LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria; 4Department of Obstetrics and Gynecology, LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria; 5Department of Medicine, Obafemi Awolowo University, Ile-Ife, Osun State, NigeriaPurpose: To determine whether low dose aspirin has any deleterious effects on renal function in elderly patients.Methods: We conducted a prospective pilot study of 30 Nigerians older than 60 years with various chronic ailments necessitating the use of low dose aspirin. Patients gave their consent, and institutional ethical clearance was obtained. Each patient's baseline samples at enrolment (before commencing aspirin use served as a control, and subsequent weekly samples were compared. The weekly mean of each parameter was calculated, and the differences of means from baseline were determined, and values were compared for statistical differences with the Statistical Package for the Social Sciences, version 16.Results: We found that a majority of patients (86.67% had basal renal functions at chronic kidney disease stages 1 and 2. When compared with the corresponding baseline parameters, the mean weekly serum and urinary electrolytes, urea, creatinine, and uric acid parameters did not change, and the P-value did not show any statistical significance. However, there was positive statistical significance for the creatinine clearance (P = 0.025. Also, unlike in previous studies, anemia and hypoalbuminemia did not affect the renal function parameters.Conclusion: This study did not show any deleterious effects with short-term, low dose (75 mg daily aspirin use on kidney functions in

  5. 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.

  6. Constitutive Expression of Thermobifida fusca Thermostable Acetylxylan Esterase Gene in Pichia pastoris

    Directory of Open Access Journals (Sweden)

    Yu-Chun Huang

    2010-12-01

    Full Text Available A gene encoding the thermostable acetylxylan esterase (AXE in Thermobifida fusca NTU22 was amplified by PCR, sequenced and cloned into the Pichia pastoris X-33 host strain using the vector pGAPZαA, allowing constitutive expression and secretion of the protein. Recombinant expression resulted in high levels of extracellular AXE production, as high as 526 U/mL in the Hinton flask culture broth. The purified enzyme showed a single band at about 28 kDa by SDS-polyacrylamide gel electrophoresis after being treated with endo-β-N-acetylglycosaminidase H; this agrees with the predicted size based on the nucleotide sequence. About 70% of the original activity remained after heat treatment at 60 °C for three hours. The optimal pH and temperature of the purified enzyme were 8.0 and 60 °C, respectively. The properties of the purified AXE from the P. pastoris transformant are similar to those of the AXE from an E. coli transformant.

  7. 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.

  8. Feruloyl esterase production by Aspergillus terreus CECT 2808 and subsequent application to enzymatic hydrolysis.

    Science.gov (United States)

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

    2016-09-01

    Ferulic acid esterases (FAE) were produced by Aspergillus terreus CECT 2808 from vine trimming shoots (VTS) and corn cob. Later, the fungal extracts thus obtained were used to enzymatically release ferulic acid (FA) from both substrates. Our findings showed a higher FAE activity in the enzymatic extracts produced on corn cob (0.070±0.004U/mL). Nevertheless, the enzymatic extracts produced on VTS demonstrated a better performance for FA release from both corn cob (2.05±0.01mg/g) and VTS (0.19±0.003mg/g). This result was probably because of the higher xylanase/FAE ratio determined in VTS extract. Therefore, an additional assay was carried out by supplementing corn cob extract with a commercial xylanase to test the influence of FAE/xylanase ratio in FA release. The results revealed the relevance of the FAE/xylanase ratio for an optimal FA release. PMID:27444329

  9. Characterization of Novel Family IV Esterase and Family I.3 Lipase from an Oil-Polluted Mud Flat Metagenome.

    Science.gov (United States)

    Kim, Hee Jung; Jeong, Yu Seok; Jung, Won Kyeong; Kim, Sung Kyum; Lee, Hyun Woo; Kahng, Hyung-Yeel; Kim, Jungho; Kim, Hoon

    2015-09-01

    Two genes encoding lipolytic enzymes were isolated from a metagenomic library constructed from oil-polluted mud flats. An esterase gene, est3K, encoded a protein of 299 amino acids (ca. 32,364 Da). Est3K was a family IV esterase with typical motifs, HGGG, and HGF. Although est3K showed high identity to many genes with no information on their enzymatic properties, Est3K showed the highest identity (36 %) to SBLip5.1 from forest soil metagenome when compared to the enzymes with reported properties. A lipase gene, lip3K, encoded a protein of 616 amino acids (ca. 64,408 Da). Lip3K belonged to family I.3 lipase with a C-terminal secretion signal and showed the highest identity (93 %) to the lipase of Pseudomonas sp. MIS38. The presence of several newly identified conserved motifs in Est3K and Lip3K are suggested. Both Est3K and Lip3K exerted their maximal activity at pH 9.0 and 50 °C. The activity of Lip3K was significantly increased by the presence of 30 % methanol. The ability of the enzymes to retain activities in the presence of methanol and the substrates may offer a merit to the biotechnological applications of the enzymes such as transesterification. The activity and the thermostability of Lip3K were increased by Ca(2+). Est3K and Lip3K preferred p-nitrophenyl butyrate (C4) and octanoate (C8), respectively, as the substrate and acted independently on the substrates with no synergistic effect. PMID:25943044

  10. Long-term use of ticagrelor in patients with prior heart attack: ticagrelor plus aspirin versus aspirin monotherapy.

    Science.gov (United States)

    Amico, Frank; Schlesinger, Alex; Mazzoni, Jennifer

    2016-01-01

    Review of: Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372:1791-1800. This Practice Pearl reviews the recent study Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared With Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54). It challenges the current standard of care of 12 months of dual antiplatelet followed by aspirin indefinitely. The study demonstrated that patients who received ticagrelor, either the 60 mg or 90 mg twice daily plus aspirin, showed a decreased risk of cardiovascular death, myocardial infarction, or stroke. The PEGASUS-TIMI 54 trial also proved that the benefit of ticagrelor was seen early and continued to accrue over time, with a median of 33 months of follow-up, meaning that the benefit persists over time. It is important to note that both doses of the ticagrelor were associated with higher incidence of bleeding, but the rates of fatal bleeding did not show any difference between the ticagrelor or placebo. PMID:26689345

  11. Association Between the P2RY12 Receptor Gene Polymorphism and Aspirin Resistance in Patients with Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Ludmila Karazhanova

    2014-12-01

    Full Text Available Introduction. Platelet activation and aggregation are key elements in the development of coronary atherosclerosis. Recent studies have shown that the two polymorphisms of platelet ADP receptor P2RY12 (haplotypes H2 and 34T are associated with increased platelet aggregation and atherothrombotic risk. It was shown that these polymorphisms promote reduced body response to antiplatelet therapy.Aim. We investigated the association of P2RY12 gene polymorphisms with aspirin resistance in patients with coronary artery disease (CAD.Methods. This case-control study included 100 cases with CAD (mean age 57.6 ± 2.8 years treated in the cardiology department of the city hospital Semey, Kazakhstan, 90 of whom suffered from myocardial infarction. The control group (n = 100 were healthy people without a history of CAD, matched on sex and age. Genotyping of polymorphisms H1/H2 in P2RY12 gene was performed by PCR. Statistical analysis was performed using SPSS v.19.0.Results. The distribution of H1/H2 genotypes P2RY12 was 42%, 34%, and 24%, respectively, in cases and 42%, 58%, and 0%, respectively, in controls. All allele frequencies were consistent with the Hardy Weinberg equilibrium (p = 0.0036 and p = 0.0001 in cases and controls, respectively. Genotype H2 was associated with risk of CAD with aspirin resistance (co-dominant model: OR = 3.75, 95% CI 0.14 - 99.88, p = 0.05 and dominant model: OR = 2.78, 95% CI 0.11 - 70.93, p = 0.05. We found significant differences in the distribution of the mutant genotype H2 between CAD patients with aspirin resistance and healthy controls (χ2 = 30.3, p < 0.05.Conclusion. We found an association of H2 haplotype in P2RY12 gene with aspirin resistance in patients with CAD. However, in order to obtain definitive conclusions about the role of genetic variants with the development of aspirin resistance in patients with CAD, there is a need for further research with a larger sample size as well as the use of selective thromboxane

  12. Biomonitoring of ecosystem degradation caused by CPO waste of Mentaya River in Central Kalimantan use of esterase isozyme electromorph method

    Directory of Open Access Journals (Sweden)

    PRABANG SETYONO

    2008-07-01

    Full Text Available The impact of CPO (Crude Palm Oil dock activity in Mentaya River of Central Borneo caused degradation of ecosystem, particularly on both mangrove and macrozoobenthos community. One of methods used for monitoring of ecosystem degradation was to determine species that were still survive under the polluted conditions. These survival species were assumed to synthesize alloenzyme that can be used as indicator. Alloenzyme was synthesized as an effort of adaptation processes toward environmental pressures caused by CPO spill on Mentaya River. Alloenzyme would be expressed as phenotypic and genotypic adaptation processes or phenotypic plasticity. Research was carried out, consisted of field research included collecting sample and environmental data (oil content, temperature, pH, electric conductivity and redox potential, and laboratory research included series analysis of water quality (DO, BOD, COD, pH, TSS, TDS and also alloenzyme content of Soneratia caseolaris L. and Macrobrachium rosenbergii de Man. The alloenzyme of root and leaves mangrove and prawn’s hepatopancreas was analyzed using Spencer starch gel electrophoresis modified method of exposed on sucrose solution. Separated components of alloenzyme were detected by special staining for Esterase isozyme. The results revealed that Soneratia caseolaris L. and Macrobrachium rosenbergii de Man were bioindicator organisms for the polluted site by oil spills from CPO loading activities. The polluted river water by oil spill from CPO activities decreased redox potential, DO, increased oil content, DHL, water temperature, pH sediment, pH water, TDS, BOD, COD, TSS. Gel electrophoretical analysis demonstrated that Mangrove Soneratia caseolaris synthesized alloenzyme consisted of complex enzymes such as EST in its root and leave cells. Those enzymes were nearly similar to those of Macrobrachium rosenbergii. The oil spill from CPO have ester bonding so its adaptation mechanism with release Esterase

  13. Expression of feruloyl esterase A from Aspergillus terreus and its application in biomass degradation.

    Science.gov (United States)

    Zhang, Shuai-Bing; Wang, Le; Liu, Yan; Zhai, Huan-Chen; Cai, Jing-Ping; Hu, Yuan-Sen

    2015-11-01

    Feruloyl esterases (FAEs) are key enzymes involved in the complete biodegradation of lignocelluloses, which could hydrolyze the ester bonds between hemicellulose and lignin. The coding sequence of a feruloyl esterase A (AtFaeA) was cloned from Aspergillus terreus and the recombinant AtFaeA was constitutively expressed in Pichia pastoris. The SDS-PAGE analysis of purified AtFaeA showed two protein bands owing to the different extent of glycosylation, and the recombinant AtFaeA had an optimum temperature of 50°C and an optimum pH of 5.0. The substrate utilization and primary sequence identity of AtFaeA demonstrated that it is a type-A feruloyl esterase. The hydrolysis of corn stalk and corncob by xylanase from Aspergillus niger could be significantly improved in concert with recombinant AfFaeA. PMID:26282562

  14. Eco-friendly surface modification on polyester fabrics by esterase treatment

    Science.gov (United States)

    Wu, Jindan; Cai, Guoqiang; Liu, Jinqiang; Ge, Huayun; Wang, Jiping

    2014-03-01

    Currently, traditional alkali deweighting technology is widely used to improve the hydrophilicity of polyester fabrics. However, the wastewater and heavy chemicals in the effluent cause enormous damage to the environment. Esterase treatment, which is feasible in mild conditions with high selectivity, can provide a clean and efficient way for polyester modification. Under the optimum conditions, the polyester fabric hydrolysis process of esterase had a linear kinetics. X-ray photoelectron spectrometry (XPS) results showed that hydroxyl and carboxyl groups were produced only on the surface of modified fiber without changing the chemical composition of the bulk. These fibers exhibited much improved fabric wicking, as well as greatly improved oily stain removal performance. Compared to the harsh alkali hydrolysis, the enzyme treatment led to smaller weight loss and better fiber integrity. The esterase treatment technology is promising to produce higher-quality polyester textiles with an environmental friendly approach.

  15. COX-2: Where are we in 2003? - Specific cyclooxygenase-2 inhibitors and aspirin-exacerbated respiratory disease

    OpenAIRE

    Crofford, Leslie J.

    2002-01-01

    The use of analgesic anti-inflammatory agents in patients with asthma is clinically challenging because of the prevalence (10–20%) of aspirin hypersensitivity. Aspirin-exacerbated respiratory disease (AERD), or aspirin-induced asthma, is characterized by asthma and rhinitis triggered by the ingestion of aspirin and non-steroidal anti-inflammatory drugs. AERD is associated with upper and lower respiratory-tract mucosal inflammation, progressive sinusitis, nasal polyposis, and asthma regardless...

  16. Aspirin induces apoptosis in vitro and inhibits tumor growth of human hepatocellular carcinoma cells in a nude mouse xenograft model

    OpenAIRE

    HOSSAIN, MOHAMMAD AKBAR; Kim, Dong Hwan; JANG, JUNG YOON; KANG, YONG JUNG; YOON, JEONG-HYUN; Moon, Jeon-OK; Chung, Hae Young; Kim, Gi-Young; Choi, Yung Hyun; Copple, Bryan L.; Kim, Nam Deuk

    2011-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to induce apoptosis in a variety of cancer cells, including colon, prostate, breast and leukemia. Among them, aspirin, a classical NSAID, shows promise in cancer therapy in certain types of cancers. We hypothesized that aspirin might affect the growth of liver cancer cells since liver is the principal site for aspirin metabolism. Therefore, we investigated the effects of aspirin on the HepG2 human hepatocellular carcinoma cell line in vi...

  17. Identification of a cocaine esterase in a strain of Pseudomonas maltophilia.

    OpenAIRE

    Britt, A J; Bruce, N C; Lowe, C R

    1992-01-01

    A strain of Pseudomonas maltophilia (termed MB11L) which was capable of using cocaine as its sole carbon and energy source was isolated by selective enrichment. An inducible esterase catalyzing the hydrolysis of cocaine to ecgonine methyl ester and benzoic acid was identified and purified 22-fold. In the presence of the solubilizing agent cholate, cocaine esterase had a native Mr of 110,000 and was shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to be a monomer. In the abse...

  18. Hydrolysis of Wheat Arabinoxylan by Two Acetyl Xylan Esterases from Chaetomium thermophilum

    DEFF Research Database (Denmark)

    Tong, Xiaoxue; Lange, Lene; Grell, Morten Nedergaard;

    2015-01-01

    The thermophilic filamentous ascomycete Chaetomium thermophilum produces functionally diverse hemicellulases when grown on hemicellulose as carbon source. Acetyl xylan esterase (EC 3.1.1.72) is an important accessory enzyme in hemicellulose biodegradation. Although the genome of C. thermophilum has...... xylanase treatment and increased to 34 % when xylanase was combined with rCtAxeA and rCtAxeB. In sum, the present study first report the biochemical characterization of two acetyl xylan esterases from C. thermophilum, which are efficient in hydrolyzing hemicellulose with potential application in biomass...

  19. Aspirin After Mini-Stroke May Help Prevent Full-Blown Stroke

    Science.gov (United States)

    ... gov/news/fullstory_158939.html Aspirin After Mini-Stroke May Help Prevent Full-Blown Stroke Study finds risk is reduced by as much ... HealthDay News) -- Taking aspirin immediately after a mini-stroke significantly reduces the risk of a major stroke, ...

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

    Directory of Open Access Journals (Sweden)

    Bianca Rocca

    2012-01-01

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