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

International Nuclear Information System (INIS)

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

1991-01-01

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-[ 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

Salicylate toxicity model of tinnitus

Directory of Open Access Journals (Sweden)

Daniel eStolzberg

2012-04-01

Full Text Available Salicylate, the active component of the common drug aspirin, has mild analgesic, antipyretic, and anti-inflammatory effects at moderate doses. At higher doses, however, salicylate temporarily induces moderate hearing loss and the perception of a high-pitch ringing in humans and animals. This phantom perception of sound known as tinnitus is qualitatively similar to the persistent subjective tinnitus induced by high-level noise exposure, ototoxic drugs or aging which affects ~14% of the general population. For over a quarter century, auditory scientists have used the salicylate toxicity model to investigate candidate biochemical and neurophysiological mechanisms underlying phantom sound perception. In this review, we summarize some of the intriguing biochemical and physiological effects associated with salicylate-induced tinnitus, some of which occur in the periphery and others in the central nervous system. The relevance and general utility of the salicylate toxicity model in understanding phantom sound perception in general are discussed.

Effect of acetyl salicylic acid (aspirin) and Prostaglandins on thyroid tissue and carbohydrate metabolism in liver of male albino rats

International Nuclear Information System (INIS)

Balasubramanian, A.; Ramakrishnan, S.

1979-01-01

Aspirin, both in chronic and acute doses, led to a considerable decrease in percentage uptake of labelled iodine (Na 131 I) and serum protein-bound iodine by the thyroid gland whereas prostaglandins (PGs) did not exhibit any significant effect on both the parameters. Simultaneous administration of aspirin and PGs caused a significant decrease in the two parameters, and on withdrawal of aspirin from the diet the two parameters were restored to normal levels, thus suggesting that the effect of aspirin on thyroid is direct and reversible. Aspirin, both in acute and chronic doses, effected decrease in glycogen levels, in vivo and in vitro incorporation of [U- 14 C] glucose into glycogen, and glycogen synthetase activity in the liver of both fed, and fasting, rat. Prostaglandins, on the other hand, resulted in a significant increase in the three parameters, thus enhancing the rate of liver glycogenesis. Normal levels were restored when both aspirin and PGs were given together. Withdrawal of aspirin also restored normal hepatic glycogenesis. Significant reduction in the activities of hepatic gluconeogenic enzymes, viz. glucose 6-phosphatase, fructose 1,6-diphosphatase, phosphopyruvate carboxylase, pyruvate carboxylase, aspartate aminotransferase and glutamate dehydrogenase was observed due to chronic and acute administration of aspirin and PGs were devoid of any significant effect on gluconeogenic enzymes, thus ruling out the mediation of PGs. (auth.)

Effect of acetyl salicylic acid (aspirin) and Prostaglandins on thyroid tissue and carbohydrate metabolism in liver of male albino rats

Energy Technology Data Exchange (ETDEWEB)

Balasubramanian, A; Ramakrishnan, S [Jawaharlal Inst. of Postgraduate Medical Education and Research, Pondicherry (India)

1979-04-01

Aspirin, both in chronic and acute doses, led to a considerable decrease in percentage uptake of labelled iodine (Na/sup 131/I) and serum protein-bound iodine by the thyroid gland whereas prostaglandins (PGs) did not exhibit any significant effect on both the parameters. Simultaneous administration of aspirin and PGs caused a significant decrease in the two parameters, and on withdrawal of aspirin from the diet the two parameters were restored to normal levels, thus suggesting that the effect of aspirin on thyroid is direct and reversible. Aspirin, both in acute and chronic doses, effected decrease in glycogen levels, in vivo and in vitro incorporation of (U-/sup 14/C) glucose into glycogen, and glycogen synthetase activity in the liver of both fed, and fasting, rat. Prostaglandins, on the other hand, resulted in a significant increase in the three parameters, thus enhancing the rate of liver glycogenesis. Normal levels were restored when both aspirin and PGs were given together. Withdrawal of aspirin also restored normal hepatic glycogenesis. Significant reduction in the activities of hepatic gluconeogenic enzymes, viz. glucose 6-phosphatase, fructose 1,6-diphosphatase, phosphopyruvate carboxylase, pyruvate carboxylase, aspartate aminotransferase and glutamate dehydrogenase was observed due to chronic and acute administration of aspirin and PGs were devoid of any significant effect on gluconeogenic enzymes, thus ruling out the mediation of PGs.

Dietary non-nutrients and haemostasis in humans : effects of salicylates, flavonoids and ginger

NARCIS (Netherlands)

Janssen, P.L.T.M.K.

1997-01-01

In this thesis we studied the content of acetylsalicylate and total salicylates in foods, and we studied the effects of the dietary non-nutrients salicylates and flavonoids and of certain foods on haemostatic parameters in humans.

Acetylsalicylic acid -aspirin- irreversibly inhibits

Effects of salicylate on the inflammatory genes expression and synaptic ultrastructure in the cochlear nucleus of rats.

Science.gov (United States)

Hu, Shou-Sen; Mei, Ling; Chen, Jian-Yong; Huang, Zhi-Wu; Wu, Hao

2014-04-01

Aspirin (salicylate), as a common drug that is frequently used for long-term treatment in a clinical setting, has the potential to cause reversible tinnitus. However, few reports have examined the inflammatory cytokines expression and alteration of synaptic ultrastructure in the cochlear nucleus (CN) in a rat model of tinnitus. The tinnitus-like behavior of rats were detected by the gap prepulse inhibition of acoustic startle (GPIAS) paradigm. We investigated the expression levels of the tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), N-methyl D-aspartate receptor subunit 2A (NR2A) mRNA and protein in the CN and compared synapses ultrastructure in the CN of tinnitus rats with normal ones. GPIAS showed that rats with long-term administration of salicylate were experiencing tinnitus, and the mRNA and protein expression levels of TNF-α and NR2A were up-regulated in chronic treatment groups, and they returned to baseline 14 days after cessation of treatment. Furthermore, compared to normal rats, repetitive salicylate-treated rats showed a greater number of presynaptic vesicles, thicker and longer postsynaptic densities, increased synaptic interface curvature. These data revealed that chronic salicylate administration markedly, but reversibly, induces tinnitus possibly via augmentation of the expression of TNF-α and NR2A and cause changes in synaptic ultrastructure in the CN. Long-term administration of salicylate causes neural plasticity changes at the CN level.

Effects of salicylic acid on post-ischaemic ventricular function and purine efflux in isolated mouse hearts.

Science.gov (United States)

Farthing, Don; Gehr, Lynne; Karnes, H Thomas; Sica, Domenic; Gehr, Todd; Larus, Terri; Farthing, Christine; Xi, Lei

2007-01-01

Acetyl salicylic acid (aspirin) is one of the most widely used drugs in the world. Various plasma concentrations of aspirin and its predominant metabolite, salicylic acid, are required for its antiarthritic (1.5-2.5 mM), anti-inflammatory (0.5-5.0 mM) or antiplatelet (0.18-0.36 mM) actions. A recent study demonstrated the inhibitory effects of both aspirin and salicylic acid on oxidative phosphorylation and ATP synthesis in isolated rat cardiac mitochondria in a dose-dependent manner (0-10 mM concentration range). In this context, the present study was conducted to determine the effects of salicylic acid on inosine efflux (a potential biomarker of acute cardiac ischaemia) as well as cardiac contractile function in the isolated mouse heart following 20 min of zero-flow global ischaemia. Inosine efflux was found at significantly higher concentrations in ischaemic hearts perfused with Krebs buffer fortified with 1.0 mM salicylic acid compared with those without salicylic acid (12575+/-3319 vs. 1437+/-348 ng ml(-1) min(-1), mean+/-SEM, n=6 per group, psalicylic acid potentiates 8.8-fold ATP nucleotide purine catabolism into its metabolites (e.g. inosine, hypoxanthine). Salicylic acid (0.1 or 1.0 mM) did not appreciably inhibit purine nucleoside phosphorylase (the enzyme converts inosine to hypoxanthine) suggesting the augmented inosine efflux was due to the salicylic acid effect on upstream elements of cellular respiration. Whereas post-ischaemic cardiac function was further depressed by 1.0 mM salicylic acid, perfusion with 0.1 mM salicylic acid led to a remarkable functional improvement despite moderately increased inosine efflux (2.7-fold). We conclude that inosine is a sensitive biomarker for detecting cardiac ischaemia and salicylic acid-induced effects on cellular respiration. However, the inosine efflux level appears to be a poor predictor of the individual post-ischaemic cardiac functional recovery in this ex vivo model.

Aspirin increases mitochondrial fatty acid oxidation

International Nuclear Information System (INIS)

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

2017-01-01

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

Metabolism of aspirin and procaine in mice pretreated with O-4-nitrophenyl methyl(phenyl)phosphinate or O-4-nitrophenyl diphenylphosphinate

International Nuclear Information System (INIS)

Joly, J.M.; Brown, T.M.

1986-01-01

Concentrations of [carboxyl- 14 C]procaine in blood of mice were increased threefold for 27 min by exposure to O-4-nitrophenyl diphenylphosphinate 2 hr prior to [carboxyl- 14 C]procaine injection ip, while there was no effect of O-4-nitrophenyl methyl(phenyl)phosphinate pretreatment. There was no effect of either organophosphinate on the primary hydrolysis of [acetyl-l- 14 C]aspirin when assessed by the expiration of [ 14 C]carbon dioxide; however, O-4-nitrophenyl diphenylphosphinate pretreatment produced transient increases in blood concentrations of both [carboxyl- 14 C]aspirin and [carboxyl- 14 C]salicylic acid following administration of [carboxyl- 14 C]aspirin. Liver carboxylesterase activity in O-4-nitrophenyl diphenylphosphinate pretreated mice was 11% of control activity. These results indicate the potential for drug interaction with O-4-nitrophenyl diphenylphosphinate but not with O-4-nitrophenyl methyl(phenyl)phosphinate. It appears that liver carboxylesterase activity has a minor role in hydrolysis of aspirin in vivo, but may be more important in procaine metabolism

Efficient scavenging of β-carotene radical cations by antiinflammatory salicylates

DEFF Research Database (Denmark)

Cheng, Hong; Liang, Ran; Han, Rui-Min

2014-01-01

by the anion of salicylic acid with 2.2 × 10 L mol s, but still of possible importance for light-exposed tissue. Surprisingly, acetylsalicylate, the aspirin anion, reacts with an intermediate rate in a reaction assigned to the anion of the mixed acetic-salicylic acid anhydride formed through base induced......The radical cation generated during photobleaching of β-carotene is scavenged efficiently by the anion of methyl salicylate from wintergreen oil in a second-order reaction approaching the diffusion limit with k = 3.2 × 10 L mol s in 9:1 v/v chloroform-methanol at 23 °C, less efficiently...... rearrangements. The relative scavenging rate of the β-carotene radical cation by the three salicylates is supported by DFT-calculations....

SALICYLATE INCREASES THE GAIN OF THE CENTRAL AUDITORY SYSTEM

Science.gov (United States)

Sun, W.; Lu, J.; Stolzberg, D.; Gray, L.; Deng, A.; Lobarinas, E.; Salvi, R. J.

2009-01-01

High doses of salicylate, the anti-inflammatory component of aspirin, induce transient tinnitus and hearing loss. Systemic injection of 250 mg/kg of salicylate, a dose that reliably induces tinnitus in rats, significantly reduced the sound evoked output of the rat cochlea. Paradoxically, salicylate significantly increased the amplitude of the sound-evoked field potential from the auditory cortex (AC) of conscious rats, but not the inferior colliculus (IC). When rats were anesthetized with isoflurane, which increases GABA-mediated inhibition, the salicylate-induced AC amplitude enhancement was abolished, whereas ketamine, which blocks N-methyl-d-aspartate receptors, further increased the salicylate-induced AC amplitude enhancement. Direct application of salicylate to the cochlea, however, reduced the response amplitude of the cochlea, IC and AC, suggesting the AC amplitude enhancement induced by systemic injection of salicylate does not originate from the cochlea. To identify a behavioral correlate of the salicylate-induced AC enhancement, the acoustic startle response was measured before and after salicylate treatment. Salicylate significantly increased the amplitude of the startle response. Collectively, these results suggest that high doses of salicylate increase the gain of the central auditory system, presumably by down-regulating GABA-mediated inhibition, leading to an exaggerated acoustic startle response. The enhanced startle response may be the behavioral correlate of hyperacusis that often accompanies tinnitus and hearing loss. Published by Elsevier Ltd on behalf of IBRO. PMID:19154777

of aspirin The use of renal enzymes indication of renal toxicity dose ...

African Journals Online (AJOL)

1983-04-30

Apr 30, 1983 ... analysis revealed that aspirin significantly increased the output of both ... Acetylsalicylic acid (Disprin) I500 mg wa administered 3 times a day .... completely removing salicylic acid and metabolites from the urine, as could be ...

Relative bioavailability studies on a locally manufactured aspirin tablets using UV spectrophotometry and HPLC

International Nuclear Information System (INIS)

Kwadzo, Ameko David

2005-11-01

Modern trends in drug analysis require use of less time consuming, efficient, cost effective, fast, reproducible, simple and convenient methods. Two analytical methods were employed for the determination, the UV spectrophotometry and the HPLC. Aspirin, which is rapidly deacetylated to salicylic acid after absorption into the plasma, is excreted in the urine. In determining the salicylic acid concentration in the urine, the absorbance was quantitated by a spectrometer at a wavelength of 540nm. Aspirin formed an amber coloured complex with ferric ions (Trinder’s reagent). The complex, which formed instantaneously at room temperature, was stable. The solution of the complex obeyed Beer’s law at 540nm, the wavelength of maximum absorption of radiation (λmax). Phenol—induced absorbance is quenched by acidifying the reaction mixture with phosphoric acid. An HPLC analytical method was used in determining the free salicylate excreted in the urine. The mobile phase employed is a validated method from the USP- XXII (1990) which consists of water, methanol and glacial acetic acid in the ratio 69: 28: 3 respectively. The chromatographic conditions involved a flow rate of 1.0ml/rnin, wavelength of maximum absorption of 236nrn, stationary phase Spherisorb S5 ODS 1 phase sep column with standard dimensions of 25.0 cm length and 4.6cm diameter and chart recorder speed of 5mm/min. The quality of the reference and the test tablets were assessed by a number of standard tests, which include uniformity of weight, friability, hardness and dissolution that fall within the BP 2000 specification. The observation from the study reveals that the relative bioavailability of aspirin (w.r.t. salicylic acid) were 103.39% and 94.93% for HPLC and UV respectively. The mean cumulative percentage of the drug excreted in both cases were ii .05% and 10.69% for test and reference respectively for HPLC and 76.45% and 80.53% for test and reference respectively for UV analysis. The cumulative amount

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

Directory of Open Access Journals (Sweden)

P. Marson

2011-06-01

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

The effect of radiation on some salicylates. 1. Steady state studies

International Nuclear Information System (INIS)

Paz, L.R. de la.

1975-01-01

This work was undertaken to obtain more quantitative information on the extent and nature of the degradation of some salicylates by ionizing radiation, especially gamma rays, and to gather data that could assist in the evaluation of the use of radiation for sterilization of this group of compounds which are extensively used as antipyretics, analgesics and anti-rheumatics. Salicylamide is not only a common medicinal, but also a model for the study of the effect of radiation on biological systems. A 3200 Ci Co-60 facility was used. Three salicylates were subjected to solid phase irradiation, namely: salicylamide, phenylsalicylate, and acetyl salicylic acid (aspirin). These compounds were purified by repeated recrystallization from water, methanol and benzene, respectively, until a constant melting point was obtained. Irradiation in the solid phase was made in doses from 2.5 to 240 Krad. Irradiation in the liquid phase (solution) was carried out in doses, ranging from 2000 to as high as 270,000 rad depending on the reactivity of the solution. The degradation products were separated by thin layer chromatography using Kieselgel F254 and SIF with fluorescence scintillator (Riedel-de Haen). The products were visualized with a Camag UV Universal lamp. Irradiation of the three salicylates showed very little decomposition even at doses very much higher than those required for radiation sterilization. Salicylamide appears to be the most stable giving an initial G(-salicylamide)-0.50. For both phenylsalicylate and acetylsalicylic acid only the G values at 150 Mrad were obtained as the amounts degraded at lower doses were too low for the sensitivity of the diffused reflectance method used. A G(-phenylsalicylate)-2 and G(-acetylsalicylate)-1.2 were obtained by this method. Salicylic acid is formed when aspirin is irradiated. It is concluded that this acid is one of the degradation products. Barring any toxic property of the minute substances formed, solid phase sterilization is

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.

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

Science.gov (United States)

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

2009-01-01

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

Ion-pair high performance liquid chromatographic retention behavior of salicylic acid and its derivatives

Energy Technology Data Exchange (ETDEWEB)

Lee, K.W.; Chung, Y.S. [Chungbuk National University, Cheongju (Korea); Oh, S.K. [Handok Pharmaceuticals Co. Ltd., Chungbuk (Korea)

1999-06-01

The ion-pair high performance liquid chromatographic elution behavior of salicylic acid and its derivatives was studied with measuring capacity factor, k', changing the concentration of ion-pairing reagent (tetrabutylammonium chloride, TBACl) in mobile phase. As a result, it was found that k' of the samples increase at pH 7.2 as the TBACl concentration increase. The derivatives of salicylic acid were separated each other at an optimum mobile phase condition which was found from the observation of the retention behavior. The optimum mobile phase condition was methanol solution(MeOH:H{sub 2}O 30:70) containing 20 mM TBACl for the determination of salicylic acid and methanol solution (MeOH:H{sub 2}O 20:80) containing 40 mM TBACl for p-aminosalicylic acid at pH 7.2. The method has been applied for the analysis of the contents of salicylic acid derivatives in an aspirin tablet and a tuberculosis curing agent. 8 refs., 4 figs., 2 tabs.

Pharmacokinetics of repeated sodium salicylate administration to laying hens: evidence for time dependent increase in drug elimination from plasma and eggs.

Directory of Open Access Journals (Sweden)

Błażej Poźniak

Full Text Available Salicylates were the first non-steroid anti-inflammatory drugs (NSAIDs to be used in any species and are still widely used in humans and livestock. However, the data on their pharmacokinetics in animals is limited, especially after repeated administration. Evidence exist that in chickens (Gallus gallus salicylate (SA may induce its own elimination. The aim of this study was to investigate salicylate pharmacokinetics and egg residues during repeated administration of sodium salicylate (SS to laying hens. Pharmacokinetics of SA was assessed during 14 d oral administration of SS at daily doses of 50 mg/kg and 200 mg/kg body weight to laying hens. On the 1st, 7th and 14th d a 24 h-long pharmacokinetic study was carried out, whereas eggs were collected daily. Salicylate concentrations in plasma and eggs were determined using high-performance liquid chromatography with ultraviolet detection and pharmacokinetic variables were calculated using a non-compartmental model. Mean residence time (MRT, minimal plasma concentration (Cmin, C16h and elimination half-life (T1/2el of SA showed gradual decrease in layers administered with a lower dose. Total body clearance (ClB increased. Layers administered with the higher dose showed a decrease only in the T1/2el. In the low dose group, SA was found only in the egg white and was low throughout the experiment. Egg whites from the higher dose group showed initially high SA levels which significantly decreased during the experiment. Yolk SA levels were lower and showed longer periods of accumulation and elimination. Repeated administration of SS induces SA elimination, although this effect may differ depending on the dose and production type of a chicken. Decreased plasma drug concentration may have clinical implications during prolonged SS treatment.

Aspirin in patients undergoing noncardiac surgery

DEFF Research Database (Denmark)

Devereaux, P J; Mrkobrada, Marko; Sessler, Daniel I

2014-01-01

BACKGROUND: There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not. METHODS: Using a 2-by-2 factorial trial design, we randomly assigned 10......,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before...... the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum...

Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis.

Science.gov (United States)

O'Brien, Andrew J; Villani, Linda A; Broadfield, Lindsay A; Houde, Vanessa P; Galic, Sandra; Blandino, Giovanni; Kemp, Bruce E; Tsakiridis, Theodoros; Muti, Paola; Steinberg, Gregory R

2015-07-15

Aspirin, the pro-drug of salicylate, is associated with reduced incidence of death from cancers of the colon, lung and prostate and is commonly prescribed in combination with metformin in individuals with type 2 diabetes. Salicylate activates the AMP-activated protein kinase (AMPK) by binding at the A-769662 drug binding site on the AMPK β1-subunit, a mechanism that is distinct from metformin which disrupts the adenylate charge of the cell. A hallmark of many cancers is high rates of fatty acid synthesis and AMPK inhibits this pathway through phosphorylation of acetyl-CoA carboxylase (ACC). It is currently unknown whether targeting the AMPK-ACC-lipogenic pathway using salicylate and/or metformin may be effective for inhibiting cancer cell survival. Salicylate suppresses clonogenic survival of prostate and lung cancer cells at therapeutic concentrations achievable following the ingestion of aspirin (Salicylate concentrations of 1 mM increased the phosphorylation of ACC and suppressed de novo lipogenesis and these effects were enhanced with the addition of clinical concentrations of metformin (100 μM) and eliminated in mouse embryonic fibroblasts (MEFs) deficient in AMPK β1. Supplementation of media with fatty acids and/or cholesterol reverses the suppressive effects of salicylate and metformin on cell survival indicating the inhibition of de novo lipogenesis is probably important. Pre-clinical studies evaluating the use of salicylate based drugs alone and in combination with metformin to inhibit de novo lipogenesis and the survival of prostate and lung cancers are warranted. © 2015 Authors; published by Portland Press Limited.

Interaction between valproic acid and aspirin in epileptic children: serum protein binding and metabolic effects.

Science.gov (United States)

Orr, J M; Abbott, F S; Farrell, K; Ferguson, S; Sheppard, I; Godolphin, W

1982-05-01

In five of six epileptic children who were taking 18 to 49 mg/kg/day valproic acid (VPA), the steady-state serum free fractions of VPA rose from 12% to 43% when antipyretic doses of aspirin were also taken. Mean total VPA half-life (t1/2) rose from 10.4 +/- 2.7 to 12.9 +/- 1.8 hr and mean free VPA t1/2 rose from 6.7 +/- to 2.1 to 8.9 +2- 3.0 hr when salicylate was present in the serum. The in vitro albumin binding association constant (ka) for VPA was decreased by salicylate, but the in vivo ka value was not affected. The 12-hr (trough) concentrations of both free and total VPA were higher in the presence of serum salicylate in five of six patients. Renal excretion of unchanged VPA decreased in five of six patients, but the VPA carboxyl conjugate metabolite-excretion patterns were not consistently affected. Salicylate appeared to displace VPA from serum albumin in vivo, but the increased VPA t1/2 and changes in VPA elimination patterns suggest that serum salicylate also altered VPA metabolism.

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

Directory of Open Access Journals (Sweden)

Deepak Voora, MD

2016-09-01

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

Aspirin-Mediated Acetylation Protects Against Multiple Neurodegenerative Pathologies by Impeding Protein Aggregation.

Science.gov (United States)

Ayyadevara, Srinivas; Balasubramaniam, Meenakshisundaram; Kakraba, Samuel; Alla, Ramani; Mehta, Jawahar L; Shmookler Reis, Robert J

2017-12-10

Many progressive neurological disorders, including Alzheimer's disease (AD), Huntington's disease, and Parkinson's disease (PD), are characterized by accumulation of insoluble protein aggregates. In prospective trials, the cyclooxygenase inhibitor aspirin (acetylsalicylic acid) reduced the risk of AD and PD, as well as cardiovascular events and many late-onset cancers. Considering the role played by protein hyperphosphorylation in aggregation and neurodegenerative diseases, and aspirin's known ability to donate acetyl groups, we asked whether aspirin might reduce both phosphorylation and aggregation by acetylating protein targets. Aspirin was substantially more effective than salicylate in reducing or delaying aggregation in human neuroblastoma cells grown in vitro, and in Caenorhabditis elegans models of human neurodegenerative diseases in vivo. Aspirin acetylates many proteins, while reducing phosphorylation, suggesting that acetylation may oppose phosphorylation. Surprisingly, acetylated proteins were largely excluded from compact aggregates. Molecular-dynamic simulations indicate that acetylation of amyloid peptide energetically disfavors its association into dimers and octamers, and oligomers that do form are less compact and stable than those comprising unacetylated peptides. Hyperphosphorylation predisposes certain proteins to aggregate (e.g., tau, α-synuclein, and transactive response DNA-binding protein 43 [TDP-43]), and it is a critical pathogenic marker in both cardiovascular and neurodegenerative diseases. We present novel evidence that acetylated proteins are underrepresented in protein aggregates, and that aggregation varies inversely with acetylation propensity after diverse genetic and pharmacologic interventions. These results are consistent with the hypothesis that aspirin inhibits protein aggregation and the ensuing toxicity of aggregates through its acetyl-donating activity. This mechanism may contribute to the neuro-protective, cardio

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

Science.gov (United States)

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

2013-01-01

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

Attenuation of salicylate-induced tinnitus by Ginkgo biloba extract in rats.

Science.gov (United States)

Jastreboff, P J; Zhou, S; Jastreboff, M M; Kwapisz, U; Gryczynska, U

1997-01-01

The effects of an extract from Ginkgo biloba, EGb 761, on tinnitus were tested using an animal model of tinnitus. Daily oral administration of EGb 761 in doses from 10 to 100 mg/ kg/day began 2 weeks before behavioral procedures and continued until the end of the experiment. Tinnitus was induced by daily administration of 321 mg/kg sodium salicylate s.c. (corresponding to 275 mg/kg/day of salicylate acid) in fourteen groups of pigmented rats, 6 animals/group. The results from salicylate- and EGb-761-treated animals were compared to control groups receiving either salicylate, saline, or EGb 761 only in doses of 100 mg/kg. Administration of EGb 761 resulted in a statistically significant decrease of the behavioral manifestation of tinnitus for doses of 25, 50 and 100 mg/kg/ day.

Contemporary management of chronic rhinosinusitis with nasal polyposis in aspirin-exacerbated respiratory disease: an evidence-based review with recommendations.

Science.gov (United States)

Levy, Joshua M; Rudmik, Luke; Peters, Anju T; Wise, Sarah K; Rotenberg, Brian W; Smith, Timothy L

2016-12-01

Chronic rhinosinusitis (CRS) in aspirin-exacerbated respiratory disease (AERD) represents a recalcitrant form of sinonasal inflammation for which a multidisciplinary consensus on patient management has not been reached. Several medical interventions have been investigated, but a formal comprehensive evaluation of the evidence has never been performed. The purpose of this article is to provide an evidence-based approach for the multidisciplinary management of CRS in AERD. A systematic review of the literature was performed and the guidelines for development of an evidence-based review with recommendations were followed. Study inclusion criteria included: adult population >18 years old; CRS based on published diagnostic criteria, and a presumptive diagnosis of AERD. We focused on reporting higher-quality studies (level 2 or higher) when available, but reported lower-quality studies if the topic contained insufficient evidence. Treatment recommendations were based on American Academy of Otolaryngology (AAO) guidelines, with defined grades of evidence and evaluation of research quality and risk/benefits associated with each treatment. This review identified and evaluated the literature on 3 treatment strategies for CRS in AERD: dietary salicylate avoidance, leukotriene modification, and desensitization with daily aspirin therapy. Based on the available evidence, dietary salicylate avoidance and leukotriene-modifying drugs are options following appropriate treatment with nasal corticosteroids and saline irrigation. Desensitization with daily aspirin therapy is recommended following revision endoscopic sinus surgery (ESS). © 2016 ARS-AAOA, LLC.

Contemporary management of chronic rhinosinusitis with nasal polyposis in aspirin exacerbated respiratory disease: an evidence-based review with recommendations

Science.gov (United States)

Levy, Joshua M.; Rudmik, Luke; Peters, Anju T.; Wise, Sarah K.; Rotenberg, Brian W.; Smith, Timothy L.

2016-01-01

Background Chronic rhinosinusitis (CRS) in aspirin exacerbated respiratory disease (AERD) represents a recalcitrant form of sinonasal inflammation for which a multidisciplinary consensus on patient management has not been reached. Several medical interventions have been investigated, but a formal comprehensive evaluation of the evidence has never been performed. The purpose of this article is to provide an evidence-based approach for the multidisciplinary management of CRS in AERD. Methods A systematic review of the literature was performed and the guidelines for development of an evidence-based review with recommendations were followed. Study inclusion criteria included: adult population>18 years old; CRS based on published diagnostic criteria and a presumptive diagnosis of AERD. We focused on reporting higher-quality studies (level 2 or higher) when available, but reported lower-quality studies if the topic contained insufficient evidence. Treatment recommendations were based on American Academy of Otolaryngology guidelines, with defined grades of evidence and evaluation of research quality and risk/benefits associated with each treatment. Results This review identified and evaluated the literature on 3 treatment strategies for CRS in AERD: dietary salicylate avoidance, leukotriene modification and desensitization with daily aspirin therapy. Conclusion Based on the available evidence, dietary salicylate avoidance and leukotriene modifying drugs are options following appropriate treatment with nasal corticosteroids and saline irrigation. Desensitization with daily aspirin therapy is recommended following revision ESS. PMID:27480830

Efficacy of wheat germ oil in alleviating certain disorders induced by aspirin administration and/or Γ-irradiation in pregnant albino rats and their foetuses

International Nuclear Information System (INIS)

Ramadan, F.L.

2007-01-01

Aspirin is one of the most commonly used nonsteroidal anti-inflammatory drugs, induces during pregnancy high incidence of developmental anomalies in pregnant rats when given on specific days during stage of organogenesis. Accordingly, this study was performed to clarify the beneficial effect of maternal intake of wheat germ oil on the effect of aspirin administration and/or radiation induced maternal and foetal detrimental impact. Pregnant albino rats were administered aspirin from the gestational day (GD), 6 to (GD) 17 at a dose of 250 mg kg/day body wt and exposed to whole body γ-irradiation at dose of 0.5 Gy for 4 times on GD 9,10,11 and 12 days from pregnancy. The extent of lipid peroxidase formation as well as estimation of alkaline phosphatase and total proteins content in tissues of liver and placenta was used as sensitive parameters of choice to evaluate tissue damage. Radiation exposure and aspirin administration induced marked elevation in lipid peroxidase (malondialdehyde), alkaline phosphatase, accompanied by decline in total protein content in placenta and liver tissues. In addition, miscellaneous malformations including anopthalmia, microtia, excencephaly, diminution of size or kypophysis were designated. The results showed that supplementation of pregnant female rats with wheat germ oil were able to reduce the high levels of malondialdehyde, alkaline phosphatase. Total protein content returned once more to its normal pattern. Also, reduction of severe deleterious symptoms of radiation and aspirin administration inducing i foetal mortality were reduced. Wheat germ oil showed to increase growth in surviving foetuses and remarkable protection against severe morphological deformities as well as biochemical, histochemical and embryological disorders

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

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

Science.gov (United States)

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

1986-05-01

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

Acute redistribution of thyroxine after the administration of univalent anions, salicylate, theophylline and barbiturates in rats

Energy Technology Data Exchange (ETDEWEB)

Langer, P; Kokesova, H; Gschwendtova, K [Slovenska Akademia Vied, Bratislava (Czechoslovakia). Ustav Experimentalni Endocrinologie

1976-01-01

Rats were injected with (/sup 125/I)L-thyroxine (T/sub 4/) ip 16 h before the experiment and samples of blood were frequently taken from polyethylene tubing inserted into the femoral artery in anaesthetized and heparin-injected animals. In each sample of plasma T/sub 4/ counts per ml were estimated with the acid of paper chromatography. Rapid decrease of circulating T/sub 4/ level was found at 20 min after iv injection of thiocyanate, iodide, fluoroborate, theophylline and salicylate and a dose-response relationship was established between such a decrease and the administered dose of salicylate (5-160 mg/400 g b.w.). A similar decrease was observed at 60 min after ip injection of some general anaesthetics or tranquilizers. An increase of T/sub 4/ fractional disposal rate was found between 120 and 480 min after the administration of some of the anaesthetics and this effect was abolished by the administration of thiocyanate. It was concluded that there are two different effects of drugs on the circulating T/sub 4/ level: 1. the immediate effect resulting apparently from a decreased plasma protein binding. 2. the prolonged effect which presumably results from the increased turnover of T/sub 4/ by peripheral tissues, the metabolic basis of which remains unexplained.

The use of preoperative aspirin in cardiac surgery: A systematic review and meta-analysis.

Science.gov (United States)

Aboul-Hassan, Sleiman Sebastian; Stankowski, Tomasz; Marczak, Jakub; Peksa, Maciej; Nawotka, Marcin; Stanislawski, Ryszard; Kryszkowski, Bartosz; Cichon, Romuald

2017-12-01

Despite the fact that aspirin is of benefit to patients following coronary artery bypass grafting (CABG), continuation or administration of preoperative aspirin before CABG or any cardiac surgical procedure remains controversial. Therefore, we performed a systematic review and meta-analysis to assess the influence of preoperative aspirin administration on patients undergoing cardiac surgery. Medline database was searched using OVID SP interface. Similar searches were performed separately in EMBASE, PubMed, and Cochrane Central Registry of Controlled Trials. Twelve randomized controlled trials and 28 observational studies met our inclusion criteria and were included in the meta-analysis. The use of preoperative aspirin in patients undergoing CABG at any dose is associated with reduced early mortality as well as a reduced incidence of postoperative acute kidney injury (AKI). Low-dose aspirin (≤160 mg/d) is associated with a decreased incidence of perioperative myocardial infarction (MI). Administration of preoperative aspirin at any dose in patients undergoing cardiac surgery increases postoperative bleeding. Despite this effect of preoperative aspirin, it did not increase the rates of surgical re-exploration due to excessive postoperative bleeding nor did it increase the rates of packed red blood cell transfusions (PRBC) when preoperative low-dose aspirin (≤160 mg/d) was administered. Preoperative aspirin increases the risk for postoperative bleeding. However, this did not result in an increased need for chest re-exploration and did not increase the rates of PRBC transfusion when preoperative low-dose (≤160 mg/d) aspirin was administered. Aspirin at any dose is associated with decreased mortality and AKI and low-dose aspirin (≤160 mg/d) decreases the incidence of perioperative MI. © 2017 Wiley Periodicals, Inc.

Chemometrics-assisted Spectrofluorimetric Determination of Two Co-administered Drugs of Major Interaction, Methotrexate and Aspirin, in Human Urine Following Acid-induced Hydrolysis.

Science.gov (United States)

Maher, Hadir M; Ragab, Marwa A A; El-Kimary, Eman I

2015-01-01

Methotrexate (MTX) is widely used to treat rheumatoid arthritis (RA), mostly along with non-steroidal anti-inflammatory drugs (NSAIDs), the most common of which is aspirin or acetyl salicylic acid (ASA). Since NSAIDs impair MTX clearance and increase its toxicity, it was necessary to develop a simple and reliable method for the monitoring of MTX levels in urine samples, when coadministered with ASA. The method was based on the spectrofluorimetric measurement of the acid-induced hydrolysis product of MTX, 4-amino-4-deoxy-10-methylpteroic acid (AMP), along with the strongly fluorescent salicylic acid (SA), a product of acid-induced hydrolysis of aspirin and its metabolites in urine. The overlapping emission spectra were resolved using the derivative method (D method). In addition, the corresponding derivative emission spectra were convoluted using discrete Fourier functions, 8-points sin xi polynomials, (D/FF method) for better elimination of interferences. Validation of the developed methods was carried out according to the ICH guidelines. Moreover, the data obtained using derivative and convoluted derivative spectra were treated using the non-parametric Theil's method (NP), compared with the least-squares parametric regression method (LSP). The results treated with Theil's method were more accurate and precise compared with LSP since the former is less affected by the outliers. This work offers the potential of both derivative and convolution using discrete Fourier functions in addition to the effectiveness of using the NP regression analysis of data. The high sensitivity obtained by the proposed methods was promising for measuring low concentration levels of the two drugs in urine samples. These methods were efficiently used to measure the drugs in human urine samples following their co-administration.

Allergic contact dermatitis from ethylhexyl salicylate and other salicylates

DEFF Research Database (Denmark)

Mortz, Charlotte G; Thormann, Henrik; Goossens, An

2010-01-01

Allergic contact dermatitis (ACD) from salicylates present in topical products is uncommon. Most publications about ACD from salicylates are case reports describing only a few patients. Cross-reactivity between salicylates is not commonly reported. This article describes allergic contact dermatitis...... from ethylhexyl salicylate used as an ultraviolet filter and fragrance compound and reviews the published literature on contact allergy to salicylates....

Differential uptake of salicylate in serum, cerebrospinal fluid, and perilymph.

Science.gov (United States)

Jastreboff, P J; Hansen, R; Sasaki, P G; Sasaki, C T

1986-10-01

After intraperitoneal administration of salicylate in anesthetized rats and guinea pigs, we found that salicylate levels in perilymph (PL) are closely related to both drug levels in cerebrospinal fluid (CSF) and in serum, with higher levels systematically observed in PL than in CSF. Further analysis suggests that salicylate is not passively transported into PL across CSF but, rather, is transported from blood directly to PL. The time course of salicylate uptake in rats reveals maximum levels at 1 1/2 hours (serum) and two to four hours (CSF and PL). On the other hand, salicylate uptake into serum and CSF of guinea pigs exhibits a longer time course, with maximum levels reached at four hours (serum) and five hours (CSF). These data, not previously available, are basic to our understanding of salicylate-related auditory effects.

Safety of continuing aspirin therapy during spinal surgery: A systematic review and meta-analysis.

Science.gov (United States)

Zhang, Chenggui; Wang, Guodong; Liu, Xiaoyang; Li, Yang; Sun, Jianmin

2017-11-01

Questions whether to continue or discontinue aspirin administration in the perioperative period of spinal surgery has not been systematically evaluated. The present systematic review is carried out to assess the impact of continuing aspirin administration on the bleeding and cardiovascular events in perispinal surgery period. Studies were retrieved through MEDLINE, EMBASE, and Springer Link Databases (search terms, aspirin, continue or discontinue, and spinal fusion), bibliographies of the articles retrieved, and the authors' reference files. We included studies that enrolled patients who underwent spinal surgery who were anticoagulated with aspirin alone and that reported bleeding or cardiovascular events as an outcome. Study quality was assessed using a validated form. 95% confidence interval (95% CI) was pooled to give summary estimates of bleeding and cardiovascular risk. We identified 4 studies assessing bleeding risk associated with aspirin continuation or cardiovascular risk with aspirin discontinuation during spinal surgery. The continuation of aspirin will not increase the risk of blood loss during the spinal surgery (95% CI, -111.72 to -0.59; P = .05). Also, there was no observed increase in the operative time (95% CI, -33.29 to -3.89; P = .01) and postoperative blood transfusion (95% CI, 0.00-0.27; P = .05). But as for the cardiovascular risk without aspirin continuation and mean hospital length of stay with aspirin continuation, we did not get enough samples to make an accurate decision about their relations with aspirin. Patients undergoing spinal surgery with continued aspirin administration do not have an increased risk for bleeding. In addition, there is no observed increase in the operation time and postoperative blood transfusion.

Pharmacokinetics and metabolic rates of acetyl salicylic acid and its metabolites in an Otomi ethnic group of Mexico.

Science.gov (United States)

Lares-Asseff, Ismael; Juárez-Olguín, Hugo; Flores-Pérez, Janett; Guillé-Pérez, Adrian; Vargas, Arturo

2004-05-01

The objective of this study was to determine pharmacokinetic differences of acetyl salicylic acid (ASA) and its metabolites: gentisic acid (GA), salicylic acid (SA) and salicyluric acid (SUA) between Otomies and Mesticians healthy subjects. Design. Ten Otomies and 10 Mesticians were included. After a single dose of aspirin given orally (15 mg/kg), blood and urine samples were collected at different times. Results. Pharmacokinetic parameters of salicylates showed significant differences, except distribution volume of SA, and elimination half-life of SUA. Metabolic rates of ASA showed significant differences for all rates between both groups. On the other hand, percentages of dose excreted were more reduced for SA and SUA for the Otomies than for the Mesticians. Conclusion. Results reflect differences in the hydrolysis way i.e. from ASA to SA and aromatic hydroxylation i.e. from SA to GA, which were slower in Otomies subjects, showing a possible pharmacokinetic differences about the capabilities of ASA biotransformation as a consequence of ethnic differences.

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

International Nuclear Information System (INIS)

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

1985-01-01

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

Diverse Data Sets Can Yield Reliable Information through Mechanistic Modeling: Salicylic Acid Clearance.

Science.gov (United States)

Raymond, G M; Bassingthwaighte, J B

This is a practical example of a powerful research strategy: putting together data from studies covering a diversity of conditions can yield a scientifically sound grasp of the phenomenon when the individual observations failed to provide definitive understanding. The rationale is that defining a realistic, quantitative, explanatory hypothesis for the whole set of studies, brings about a "consilience" of the often competing hypotheses considered for individual data sets. An internally consistent conjecture linking multiple data sets simultaneously provides stronger evidence on the characteristics of a system than does analysis of individual data sets limited to narrow ranges of conditions. Our example examines three very different data sets on the clearance of salicylic acid from humans: a high concentration set from aspirin overdoses; a set with medium concentrations from a research study on the influences of the route of administration and of sex on the clearance kinetics, and a set on low dose aspirin for cardiovascular health. Three models were tested: (1) a first order reaction, (2) a Michaelis-Menten (M-M) approach, and (3) an enzyme kinetic model with forward and backward reactions. The reaction rates found from model 1 were distinctly different for the three data sets, having no commonality. The M-M model 2 fitted each of the three data sets but gave a reliable estimates of the Michaelis constant only for the medium level data (K m = 24±5.4 mg/L); analyzing the three data sets together with model 2 gave K m = 18±2.6 mg/L. (Estimating parameters using larger numbers of data points in an optimization increases the degrees of freedom, constraining the range of the estimates). Using the enzyme kinetic model (3) increased the number of free parameters but nevertheless improved the goodness of fit to the combined data sets, giving tighter constraints, and a lower estimated K m = 14.6±2.9 mg/L, demonstrating that fitting diverse data sets with a single model

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

Science.gov (United States)

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

2015-01-01

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

Performing Aspirin Desensitization in Aspirin-Exacerbated Respiratory Disease.

Science.gov (United States)

Waldram, Jeremy D; Simon, Ronald A

2016-11-01

Aspirin-exacerbated respiratory disease (AERD) is characterized by chronic rhinosinusitis with nasal polyps, asthma, and reactions to cyclooxygenase-1-inhibiting drugs. This condition is often refractory to standard medical treatments and results in aggressive nasal polyposis that often requires multiple sinus surgeries. Aspirin desensitization followed by daily aspirin therapy is an important treatment option, and its efficacy has been validated in multiple research studies. Aspirin desensitization is not without risk, but specific protocols and recommendations exist to mitigate the risk. Most patients with AERD can undergo aspirin desensitization in an outpatient setting under the supervision of an allergist. Copyright © 2016 Elsevier Inc. All rights reserved.

Aspirin Desensitization

Science.gov (United States)

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

Salicylate-induced changes in spontaneous activity of single units in the inferior colliculus of the guinea pig.

Science.gov (United States)

Jastreboff, P J; Sasaki, C T

1986-11-01

Changes in spontaneous neuronal activity of the inferior colliculus in albino guinea pigs before and after administration of sodium salicylate were analyzed. Animals were anesthetized with pentobarbital, and two microelectrodes separated by a few hundred microns were driven through the inferior colliculus. After collecting a sufficiently large sample of cells, sodium salicylate (450 mg/kg) was injected i.p. and recordings again made 2 h after the injection. Comparison of spontaneous activity recorded before and after salicylate administration revealed highly statistically significant differences (p less than 0.001). After salicylate, the mean rate of the cell population increased from 29 to 83 Hz and the median from 26 to 74 Hz. Control experiments in which sodium salicylate was replaced by saline injection revealed no statistically significant differences in cell discharges. Recordings made during the same experiments from lobulus V of the cerebellar vermis revealed no changes in response to salicylate. The observed changes in single-unit activity due to salicylate administration may represent the first systematic evidence of a tinnituslike phenomenon in animals.

Could Aspirin and Diets High in Fiber Act Synergistically to Reduce the Risk of Colon Cancer in Humans?

Directory of Open Access Journals (Sweden)

Pan Pan

2018-01-01

Full Text Available Early inhibition of inflammation suppresses the carcinogenic process. Aspirin is the most commonly used non-steroid anti-inflammatory drugs (NSAIDs, and it irreversibly inhibits cyclooxygenase-1 and -2 (COX1, COX2. Multiple randomized clinical trials have demonstrated that aspirin offers substantial protection from colon cancer mortality. The lower aspirin doses causing only minimal gastrointestinal disturbance, ideal for long-term use, can achieve only partial and transitory inhibition of COX2. Aspirin’s principal metabolite, salicylic acid, is also found in fruits and vegetables that inhibit COX2. Other phytochemicals such as curcumin, resveratrol, and anthocyanins also inhibit COX2. Such dietary components are good candidates for combination with aspirin because they have little or no toxicity. However, obstacles to using phytochemicals for chemoprevention, including bioavailability and translational potential, must be resolved. The bell/U-shaped dose–response curves seen with vitamin D and resveratrol might apply to other phytochemicals, shedding doubt on ‘more is better’. Solutions include: (1 using special delivery systems (e.g., nanoparticles to retain phytochemicals; (2 developing robust pharmacodynamic biomarkers to determine efficacy in humans; and (3 selecting pharmacokinetic doses relevant to humans when performing preclinical experiments. The combination of aspirin and phytochemicals is an attractive low-cost and low-toxicity approach to colon cancer prevention that warrants testing, particularly in high-risk individuals.

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 ...

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

Science.gov (United States)

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

2013-01-01

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

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.

Aspirin decreases platelet uptake on Dacron vascular grafts in baboons

International Nuclear Information System (INIS)

Mackey, W.C.; Connolly, R.J.; Callow, A.D.

1984-01-01

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

Fermentation products of solvent tolerant marine bacterium Moraxella spp. MB1 and its biotechnological applications in salicylic acid bioconversion.

Directory of Open Access Journals (Sweden)

Solimabi Wahidullah

Full Text Available As part of a proactive approach to environmental protection, emerging issues with potential impact on the environment is the subject of ongoing investigation. One emerging area of environmental research concerns pharmaceuticals like salicylic acid, which is the main metabolite of various analgesics including aspirin. It is a common component of sewage effluent and also an intermediate in the degradation pathway of various aromatic compounds which are introduced in the marine environment as pollutants. In this study, biotransformation products of salicylic acid by seaweed, Bryopsis plumosa, associated marine bacterium, Moraxella spp. MB1, have been investigated. Phenol, conjugates of phenol and hydroxy cinnamic acid derivatives (coumaroyl, caffeoyl, feruloyl and trihydroxy cinnamyl with salicylic acid (3-8 were identified as the bioconversion products by electrospray ionization mass spectrometry. These results show that the microorganism do not degrade phenolic acid but catalyses oxygen dependent transformations without ring cleavage. The degradation of salicylic acid is known to proceed either via gentisic acid pathway or catechol pathway but this is the first report of biotransformation of salicylic acid into cinnamates, without ring cleavage. Besides cinnamic acid derivatives (9-12, metabolites produced by the bacterium include antimicrobial indole (13 and β-carbolines, norharman (14, harman (15 and methyl derivative (16, which are beneficial to the host and the environment.

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.

The analysis of methyl salicylate and salicylic acid from Chinese herbal medicine ingestion.

Science.gov (United States)

Parker, Dawn; Martinez, Christina; Stanley, Christina; Simmons, Jerry; McIntyre, Iain M

2004-04-01

This paper presents a multi-drug fatality in which methyl salicylate was ingested. It is presented to inform the toxicological community that a particularly expeditious method of detection for methyl salicylate exists. Previously published methods for the analysis of methyl salicylate include a gas chromatographic-mass spectrometric method and an alkaline/acidic extraction followed by high-performance liquid chromatographic (HPLC) analysis. This article describes a method for analyzing methyl salicylate using HPLC, in which a simple, rapid extraction procedure is used. Using a previously published HPLC method, methyl salicylate and salicylic acid were easily identified in biological specimens. Methyl salicylate and salicylic acid were detected using an extraction solution of acetonitrile coupled with internal standard and then analyzed by HPLC-diode-array detection. Because of its concentrated liquid form, methyl salicylate ingestion can cause rapid onset salicylate toxicity. As the potentially fatal methyl salicylate forms are readily available and easily found on drugstore shelves, the need to rapidly detect and quantitate salicylic acid concentrations that are due to methyl salicylate ingestion may arise. In the case presented, the peripheral blood concentration of salicylic acid from methyl salicylate ingestion was 320 mg/L, and the concentration in gastric contents was 820 mg. It alone was not the cause of death, however. The discovery of the ability to detect and quantitate methyl salicylate was due to its suspected ingestion.

Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution.

Science.gov (United States)

Suzuki, Takahiro; Yoshida, Norimasa; Nakabe, Nami; Isozaki, Yutaka; Kajikawa, Hirokazu; Takagi, Tomohisa; Handa, Osamu; Kokura, Satoshi; Ichikawa, Hiroshi; Naito, Yuji; Matsui, Hirofumi; Yoshikawa, Toshikazu

2008-03-01

Aspirin and nonsteroidal anti-inflammatory agents are known to induce gastroduodenal complications such as ulcer, bleeding, and dyspepsia. In this study, we examined the prophylactic effect of rebamipide, an anti-ulcer agent with free-radical scavenging and anti-inflammatory effect, on acidified aspirin-induced gastric mucosal injury in rats. In addition, we investigated the mucosal barrier functions disrupted by aspirin. Oral administration of acidified aspirin resulted in linear hemorrhagic erosions with increasing myeloperoxidase activity and thiobarbituric acid-reactive substance concentrations in the gastric mucosa. Rebamipide suppressed these acidified aspirin-induced gastric lesions and inflammatory changes significantly, and its protective effect was more potent in the case of repeated (twice daily for 3 days) treatment than single treatment before aspirin administration. Immunostaining of zonula occludens (ZO)-1, one of the tight junctional proteins, was strengthened in rat gastric mucosa after repeated administration of rebamipide. In addition, aspirin induced the increasing transport of fluorescine isothiocyanate-labeled dextrans with localized disruption and decreased expression of ZO-1 protein on rat gastric mucosal cell line RGM-1. Rebamipide effectively prevented aspirin-induced permeability changes and disruption of ZO-1 distribution. These results suggest that rebamipide protects against aspirin-induced gastric mucosal lesions by preserving gastric epithelial cell-to cell integrity in addition to the anti-inflammatory effects.

Aspirin inhibition of platelet deposition at angioplasty sites: demonstration by platelet scintigraphy

International Nuclear Information System (INIS)

Cuningham, D.A.; Kumar, B.; Siegel, B.A.; Gilula, L.A.; Totty, W.G.; Welch, M.J.

1984-01-01

In-111 platelet scintigraphy was used to evaluate the effects of prior aspirin administration on the accumulation of In-111-labeled autologous platelets at sites of arterial injury resulting from iliac, femoral, or popliteal transluminal angioplasty in a nonrandomized study of 17 men. The degree of platelet localization at angioplasty sites was significantly less in nine men who had received aspirin in varying doses within the 4 days before angioplasty than in eight men who had not received aspirin for at least two weeks. The results suggest that aspirin treatment before angioplasty limits the early platelet deposition at the angioplasty site in men

Plasma salicylate from methyl salicylate cream compared to oil of wintergreen.

Science.gov (United States)

Wolowich, William R; Hadley, Carmen M; Kelley, Michael T; Walson, Philip D; Casavant, Marcel J

2003-01-01

Poison Control Centers follow the acetylsalicylic acid (ASA) treatment guideline to manage unintentional ingestions of topical methyl salicylate liniments. For example, one teaspoon of 30% methyl salicylate cream such as Ben Gay provides an "ASA equivalent dose" of 180 mg/kg for a 10 kg child. The ASA treatment guideline advises emesis with syrup of Ipecac and 24 h home followup for this dose. Both the ASA conversion factor to yield the ASA equivalent dose and the treatment guideline assume 100% bioavailability of the salicylate. The nature of this topical dosage product led the investigators to expect less than complete absorption of methyl salicylate. To compare plasma concentrations of salicylate from ingested methyl salicylate cream with plasma concentrations of salicylate from ingested oil of wintergreen. Four adult volunteers consented to an open label, four-way crossover design, with randomization to the following treatments: 1 mL Oil of Wintergreen, U.S.P., 6.7 g of Ben Gay 15% and 20 g of Ben Gay 15% and also to hold 5 g of Ben Gay 15% cream in the buccal cavity for 1 minute and then expectorate. Plasma was collected for salicylate determination, and the results analyzed with a noncompartmental pharmacokinetic model. No plasma salicylate was detected after buccal treatment phase. Relative bioavailability for the low-dose treatment was 0.5 compared to oil of wintergreen. Plasma salicylate concentrations from methyl salicylate cream are not equal to those achieved after ingestion of oil of wintergreen. Dosage formulation must be considered when predicting toxicity.

Aspirin augments hyaluronidase induced adhesion inhibition ...

African Journals Online (AJOL)

Postoperative adhesions occur after virtually all abdomino-pelvic surgery and are the leading cause of intestinal obstruction and other gynaecologic problems. We used an animal model to test the efficacy of combined administration of aspirin and hyaluronidase on adhesion formation. Adhesions were induced using ...

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 ...

Spinal cholinergic involvement after treatment with aspirin and paracetamol in rats

DEFF Research Database (Denmark)

Abelson, Klas S P; Kommalage, Mahinda; Höglund, A Urban

2004-01-01

Aspirin and paracetamol have been shown to suppress non-inflammatory pain conditions like thermal, visceral and mechanical pain in mice and rats. The non-inflammatory antinociception appears to be mediated by central receptor mechanisms, such as the cholinergic system. In this study, we tested...... the hypothesis that the non-inflammatory antinociception of aspirin and paracetamol could be mediated by an increase of intraspinal acetylcholine release. Microdialysis probes were placed intraspinally in anesthetized rats for acetylcholine sampling. Subcutaneously administered aspirin 100 and 300 mg....../kg increased, while paracetamol 300 mg/kg decreased intraspinal acetylcholine release. Intraspinal drug administration did not affect acetylcholine release. Our results suggest that an increased intraspinal acetylcholine release could be involved in part of the non-inflammatory pain suppression by aspirin...

Metabolome analysis of effect of aspirin on Drosophila lifespan extension.

Science.gov (United States)

Song, Chaochun; Zhu, Chenxing; Wu, Qi; Qi, Jiancheng; Gao, Yue; Zhang, Zhichao; Gaur, Uma; Yang, Deying; Fan, Xiaolan; Yang, Mingyao

2017-09-01

Effective approaches for drug development involve the repurposing of existing drugs which are already approved by the FDA. Aspirin has been shown to have many health benefits since its discovery as a nonsteroidal anti-inflammatory drug (NSAID) to treat pain and inflammation. Recent experiments demonstrated the longevity effects of aspirin in Drosophila, but its mechanism remains to be explored. In order to elucidate the effects of drug on metabolism, we carried out the metabolic analysis of aspirin-treated flies. The results identified 404 active metabolites in addition to the extended lifespan and improved healthspan in fly. There were 28 metabolites having significant changes between aspirin-treated group and the control group, out of which 22 compounds were found to have detailed information. These compounds are reported to have important functions in energy metabolism, amino sugar metabolism, and urea metabolism, indicating that aspirin might be playing positive roles in the fly's lifespan and healthspan improvement. Because of the conservation of major longevity pathways and mechanisms in different species, the health benefits of aspirin administration could be extended to other animals and humans as well. Copyright © 2017 Elsevier Inc. All rights reserved.

Aspirin and Omeprazole

Science.gov (United States)

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

Effect of aspirin on the pharmacokinetics and absorption of panax notoginseng saponins.

Science.gov (United States)

Tian, Zhihao; Pang, Huanhuan; Zhang, Qiang; Du, Shouying; Lu, Yang; Zhang, Lin; Bai, Jie; Li, Pengyue; Li, Danqi; Zhao, Mengdi; Chen, Xiaonan

2018-02-01

Panax notoginseng saponins, a traditional Chinese medicine extraction, and aspirin are both widely used to treat cerebral infarction in China. Good results in clinical practice have been achieved, when Panax notoginseng saponins was taken together with aspirin. To investigate the interaction of the two drugs in vivo, the concentration of notoginsenoside R 1 , ginsenoside Rg 1 , Rb 1 , Re and Rd. in blood were simultaneously measured by UPLC/MS/MS. Sample preparation was carried out by the protein precipitation technique with an internal standard saikosaponin A standard. The separation of six components was achieved by using an ACQUITY UPLC ®BEH C18 column (1.7μm 2.1×100mm) by gradient elution using water (containing 0.2% formic acid) and acetonitrile (containing 0.2% formic acid) as the mobile phase at a flow rate of 0.2mL/min. The pharmacokinetic parameters were determined using non-compartmental analysis. The transport of notoginsenoside R 1 , ginsenoside Rg 1 , Rb 1 , Re and Rd. in MDCK -MDR1 cell monolayer was also used to verify the conclusion of pharmacokinetic drug-drug interaction and study the mechanism of drug interaction. The concentrations of the five components increased in a certain extent when the two drugs administered together in rats. The values of apparent permeability coefficients were significantly increased when the two drugs were used together. Aspirin and salicylic acid could destroy the tight junction protein and open the intercellular space to increase the absorption of Panax notoginseng saponins. Pharmacokinetic drug-drug interaction in vivo existed between Panax notoginseng saponins and aspirin. The drug-drug interaction mainly occurred in the process of absorption. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

2013-11-01

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

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

International Nuclear Information System (INIS)

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

2012-01-01

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 phox , p47 phox , p67 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 2 O 2 . Since SA had similar effect as ASA on AT1R expression, we suggest that ASA's effect is mediated by its SA moiety. -- Highlights: ► Aspirin in therapeutic concentrations decreases mouse cardiac fibroblast growth and collagen

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

The effect of the NMDA channel blocker memantine on salicylate-induced tinnitus in rats.

Science.gov (United States)

Ralli, M; Troiani, D; Podda, M V; Paciello, F; Eramo, S L M; de Corso, E; Salvi, R; Paludetti, G; Fetoni, A R

2014-06-01

Short-term tinnitus develops shortly after the administration of a high dose of salicylate. Since salicylate selectively potentiates N-methyl- D-aspartate (NMDA) currents in spiral ganglion neurons, it may play a vital role in tinnitus by amplifying NMDA-mediated neurotransmission. The aim of this study was to determine whether systemic treatment with a NMDA channel blocker, memantine, could prevent salicylate-induced tinnitus in animals. Additional experiments were performed to evaluate the effect of memantine on the auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) to test for changes in hearing function. Thirty-six rats were divided into 3 groups and treated daily for four consecutive days. One group (n = 12) was injected with salicylate (300 mg/kg/d, IP), the second (n = 12) was treated with memantine (5 mg/kg/d, IP) and the third group (n = 12) was injected with salicylate and memantine. All rats were tested for tinnitus and hearing loss at 2, 24, 48 and 72 h after the first drug administration and 24 h post treatment; tinnituslike behaviour was assessed with gap prepulse inhibition of acoustic startle (GPIAS), and hearing function was measured with DPOAE, ABR and noise burst prepulse inhibition of acoustic startle (NBPIAS). Rats in the salicylate group showed impaired GPIAS indicative of transient tinnitus-like behaviour near 16 kHz that recovered 24 h after the last salicylate treatment. Memantine did not cause a significant change in GPIAS. Combined injection of salicylate and memantine significantly attenuated GPIAS tinnitus-like behaviour at 48 hours after the first injection. None of the treatments induced permanent threshold shifts in the ABR and DPOAE, which recovered completely within one day post treatment. Animals treated with salicylate plus memantine showed results comparable to animals treated with salicylate alone, confirming that there is no effect of memantine on DPOAE which reflects OHC function. The

In vitro metabolism of nitric oxide-donating aspirin: the effect of positional isomerism.

Science.gov (United States)

Gao, Jianjun; Kashfi, Khosrow; Rigas, Basil

2005-03-01

NO-donating aspirin (NO-ASA) is a potentially important chemopreventive agent against cancer. Since positional isomerism affects strongly its potency in inhibiting colon cancer cell growth, we studied the metabolic transformations of its ortho-, meta-, and para-isomers in rat liver and colon cytosolic, microsomal, and mitochondrial fractions as well as in intact HT-29 human colon cancer cells. NO-ASA and metabolites were determined by high-performance liquid chromatography and products identified by mass spectroscopy, as required. For all three isomers, the acetyl group on the ASA moiety was hydrolyzed rapidly. This was followed by hydrolysis of the ester bond linking the salicylate anion to the spacer. The ortho- and para-isomers produced salicylic acid and a putative intermediate consisting of the remainder of the molecule, which via a rapid step generated nitrate, (hydroxymethyl)phenol, and a conjugate of spacer with glutathione. The meta-isomer, in contrast, generated salicylic acid and (nitroxymethyl)phenol, the latter leading to (hydroxymethyl)phenol and the glutathione-spacer conjugate. This metabolic pathway takes place in its entirety only in the cytosolic fraction of the tissues tested and in intact human colon cancer cells, perhaps reflecting exposure to the cytosolic glutathione S-transferase, which catalyzes the formation of the spacer-glutathione conjugate. Thus, the three positional isomers of NO-ASA differ in their metabolism and these differences correlate with their differential effects on cancer cell growth, underscoring the importance of positional isomerism in modulating drug effects.

Influence of aspirin and non-aspirin NSAID use on ovarian and endometrial cancer

DEFF Research Database (Denmark)

Verdoodt, F.; Kjaer, S. K.; Friis, S.

2017-01-01

Increasing evidence supports a role for aspirin use in reducing the incidence and mortality of several cancer types. This has spurred a new wave of interest in this widely used drug. In this review, we present and evaluate the epidemiologic evidence of the association between the use of aspirin....... Overall, observational studies indicate modest reductions in risk of ovarian and endometrial cancer with aspirin use, whereas the results for non-aspirin NSAID use are equivocal. The strongest inverse associations have been reported for long-term consistent aspirin use, notably among subgroups of users (e.......g., those with high body mass index). Few studies have evaluated the influence of NSAID use on the mortality of ovarian or endometrial cancer, and substantial heterogeneity of study characteristics and results preclude any conclusions. Additional studies of aspirin and non-aspirin NSAID use and ovarian...

Salicylate-induced changes in auditory thresholds of adolescent and adult rats.

Science.gov (United States)

Brennan, J F; Brown, C A; Jastreboff, P J

1996-01-01

Shifts in auditory intensity thresholds after salicylate administration were examined in postweanling and adult pigmented rats at frequencies ranging from 1 to 35 kHz. A total of 132 subjects from both age levels were tested under two-way active avoidance or one-way active avoidance paradigms. Estimated thresholds were inferred from behavioral responses to presentations of descending and ascending series of intensities for each test frequency value. Reliable threshold estimates were found under both avoidance conditioning methods, and compared to controls, subjects at both age levels showed threshold shifts at selective higher frequency values after salicylate injection, and the extent of shifts was related to salicylate dose level.

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.

Aspirin induces IL-4 production: augmented IL-4 production in aspirin-exacerbated respiratory disease

Science.gov (United States)

Kong, Su-Kang; Soo Kim, Byung; Gi Uhm, Tae; Soo Chang, Hun; Sook Park, Jong; Woo Park, Sung; Park, Choon-Sik; Chung, Il Yup

2016-01-01

Aspirin hypersensitivity is a hallmark of aspirin-exacerbated respiratory disease (AERD), a clinical syndrome characterized by the severe inflammation of the respiratory tract after ingestion of cyclooxygenase-1 inhibitors. We investigated the capacity of aspirin to induce interleukin-4 (IL-4) production in inflammatory cells relevant to AERD pathogenesis and examined the associated biochemical and molecular pathways. We also compared IL-4 production in peripheral blood mononuclear cells (PBMCs) from patients with AERD vs aspirin-tolerant asthma (ATA) upon exposure to aspirin. Aspirin induced IL-4 expression and activated the IL-4 promoter in a report assay. The capacity of aspirin to induce IL-4 expression correlated with its activity to activate mitogen-activated protein kinases, to form DNA–protein complexes on P elements in the IL-4 promoter and to synthesize nuclear factor of activated T cells, critical transcription factors for IL-4 transcription. Of clinical importance, aspirin upregulated IL-4 production twice as much in PBMCs from patients with AERD compared with PBMCs from patients with ATA. Our results suggest that IL-4 is an inflammatory component mediating intolerance reactions to aspirin, and thus is crucial for AERD pathogenesis. PMID:27534531

Up-regulation of Ca2+/CaMKII/CREB signaling in salicylate-induced tinnitus in rats.

Science.gov (United States)

Zhao, Jiuhan; Wang, Biao; Wang, Xiaohong; Shang, Xiuli

2018-02-09

The purpose of the study was to investigate the changes of Ca 2+ /calmodulin-dependent protein kinases II (CaMKII)/cAMP response element-binding protein (CREB) signaling pathway in a rat tinnitus model. Eighteen Wistar rats were randomly divided into three groups: normal control (NC), normal saline (NS), and tinnitus model (TM) groups. Tinnitus model was induced by intraperitoneal injection of salicylate. The concentration of intracellular calcium level in auditory cortex cells was determined using Fura-2 acetoxymethyl ester (Fura-2 AM) method with fluorospectrophotometer. Expressions of calmodulin (CaM), N-methyl-D-aspartate receptor 2B subunit (NR2B), calcium-calmodulin kinase II (CaMKII), and cAMP response element-binding protein (CREB) were detected with Western blot. Tinnitus model was successfully established by the intraperitoneal administration of salicylate in rats. Compared with rats in NC and NS groups, salicylate administration significantly elevated CaM, NR2B, phospho-CaMKII and phospho-CREB expression in auditory cortex from tinnitus model group (p salicylate administration causes tinnitus symptoms and elevates Ca 2+ /CaMKII/CREB signaling pathway in auditory cortex cells. Our study likely provides a new understanding of the development of tinnitus.

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

Science.gov (United States)

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

2011-06-01

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

[Aspirin and colorectal cancer].

Science.gov (United States)

Grancher, Adrien; Michel, Pierre; Di Fiore, Frédéric; Sefrioui, David

2018-02-01

Colorectal cancer is a worldwide public health problem. Aspirin has been identified as a protective factor against the apparition of colorectal cancer. There are several mechanisms about the actions by aspirin on colorectal tumorogenesis. These are not perfectly known nowadays. On one hand, there are direct mechanisms on colorectal mucosa, on the other hand there are indirect mechanisms through platelet functions. Aspirin also plays a role by its anti-inflammatory action and the stimulation of antitumor immunity. Several studies show that long-term treatment with low-doses of aspirin decreases the incidence of adenomas and colorectal cancers. In the United States, aspirin is currently recommended for primary prevention of the risk of colorectal cancer in all patients aged 50 to 59, with a 10-year risk of cardiovascular event greater than 10 %. However, primary prevention with aspirin should not be a substitute for screening in colorectal cancer. Furthermore, aspirin seems to be beneficial when used in post-diagnosis of colorectal cancer. It could actually decrease the risk of metastasis in case of a localized colorectal cancer, and increase the survival in particular, concerning PIK3CA mutated tumors. The association of aspirin with neoadjuvant treatment of colorectal cancer by radiochimiotherapy seems to have beneficial effects. French prospective randomized study is currently being conducted to investigate postoperative aspirin in colorectal cancers with a PIK3CA mutation. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Therapeutic utility of aspirin in the ApcMin/+ murine model of colon carcinogenesis

International Nuclear Information System (INIS)

Reuter, Brian K; Zhang, Xiao-Jing; Miller, Mark JS

2002-01-01

In recent years it has become evident that nonsteroidal anti-inflammatory drugs, in particular aspirin represent a potential class of cancer chemotherapeutic agents. Despite the wealth of knowledge gained from epidemiological, clinical and animal studies, the effectiveness of aspirin to treat established gastrointestinal cancer has not been determined. The present study examines the ability of aspirin to treat established polyposis in Min/+ mice. Min/+ mice with established polyposis were treated orally once daily from 12–16 weeks of age with either drug vehicle or aspirin (25 mg/kg). Upon completion of treatment, the number, location and size of intestinal tumours was determined. Additional variables examined were the number of apoptotic cells within tumours and COX activity. Administration of aspirin for 4 weeks to Min/+ mice produce no effect on tumour number compared to vehicle-treated Min/+ mice (65 ± 8 vs. 63 ± 9, respectively). In addition, aspirin had no effect on tumour size or location. However, aspirin treatment produced a greater than 2-fold (p < 0.05) increase in the number of apoptotic positive cells within tumours and significantly decreased hepatic PGE 2 content. Aspirin was found to have no effect on tumour number and size when administered to Min/+ mice with established polyposis. The findings in the present study call in to question the utility of aspirin as a stand-alone treatment for established GI cancer. However, aspirin's ability to significantly promote apoptosis may render it suitable for use in combinatorial chemotherapy

Long-term sinonasal outcomes of aspirin desensitization in aspirin exacerbated respiratory disease.

Science.gov (United States)

Cho, Kyu-Sup; Soudry, Ethan; Psaltis, Alkis J; Nadeau, Kari C; McGhee, Sean A; Nayak, Jayakar V; Hwang, Peter H

2014-10-01

This study aimed to assess sinonasal outcomes in patients with aspirin exacerbated respiratory disease (AERD) undergoing aspirin desensitization following endoscopic sinus surgery (ESS). Case series with chart review. University hospital. A retrospective review of sinonasal outcomes was conducted for 30 AERD patients undergoing aspirin desensitization and maintenance therapy following ESS. Sinonasal outcomes were prospectively assessed by the Sinonasal Outcomes Test-22 (SNOT-22) and endoscopic polyp grading system. Data were collected preoperatively, 1 and 4 weeks postsurgery (before desensitization), and 1, 6, 12, 18, 24, and 30 months after aspirin desensitization. Twenty-eight of 30 patients (93.3%) successfully completed aspirin desensitization, whereas 2 of 30 (6.7%) were unable to complete desensitization due to respiratory intolerance. Of the 21 patients who successfully completed a minimum of 24 weeks of follow-up, 20 (95.2%) patients demonstrated sustained endoscopic and symptomatic improvement for a median follow-up period of 33 months. After surgical treatment but before desensitization, patients experienced significant reductions in SNOT-22 and polyp grade scores. In the first 6 months after aspirin desensitization, patients experienced further significant reductions in SNOT-22 scores, whereas polyp grade remained stable. The improvements in symptom endoscopic scores were preserved throughout the follow-up period after desensitization. No patients required additional sinus surgery. One patient had to discontinue aspirin therapy due to gastrointestinal side effects. No other adverse reactions to aspirin were noted. Aspirin desensitization following ESS appears to be a well-tolerated and effective adjunctive therapy for long-term control of nasal polyposis in patients with AERD. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Influencing of resorption and side-effects of salicylic acid by complexing with β-cyclodextrin

International Nuclear Information System (INIS)

Szejtli, J.; Gerloczy, A.; Sebestyen, G.; Fonagy, A.

1981-01-01

After oral administration of 14 C-labelled salicylic acid and its β-cyclodextrin complex to rats, the radioactivity level of the blood reached its maximum during the first 2 h. The blood level obtained with the complex is somewhat but not significantly lower than with free acid. Since the resorption of cyclodextrin is a considerably slower process, it is very likely that the resorption of salicylic acid takes place in the form of free acid after dissociation of the complex. The urinary excretion cumulative curves showed that the free salicylic acid was completely excreted, while about 10% of the salicylic acid administered in the form of complex is lost. The cyclodextrin complex formation increased the pK values of all hydroxybenzoic acids. Direct observations revealed that complex formation decreased the stomach-irritating effect of salicylic acid. The ratio of radioactivity was nearly the same in the organs of animals treated by both free salicylic and cyclodextrin complex. (author)

Treatment of post-electroconvulsive therapy headache with topical methyl salicylate.

Science.gov (United States)

Logan, Christopher J; Stewart, Jonathan T

2012-06-01

Headache after administration of electroconvulsive therapy (ECT) is common, affecting approximately half of patients treated. Post-ECT headache is typically treated with acetaminophen or nonsteroidal anti-inflammatory drugs but occasionally requires agents such as sumatriptan, opioids, or β-blockers. We report on a patient whose severe post-ECT headaches responded completely to methyl salicylate ointment, applied to the area of his temporalis and masseter muscles. Topical methyl salicylate is generally well tolerated and may be a viable option for some patients with post-ECT headache.

Extraction and spectrophotometric determination of vanadium(V) with N-hydroxy-N-m-tolyl-N'-(2-methyl-5-chloro)-phenyl-p-toluamidine hydrochloride in presence of salicylic, anthranilic and phthalic acids

Energy Technology Data Exchange (ETDEWEB)

Patel, K S; Deb, K K; Mishra, R [Ravishankar Univ., Raipur (India). Dept. of Chemistry

1981-02-01

The present work deals with the solvent extraction and simultaneous spectrophotometric determination of microgram quantities of vanadium(V) as mixed ligand complex with N-hydroxy-N-m-tolyl-N'-(2-methyl-5-chloro)-phenyl-p-toluamidine hydrochloride (HTMCPTH) and six carboxylic acids viz. salicylic, acetylsalicylic (aspirin), sulfosalicylic, anthranilic, N-phenyl-anthranilic and phthalic. The method presented here is simple, rapid, sensitive and reasonably selective.

Extraction and spectrophotometric determination of vanadium(V) with N-hydroxy-N-m-tolyl-N'-(2-methyl-5-chloro)-phenyl-p-toluamidine hydrochloride in presence of salicylic, anthranilic and phthalic acids

International Nuclear Information System (INIS)

Patel, K.S.; Deb, K.K.; Mishra, R.

1981-01-01

The present work deals with the solvent extraction and simultaneous spectrophotometric determination of microgram quantities of vanadium(V) as mixed ligand complex with N-hydroxy-N-m-tolyl-N'-(2-methyl-5-chloro)-phenyl-p-toluamidine hydrochloride (HTMCPTH) and six carboxylic acids viz. salicylic, acetylsalicylic (aspirin), sulfosalicylic, anthranilic, N-phenyl-anthranilic and phthalic. The method presented here is simple, rapid, sensitive and reasonably selective. (author)

Aspirin resistance following pediatric cardiac surgery.

Science.gov (United States)

Cholette, Jill M; Mamikonian, Lara; Alfieris, George M; Blumberg, Neil; Lerner, Norma B

2010-09-01

Aspirin is often used to prevent thrombosis in pediatric cardiac surgery. The primary study aim was to assess aspirin resistance in this context. Secondary aims were to evaluate (1) the relationship between elevated inflammatory markers and thrombosis and (2) aspirin's effect on these levels. This was a prospective observational study of children undergoing cardiac surgery managed with and without aspirin. Aspirin response was assessed using the VerifyNow system and urinary 11-dehydrothromboxane B2 (uTxB2) measurements. Laboratory studies of inflammation were also obtained. 101 subjects were studied; 50 received aspirin. Six subjects (5.9%), 5 aspirin-treated, experienced symptomatic thrombosis. When measured by VerifyNow resistance was 43% after aspirin suppositories and 14% after additional days of oral aspirin. There was no correlation with thrombosis. Upper quartile post-operative day (POD) #5 uTxB2 was correlated with thrombosis in aspirin treated subjects (pchildren with high levels of uTxB2 despite aspirin therapy and/or those with elevated preoperative CRP are at increased risk for thrombosis. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Comparative assessment of captopril and aspirin administration during dynamic renal scintigraphy in diagnosing renovascular hypertension

International Nuclear Information System (INIS)

Kostadinova, I.; Simeonova, A.

1997-01-01

The shortcoming of the captopril test used as a noninvasing screening method in diagnosing renovascular hypertension (RVH) is that in the course of study, ACE-inhibitors (angiotensin-converting enzymes) and diuretics should be discontinued from the therapeutic scheme of patients. The authors compare it to the alternative one with aspirin. The study covers eight patients with angiographic evidence of RVH with significant unilateral stenosis of the renal artery. The obtained results are evaluated on the ground of quantitative (T max , T 1/2 , divided renal function and retention index), as well as qualitative criteria (visual assay). As shown by the results the functional effect of captopril is rather markedly expressed in 6 patients, and the effect of aspirin - in 2. It is concluded that captopril test is more accurate in demonstrating RVH, but in patients with firm clinical evidence of a significant angiotensin II-dependent RVH and negative captopril test, it is advisable to apply aspirin test with a view to differentiate renovascular from essential hypertension

Effect of intravenous sodium salicylate administration prior to castration on plasma cortisol and electroencephalography parameters in calves.

Science.gov (United States)

Bergamasco, L; Coetzee, J F; Gehring, R; Murray, L; Song, T; Mosher, R A

2011-12-01

Nociception is an unavoidable consequence of many routine management procedures such as castration in cattle. This study investigated electroencephalography (EEG) parameters and cortisol levels in calves receiving intravenous sodium salicylate in response to a castration model. Twelve Holstein calves were randomly assigned to the following groups: (i) castrated, untreated controls, (ii) 50 mg/kg sodium salicylate IV precastration, were blood sampled at 0, 5, 10, 20, 30, 45, 60, 90, 120, 150, 180, 240, 360, and 480 min postcastration. The EEG recording included baseline, castration, immediate recovery (0-5 min after castration), middle recovery (5-10 min after castration), and late recovery (10-20 min after castration). Samples were analyzed by competitive chemiluminescent immunoassay and fluorescence polarization immunoassay for cortisol and salicylate, respectively. EEG visual inspection and spectral analysis were performed. Statistical analyses included anova repeated measures and correlations between response variable. No treatment effect was noted between the two groups for cortisol and EEG measurements, namely an attenuation of acute cortisol response and EEG desynchronization in sodium salicylate group. Time effects were noted for EEG measurements, cortisol and salicylates levels. Significant correlations between cortisol and EEG parameters were noted. These findings have implications for designing effective analgesic regimens, and they suggest that EEG can be useful to monitor pain attributable to castration. © 2011 Blackwell Publishing Ltd.

Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events.

Science.gov (United States)

Squizzato, Alessandro; Bellesini, Marta; Takeda, Andrea; Middeldorp, Saskia; Donadini, Marco Paolo

2017-12-14

Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. Adding a second antiplatelet drug to aspirin may produce additional benefit for people at high risk and people with established cardiovascular disease. This is an update to a previously published review from 2011. To review the benefit and harm of adding clopidogrel to aspirin therapy for preventing cardiovascular events in people who have coronary disease, ischaemic cerebrovascular disease, peripheral arterial disease, or were at high risk of atherothrombotic disease, but did not have a coronary stent. We updated the searches of CENTRAL (2017, Issue 6), MEDLINE (Ovid, 1946 to 4 July 2017) and Embase (Ovid, 1947 to 3 July 2017) on 4 July 2017. We also searched ClinicalTrials.gov and the WHO ICTRP portal, and handsearched reference lists. We applied no language restrictions. We included all randomised controlled trials comparing over 30 days use of aspirin plus clopidogrel with aspirin plus placebo or aspirin alone in people with coronary disease, ischaemic cerebrovascular disease, peripheral arterial disease, or at high risk of atherothrombotic disease. We excluded studies including only people with coronary drug-eluting stent (DES) or non-DES, or both. We collected data on mortality from cardiovascular causes, all-cause mortality, fatal and non-fatal myocardial infarction, fatal and non-fatal ischaemic stroke, major and minor bleeding. The overall treatment effect was estimated by the pooled risk ratio (RR) with 95% confidence interval (CI), using a fixed-effect model (Mantel-Haenszel); we used a random-effects model in cases of moderate or severe heterogeneity (I 2 ≥ 30%). We assessed the quality of the evidence using the GRADE approach. We used GRADE profiler (GRADE Pro) to import data from Review Manager to create a 'Summary of findings' table. The search identified 13 studies in addition to the two studies in the previous version of our systematic review. Overall

Salicylate, diflunisal and their metabolites inhibit CBP/p300 and exhibit anticancer activity.

Science.gov (United States)

Shirakawa, Kotaro; Wang, Lan; Man, Na; Maksimoska, Jasna; Sorum, Alexander W; Lim, Hyung W; Lee, Intelly S; Shimazu, Tadahiro; Newman, John C; Schröder, Sebastian; Ott, Melanie; Marmorstein, Ronen; Meier, Jordan; Nimer, Stephen; Verdin, Eric

2016-05-31

Salicylate and acetylsalicylic acid are potent and widely used anti-inflammatory drugs. They are thought to exert their therapeutic effects through multiple mechanisms, including the inhibition of cyclo-oxygenases, modulation of NF-κB activity, and direct activation of AMPK. However, the full spectrum of their activities is incompletely understood. Here we show that salicylate specifically inhibits CBP and p300 lysine acetyltransferase activity in vitro by direct competition with acetyl-Coenzyme A at the catalytic site. We used a chemical structure-similarity search to identify another anti-inflammatory drug, diflunisal, that inhibits p300 more potently than salicylate. At concentrations attainable in human plasma after oral administration, both salicylate and diflunisal blocked the acetylation of lysine residues on histone and non-histone proteins in cells. Finally, we found that diflunisal suppressed the growth of p300-dependent leukemia cell lines expressing AML1-ETO fusion protein in vitro and in vivo. These results highlight a novel epigenetic regulatory mechanism of action for salicylate and derivative drugs.

Lack of dose dependent kinetics of methyl salicylate-2-O-β-D-lactoside in rhesus monkeys after oral administration.

Science.gov (United States)

He, Yangyang; Yan, Yu; Zhang, Tiantai; Ma, Yinzhong; Zhang, Wen; Wu, Ping; Song, Junke; Wang, Shuang; Du, Guanhua

2015-04-22

Methyl salicylate-2-O-β-d-lactoside (MSL) is one of the main active components isolated from Gaultheria yunnanensis, which is a traditional Chinese medicine used to treat arthritis and various aches and pains. Pharmacological researches showed that MSL had various effective activities in both in vivo and in vitro experiments. However, the pharmacokinetics features and oral bioavailability of MSL in primates were not studied up to now. To study the pharmacokinetics of different doses of MSL in rhesus monkeys and investigate the absolute bioavailability of MSL after oral administration. Male and female rhesus monkeys were either orally administrated with MSL 200, 400 and 800 mg/kg or received an intravenous dose of 20mg/kg randomly. The levels of MSL and salicylic acid (SA) in plasma were simultaneous measured by a simple, sensitive and reproducible high performance liquid chromatography method. Mean peak plasma concentration values for groups treated with 200, 400 and 800 mg/kg doses ranged from 48.79 to 171.83 μg/mL after single-dose oral administration of MSL, and mean area under the concentration-time curve values ranged from 195.16 to 1107.76 μg/mL h. Poor linearity of the kinetics of SA after oral administration of MSL was observed in the regression analysis of the Cmax-dose plot (r(2)=0.812), CL-dose plot (r(2)=0.225) and AUC(0-t)-dose plot (r(2)=0.938). Absolute bioavailability of MSL was assessed to be 118.89 ± 57.50, 213.54 ± 58.98 and 168.72 ± 76.58%, respectively. Bioavailability of MSL after oral administration in rhesus monkeys was measured for the first time. Pharmacokinetics parameters did not appear to be dose proportional among the three oral doses of treatments, and MSL showed an apparent absolute bioavailability in excess of 100% in rhesus monkeys based on the present study. In addition, a rapid, sensitive and reliable HPLC method was established and demonstrated for the research of traditional Chinese medicine in this study. Copyright �

Effects of aspirin, carprofen, deracoxib, and meloxicam on platelet function and systemic prostaglandin concentrations in healthy dogs.

Science.gov (United States)

Blois, Shauna L; Allen, Dana G; Wood, R Darren; Conlon, Peter D

2010-03-01

To determine effects of therapeutic dosages of aspirin, carprofen, deracoxib, and meloxicam on platelet function and systemic prostaglandin concentrations in healthy dogs. 10 hound-crossbred dogs. Aspirin (10 mg/kg, PO, q 12 h), carprofen (4.4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), meloxicam (0.1 mg/kg, PO, q 24 h), and a placebo were administered for 7 days in a random order to each of 10 healthy dogs; there was a 21-day washout period between subsequent treatments. One-stage prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, and plasma concentrations of thromboxane (TX)B(2) and 6-keto prostaglandin (PG)F(1alpha) were measured before and after treatment administration. Platelet function was assessed by use of a platelet-function analyzer and aggregation. Aspirin, carprofen, and meloxicam did not significantly affect platelet function. Deracoxib caused a mild decrease in platelet aggregation induced by 50microM ADP. Platelet number, Hct, PT, aPTT, and plasma TXB(2) and 6-keto PGF(1alpha) concentrations were unchanged after NSAID administration. Meloxicam administration resulted in a significant decrease in fibrinogen concentration, but results remained within the laboratory reference interval. Oral administration of commonly used NSAIDs at therapeutic dosages in healthy dogs did not alter plasma TXB(2) and 6-keto PGF(1alpha) concentrations. Deracoxib administration resulted in a minor abnormality in platelet aggregation. Anti-inflammatory doses of aspirin did not affect platelet function as measured by use of optical aggregometry and a platelet-function analyzer. Further evaluation of the effects of aspirin and cyclooxygenase-2-selective inhibitors on hemostasis should be performed.

Aspirin attenuates spontaneous recurrent seizures in the chronically epileptic mice.

Science.gov (United States)

Zhu, Kun; Hu, Ming; Yuan, Bo; Liu, Jian-Xin; Liu, Yong

2017-08-01

Neuroinflammatory processes are pathologic hallmarks of both experimental and human epilepsy, and could be implicated in the neuronal hyperexcitability. Aspirin represents one of the non-selective nonsteroidal anti-inflammatory drugs with fewer side effects in long-term application. This study was carried out to assess the anti-epileptic effects of aspirin when administered during the chronic stage of temporal lobe epilepsy [TLE] in mice. The alteration of hippocampal neurogenesis was also examined for raising a possible mechanism underlying the protective effect of anti-inflammatory treatment in the TLE. Two months after pilocarpine-induced status epilepticus, the chronically epileptic mice were treated with aspirin (20 mg, 60 mg or 80 mg/kg) once a day for 10 weeks. Spontaneous recurrent seizures were monitored by video camera for 2 weeks. To evaluate the profile of hippocampal neurogenesis, the newly generated cells in the dentate gyrus were labeled by the proliferation marker BrdU. The newborn neurons that extended axons to CA3 area were visualized by cholera toxin B subunit retrograde tracing. Administration of aspirin with a dosage of 60 mg or 80 mg/kg initiated at 2 months after pilocarpine-induced status epilepticus significantly reduced the frequency and duration of spontaneous recurrent seizures. Aspirin treatment also increased the number of newborn neurons with anatomic integration through improving the survival of the newly generated cells. Aspirin treatment during the chronic stage of TLE could attenuate the spontaneous recurrent seizures in mice. Promotion of hippocampal neurogenesis and inhibition of COX-PGE2 pathway might partly contribute to this anti-epileptic effect. Highlights • Aspirin attenuates spontaneous recurrent seizures of chronically epileptic mice • Aspirin increases neurogenesis of chronically epileptic hippocampus by improving the survival of newly generated cells • Promotion of hippocampal neurogenesis and inhibition

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

Science.gov (United States)

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

2017-05-10

Acetylsalicylic acid (Aspirin, ASA) is a famous drug for cardiovascular diseases in recent years. Effects of ASA dosage on the metabolic profile have not been fully understood. The purpose of our study is to establish a rapid and reliable method to quantify ASA metabolites in biological matrices, especially for glucuronide metabolites whose standards are not commercially available. Then we applied this method to evaluate the effects of ASA dosage on the metabolic and excretion profile of ASA metabolites in rat urine. Salicylic acid (SA), gentisic acid (GA) and salicyluric acid (SUA) were determined directly by UHPLC-MS/MS, while salicyl phenolic glucuronide (SAPG) and salicyluric acid phenolic glucuronide (SUAPG) were quantified indirectly by measuring the released SA and SUA from SAPG and SUAPG after β-glucuronidase digestion. SUA and SUAPG were the major metabolites of ASA in rat urine 24h after ASA administration, which accounted for 50% (SUA) and 26% (SUAPG). When ASA dosage was increased, the contributions dropped to 32% and 18%, respectively. The excretion of other three metabolites (GA, SA and SAPG) however showed remarkable increases by 16%, 6% and 4%, respectively. In addition, SUA and SUAPG were mainly excreted in the time period of 12-24h, while GA was excreted in the earlier time periods (0-4h and 4-8h). SA was mainly excreted in the time period of 0-4h and 12-24h. And the excretion of SAPG was equally distributed in the four time periods. We went further to show that the excretion of five metabolites in rat urine was delayed when ASA dosage was increased. In conclusion, we have developed a rapid and sensitive method to determine the five ASA metabolites (SA, GA, SUA, SAPG and SUAPG) in rat urine. We showed that ASA dosage could significantly influence the metabolic and excretion profile of ASA metabolites in rat urine. Copyright © 2016 Elsevier B.V. All rights reserved.

Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events

NARCIS (Netherlands)

Squizzato, Alessandro; Bellesini, Marta; Takeda, Andrea; Middeldorp, Saskia; Donadini, Marco Paolo

2017-01-01

Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. Adding a second antiplatelet drug to aspirin may produce additional benefit for people at high risk and people with established cardiovascular disease. This is an update to a previously published review

Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular disease

NARCIS (Netherlands)

Squizzato, Alessandro; Keller, Tymen; Romualdi, Erica; Middeldorp, Saskia

2011-01-01

Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. Adding a second antiplatelet drug to aspirin may produce additional benefit for those at high risk and those with established cardiovascular disease. To quantify the benefit and harm of adding clopidogrel

Taking Aspirin to Protect Your Heart

Science.gov (United States)

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

Aspirin for Primary Prevention.

Science.gov (United States)

Richman, Ilana B; Owens, Douglas K

2017-07-01

Aspirin reduces the risk of nonfatal myocardial infarction and stroke, and the risk of colorectal cancer. Aspirin increases the risk of gastrointestinal and intracranial bleeding. The best available evidence supports initiating aspirin in select populations. In 2016, the US Preventive Services Task Force recommended initiating aspirin for the primary prevention of both cardiovascular disease and colorectal cancer among adults ages 50 to 59 who are at increased risk for cardiovascular disease. Adults 60 to 69 who are at increased cardiovascular disease risk may also benefit. There remains considerable uncertainty about whether younger and older patients may benefit. Copyright © 2017 Elsevier Inc. All rights reserved.

Synthesis of isotopically labelled salicylates

International Nuclear Information System (INIS)

Hawkins, D.R.; Pryor, R.W.

1981-01-01

[ 13 C-carboxyl]Salicylic acid has been prepared by carbonation of 2-benzyloxybromobenzene followed by reductive debenzylation. Deuterium and tritium labelled salicylic acid and 2 H 2 / 13 C-salicylic acid were prepared by reduction of the 3,5-dibromo derivatives using Raney Ni-Al. Deuterium labelled salicylic acid containing up to four deuterium atoms was prepared by catalytic exchange with Raney Ni-Al in 5% NaOD/D 2 O. (author)

Salicylic Acid Topical

Science.gov (United States)

... the package label for more information.Apply a small amount of the salicylic acid product to one or two small areas you want to treat for 3 days ... know that children and teenagers who have chicken pox or the flu should not use topical salicylic ...

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 ...

Dgroup: DG01504 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available ory drug, salicylic acid derivatives ... DG00015 ... Acetylsalicylic acid ... D00109 ... Aspirin (JP17/USP); Aspalon (JAN) ... D05181 ... Aspirin... aluminum (JP17) ... D07579 ... Aspirin calcium salt ... D07580 ... Aspirin DL-lysine (JAN) ... D07581 ... Aspirin... magnesium salt ... D07582 ... Aspirin sodium ... DG00099 ... Olsalazine ... D0

Dgroup: DG01712 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available salicylic acid ... D00109 ... Aspirin (JP17/USP); Aspalon (JAN) ... D05181 ... Aspirin aluminum (JP17) ... D07579 ... Aspirin... calcium salt ... D07580 ... Aspirin DL-lysine (JAN) ... D07581 ... Aspirin magnesium salt ... D07582 ... Aspirin sodium DG0... DG01712 DGroup Antiplatelet agent Platelet aggregation inhibitor ... DG00015 ... Acetyl

Aspirin for Evidence-Based Preeclampsia Prevention trial: effect of aspirin in prevention of preterm preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history.

Science.gov (United States)

Poon, Liona C; Wright, David; Rolnik, Daniel L; Syngelaki, Argyro; Delgado, Juan Luis; Tsokaki, Theodora; Leipold, Gergo; Akolekar, Ranjit; Shearing, Siobhan; De Stefani, Luciana; Jani, Jacques C; Plasencia, Walter; Evangelinakis, Nikolaos; Gonzalez-Vanegas, Otilia; Persico, Nicola; Nicolaides, Kypros H

2017-11-01

The Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention trial demonstrated that in women who were at high risk for preterm preeclampsia with delivery at aspirin administration from 11 to 14 until 36 weeks' gestation was associated with a significant reduction in the incidence of preterm preeclampsia (odds ratio 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). We sought to examine whether there are differences in the effect of aspirin on the incidence of preterm preeclampsia in the Aspirin for Evidence-Based Preeclampsia Prevention trial in subgroups defined according to maternal characteristics and medical and obstetrical history. This was a secondary analysis of data from the Aspirin for Evidence-Based Preeclampsia Prevention trial. Subgroup analysis was performed to assess evidence of differences in the effect of aspirin on incidence of preterm preeclampsia in subgroups defined by maternal age (aspirin effect in subgroups defined according to maternal characteristics and obstetrical history. In participants with chronic hypertension preterm preeclampsia occurred in 10.2% (5/49) in the aspirin group and 8.2% (5/61) in the placebo group (adjusted odds ratio, 1.29; 95% confidence interval, 0.33-5.12). The respective values in those without chronic hypertension were 1.1% (8/749) in the aspirin group and 3.9% (30/761) in the placebo group (adjusted odds ratio, 0.27; 95% confidence interval, 0.12-0.60). In all participants with adherence of ≥90% the adjusted odds ratio in the aspirin group was 0.24 (95% confidence interval, 0.09-0.65); in the subgroup with chronic hypertension it was 2.06 (95% confidence interval, 0.40-10.71); and in those without chronic hypertension it was 0.05 (95% confidence interval, 0.01-0.41). For the complete data set the test of interaction was not significant at the 5% level (P = .055), but in those with adherence ≥90%, after adjustment for multiple comparisons

Effect of aspirin desensitization on T-cell cytokines and plasma lipoxins in aspirin-exacerbated respiratory disease.

Science.gov (United States)

Aksu, Kurtuluş; Kurt, Emel; Alatas, Özkan; Gülbas, Zafer

2014-01-01

The pathogenesis of aspirin-exacerbated respiratory disease (AERD) is thought to be based on, mainly, overproduction of eicosanoid lipid mediators and on defective anti-inflammatory regulators. Aspirin desensitization treatment, the mainstay of controlling asthma and rhinitis in AERD patients, however, is the least understood aspect of the disease. The study was designed to determine the effect of aspirin desensitization on T-lymphocyte cytokine expression and on plasma lipoxin levels in AERD. Spirometry, skin-prick test and asthma control test were documented and intracellular cytokine expression in T lymphocytes and plasma lipoxin levels were measured in 23 AERD patients, 17 aspirin-tolerant asthmatic (ATA) patients, and 16 healthy controls. In the AERD group nasal symptom and smell scores were assessed. Of the 23 AERD patients 15 accepted to undergo aspirin desensitization protocol and 14 of them were desensitized successfully. In the desensitized AERD group, cytokine and lipoxin measurements were repeated after 1-month aspirin treatment. CD4(+) IL-10 levels were higher in AERD patients than in healthy controls and CD4(+) interferon (IFN) gamma levels were higher in AERD and ATA patients than in controls. Plasma lipoxin-A4 and 15-epi-lipoxin-A4 levels were similar among the three study groups. In the AERD group, subjects underwent aspirin desensitization followed by a 1-month aspirin treatment. Clinical parameters improved and CD4(+) IFN-gamma levels decreased significantly. No significant change in lipoxin levels was recorded. CD4(+) IFN-gamma and CD4(+) IL-10 levels in AERD patients after 1-month aspirin desensitization treatment were similar to the healthy controls. The study confirms aspirin desensitization is effective clinically in AERD patients and suggests that IFN gamma and IL-10 expression in CD4(+) T lymphocytes may be related to the mechanism of action.

Synthesis of 125 I - Salicyl Hydroxamic Acid for Urinary Bladder Imaging

International Nuclear Information System (INIS)

Ibrahim, I.T.; Abou EL Zahab, M.; Hamed, M.

2015-01-01

Salicylhydroxamic acid is a salicylate derivative. Radiolabeling of Salicyl hydroxamic acid ( SHA ) with iodine-125 may have considerable interest for imaging of urinary bladder. This study is aimed to optimize the radiolabeling yield of Salicyl hydroxamic with radio iodine (125-123) using chloramine - T (CAT) as an oxidizing agent with respect to factors that affect the reaction conditions such as SHA amount, CAT amount, reaction time and ph of the reaction mixture. In - vitro stability of the radiolabeled complex was checked and it was found to be stable for up to 24 h. 125 I-SHA was injected via intravenous administration routes into normal male Sprague – Dawley rats. Bio - distribution studies have revealed that 125 I-SHA was excreted in urine with extent that it could give a clear image for urinary bladder especially if the bladder it tightly closed. The amount of 125 I - Salicyl hydroxamic excreted was increased in case of giving potassium bicarbonate to rat before injection of 125 I-SHA. The result of biodistribution study of 125 I - SHA in experimental animal suggest ed the possibility of using 123 I-SHA to image the urinary bladder

Pharmacokinetics of methyl salicylate-2-O-β-D-lactoside, a novel salicylic acid analog isolated from Gaultheria yunnanensis, in dogs.

Science.gov (United States)

Zhang, Dan; Ma, Xiaowei; Xin, Wenyu; Huang, Chao; Zhang, Weiku; Zhang, Tiantai; Du, Guanhua

2013-12-01

Methyl salicylate-2-O-β-D-lactoside (MSL), a natural salicylate derivative of Gaultheria yunnanensis (Franch.) Rehder (G. yunnanensis), has been shown to provide a beneficial anti-inflammatory effect in animal models. Studies on the pharmacokinetics and bioavailability of MSL can provide both a substantial foundation for understanding its mechanism and empirical evidence to support its use in clinical practice. A simple and sensitive high-performance liquid chromatography (HPLC) method, coupled with ultraviolet analyte detection, was developed for determining the concentration of MSL and its metabolite in beagle plasma. Chromatographic separation was achieved on a Agilent Zorbax SB-C18 column (5 μM,4.6 × 250 mm). The mobile phase consisted of aqueous solution containing 0.1% phosphoric acid and acetonitrile (82:90, v/v), at a flow rate of 1 mL/min. Validation of the assay demonstrated that the developed HPLC method was sensitive, accurate and selective for the determination of MSL and its metabolite in dog plasma. After orally administering three doses of MSL, it could no longer be detected in dog plasma and its metabolite, salicylic acid, was detected. Salicylic acid showed a single peak in the plasma concentration-time curves and linear pharmacokinetics following the three oral doses (r(2) > 0.99). In contrast, only MSL was detected in plasma following intravenous administration. These results will aid in understanding the pharmacological significance of MSL. The developed method was successfully used for evaluation of the oral and intravenous pharmacokinetic profile of MSL in dogs. Copyright © 2013 John Wiley & Sons, Ltd.

Comparative bioequivalence assessment of aspirin tablets marketed ...

African Journals Online (AJOL)

Purpose: In the last few years, aspirin has become a life saver against cardiovascular accidents. This investigation was carried out to determine possible bioequivalence between regular aspirin and soluble aspirin tablets marketed in Nigeria. Methods: The in vivo bioavailability profiles of three commercial brands of aspirin ...

[Low-dose aspirin in patients with diabete melitus: risks and benefits regarding macro and microvascular complications].

Science.gov (United States)

Camargo, Eduardo G; Gross, Jorge Luiz; Weinert, Letícia S; Lavinsky, Joel; Silveiro, Sandra P

2007-04-01

Aspirin is recommended as cardiovascular disease prevention in patients with diabetes mellitus. Due to the increased risk of bleeding and because of the hypothesis that there could be a worsening of microvascular complications related to aspirin, there has been observed an important underutilization of the drug. However, it is now known that aspirin is not associated with a deleterious effect on diabetic retinopathy and there is evidence indicating that it also does not affect renal function with usual doses (150 mg/d). On the other hand, higher doses may prove necessary, since recent data suggest that diabetic patients present the so called "aspirin resistance". The mechanisms of this resistance are not yet fully understood, being probably related to an abnormal intrinsic platelet activity. The employment of alternative antiplatelet strategies or the administration of higher aspirin doses (150-300 mg/d) should be better evaluated regarding effective cardiovascular disease prevention in diabetes as well as the possible effects on microvascular complications.

Salicylic acid-independent plant defence pathways

OpenAIRE

Pieterse, C.M.J.; Loon, L.C. van

1999-01-01

Salicylic acid is an important signalling molecule involved in both locally and systemically induced disease resistance responses. Recent advances in our understanding of plant defence signalling have revealed that plants employ a network of signal transduction pathways, some of which are independent of salicylic acid. Evidence is emerging that jasmonic acid and ethylene play key roles in these salicylic acid-independent pathways. Cross-talk between the salicylic acid-dependent and the salicy...

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 ...

Cytokine expression before and after aspirin desensitization therapy in aspirin-exacerbated respiratory disease.

Science.gov (United States)

Aktas, Ayse; Kurt, Emel; Gulbas, Zafer

2013-12-01

Aspirin exacerbated respiratory disease (AERD) is induced by acetylsalicylic acid (ASA) and/or nonsteroidal antiinflammatory drugs (NSAIDs). Effects of desensitization on many mediators have been examined previously, but few studies addressed the influence of desensitization on T lymphocytes and T lymphocyte-derived cytokines. This study was performed to examine peripheral blood lymphocyte (PBL) cytokine expression in aspirin-sensitive patients who have asthma before and after aspirin desensitization. In this study, the release of interleukin-2 (IL-2), interleukin-4 (IL-4), and interferon-gamma (IFN-γ) by CD4+ T lymphocytes prior to aspirin desensitization were also measured at intracellular levels, and expression of these cytokines after 1 month aspirin desensitization was evaluated. Twelve patients with AERD were included in the study. Two different control groups were formed, one consisted of 15 healthy people and second 12 aspirin tolerant asthmatic (ATA) patients using aspirin. A blood sample was collected prior to desensitization, and the tests were repeated by taking a second blood sample 1 month after the 4-day desensitization treatment. The proportion of lymphocytes secreting IFN-γ in the study group was 15.61 ± 4.40 % before desensitization and 15.08 ± 5.89 % after desensitization. The rate of IFN-γ secreting CD4+ T lymphocytes was 20.51 ± 4.41 % in the normal control group and 16.07 ± 5.7 % in the ATA group (p = 0.021). The ratio of CD4+ T lymphocyte secreting IFN-γ was reduced in patients with AERD before desensitization compared to normal control group (p = 0.040). The levels of IL-2, IL-4, and the subsets of lymphocyte were not different before and after desensitization compared to control groups.

Simultaneous Determination of Salicylic Acid, Jasmonic Acid, Methyl Salicylate, and Methyl Jasmonate from Ulmus pumila Leaves by GC-MS

Directory of Open Access Journals (Sweden)

Zhi-hong Huang

2015-01-01

Full Text Available Salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate are important phytohormones and defensive signaling compounds, so it is of great importance to determine their levels rapidly and accurately. The study uses Ulmus pumila leaves infected by Tetraneura akinire Sasaki at different stages as materials; after extraction with 80% methanol and ethyl acetate and purification with primary secondary amine (PSA and graphitized carbon blacks (GCB, the contents of signal compounds salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate were determined by GC-MS. The results showed that the level of salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate increased remarkably in U. pumila once infected by T. akinire Sasaki, but the maximums of these four compounds occurred at different times. Salicylic acid level reached the highest at the early stage, and jasmonic acid level went to the maximum in the middle stage; by contrast, change of content of methyl salicylate and methyl jasmonate was the quite opposite.

Simultaneous Determination of Salicylic Acid, Jasmonic Acid, Methyl Salicylate, and Methyl Jasmonate from Ulmus pumila Leaves by GC-MS.

Science.gov (United States)

Huang, Zhi-Hong; Wang, Zhi-Li; Shi, Bao-Lin; Wei, Dong; Chen, Jian-Xin; Wang, Su-Li; Gao, Bao-Jia

2015-01-01

Salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate are important phytohormones and defensive signaling compounds, so it is of great importance to determine their levels rapidly and accurately. The study uses Ulmus pumila leaves infected by Tetraneura akinire Sasaki at different stages as materials; after extraction with 80% methanol and ethyl acetate and purification with primary secondary amine (PSA) and graphitized carbon blacks (GCB), the contents of signal compounds salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate were determined by GC-MS. The results showed that the level of salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate increased remarkably in U. pumila once infected by T. akinire Sasaki, but the maximums of these four compounds occurred at different times. Salicylic acid level reached the highest at the early stage, and jasmonic acid level went to the maximum in the middle stage; by contrast, change of content of methyl salicylate and methyl jasmonate was the quite opposite.

Pigmentation, anesthesia, behavioral factors, and salicylate uptake.

Science.gov (United States)

Jastreboff, P J; Issing, W; Brennan, J F; Sasaki, C T

1988-02-01

In four experiments, 54 pigmented rats were used to examine the time course of sodium salicylate uptake in serum, cerebrospinal fluid, and perilymph. Subjects were tested under sodium pentobarbital anesthesia or while conscious. Compared with previously reported data from albino rats, pigmented subjects generally showed increased salicylate uptake. Moreover, the data suggested two different, time-dependent clearance mechanisms in conscious animals not observed in anesthetized rats. Daily injections of salicylate did not produce an accumulation of salicylate in serum. Systematically higher levels of salicylate were observed in perilymph compared with cerebrospinal fluid. Behavioral procedures, including water deprivation and conditioned suppression of ongoing drinking levels, had no effect on salicylate levels.

Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial.

Science.gov (United States)

Halkes, P H A; van Gijn, J; Kappelle, L J; Koudstaal, P J; Algra, A

2006-05-20

Results of trials of aspirin and dipyridamole combined versus aspirin alone for the secondary prevention of vascular events after ischaemic stroke of presumed arterial origin are inconsistent. Our aim was to resolve this uncertainty. We did a randomised controlled trial in which we assigned patients to aspirin (30-325 mg daily) with (n=1363) or without (n=1376) dipyridamole (200 mg twice daily) within 6 months of a transient ischaemic attack or minor stroke of presumed arterial origin. Our primary outcome event was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever happened first. Treatment was open, but auditing of outcome events was blinded. Primary analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN73824458) and with (NCT00161070). Mean follow-up was 3.5 years (SD 2.0). Median aspirin dose was 75 mg in both treatment groups (range 30-325); extended-release dipyridamole was used by 83% (n=1131) of patients on the combination regimen. Primary outcome events arose in 173 (13%) patients on aspirin and dipyridamole and in 216 (16%) on aspirin alone (hazard ratio 0.80, 95% CI 0.66-0.98; absolute risk reduction 1.0% per year, 95% CI 0.1-1.8). Addition of the ESPRIT data to the meta-analysis of previous trials resulted in an overall risk ratio for the composite of vascular death, stroke, or myocardial infarction of 0.82 (95% CI 0.74-0.91). Patients on aspirin and dipyridamole discontinued trial medication more often than those on aspirin alone (470 vs 184), mainly because of headache. The ESPRIT results, combined with the results of previous trials, provide sufficient evidence to prefer the combination regimen of aspirin plus dipyridamole over aspirin alone as antithrombotic therapy after cerebral ischaemia of arterial origin.

21 CFR 556.590 - Salicylic acid.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Salicylic acid. 556.590 Section 556.590 Food and... Residues of New Animal Drugs § 556.590 Salicylic acid. A tolerance of zero is established for residues of salicylic acid in milk from dairy animals. ...

21 CFR 201.314 - Labeling of drug preparations containing salicylates.

Science.gov (United States)

2010-04-01

... distributor, be labeled for use by adults only. If their labeling and advertising clearly offer them for... clearly offered for administration to adults only. (f) If the labeling or advertising of a salicylate... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Labeling of drug preparations containing...

The risk of venous thromboembolism with aspirin compared to anticoagulants after hip and knee arthroplasty.

Science.gov (United States)

Chu, Janet N; Maselli, Judith; Auerbach, Andrew D; Fang, Margaret C

2017-07-01

Recent guidelines include aspirin as an option to prevent venous thromboembolism (VTE) in selected patients undergoing hip or knee replacement surgery. However, the efficacy of aspirin after arthroplasty has not been well-defined, particularly in more contemporary patient populations. We compared rates of post-operative VTE between patients who received aspirin-only versus anticoagulants after hip or knee arthroplasty, using data from a large US-based administrative database. We conducted a retrospective cohort study of 231,780 adults who underwent total knee arthroplasty and 110,621 who underwent total hip arthroplasty in 2009-2012 and who received pharmacologic VTE prophylaxis (aspirin or anticoagulant) within the first 7days after surgery. We compared the risk of post-operative VTE between patients receiving aspirin-only vs. anticoagulants, controlling for clinical and hospital characteristics using multivariable logistic regression with propensity score adjustment. Aspirin-only prophylaxis was administered to 7.5% of patients after knee arthroplasty and 8.0% after hip arthroplasty. Post-operative VTE was diagnosed in 2217 (0.96%) patients after knee arthroplasty and 454 (0.41%) after hip arthroplasty. Compared to anticoagulants, aspirin was not associated with a higher risk for post-operative VTE either after knee arthroplasty (adjusted odds ratio and 95% confidence interval [OR] 0.34 [0.24-0.48]) or hip arthroplasty (OR 0.82 [0.45-1.51]). Aspirin was uncommonly administered as the sole prophylactic agent after hip or knee arthroplasty in this study. However, patients who received aspirin-only had similar rates of post-operative VTE compared to patients who received anticoagulants. Further research should focus on distinguishing which patients benefit more from anticoagulants versus aspirin after arthroplasty. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of salicylate on 3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity in rats.

Science.gov (United States)

Yeh, S Y

1997-11-01

The drug 3,4-methylenedioxymethamphetamine (MDMA) is a serotonergic neurotoxicant that causes hyperthermia and depletion of serotonin (5-HT) and 5-hydroxy-indole-3-acetic acid (5-HIAA) in the central nervous system. Formation of neurotoxic metabolites of MDMA, e.g., 2,4,5-trihydroxy-methamphetamine and 2,4,5-trihydroxyamphetamine, involves hydroxyl and/or superoxide free radicals. The present study was designed to determine whether the hydroxyl free-radical-trapping agent salicylate could provide protection against MDMA neurotoxicity in rats. In the acute studies, sodium salicylate (12.5-400 mg/kg, calculated as free acid) was injected interperitoneally (i.p.) 1 h before subcutaneous (s.c.) injections of MDMA (20 mg/kg as base). In the chronic studies, sodium salicylate (3.1-100 mg/kg) was injected i.p. 1 h before repeated s.c. injections of MDMA (10 mg/kg as base, twice daily, at 0830 and 1730 h for 4 consecutive days). Repeated MDMA administration depleted contents of 5-HT and 5-HIAA in the frontal cortex, hippocampus and striatum. Coadministration of salicylate plus MDMA did not significantly alter MDMA-induced depletion of 5-HT and 5-HIAA in these tissues. Thus, salicylate, a hydroxyl free-radical-trapping agent, does not protect against MDMA-induced hyperthermia and depletion of 5-HT and 5-HIAA. These observations suggest that MDMA-induced neurotoxicity may occur mainly through the production of superoxide or other radicals rather than hydroxyl free radicals. Salicylate actually potentiated MDMA-induced hyperthermia and lethality, findings that might be of clinical relevance.

Long-term efficacy of aspirin desensitization in aspirin-exacerbated respiratory disease. Review of two clinical cases

Directory of Open Access Journals (Sweden)

Julio César Cambray-Gutiérrez

2016-05-01

Clinical cases: two patients diagnosed with respiratory disease exacerbated by aspirin, with poor asthma control and need for multiple polypectomies, despite optimal pharmacological management, carrying out protocol desensitization to aspirin (AAS successful, now after 4 years of having carried out, they have adequate asthma control without need for polypectomies with a maintenance dose of aspirin 150 mg/day.

Aspirin challenge and desensitization: how, when and why.

Science.gov (United States)

Cortellini, Gabriele; Caruso, Cristiano; Romano, Antonino

2017-08-01

To investigate the current approach to aspirin challenge (drug provocation) and/or desensitization in patients with histories of hypersensitivity reactions to it, particularly in those with cardiovascular diseases. The literature indicates that patients with coronary artery disease (CAD), including those with an acute coronary syndrome, may safely undergo low-dose aspirin challenge and/or desensitization. Recently, flowcharts regarding challenge/desensitization procedures with aspirin in patients with CAD and histories of aspirin hypersensitivity reactions have become available. Aspirin desensitization and continuous aspirin therapy constitute an effective option in patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory diseases (NERD) who have suboptimally controlled asthma or rhinosinusitis, or require multiple revision polypectomies. The use of aspirin has proven to reduce morbidity and mortality associated with CAD. There is a general consensus on aspirin's effectiveness in secondary prevention of CAD. Therefore, aspirin desensitization is necessary in patients with CAD and histories of hypersensitivity reactions to it. The effectiveness of aspirin desensitization and continuous therapy in patients with NERD has been shown in numerous studies. However, shared selection criteria of candidates for aspirin challenge/desensitization procedures, and simple and homogeneous protocols are necessary. Moreover, preventive safety measures are still needed in order to reduce the potential risks of these procedures.

Daily Aspirin Therapy: Understand the Benefits and Risks

Science.gov (United States)

Daily aspirin therapy: Understand the benefits and risks Daily aspirin therapy can be a lifesaving option, but it's not ... everyone. Get the facts before considering a daily aspirin. By Mayo Clinic Staff Daily aspirin therapy may ...

Pharmacokinetics of salicylate in rabbits with acute kidney failure

International Nuclear Information System (INIS)

Laznicek, M.; Melicharova, L.; Kvetina, J.; Laznickova, A.

1989-01-01

Changes in the pharmacokinetics and metabolism of sodium salicylate were studied in rabbits with acute renal failure induced by intravenous administration of uranyl nitrate hexahydrate in a dose of 0.2 mg kg -1 . 14 C-labelled salicylic acid, 99m Tc-complex and 125 I-hippuran were used to study the metabolism. The 99m Tc and 125 I activities were measured with a Tesla gamma counter or beta-gamma spectrometer NE 8312. The 14 C activity was measured using beta spectrometer Rack beta 1219. The 99m Tc activity was determined immediately after the experiment, the 14 C activity was determined after 4 days. The drug concentration was determined by comparing the activities of the sample and the standard activities. (J.J.). 6 figs., 1 tab., 18 refs

Comparison and analysis on the serum-binding characteristics of aspirin-zinc complex and aspirin.

Science.gov (United States)

Zhang, Hua-Xin; Zhang, Qun; Wang, Hong-Lin; Li, Li-Wei

2017-09-01

This study was designed to compare the protein-binding characteristics of aspirin-zinc complex (AZN) with those of aspirin itself. AZN was synthesized and interacted with a model transport protein, human serum albumin (HSA). Three-dimensional fluorescence, ultraviolet-visible and circular dichroism (CD) spectra were used to characterize the interaction of AZN with HSA under physiological conditions. The interaction mechanism was explored using a fluorescence quenching method and thermodynamic calculation. The binding site and binding locality of AZN on HSA were demonstrated using a fluorescence probe technique and Förster non-radiation energy transfer theory. Synchronous fluorescence and CD spectra were employed to reveal the effect of AZN on the native conformation of the protein. The HSA-binding results for AZN were compared with those for aspirin under consistent experimental conditions, and indicated that aspirin acts as a guide in AZN when binding to Sudlow's site I, in subdomain IIA of the HSA molecule. Moreover, compared with aspirin, AZN showed greater observed binding constants with, but smaller changes in the α-helicity of, HSA, which proved that AZN might be easier to transport and have less toxicity in vivo. Copyright © 2017 John Wiley & Sons, Ltd.

Mechanisms of aspirin-sensitive asthma

Directory of Open Access Journals (Sweden)

Sun Ying

2004-01-01

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

Aspirin provocation increases 8-iso-PGE2 in exhaled breath condensate of aspirin-hypersensitive asthmatics.

Science.gov (United States)

Mastalerz, Lucyna; Januszek, Rafał; Kaszuba, Marek; Wójcik, Krzysztof; Celejewska-Wójcik, Natalia; Gielicz, Anna; Plutecka, Hanna; Oleś, Krzysztof; Stręk, Paweł; Sanak, Marek

2015-09-01

Isoprostanes are bioactive compounds formed by non-enzymatic oxidation of polyunsaturated fatty acids, mostly arachidonic, and markers of free radical generation during inflammation. In aspirin exacerbated respiratory disease (AERD), asthmatic symptoms are precipitated by ingestion of non-steroid anti-inflammatory drugs capable for pharmacologic inhibition of cyclooxygenase-1 isoenzyme. We investigated whether aspirin-provoked bronchoconstriction is accompanied by changes of isoprostanes in exhaled breath condensate (EBC). EBC was collected from 28 AERD subjects and 25 aspirin-tolerant asthmatics before and after inhalatory aspirin challenge. Concentrations of 8-iso-PGF2α, 8-iso-PGE2, and prostaglandin E2 were measured using gas chromatography/mass spectrometry. Leukotriene E4 was measured by immunoassay in urine samples collected before and after the challenge. Before the challenge, exhaled 8-iso-PGF2α, 8-iso-PGE2, and PGE2 levels did not differ between the study groups. 8-iso-PGE2 level increased in AERD group only (p=0.014) as a result of the aspirin challenge. Urinary LTE4 was elevated in AERD, both in baseline and post-challenge samples. Post-challenge airways 8-iso-PGE2 correlated positively with urinary LTE4 level (p=0.046), whereas it correlated negatively with the provocative dose of aspirin (p=0.027). A significant increase of exhaled 8-iso-PGE2 after inhalatory challenge with aspirin was selective and not present for the other isoprostane measured. This is a novel finding in AERD, suggesting that inhibition of cyclooxygenase may elicit 8-iso-PGE2 production in a specific mechanism, contributing to bronchoconstriction and systemic overproduction of cysteinyl leukotrienes. Copyright © 2015 Elsevier Inc. All rights reserved.

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...

Salicylate-induced changes in immediate-early genes in the hippocampal CA1 area.

Science.gov (United States)

Wu, Hao; Xu, Feng-Lei; Yin, Yong; Da, Peng; You, Xiao-Dong; Xu, Hui-Min; Tang, Yan

2015-08-01

Studies have suggested that salicylate affects neuronal function via interactions with specific membrane channels/receptors. However, the effect of salicylate on activity and synaptic morphology of the hippocampal Cornu Ammonis (CA) 1 area remains to be elucidated. The activation of immediate-early genes (IEGs) was reported to correlate with neuronal activity, in particular activity-regulated cytoskeleton-associated protein and early growth response gene 1. The aim of the present study was to evaluate the expression of these IEGs, as well that of N-methyl D-aspartate (NMDA) receptor subunit 2B in rats following acute and chronic salicylate treatment. Protein and messenger RNA levels of all three genes were increased in rats following chronic administration of salicylate (300 mg/kg for 10 days), returning to baseline levels 14 days post-cessation of treatment. The transient upregulation of gene expression following treatment was accompanied by ultrastructural alterations in hippocampal CA1 area synapses. An increase in synaptic interface curvature was observed as well as an increased number of presynaptic vesicles; in addition, postsynaptic densities thickened and lengthened. In conclusion, the results of the present study indicated that chronic exposure to salicylate may lead to structural alteration of hippocampal CA1 neurons, and it was suggested that this process occurs through induced expression of IEGs via NMDA receptor activation.

Methamphetamine-induced dopaminergic toxicity prevented owing to the neuroprotective effects of salicylic acid.

Science.gov (United States)

Thrash-Williams, Bessy; Karuppagounder, Senthilkumar S; Bhattacharya, Dwipayan; Ahuja, Manuj; Suppiramaniam, Vishnu; Dhanasekaran, Muralikrishnan

2016-06-01

Methamphetamine (Schedule-II drug, U.S. Drug Enforcement Administration) is one of the most abused illicit drug following cocaine, marijuana, and heroin in the USA. There are numerous health impairments and substantial economic burden caused by methamphetamine abuse. Salicylic acid, potent anti-inflammatory drug and a known neuroprotectant has shown to protect against toxicity-induced by other dopaminergic neurotoxins. Hence, in this study we investigated the neuroprotective effects of salicylic acid against methamphetamine-induced toxicity in mice. The current study investigated the effects of sodium salicylate and/or methamphetamine on oxidative stress, monoamine oxidase, mitochondrial complex I & IV activities using spectrophotometric and fluorimetric methods. Behavioral analysis evaluated the effect on movement disorders-induced by methamphetamine. Monoaminergic neurotransmitter levels were evaluated using high pressure liquid chromatography-electrochemical detection. Methamphetamine caused significant generation of reactive oxygen species and decreased complex-I activity leading to dopamine depletion. Striatal dopamine depletion led to significant behavioral changes associated with movement disorders. Sodium salicylate (50 & 100mg/kg) significantly scavenged reactive oxygen species, blocked mitochondrial dysfunction and exhibited neuroprotection against methamphetamine-induced neurotoxicity. In addition, sodium salicylate significantly blocked methamphetamine-induced behavioral changes related to movement abnormalities. One of the leading causative theories in nigral degeneration associated with movement disorders such as Parkinson's disease is exposure to stimulants, drugs of abuse, insecticide and pesticides. These neurotoxic substances can induce dopaminergic neuronal insult by oxidative stress, apoptosis, mitochondrial dysfunction and inflammation. Salicylic acid due to its antioxidant and anti-inflammatory effects could provide neuroprotection against the

Effects of aspirin on distortion product fine structure: interpreted by the two-source model for distortion product otoacoustic emissions generation.

Science.gov (United States)

Rao, Aparna; Long, Glenis R

2011-02-01

Distortion product otoacoustic emission (DPOAE) fine structure is due to the interaction of two major components coming from different places in the cochlea. One component is generated from the region of maximal overlap of the traveling waves generated by the two primaries and is attributed to nonlinear distortion (nonlinear component). The other component arises predominantly from the tonotopic region of the distortion product and is attributed to linear coherent reflection (reflection component). Aspirin (salicylate) ototoxicity can cause reversible hearing loss and reduces otoacoustic emission generation in the cochlea. The two components are expected to be affected differentially by cochlear health. Changes in DPOAE fine structure were recorded longitudinally in three subjects before, during, and after aspirin consumption. Full data sets were analyzed for two subjects, but only partial data could be analyzed from the third subject. Resulting changes in the two components of DPOAE fine structure revealed variability among subjects and differential effects on the two components. For low-intensity primaries, both components were reduced with the reflection component being more vulnerable. For high-intensity primaries, the nonlinear component showed little or no change, but the reflection component was always reduced.

Expression of immediate-early genes in the dorsal cochlear nucleus in salicylate-induced tinnitus.

Science.gov (United States)

Hu, Shou-Sen; Mei, Ling; Chen, Jian-Yong; Huang, Zhi-Wu; Wu, Hao

2016-02-01

Spontaneous neuronal activity in dorsal cochlear nucleus (DCN) may be involved in the physiological processes underlying salicylate-induced tinnitus. As a neuronal activity marker, immediate-early gene (IEG) expression, especially activity-dependent cytoskeletal protein (Arc/Arg3.1) and the early growth response gene-1 (Egr-1), appears to be highly correlated with sensory-evoked neuronal activity. However, their relationships with tinnitus induced by salicylate have rarely been reported in the DCN. In this study, we assessed the effect of acute and chronic salicylate treatment on the expression of N-methyl D-aspartate receptor subunit 2B (NR2B), Arg3.1, and Egr-1. We also observed ultrastructural alterations in the DCN synapses in an animal model of tinnitus. Levels of mRNA and protein expression of NR2B and Arg3.1 were increased in rats that were chronically administered salicylate (200 mg/kg, twice daily for 3, 7, or 14 days). These levels returned to baseline 14 days after cessation of treatment. However, no significant changes were observed in Egr-1 gene expression in any groups. Furthermore, rats subjected to long-term salicylate administration showed more presynaptic vesicles, thicker and longer postsynaptic densities, and increased synaptic interface curvature. Alterations of Arg3.1 and NR2B may be responsible for the changes in the synaptic ultrastructure. These changes confirm that salicylate can cause neural plasticity changes at the DCN level.

The role of aspirin desensitization in patients with aspirin-exacerbated respiratory disease (AERD).

Science.gov (United States)

Spies, Jonas Willian; Valera, Fabiana Cardoso Pereira; Cordeiro, Daniel Loiola; de Mendonça, Taís Nociti; Leite, Marcelo Gonçalves Junqueira; Tamashiro, Edwin; Arruda, Luiza Karla; Anselmo-Lima, Wilma Terezinha

2016-01-01

Aspirin-exacerbated respiratory disease (AERD) consists of a classic tetrad: moderate/severe asthma, chronic rhinosinusitis, nasal polyps, and intolerance to aspirin or other nonsteroidal anti-inflammatory drugs. Clinical control with drugs, surgery, and desensitization are treatment options. To evaluate the efficacy and tolerability of aspirin desensitization in patients with AERD. Periodic symptom assessment and endoscopy in patients with AERD undergoing surgery who were desensitized. Seventeen patients were desensitized. Eight patients completed the desensitization and were followed for a minimum of a one-year period (mean 3.1 years). These patients showed improvement in all symptoms. Moreover, surgical reassessment was not indicated in any of these patients and there was a decrease in costs with medication and procedures. Eight patients did not complete desensitization, mainly due to procedure intolerance and uncontrolled asthma, whereas another patient was lost to follow-up. Aspirin desensitization, when tolerated, was effective in patients with AERD and with poor clinical/surgical response. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Synthesis, Characterization, and Anti-Inflammatory Activities of Methyl Salicylate Derivatives Bearing Piperazine Moiety.

Science.gov (United States)

Li, Jingfen; Yin, Yong; Wang, Lisheng; Liang, Pengyun; Li, Menghua; Liu, Xu; Wu, Lichuan; Yang, Hua

2016-11-23

In this study, a new series of 16 methyl salicylate derivatives bearing a piperazine moiety were synthesized and characterized. The in vivo anti-inflammatory activities of target compounds were investigated against xylol-induced ear edema and carrageenan-induced paw edema in mice. The results showed that all synthesized compounds exhibited potent anti-inflammatory activities. Especially, the anti-inflammatory activities of compounds M15 and M16 were higher than that of aspirin and even equal to that of indomethacin at the same dose. In addition, the in vitro cytotoxicity activities and anti-inflammatory activities of four target compounds were performed in RAW264.7 macrophages, and compound M16 was found to significantly inhibit the release of lipopolysaccharide (LPS)-induced interleukin (IL)-6 and tumor necrosis factor (TNF)-α in a dose-dependent manner. In addition, compound M16 was found to attenuate LPS induced cyclooxygenase (COX)-2 up-regulation. The current preliminary study may provide information for the development of new and safe anti-inflammatory agents.

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

Radiation chemistry of salicylic and methyl substituted salicylic acids: Models for the radiation chemistry of pharmaceutical compounds

International Nuclear Information System (INIS)

Ayatollahi, Shakiba; Kalnina, Daina; Song, Weihua; Turks, Maris; Cooper, William J.

2013-01-01

Salicylic acid and its derivatives are components of many medications and moieties found in numerous pharmaceutical compounds. They have been used as models for various pharmaceutical compounds in pharmacological studies, for the treatment of pharmaceuticals and personal care products (PPCPs), and, reactions with natural organic matter (NOM). In this study, the radiation chemistry of benzoic acid, salicylic acid and four methyl substituted salicylic acids (MSA) is reported. The absolute bimolecular reaction rate constants for hydroxyl radical reaction with benzoic and salicylic acids as well as 3-methyl-, 4-methyl-, 5-methyl-, and 6-methyl-salicylic acid were determined (5.86±0.54)×10 9 , (1.07±0.07)×10 10 , (7.48±0.17)×10 9 , (7.31±0.29)×10 9 , (5.47±0.25)×10 9 , (6.94±0.10)×10 9 (M −1 s −1 ), respectively. The hydrated electron reaction rate constants were measured (3.02±0.10)×10 9 , (8.98±0.27)×10 9 , (5.39±0.21)×10 9 , (4.33±0.17)×10 9 , (4.72±0.15)×10 9 , (1.42±0.02)×10 9 (M −1 s −1 ), respectively. The transient absorption spectra for the six model compounds were examined and their role as model compounds for the radiation chemistry of pharmaceuticals investigated. - Highlights: • Free radical chemistry of salicylic and 4 methyl salicylic acids is investigated. • The transient absorptions spectra for model compounds are measured. • Absolute bimolecular reaction rate constants for hydroxyl radical are determined. • Solvated electron reaction rate constants are calculated. • The use of salicylic acids as models for pharmaceuticals is explored

21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

Science.gov (United States)

2010-04-01

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

Aspirin and omeprazole for secondary prevention of cardiovascular disease in patients at risk for aspirin-associated gastric ulcers.

Science.gov (United States)

García-Rayado, Guillermo; Sostres, Carlos; Lanas, Angel

2017-08-01

Cardiovascular disease is the most important cause of morbidity and mortality in the world and low-dose aspirin is considered the cornerstone of the cardiovascular disease prevention. However, low-dose aspirin use is associated with gastrointestinal adverse effects in the whole gastrointestinal tract. In this setting, co-therapy with a proton pump inhibitor is the most accepted strategy to reduce aspirin related upper gastrointestinal damage. In addition, some adverse effects have been described with proton pump inhibitors long term use. Areas covered: Low-dose aspirin related beneficial and adverse effects in cardiovascular system and gastrointestinal tract are reviewed. In addition, this manuscript summarizes current data on upper gastrointestinal damage prevention and adverse events with proton pump inhibition. Finally, we discuss the benefit/risk ratio of proton pump inhibitor use in patients at risk of gastrointestinal damage taking low-dose aspirin. Expert commentary: Nowadays, with the current available evidence, the combination of low-dose aspirin with proton pump inhibitor is the most effective therapy for cardiovascular prevention in patients at high gastrointestinal risk. However, further studies are needed to discover new effective strategies with less related adverse events.

Low-Dose Aspirin Treatment Alleviates Gamma Irradiation Impaired Fertility in Female Albino Rats

International Nuclear Information System (INIS)

Ibrahim, M.F.

2013-01-01

elevated malondialdehyde (MDA) and reduced glutathione (GSH) levels compared to the related serum control values. The radiation effect was extended to Subgroup 2 that revealed apparent infertility. Moreover, Aspirin oral daily administration caused a remarkable reduction in both FSH and LH hormones alongside with elevated progesterone and PRL levels with no noted E2 level changes (Group 3). However the same treatment accelerated both the fertility and re productivity rates of Subgroup 3. However, the results of the present study revealed the potency of the anti-inflammatory drug Aspirin when administered post radiation exposure (Group 4) in ameliorating the abrupt irradiation induced hormonal imbalance and the significant elevation in serum MDA in addition to its ability in alleviating the radiation induced reproductive disorders (Subgroup 4). In conclusion, oxidative stress caused by radiation exposure of cycling female rats induced marked disturbance in their hormonal balance leading to negative fertility outcomes that has been ameliorated by Aspirin therapy.

Aspirin Versus Aspirin Plus Clopidogrel as Antithrombotic Treatment Following Transcatheter Aortic Valve Replacement With a Balloon-Expandable Valve: The ARTE (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation) Randomized Clinical Trial.

Science.gov (United States)

Rodés-Cabau, Josep; Masson, Jean-Bernard; Welsh, Robert C; Garcia Del Blanco, Bruno; Pelletier, Marc; Webb, John G; Al-Qoofi, Faisal; Généreux, Philippe; Maluenda, Gabriel; Thoenes, Martin; Paradis, Jean-Michel; Chamandi, Chekrallah; Serra, Vicenç; Dumont, Eric; Côté, Mélanie

2017-07-10

The aim of this study was to compare aspirin plus clopidogrel with aspirin alone as antithrombotic treatment following transcatheter aortic valve replacement (TAVR) for the prevention of ischemic events, bleeding events, and death. Few data exist on the optimal antithrombotic therapy following TAVR. This was a randomized controlled trial comparing aspirin (80 to 100 mg/day) plus clopidogrel (75 mg/day) (dual antiplatelet therapy [DAPT]) versus aspirin alone (single-antiplatelet therapy [SAPT]) in patients undergoing TAVR with a balloon-expandable valve. The primary endpoint was the occurrence of death, myocardial infarction (MI), stroke or transient ischemic attack, or major or life-threatening bleeding (according to Valve Academic Research Consortium 2 definitions) within the 3 months following the procedure. The trial was prematurely stopped after the inclusion of 74% of the planned study population. A total of 222 patients were included, 111 allocated to DAPT and 111 to SAPT. The composite of death, MI, stroke or transient ischemic attack, or major or life-threatening bleeding tended to occur more frequently in the DAPT group (15.3% vs. 7.2%, p = 0.065). There were no differences between groups in the occurrence of death (DAPT, 6.3%; SAPT, 3.6%; p = 0.37), MI (DAPT, 3.6%; SAT, 0.9%; p = 0.18), or stroke or transient ischemic attack (DAPT, 2.7%; SAPT, 0.9%; p = 0.31) at 3 months. DAPT was associated with a higher rate of major or life-threatening bleeding events (10.8% vs. 3.6% in the SAPT group, p = 0.038). There were no differences between groups in valve hemodynamic status post-TAVR. This small trial showed that SAPT (vs. DAPT) tended to reduce the occurrence of major adverse events following TAVR. SAPT reduced the risk for major or life-threatening events while not increasing the risk for MI or stroke. Larger studies are needed to confirm these results. (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation: The ARTE

PFA-100-measured aspirin resistance is the predominant risk factor for hospitalized cardiovascular events in aspirin-treated patients: A 5-year cohort study.

Science.gov (United States)

Chen, H Y; Chou, P

2018-04-01

Aspirin therapy is the clinical gold standard for the prevention of cardiovascular events. However, cardiovascular events still develop in some patients undergoing aspirin therapy. Many laboratory methods exist for measuring aspirin resistance. Using the platelet Function Analyzer (PFA)-100 system, we aimed to determine the effect of aspirin resistance on hospitalized cardiovascular events (hCVE) in a 5-year follow-up cohort. We also sought to determine the impact of aspirin resistance on the relationship between common cardiovascular risk factors and cardiovascular hospitalization. Aspirin resistance was evaluated in aspirin-treated patients from the outpatient department. A total of 465 patients during a 5-year follow-up period were included in this study. The primary endpoint of the study was hospitalization for any acute cardiovascular event. The prevalence and associated risk factors of acute cardiovascular events were evaluated. Aspirin resistance was prevalent in 91 (20.0%) of 465 patients. Prior hospitalization history of cardiovascular events was highly associated with aspirin resistance (P = .001). At the 5-year follow-up, cardiovascular events were found to have developed in 11 patients (8 stroke and 3 myocardial infarction) who exhibited aspirin resistance (12.1%) and in 9 (4 stroke and 5 myocardial infarction) patients who did not exhibit aspirin resistance (2.4%) (P resistance and cardiovascular events (adjusted odds ratio 4.28; 95% CI: 1.64-11.20; P = .03). PFA-100 measurements of aspirin resistance correlate with hCVE, as evidenced by both the past medical history and the 5-year follow-up. The logistic regression analysis results showed that aspirin resistance plays a larger role in hospitalized cardiovascular disease than do other cardiovascular risk factors. © 2017 John Wiley & Sons Ltd.

The effect of aspirin nanoemulsion on TNFα and iNOS in gastric tissue in comparison with conventional aspirin

Directory of Open Access Journals (Sweden)

Mahmoud FA

2015-08-01

Full Text Available Fatma Abd Elhalim Mahmoud,1,2 Khalid S Hashem,3 Asmaa Mohammed M Hussein Elkelawy21Medical Pharmacology Department, Faculty of Medicine, Cairo University, Giza, 2Clinical Pharmacology Department, Faculty of Medicine, 3Biochemistry Department, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, EgyptBackground: No dose of aspirin is free of bleeding risk. Even at a dose as low as 75 mg/day, the risk of upper gastrointestinal bleeding is twice as high as among nonusers. Nanoemulsions (NEs are emulsion systems with droplet size in nanometer scale in which oil or water droplets are finely dispersed in the opposite phase with the help of a suitable surfactant to stabilize the system.Objectives: The objective of this study was to determine the effect of aspirin NE in comparison to conventional aspirin.Materials and methods: A total of 24 male rats were used in the study and arbitrarily assigned to four groups. Group 1 was the control group, and was given saline. Group 2 was given blank NE 1.5 mL/kg orally. Group 3 was given aspirin 30 mg/kg body weight orally. Group 4 was given aspirin NE 30 mg/kg body weight orally. Rats were killed, and gastric tissue was quickly excised after dissection of the animals. The tissues were divided into three pieces. The first one was kept in formalin 10% for pathological investigation. The second piece was kept in liquid nitrogen for molecular investigation. The third piece was homogenized in ten volumes of ice-cold phosphate-buffered saline (pH 7 using a Teflon homogenizer until a uniform suspension was obtained. The homogenate was centrifuged at 4,000 rpm for 30 minutes at 4°C to separate the supernatant from cellular debris. The supernatant was then used for the estimation of biochemical assays.Results: The present study shows that aspirin has a toxic effect on the stomach as a result of inducing marked oxidative damage and the release of reactive oxygen species. This was shown by the significant

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 ...

ESPRIT: is aspirin plus dipyridamole superior to aspirin alone in TIA or minor stroke patients?

Science.gov (United States)

Rouhl, R P W; Lodder, J

2008-11-01

Transient ischemic attack (TIA) or a (minor) ischemic stroke increases the risk of a recurrent stroke or death. Antiplatelet therapy with aspirin or clopidogrel is, in the absence of a potential cardiac embolic source, common practice to lower this risk. Until recently, adjuvant dipyridamole or low intensity oral anticoagulation were not generally prescribed in secondary prevention. In this article, we will summarize and discuss the published results of the European/Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT). In this trial, treatments with anticoagulants, aspirin alone and the combination of aspirin plus dipyridamole were compared, in a multicenter, three-armed, randomized, open-label study in patients with TIA or minor stroke.

Rivaroxaban with or without aspirin in stable cardiovascular disease

DEFF Research Database (Denmark)

Eikelboom, John W; Connolly, Stuart J; Bosch, Jackie

2017-01-01

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive...... rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after...... a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P

Acetyl salicylic acid induced-urticaria and/or angioedema in atopic children.

Science.gov (United States)

Botey, J; Navarro, C; Aulesa, C; Marín, A; Eseverri, J L

1988-01-01

From the report of Hirschberg, only 3 years after aspirin synthesis, there have been numerous works dedicated to showing the different types of adverse reactions found following aspirin administration. However, there are few publications on the process of urticaria and/or acute angioedema induced by ASA and few reported cases were found in children. Thus, we present 6 atopic children with urticaria and/or angioedema related with ASA. A carefully detailed history, oral provocation with ASA, oral provocation with other NSAI and HBDT with ASA were done to all of them. The oral provocation with ASA was positive in 5 of the 6 cases. The provocations with the rest of the NSAI and tartrazine and sodium benzoate were negative in all of the patients. The HBDT was positive in 5 of the cases. In conclusion, we insist that aspirin intolerance is not infrequent in infancy and it is not rare to see urticaria and or angioedema, in spite of the fact that asthmatics, atopics or non atopics, usually present as bronchospasm. We also believe that the HBDT can be a method of diagnosis used in these cases.

Antiplatelet therapy: aspirin resistance and all that jazz!

Science.gov (United States)

Divani, Afshin A; Zantek, Nicole D; Borhani-Haghighi, Afshin; Rao, Gundu H R

2013-01-01

Platelets play a crucial role in the pathogenesis of atherosclerosis, thrombosis, and stroke. Aspirin used alone or in combination with other antiplatelet drugs has been shown to offer significant benefit to patients at high risk of vascular events. Resistance to the action of aspirin may decrease this benefit. Aspirin resistance has been defined by clinical and/or laboratory criteria; however, detection by laboratory methods prior to experiencing a clinical event will likely provide the greatest opportunity for intervention. Numerous laboratory methods with different cutoff points have been used to evaluate the resistance. Noncompliance with aspirin treatment has also confounded studies. A single assay is currently insufficient to establish resistance. Combinations of results to confirm compliance and platelet inhibition may identify "at-risk" individuals who truly have aspirin resistance. The most effective strategy for managing patients with aspirin resistance is unknown; however, studies are currently underway to address this issue.

Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease.

Science.gov (United States)

Eikelboom, John W; Connolly, Stuart J; Bosch, Jackie; Dagenais, Gilles R; Hart, Robert G; Shestakovska, Olga; Diaz, Rafael; Alings, Marco; Lonn, Eva M; Anand, Sonia S; Widimsky, Petr; Hori, Masatsugu; Avezum, Alvaro; Piegas, Leopoldo S; Branch, Kelley R H; Probstfield, Jeffrey; Bhatt, Deepak L; Zhu, Jun; Liang, Yan; Maggioni, Aldo P; Lopez-Jaramillo, Patricio; O'Donnell, Martin; Kakkar, Ajay K; Fox, Keith A A; Parkhomenko, Alexander N; Ertl, Georg; Störk, Stefan; Keltai, Matyas; Ryden, Lars; Pogosova, Nana; Dans, Antonio L; Lanas, Fernando; Commerford, Patrick J; Torp-Pedersen, Christian; Guzik, Tomek J; Verhamme, Peter B; Vinereanu, Dragos; Kim, Jae-Hyung; Tonkin, Andrew M; Lewis, Basil S; Felix, Camilo; Yusoff, Khalid; Steg, P Gabriel; Metsarinne, Kaj P; Cook Bruns, Nancy; Misselwitz, Frank; Chen, Edmond; Leong, Darryl; Yusuf, Salim

2017-10-05

We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; Paspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; Paspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).

Salicylic acid as a peeling agent: a comprehensive review.

Science.gov (United States)

Arif, Tasleem

2015-01-01

Salicylic acid has been used to treat various skin disorders for more than 2,000 years. The ability of salicylic acid to exfoliate the stratum corneum makes it a good agent for peeling. In particular, the comedolytic property of salicylic acid makes it a useful peeling agent for patients with acne. Once considered as a keratolytic agent, the role of salicylic acid as a desmolytic agent, because of its ability to disrupt cellular junctions rather than breaking or lysing intercellular keratin filaments, is now recognized and is discussed here. Salicylic acid as a peeling agent has a number of indications, including acne vulgaris, melasma, photodamage, freckles, and lentigines. The efficacy and safety of salicylic acid peeling in Fitzpatrick skin types I-III as well as in skin types V and VI have been well documented in the literature. This paper reviews the available data and literature on salicylic acid as a peeling agent and its possible indications. Its properties, efficacy and safety, the peeling procedure, and possible side effects are discussed in detail. An account of salicylism is also included.

Role of Aspirin in Breast Cancer Survival.

Science.gov (United States)

Chen, Wendy Y; Holmes, Michelle D

2017-07-01

Chemotherapy and hormonal therapy have significantly decreased breast cancer mortality, although with considerable side effects and financial costs. In the USA, over three million women are living after a breast cancer diagnosis and are eager for new treatments that are low in toxicity and cost. Multiple observational studies have reported improved breast cancer survival with regular aspirin use. Furthermore, pooled data from five large randomized trials of aspirin for cardiovascular disease showed that subjects on aspirin had decreased risk of cancer mortality and decreased risk of metastatic cancer. Although the potential mechanism for aspirin preventing breast cancer is not known, possible pathways may involve platelets, inflammation, cyclooxygenase (COX) 2, hormones, or PI3 kinase. This review article summarizes the current epidemiologic and clinical trial evidence as well as possible underlying mechanisms that justify current phase III randomized trials of aspirin to improve breast cancer survival.

Preventive Effect of Aspirin Eugenol Ester on Thrombosis in κ-Carrageenan-Induced Rat Tail Thrombosis Model.

Directory of Open Access Journals (Sweden)

Ning Ma

Full Text Available Based on the prodrug principle, aspirin eugenol ester (AEE was synthesized, which can reduce the side effects of aspirin and eugenol. As a good candidate for new antithrombotic and anti-inflammatory medicine, it is essential to evaluate its preventive effect on thrombosis. Preventive effect of AEE was investigated in κ-carrageenan-induced rat tail thrombosis model. AEE suspension liquids were prepared in 0.5% sodium carboxymethyl cellulose (CMC-Na. AEE was administrated at the dosage of 18, 36 and 72 mg/kg. Aspirin (20 mg/kg, eugenol (18 mg/kg and 0.5% CMC-Na (30 mg/kg were used as control drug. In order to compare the effects between AEE and its precursor, integration of aspirin and eugenol group (molar ratio 1:1 was also designed in the experiment. After drugs were administrated intragastrically for seven days, each rat was injected intraperitoneally with 20 mg/kg BW κ-carrageen dissolved in physiological saline to induce thrombosis. The length of tail-thrombosis was measured at 24 and 48 hours. The blank group just was given physiological saline for seven days without κ-carrageenan administrated. The results indicated that AEE significantly not only reduced the average length of thrombus, PT values and FIB concentration, but also reduced the red blood cell (RBC, hemoglobin (HGB, hematocrit (HCT and platelet (PLT. The effects of AEE on platelet aggregation and anticoagulant in vitro showed that AEE could inhibit adenosine diphosphate (ADP-induced platelet aggregation as dose-dependence but no notable effect on blood clotting. From these results, it was concluded that AEE possessed positive effect on thrombosis prevention in vivo through the reduction of FIB, PLT, inhibition of platelet aggregation and the change of TT and PT values.

Salicylic acid as a peeling agent: a comprehensive review

Directory of Open Access Journals (Sweden)

Arif T

2015-08-01

Full Text Available Tasleem Arif Postgraduate Department of Dermatology, STD and Leprosy, Government Medical College, Srinagar, Jammu and Kashmir, India Abstract: Salicylic acid has been used to treat various skin disorders for more than 2,000 years. The ability of salicylic acid to exfoliate the stratum corneum makes it a good agent for peeling. In particular, the comedolytic property of salicylic acid makes it a useful peeling agent for patients with acne. Once considered as a keratolytic agent, the role of salicylic acid as a desmolytic agent, because of its ability to disrupt cellular junctions rather than breaking or lysing intercellular keratin filaments, is now recognized and is discussed here. Salicylic acid as a peeling agent has a number of indications, including acne vulgaris, melasma, photodamage, freckles, and lentigines. The efficacy and safety of salicylic acid peeling in Fitzpatrick skin types I–III as well as in skin types V and VI have been well documented in the literature. This paper reviews the available data and literature on salicylic acid as a peeling agent and its possible indications. Its properties, efficacy and safety, the peeling procedure, and possible side effects are discussed in detail. An account of salicylism is also included. Keywords: acne vulgaris, desmolytic agent, melasma, photodamage, salicylic acid 

Safety and feasibility of liver resection with continued antiplatelet therapy using aspirin.

Science.gov (United States)

Monden, Kazuteru; Sadamori, Hiroshi; Hioki, Masayoshi; Ohno, Satoshi; Saneto, Hiromi; Ueki, Toru; Yabushita, Kazuhisa; Ono, Kazumi; Sakaguchi, Kousaku; Takakura, Norihisa

2017-07-01

Aspirin is widely used for the secondary prevention of ischemic stroke and cardiovascular disease. Perioperative aspirin may decrease thrombotic morbidity, but may also increase hemorrhagic morbidity. In particular, liver resection carries risks of bleeding, leading to higher risks of hemorrhagic morbidity. Our institution has continued aspirin therapy perioperatively in patients undergoing liver resection. This study examined the safety and feasibility of liver resection while continuing aspirin. We retrospectively evaluated 378 patients who underwent liver resection between January 2010 and January 2016. Patients were grouped according to preoperative aspirin prescription: patients with aspirin therapy (aspirin users, n = 31); and patients without use of aspirin (aspirin non-users, n = 347). Aspirin users were significantly older (P aspirin users than among aspirin non-users, no significant difference was identified. No postoperative hemorrhage was seen among aspirin users. Liver resection can be safely performed while continuing aspirin therapy without increasing hemorrhagic morbidity. Our results suggest that interruption of aspirin therapy is unnecessary for patients undergoing liver resection. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Enhancement of aspirin capsulation by porous particles including iron hydrous oxide

International Nuclear Information System (INIS)

Saito, Kenji; Koishi, Masumi; Hosoi, Fumio; Makuuchi, Keizo.

1986-01-01

Polymer-coated porous particles containing aspirin as a drug were prepared and the release of rate of aspirin was studied. The impregnation of aspirin was carried out by post-graft polymerization, where methyl methacrylate containing aspirin was treated with porous particles including iron oxide, pre-irradiated with γ-ray form Co-60. Release of aspirin from modified particles was examined with 50 % methanol solution. The amount of aspirin absorbed in porous particles increased by grafting of methyl methacrylate. The particles treated with iron hydrous oxide sols before irradiation led to the increment of aspirin absorption. Diffusion of aspirin through the polymer matrix and the gelled layer was the limiting process in the aspirin release from particles. The rate of aspirin released from modified particles including iron hydrous oxide wasn't affected by the grafting of methyl methacrylate. (author)

Safety of ultrasound-guided transrectal extended prostate biopsy in patients receiving low-dose aspirin

Directory of Open Access Journals (Sweden)

Ioannis Kariotis

2010-06-01

Full Text Available PURPOSE: To determine whether the peri-procedural administration of low-dose aspirin increases the risk of bleeding complications for patients undergoing extended prostate biopsies. MATERIALS AND METHODS: From February 2007 to September 2008, 530 men undergoing extended needle biopsies were divided in two groups; those receiving aspirin and those not receiving aspirin. The morbidity of the procedure, with emphasis on hemorrhagic complications, was assessed prospectively using two standardized questionnaires. RESULTS: There were no significant differences between the two groups regarding the mean number of biopsy cores (12.9 ± 1.6 vs. 13.1 ± 1.2 cores, p = 0.09. No major biopsy-related complications were noted. Statistical analysis did not demonstrate significant differences in the rate of hematuria (64.5% vs. 60.6%, p = 0.46, rectal bleeding (33.6% vs. 25.9%, p = 0.09 or hemospermia (90.1% vs. 86.9%, p = 0.45. The mean duration of hematuria and rectal bleeding was significantly greater in the aspirin group compared to the control group (4.45 ± 2.7 vs. 2.4 ± 2.6, p = < 0.001 and 3.3 ± 1.3 vs. 1.9 ± 0.7, p < 0.001. Multivariate logistic regression analysis revealed that only younger patients (mean age 60.1 ± 5.8 years with a lower body mass index (< 25 kg/m2 receiving aspirin were at a higher risk (odds ratio = 3.46, p = 0.047 for developing hematuria and rectal bleeding after the procedure. CONCLUSIONS: The continuing use of low-dose aspirin in patients undergoing extended prostatic biopsy is a relatively safe option since it does not increase the morbidity of the procedure.

Effect of misoprostol on patients with aspirin-exacerbated respiratory disease undergoing aspirin challenge and desensitization.

Science.gov (United States)

Walters, Kristen M; Simon, Ronald A; Woessner, Katharine M; Wineinger, Nathan E; White, Andrew A

2017-07-01

Prostaglandin E 2 (PGE 2 ) is an anti-inflammatory compound that inhibits 5-lipoxygenase activity. Diminished PGE 2 regulation in aspirin-exacerbated respiratory disease (AERD) leads to respiratory reactions on cyclooxygenase 1 inhibition. In vitro studies have found that exogenous PGE 2 stabilizes inflammatory mediator release. To examine whether misoprostol (oral prostaglandin E 1 analogue) use during aspirin challenge and desensitization might decrease the severity of aspirin-induced symptoms and make desensitization safer for patients with AERD. Forty-five patients undergoing aspirin challenge and/or desensitization were randomized to misoprostol (n = 30) or placebo (n = 15) and compared with a group of historical controls (n = 31). Misoprostol (200 μg) was administered at 30 minutes, 90 minutes, and 4 hours after the first dose of nasal ketorolac. Measured end points included change in forced expiratory volume in 1 second (FEV 1 ), peak nasal inspiratory flow rate (PNIF), number of treatments received for induced reactions, and adverse gastrointestinal effects. A difference in FEV 1 and PNIF reduction was detected between misoprostol and placebo (P = .03) and misoprostol and historical controls (P = .01), respectively, during nasal ketorolac challenge. No difference was detected among aspirin reactors. Among all reactors, no difference in magnitude was found for FEV 1 (P = .13) or PNIF (P = .07) reduction across all 3 groups. Total treatment requirement was similar (P = .14). Patients receiving misoprostol were more likely to report adverse gastrointestinal effects (P = .02). The addition of misoprostol to current aspirin challenge and/or desensitization protocols reveals no protective effect in reducing the intensity of nonsteroidal anti-inflammatory drug-induced symptoms and is not recommended based on the findings in this study. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A pulse radiolysis study of salicylic acid and 5-sulpho-salicylic acid in aqueous solutions

International Nuclear Information System (INIS)

Kishore, Kamal; Mukherjee, T.

2006-01-01

Reactions of H, OH, e aq - and some one-electron oxidants have been studied with salicylic acid and 5-sulpho-salicylic acid in aqueous solutions. Rate constants for the reaction of e aq - with these compounds were of the order of 10 9 dm 3 mol -1 s -1 and this reaction led to the formation of reducing radicals which could transfer electron to methyl viologen. Other one-electron reductants were not able to reduce these compounds. OH radicals reacted with these compounds by addition pathway with very high rate constants (>10 10 dm 3 mol -1 s -1 ) while O - radical anions could oxidize these molecules to give phenoxyl type of radicals. Amongst the one-electron oxidants, only N 3 radicals and SO 4 - radicals could oxidize salicylic acid while 5-sulpho-salicylic acid could be oxidized only by SO 4 - radicals indicating that while one-electron reduction potential for semi-oxidized SA may be o1 for N 3 ? radical), it is more than 1.33V vs. NHE for semi-oxidized SSA species

Up-regulation of Ciliary Neurotrophic Factor in Astrocytes by Aspirin

Science.gov (United States)

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

2013-01-01

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

Aspirin in the Chemoprevention of Colorectal Neoplasia: An Overview

Science.gov (United States)

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

2011-01-01

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

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.

Aspirin Reduces Cardiac Interstitial Fibrosis by Inhibiting Erk1/2-Serpine2 and P-Akt Signalling Pathways.

Science.gov (United States)

Li, Xuelian; Wang, GuoYuan; QiLi, MuGe; Liang, HaiHai; Li, TianShi; E, XiaoQiang; Feng, Ying; Zhang, Ying; Liu, Xiao; Qian, Ming; Xu, BoZhi; Shen, ZhiHang; Gitau, Samuel Chege; Zhao, DanDan; Shan, HongLi

2018-01-01

Cardiac interstitial fibrosis is an abnormality of various cardiovascular diseases, including myocardial infarction, hypertrophy, and atrial fibrillation, and it can ultimately lead to heart failure. However, there is a lack of practical therapeutic approaches to treat fibrosis and reverse the damage to the heart. The purpose of this study was to investigate the effect of long-term aspirin administration on pressure overload-induced cardiac fibrosis in mice and reveal the underlying mechanisms of aspirin treatment. C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with 10 mg·kg-1·day-1 of aspirin for 4 weeks. Masson staining and a collagen content assay were used to detect the effects of aspirin on cardiac fibrosis in vivo and in vitro. Western blot and qRT-PCR were applied to examine the impact of aspirin on extracellular signal-regulated kinases (Erks), p-Akt/β-catenin, SerpinE2, collagen I, and collagen III levels in the mice heart. Aspirin significantly suppressed the expression of α-smooth muscle actin (α-SMA; 1.19±0.19-fold) and collagen I (0.95±0.09-fold) in TAC mice. Aspirin, at doses of 100 and 1000 µM, also significantly suppressed angiotensin II-induced α-SMA and collagen I in cultured CFs. The enhanced phosphorylation of Erk1/2 caused by TAC (p-Erk1, 1.49±0.19-fold; p-Erk2, 1.96±0.68-fold) was suppressed by aspirin (p-Erk1, 1.04±0.15-fold; p-Erk2, 0.87±0.06-fold). SerpinE2 levels were suppressed via the Erk1/2 signalling pathway following treatment with aspirin (1.36±0.12-fold for TAC; 1.06±0.07-fold for aspirin+TAC). The p-Akt and β-catenin levels were also significantly inhibited in vivo and in vitro. Our study reveals a novel mechanism by which aspirin alleviates pressure overload-induced cardiac interstitial fibrosis in TAC mice by suppressing the p-Erk1/2 and p-Akt/β-catenin signalling pathways. © 2018 The Author(s). Published by S. Karger AG, Basel.

Talk with Your Doctor about Taking Aspirin Every Day

Science.gov (United States)

... t sure why this works. Can taking aspirin every day cause any side effects? Taking aspirin isn't ... read these benefits and risks of taking aspirin every day . Next section Talk with Your Doctor Previous section ...

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.

Influence of aspirin and non-aspirin NSAID use on ovarian and endometrial cancer: Summary of epidemiologic evidence of cancer risk and prognosis.

Science.gov (United States)

Verdoodt, F; Kjaer, S K; Friis, S

2017-06-01

Increasing evidence supports a role for aspirin use in reducing the incidence and mortality of several cancer types. This has spurred a new wave of interest in this widely used drug. In this review, we present and evaluate the epidemiologic evidence of the association between the use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) and the incidence and prognosis of ovarian and endometrial cancer. The evidence of a preventive effect of NSAID use on risk of ovarian or endometrial cancer is based primarily on results from observational studies and, consequently, is only suggestive. Overall, observational studies indicate modest reductions in risk of ovarian and endometrial cancer with aspirin use, whereas the results for non-aspirin NSAID use are equivocal. The strongest inverse associations have been reported for long-term consistent aspirin use, notably among subgroups of users (e.g., those with high body mass index). Few studies have evaluated the influence of NSAID use on the mortality of ovarian or endometrial cancer, and substantial heterogeneity of study characteristics and results preclude any conclusions. Additional studies of aspirin and non-aspirin NSAID use and ovarian or endometrial cancer risk and prognosis are warranted. In the present review, we discuss the importance of comprehensive exposure definitions (i.e., duration, timing, consistency and intensity/dose) and evaluation of potential effect modification according to user characteristics, with the aim of identifying women who may experience the largest benefit of aspirin or non-aspirin NSAID use on risk or prognosis of ovarian and endometrial cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2017-01-01

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

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

International Nuclear Information System (INIS)

Malik, M.I.

2013-01-01

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)

A Review on the Relationship between Aspirin and Bone Health

Directory of Open Access Journals (Sweden)

Kok-Yong Chin

2017-01-01

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

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...

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

Science.gov (United States)

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

2011-01-01

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

Intracellular erythrocyte platelet-activating factor acetylhydrolase I inactivates aspirin in blood.

Science.gov (United States)

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

2011-10-07

Aspirin (acetylsalicylic acid) prophylaxis suppresses major adverse cardiovascular events, but its rapid turnover limits inhibition of platelet cyclooxygenase activity and thrombosis. Despite its importance, the identity of the enzyme(s) that hydrolyzes the acetyl residue of circulating aspirin, which must be an existing enzyme, remains unknown. We find that circulating aspirin was extensively hydrolyzed within erythrocytes, and chromatography indicated these cells contained a single hydrolytic activity. Purification by over 1400-fold and sequencing identified the PAFAH1B2 and PAFAH1B3 subunits of type I platelet-activating factor (PAF) acetylhydrolase, a phospholipase A(2) with selectivity for acetyl residues of PAF, as a candidate for aspirin acetylhydrolase. Western blotting showed that catalytic PAFAH1B2 and PAFAH1B3 subunits of the type I enzyme co-migrated with purified erythrocyte aspirin hydrolytic activity. Recombinant PAFAH1B2, but not its family member plasma PAF acetylhydrolase, hydrolyzed aspirin, and PAF competitively inhibited aspirin hydrolysis by purified or recombinant erythrocyte enzymes. Aspirin was hydrolyzed by HEK cells transfected with PAFAH1B2 or PAFAH1B3, and the competitive type I PAF acetylhydrolase inhibitor NaF reduced erythrocyte hydrolysis of aspirin. Exposing aspirin to erythrocytes blocked its ability to inhibit thromboxane A(2) synthesis and platelet aggregation. Not all individuals or populations are equally protected by aspirin prophylaxis, the phenomenon of aspirin resistance, and erythrocyte hydrolysis of aspirin varied 3-fold among individuals, which correlated with PAFAH1B2 and not PAFAH1B3. We conclude that intracellular type I PAF acetylhydrolase is the major aspirin hydrolase of human blood.

Phenomenology, pathogenesis, diagnosis and treatment of aspirin-sensitive rhinosinusitis.

Science.gov (United States)

Schapowal, A G; Simon, H U; Schmitz-Schumann, M

1995-01-01

Aspirin-sensitive rhinosinusitis is a non-allergic, non-infectious perennial eosinophilic rhinitis starting in middle age and rarely seen in children. It may also been seen in atopic patients who have developed a mixed type rhinitis with recurrent airway infections. There is an intolerance to aspirin and most other NSAID. An intolerance to tartrazine, food additives, alcohol, narcotics and local anaesthetics can follow. Most aspirin-sensitive patients develop nasal polyps. Untreated, it can lead to asthma. The frequency of aspirin intolerance is 6.18% in patients with perennial rhinitis and 14.68% in patients with nasal polyps. Immunologic studies of the blood and the nasal polyps show a hyperreactive immune system with an activation of the eosinophil granulocytes due to a TH1-lymphocyte-activation. In atopic subjects with a mixed type rhinitis, we found a TH2- and B-lymphocyte-activation as well. Inhibition of eosinophil apoptosis might be a second remarkable change in the immune system of aspirin-sensitive patients. A key pathogenic event for aspirin sensitivity is the change of the leukotriene pathway for arachidonic acid metabolism releasing high amounts of leukotrienes LTC4, LTD4 and LTE4, effective chemoattractants and activators of inflammatory cells. For the diagnosis of aspirin intolerance, nasal, bronchial and oral challenge are available. The sensitivity of nasal challenge with lysine-aspirin for the diagnosis of aspirin-sensitive rhinitis is 0.93, the specificity 0.97. It is the safest test in aspirin-sensitive asthmatics causing bronchial side effects only in 0.45%. Therapy of aspirin-sensitive rhinosinusitis includes avoidance of aspirin and NSAID. A general down regulation of the immune response with glucocorticosteroids is an effective means. We prefer a maintenance dose of budesonid 400 micrograms a day. Systemic steroids for a reversibility test or in exacerbation due to viral infection are given in a dose of 50 mg a day for one week. If steroids

Aspirin desensitization for patients with aspirin-exacerbated respiratory disease: A randomized double-blind placebo-controlled trial.

Science.gov (United States)

Esmaeilzadeh, Hossein; Nabavi, Mohammad; Aryan, Zahra; Arshi, Saba; Bemanian, Mohammad Hassan; Fallahpour, Morteza; Mortazavi, Negar

2015-10-01

The effect of aspirin desensitization (AD) on immunologic profile of patients with AERD has been poorly understood. This study is aimed at investigating the effect of AD on clinical and immunological markers of patients with AERD. This randomized double-blind placebo-controlled trial comprised 34 adult patients (67.6% female) with chronic rhinosinusitis, nasal polyps, and aspirin-intolerant asthma. The active group underwent AD over a 2-day period with increasing doses of aspirin (60, 125, 325, and 625 mg), followed by receiving aspirin 625 mg twice daily for 6 months. Symptom scores and medication needs of patients with AERD who have undergone AD were significantly lower compared to the placebo group after 6 months (7.5 ± 3.5 vs. 10.6 ± 3.8 and 9.3 ± 2.0 vs. 11.0 ± 3.1, respectively, all p < 0.05). However, no significant difference was observed in serum concentration of IL-10, IFN-γ, and TGF-β between two groups neither at baseline nor at the end of study. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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

2016-04-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) adversely interact with aspirin, diminishing its antiplatelet effect and potentially placing patients at an increased risk for recurrent thrombotic events. This crossover study aimed to determine whether the topical NSAID diclofenac epolamine 1.3% patch or oral diclofenac 50 mg interfered with the antiplatelet effects of aspirin 325 mg. Twelve healthy men and women aged 18-50 were included. Participants were randomized into 5 treatment arms: aspirin, diclofenac potassium 50 mg, diclofenac patch, diclofenac potassium plus ASA 325 mg, and diclofenac patch plus aspirin. Platelet responsiveness was determined using whole-blood impedance aggregation (WBA) to collagen 1 μg/mL and arachidonic acid (AA) 0.5 mM and was sampled every 2 hours. No significant difference in platelet function was observed following the diclofenac patch and aspirin vs aspirin alone. Oral diclofenac produced a mixed effect with significant reduction in platelet inhibition at hour 2 and hour 8 following aspirin administration. Topical diclofenac does not significantly interfere with the antiplatelet effects of aspirin and may be a safer alternative to the oral formulation. © 2015, The American College of Clinical Pharmacology.

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.

Polarography of uranium(VI)-salicylic acid system

International Nuclear Information System (INIS)

Salah, El-Maraghy B.

1980-01-01

Uranium(VI)-salicylic acid system has been studied polarographically in perchloric acid medium. Varying concentrations of HClO 4 and salicylic acid have been used. The nature of the polarographic waves is irreversible. (author)

Polarography of uranium(VI)-salicylic acid system

Energy Technology Data Exchange (ETDEWEB)

Salah, E M.B. [Ain Shams Univ., Cairo (Egypt). Faculty of Education

1980-08-01

Uranium(VI)-salicylic acid system has been studied polarographically in perchloric acid medium. Varying concentrations of HClO/sub 4/ and salicylic acid have been used. The nature of the polarographic waves is irreversible.

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

Science.gov (United States)

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

2017-02-01

Aspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. Important to this function is its ability to irreversibly acetylate cyclooxygenases at active site serines. Aspirin has the potential to acetylate other amino acid side-chains, leading to the possibility that aspirin-mediated lysine acetylation could explain some of its as-yet unexplained drug actions or side-effects. Using isotopically labeled aspirin-d 3 , in combination with acetylated lysine purification and LC-MS/MS, we identified over 12000 sites of lysine acetylation from cultured human cells. Although aspirin amplifies endogenous acetylation signals at the majority of detectable endogenous sites, cells tolerate aspirin mediated acetylation very well unless cellular deacetylases are inhibited. Although most endogenous acetylations are amplified by orders of magnitude, lysine acetylation site occupancies remain very low even after high doses of aspirin. This work shows that while aspirin has enormous potential to alter protein function, in the majority of cases aspirin-mediated acetylations do not accumulate to levels likely to elicit biological effects. These findings are consistent with an emerging model for cellular acetylation whereby stoichiometry correlates with biological relevance, and deacetylases act to minimize the biological consequences of nonspecific chemical acetylations. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Salicylate Hepatitis

African Journals Online (AJOL)

1974-04-09

Apr 9, 1974 ... F. SPEKTOR, M.B. CH.B. Department of Pathology, Groote Schuur Hospital and Uni-' versity of Cape ... salicylate 10 g daily, the SGOT rose to I050 Transac units while the ... Four days later a liver biopsy was performed with.

Salicylate-spectrophotometric determination of inorganic monochloramine

International Nuclear Information System (INIS)

Tao Hui; Chen Zhonglin; Li Xing; Yang Yanling; Li Guibai

2008-01-01

On the basis of classical Berthelot reaction, a simple salicylate-spectrophotometric method was developed for quantitative determination of inorganic monochloramine in water samples. With the catalysis of disodium pentacyanonitrosylferrate(III), inorganic monochloramine reacts with salicylate in equimolar to produce indophenol compound which has an intense absorption at 703 nm. Parameters that influence method performance, such as pH, dosage of salicylate and nitroprussiate and reaction time, were modified to enhance the method performance. By using this method, inorganic monochloramine can be distinguished from organic chloramines and other inorganic chlorine species, such as free chlorine, dichloramine, and trichloramine. The molar absorptivities of the final products formed by these compounds are below ±3% of inorganic monochloramine, because of the α-N in them have only one exchangeable hydrogen atom, and cannot react with salicylate to produce the indophenol compound. The upper concentrations of typical ions that do not interfere with the inorganic monochloramine determination are also tested to be much higher than that mostly encountered in actual water treatment. Case study demonstrates that the results obtained from this method are lower than DPD-titrimetric method because the organic chloramines formed by chlorination of organic nitrogenous compounds give no response in the newly established method. And the result measured by salicylate-spectrophotometric method is coincident with theoretical calculation

Effect of aspirin and prostaglandins on the carbohydrate metabolism in albino rats.: glucose oxidation through different pathways and glycolytic enzymes

International Nuclear Information System (INIS)

Balasubramanian, A.; Ramakrishnan, S.

1980-01-01

The effect of chronic and acute doses of aspirin and prostaglandins F2α and E2 individually on the oxidation of glucose through Embden Meyerhof-TCA cycle and pentose phosphate pathways and some key glycolytic enzymes of liver were studied in male albino rats. Studies were extended to find the combined effect of PGF2α and E2 with an acute dose of aspirin. There was increased utilisation of both 1- 14 C glucose and 6- 14 C glucose on aspirin treatment. However, the metabolism through the EM-TCA pathway was more pronounced as shown by a reduced ratio of 14 CO 2 from 1- 14 C and 6- 14 C glucose. Two hepatic key glycolytic enzymes viz. hexokinase and pyruvate kinase were increased due to aspirin treatment. Withdrawal of aspirin corrected the above impaired carbohydrate metabolism in liver. Prostaglandin F2α also caused a reduction in the utilisation of 1- 14 C glucose, while PGE2 recorded an increase in the utilisation of both 1- 14 C and 6- 14 C glucose when compared to controls, indicating that different members of prostaglandins could affect metabolisms and differently. Administration of the PGs and aspirin together showed an increase in the utilisation of 6- 14 C glucose. (auth.)

THE EFFECT OF SALICYLATES ON THE PRECIPITATION OF ANTIGEN WITH ANTIBODY.

Science.gov (United States)

Coburn, A F; Kapp, E M

1943-02-01

1. Sodium salicylate modifies the precipitation of normal rabbit serum protein by sodium tungstate, and partially inhibits the precipitation of horse serum euglobulin by rabbit antiserum. Sodium salicylate added to a system containing crystalline egg albumin and its antibody partly prevents the formation of precipitate, the degree of inhibition being related to the concentration of salicylate. 2. Precipitation in the equivalence zone is more readily prevented by salicylate than precipitation in the region of antibody excess, the immune system becoming progressively less sensitive to the action of salicylate as the excess of antibody becomes larger. 3. Formed precipitates were partly dissolved following resuspension in the presence of salicylate. 4. The salicylate effect on immune precipitation is reversible, and appears to be due to inactivation of antibody. 5. Salicylate was more effective in preventing specific precipitation than other anions of a lyotropic series tested.

Aspirin resistance: Prevalence and clinical outcome in Egypt

Directory of Open Access Journals (Sweden)

Ahmed Salah

2015-04-01

Results: Prevalence of aspirin resistance was 48% in our study group. Aspirin resistance was significantly higher in patients with family history of CAD (p = 0.044, smoking (p = 0.011, history of MI (p = 0.024, history of percutaneous coronary intervention (PCI (p = 0.001, and concomitant NSAIDs intake (p = 0.047. Moreover, aspirin resistance was more common among patients with multi-vessel CAD (p = 0.024. Aspirin-resistant patients had a significantly higher rate of UA (p = 0.001 and all major adverse cardiac events (MACE (p < 0.001.

The clinical dilemma of "silent desensitization" in aspirin-exacerbated respiratory disease.

Science.gov (United States)

White, Andrew A; Bosso, John V; Stevenson, Donald D

2013-01-01

Aspirin desensitization is a treatment option for patients with aspirin-exacerbated respiratory disease (AERD). Some patients with an excellent history of aspirin or nonsteroidal anti-inflammatory drug (NSAID) reactions have negative aspirin challenges/desensitization. This study discusses the clinical entity of silent desensitization in AERD and the dilemma that this presents to the practicing allergist/immunologist. We discuss a series of patients with a strong history of NSAID reactions who initially underwent a negative challenge/silent desensitization. These patients were subsequently proven to have AERD after a second positive aspirin challenge. Silent desensitization is an uncommon but important outcome to recognize in AERD. Clinicians performing aspirin desensitization should understand that this can occur and consider a second confirmatory aspirin challenge in some patients.

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.

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 reduce...... and preoperative chronic aspirin use. At the time of randomisation, a subpopulation agreed to a single measurement of serum creatinine between 3 and 12 months after surgery, and the authors will examine intervention effects on this outcome. ETHICS AND DISSEMINATION: The authors were competitively awarded a grant...

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).

Low dose aspirin as adjuvant treatment for venous leg ulceration: pragmatic, randomised, double blind, placebo controlled trial (Aspirin4VLU).

Science.gov (United States)

Jull, Andrew; Wadham, Angela; Bullen, Chris; Parag, Varsha; Kerse, Ngaire; Waters, Jill

2017-11-24

Objective  To determine the effect of low dose aspirin on ulcer healing in patients with venous leg ulcers. Design  Pragmatic, community based, parallel group, double blind, randomised controlled trial. Setting  Five community nursing centres in New Zealand. Participants  251 adults with venous leg ulcers who could safely be treated with aspirin or placebo: 125 were randomised to aspirin and 126 to placebo. Interventions  150 mg oral aspirin daily or matching placebo for up to 24 weeks treatment, with compression therapy as standard background treatment. Main outcome measures  The primary outcome was time to complete healing of the reference ulcer (largest ulcer if more than one ulcer was present). Secondary outcomes included proportion of participants healed, change in ulcer area, change in health related quality of life, and adverse events. Analysis was by intention to treat. Results  The median number of days to healing of the reference ulcer was 77 in the aspirin group and 69 in the placebo group (hazard ratio 0.85, 95% confidence interval 0.64 to 1.13, P=0.25). The number of participants healed at the endpoint was 88 (70%) in the aspirin group and 101 (80%) in the placebo group (risk difference -9.8%, 95% confidence interval -20.4% to 0.9%, P=0.07). Estimated change in ulcer area was 4.1 cm 2 in the aspirin group and 4.8 cm 2 in the placebo group (mean difference -0.7 cm 2 , 95% confidence interval -1.9 to 0.5 cm 2 , P=0.25). 40 adverse events occurred among 29 participants in the aspirin group and 37 adverse events among 27 participants in the placebo group (incidence rate ratio 1.1, 95% confidence interval 0.7 to 1.7, P=0.71). Conclusion  Our findings do not support the use of low dose aspirin as adjuvant treatment for venous leg ulcers. Trial registration  ClinicalTrials.gov NCT02158806. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Early aspirin use and the development of cardiac allograft vasculopathy.

Science.gov (United States)

Kim, Miae; Bergmark, Brian A; Zelniker, Thomas A; Mehra, Mandeep R; Stewart, Garrick C; Page, Deborah S; Woodcome, Erica L; Smallwood, Jennifer A; Gabardi, Steven; Givertz, Michael M

2017-12-01

Cardiac allograft vasculopathy (CAV) remains a leading cause of morbidity and mortality after orthotopic heart transplantation (OHT). Little is known about the influence of aspirin on clinical expression of CAV. We followed 120 patients with OHT at a single center for a median of 7 years and categorized them by the presence or absence of early aspirin therapy post-transplant (aspirin treatment ≥6 months in the first year). The association between aspirin use and time to the primary end-point of angiographic moderate or severe CAV (International Society for Heart and Lung Transplantation grade ≥2) was investigated. Propensity scores for aspirin treatment were estimated using boosting models and applied by inverse probability of treatment weighting (IPTW). Despite a preponderance of risk factors for CAV among patients receiving aspirin (male sex, ischemic heart disease as the etiology of heart failure, and smoking), aspirin therapy was associated with a lower rate of moderate or severe CAV at 5 years. Event-free survival was 95.9% for patients exposed to aspirin compared with 79.6% for patients without aspirin exposure (log-rank p = 0.005). IPTW-weighted Cox regression revealed a powerful inverse association between aspirin use and moderate to severe CAV (adjusted hazard ratio 0.13; 95% confidence interval 0.03-0.59), which was directionally consistent for CAV of any severity (adjusted hazard ratio 0.50; 95% confidence interval 0.23-1.08). This propensity score-based comparative observational analysis suggests that early aspirin exposure may be associated with a reduced risk of development of moderate to severe CAV. These findings warrant prospective validation in controlled investigations. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

The Role of Aspirin in the Prevention of Cardiovascular Disease

Science.gov (United States)

Ittaman, Sunitha V.; VanWormer, Jeffrey J.; Rezkalla, Shereif H.

2014-01-01

Aspirin therapy is well-accepted as an agent for the secondary prevention of cardiovascular events and current guidelines also define a role for aspirin in primary prevention. In this review, we describe the seminal trials of aspirin use in the context of current guidelines, discuss factors that may influence the effectiveness of aspirin therapy for cardiovascular disease prevention, and briefly examine patterns of use. The body of evidence supports a role for aspirin in both secondary and primary prevention of cardiovascular events in selected population groups, but practice patterns may be suboptimal. As a simple and inexpensive prophylactic measure for cardiovascular disease, aspirin use should be carefully considered in all at-risk adult patients, and further measures, including patient education, are necessary to ensure its proper use. PMID:24573704

Decreased proinflammatory cytokine production by peripheral blood mononuclear cells from vitiligo patients following aspirin treatment

International Nuclear Information System (INIS)

Zailaie, Mohammad Z.

2005-01-01

Limited studies have shown that treatment of cells with aspirin modulates their cytokine production. Consequently, the aim of the present study is to investigate the pattern of important proinflammatory cytokines production by stimulated peripheral blood mononuclear cells (PBMC) from patients with active vitiligo following long-term treatment with low-dose oral aspirin. The study was conducted at the Vitiligo Unit, King Abdul-Aziz University Medical Center, Jeddah, Kingdom of Saudi Arabia between March and October 2003. Thirty-two patients (18 females and 14 males) with non-segmental vitiligo were divided into 2 equal groups, one group received a daily single dose of oral aspirin (300 mg) and the other group received placebo for a period of 12 weeks. The concentrations of interleukin (IL)-1beta, IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) were determined in the supernatant of isolated cultured PMBC after being stimulated with bacterial lipopolysaccharide (LPS), before the start of aspirin treatment and at end of treatment period. Cytokine levels were measured using the quantitative sandwich enzyme-linked immunosorbent assay (ELISA) technique, utilizing commercially available kits. The proinflammatory cytokine production by the PBMC of patients with active vitiligo was significantly increased compared to normal controls. Thus, the relative percentage increase in the production of IL-1beta, IL-6, IL-8 and TNF-alpha was: 39.4%, 110.5% (p<0.05), 91.5% (p<0.01), and 37% (p<0.05). At the end of treatment, proinflammatory cytokine production in the aspirin-treated group of active vitiligo patients was significantly decreased compared to the placebo group. Thus, the relative percentage decrease in the production of IL-1beta IL-6, IL-8 and TNF-alpha was: 42.5%, 45.2% (p<0.05), 30.8% (p<0.01), and 50.6% (p<0.05). The vitiligo activity was arrested in all aspirin-treated patients, while 2 patients demonstrated significant repigmentation.Chronic administration of

Technetium-aspirin molecule complexes

International Nuclear Information System (INIS)

El-Shahawy, A.S.; Mahfouz, R.M.; Aly, A.A.M.; El-Zohry, M.

1993-01-01

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

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

Science.gov (United States)

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

2014-01-01

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

Regular Use of Aspirin or Non-Aspirin Nonsteroidal Anti-Inflammatory Drugs Is Not Associated With Risk of Incident Pancreatic Cancer in Two Large Cohort Studies.

Science.gov (United States)

Khalaf, Natalia; Yuan, Chen; Hamada, Tsuyoshi; Cao, Yin; Babic, Ana; Morales-Oyarvide, Vicente; Kraft, Peter; Ng, Kimmie; Giovannucci, Edward; Ogino, Shuji; Stampfer, Meir; Cochrane, Barbara B; Manson, JoAnn E; Clish, Clary B; Chan, Andrew T; Fuchs, Charles S; Wolpin, Brian M

2018-04-01

Use of aspirin and/or non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of several cancers, but it is not clear if use of these drugs is associated with risk of pancreatic cancer. We evaluated aspirin and non-aspirin NSAID use and risk of pancreatic adenocarcinoma in 141,940 participants from the Health Professionals Follow-up Study and Nurses' Health Study using multivariable-adjusted Cox proportional hazards regression. We considered several exposure classifications to model differing lag times between NSAID exposure and cancer development. We also conducted a nested case-control study of participants from 3 prospective cohorts using conditional logistic regression to evaluate pre-diagnosis levels of plasma salicylurate, a major metabolite of aspirin, in 396 pancreatic cancer cases and 784 matched individuals without pancreatic cancer (controls). In the prospective cohort study, 1122 participants developed pancreatic adenocarcinoma over 4.2 million person-years. Use of aspirin or non-aspirin NSAIDs was not associated with pancreatic cancer risk, even after considering several latency exposure classifications. In a pre-planned subgroup analysis, regular aspirin use was associated with reduced pancreatic cancer risk among participants with diabetes (relative risk, 0.71; 95% CI, 0.54-0.94). In the nested case-control study, pre-diagnosis levels of salicylurate were not associated with pancreatic cancer risk (odds ratio, 1.08; 95% CI, 0.72-1.61; P trend 0.81; comparing participants in the highest quintile with those in the lowest quintile of plasma salicylurate). Regular aspirin or non-aspirin NSAID use was not associated with future risk of pancreatic cancer in participants from several large prospective cohort studies. A possible reduction in risk for pancreatic cancer among people with diabetes who regularly use aspirin should be further examined in preclinical and human studies. Copyright © 2018 AGA Institute. Published by Elsevier

Aspirin responsiveness changes in obese patients following bariatric surgery.

Science.gov (United States)

Norgard, Nicholas B; Monte, Scott V; Fernandez, Stanley F; Ma, Qing

2017-08-01

Bariatric surgery has emerged as a promising treatment option for weight loss and to counter the metabolic consequences of obesity. Obesity has been linked to a hyperaggregable state, as well as a blunted response to aspirin. This pilot study assessed the hypothesis that bariatric surgery would lead to an improvement in aspirin-induced platelet inhibition and a reduction in platelet aggregability. Fifteen patients scheduled to undergo bariatric surgery were administered two 7-day courses of aspirin 81 mg: the first course administered before surgery and the second was 3 months following surgery. Platelet aggregation was measured before and after each aspirin course using VerifyNow-Aspirin. The primary endpoint was the change in on-treatment aspirin reactive units (ARU) pre- and postsurgery. Data from bariatric surgery study patients were compared to data of normal weighted subjects gathered in a previous study. Roux-en-Y gastric bypass was performed in 80%, and 20% underwent sleeve gastrectomy. The mean starting body mass index (BMI) was 46.9 kg/m 2 . Patients lost on average 24.5 kg, resulting in a postsurgical BMI of 38.5 kg/m 2 . Postbariatric surgery, off-treatment ARU was significantly reduced from presurgery levels (602±59 vs 531±78; P=.035). On-aspirin platelet reactivity was also significantly reduced following surgery (469±60 vs 432±143, P=.03). There was a significant correlation between the extent of weight loss and the degree of improvement in on-aspirin platelet reactivity (r 2 =.49, P=.024). Presurgery on-aspirin platelet reactivity was significantly higher in obese patients compared to normal weighted subjects (469±60 vs 419±52; P=.016) and reduced to the baseline after the surgery (432±63 vs 419±52; P=.54). Aspirin-induced platelet inhibition may be more potent following bariatric surgery. The mechanisms behind this improvement require further investigation. © 2017 John Wiley & Sons Ltd.

The effect of sodium salicylate injection on spatial learning and memory of rat

Directory of Open Access Journals (Sweden)

Leila Azimi

2011-11-01

Full Text Available Background: Cyclooxygenase (COX enzyme known as a regulatory factor in synaptic plasticity. It has been reported that synaptic plasticity is one of the mechanisms involved in learning and memory processes. In the current study peripheral injection's effects of sodium salicylate (as a non selective COX inhibitor on spatial learning and memory have been investigated.Methods: Four groups of male rats received different doses of sodium salicylate (0, 200, 300, 400 mg/kg; i.p.. Studies were performed using Morris Water Maze (MWM. Spatial learning and memory parameters were subjected to the one- and two-way analyses of variance (ANOVAs followed by Tukey’s post hoc test.Results: Data showed that intraperitoneal injection of sodium salicylate had not significant effect on spatial learning parameters (including escape latency and traveled distance to hidden platform in training days; but administration of high dose of the drug (400 mg/kg significantly increased the percentage of time that animals spent in the target quadrant in probe trial testing. Conclusion: Peripheral injection of the COX inhibitor has no significant effect on spatial learning; but potentiates spatial memory consolidation using MWM.

Effect of aspirin on tumour cell colony formation and evolution.

Science.gov (United States)

Wodarz, Dominik; Goel, Ajay; Boland, C Richard; Komarova, Natalia L

2017-09-01

Aspirin is known to reduce the risk of colorectal cancer (CRC) incidence, but the underlying mechanisms are not fully understood. In a previous study, we quantified the in vitro growth kinetics of different CRC tumour cell lines treated with varying doses of aspirin, measuring the rate of cell division and cell death. Here, we use these measured parameters to calculate the chances of successful clonal expansion and to determine the evolutionary potential of the tumour cell lines in the presence and absence of aspirin. The calculations indicate that aspirin increases the probability that a single tumour cell fails to clonally expand. Further, calculations suggest that aspirin increases the evolutionary potential of an expanding tumour cell colony. An aspirin-treated tumour cell population is predicted to result in the accumulation of more mutations (and is thus more virulent and more difficult to treat) than a cell population of the same size that grew without aspirin. This indicates a potential trade-off between delaying the onset of cancer and increasing its evolutionary potential through chemoprevention. Further work needs to investigate to what extent these findings apply to in vivo settings, and to what degree they contribute to the epidemiologically documented aspirin-mediated protection. © 2017 The Author(s).

Once- versus twice-daily aspirin treatment in patients with essential thrombocytosis

DEFF Research Database (Denmark)

Larsen, Mads Lamm; Pedersen, Oliver Heidmann; Hvas, Anne-Mette

2018-01-01

Insufficient platelet inhibition has been reported in up to 40% of aspirin-treated patients, including patients with essential thrombocytosis. To maintain sufficient platelet inhibition, a shorter dosing interval with aspirin has been suggested. We aimed to investigate the antiplatelet effect...... of low-dose aspirin given twice-daily compared to standard once-daily dosing in patients with essential thrombocytosis. We included 22 patients, who were treated for 7 days with standard once-daily aspirin (75 mg once-daily) followed by 7 days treatment of twice-daily aspirin (37.5 mg twice......-daily). The two regimens were separated by 14 days aspirin washout. Blood samples were obtained 1h and 24h/12h after the last pill intake in each regimen. The effect of aspirin was evaluated by: (1) platelet aggregation measured by whole blood impedance aggregometry (Multiplate® Analyser) using arachidonic acid...

Effects of Tumor Necrosis Factor Blocker on Salicylate-Induced Tinnitus in Mice.

Science.gov (United States)

Hwang, Juen-Haur; Huang, David Chang-Wei; Lu, Yin-Chang; Yang, Wei-Shiung; Liu, Tien-Chen

2017-06-01

Neuroinflammation is considered a novel mechanism for acute tinnitus. Here, we investigated the effects of a tumor necrosis factor (TNF) blocker on the gene expression of inflammatory-cytokine in the cochlea in a tinnitus animal model. Enbrel® (30 mg/kg, intraperitoneally (i.p.)) were administrated to the mice with the salicylate induced tinnitus for 3 days. Tinnitus score and mRNA expression levels of TNFR1, TNFR2, and N-methyl-d-aspartate receptor subunit 2B (NR2B) and its downstream regulatory element antagonist modulator (DREAM) in the cochlea of mice were measured and compared to the control. The tinnitus score significantly decreased in the Enbrel® treated group. The mRNA levels of both TNFR1 and TNFR2 were significantly lower in the treatment than in the control group. The mRNA levels of NR2B and DREAM followed a similar trend. we found that treatment with 30 mg/ kg Enbrel® decreased salicylate-induced behavior associated with tinnitus and reduced the mRNA expression levels of TNFR1/R2, NR2B, and DREAM in the cochlea of mice. These findings supported the hypothesis that neuroinflammation might be a novel mechanism for salicylate-induced tinnitus.

Monitoring aspirin therapy with the Platelet Function Analyzer-100

DEFF Research Database (Denmark)

Mortensen, Jette; Poulsen, Tina Svenstrup; Grove, Erik Lerkevang

2008-01-01

OBJECTIVE: Low platelet response to aspirin has been reported to be associated with a high incidence of vascular events. The reported prevalence of aspirin low-responsiveness varies, which may be explained by poor reproducibility of the methods used to evaluate aspirin response and low compliance....... The Platelet Function Analyzer-100 (PFA-100) is a commonly used platelet function test. We aimed to assess the reproducibility of the PFA-100 and the agreement with optical platelet aggregometry (OPA) in healthy volunteers and in patients with coronary artery disease (CAD) treated with low-dose aspirin....... MATERIAL AND METHODS: Twenty-one healthy volunteers and 43 patients with CAD took part in the study. During treatment with aspirin 75 mg daily, all participants had platelet function assessed in duplicate with the PFA-100 and OPA on 4 consecutive days. Additionally, platelet function was assessed before...

Salicylic acid derivatives: synthesis, features and usage as therapeutic tools.

Science.gov (United States)

Ekinci, Deniz; Sentürk, Murat; Küfrevioğlu, Ömer İrfan

2011-12-01

In the field of medicinal chemistry, there is a growing interest in the use of small molecules. Although acetyl salicylic acid is well known for medical applications, little is known about other salicylic acid derivatives, and there is serious lack of data and information on the effects and biological evaluation that connect them. This review covers the synthesis and drug potencies of salicylic acid derivatives. After a brief overview of the information on salicylic acid and its features, a detailed review of salicylic acids as drugs and prodrugs, usage as cyclooxygenase inhibitors, properties in plants, synthesis and recent patents, is developed. Salicylic acid research is still an important area and innovations continue to arise, which offer hope for new therapeutics in related fields. It is anticipated that this review will guide the direction of long-term drug/nutraceutical safety trials and stimulate ideas for future research.

Aspirin for Evidence-Based Preeclampsia Prevention trial: influence of compliance on beneficial effect of aspirin in prevention of preterm preeclampsia.

Science.gov (United States)

Wright, David; Poon, Liona C; Rolnik, Daniel L; Syngelaki, Argyro; Delgado, Juan Luis; Vojtassakova, Denisa; de Alvarado, Mercedes; Kapeti, Evgenia; Rehal, Anoop; Pazos, Andrea; Carbone, Ilma Floriana; Dutemeyer, Vivien; Plasencia, Walter; Papantoniou, Nikos; Nicolaides, Kypros H

2017-12-01

The Aspirin for Evidence-Based Preeclampsia Prevention trial was a multicenter study in women with singleton pregnancies. Screening was carried out at 11-13 weeks' gestation with an algorithm that combines maternal factors and biomarkers (mean arterial pressure, uterine artery pulsatility index, and maternal serum pregnancy-associated plasma protein A and placental growth factor). Those with an estimated risk for preterm preeclampsia of >1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg/d) vs placebo from 11-14 until 36 weeks' gestation. Preterm preeclampsia with delivery at preeclampsia in the Aspirin for Evidence-Based Preeclampsia Prevention trial. This was a secondary analysis of data from the trial. The proportion of prescribed tablets taken was used as an overall measure of compliance. Logistic regression analysis was used to estimate the effect of aspirin on the incidence of preterm preeclampsia according to compliance of preeclampsia at screening and the participating center. The choice of cut-off of 90% was based on an exploratory analysis of the treatment effect. Logistic regression analysis was used to investigate predictors of compliance ≥90% among maternal characteristics and medical history. Preterm preeclampsia occurred in 5/555 (0.9%) participants in the aspirin group with compliance ≥90%, in 8/243 (3.3%) of participants in the aspirin group with compliance preeclampsia was 0.24 (95% confidence interval, 0.09-0.65) for compliance ≥90% and 0.59 (95% confidence interval, 0.23-1.53) for compliance preeclampsia and negatively associated with smoking, maternal age preeclampsia in a previous pregnancy. The beneficial effect of aspirin in the prevention of preterm preeclampsia appears to depend on compliance. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of Ticagrelor Plus Aspirin, Ticagrelor Alone, or Aspirin Alone on Saphenous Vein Graft Patency 1 Year After Coronary Artery Bypass Grafting: A Randomized Clinical Trial.

Science.gov (United States)

Zhao, Qiang; Zhu, Yunpeng; Xu, Zhiyun; Cheng, Zhaoyun; Mei, Ju; Chen, Xin; Wang, Xiaowei

2018-04-24

The effect of ticagrelor with or without aspirin on saphenous vein graft patency in patients undergoing coronary artery bypass grafting (CABG) is unknown. To compare the effect of ticagrelor + aspirin or ticagrelor alone vs aspirin alone on saphenous vein graft patency 1 year after CABG. Randomized, multicenter, open-label, clinical trial among 6 tertiary hospitals in China. Eligible patients were aged 18 to 80 years with indications for elective CABG. Patients requiring urgent revascularization, concomitant cardiac surgery, dual antiplatelet or vitamin K antagonist therapy post-CABG, and who were at risk of serious bleeding were excluded. From July 2014 until November 2015, 1256 patients were identified and 500 were enrolled. Follow-up was completed in January 2017. Patients were randomized (1:1:1) to start ticagrelor (90 mg twice daily) + aspirin (100 mg once daily) (n = 168), ticagrelor (90 mg twice daily) (n = 166), or aspirin (100 mg once daily) (n = 166) within 24 hours post-CABG. Neither patients nor treating physicians were blinded to allocation. Primary outcome was saphenous vein graft patency 1 year after CABG (FitzGibbon grade A) adjudicated independently by a committee blinded to allocation. Saphenous vein graft patency was assessed by multislice computed tomographic angiography or coronary angiography. Among 500 randomized patients (mean age, 63.6 years; women, 91 [18.2%]), 461 (92.2%) completed the trial. Saphenous vein graft patency rates 1 year post-CABG were 88.7% (432 of 487 vein grafts) with ticagrelor + aspirin; 82.8% (404 of 488 vein grafts) with ticagrelor alone; and 76.5% (371 of 485 vein grafts) with aspirin alone. The difference between ticagrelor + aspirin vs aspirin alone was statistically significant (12.2% [95% CI, 5.2% to 19.2%]; P aspirin alone was not statistically significant (6.3% [95% CI, -1.1% to 13.7%]; P = .10). Five major bleeding episodes occurred during 1 year of follow-up (3 with

40 CFR 721.10089 - Modified salicylic acid, zirconium complex (generic).

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Modified salicylic acid, zirconium... Specific Chemical Substances § 721.10089 Modified salicylic acid, zirconium complex (generic). (a) Chemical... as modified salicylic acid, zirconium complex (PMN P-00-552) is subject to reporting under this...

Aspirin effects on lymphocyte cyclic AMP levels in normal human subjects.

Science.gov (United States)

Snider, D E; Parker, C W

1976-01-01

In purified lymphocytes from the peripheral blood of healthy human subjects who had ingested therapeutic doses of aspirin, there was a significant decrease in resting cyclic AMP levels as well as a partial inhibition of the rise in cyclic AMP with isoproterenol or prostaglandin E1. These changes were seen as early as 30 min after aspirin ingestion and did not appear to result from aspirin effects on lymphocyte recovery, purity, viability, or relative number of thymus- or bone marrow-derived lymphocytes. In contrast, the direct addition of aspirin to suspensions of purified peripheral lymphocytes did not significantly alter their cyclic AMP levels. However, an effect of aspirin could be obtained in vitro if aspirin was added to unprocessed whole blood during the dextran sedimentation phase of the cell purification. Thus the effect of aspirin on lymphocyte cyclic AMP metabolism, may be indirect, through other cells present in the peripheral blood. PMID:182720

Highly sensitive electrochemical detection of methyl salicylate using electroactive gold nanoparticles.

Science.gov (United States)

Umasankar, Yogeswaran; Ramasamy, Ramaraja P

2013-11-07

Electrochemical sensing of methyl salicylate, a key plant volatile has been achieved using a gold nanoparticle (AuNP) modified screen printed carbon electrode (SPCE). The electrochemical response of planar gold electrodes, SPCE and AuNP-SPCE in alkaline electrolyte in the presence and absence of methyl salicylate were studied to understand the amperometric response of various electrochemical reactions. The reaction mechanism includes hydrolysis of methyl salicylate and the oxidation of negative species. The electrochemical responses were recorded using cyclic voltammetry and differential pulse voltammetry techniques, where the results showed characteristic signals for methyl salicylate oxidation. Among the examined electrodes, AuNP-SPCE possessed three fold better sensitivity than planar gold and 35 times better sensitivity than SPCE (at 0.5 V). The methyl salicylate sensing by AuNP-SPCE possessed 95% of its methyl salicylate response. The electroanalytical results of soybean extract showed that AuNP-SPCE can be employed for the determination of methyl salicylate in real samples.

Microparticle Shedding by Erythrocytes, Monocytes and Vascular Smooth Muscular Cells Is Reduced by Aspirin in Diabetic Patients.

Science.gov (United States)

Chiva-Blanch, Gemma; Suades, Rosa; Padró, Teresa; Vilahur, Gemma; Peña, Esther; Ybarra, Juan; Pou, Jose M; Badimon, Lina

2016-07-01

Diabetes mellitus is associated with an enhanced risk for cardiovascular disease and its prevalence is increasing. Diabetes induces metabolic stress on blood and vascular cells, promoting platelet activation and vascular dysfunction. The level of vascular cell activation can be measured by the number and phenotype of microparticles found in the circulation. The aim of this study was to investigate the effect of a platelet-inhibitory dose of aspirin on the number and type of microparticles shed to the circulation. Forty-three diabetic patients were enrolled in the study and received a daily dose of 100mg of aspirin for 10 days to cover the average platelet life-span in the circulation. Before and after the intervention period, circulating microparticles were characterized and quantified by flow cytometry. Type 1 diabetic patients had about twice the number of tissue factor-positive circulating microparticles (derived both from platelets and monocytes) and endothelial-derived E-selectin positive microparticles than type 2 diabetic patients. Aspirin therapy significantly inhibited platelets since cyclooxygenase 1 derived thromboxane generation levels were reduced by 99%. Microparticles derived from erythrocytes, activated monocytes, and smooth muscle cells were significantly reduced after 10 days of aspirin administration. These results indicate that: a) vascular and blood cells in type 1 diabetic patients are exposed to more sustained stress shown by their specific microparticle origin and levels; b) aspirin therapy inhibits vascular wall cell activation and microparticle shedding, and c) the effects of aspirin are similar in type 1 and 2 diabetes. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Influence of aspirin therapy in the ulcer associated with chronic venous insufficiency.

Science.gov (United States)

del Río Solá, Ma Lourdes; Antonio, Jose; Fajardo, González; Vaquero Puerta, Carlos

2012-07-01

To determine the effect of aspirin on ulcer healing rate in patients with chronic venous insufficiency, and to establish prognostic factors that influence ulcer evolution. Between 2001 and 2005, 78 patients with ulcerated lesions of diameter >2 cm and associated with chronic venous insufficiency were evaluated in our hospital. Of these, 51 patients (22 men, 29 women) with mean age of 60 years (range: 36-86) were included in a prospective randomized trial with a parallel control group. The treatment group received 300 mg of aspirin and the control group received no drug treatment; in both groups, healing was associated with standard compression therapy. During follow-up, held weekly in a blinded fashion, there was ulcer healing as well as cases of recurrence. Results were analyzed by intention-to-treat approach. Cure rate was estimated using Kaplan-Meier survival analysis, and the influence of prognostic factors was analyzed by applying the Cox proportional hazards model. In the presence of gradual compression therapy, healing occurred more rapidly in patients receiving aspirin versus the control subjects (12 weeks in the treated group vs. 22 weeks in the control group), with a 46% reduction in healing time. The main prognostic factor was estimated initial area of injury (P = 0.032). Age, sex, systemic therapy, and infection showed little relevance to evolution. The administration of aspirin daily dose of 300 mg shortens the healing time of ulcerated lesions in the chronic venous insufficiency (CVI). The main prognostic factor for healing of venous ulcerated lesions is the initial surface area of the ulcer. Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

Effect of Aspirin in Postoperative Management of Adult Ischemic Moyamoya Disease.

Science.gov (United States)

Zhao, Yahui; Zhang, Qian; Zhang, Dong; Zhao, Yuanli

2017-09-01

Aspirin has been implicated in the postoperative management of moyamoya disease (MMD) in order to avoid bypass failure and decrease the incidence of subsequent stroke. However, its effect has not been completely determined yet. In this study, we retrospectively reviewed data of 184 adult patients (197 hemispheres) presented with ischemic-onset MMD who had undergone direct or combined revascularization in our hospital, to clarify the effect of postoperative aspirin therapy in the management of moyamoya disease. Fifty-nine hemispheres that had been administered with aspirin (100 mg/day) after bypass surgery were defined as the "aspirin group," whereas 138 that hadn't been given aspirin postoperatively were defined as the "control group". Among 197 hemispheres, the mortality rate was 0. The incidence of postoperative newly developed infarction, transient ischemic attack, and hemorrhage were not significantly different between the aspirin and control groups. The patency rate of bypass graft was not significantly different between the groups, either. Notably, more patients experienced major stroke in the control group (9/138) than the aspirin group (1/59), but no statistical difference was found (P > 0.05). In the aspirin group, more patients had improved outcome than the control group (P = 0.04). Our findings showed that aspirin might not decrease the incidence of postoperative ischemic stroke or increase patency rate of bypass graft, but it does not increase the risk of hemorrhages, either. Also, postoperative aspirin therapy might improve outcome. More studies are needed to provide evidence for postoperative antiplatelet therapy in MMD management. Copyright © 2017 Elsevier Inc. All rights reserved.

Glycerol Salicylate-based Pulp-Capping Material Containing Portland Cement.

Science.gov (United States)

Portella, Fernando Freitas; Collares, Fabrício Mezzomo; Santos, Paula Dapper; Sartori, Cláudia; Wegner, Everton; Leitune, Vicente Castelo Branco; Samuel, Susana Maria Werner

2015-01-01

The purpose of this study was to evaluate the water sorption, solubility, pH and ability to diffuse into dentin of a glycerol salicylate-based, pulp-capping cement in comparison to a conventional calcium hydroxide-based pulp capping material (Hydcal). An experimental cement was developed containing 60% glycerol salicylate resin, 10% methyl salicylate, 25% calcium hydroxide and 5% Portland cement. Water sorption and solubility were determined based on mass changes in the samples before and after the immersion in distilled water for 7 days. Material discs were stored in distilled water for 24 h, 7 days and 28 days, and a digital pHmeter was used to measure the pH of water. The cement's ability to diffuse into bovine dentin was assessed by Raman spectroscopy. The glycerol salicylate-based cement presented higher water sorption and lower solubility than Hydcal. The pH of water used to store the samples increased for both cements, reaching 12.59 ± 0.06 and 12.54 ± 0.05 after 7 days, for Hydcal and glycerol salicylate-based cements, respectively. Both cements were able to turn alkaline the medium at 24 h and sustain its alkalinity after 28 days. Hydcal exhibited an intense diffusion into dentin up to 40 µm deep, and the glycerol salicylate-based cement penetrated 20 µm. The experimental glycerol salicylate-based cement presents good sorption, solubility, ability to alkalize the surrounding tissues and diffusion into dentin to be used as pulp capping material.

A computational prospect to aspirin side effects: aspirin and COX-1 interaction analysis based on non-synonymous SNPs.

Science.gov (United States)

Marjan, Mojtabavi Naeini; Hamzeh, Mesrian Tanha; Rahman, Emamzadeh; Sadeq, Vallian

2014-08-01

Aspirin (ASA) is a commonly used nonsteroidal anti-inflammatory drug (NSAID), which exerts its therapeutic effects through inhibition of cyclooxygenase (COX) isoform 2 (COX-2), while the inhibition of COX-1 by ASA leads to apparent side effects. In the present study, the relationship between COX-1 non-synonymous single nucleotide polymorphisms (nsSNPs) and aspirin related side effects was investigated. The functional impacts of 37 nsSNPs on aspirin inhibition potency of COX-1 with COX-1/aspirin molecular docking were computationally analyzed, and each SNP was scored based on DOCK Amber score. The data predicted that 22 nsSNPs could reduce COX-1 inhibition, while 15 nsSNPs showed increasing inhibition level in comparison to the regular COX-1 protein. In order to perform a comparing state, the Amber scores for two Arg119 mutants (R119A and R119Q) were also calculated. Moreover, among nsSNP variants, rs117122585 represented the closest Amber score to R119A mutant. A separate docking computation validated the score and represented a new binding position for ASA that acetyl group was located within the distance of 3.86Å from Ser529 OH group. This could predict an associated loss of activity of ASA through this nsSNP variant. Our data represent a computational sub-population pattern for aspirin COX-1 related side effects, and provide basis for further research on COX-1/ASA interaction. Copyright © 2014 Elsevier Ltd. All rights reserved.

Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations.

Science.gov (United States)

Sheth, Harsh; Northwood, Emma; Ulrich, Cornelia M; Scherer, Dominique; Elliott, Faye; Barrett, Jennifer H; Forman, David; Wolf, C Roland; Smith, Gillian; Jackson, Michael S; Santibanez-Koref, Mauro; Haile, Robert; Casey, Graham; Jenkins, Mark; Win, Aung Ko; Hopper, John L; Marchand, Loic Le; Lindor, Noralane M; Thibodeau, Stephen N; Potter, John D; Burn, John; Bishop, D Timothy

2018-01-01

Regular aspirin use is associated with reduced risk of colorectal cancer (CRC). Variation in aspirin's chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs). We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs) and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All Paspirin use and CRC risk (Pinteraction = 0.01 and 0.02, respectively); stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95% CI = 0.68-0.86; rs1105879 OR = 0.77 95% CI = 0.69-0.86) compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only (Pinteraction = 0.006 and 0.008, respectively), with the direction of association similar to that observed for CRC. Additionally, they showed interaction between any non-steroidal anti-inflammatory drugs (including aspirin) use and CRC risk (Pinteraction = 0.01 for both). All gene x environment (GxE) interactions however were not significant after multiple test correction. Candidate gene investigation indicated no evidence of GxE interaction between genetic variants in genes involved in aspirin pathways, regular aspirin use and colorectal cancer

Aspirin and clopidogrel resistance: methodological challenges and opportunities

Directory of Open Access Journals (Sweden)

Armen Yuri Gasparyan

2010-03-01

Full Text Available Armen Yuri GasparyanClinical Research Unit, Russell’s Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, West Midlands, UKAbstract: Antiplatelet drug resistance is one of the urgent issues in current cardiovascular medicine. Many platelet function tests have been used to define responsiveness of patients with cardiovascular disease to aspirin and clopidogrel. In most studies, cut-off values of platelet function tests for defining responsiveness to antiplatelets were chosen arbitrarily. Different tests provided wide-ranging figures of the prevalence of aspirin and clopidogrel resistance, suggesting poor correlation between currently available platelet function tests. Measurement of platelet size seems to be a promising approach for monitoring antiplatelet drug therapy. This commentary highlights some limitations of studies on aspirin and clopidogrel resistance in patients undergoing coronary interventions.Keywords: aspirin, clopidogrel, resistance, cardiovascular disease, platelet function tests

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.

Are one or two dangerous? Methyl salicylate exposure in toddlers.

Science.gov (United States)

Davis, Jonathan E

2007-01-01

Serious toxicity can result from exposure to small amounts of methyl salicylate. Methyl salicylate is widely available as a component in many over-the-counter brands of creams, ointments, lotions, liniments and medicated oils intended for topical application to relieve musculoskeletal aches and pains. Among the most potent forms of methyl salicylate is oil of wintergreen (98% methyl salicylate). Other products with varying concentrations of methyl salicylate are ubiquitous throughout many parts of the world, including a number of products marketed as Asian herbal remedies. The toxic potential of all of these formulations is often underestimated by health care providers and the general public. A comprehensive review of the existing medical literature on methyl salicylate poisoning was performed, and data compiled over the past two decades by the American Association of Poison Control Centers (AAPCC) was examined. Methyl salicylate continues to be a relatively common source of pediatric exposures. Persistent reports of life-threatening and fatal toxicity were found. In children less than 6 years of age, a teaspoon (5 mL) or less of oil of wintergreen has been implicated in several well-documented deaths. More needs to be done to educate both health care providers and the general public regarding the dangers of these widely available formulations.

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

Aspirin and Risk of Subarachnoid Hemorrhage: Systematic Review and Meta-Analysis.

Science.gov (United States)

Phan, Kevin; Moore, Justin M; Griessenauer, Christoph J; Ogilvy, Christopher S; Thomas, Ajith J

2017-05-01

Recent studies have suggested that the use of low-dose aspirin may reduce the risk of aneurysmal subarachnoid hemorrhage (aSAH). We aimed to evaluate any association between aspirin use and risk of aSAH based on the literature, and whether this is influenced by duration or frequency of aspirin use. A search of electronic databases was done from inception to September 2016. For each study, data on risk of aSAH in aspirin versus nonaspirin users were used to generate odds ratios and 95% confidence intervals, and combined using inverse variance-weighted averages of logarithmic odds ratios in a random-effects models. From 7 included studies, no significant difference was noted between aspirin use of any duration or frequency and nonaspirin users (odds ratio, 1.00; 95% confidence interval, 0.81-1.24; P =0.99). We found a significant association between short-term use of aspirin (3 years of durations of use. No significant association was found between infrequent aspirin use (≤2× per week) or frequent use (≥3× per week) with risk of aSAH. Current evidence suggests that short-term (aspirin is associated with increased risk of aSAH. Limitations include substantial heterogenity of the included studies. The role of long-term aspirin in reducing risk of aSAH remains unclear and ideally should be addressed by an appropriately designed randomized controlled trial. © 2017 American Heart Association, Inc.

Synthesis of 3H-3-azido-salicyl-N-(n-decyl) amide

International Nuclear Information System (INIS)

Lu Bin; Xu Jianxing; Chen Shizhi

2000-01-01

A novel method for the synthesis of molecular probe of ubiquinone-binding protein is described. With 3-nitrosalicylic acid and decylamine as initial compounds and under the existence of DCC, the 3-nitro-salicyl-N-(n-decyl)amide is synthesized at room temperature. Then, 3-nitro-salicyl-N-(n-decyl)amide is reduced by hydrogen with 5 % Pd/C as catalyst to form 3-amino-salicyl-N-(n-decyl)amide which is exchanged with tritium to be 3 H-3-amino-salicyl-N-(n-decyl)amide. At the temperature below 5 degree C, 3 H-3-amino-salicyl-N-(n-decyl)amide reacts with NaNO 2 and HCl, and the 3-diazo-salicyl-N-(n-decyl)amide is formed in an ice salt bath. As soon as the reaction is completed, NaN 3 is added to the mixture and stirred for 3 h at the temperature between 0 - 5 degree C and in the dark, the molecular probe of studying ubiquinone-binding protein, i. e., 3 H-3-azido-salicyl-N-(n-decyl)amide is produced

Anaesthesia in aspirin-induced asthma.

Science.gov (United States)

Celiker, V; Basgül, E

2003-01-01

The triad of bronchial asthma, nasal polyposis, and intolerance to aspirin and aspirin-like chemicals are designated aspirin-induced asthma (AIA) or Samter's syndrome. The exact mechanism of the disease is unknown but it is thought to be a disorder of arachidonic acid metabolism. These patients are frequently referred to allergy clinics for preoperative evaluation for possible anesthetic agent sensitivity, requiring anesthesia for nasal polypectomy or several other reasons. Anesthetists must be aware of their pulmonary dysfunction, because the anesthetic management of asthma requires a specific approach. Marked cross-sensitivity with NSAIDs, which may also precipitate severe bronchospasm and adverse reactions, is the main problem faced by anesthetists in postoperative pain management. This article discusses the relationship between AIA and anesthesia. We also present our experience with 47 patients diagnosed with AIA between 1991 and 2003 in the department of chest diseases and adult allergy unit who underwent surgery requiring general anesthesia. In conclusion, preoperative evaluation of these patients and collaboration between the allergists and anesthesiologists is essential to prevent preoperative, perioperative and postoperative complications.

Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations.

Directory of Open Access Journals (Sweden)

Harsh Sheth

Full Text Available Regular aspirin use is associated with reduced risk of colorectal cancer (CRC. Variation in aspirin's chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs. We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All P<0.05. Association for SNP rs6983267 in the CCAT2 gene only was noteworthy after multiple test correction (P = 0.001. Site-specific analysis showed association between SNPs rs1799853 and rs2302615 with reduced colon cancer risk only (P = 0.01 and P = 0.004, respectively, however neither reached significance threshold following multiple test correction. Meta-analysis of SNPs rs2070959 and rs1105879 in UGT1A6 gene showed interaction between aspirin use and CRC risk (Pinteraction = 0.01 and 0.02, respectively; stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95% CI = 0.68-0.86; rs1105879 OR = 0.77 95% CI = 0.69-0.86 compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only (Pinteraction = 0.006 and 0.008, respectively, with the direction of association similar to

Regular use of aspirin and pancreatic cancer risk

Directory of Open Access Journals (Sweden)

Mahoney Martin C

2002-09-01

Full Text Available Abstract Background Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs has been consistently associated with reduced risk of colorectal cancer and adenoma, and there is some evidence for a protective effect for other types of cancer. As experimental studies reveal a possible role for NSAIDs is reducing the risk of pancreatic cancer, epidemiological studies examining similar associations in human populations become more important. Methods In this hospital-based case-control study, 194 patients with pancreatic cancer were compared to 582 age and sex-matched patients with non-neoplastic conditions to examine the association between aspirin use and risk of pancreatic cancer. All participants received medical services at the Roswell Park Cancer Institute in Buffalo, NY and completed a comprehensive epidemiologic questionnaire that included information on demographics, lifestyle factors and medical history as well as frequency and duration of aspirin use. Patients using at least one tablet per week for at least six months were classified as regular aspirin users. Unconditional logistic regression was used to compute crude and adjusted odds ratios (ORs with 95% confidence intervals (CIs. Results Pancreatic cancer risk in aspirin users was not changed relative to non-users (adjusted OR = 1.00; 95% CI 0.72–1.39. No significant change in risk was found in relation to greater frequency or prolonged duration of use, in the total sample or in either gender. Conclusions These data suggest that regular aspirin use may not be associated with lower risk of pancreatic cancer.

Use and Misuse of Aspirin in Primary Cardiovascular Prevention

Directory of Open Access Journals (Sweden)

Sergio Coccheri

2017-04-01

Full Text Available The use of low-dose aspirin in primary prevention of cardiovascular (CV events in healthy or apparently healthy people is a widely debated topic. Many arguments indicate that “primary prevention” is only a conventional definition and that the transition from primary to secondary prevention represents a continuum of increasing levels of CV risk. Although there are no direct proofs of a different efficacy of aspirin at different CV risk levels, in low-risk populations aspirin will appear to be less efficient. In fact, the lower number of events occurring in patients at low risk yields lower absolute numbers of events prevented. As many as 6 meta-analyses of trials of primary CV prevention with aspirin versus placebo, performed between 2009 and 2016, confirmed the above concepts and showed a concordant, significant reduction in nonfatal myocardial infarction, with no significant effects on stroke, as well as on CV and all-cause mortality. The recent demonstration of a moderate protective effect of aspirin on cancer (especially colorectal confers, however, additional value to the use of aspirin, although unusually long durations of treatment and optimal daily compliance seem to be necessary. Because aspirin increases the bleeding risk, the evaluation of its net clinical benefit is an important point of debate. Thus, it is justified to search for a cutoff level of global CV risk above which the net clinical benefit of aspirin becomes evident. Such a threshold value has been calculated considering the data of 9 primary prevention trials, by the Thrombosis Group of the European Society of Cardiology, and has been indicated as a risk value of 2 or more major CV events per 100 persons per year. Also, in the recent 2016 US Guidelines, the main criterion adopted for the indication of aspirin is the level of global CV risk (suggested cutoff is 1 or more major CV events per 100 persons per year. Beyond the different values selected, it is seems very

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

Science.gov (United States)

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

2017-11-01

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

Novel Pathway of Salicylate Degradation by Streptomyces sp. Strain WA46

OpenAIRE

Ishiyama, Daisuke; Vujaklija, Dusica; Davies, Julian

2004-01-01

A novel salicylate-degrading Streptomyces sp., strain WA46, was identified by UV fluorescence on solid minimal medium containing salicylate; trace amounts of gentisate were detected by high-pressure liquid chromatography when strain WA46 was grown with salicylate. PCR amplification of WA46 DNA with degenerate primers for gentisate 1,2-dioxygenase (GDO) genes produced an amplicon of the expected size. Sequential PCR with nested GDO primers was then used to identify a salicylate degradation gen...

Simultaneous silencing of ACSL4 and induction of GADD45B in hepatocellular carcinoma cells amplifies the synergistic therapeutic effect of aspirin and sorafenib

Science.gov (United States)

Xia, Hongping; Lee, Kee Wah; Chen, Jianxiang; Kong, Shik Nie; Sekar, Karthik; Deivasigamani, Amudha; Seshachalam, Veerabrahma Pratap; Goh, Brian Kim Poh; Ooi, London Lucien; Hui, Kam M

2017-01-01

Sorafenib is currently the only US Food and Drug Administration (FDA)-approved molecular inhibitor for the systemic therapy of advanced hepatocellular carcinoma (HCC). Aspirin has been studied extensively as an anti-inflammation, cancer preventive and therapeutic agent. However, the potential synergistic therapeutic effects of sorafenib and aspirin on advanced HCC treatment have not been well studied. Drug combination studies and their synergy quantification were performed using the combination index method of Chou-Talalay. The synergistic therapeutic effects of sorafenib and aspirin were evaluated using an orthotopic mouse model of HCC and comprehensive gene profiling analyses were conducted to identify key factors mediating the synergistic therapeutic effects of sorafenib and aspirin. Sorafenib was determined to act synergistically on HCC cells with aspirin in vitro. Using Hep3B and HuH7 HCC cells, it was demonstrated that sorafenib and aspirin acted synergistically to induce apoptosis. Mechanistic studies demonstrated that combining sorafenib and aspirin yielded significant synergistically anti-tumor effects by simultaneously silencing ACSL4 and the induction of GADD45B expression in HCC cells both in vitro and in the orthotopic HCC xenograft mouse model. Importantly, clinical evidence has independently corroborated that survival of HCC patients expressing ACSL4highGADD45Blow was significantly poorer compared to patients with ACSL4lowGADD45Bhigh, thus demonstrating the potential clinical value of combining aspirin and sorafenib for HCC patients expressing ACSL4highGADD45Blow. In conclusion, sorafenib and aspirin provide synergistic therapeutic effects on HCC cells that are achieved through simultaneous silencing of ACSL4 and induction of GADD45B expression. Targeting HCC with ACSL4highGADD45Blow expression with aspirin and sorafenib could provide potential synergistic therapeutic benefits. PMID:28900541

Effect of indomethacin, diclofenac sodium and sodium salicylate on peripheral blood cell counts in sublethally gamma-irradiated mice

International Nuclear Information System (INIS)

Pospisil, M.; Netikova, J.; Kozubik, A.; Pipalova, I.

1989-01-01

Treatment with indomethacin and diclofenac sodium was found to increase granulocyte counts in the blood of sublethally gamma-irradiated mice. Treatment with sodium salicylate was ineffective in this respect, administration of sodium salicylate together with indomethacin even decreased the indomethacin-induced effects. The results suggest that the hemopoiesis-stimulating effects of non-steroidal anti-flammatory drugs cannot be correlated with the anti-inflammatory activity but rather with the side effects of these compounds, including the action on gastro-intestinal prostanoid production. This conclusion doubts on the possibility of the usefulness of non-steroidal anti-inflammatory drugs in conditions of the radiation syndrome. (orig.) [de

Cardioprotective aspirin users and their excess risk of upper gastrointestinal complications.

Science.gov (United States)

Hernández-Díaz, Sonia; García Rodríguez, Luis A

2006-09-20

To balance the cardiovascular benefits from low-dose aspirin against the gastrointestinal harm caused, studies have considered the coronary heart disease risk for each individual but not their gastrointestinal risk profile. We characterized the gastrointestinal risk profile of low-dose aspirin users in real clinical practice, and estimated the excess risk of upper gastrointestinal complications attributable to aspirin among patients with different gastrointestinal risk profiles. To characterize aspirin users in terms of major gastrointestinal risk factors (i.e., advanced age, male sex, prior ulcer history and use of non-steroidal anti-inflammatory drugs), we used The General Practice Research Database in the United Kingdom and the Base de Datos para la Investigación Farmacoepidemiológica en Atención Primaria in Spain. To estimate the baseline risk of upper gastrointestinal complications according to major gastrointestinal risk factors and the excess risk attributable to aspirin within levels of these factors, we used previously published meta-analyses on both absolute and relative risks of upper gastrointestinal complications. Over 60% of aspirin users are above 60 years of age, 4 to 6% have a recent history of peptic ulcers and over 13% use other non-steroidal anti-inflammatory drugs. The estimated average excess risk of upper gastrointestinal complications attributable to aspirin is around 5 extra cases per 1,000 aspirin users per year. However, the excess risk varies in parallel to the underlying gastrointestinal risk and might be above 10 extra cases per 1,000 person-years in over 10% of aspirin users. In addition to the cardiovascular risk, the underlying gastrointestinal risk factors have to be considered when balancing harms and benefits of aspirin use for an individual patient. The gastrointestinal harms may offset the cardiovascular benefits in certain groups of patients where the gastrointestinal risk is high and the cardiovascular risk is low.

Aspirin desensitization in patients undergoing percutaneous coronary intervention: a survey of current practice.

Science.gov (United States)

Chapman, Andrew R; Rushworth, Gordon F; Leslie, Stephen J

2013-01-01

Aspirin remains the mainstay of anti-platelet therapy in cardiac patients. However, if a patient is allergic to aspirin and dual anti-platelet therapy is indicated - such as with percutaneous coronary intervention (PCI), then there is no clear guidance. One possibility is aspirin desensitization. A variety of protocols exist for the rapid desensitization of patients with aspirin allergy. The aim of this survey was to assess current knowledge and practice regarding aspirin desensitization in the UK. We conducted a UK wide survey of all UK 116 PCI centers and obtained complete responses from 40 (35.4%) centers. Of these, just 7 (17.5%) centers had previously desensitised patients; 29 (87.9%) centers suggested a lack of a local protocol prevented them from desensitizing, with 10 (30.3%) unsure of how to conduct desensitization. Only 5 (12.5%) centers had a local policy for aspirin desensitization although 25 (64.1%) units had a clinical strategy for dealing with aspirin allergy; the majority (72%) giving higher doses of thienopyridine class drugs. In the UK, there appears to be no consistent approach to patients with aspirin allergy. Patients undergoing PCI benefit from dual anti-platelet therapy (including aspirin), and aspirin desensitization in those with known allergy may facilitate this. Sustained effort should be placed on encouraging UK centers to use desensitization as a treatment modality prior to PCI rather than avoiding aspirin altogether.

Salicylic acid as a peeling agent: a comprehensive review

OpenAIRE

Arif, Tasleem

2015-01-01

Tasleem Arif Postgraduate Department of Dermatology, STD and Leprosy, Government Medical College, Srinagar, Jammu and Kashmir, India Abstract: Salicylic acid has been used to treat various skin disorders for more than 2,000 years. The ability of salicylic acid to exfoliate the stratum corneum makes it a good agent for peeling. In particular, the comedolytic property of salicylic acid makes it a useful peeling agent for patients with acne. Once considered as a keratolytic agent, the role of s...

Preoperative Aspirin Does Not Increase Transfusion or Reoperation in Isolated Valve Surgery.

Science.gov (United States)

Goldhammer, Jordan E; Herman, Corey R; Berguson, Mark W; Torjman, Marc C; Epstein, Richard H; Sun, Jian-Zhong

2017-10-01

Preoperative aspirin has been studied in patients undergoing isolated coronary artery bypass graft surgery. However, there is a paucity of clinical data available evaluating perioperative aspirin in other cardiac surgical procedures. This study was designed to investigate the effects of aspirin on bleeding and transfusion in patients undergoing non-emergent, isolated, heart valve repair or replacement. Retrospective, cohort study. Academic medical center. A total of 694 consecutive patients having non-emergent, isolated, valve repair or replacement surgery at an academic medical center were identified. Of the 488 patients who met inclusion criteria, 2 groups were defined based on their preoperative use of aspirin: those taking (n = 282), and those not taking (n = 206) aspirin within 5 days of surgery. Binary logistic regression was used to examine relationships among demographic and clinical variables. No significant difference was found between the aspirin and non-aspirin groups with respect to the percentage receiving red blood cell (RBC) transfusion, mean RBC units transfused in those who required transfusion, massive transfusion of RBC, or amounts of fresh frozen plasma, cryoprecipitate, or platelets. Aspirin was not associated with an increase in the rate of re-exploration for bleeding (5.3% v 6.3%, p = 0.478). Major adverse cardiocerebral events (MACE), 30-day mortality, and 30-day readmission rates were not statistically different between the aspirin-and non-aspirin-treated groups. Preoperative aspirin therapy in elective, isolated, valve surgery did not result in an increase in transfusion or reoperation for bleeding and was not associated with reduced readmission rate, MACE, or 30-day mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

Overexpression of a soybean salicylic acid methyltransferase gene confers resistance to soybean cyst nematode

Science.gov (United States)

Salicylic acid plays a critical role in activating plant defence responses after pathogen attack. Salicylic acid methyltransferase (SAMT) modulates the level of salicylic acid by converting salicylic acid to methyl salicylate. Here, we report that a SAMT gene from soybean (GmSAMT1) plays a role in s...

Weighing the Anti-Ischemic Benefits and Bleeding Risks from Aspirin Therapy: a Rational Approach.

Science.gov (United States)

Dugani, Sagar; Ames, Jeffrey M; Manson, JoAnn E; Mora, Samia

2018-02-21

The role of aspirin in secondary cardiovascular prevention is well understood; however, the role in primary prevention is less clear, and requires careful balancing of potential benefits with risks. Here, we summarize the evidence base on the benefits and risks of aspirin therapy, discuss clinical practice guidelines and decision support tools to assist in initiating aspirin therapy, and highlight ongoing trials that may clarify the role of aspirin in cardiovascular disease prevention. In 2016, the USPSTF released guidelines on the use of aspirin for primary prevention. Based on 11 trials (n = 118,445), aspirin significantly reduced all-cause mortality and nonfatal myocardial infarction, and in 7 trials that evaluated aspirin ≤ 100 mg/day, there was significant reduction in nonfatal stroke. The USPSTF recommends individualized use of aspirin based on factors including age, 10-year atherosclerotic cardiovascular disease risk score, and bleeding risk. Several ongoing trials are evaluating the role of aspirin in primary prevention, secondary prevention, and in combination therapy for atrial fibrillation. Evidence-based approaches to aspirin use should consider the anti-ischemic benefits and bleeding risks from aspirin. In this era of precision medicine, tools that provide the personalized benefit to risk assessment, such as the freely available clinical decision support tool (Aspirin-Guide), can be easily incorporated into the electronic health record and facilitate more informed decisions about initiating aspirin therapy for primary prevention. Aspirin has a complex matrix of benefits and risks, and its use in primary prevention requires individualized decision-making. Results from ongoing trials may guide healthcare providers in identifying appropriate candidates for aspirin therapy.

Effect of Aspirin Supplementation on Hemodynamics in Older Firefighters.

Science.gov (United States)

Lane-Cordova, Abbi D; Ranadive, Sushant M; Yan, Huimin; Kappus, Rebecca M; Sun, Peng; Bunsawat, Kanokwan; Smith, Denise L; Horn, Gavin P; Ploutz-Snyder, Robert; Fernhall, B O

2015-12-01

Cardiovascular events are the leading cause of line-of-duty fatality for firefighters. Aspirin reduces the risk of cardiovascular events in men and may reduce fatalities in older (>40 yr) firefighters. We hypothesized that both chronic and acute aspirin supplementation would improve vascular function after live firefighting but that chronic supplementation would also improve resting hemodynamics. Twenty-four firefighters (40-60 yr) were randomly assigned to acute or chronic aspirin supplementation or placebo in a balanced, crossover design. Arterial stiffness, brachial and central blood pressures, as well as forearm vasodilatory capacity and blood flow were measured at rest and immediately after live firefighting. Total hyperemic blood flow (area under the curve (AUC)) was increased (P 0.05 for interaction). Arterial stiffness/central blood pressure increased (P < 0.04) with no effect of aspirin (from 0.0811 ± 0.001 to 0.0844 ± 0.003 m·s·mm⁻¹ Hg⁻¹ in aspirin condition versus 0.0802 ± 0.002 to 0.0858 ± 0.002 m·s⁻¹·mm Hg⁻¹ in placebo condition), whereas peripheral and central systolic and pulse pressures decreased after firefighting across conditions (P < 0.05). Live firefighting resulted in increased AUC and pressure-controlled arterial stiffness and decreased blood pressure in older firefighters, but aspirin supplementation did not affect macro- or microvascular responsiveness at rest or after firefighting.

An assessment of aspirin use in a Nigerian diabetes outpatient clinic.

Science.gov (United States)

Kolawole, B A; Adebayo, R A; Aloba, O O

2004-01-01

We have conducted this study to assess the use of aspirin among adult diabetic outpatients in our hospital. The records of all patients attending the weekly Diabetes clinic of the Wesley Guild Hospital (WGH), Ilesa, Osun state, Nigeria over one month were reviewed and aspirin use evaluated in light of the American Diabetes Association position statement (2003) on aspirin therapy in diabetes. Eighty-two patients in all were studied. Fourty three (52.4%) were males, 39 (47.6%) were females. Their mean age was 59.1 +/- 10.7 yrs (range 31-81). All were type 2 and had been diabetic for a mean of 5.2 +/- 5.7 yrs (1-26yrs). Concurrent hypertension, another major risk factor for cardiovascular disease was found in 71.9% and 12.2% were obese. Aspirin use was contraindicated in 1.2%. All other patients had at least one indication for the use of aspirin based on the ADA criteria but only 39% were taking aspirin regularly. The results of this present study suggest that aspirin is still grossly under utilised in clinic patients with diabetes despite proven benefits. There is need to stimulate awareness amongst health care providers.

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

African Journals Online (AJOL)

Dr J. T. Ekanem

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

Systemic aspirin and systemic vitamin E in senile cataracts : cataract V

Directory of Open Access Journals (Sweden)

Sharma Y

1989-01-01

Full Text Available We undertook a prospective study in senile cataract patients using systemic aspirin and systemic vitamin E. Vitamin E treated eyes did show less progression of PSC opacities extent and less new nuclear opacities during the follow-up, but overall vitamin E treated eyes did no better than the control group eyes. More eyes in systemic aspirin treated group maintained the initial vision and loss of vision in the aspirin group was also less marked. Aspirin also caused a significant less mean increase in cortical opacity extent, nuclear/opacity and density and PSC opacity extent and density as well as in ophthalmoscopically graded opacity extent and density. We suggest that aspirin is a potential drug which should be further evaluated in large double blind photodocumentated studies. The present data does not justify the recommendation that aspirin be prescribed for slowing down cataract progression. This must await large studies and confirmation.

Salicylate removal by charcoal heamoperfusion in experimental intoxication in dogs

International Nuclear Information System (INIS)

Brookings, C.H.; Ramsey, J.D.

1975-01-01

The removal of salicylate by extracorporeal circulation of blood through a column of encapsulated charcoal (haemoperfusion) has been studied experimentally in intoxicated dogs (greyhounds). The average time taken to reduce the whole blood salicylate level to one-half of the initial equilibrium level in 30 kg dogs was 2 hrs. A half-life of 3 hrs is predicted for salicylate removal by haemoperfusion in a 70 kg man and this rate of removal is shown to be comparable to that reported for haemodialysis. No unacceptable adverse physiological, biochemical, or haematological effects were found to result from haemoperfusion. The possible use of this technique in the management of severe salicylate poisoning in man is discussed. Haemoperfusion is foreseen as providing a method of rapid removal of salicylate in circumstances where forced diuresis is contra-indicated or inadequate and haemodialysis is not readily available. (orig.) [de

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.

Should patients prescribed long-term low-dose aspirin receive proton pump inhibitors? A systematic review and meta-analysis

NARCIS (Netherlands)

Tran-Duy, A.; Vanmolkot, F. H.; Joore, M. A.; Hoes, A. W.; Stehouwer, C. D. A.

2015-01-01

Background: Several clinical guidelines recommend the use of proton pump inhibitors (PPIs) in patients taking low-dose aspirin but report no or limited supporting data. We conducted a systematic review and meta-analysis to examine the effects of co-administration of PPIs in patients taking low-dose

The Effect of Combined Aspirin and Clopidogrel Treatment on Cancer Incidence.

Science.gov (United States)

Leader, Avi; Zelikson-Saporta, Ravit; Pereg, David; Spectre, Galia; Rozovski, Uri; Raanani, Pia; Hermoni, Doron; Lishner, Michael

2017-07-01

Multiple studies have shown an association between aspirin treatment and a reduction in newly diagnosed cancer. Conversely, there are conflicting clinical and laboratory data on the effect of combined clopidogrel and aspirin therapy on cancer incidence, including analyses suggesting an increased cancer risk. No large-scale cohort study has been performed to address this issue in a heterogeneous real-world scenario. We investigated the effect of clopidogrel and aspirin on cancer incidence compared with aspirin alone and no antiplatelet therapy. A population-based historical cohort study of subjects aged ≥50 years covered by Clalit Health Services, an Israeli health maintenance organization, was performed. Patients treated with the newer antiplatelet drugs, prasugrel or ticagrelor, which, like clopidogrel, inhibit adenosine diphosphate receptors, and those with prior cancer were excluded. Prescription records of antiplatelet medication were retrieved. The cohort included 183,912 subjects diagnosed with 21,974 cancer cases based upon the International Classification of Diseases, Ninth Revision. Dual aspirin and clopidogrel was prescribed in 9.6%, while 49% received aspirin alone and 41% used neither. Compared with nonusers, there was a lower risk of cancer in subjects exposed to aspirin with (hazard ratio [HR] 0.46; 95% confidence interval [CI], 0.44-0.49) or without clopidogrel (HR 0.54; 95% CI, 0.52-0.56), on long-term follow-up. Combined treatment was associated with a lower cancer risk than the aspirin-only group (HR 0.92; 95% CI, 0.86-0.97). Dual clopidogrel and aspirin treatment is safe regarding the cancer risk. This study generates the hypothesis that clopidogrel may reduce cancer incidence. Copyright © 2017 Elsevier Inc. All rights reserved.

Salicylate toxicity from ingestion of traditional massage oil

Science.gov (United States)

Muniandy, Rajesh Kumar; Sinnathamby, Vellan

2012-01-01

A 16-month-old child developed a brief generalised tonic–clonic fitting episode and vomiting at home, after accidental ingestion of traditional massage oil. As the patient presented with clinical features of salicylate toxicity, appropriate management was instituted. He was admitted to the intensive care unit for multiorgan support. The child was discharged well 1 week after the incident. Methyl-salicylate is a common component of massage oils which are used for topical treatment of joint and muscular pains. However, these massage oils may be toxic when taken orally. Early recognition of the salicylate toxicity is very important in producing a good patient outcome. PMID:22922924

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

Directory of Open Access Journals (Sweden)

Isnatin Miladiyah

2016-01-01

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

ESR investigation of gamma-irradiated Aspirin

International Nuclear Information System (INIS)

Cozar, O.; Chis, V.; David, L.; Damian, G.; Barbur, I.

1997-01-01

Electron spin resonance spectroscopy was used to investigate the radiation damage in a powder of 2-acetoxybenzoic acid (Aspirin). Three types of radicals occur by γ-irradiation of Aspirin at room temperature. Two of them are result of hydrogen abstraction while the third is produced by hydrogen addition at one of the carbon atoms of the ring. The relative yielding of the free radicals as a function of absorbed dose in the range of 2.4 kGy to 160 kGy is also discussed. (author)

Evaluation of aspirin therapy on intracardiac thrombi using indium-111-oxine platelet scintigraphy, two-dimentional echocardiography and left ventriculography

International Nuclear Information System (INIS)

Shibuya, Masanori; Irino, Tadayoshi; Yoshioka, Toshiharu; Sugimoto, Tsuyoshi; Tsuji, Kazuo; Naka, Masashi; Arai, Hidekazu.

1984-01-01

Left ventriculography (LVG), two-dimensional echocardiography (2-DE) and indium-111-oxine platelet scintigraphy were performed in five patients with intracardiac thrombi. Thrombi were visible in 7 sites (5 in the ventricle and 2 in the atrium) by platelet scintigraphy, in 4 sites (3 in the ventricle and 1 in the atrium) by 2-DE, and in 4 sites (4 in the ventricle) by LVG. When aspirin was administered to the patients, platelet scintigraphy had become negative for thrombi in 5 sites and false-negative for them in 2 sites. However, thrombi were detected in 6 sites after the withdrawal of aspirin. On the other hand, thrombi were detected in 4 sites by 2-DE, irrespective of the administration of aspirin. Indium-111-oxine platelet scintigraphy has proved to not only have higher sensitivity for detecting thrombi but also to be capable of observing the coagulation status of platelets on the thrombi. It is therefore considered very helpful in assessing anticoagulation therapy. (Namekawa, K)

Detection of methyl salicylate using bi-enzyme electrochemical sensor consisting salicylate hydroxylase and tyrosinase.

Science.gov (United States)

Fang, Yi; Bullock, Hannah; Lee, Sarah A; Sekar, Narendran; Eiteman, Mark A; Whitman, William B; Ramasamy, Ramaraja P

2016-11-15

Volatile organic compounds have been recognized as important marker chemicals to detect plant diseases caused by pathogens. Methyl salicylate has been identified as one of the most important volatile organic compounds released by plants during a biotic stress event such as fungal pathogen infection. Advanced detection of these marker chemicals could help in early identification of plant diseases and has huge significance for agricultural industry. This work describes the development of a novel bi-enzyme based electrochemical biosensor consisting of salicylate hydroxylase and tyrosinase enzymes immobilized on carbon nanotube modified electrodes. The amperometric detection using the bi-enzyme platform was realized through a series of cascade reactions that terminate in an electrochemical reduction reaction. Electrochemical measurements revealed that the sensitivity of the bi-enzyme sensor was 30.6±2.7µAcm(-2)µM(-1) and the limit of detection and limit of quantification were 13nM (1.80ppb) and 39nM (5.39ppb) respectively. Interference studies showed no significant interference from the other common plant volatile compounds. Synthetic analyte studies revealed that the bi-enzyme based biosensor can be used to reliably detect methyl salicylate released by unhealthy plants. Copyright © 2016. Published by Elsevier B.V.

Failure of ethamsylate to reduce aspirin-induced gastric mucosal bleeding in humans.

Science.gov (United States)

Daneshmend, T K; Stein, A G; Bhaskar, N K; Hawkey, C J

1989-07-01

1. We investigated the effect of the haemostatic agent ethamsylate on aspirin-induced gastric mucosal bleeding. 2. Eighteen healthy subjects were studied three times: at the end of 48 h periods of treatment with (a) placebo, (b) aspirin 600 mg four times daily, (9 doses) and (c) aspirin 600 mg four times daily with each dose preceded by ethamsylate 500 mg. 3. At the end of each treatment period gastric mucosal bleeding into timed gastric washings was quantified using the orthotolidine reaction. 4. Aspirin increased bleeding from a rate on placebo of 1.2 microliters 10 min-1 geometric mean (95% confidence limits) (0.7-1.8) microliters 10 min-1 to 20.0 (11.6-34.2) microliters 10 min-1, (P less than 0.01). The rate of bleeding after aspirin preceded by ethamsylate [14.1 (8.5-23.4) microliters 10 min-1] was not significantly different from that after aspirin alone. 5. We conclude that ethamsylate does not reduce acute aspirin-induced gastric mucosal bleeding in healthy humans.

Prevalence of aspirin resistance in patients with an evolving acute myocardial infarction

DEFF Research Database (Denmark)

Poulsen, Tina Svenstrup; Jørgensen, Bo; Korsholm, Lars

2007-01-01

OBJECTIVE: To study the prevalence and importance of aspirin resistance in patients with an evolving acute myocardial infarction (AMI) by use of the Platelet Function Analyzer-100. INTRODUCTION: Previous studies have demonstrated the existence of aspirin resistance, but the clinical relevance...... of the phenomenon remains to be clarified. If aspirin resistant patients comprise a high-risk subgroup, it might be expected that the prevalence of aspirin resistance in patients with AMI would be higher than in patients without AMI. We hypothesized that the prevalence of aspirin resistance in patients with AMI...... was twice the prevalence in patients without AMI. METHODS: We included 298 consecutive patients with known cardiovascular disease who were admitted to hospital with symptoms suggestive of an AMI. All had been taking aspirin 150 mg/day for at least 7 days prior to hospital admission. Platelet function...

Effect of Aspirin on Spinal Cord Injury: An Experimental Study

Directory of Open Access Journals (Sweden)

Hamed Reihani Kermani

2016-05-01

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

Aspirin induces morphological transformation to the secretory state in isolated rabbit parietal cells.

Science.gov (United States)

Murthy, U K; Levine, R A

1991-08-01

The morphological response of rabbit parietal cells to aspirin was evaluated by grading several ultra-structural features including the extent of the tubulovesicular system, intracellular secretory canaliculi, and microvilli. After exposure of isolated parietal cells and gastric glands to aspirin or histamine, there was an approximately twofold increase in the ratio of secretory to nonsecretory parietal cells, and depletion of extracellular Ca2+ abolished the aspirin-induced morphological changes. Morphometry in parietal cells showed that aspirin induced a sixfold increase in secretory canalicular membrane elaboration. Aspirin potentiated histamine-induced parietal cell respiration and aminopyrine uptake ratio but did not increase basal respiration or aminopyrine uptake, suggesting an apparent dissociation from aspirin-induced morphological changes.

Aspirin and heart disease

Science.gov (United States)

... medlineplus.gov/ency/patientinstructions/000092.htm Aspirin and heart disease To use the sharing features on this page, ... healthy people who are at low risk for heart disease. You provider will consider your overall medical condition ...

Low-Dose Aspirin in Heart Failure Not Complicated by Atrial Fibrillation

DEFF Research Database (Denmark)

Madelaire, Christian; Gislason, Gunnar; Kristensen, Søren L

2018-01-01

OBJECTIVES: This study sought to assess safety and effectiveness of low-dose aspirin in heart failure (HF) not complicated by atrial fibrillation. BACKGROUND: Despite lack of evidence, low-dose aspirin is widely used in patients with HF and sinus rhythm with and without prior ischemic heart disease....... METHODS: The study included 12,277 patients with new-onset HF during 2007 to 2012 who had no history of atrial fibrillation. Of 5,450 patients using low-dose aspirin at baseline, 3,840 were propensity matched to non-aspirin users in a 1:1 ratio. Propensity-matched Cox models were calculated with respect...... to the primary composite outcome of all-cause mortality, myocardial infarction, and stroke and the secondary outcomes of bleeding and HF readmission. RESULTS: The composite outcome occurred in 1,554 (40.5%) patients in the aspirin group and 1,604 (41.8%) patients in the non-aspirin group. Aspirin use...

Studying the properties of the new class of organic scintillators-salicylic acid derivatives

International Nuclear Information System (INIS)

Mandzhukov, I.G.; Mandzhukova, B.V.; Bonchev, Ts.V.; Lazarova, G.I.

1981-01-01

Li, Na, K, Mg, Ca, Sr, Ba, La, Cd, Al, Sn, NH 4 salicylates are synthesized. Their relative scintillation efficiency during irradiation with α-particles of 5.156 MeV energy (sup(239)Pu) is determined. Scintillation efficiency of salicylates has been evaluated by comparing amplitude of scintillation pulse from salicylate with pulse amplitude from anthracene and other classical scintillators. Amplitude analysis has been conducted by standard methods. The analysis of the results obtained shows that sodium salicylate has the highest relative scintillation efficiency comparable with naphthalene efficiency. Salicylates of alkali Li and K metals as well as Ca and Cd salicylates have high relative scintillation efficiency. It is concluded that the investigated salicylates can be used for detection of (n, α), (n, p) and other reactions accompanying neutron capture not only during their reactions but by measuring activity induced in the scintillator [ru

Salicylic acid induces apoptosis in colon carcinoma cells grown in-vitro: Influence of oxygen and salicylic acid concentration

International Nuclear Information System (INIS)

Zitta, Karina; Meybohm, Patrick; Bein, Berthold; Huang, Ying; Heinrich, Christin; Scholz, Jens; Steinfath, Markus; Albrecht, Martin

2012-01-01

In solid tumors the hypoxic environment can promote tumor progression and resistance to therapy. Recently, acetylsalicylic acid a major component of analgesic drugs and its metabolite salicylic acid (SA) have been shown to reduce the risk of colon cancer, but the mechanisms of action remain still unclear. Here we elucidate the effects of physiologically relevant concentrations of SA on colon carcinoma cells (CaCo-2) grown under normoxic and hypoxic conditions. Western blotting, caspase-3/7 apoptosis assays, MTS cell-proliferation assays, LDH cytotoxicity assays and hydrogen peroxide measurements were performed to investigate the effects of 1 and 10 μM SA on CaCo-2 cells grown under normoxic conditions and cells exposed to hypoxia. Under normoxic conditions, SA did not influence cell proliferation or LDH release of CaCo-2 cells. However, caspase-3/7 activity was significantly increased. Under hypoxia, cell proliferation was reduced and LDH release and caspase-3/7 activities were increased. None of these parameters was altered by the addition of SA under hypoxic conditions. Hypoxia increased hydrogen peroxide concentrations 300-fold and SA significantly augmented the release of hydrogen peroxide under normoxic, but not under hypoxic conditions. Phosphorylation of the pro-survival kinases akt and erk1/2 was not changed by SA under hypoxic conditions, whereas under normoxia SA reduced phosphorylation of erk1/2 after 2 hours. We conclude that in colon carcinoma cells effects of SA on apoptosis and cellular signaling are dependent on the availability of oxygen. -- Highlights: ► Effects of salicylic acid on colon carcinoma cells grown under normoxic and hypoxic conditions ► Salicylic acid increases caspase-3/7 activity and hydrogen peroxide release under normoxia ► Salicylic acid decreases pro-survival erk-1/2 phosphorylation under normoxia ► Salicylic acid does not influence any of the investigated parameters under hypoxia

Simultaneous Determination of Salicylic Acid, Jasmonic Acid, Methyl Salicylate, and Methyl Jasmonate from Ulmus pumila Leaves by GC-MS

OpenAIRE

Huang, Zhi-hong; Wang, Zhi-li; Shi, Bao-lin; Wei, Dong; Chen, Jian-xin; Wang, Su-li; Gao, Bao-jia

2015-01-01

Salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate are important phytohormones and defensive signaling compounds, so it is of great importance to determine their levels rapidly and accurately. The study uses Ulmus pumila leaves infected by Tetraneura akinire Sasaki at different stages as materials; after extraction with 80% methanol and ethyl acetate and purification with primary secondary amine (PSA) and graphitized carbon blacks (GCB), the contents of signal compounds sa...

Boron removal from aqueous solutions by activated carbon impregnated with salicylic acid

International Nuclear Information System (INIS)

Celik, Z. Ceylan; Can, B.Z.; Kocakerim, M. Muhtar

2008-01-01

In this study, the removal of boric acid from aqueous solution by activated carbon impregnated with salicylic acid was studied in batch system. pH, adsorbent amount, initial boron concentration, temperature, shaking rate and salicylic acid film thickness were chosen as parameters. Boron removal efficiencies increased with increasing adsorbent amount, temperature and pH, decreasing initial boron concentration. As thickness of salicylic acid film on activated carbon becomes thin up to 0.088 nm, the efficiency increased, and then, the efficiency decreased with becoming thinner than 0.088 nm of salicylic acid film. Shaking rate was no effect on removal efficiency. In result, it was determined that the use of salicylic acid as an impregnant for activated carbon led to the increase of the amount of boron adsorbed. A lactone ring, being the most appropriate conformation, forms between boric acid and -COOH and -OH groups of salicylic acid

Boron removal from aqueous solutions by activated carbon impregnated with salicylic acid

Energy Technology Data Exchange (ETDEWEB)

Celik, Z. Ceylan [Department of Environmental Engineering, Atatuerk University, Faculty of Engineering, Erzurum (Turkey)], E-mail: zcelik@atauni.edu.tr; Can, B.Z. [Department of Environmental Engineering, Atatuerk University, Faculty of Engineering, Erzurum (Turkey); Kocakerim, M. Muhtar [Department of Chemical Engineering, Atatuerk University, Faculty of Engineering, 25240 Erzurum (Turkey)

2008-03-21

In this study, the removal of boric acid from aqueous solution by activated carbon impregnated with salicylic acid was studied in batch system. pH, adsorbent amount, initial boron concentration, temperature, shaking rate and salicylic acid film thickness were chosen as parameters. Boron removal efficiencies increased with increasing adsorbent amount, temperature and pH, decreasing initial boron concentration. As thickness of salicylic acid film on activated carbon becomes thin up to 0.088 nm, the efficiency increased, and then, the efficiency decreased with becoming thinner than 0.088 nm of salicylic acid film. Shaking rate was no effect on removal efficiency. In result, it was determined that the use of salicylic acid as an impregnant for activated carbon led to the increase of the amount of boron adsorbed. A lactone ring, being the most appropriate conformation, forms between boric acid and -COOH and -OH groups of salicylic acid.

Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease

NARCIS (Netherlands)

Eikelboom, John W.; Connolly, Stuart J.; Bosch, Jackie; Dagenais, Gilles R.; Hart, Robert G.; Shestakovska, Olga; Diaz, Rafael; Alings, Marco; Lonn, Eva M.; Anand, Sonia S.; Widimsky, Petr; Hori, Masatsugu; Avezum, Alvaro; Piegas, Leopoldo S.; Branch, Kelley R. H.; Probstfield, Jeffrey; Bhatt, Deepak L.; Zhu, Jun; Liang, Yan; Maggioni, Aldo P.; Lopez-Jaramillo, Patricio; O'Donnell, Martin; Kakkar, Ajay K.; Fox, Keith A. A.; Parkhomenko, Alexander N.; Ertl, Georg; Störk, Stefan; Keltai, Matyas; Ryden, Lars; Pogosova, Nana; Dans, Antonio L.; Lanas, Fernando; Commerford, Patrick J.; Torp-Pedersen, Christian; Guzik, Tomek J.; Verhamme, Peter B.; Vinereanu, Dragos; Kim, Jae-Hyung; Tonkin, Andrew M.; Lewis, Basil S.; Felix, Camilo; Yusoff, Khalid; Steg, P. Gabriel; Metsarinne, Kaj P.; Cook Bruns, Nancy; Misselwitz, Frank; Chen, Edmond; Leong, Darryl; Hashimoto, S.; Maas, M.

2017-01-01

We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg

Synthesis and antifungal activity of new salicylic acid derivatives

Directory of Open Access Journals (Sweden)

Wodnicka Alicja

2017-03-01

Full Text Available A simple one-step procedure for synthesis of 1-methoxy-1-oxoalkan-2-yl salicylates and 1-methoxy-1-oxoalkan-2-yl 2-[(1-methoxy-1-oxoalkan-2-yloxy]benzoates by reaction of salicylic acid with several methyl 2-bromoalkanoates was developed. The reactions were carried out in N,N-dimethylformamide (DMF in the presence of anhydrous potassium carbonate. Conditions for regioselective synthesis of target compounds were established. The developed procedure could be easily applied in the industrial production process. The new salicylic acid derivatives were obtained with satisfactory yields and were characterized by MS and 1H NMR spectra. The fungicidal activity of the prepared compounds was tested in vitro against seven species of plant pathogenic fungi. The best results were observed for 1-methoxy-1-oxoalkan-2-yl salicylates which showed moderate or good activity against Botrytis cinerea and Rhizoctonia solani.

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

Plant methyl salicylate induces defense responses in the rhizobacterium Bacillus subtilis.

Science.gov (United States)

Kobayashi, Kazuo

2015-04-01

Bacillus subtilis is a rhizobacterium that promotes plant growth and health. Cultivation of B. subtilis with an uprooted weed on solid medium produced pleat-like architectures on colonies near the plant. To test whether plants emit signals that affect B. subtilis colony morphology, we examined the effect of plant-related compounds on colony morphology. Bacillus subtilis formed mucoid colonies specifically in response to methyl salicylate, which is a plant-defense signal released in response to pathogen infection. Methyl salicylate induced mucoid colony formation by stimulating poly-γ-glutamic acid biosynthesis, which formed enclosing capsules that protected the cells from exposure to antimicrobial compounds. Poly-γ-glutamic acid synthesis depended on the DegS-DegU two-component regulatory system, which activated DegSU-dependent gene transcription in response to methyl salicylate. Bacillus subtilis did not induce plant methyl salicylate production, indicating that the most probable source of methyl salicylate in the rhizosphere is pathogen-infected plants. Methyl salicylate induced B. subtilis biosynthesis of the antibiotics bacilysin and fengycin, the latter of which exhibited inhibitory activity against the plant pathogenic fungus Fusarium oxysporum. We propose that B. subtilis may sense plants under pathogen attack via methyl salicylate, and express defense responses that protect both B. subtilis and host plants in the rhizosphere. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

Interaction of salicylate and noise results in mortality of rats.

Science.gov (United States)

Brennan, J F; Jastreboff, P J

1989-08-15

Survival as a function of salicylate dose and the intensity of environmental noise was investigated in 150 adult female pigmented rats. Rats were assigned to groups (n = 6/group) defined by combinations of salicylate levels from 0-(saline) to 300 mg/kg, injected subcutaneously, and noise levels from ambient noise to 98 dB SPL, presented daily for 10-h periods for up to 17 days. Mortality occurred in groups exposed to the higher combinations of salicylate and noise.

Effects of aspirin and enoxaparin in a rat model of liver fibrosis.

Science.gov (United States)

Li, Chen-Jie; Yang, Zhi-Hui; Shi, Xiao-Liu; Liu, De-Liang

2017-09-21

To examine the effects of aspirin and enoxaparin on liver function, coagulation index and histopathology in a rat model of liver fibrosis. METHODS Forty-five male Sprague-Dawley rats were randomly divided into the control group (n = 5) and model group (n = 40). Thioacetamide (TAA) was used to induce liver fibrosis in the model group. TAA-induced fibrotic rats received TAA continuously (n = 9), TAA + low-dose aspirin (n = 9), TAA + high-dose aspirin (n = 9) or TAA + enoxaparin (n = 9) for 4 wk. All rats were euthanized after 4 wk, and both hematoxylin-eosin and Masson staining were performed to observe pathological changes in liver tissue. Liver fibrosis was assessed according to the METAVIR score. Compared with untreated cirrhotic controls, a significant improvement in fibrosis grade was observed in the low-dose aspirin, high-dose aspirin and enoxaparin treated groups, especially in the high-dose aspirin treated group. Alanine aminotransferase and total bilirubin were higher, albumin was lower and both prothrombin time and international normalized ratio were prolonged in the four treatment groups compared to controls. No significant differences among the four groups were observed. Aspirin and enoxaparin can alleviate liver fibrosis in this rat model.

Effect of chronic aspirin ingestion on epithelial proliferation in rat fundus, antrum, and duodenum

International Nuclear Information System (INIS)

Eastwood, G.L.; Quimby, G.F.

1972-01-01

We studied the effect of chronic aspirin ingestion on gastroduodenal epithelial proliferation by feeding rats aspirin in the drinking water. A control group of rats received plain water. At the end of 4 wk, [3H]-thymidine was given intravenously to label proliferating cells, and the rats were killed 1 h later. Sections of fundus, antrum, and proximal duodenum were processed for light autoradiography. We found that chronic aspirin ingestion stimulated epithelial proliferation in fundic mucosa but had no effect in the antrum. In the duodenum, aspirin increased proliferation in the lowest four crypt-cell positions, which most likely indicates an increase in stem-cell production. None of the tissues contained evidence of inflammation or ulceration. The proliferative effects of aspirin may help explain the previously observed phenomenon of mucosal adaptation in the rat after repeated exposure to aspirin. Further, if human gastroduodenal epithelium responds in a similar manner to chronic aspirin exposure, the effects on proliferation may explain in part the distribution of aspirin-associated ulcers

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

Science.gov (United States)

Aresta, Antonella; Zambonin, Carlo

2016-03-20

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

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 ...

By inhibiting PFKFB3, aspirin overcomes sorafenib resistance in hepatocellular carcinoma.

Science.gov (United States)

Li, Sainan; Dai, Weiqi; Mo, Wenhui; Li, Jingjing; Feng, Jiao; Wu, Liwei; Liu, Tong; Yu, Qiang; Xu, Shizan; Wang, Wenwen; Lu, Xiya; Zhang, Qinghui; Chen, Kan; Xia, Yujing; Lu, Jie; Zhou, Yingqun; Fan, Xiaoming; Xu, Ling; Guo, Chuanyong

2017-12-15

Hepatocellular carcinoma (HCC) is one of the few cancers with a continuous increase in incidence and mortality. Drug resistance is a major problem in the treatment of HCC. In this study, two sorafenib-resistant HCC cell lines and a nude mouse subcutaneously tumor model were used to explore the possible mechanisms leading to sorafenib resistance, and to investigate whether aspirin could increase the sensitivity of hepatoma cells to sorafenib. The combination of aspirin and sorafenib resulted in a synergistic antitumor effect against liver tumors both in vitro and in vivo. High glycolysis and PFKFB3 overexpression occupied a dominant position in sorafenib resistance, and can be targeted and overcome by aspirin. Aspirin plus sorafenib induced apoptosis in tumors without inducing weight loss, hepatotoxicity or inflammation. Our results suggest that aspirin overcomes sorafenib resistance and their combination may be an effective treatment approach for HCC. © 2017 UICC.

Gastro-protective effect of methanol extract of Vernonia amygdalina (del. leaf on aspirin-induced gastric ulcer in Wistar rats

Directory of Open Access Journals (Sweden)

Modinat A. Adefisayo

Full Text Available This study investigated the protective effects of methanol extract of Vernonia amygdalina leaf (MEVA on aspirin induced gastric ulcer in rats. Thirty Wistar rats, 150–200 g were divided into six groups as follows: Group 1 (control rats received 2 mL/kg of propylene glycol for 28 consecutive days. Group 2 (Ulcer Control received 150 mg/kg/day of aspirin suspended in 3 mL of 1% carboxymethylcellulose in water orally for 3 consecutive days during which the rats were fasted for the induction of ulcer. Group 3 received cimetidine at 100 mg/kg/day orally for 28 consecutive days and thereafter treated as group 2. Groups 4, 5 and 6 received MEVA orally at 200, 300 and 400 mg/kg/day respectively for 28 consecutive days and thereafter were treated with aspirin as group 2. All the animals were sacrifice at the end of the study to determine the gastric pH, gastric acidity, gastric ulcer score, haematological indices, superoxide dismutase (SOD activity, reduced glutathione (GSH and Lipid peroxidation (LPO levels. The result showed that aspirin significantly (p < 0.05 increased gastric ulcer score and index, decreased gastric pH, gastric acidity, SOD activity, GSH level as well as increased LPO level. It induced significant necrosis of the stomach tissue. Administration of MEVA significantly (p < 0.05 increased gastric pH, but decreased gastric acid secretion and reversed alteration of haematological parameters. It also significantly (p < 0.05 increased SOD activity, GSH level and decreased LPO level. The results suggest that Vernonia amygdalina possesses gastro-protective properties against aspirin-induced gastric ulcer. Keywords: Vernonia amygdalina, Aspirin, Gastric ulcer, Antioxidant, Rat

COAST (Cisplatin ototoxicity attenuated by aspirin trial): A phase II double-blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing-loss.

Science.gov (United States)

Crabb, Simon J; Martin, Karen; Abab, Julia; Ratcliffe, Ian; Thornton, Roger; Lineton, Ben; Ellis, Mary; Moody, Ronald; Stanton, Louise; Galanopoulou, Angeliki; Maishman, Tom; Geldart, Thomas; Bayne, Mike; Davies, Joe; Lamb, Carolynn; Popat, Sanjay; Joffe, Johnathan K; Nutting, Chris; Chester, John; Hartley, Andrew; Thomas, Gareth; Ottensmeier, Christian; Huddart, Robert; King, Emma

2017-12-01

Cisplatin is one of the most ototoxic chemotherapy drugs, resulting in a permanent and irreversible hearing loss in up to 50% of patients. Cisplatin and gentamicin are thought to damage hearing through a common mechanism, involving reactive oxygen species in the inner ear. Aspirin has been shown to minimise gentamicin-induced ototoxicity. We, therefore, tested the hypothesis that aspirin could also reduce ototoxicity from cisplatin-based chemotherapy. A total of 94 patients receiving cisplatin-based chemotherapy for multiple cancer types were recruited into a phase II, double-blind, placebo-controlled trial and randomised in a ratio of 1:1 to receive aspirin 975 mg tid and omeprazole 20 mg od, or matched placebos from the day before, to 2 days after, their cisplatin dose(s), for each treatment cycle. Patients underwent pure tone audiometry before and at 7 and 90 days after their final cisplatin dose. The primary end-point was combined hearing loss (cHL), the summed hearing loss at 6 kHz and 8 kHz, in both ears. Although aspirin was well tolerated, it did not protect hearing in patients receiving cisplatin (p-value = 0.233, 20% one-sided level of significance). In the aspirin arm, patients demonstrated mean cHL of 49 dB (standard deviation [SD] 61.41) following cisplatin compared with placebo patients who demonstrated mean cHL of 36 dB (SD 50.85). Women had greater average hearing loss than men, and patients treated for head and neck malignancy experienced the greatest cHL. Aspirin did not protect from cisplatin-related ototoxicity. Cisplatin and gentamicin may therefore have distinct ototoxic mechanisms, or cisplatin-induced ototoxicity may be refractory to the aspirin regimen used here. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Syntheses and pyrolytic studies of salicylate derivatives of ...

African Journals Online (AJOL)

New salicylate derivatives of heteronucleic-μ-oxoisopropoxide [SnO2AlB(OPri)4] have been synthesized by the thermal condensation of μ-oxoisopropoxide and methyl/ethyl/phenyl/phenyl ethyl salicylates in different molar ratios (1:1-1:2) yielding the compounds of the type [SnO2AlB(OPri)4-n(RSAL)n] (where n is 1-2 and ...

Complexes of salicylic acid and its derivatives

Energy Technology Data Exchange (ETDEWEB)

Tel' zhenskaya, P N; Shvarts, E M [AN Latvijskoj SSR, Riga. Inst. Neorganicheskoj Khimii

1977-01-01

A generalization and systematization have been made of literature data on complexing of various elements, including beryllium, cadmium, boron, indium, rare-earth elements, actinides, and transition elements with salicylic acid and it derivatives (amino-, nitro- and halosalicylic acids). The effect of the position and nature of the substitute, in the case of salicylic acid derivatives, on the complexing process is discussed. Certain physicochemical properties of the complexes under consideration are described along with data indicative of their stability.

Safety of low-dose aspirin in endovascular treatment for intracranial atherosclerotic stenosis.

Directory of Open Access Journals (Sweden)

Ning Ma

Full Text Available OBJECTIVES: To evaluate the safety of low-dose aspirin plus clopidogrel versus high-dose aspirin plus clopidogrel in prevention of vascular risk within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment. METHODS: From January 2012 to December 2013, this prospective and observational study enrolled 370 patients with symptomatic intracranial atherosclerotic stenosis of ≥70% with poor collateral undergoing intracranial endovascular treatment. Antiplatelet therapy consists of aspirin, at a low-dose of 100 mg or high-dose of 300 mg daily; clopidogrel, at a dose of 75 mg daily for 5 days before endovascular treatment. The dual antiplatelet therapy continued for 90 days after intervention. The study endpoints include acute thrombosis, subacute thrombosis, stroke or death within 90 days after intervention. RESULTS: Two hundred and seventy three patients received low-dose aspirin plus clopidogrel and 97 patients received high-dose aspirin plus clopidogrel before intracranial endovascular treatment. Within 90 days after intervention, there were 4 patients (1.5% with acute thrombosis, 5 patients (1.8% with subacute thrombosis, 17 patients (6.2% with stroke, and 2 death (0.7% in low-dose aspirin group, compared with no patient (0% with acute thrombosis, 2 patient (2.1% with subacute thrombosis, 6 patients (6.2% with stroke, and 2 death (2.1% in high-dose aspirin group, and there were no significant difference in all study endpoints between two groups. CONCLUSION: Low-dose aspirin plus clopidogrel is comparative in safety with high-dose aspirin plus clopidogrel within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment.

Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism

DEFF Research Database (Denmark)

Weitz, Jeffrey I; Lensing, Anthonie W A; Prins, Martin H

2017-01-01

BACKGROUND: Although many patients with venous thromboembolism require extended treatment, it is uncertain whether it is better to use full- or lower-intensity anticoagulation therapy or aspirin. METHODS: In this randomized, double-blind, phase 3 study, we assigned 3396 patients with venous...... thromboembolism to receive either once-daily rivaroxaban (at doses of 20 mg or 10 mg) or 100 mg of aspirin. All the study patients had completed 6 to 12 months of anticoagulation therapy and were in equipoise regarding the need for continued anticoagulation. Study drugs were administered for up to 12 months...... in 17 of 1107 patients (1.5%) receiving 20 mg of rivaroxaban and in 13 of 1127 patients (1.2%) receiving 10 mg of rivaroxaban, as compared with 50 of 1131 patients (4.4%) receiving aspirin (hazard ratio for 20 mg of rivaroxaban vs. aspirin, 0.34; 95% confidence interval [CI], 0.20 to 0.59; hazard ratio...

Should This Patient Receive Aspirin?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Science.gov (United States)

Burns, Risa B; Graham, Kelly; Sawhney, Mandeep S; Reynolds, Eileen E

2017-12-05

Aspirin exerts antiplatelet effects through irreversible inhibition of cyclooxygenase-1, whereas its anticancer effects may be due to inhibition of cyclooxygenase-2 and other pathways. In 2009, the U.S. Preventive Services Task Force endorsed aspirin for primary prevention of cardiovascular disease. However, aspirin's role in cancer prevention is still emerging, and no groups currently recommend its use for this purpose. To help physicians balance the benefits and harms of aspirin in primary disease prevention, the Task Force issued a guideline titled, "Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer" in 2016. In the evidence review conducted for the guideline, cardiovascular disease mortality and colorectal cancer mortality were significantly reduced among persons taking aspirin. However, there was no difference in nonfatal stroke, cardiovascular disease mortality, or all-cause mortality, nor in total cancer mortality, among those taking aspirin. Aspirin users were found to be at increased risk for major gastrointestinal bleeding. In this Beyond the Guidelines, the guideline is reviewed and 2 experts discuss how they would apply it to a 57-year-old man considering starting aspirin for primary prevention. Our experts review the data on which the guideline is based, discuss how they would balance the benefits and harms of aspirin therapy, and explain how they would incorporate shared decision making into clinical practice.

Aspirin for the prevention of recurrent venous thromboembolism: the INSPIRE collaboration.

Science.gov (United States)

Simes, John; Becattini, Cecilia; Agnelli, Giancarlo; Eikelboom, John W; Kirby, Adrienne C; Mister, Rebecca; Prandoni, Paolo; Brighton, Timothy A

2014-09-23

In patients with a first unprovoked venous thromboembolism (VTE) the risk of recurrent VTE remains high after anticoagulant treatment is discontinued. The Aspirin for the Prevention of Recurrent Venous Thromboembolism (the Warfarin and Aspirin [WARFASA]) and the Aspirin to Prevent Recurrent Venous Thromboembolism (ASPIRE) trials showed that aspirin reduces this risk, but they were not individually powered to detect treatment effects for particular outcomes or subgroups. An individual patient data analysis of these trials was planned, before their results were known, to assess the effect of aspirin versus placebo on recurrent VTE, major vascular events (recurrent VTE, myocardial infarction, stroke, and cardiovascular disease death) and bleeding, overall and within predefined subgroups. The primary analysis, for VTE, was by intention to treat using time-to-event data. Of 1224 patients, 193 had recurrent VTE over 30.4 months' median follow-up. Aspirin reduced recurrent VTE (7.5%/yr versus 5.1%/yr; hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.51-0.90; P=0.008), including both deep-vein thrombosis (HR, 0.66; 95% CI, 0.47-0.92; P=0.01) and pulmonary embolism (HR, 0.66; 95% CI, 0.41-1.06; P=0.08). Aspirin reduced major vascular events (8.7%/yr versus 5.7%/yr; HR, 0.66; 95% CI, 0.50-0.86; P=0.002). The major bleeding rate was low (0.4%/yr for placebo and 0.5%/yr for aspirin). After adjustment for treatment adherence, recurrent VTE was reduced by 42% (HR, 0.58; 95% CI, 0.40-0.85; P=0.005). Prespecified subgroup analyses indicate similar relative, but larger absolute, risk reductions in men and older patients. Aspirin after anticoagulant treatment reduces the overall risk of recurrence by more than a third in a broad cross-section of patients with a first unprovoked VTE, without significantly increasing the risk of bleeding. www.anzctr.org.au. Unique identifier: ACTRN12611000684921. © 2014 American Heart Association, Inc.

Role of Acetyl Salicylic Acid in Controlling the DOCA-Salt Induced Hypertension in Rats by Stimulating the Synthesis of r-Cortexin in the Kidney.

Science.gov (United States)

Maji, Uttam Kumar; Jana, Pradipta; Chatterjee, Mitali; Karmakar, Sanmay; Saha, Arup; Ghosh, Tamal Kanti

2018-03-01

Hypertension is a metabolic disease which is caused by vasoconstriction and that results into elevated blood pressure. A chronic hypertensive condition affects and even damages to various systems in the body. Presence of renal cortexin (r-cortexin), an antihypertensive protein, which is released from the kidney cortex controls the blood pressure. The effect of r-cortexin was mediated through nitric oxide (NO), a universal vasodilating agent. In our study, acetyl salicylic acid (aspirin), a well-known activator of the endothelial nitric oxide synthase (eNOS) induced r-cortexin synthesis. The hypertensive rat model was prepared by injecting deoxy corticosterone acetate (DOCA). Synthesis of r-cortexin was measured by the anti-r-cortexin antibody which was raised in adult white Wister albino rat model. NO level was determined by using methemoglobin method and later confirmed by chemiluminescence method. Change in blood pressure was determined indirectly by using NIBP monitoring system. Aspirin increased the r-cortexin expression from 64.36 ± 12.6 nM to 216.7 ± 21.31 nM in DOCA induced hypertensive rats. The mechanism was proved with the findings of increased level of NO from 0.4 to 1.9 µM. The DOCA induced blood pressure was also decreased from 139.39 ± 7.36 mm of Hg to 116.57 ± 6.89 mm of Hg in case of systolic blood pressure and in case of diastolic pressure from 110.41 ± 7 mm of Hg to 86.4 ± 2.76 mm of Hg that are quite approximate. So, from this study it has been found that aspirin induces the r-cortexin synthesis in kidney cortex through the activation of eNOS in DOCA induced hypertensive rats.

Moessbauer study of iron(III) salicylates

Energy Technology Data Exchange (ETDEWEB)

Mahesh, K; Sharma, N D; Gupta, D C [Kurukshetra Univ. (India). Dept. of Physics; Puri, D M [Kurukshetra Univ. (India). Dept. of Chemistry

1979-07-01

Moessbauer infrared and magnetic studies of different basic salicylates of iron(III) are reported. Comparison of observed isomer shift and quadrupole splitting with the earlier work allows to assign the trinuclear chain structure to the complexes wherein the central iron atom in the chain is considered to be octahedrally coordinated in case of salicylate and 4-aminosalicylate derivatives, and pentacoordinated for the thiosalicylate with the terminal iron atom in tetrahedral symmetry. The Moessbauer parameters and ..mu..sub(eff)-value indicate the high spin state of the central iron atom and low spin state for the terminal ones.

Dipyridamole plus aspirin versus aspirin alone in the secondary prevention after TIA or stroke: a meta-analysis by risk

OpenAIRE

Halkes, P.H.A.; Gray, Laura J.; Bath, Philip M.W.; Diener, Hans-Christoph; Guiraud-Chaumeil, B.

2008-01-01

Objectives: Our aim was to study the effect of combination therapy with aspirin and dipyridamole (A+D) over aspirin alone (ASA) in secondary prevention after transient \\ud ischemic attack or minor stroke of presumed arterial origin and to perform subgroup analyses to identify patients that might benefit most from secondary prevention with A+D.\\ud Data sources: The previously published meta-analysis of individual patient data was updated with data from ESPRIT (N=2,739); trials without data on ...

Aspirin counteracts cancer stem cell features, desmoplasia and gemcitabine resistance in pancreatic cancer

Science.gov (United States)

Zhang, Yiyao; Liu, Li; Fan, Pei; Bauer, Nathalie; Gladkich, Jury; Ryschich, Eduard; Bazhin, Alexandr V.; Giese, Nathalia A.; Strobel, Oliver; Hackert, Thilo; Hinz, Ulf; Gross, Wolfgang; Fortunato, Franco; Herr, Ingrid

2015-01-01

Pancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor prognosis. An inflammatory microenvironment triggers the pronounced desmoplasia, the selection of cancer stem-like cells (CSCs) and therapy resistance. The anti-inflammatory drug aspirin is suggested to lower the risk for PDA and to improve the treatment, although available results are conflicting and the effect of aspirin to CSC characteristics and desmoplasia in PDA has not yet been investigated. We characterized the influence of aspirin on CSC features, stromal reactions and gemcitabine resistance. Four established and 3 primary PDA cell lines, non-malignant cells, 3 patient tumor-derived CSC-enriched spheroidal cultures and tissues from patients who did or did not receive aspirin before surgery were analyzed using MTT assays, flow cytometry, colony and spheroid formation assays, Western blot analysis, antibody protein arrays, electrophoretic mobility shift assays (EMSAs), immunohistochemistry and in vivo xenotransplantation. Aspirin significantly induced apoptosis and reduced the viability, self-renewal potential, and expression of proteins involved in inflammation and stem cell signaling. Aspirin also reduced the growth and invasion of tumors in vivo, and it significantly prolonged the survival of mice with orthotopic pancreatic xenografts in combination with gemcitabine. This was associated with a decreased expression of markers for progression, inflammation and desmoplasia. These findings were confirmed in tissue samples obtained from patients who had or had not taken aspirin before surgery. Importantly, aspirin sensitized cells that were resistant to gemcitabine and thereby enhanced the therapeutic efficacy. Aspirin showed no obvious toxic effects on normal cells, chick embryos or mice. These results highlight aspirin as an effective, inexpensive and well-tolerated co-treatment to target inflammation, desmoplasia and CSC features PDA. PMID:25846752

Aspirin administered to women at 100 mg every other day produces less platelet inhibition than aspirin administered at 81 mg per day: implications for interpreting the women's health study.

Science.gov (United States)

Swaim, Lisa; Hillman, Robert S

2009-07-01

We aimed to determine the relative level of platelet inhibition achieved with low-dose aspirin (81 mg daily) compared with a very low-dose (100 mg every other day). The Womens Health Study (WHS) found that a dose of 100 mg every other day of aspirin provided protection against stroke as primary prophylaxis, but not myocardial infarction. In the United States, the most commonly prescribed dose of aspirin for primary prophylaxis is 81 mg per day. As a result, it is important to know whether these doses are equivalent before extrapolating the results of the WHS to women in the U.S. To achieve this goal, we have studied the effects of these two dosing regimens on platelet function in healthy women meeting the WHS inclusion criteria using a randomized design. We enrolled 49 healthy female volunteers and used a sequential, crossover design to compare the two regimens. The participants received a 17-day course of each aspirin-dosing regimen separated by a 7-day washout period. The degree of platelet inhibition was measured on days 14-17 of each dosing regimen using a point-of-care platelet function assay utilizing arachidonic acid to activate platelets (VerifyNow-Aspirin). Participants platelet response, expressed as Aspirin Response Unit (ARU) attained a significantly greater level of platelet inhibition on days 14-17 while taking aspirin 81 mg daily compared to aspirin 100 mg every other day (31.3% vs. 12.7%, P or=550 ARU, a value correlated with clinical outcomes in several studies, with the 100 mg every other day regimen (72.0% vs. 6.4% with 81 mg daily, P day regimen also resulted in more day-to-day variability in platelet function (P = 0.0002). We found significantly less inhibition of platelet function with the dose used in the WHS than the usual U.S. dose. We observed that the degree of platelet inhibition was significantly less with aspirin 100 mg every other day compared with aspirin 81 mg daily, suggesting that results of the Women's Health Study may have

Employment of the porous particles for preparation of the capsules containing aspirin and drug release property

International Nuclear Information System (INIS)

Hosoi, Fumio; Makuuchi, Keizo; Saito, Kenji; Koishi, Masumi.

1985-01-01

Polymer-coated porous particles containing aspirin as a drug were prepared and the rate of release of aspirin was studied. The impregnation of aspirin was carried out by post-graft polymerization, where methyl methacrylate or methacrylic acid was treated with porous particles, pre-irradiated with γ-ray from 60 Co, in the presence of aspirin. Release of aspirin from modified particles was tested with 50 % methanol solution and/or pH 5.2 buffer solution of acetic acid. The amount of aspirin released from capsules increased with time and reached a constant values after 140 h. The amount of aspirin absorbed in porous particles was increased with graft polymerization. In addition, absorption of aspirin in porous particles was significantly enhanced by treating the particle surface with TiO 2 before irradiation. The amount of aspirin released was linearly to the square root of time. It was concluded that the diffusion of aspirin through the polymer matrix was the rate limiting step. (author)

Effect of different aspirin doses on arterial thrombosis after canine carotid endarterectomy: a scanning electron microscope and indium-111-labeled platelet study

International Nuclear Information System (INIS)

Ercius, M.S.; Chandler, W.F.; Ford, J.W.; Swanson, D.P.; Burke, J.C.

1984-01-01

Although it is widely accepted that aspirin inhibits platelet aggregation in arterial thrombosis, the appropriate dosage of aspirin remains quite controversial. The purpose of this study was to determine the effect of different doses of aspirin (0.5 mg/kg vs. 10 mg/kg) on mural thrombus formation after carotid endarterectomy. Eighteen hours after oral aspirin administration, 20 endarterectomies were performed on mongrel dogs with the use of the operating microscope. Blood flow was then restored for 3 hours and the vessels were prepared for investigation with the scanning electron microscope. Ten endarterectomies were also performed on unmedicated dogs as controls. Five minutes before vessel unclamping, autologous indium-111-labeled platelets were administered intravenously, and the endarterectomized portions of the vessels were studied with a gamma counter system after harvesting. Group 1, the control group, revealed extensive mural thrombus consisting of platelet aggregates, fibrin, red blood cells, and white blood cells. Six of the 10 vessels in Group 2, premedicated with 0.5 mg of aspirin per kg, demonstrated varying amounts of mural thrombus. Group 3 (10 vessels), premedicated with 10 mg of aspirin per kg, revealed a platelet monolayer completely covering the exposed vessel wall media, with scattered white blood cells and infrequent fine fibrin strands overlying the platelet surface. The mean (+/- SD) radioactivity per group expressed as counts/minute/mm2 was: Group 1--2055.3 +/- 1905.5, log . 7.253 +/- 0.926; Group 2--1235.6 +/- 1234.3, log . 6.785 +/- 0.817; Group 3--526 +/- 433.06, log . 5.989 +/- 0.774

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

OpenAIRE

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

2016-01-01

This work is supported by Cancer Research UK Grant C434/A13067 (M.H.T & R.T.H) and Wellcome Trust Grant 098391/Z/12/7 (R.T.H.). Aspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. Important to this function is its ability to irreversibly acetylate cyclooxygenases at active site serines. Aspirin has the potential to acetylate other amino-acid side-chains, leading to the possibility that aspirin-mediated lysine acetylation could explain some of its as-yet...

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

Science.gov (United States)

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

2016-01-01

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

Extraction of scandium salicylate by tetraethyldiamidoheptyl phosphate

Energy Technology Data Exchange (ETDEWEB)

Kamenev, V F; Fadeeva, V I; Zyk, N V [Moskovskij Gosudarstvennyj Univ. (USSR). Kafedra Analiticheskoj Khimii

1976-11-01

Scandium salicylate is extracted with chloroform in a narrow pH range 3-4 and at the maximum concentration of salicylic acid (H/sub 2/A) in an organic phase, the distribution coefficient reaches 0.1. In the presence of tetraethyldiamideheptylphosphate (DAHP) the zone of maximum extraction grows and the distribution coefficient increases. The ratio of the components in the complex extracted is Sc:H/sub 2/A:DAHPh=1:3:2. The extraction constant is Ksub(ex)=(2.00+-0.02).

Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: nationwide propensity score matched study

DEFF Research Database (Denmark)

Charlot, Mette; Grove, Erik; Hansen, Peter Riis

2011-01-01

OBJECTIVE: To examine the effect of proton pump inhibitors on adverse cardiovascular events in aspirin treated patients with first time myocardial infarction. DESIGN: Retrospective nationwide propensity score matched study based on administrative data. Setting All hospitals in Denmark. PARTICIPANTS...... analysis showed no increase in risk related to use of H(2) receptor blockers (1.04, 0.79 to 1.38; P=0.78). Conclusion In aspirin treated patients with first time myocardial infarction, treatment with proton pump inhibitors was associated with an increased risk of adverse cardiovascular events....

Aspirin and its related non-steroidal anti-inflammatory drugs

African Journals Online (AJOL)

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

Functional analysis of a tomato salicylic acid methyl transferase and its role in synthesis of the flavor volatile methyl salicylate.

Science.gov (United States)

Tieman, Denise; Zeigler, Michelle; Schmelz, Eric; Taylor, Mark G; Rushing, Sarah; Jones, Jeffrey B; Klee, Harry J

2010-04-01

Methyl salicylate (MeSA) is a volatile plant secondary metabolite that is an important contributor to taste and scent of many fruits and flowers. It is synthesized from salicylic acid (SA), a phytohormone that contributes to plant pathogen defense. MeSA is synthesized by members of a family of O-methyltransferases. In order to elaborate the mechanism of MeSA synthesis in tomato, we screened a set of O-methyltransferases for activity against multiple substrates. An enzyme that specifically catalyzes methylation of SA, SlSAMT, as well as enzymes that act upon jasmonic acid and indole-3-acetic acid were identified. Analyses of transgenic over- and under-producing lines validated the function of SlSAMT in vivo. The SlSAMT gene was mapped to a position near the bottom of chromosome 9. Analysis of MeSA emissions from an introgression population derived from a cross with Solanum pennellii revealed a quantitative trait locus (QTL) linked to higher fruit methyl salicylate emissions. The higher MeSA emissions associate with significantly higher SpSAMT expression, consistent with SAMT gene expression being rate limiting for ripening-associated MeSA emissions. Transgenic plants that constitutively over-produce MeSA exhibited only slightly delayed symptom development following infection with the disease-causing bacterial pathogen, Xanthomonas campestris pv. vesicatoria (Xcv). Unexpectedly, pathogen-challenged leaves accumulated significantly higher levels of SA as well as glycosylated forms of SA and MeSA, indicating a disruption in control of the SA-related metabolite pool. Taken together, the results indicate that SlSAMT is critical for methyl salicylate synthesis and methyl salicylate, in turn, likely has an important role in controlling SA synthesis.

Impact of aspirin on fetal growth in diabetic pregnancies according to White classification.

Science.gov (United States)

Adkins, Katlynn; Allshouse, Amanda A; Metz, Torri D; Heyborne, Kent D

2017-10-01

Current US Preventive Services Task Force and other guidelines recommend low-dose aspirin for all pregnant women with pregestational diabetes mellitus to prevent preeclampsia and small-for-gestational-age birth. The Maternal-Fetal Medicine Units High-Risk Aspirin trial did not show a reduction in either preeclampsia or small-for-gestational-age birth in diabetic women. Our objective was to reassess the impact of aspirin on fetal growth in diabetic pregnancies overall and according to White classification. We hypothesized that aspirin improves fetal growth in pregnancies with vascular complications of diabetes at highest risk for poor fetal growth. We conducted secondary analysis of the cohort of diabetic women enrolled in the Maternal-Fetal Medicine Units High-Risk Aspirin trial. The impact of aspirin prophylaxis on birthweight was assessed in the overall cohort and in 2 groups categorized according to White classification as nonvascular (White class B, C, D) or vascular (White class R, F, RF). Birthweight was converted to Z-score normalized for gestational age at delivery and neonatal sex. Difference in birthweight Z-score between aspirin and placebo was tested with a 2-sample t test. The effect of vascular group, aspirin vs placebo randomization, and the interaction of the 2 on normalized birthweight percentile was estimated with linear regression with a multivariable model including covariates body mass index, tobacco use, race, and parity. The percentage of small and large-for-gestational-age newborns born to aspirin- vs placebo-treated women was compared between groups using Pearson exact χ 2 analysis, and an adjusted model was estimated by logistic regression. All 444 women with pregestational diabetes and complete outcome data were included (53 vascular, 391 nonvascular). Aspirin was significantly associated with a higher birthweight Z-score (0.283; 95% confidence interval, 0.023-0.544) in the overall cohort (P = .03). In the adjusted model, the

Surface enhanced Raman spectroscopic studies on aspirin : An experimental and theoretical approach

International Nuclear Information System (INIS)

Premkumar, R.; Premkumar, S.; Parameswari, A.; Mathavan, T.; Benial, A. Milton Franklin; Rekha, T. N.

2016-01-01

Surface enhanced Raman scattering (SERS) studies on aspirin molecule adsorbed on silver nanoparticles (AgNPs) were investigated by experimental and density functional theory approach. The AgNPs were synthesized by the solution-combustion method and characterized by the X-ray diffraction and high resolution-transmission electron microscopy techniques. The averaged particle size of synthesized AgNPs was calculated as ∼55 nm. The normal Raman spectrum (nRs) and SERS spectrum of the aspirin were recorded. The molecular structure of the aspirin and aspirin adsorbed on silver cluster were optimized by the DFT/ B3PW91 method with LanL2DZ basis set. The vibrational frequencies were calculated and assigned on the basis of potential energy distribution calculation. The calculated nRs and SERS frequencies were correlated well with the observed frequencies. The flat-on orientation was predicted from the nRs and SERS spectra, when the aspirin adsorbed on the AgNPs. Hence, the present studies lead to the understanding of adsorption process of aspirin on the AgNPs, which paves the way for biomedical applications.

Surface enhanced Raman spectroscopic studies on aspirin : An experimental and theoretical approach

Energy Technology Data Exchange (ETDEWEB)

Premkumar, R.; Premkumar, S.; Parameswari, A.; Mathavan, T.; Benial, A. Milton Franklin, E-mail: miltonfranklin@yahoo.com [Department of Physics, N.M.S.S.V.N College, Madurai-625019, Tamilnadu, India. (India); Rekha, T. N. [PG and Research Department of Physics, Lady Doak College, Madurai-625 002, Tamilnadu, India. (India)

2016-05-06

Surface enhanced Raman scattering (SERS) studies on aspirin molecule adsorbed on silver nanoparticles (AgNPs) were investigated by experimental and density functional theory approach. The AgNPs were synthesized by the solution-combustion method and characterized by the X-ray diffraction and high resolution-transmission electron microscopy techniques. The averaged particle size of synthesized AgNPs was calculated as ∼55 nm. The normal Raman spectrum (nRs) and SERS spectrum of the aspirin were recorded. The molecular structure of the aspirin and aspirin adsorbed on silver cluster were optimized by the DFT/ B3PW91 method with LanL2DZ basis set. The vibrational frequencies were calculated and assigned on the basis of potential energy distribution calculation. The calculated nRs and SERS frequencies were correlated well with the observed frequencies. The flat-on orientation was predicted from the nRs and SERS spectra, when the aspirin adsorbed on the AgNPs. Hence, the present studies lead to the understanding of adsorption process of aspirin on the AgNPs, which paves the way for biomedical applications.

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 each intervention has the potential for harm. OBJECTIVE: To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury. DESIGN, SETTING, AND PARTICIPANTS: A 2 × 2 factorial randomized, blinded, clinical trial of 6905...... patients undergoing noncardiac surgery from 88 centers in 22 countries with consecutive patients enrolled between January 2011 and December 2013. INTERVENTIONS: Patients were assigned to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days...

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

International Nuclear Information System (INIS)

Ashida, Noboru; Kishihata, Masako; Tien, Dat Nguyen; Kamei, Kaeko; Kimura, Takeshi; Yokode, Masayuki

2014-01-01

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

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

Salicylic acid induces apoptosis in colon carcinoma cells grown in-vitro: Influence of oxygen and salicylic acid concentration

Energy Technology Data Exchange (ETDEWEB)

Zitta, Karina; Meybohm, Patrick; Bein, Berthold; Huang, Ying; Heinrich, Christin; Scholz, Jens; Steinfath, Markus; Albrecht, Martin, E-mail: Albrecht@anaesthesie.uni-kiel.de

2012-04-15

In solid tumors the hypoxic environment can promote tumor progression and resistance to therapy. Recently, acetylsalicylic acid a major component of analgesic drugs and its metabolite salicylic acid (SA) have been shown to reduce the risk of colon cancer, but the mechanisms of action remain still unclear. Here we elucidate the effects of physiologically relevant concentrations of SA on colon carcinoma cells (CaCo-2) grown under normoxic and hypoxic conditions. Western blotting, caspase-3/7 apoptosis assays, MTS cell-proliferation assays, LDH cytotoxicity assays and hydrogen peroxide measurements were performed to investigate the effects of 1 and 10 {mu}M SA on CaCo-2 cells grown under normoxic conditions and cells exposed to hypoxia. Under normoxic conditions, SA did not influence cell proliferation or LDH release of CaCo-2 cells. However, caspase-3/7 activity was significantly increased. Under hypoxia, cell proliferation was reduced and LDH release and caspase-3/7 activities were increased. None of these parameters was altered by the addition of SA under hypoxic conditions. Hypoxia increased hydrogen peroxide concentrations 300-fold and SA significantly augmented the release of hydrogen peroxide under normoxic, but not under hypoxic conditions. Phosphorylation of the pro-survival kinases akt and erk1/2 was not changed by SA under hypoxic conditions, whereas under normoxia SA reduced phosphorylation of erk1/2 after 2 hours. We conclude that in colon carcinoma cells effects of SA on apoptosis and cellular signaling are dependent on the availability of oxygen. -- Highlights: Black-Right-Pointing-Pointer Effects of salicylic acid on colon carcinoma cells grown under normoxic and hypoxic conditions Black-Right-Pointing-Pointer Salicylic acid increases caspase-3/7 activity and hydrogen peroxide release under normoxia Black-Right-Pointing-Pointer Salicylic acid decreases pro-survival erk-1/2 phosphorylation under normoxia Black-Right-Pointing-Pointer Salicylic acid does

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…

Kinetic study on the photocatalytic degradation of salicylic acid using ZnO catalyst

International Nuclear Information System (INIS)

Nageswara Rao, A.; Sivasankar, B.; Sadasivam, V.

2009-01-01

The photocatalytic degradation of salicylic acid was studied by a batch process using ZnO as the catalyst on irradiation with UV light. The effect of process parameters such as pH, catalyst loading and initial concentration of salicylic acid on the extent of degradation was investigated. The degradation of salicylic acid was found to be effective in the neutral pH range. The optimum catalyst loading was observed at 2.0 g/L. The process followed first order kinetics and the apparent rate constant decreased with increase in the initial concentration of salicylic acid. The mechanism for the degradation of salicylic acid could be explained on the basis of Langmuir-Hinshelwood mechanism. The complete mineralization of salicylic acid was observed in the presence of ZnO photocatalyst. The ZnO was found to be quite stable and undergoes photocorrosion only to a negligible extent.

Protective role of wheat germ oil against certain functional and structural disorders produced by repeated aspirin administration and/or gamma irradiation during pregnancy

International Nuclear Information System (INIS)

Hafez, M.N.; Ramadan, F.L.

2006-01-01

Aspirin is one of the most commonly used non-steroidal anti-inflammatory drugs. The biggest problem remains its harshness on the stomach with effects ranging from nausea, heartburn to bleeding ulcer. During pregnancy, high incidence of developmental anomalies occurs in pregnant female rats given aspirin on specific days during organogenesis. Moreover, radiation exposure is considered to be a major pathogenic factor. Hence, the objective of this study is to counter these malformations in pregnant rats and their fetuses by using wheat germ oil, which is a natural vegetable oil and it is an excellent source of vitamin E, octacosanol and linolenic, which may be beneficial in neutralizing the oxidative free radicals. Aspirin when administered to pregnant rats as multiple dosing from gestational day (GD) 6 to GD 17 (250 mg/Kg/day) or whole body gamma irradiation of rats (0.5 Gy up to 2 Gy) on GDs 9, 10, 11 and 12, the maternal rat's stomach showed sloughing of the superficial parts of mucosa as well as scattered deep erosions. There were areas of necrosis and mononuclear cellular infiltration. In addition, thickened submucosal blood vessels with excess collagen fibres deposition and decreased mucus secretion were also noticed. Combined treatment revealed increased extent of mucosal damage, where erosive and atrophic changes became more obvious. In parallel, there was a significant increase in serum amylase level, while calcium level was significantly decreased. Fetal vertebrae bone and cartilage are also relatively sensitive to aspirin and / or gamma irradiation. There are reduction in the numbers of mitoses and disorderly maturation followed by the asymptomatic degeneration and necrosis of less mature elements. Bleeding was seen in the periosteum of vertebrae. Also, the trabecular of ossification were very thin and less than normal. These changes were also accompanied with decreased mucus secretion

An Hourly Dose-Escalation Desensitization Protocol for Aspirin-Exacerbated Respiratory Disease.

Science.gov (United States)

Chen, Justin R; Buchmiller, Brett L; Khan, David A

2015-01-01

Aspirin desensitization followed by maintenance therapy effectively improves symptom control in patients with aspirin exacerbated respiratory disease (AERD). The majority of current desensitization protocols use 3-hour dosing intervals and often require 2 to 3 days to complete. We evaluated hourly dose escalations in a subset of patients with chronic rhinosinusitis, nasal polyps, and asthma who historically reacted to aspirin within 1 hour or were avoiding aspirin with the goal of developing a safe and efficient desensitization protocol. Fifty-seven aspirin desensitizations were performed under the hourly protocol. All patients had refractory nasal polyposis as an indication for aspirin desensitization. The clinical characteristics of each subject were analyzed in relation to aspects of his or her reactions during the procedure. Ninety-eight percent of study patients were successfully treated under the hourly protocol, including those with a history of severe reactions and intubation. None required further medication than is available in an outpatient allergy clinic. A total of 96% of reactors recorded a bronchial or naso-ocular reaction within 1 hour of the preceding dose. Of the total patients on this protocol, 40% were able to complete the procedure in a single day, and 60% within 2 days. Patients with AERD who have a history of symptoms less than 1 hour after aspirin exposure can be safely desensitized with a 1-hour dose-escalation protocol that can often be completed in a single day. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Aspirin for Prophylaxis Against Venous Thromboembolism After Orthopaedic Oncologic Surgery.

Science.gov (United States)

Mendez, Gregory M; Patel, Yash M; Ricketti, Daniel A; Gaughan, John P; Lackman, Richard D; Kim, Tae Won B

2017-12-06

Patients who undergo orthopaedic oncologic surgical procedures are at increased risk of developing a venous thromboembolism (VTE). Guidelines from surgical societies are shifting to include aspirin as a postoperative VTE prophylactic agent. The purpose of this study was to review our experience using aspirin as postoperative VTE prophylaxis for orthopaedic oncologic surgical procedures. This study was a retrospective review of patients diagnosed with a primary malignant soft-tissue or bone tumor or metastatic carcinoma. Demographic information, histopathologic diagnosis, VTE history, surgical procedure, and VTE prophylaxis were analyzed. VTE rates in the overall and prophylactic-specific cohorts were recorded and compared. A total of 142 distinct surgical procedures in 130 patients were included. VTE prophylaxis with aspirin was used after 103 procedures, and non-aspirin prophylaxis was used after 39. In 33 cases, imaging was used to investigate for VTE because of clinical signs and symptoms. VTE developed after 7 (4.9%) of the 142 procedures. There were 6 deep venous thromboses (DVTs) and 1 pulmonary embolism, and 2 of the VTEs presented in patients with a VTE history. VTE developed in 2.9% (3) of the 103 aspirin cases and 10.3% (4) of the 39 non-aspirin cases. No patient in the aspirin group who had been diagnosed with metastatic carcinoma, malignant soft-tissue sarcoma, lymphoma, or multiple myeloma developed a VTE. Risk factors for VTE development included diabetes mellitus (odds ratio [OR] = 10.40, 95% confidence interval [CI] = 1.61 to 67.30), a history of VTE (OR = 7.26, 95% CI = 1.19 to 44.25), postoperative transfusion (OR = 34.50, 95% CI = 3.94 to 302.01), and estimated blood losses of 250 mL (OR = 1.50, 95% CI = 1.11 to 2.03), 500 mL (OR = 2.26, 95% CI = 1.23 to 4.13), and 1,000 mL (OR = 5.10, 95% CI = 1.52 to 17.04). Aspirin may be a suitable and effective option for VTE chemoprophylaxis in patients treated with orthopaedic oncologic surgery, especially

Aspirin use and early age-related macular degeneration: a meta-analysis.

Science.gov (United States)

Kahawita, Shyalle K; Casson, Robert J

2014-02-01

The aim of this review was to evaluate the evidence for an association between Aspirin use and early age-related macular degeneration (ARMD). A literature search was performed in 5 databases with no restrictions on language or date of publication. Four studies involving 10292 individuals examining the association between aspirin and ARMD met the inclusion criteria. Meta-analysis was carried out by Cochrane Collaboration Review Manager 5.2 software (Cochrane Collaboration, Copenhagen, Denmark). The pooled odd ratios showed that Aspirin use was associated with early ARMD (pooled odds ratio 1.43, 95% CI 1.09-1.88). There is a small but statistically significant association between Aspirin use and early ARMD, which may warrant further investigation. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Use of Aspirin postdiagnosis improves survival for colon cancer patients

NARCIS (Netherlands)

E. Bastiaannet (Esther); K. Sampieri (K.); O.M. Dekkers (Olaf); A.J. de Craen (Anton); M.P.P. van Herk-Sukel (Myrthe); V.E.P.P. Lemmens (Valery); C.B.M. van den Broek (Colette); J.W.W. Coebergh (Jan Willem); R.M.C. Herings (Ron); C.J.H. van de Velde (Cornelis); R. Fodde (Riccardo); G.-J. Liefers (Gerrit-Jan)

2012-01-01

textabstractBackground: The preventive role of non-steroid anti-inflammatory drugs (NSAIDs) and aspirin, in particular, on colorectal cancer is well established. More recently, it has been suggested that aspirin may also have a therapeutic role. Aim of the present observational population-based

High-performance liquid chromatographic determination of certain salicylates and their major metabolites in plasma following topical administration of a liniment to healthy subjects.

Science.gov (United States)

Dadgar, D; Climax, J; Lambe, R; Darragh, A

1985-08-09

The liniment used is a topical analgesic and anti-inflammatory preparation containing two active constituents, 3-phenylpropylsalicylate and ethyl-5-methoxysalicylate, in solution in isobutyl decanoate. It is known that 3-phenylpropylsalicylate is metabolised to salicylic acid and salicyluric acid and ethyl-5-methoxysalicylate is metabolised to 5-methoxysalicylic acid and gentisic acid. In the present study the separation of the salicylates and their metabolites was carried out on a Waters mu Bondapak C18 column using two different mobile phases, methanol-water (80:20) for the parent drugs and methanol-5% aqueous acetic acid (27:73) for their metabolites. The salicylates and their metabolites were detected by absorption at 310 nm. The limits of detection for parent drugs and metabolites were respectively 0.2 and 0.1 microgram/ml in plasma, using a 1-ml plasma sample and a 20-microliter injection from a reconstituted volume of 250 microliter. Mean percentage coefficients of variation for intra-assay and inter-assay precision were between 3.3 +/- 1.9% to 9.1 +/- 3.7% and 6.8 +/- 2.2% to 15.7 +/- 10.1%, respectively. Linearity, as measured by the correlation coefficient of intra-assay linear regression curves, was better than 0.998 in all cases.

Salicylate-induced abnormal activity in the inferior colliculus of rats.

Science.gov (United States)

Chen, G D; Jastreboff, P J

1995-02-01

The evaluation of the spontaneous activity of 471 units from the external nucleus of the IC revealed that salicylate induces an increase of the spontaneous activity and the emergence of a bursting type of activity longer than 4 spikes. For sharply tuned units, the affected cells were from the frequency range of 10-16 kHz, which corresponds to the behaviorally measured pitch of salicylate-induced tinnitus in rats. An exogenous calcium supplement, provided under the conditions shown to attenuate the behavioral manifestation of salicylate-induced tinnitus, abolished the modification of the spontaneous activity induced by salicylate. Finally, profound changes of activity were observed for cells not responding to contralateral sound. We propose that the observed long bursts of discharges represent tinnitus-related neuronal activity. The results are consistent with the hypothesis that GABA-mediated disinhibition is involved in the processing of tinnitus-related neuronal activity.

Formation of molecular complexes of salicylic acid, acetylsalicylic acid, and methyl salicylate in a mixture of supercritical carbon dioxide with a polar cosolvent

Science.gov (United States)

Petrenko, V. E.; Antipova, M. L.; Gurina, D. L.; Odintsova, E. G.

2015-08-01

The solvate structures formed by salicylic acid, acetylsalicylic acid, and methyl salicylate in supercritical (SC) carbon dioxide with a polar cosolvent (methanol, 0.03 mole fractions) at a density of 0.7 g/cm3 and a temperature of 318 K were studied by the molecular dynamics method. Salicylic and acetylsalicylic acids were found to form highly stable hydrogen-bonded complexes with methanol via the hydrogen atom of the carboxyl group. For methyl salicylate in which the carboxyl hydrogen is substituted by a methyl radical, the formation of stable hydrogen bonds with methanol was not revealed. The contribution of other functional groups of the solute to the interactions with the cosolvent was much smaller. An analysis of correlations between the obtained data and the literature data on the cosolvent effect on the solubility of the compounds in SC CO2 showed that the dissolving ability of SC CO2 with respect to a polar organic substance in the presence of a cosolvent increased only when stable hydrogen-bonded complexes are formed between this substance and the cosolvent.

Aspirin: 120 years of innovation. A report from the 2017 Scientific Conference of the International Aspirin Foundation, 14 September 2017, Charité, Berlin.

Science.gov (United States)

Walker, Jaqui; Hutchison, Pippa; Ge, Junbo; Zhao, Dong; Wang, Yongjun; Rothwell, Peter M; Gaziano, J Michael; Chan, Andrew; Burn, John; Chia, John; Langley, Ruth; O'Donnell, Valerie; Rocca, Bianca; Hawkey, Chris

2018-01-01

Acetylsalicylic acid was first synthesised by Dr FeIix Hoffman on 10th August 1897 and Aspirin was born. It quickly became the best-known pain killer in the world and in the 120 years since this event, aspirin has continued to attract interest, innovation and excitement. Set within the walls of the preserved ruins of Rudolf Virchow's lecture hall at Charité, within Berlin's Museum of Medical History, the International Aspirin Foundation's 28th Scientific Conference served to facilitate international, multi-disease, multidisciplinary discussion about the current understanding of aspirin's mechanisms of action and its utility in modern medicine as well as ideas for future research into its multifaceted applications to enhance global health. In addition to the delegates in Berlin, 300 medical doctors at the 19th Annual Scientific Congress of the Chinese Society of Cardiology were able to join the cardiology sessions from Taiyuan, Shangxi province via a live streaming link to and from China. This led to useful discussion and allowed a truly international perspective to the meeting.

Alleviation of mortality induced by salicylate and stress.

Science.gov (United States)

Jastreboff, P J; Brennan, J F

1994-05-15

Protection from the deleterious effects of the interaction of environmental stress and salicylate by calcium supplement was investigated in 96 pigmented rats. Within a 2 x 2 x 4 factorial design, rats were assigned to groups defined by: A) ad lib access to 1) plain tap water, or 2) 50 mM calcium chloride solution; B) exposure to stressors consisting of daily 10 h periods of 1) 98 dB SPL noise, or 2) confinement precluding movements; C) daily injections of 233, 350, or 410 mg/kg of sodium salicylate or the saline vehicle. For subjects maintained on tap water, weight loss and mortality increased with salicylate levels, with all subjects dying in the group drinking water and injected with 410 mg/kg. Calcium protected all of the subjects in the noise stress group but not in the confined group.

Spectrophotometric determination of tungsten with salicylic acid

International Nuclear Information System (INIS)

Goncalves, Z.C.

1976-10-01

The method comprises the complexation of tungsten with salicylic acid in concentrated sulphuric acid yielding a reddish color. The maximum absorbance of the complex lies within 410-420 nm, 420 nm being the chosen wavelenght. The final concentration of salicylic acid is 0,080 g/ml. The sensitivity is 0,13 μg W(%T) -1 ml -1 . Titanium, vanadium, rhenium, niobium and molybdenum interferes and must be separated, titanium being the strongest interferent. The separation procedures, advantages of the process, stoichiometric relations and equilibrium constant are discussed. (Author) [pt

Salicylate Toxicity from Genital Exposure to a Methylsalicylate-Containing Rubefacient

Science.gov (United States)

Thompson, Trevonne M.; Toerne, Theodore; Erickson, Timothy B.

2016-01-01

Methylsalicylate-containing rubefacients have been reported to cause salicylate poisoning after ingestion, topical application to abnormal skin, and inappropriate topical application to normal skin. Many over-the-counter products contain methylsalicylate. Topical salicylates rarely produce systemic toxicity when used appropriately; however, methylsaliclyate can be absorbed through intact skin. Scrotal skin can have up to 40-fold greater absorption compared to other dermal regions. We report a unique case of salicylate poisoning resulting from the use of a methylsalicylate-containing rubefacient to facilitate masturbation in a male teenager. Saliclyate toxicity has not previously been reported from the genital exposure to methylsaliclyate. PMID:26973745

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.

40 CFR 180.1189 - Methyl salicylate; exemption from the requirement of a tolerance.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Methyl salicylate; exemption from the... Exemptions From Tolerances § 180.1189 Methyl salicylate; exemption from the requirement of a tolerance. The biochemical pesticide methyl salicylate is exempt from the requirement of a tolerance for residues in or on...

Expression of immediate-early genes in the inferior colliculus and auditory cortex in salicylate-induced tinnitus in rat.

Science.gov (United States)

Hu, S S; Mei, L; Chen, J Y; Huang, Z W; Wu, H

2014-03-12

Tinnitus could be associated with neuronal hyperactivity in the auditory center. As a neuronal activity marker, immediate-early gene (IEG) expression is considered part of a general neuronal response to natural stimuli. Some IEGs, especially the activity-dependent cytoskeletal protein (Arc) and the early growth response gene-1 (Egr-1), appear to be highly correlated with sensory-evoked neuronal activity. We hypothesize, therefore, an increase of Arc and Egr-1 will be observed in a tinnitus model. In our study, we used the gap prepulse inhibition of acoustic startle (GPIAS) paradigm to confirm that salicylate induces tinnitus-like behavior in rats. However, expression of the Arc gene and Egr-1 gene were decreased in the inferior colliculus (IC) and auditory cortex (AC), in contradiction of our hypothesis. Expression of N-methyl d-aspartate receptor subunit 2B (NR2B) was increased and all of these changes returned to normal 14 days after treatment with salicylate ceased. These data revealed long-time administration of salicylate induced tinnitus markedly but reversibly and caused neural plasticity changes in the IC and the AC. Decreased expression of Arc and Egr-1 might be involved with instability of synaptic plasticity in tinnitus.

Hydroxyl radical induced degradation of salicylates in aerated aqueous solution

International Nuclear Information System (INIS)

Szabó, László; Tóth, Tünde; Homlok, Renáta; Rácz, Gergely; Takács, Erzsébet; Wojnárovits, László

2014-01-01

Ionizing radiation induced degradation of acetylsalicylic acid, its hydrolysis product salicylic acid and a salicylic acid derivative 5-sulpho-salicylic acid, was investigated in dilute aqueous solutions by UV–vis spectrophotometry, HPLC separation and diode-array or MS/MS detection, chemical oxygen demand, total organic carbon content and by Vibrio fischeri toxicity measurements. Hydroxyl radicals were shown to degrade these molecules readily, and first degradation products were hydroxylated derivatives in all cases. Due to the by-products, among them hydrogen peroxide, the toxicity first increased and then decreased with the absorbed dose. With prolonged irradiation complete mineralization was achieved. - Highlights: • In OH induced reactions of salicylates first products are hydroxylated derivatives. • With prolonged irradiation dihydroxy derivatives also form. • In aerated solutions the one-electron oxidant OH induces 3–4 oxidations. • Toxicity first increases and then decreases with dose mainly due to H 2 O 2 formation. • The toxicity in tap water is smaller than in pure water

Aspirin Induces Apoptosis through Release of Cytochrome c from Mitochondria

Directory of Open Access Journals (Sweden)

Katja C. Zimmermann

2000-01-01

Full Text Available Nonsteroidal anti-inflammatory drugs (NSAID reduce the risk for cancer, due to their anti proliferative and apoptosis-inducing effects. A critical pathway for apoptosis involves the release of cytochrome c from mitochondria, which then interacts with Apaf-1 to activate caspase proteases that orchestrate cell death. In this study we found that treatment of a human cancer cell line with aspirin induced caspase activation and the apoptotic cell morphology, which was blocked by the caspase inhibitor zVAD-fmk. Further analysis of the mechanism underlying this apoptotic event showed that aspirin induces translocation of Bax to the mitochondria and triggers release of cytochrome c into the cytosol. The release of cytochrome c from mitochondria was inhibited by overexpression of the antiapoptotic protein Bcl-2 and cells that lack Apaf-1 were resistant to aspirin-induced apoptosis. These data provide evidence that the release of cytochrome c is an important part of the apoptotic mechanism of aspirin.

Indomethacin and salicylate decrease epinephrine-induced glycogenolysis

International Nuclear Information System (INIS)

Miller, J.D.; Ganguli, S.; Artal, R.; Sperling, M.A.

1985-01-01

Epinephrine (E) produces an immediate (0-30 minutes) rise in hepatic glucose production (Ra), largely due to activation of glycogenolysis; thereafter, E-stimulated gluconeogenesis becomes the major factor maintaining glucose production. To investigate the possible role of arachidonic acid metabolites on Ra during E stimulation, the authors infused E in trained conscious dogs before and during administration of two inhibitors of arachidonic acid metabolism, indomethacin (INDO) and salicylate (S). On separate days, experimental animals were treated with both oral and IV INDO and oral acetylsalicylic acid and IV sodium salicylate. Ra and glucose utilization (Rd), both in mg x kg-1 min-1, were calculated by isotope dilution using 3- 3 H-glucose. After achieving steady state specific activity, control (C) and experimental animals (n . 6 per group) received E (0.1 ug x kg-1 min-1) for 150 minutes, raising plasma levels to approximately 1500 pg/mL in each group. In C, plasma glucose (G; mg/dL) rose by 17 +/- 5 at 10 minutes and 19 +/- 3 at 20 minutes due to an initial spike in Ra (2.7 +/- 0.2 to 4.9 +/- 0.5; P less than 0.01) at 10 minutes. INDO and S treatment attenuated this initial (10-20 minutes) rise in G (P less than 0.05) due to a lower stimulated Ra at 10 minutes (3.3 +/- 0.1 with INDO; 3.0 +/- 0.5 with S; P less than 0.05). After 20 minutes Ra was not different in the 3 groups; no overall differences in Rd, glucose clearance, or plasma insulin levels occurred with INDO or S treatment

Protective Effects of Pinus halepensis L. Essential Oil on Aspirin-induced Acute Liver and Kidney Damage in Female Wistar Albino Rats.

Science.gov (United States)

Bouzenna, Hafsia; Samout, Noura; Amani, Etaya; Mbarki, Sakhria; Tlili, Zied; Rjeibi, Ilhem; Elfeki, Abdelfattah; Talarmin, Hélène; Hfaiedh, Najla

2016-08-01

Aromatic and medicinal plants are sources of natural antioxidants thanks to their secondary metabolites. Administration of Pinus halepensis L. (Pinaceae family) in previous studies was found to alleviate deleterious effects of aspirin-induced damage on liver and kidney. The present study, carried out on female rats, evaluates the effects of P. halepensis L. essential oil (EOP) on aspirin (A)-induced damage to liver and kidney. The animals used in this study were rats (n=28) divided into 4 groups of 7 each: (1) a control group (C); (2) a group given NaCl for 56 days then treated with (A) (600 mg/kg) for 4 days (A); (3) a group fed with (EOP) for 56 days then (A) for 4 days; and a group fed with only (EOP) for 56 days and given NaCl for 4 days. Estimations of biochemical parameters in blood were determined using kit methods (Spinreact). Lipid peroxidation levels (TBARS), superoxide dismutase (SOD) and catalase (CAT), glutathione peroxidase (GPx) activities were determined. Histopathological study was done by immersing pieces of both organs in a fixative solution followed by paraffin embeddeding and hematoxylin-eosin staining. Under our experimental conditions, Aspirin at dose 600 mg/kg body weight induced an increase of serum biochemical parameters as well as an oxidative stress in both organs. An increase occurred in TBARS by 108% and 55%, a decrease in SOD by 78% and 53%, CAT by 53% and 78%, and GPx by 78% and 51% in liver and kidney, respectively, compared to control. Administration of EOP given to rats enabled correction in these parameters. It could be concluded that the treatment with P. halepensis L. essential oil inhibited aspirin-induced liver and kidney damage.

Radiation protection with mesalamine (5-amino salicylic acid)

International Nuclear Information System (INIS)

Onoda, James M.; Court, Wayne S.; Feldmeier, John J.; Alecu, Rodica

1996-01-01

Purpose: Radiation proctitis induced during the therapy of rectal and prostate cancers, and radiation injuries in general, are often the principal dose limiting factor limiting dose escalation for radiation therapy. Thus, there has been a continuous search for radioprotective agents, especially those that could selectively protect normal tissues, as opposed to the target cancer. 5-amino salicylic acid (5ASA) is in clinical use as Mesalamine for the local treatment of ulcerative proctitis. Inasmuch as other investigators have identified 5ASA as a free radical scavenger, we determined whether pretreatment with 5ASA could confer radiation protection. Materials and Methods: Adult male C57BL/6J mice obtained from Jackson Laboratories were employed for these studies. We determined LD50 for acute gastrointestinal death for young (≤ 10 weeks old, ≤ 25 gms body weight) and aged (≥ 1 year old, ≥ 35 gms body weight) animals exposed to single fractions (1 - 20 Gy) from three different radiation sources, Cs 137 , 270 KeV x-rays, and a 4 MeV linear accelerator. Experimental mice were pre- or post-treated with 5ASA in an acidified isotonic saline solution by oral, rectal, or intraperitoneal administration. Animals were housed, maintained by AAALAC standards and treated with antibiotics or acidified water post radiation exposure to control opportunistic infections. Animals were scored for death when moribund. Results: 5ASA was found to be radioprotective by oral, rectal or intraperitoneal administration when given 15 to 90 minutes prior to radiation exposure. Administration of drug following radiation exposure failed to confer radioprotection. We determined a dose effect for 5ASA with maximum tolerated dose of 200 mg/kg administered ip 30 minutes prior to 11 Gy whole body exposure. Dose modification and radioprotection by 5ASA were determined by LD50(6), LD50(30), or LD50(365). More recently, we determined that 5ASA conferred significant radioprotection to mice exposed to

European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP): a randomized trial.

Science.gov (United States)

Landolfi, R; Marchioli, R

1997-01-01

Thrombotic complications characterize the clinical course of polycythemia vera (PV) and represent the main cause of morbidity and mortality. However, uncertainty still exists as to the benefit/risk ratio of aspirin prophylaxis in this setting. In vivo platelet biosynthesis of thromboxane A2 is enhanced and can be suppressed by low-dose aspirin in PV, thus providing a rationale for assessing the efficacy and safety of a low-dose aspirin regimen in these patients. The Gruppo Italiano Studio Policitemia Vera has recently performed a pilot study on 112 patients randomized to receive aspirin, 40 mg daily, or placebo and followed for 16 +/- 6 months (mean +/- SD). This study showed that low-dose aspirin is well tolerated in PV patients, and that a large-scale efficacy trial is feasible in this setting. In this article we report the protocol of the European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) study, which is a randomized trial designed to assess the risk/benefit ratio of low-dose aspirin in PV. To estimate the size and the follow-up duration required for the ECLAP trial, a retrospective analysis of the clinical epidemiology of a large PV population has recently been completed by the Gruppo Italiano Studio Policitemia Vera. On this basis, approximately 3500 patients will be enrolled in the ECLAP study with a follow-up of 3 to 4 years. The uncertainty principle will be used as the main eligibility criterion: Polycythemic patients of any age, having no clear indication for or contraindication to aspirin treatment, will be randomized in a double-blind fashion to receive oral aspirin (100 mg daily) or placebo. According to current therapeutic recommendations, the basic treatment of randomized patients should be aimed at maintaining the hematocrit value 50. Randomization will be stratified by participating center. The study is funded by the European Union BIOMED 2 program.

Evidence for formation of hydroxyl radicals during reperfusion after global cerebral ischaemia in rats using salicylate trapping and microdialysis

DEFF Research Database (Denmark)

Christensen, Thomas; Bruhn, T; Balchen, T

1994-01-01

Systemic administration of salicylate (SA) to rats (100 mg kg-1 i.p. ) was used as an in vivo trap of hydroxyl radicals (.OH). In the brain SA reacts with hydroxyl radicals to form the stable adducts 2, 3- and 2,5 dihydroxybenzoic acid (DHBAs) which can thus be taken as an index of .OH formation...

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

NARCIS (Netherlands)

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

1996-01-01

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

Aspirin exerts high anti-cancer activity in PIK3CA-mutant colon cancer cells.

Science.gov (United States)

Gu, Mancang; Nishihara, Reiko; Chen, Yang; Li, Wanwan; Shi, Yan; Masugi, Yohei; Hamada, Tsuyoshi; Kosumi, Keisuke; Liu, Li; da Silva, Annacarolina; Nowak, Jonathan A; Twombly, Tyler; Du, Chunxia; Koh, Hideo; Li, Wenbin; Meyerhardt, Jeffrey A; Wolpin, Brian M; Giannakis, Marios; Aguirre, Andrew J; Bass, Adam J; Drew, David A; Chan, Andrew T; Fuchs, Charles S; Qian, Zhi Rong; Ogino, Shuji

2017-10-20

Evidence suggests that nonsteroidal anti-inflammatory drug aspirin (acetylsalicylic acid) may improve patient survival in PIK3CA -mutant colorectal carcinoma, but not in PIK3CA -wild-type carcinoma. However, whether aspirin directly influences the viability of PIK3CA -mutant colon cancer cells is poorly understood. We conducted in vitro experiments to test our hypothesis that the anti-proliferative activity of aspirin might be stronger for PIK3CA -mutant colon cancer cells than for PIK3CA -wild-type colon cancer cells. We measured the anti-proliferative effect of aspirin at physiologic concentrations in seven PIK3CA -mutant and six PIK3CA -wild-type human colon cancer cell lines. After exposure to aspirin, the apoptotic index and cell cycle phase of colon cancer cells were assessed. In addition, the effect of aspirin was examined in parental SW48 cells and SW48 cell clones with individual knock-in PIK3CA mutations of either c.3140A>G (p.H1047R) or c.1633G>A (p.E545K). Aspirin induced greater dose-dependent loss of cell viability in PIK3CA -mutant cells than in PIK3CA -wild-type cells after treatment for 48 and 72 hours. Aspirin treatment also led to higher proportions of apoptotic cells and G0/G1 phase arrest in PIK3CA -mutant cells than in PIK3CA -wild-type cells. Aspirin treatment of isogenic SW48 cells carrying a PIK3CA mutation, either c.3140A>G (p.H1047R) or c.1633G>A (p. E545K), resulted in a more significant loss of cell viability compared to wild-type controls. Our findings indicate that aspirin causes cell cycle arrest, induces apoptosis, and leads to loss of cell viability more profoundly in PIK3CA -mutated colon cancer cells than in PIK3CA -wild-type colon cancer cells. These findings support the use of aspirin to treat patients with PIK3CA -mutant colon cancer.

Combining aspirin with angiotensin converting enzyme inhibitors in heart failure: how safe is it?

Science.gov (United States)

Mehta, H; Mahajan, A; Bansal, N; Vaidya, S; Pathak, L

1998-11-01

The above discussion on the interaction of aspirin and ACE inhibitors seems to suggest that aspirin in high doses may have adverse interaction with ACE inhibitors in patients with heart failure but the data obtained is not sufficient or conclusive to recommended omission of aspirin in patients with heart failure. This raises a query in the mind of the physician whether to use a combination or not? The role of aspirin in the early period after myocardial infarction is well established so is the role of ACE inhibitors. Hence in patients with myocardial infarction and preserved left ventricular function it would not be wrong to administer combination of ACE inhibitors and aspirin. Albeit at a lower dose. In patients with large myocardial infarction or heart failure, warfarin may be an option but still needs to be documented in large trials. As suggested long term use of aspirin after infarction is still ambiguous and may be harmful in patients with heart failure with its anticedent side effects. But long term benefits of ACE inhibitors in heart failure are well documented. Hence if a choice has to be made whether to discontinue either of the two drugs it would be preferable to stop the aspirin. To answer the issue of use of aspirin in patients with heart failure it would be essential to conduct a double blind randomized trial comparing known anti-thrombotic treatment, aspirin and anti-coagulants on mortality in patients with heart failure, especially caused by coronary artery disease. Such a trial is underway at the present and till the results are available it should be left to clinical judgement of the physician whether to administer aspirin in patients with heart failure after weighing the benefits versus risk.

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

Science.gov (United States)

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

2018-01-01

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

Transrectal ultrasound-guided biopsy of the prostate: aspirin increases the incidence of minor bleeding complications

International Nuclear Information System (INIS)

Halliwell, O.T.; Yadegafar, G.; Lane, C.; Dewbury, K.C.

2008-01-01

Aim: To assess whether patients taking aspirin were more likely to experience bleeding complications after transrectal ultrasound (TRUS)-guided prostate biopsy. Materials and methods: Three hundred and eighty-seven patients taking aspirin who underwent prostate biopsy over a 3.5 year period and 731 patients not taking aspirin over a 2 year period returned a questionnaire assessing the incidence and severity of bleeding complications. Results: Patients taking aspirin had a significantly higher cumulative incidence of haematuria and rectal bleeding, but not of haemospermia. They also had a longer mean duration of bleeding, but no increase in bleeding severity. Severe bleeding was very uncommon in both groups and no patients required intervention for bleeding complications. Conclusion: Aspirin exacerbates minor bleeding complications in patients undergoing TRUS guided biopsy of the prostate, but in this large group of aspirin-taking patients no dangerous bleeding complications were encountered. It may be that the risks associated with aspirin cessation outweigh the risks of haemorrhagic complications

Transrectal ultrasound-guided biopsy of the prostate: aspirin increases the incidence of minor bleeding complications

Energy Technology Data Exchange (ETDEWEB)

Halliwell, O.T. [Department of Radiology, Southampton General Hospital, Southampton (United Kingdom)], E-mail: hallo99@doctors.org.uk; Yadegafar, G. [Public Health Sciences and Medical Statistics Division, School of Medicine, Southampton General Hospital, Southampton University, Southampton (United Kingdom); Lane, C.; Dewbury, K.C. [Department of Radiology, Southampton General Hospital, Southampton (United Kingdom)

2008-05-15

Aim: To assess whether patients taking aspirin were more likely to experience bleeding complications after transrectal ultrasound (TRUS)-guided prostate biopsy. Materials and methods: Three hundred and eighty-seven patients taking aspirin who underwent prostate biopsy over a 3.5 year period and 731 patients not taking aspirin over a 2 year period returned a questionnaire assessing the incidence and severity of bleeding complications. Results: Patients taking aspirin had a significantly higher cumulative incidence of haematuria and rectal bleeding, but not of haemospermia. They also had a longer mean duration of bleeding, but no increase in bleeding severity. Severe bleeding was very uncommon in both groups and no patients required intervention for bleeding complications. Conclusion: Aspirin exacerbates minor bleeding complications in patients undergoing TRUS guided biopsy of the prostate, but in this large group of aspirin-taking patients no dangerous bleeding complications were encountered. It may be that the risks associated with aspirin cessation outweigh the risks of haemorrhagic complications.

Lower mortality rate in elderly patients with community-onset pneumonia on treatment with aspirin.

Science.gov (United States)

Falcone, Marco; Russo, Alessandro; Cangemi, Roberto; Farcomeni, Alessio; Calvieri, Camilla; Barillà, Francesco; Scarpellini, Maria Gabriella; Bertazzoni, Giuliano; Palange, Paolo; Taliani, Gloria; Venditti, Mario; Violi, Francesco

2015-01-06

Pneumonia is complicated by high rate of mortality and cardiovascular events (CVEs). The potential benefit of aspirin, which lowers platelet aggregation by inhibition of thromboxane A2 production, is still unclear. The aim of the study was to assess the impact of aspirin on mortality in patients with pneumonia. Consecutive patients admitted to the University-Hospital Policlinico Umberto I (Rome, Italy) with community-onset pneumonia were recruited and prospectively followed up until discharge or death. The primary end point was the occurrence of death up to 30 days after admission; the secondary end point was the intrahospital incidence of nonfatal myocardial infarction and ischemic stroke. One thousand and five patients (age, 74.7±15.1 years) were included in the study: 390 were receiving aspirin (100 mg/day) at the time of hospitalization, whereas 615 patients were aspirin free. During the follow-up, 16.2% of patients died; among these, 19 (4.9%) were aspirin users and 144 (23.4%; PFiO(2) ratio <300 negatively influenced survival, whereas aspirin therapy was associated with improved survival. Compared to patients receiving aspirin, the propensity score adjusted analysis confirmed that patients not taking aspirin had a hazard ratio of 2.07 (1.08 to 3.98; P=0.029) for total mortality. This study shows that chronic aspirin use is associated with lower mortality rate within 30 days after hospital admission in a large cohort of patients with pneumonia. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Determination of trace element impurities in aspirin tablets by neutron activation analysis

International Nuclear Information System (INIS)

Iskander, F.Y.; Klein, D.E.; Bauer, T.L.

1986-01-01

Twenty-five trace and minor elements in five different Egyptian aspirin brands (Aspo, Askin, Aspocid, Aspeol and Rivo) were determined by instrumental neutron activation analysis. It was concluded that the concentration of As, Ba, Br, Co, Cr, Fe (except in Aspocid), Mg, Mn, Rb, Se, Sr and Zn in the Egyptian brands is below or within the concentration range reported for these elements in 16 American aspirin and aspirin-like brands. (author)

Aspirin for acute treatment of episodic tension-type headache in adults.

Science.gov (United States)

Derry, Sheena; Wiffen, Philip J; Moore, R Andrew

2017-01-13

Tension-type headache (TTH) affects about 1 person in 5 worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (two to 14 headache days per month), and chronic TTH (15 headache days per month or more). Aspirin is one of a number of analgesics suggested for acute treatment of episodic TTH. To assess the efficacy and safety of aspirin for acute treatment of episodic tension-type headache (TTH) in adults compared with placebo or any active comparator. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and the Oxford Pain Relief Database from inception to September 2016, and also reference lists of relevant published studies and reviews. We sought unpublished studies by asking personal contacts and searching online clinical trial registers and manufacturers' websites. We included randomised, double-blind, placebo-controlled studies (parallel-group or cross-over) using oral aspirin for symptomatic relief of an acute episode of TTH. Studies had to be prospective, with participants aged 18 years or over, and include at least 10 participants per treatment arm. Two review authors independently assessed studies for inclusion and extracted data. For various outcomes (predominantly those recommended by the International Headache Society (IHS)), we calculated the risk ratio (RR) and number needed to treat for one additional beneficial outcome (NNT), one additional harmful outcome (NNH), or to prevent one event (NNTp) for oral aspirin compared to placebo or an active intervention.We assessed the evidence using GRADE and created a 'Summary of findings' table. We included five studies enrolling adults with frequent episodic TTH; 1812 participants took medication, of which 767 were included in comparisons of aspirin 1000 mg with placebo, and 405 in comparisons of aspirin 500 mg or 650 mg with placebo. Not all of these participants provided data for outcomes of interest in this review

Effect of preoperatively continued aspirin use on early and mid-term outcomes in off-pump coronary bypass surgery: a propensity score-matched study of 1418 patients.

Directory of Open Access Journals (Sweden)

Fucheng Xiao

Full Text Available To date, effect of preoperatively continued aspirin administration in off-pump coronary artery bypass grafting (CABG is less known. We aimed to assess the effect of preoperatively continued aspirin use on early and mid-term outcomes in patients receiving off-pump CABG.From October 2009 to September 2013 at the Fuwai Hospital, 709 preoperative aspirin users were matched with unique 709 nonaspirin users using propensity score matching to obtain risk-adjusted outcome comparisons between the two groups. Early outcomes were in-hospital death, stroke, intra- and post-operative blood loss, reoperation for bleeding and blood product transfusion. Major adverse cardiac events (death, myocardial infarction or repeat revascularization, angina recurrence and cardiogenic readmission were considered as mid-term endpoints.There were no significant differences among the groups in baseline characteristics after propensity score matching. The median intraoperative blood loss (600 ml versus 450 ml, P = 0.56, median postoperative blood loss (800 ml versus 790 ml, P = 0.60, blood transfusion requirements (25.1% versus 24.4%, P = 0.76 and composite outcome of in-hospital death, stroke and reoperation for bleeding (2.8% versus 1.6%, P = 0.10 were similar in aspirin and nonaspirin use group. At about 4 years follow-up, no significant difference was observed among the aspirin and nonaspirin use group in major adverse cardiac events free survival estimates (95.7% versus 91.5%, P = 0.23 and freedom from cardiogenic readmission (88.5% versus 85.3%, P = 0.77 whereas the angina recurrence free survival rates was 83.7% and 73.9% in the aspirin and nonaspirin use group respectively (P = 0.02, with odd ratio for preoperative aspirin estimated at 0.71 (95% confidence interval, 0.49-1.04, P = 0.08.Preoperatively continued aspirin use was not associated with increased risk of intra- and post-operative blood loss, blood transfusion requirements and composite outcome of in

Generalization of conditioned suppression during salicylate-induced phantom auditory perception in rats.

Science.gov (United States)

Brennan, J F; Jastreboff, P J

1991-01-01

Tonal frequency generalization was examined in a total of 114 pigmented male rats, 60 of which were tested under the influence of salicylate-induced phantom auditory perception, introduced before or after lick suppression training. Thirty control subjects received saline injections, and the remaining 24 subjects served as noninjected controls of tonal background effects on generalization. Rats were continuously exposed to background noise alone or with a superimposed tone. Offset of background noise alone (Experiment I), or combined with onset or continuation of the tone (Experiments II and III) served as the conditioned stimulus (CS). In Experiment I, tone presentations were introduced only after suppression training. Depending on the time of salicylate introduction, a strong and differential influence on generalization gradients was observed, which is consistent with subjects' detection of salicylate-induced, high-pitched sound. Moreover, when either 12- or 3 kHz tones were introduced before or after Pavlovian training to mimic salicylate effects in 24 rats, the distortions in generalization gradients resembled trends obtained from respective salicylate injected groups. Experiments II and III were aimed at evaluating the masking effect of salicylate-induced phantom auditory perception on external sounds, with a 5- or a 10-kHz tone imposed continuously on the noise or presented only during the CS. Tests of tonal generalization to frequencies ranging from 4- to 11- kHz showed that in this experimental context salicylate-induced perception did not interfere with the dominant influence of external tones, a result that further strengthens the conclusion of Experiment I.

Aspirin in Patients With Previous Percutaneous Coronary Intervention Undergoing Noncardiac Surgery

DEFF Research Database (Denmark)

Graham, Michelle M; Sessler, Daniel I; Parlow, Joel L

2018-01-01

Background: Uncertainty remains about the effects of aspirin in patients with prior percutaneous coronary intervention (PCI) having noncardiac surgery. Objective: To evaluate benefits and harms of perioperative aspirin in patients with prior PCI. Design: Nonprespecified subgroup analysis of a mul...

Aspirin Metabolomics in Colorectal Cancer Chemoprevention | Division of Cancer Prevention

Science.gov (United States)

Substantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well-established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in humans, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which

The role of nitric oxide in aspirin induced thrombolysis in vitro and the purification of aspirin activated nitric oxide synthase from human blood platelets.

Science.gov (United States)

Karmohapatra, Soumendra K; Chakraborty, Kushal; Kahn, Nighat N; Sinha, Asru K

2007-11-01

Aspirin, a well-known inhibitor of platelet aggregation, is extensively used for the prevention/treatment of coronary artery disease. The beneficial and antithrombotic effects of the compound are related to the inhibition of platelet cyclooxygenase. It is currently believed that aspirin has no effect on the formed thrombus, which results in coronary artery disease. It was found that the exposure of platelets to 4.0 microM aspirin either in vitro or in vivo resulted in fibrinolysis of the formed "clot" produced by the recalcification of platelet-rich plasma due to the production of NO in these cells by the compound. The lysis of clot in the presence of aspirin was found to be related to the fibrinolysis with simultaneous appearance of fibrin degradation products due to the generation of serine proteinase activity by NO in the assay mixture. The aspirin activated nitric oxide synthase that catalyzed the synthesis of NO in platelets was solubilized by Triton X-100 treatment and purified to homogeneity by chromatography on DEAE cellulose and Sephadex G-50 columns. The enzyme was found to be a single chain polypeptide with M.W. 19 kDa. The treatment of human plasminogen with NO was found to directly activate the zymogen to plasmin with the production of preactivation peptide in the absence of cofactors, or cells without the formation of cyclic GMP in the assay mixture. (c) 2007 Wiley-Liss, Inc.

Mobility and molecular ions of dimethyl methyl phosphonate, methyl salicylate and acetone

Science.gov (United States)

Nowak, D. M.

1983-06-01

The mobilities of positive and negative reactant ions are reported for (H2O)nH(+); (H2O)2O2 and (H2O)2CO3(-) ion clusters. The formation of positive DMMP monomer and dimer is reported, and equilbria molecular reactions are reported. Acetone is reported as forming a dimer at 81 ppb with a reduced mobility (K sub o) of 1.82, Methyl salicylate is shown to form a protonated and hydrated positive monomer. Mixtures of DMMP and methyl salicylate with acetone showed a substantial change in DMMP ion clustering and little or no change in the methyl salicylate mobility spectra. Negative ions were not observed for DMMP, methyl salicylate, acetone and the mixtures under the conditions reported.

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

Transparent plastic scintillators for neutron detection based on lithium salicylate

International Nuclear Information System (INIS)

Mabe, Andrew N.; Glenn, Andrew M.; Carman, M. Leslie; Zaitseva, Natalia P.; Payne, Stephen A.

2016-01-01

Transparent plastic scintillators with pulse shape discrimination containing "6Li salicylate have been synthesized by bulk polymerization with a maximum "6Li loading of 0.40 wt%. Photoluminescence and scintillation responses to gamma-rays and neutrons are reported herein. Plastics containing "6Li salicylate exhibit higher light yields and permit a higher loading of "6Li as compared to previously reported plastics based on lithium 3-phenylsalicylate. However, pulse shape discrimination performance is reduced in lithium salicylate plastics due to the requirement of adding more nonaromatic monomers to the polymer matrix as compared to those based on lithium 3-phenylsalicylate. Reduction in light yield and pulse shape discrimination performance in lithium-loaded plastics as compared to pulse shape discrimination plastics without lithium is interpreted in terms of energy transfer interference by the aromatic lithium salts. - Highlights: • Plastic scintillator with 0.4% "6Li loading is reported using lithium salicylate. • Influence of lithium salts on the scintillation mechanism is explored. • New lithium-loaded scintillator provides improved light yield and reduced cost.

Solubility of salicylic acid in pure alcohols at different temperatures

International Nuclear Information System (INIS)

Lim, Junhyuk; Jang, Sunghyun; Cho, Hye Kyoung; Shin, Moon Sam; Kim, Hwayong

2013-01-01

Highlights: ► Solubility data of salicylic acid in pure alkanols were measured. ► The experimental data were correlated with NRTL, UNIQUAC and Wilson models. ► The data are fit well with all three models for the six pure alcohols studied. ► Adjustable interaction parameters were suggested. - Abstract: This work focused on the experimental measurements and the numerical calculations of the solubility of salicylic acid in various alcohols. The solubility of salicylic acid in pure alcohols was determined using a (solid + liquid) equilibrium measurement apparatus at temperatures ranging from (278.15 to 318.15) K. Also, the melting temperature and fusion enthalpy of salicylic acid were determined by a differential scanning calorimeter (TA instrument Q100). The experimental results were correlated with the equation for solubility of a solid in a liquid with the nonrandom two liquid (NRTL), universal quasi-chemical (UNIQUAC) and Wilson models for liquid phase activity coefficients to validate the quality of the data taken. Adjustable interaction parameters were also provided. The experimental data fit appropriately with all three models for the pure alcohols studied.

Nonprescription analgesics and their use in solid-organ transplantation: a review.

Science.gov (United States)

Gabardi, Steven; Luu, Linh

2004-09-01

To review the pharmacology, adverse events, drug interactions, and use of the nonprescription analgesics in solid-organ transplant recipients. Studies evaluating nonprescription analgesics in solid-organ transplantation were considered for evaluation. English-language studies were selected for inclusion. Nonprescription analgesics (aspirin, choline salicylate, magnesium salicylate, sodium salicylate, ibuprofen, ketoprofen, naproxen sodium, and acetaminophen) are the most commonly purchased over-the-counter agents in the United States. These agents, although generally considered safe, have been associated with a number of toxicities. The salicylates and nonsteroidal anti-inflammatory drugs have been associated with gastrointestinal damage, hematologic changes, liver and kidney dysfunction, and breathing difficulties. Acetaminophen has been shown to induce hematologic changes and liver and renal dysfunction. A closer look at the nonprescription analgesics reveals their potential for harm when used by solid-organ transplant recipients. In this patient population, the salicylates and nonsteroidal anti-inflammatory drugs should generally be avoided if possible, because of their potential toxicities, especially renal dysfunction. Low-dose aspirin, for the prevention of cardiovascular and cardiocerebral events, appears to be safe, but patients must still be followed closely. Acetaminophen is generally considered the nonprescription analgesic and antipyretic of choice in transplant recipients because of its favorable toxicity profile. However, it is imperative that patients and transplant practitioners are aware that this agent is not without toxicities and proper monitoring is advised.

Reduction of NANOG Mediates the Inhibitory Effect of Aspirin on Tumor Growth and Stemness in Colorectal Cancer

Directory of Open Access Journals (Sweden)

Hefei Wang

2017-11-01

Full Text Available Background/Aims: Cancer stem cells (CSCs are considered to be responsible for tumor relapse and metastasis, which serve as a potential therapeutic target for cancer. Aspirin has been shown to reduce cancer risk and mortality, particularly in colorectal cancer. However, the CSCs-suppressing effect of aspirin and its relevant mechanisms in colorectal cancer remain unclear. Methods: CCK8 assay was employed to detect the cell viability. Sphere formation assay, colony formation assay, and ALDH1 assay were performed to identify the effects of aspirin on CSC properties. Western blotting was performed to detect the expression of the stemness factors. Xenograft model was employed to identify the anti-cancer effects of aspirin in vivo. Unpaired Student t test, ANOVA test and Kruskal-Wallis test were used for the statistical comparisons. Results: Aspirin attenuated colonosphere formation and decreased the ALDH1 positive cell population of colorectal cancer cells. Aspirin inhibited xenograft tumor growth and reduced tumor cells stemness in nude mice. Consistently, aspirin decreased the protein expression of stemness-related transcription factors, including c-Myc, OCT4 and NANOG. Suppression of NANOG blocked the effect of aspirin on sphere formation. Conversely, ectopic expression of NANOG rescued the aspirin-repressed sphere formation, suggesting that NANOG is a key downstream target. Moreover, we found that aspirin repressed NANOG expression in protein level by decreasing its stability. Conclusion: We have provided new evidence that aspirin attenuates CSC properties through down-regulation of NANOG, suggesting aspirin as a promising therapeutic agent for colorectal cancer treatment.

Failure of ethamsylate to reduce aspirin-induced gastric mucosal bleeding in humans.

OpenAIRE

Daneshmend, T K; Stein, A G; Bhaskar, N K; Hawkey, C J

1989-01-01

1. We investigated the effect of the haemostatic agent ethamsylate on aspirin-induced gastric mucosal bleeding. 2. Eighteen healthy subjects were studied three times: at the end of 48 h periods of treatment with (a) placebo, (b) aspirin 600 mg four times daily, (9 doses) and (c) aspirin 600 mg four times daily with each dose preceded by ethamsylate 500 mg. 3. At the end of each treatment period gastric mucosal bleeding into timed gastric washings was quantified using the orthotolidine reactio...

Functionalized bimodal mesoporous silicas as carriers for controlled aspirin delivery

International Nuclear Information System (INIS)

Gao Lin; Sun Jihong; Li Yuzhen

2011-01-01

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 f t =kt n was employed to analyze the dissolution data in details. It is indicated that the bimodal mesopores are beneficial for unrestricted drug molecules diffusing and therefore lead to a higher loading and faster releasing than that of MCM-41. The results show that the aspirin delivery properties are influenced considerably by the mesoporous matrix, whereas the large pore of bimodal mesoporous silica is the key point for the improved controlled-release properties. - Graphical abstract: Loading (A) and release profiles (B) of aspirin in N-BMMs and N-MCM-41 indicated that BMMs have more drug loading capacity and faster release rate than that MCM-41. Highlights: → Bimodal mesoporous silicas (BMMs) and MCM-41 modified with amino group via post-treatment procedure. → Loading and release profiles of aspirin in modified BMMs and MCM-41. → Modified BMMs have more drug loading capacity and faster release rate than that modified MCM-41.

Microautoradiography of 14C-salicylic acid in the skin of guinea-pig

International Nuclear Information System (INIS)

Washitake, Mitsunori; Ozawa, Yasuo; Anmo, Toshio; Tanaka, Ichiro

1974-01-01

The concentration of salicylic acid in guinea-pig skin was examined by microautoradiography. The retention of salicylic acid in the stratum corneum was observed. It was considered that the rate of transfer of the drug into the stratum corneum was small and that the stratum corneum became the barrier for permeability of the skin. The distribution of salicylic acid in other parts of the skin was uniform and no retention of the drug in any special parts was observed. The plasma level showed less percutaneous absorption of the drug when it was applied as liquid paraffin solution than when it was applied as an aqueous solution. The amount of salicylic acid absorbed from damaged skin was extremely large and, in this case, disappearance of the drug from the skin was fast. (author)

Low-dose aspirin or other nonsteroidal anti-inflammatory drug use and prostate cancer risk

DEFF Research Database (Denmark)

Skriver, Charlotte; Dehlendorff, Christian; Borre, Michael

2016-01-01

PURPOSE: Increasing evidence suggests that aspirin use may protect against prostate cancer. In a nationwide case-control study, using Danish high-quality registry data, we evaluated the association between the use of low-dose aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs......) and the risk of prostate cancer. METHODS: We identified 35,600 patients (cases) with histologically verified prostate cancer during 2000-2012. Cases were matched to 177,992 population controls on age and residence by risk-set sampling. Aspirin and nonaspirin NSAID exposure was defined by type, estimated dose......, duration, and consistency of use. We used conditional logistic regression to estimate odds ratios (ORs), with 95 % confidence intervals (CIs), for prostate cancer associated with low-dose aspirin (75-150 mg) or nonaspirin NSAID use, adjusted for potential confounders. RESULTS: Use of low-dose aspirin...

Prophylactic low-dose aspirin is effective antithrombotic therapy for combination treatments of thalidomide or lenalidomide in myeloma.

Science.gov (United States)

Niesvizky, Ruben; Martínez-Baños, Déborah; Jalbrzikowski, Jessica; Christos, Paul; Furst, Jessica; De Sancho, Maria; Mark, Tomer; Pearse, Roger; Mazumdar, Madhu; Zafar, Faiza; Pekle, Karen; Leonard, John; Jayabalan, David; Coleman, Morton

2007-12-01

Multiple myeloma (MM) patients have a propensity for thromboembolic events (TE), and treatment with thalidomide/dexamethasone or lenalidomide/dexamethasone increases this risk. This report describes the use of low-dose aspirin (81 mg) as primary thromboprophylaxis in three series of MM patients receiving thalidomide or lenalidomide with other drugs. In the first regimen (clarithromycin, thalidomide, dexamethasone), initiation of low-dose aspirin negated the occurrence of any further TE. In a second study, prophylactic aspirin given with thalidomide/dexamethasone resulted in a rate of TE similar to that seen with dexamethasone alone (without aspirin). A third study (n = 72) evaluated thrombosis rates with aspirin and a lenalidomide-containing regimen (clarithromycin, lenalidomide, dexamethasone). Of nine occurrences of thromboembolism, five were associated with aspirin interruption or poor compliance. Low-dose aspirin appears to reduce the incidence of thrombosis with these regimens. Routine use of aspirin as antithrombotic prophylaxis in MM patients receiving immunomodulatory drugs with corticosteroids is warranted.

Use and misuse of aspirin in rural Ethiopia | Duncan | East African ...

African Journals Online (AJOL)

Objectives: To investigate ability to distinguish simple analgesics, to document misconceptions about aspirin use, and to identify strategies to diminish potentially harmful aspirin use in Ethiopia. Design: Qualitative study (eight focus group discussions) used to inform cross-sectional survey. Setting: Butajira, a small town in ...

Trace element impurity determination in aspirin tablets by INAA

International Nuclear Information System (INIS)

Miyoshi, E.K.; Saiki, M.

2009-01-01

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)

The difference in association between aspirin use and other thrombocyte aggregation inhibitors and survival in patients with colorectal cancer.

Science.gov (United States)

Frouws, M A; Rademaker, E; Bastiaannet, E; van Herk-Sukel, M P P; Lemmens, V E; Van de Velde, C J H; Portielje, J E A; Liefers, G J

2017-05-01

Several studies have suggested that the association between aspirin and improved cancer survival is mediated through the mechanism of aspirin as thrombocyte aggregation inhibitors (TAI). The aim of this study was to provide epidemiological evidence for this mechanism assessing the association between overall survival and the use of aspirin and non-aspirin TAI in patients with colorectal cancer. In this observational study, data from the Netherlands Comprehensive Cancer Organisation were linked to PHARMO Database Network. Patients using aspirin or aspirin in combination with non-aspirin TAI (dual users) were selected and compared with non-users. The association between overall survival and the use of (non-)aspirin TAI was analysed using Cox regression models with the use of (non-)aspirin TAI as a time-varying covariate. In total, 9196 patients were identified with colorectal cancer and 1766 patients used TAI after diagnosis. Non-aspirin TAI were mostly clopidogrel and dipyridamole. Aspirin use was associated with a significant increased overall survival and hazard ratio (HR) 0.41 (95% confidence interval [CI] 0.37-0.47), and the use of non-aspirin TAI was not associated with survival of HR 0.92 (95% CI 0.70-1.22). Dual users did not have an improved overall survival when compared with patients using solely aspirin. Aspirin use after diagnosis of colorectal cancer was associated with significantly lower mortality rates and this effect remained significant after adjusting for potential confounders. No additional survival benefit was observed in patients using both aspirin and another TAI. Copyright © 2017 Elsevier Ltd. All rights reserved.

The atmospheric chemistry of methyl salicylate - reactions with atomic chlorine and with ozone

Energy Technology Data Exchange (ETDEWEB)

Canosa-Mas, C.E.; Duffy, J.M.; Thompson, K.C.; Wayne, R.P. [Physical and Theoretical Chemical Lab., Oxford (United Kingdom); King, M.D. [King' s College, London (United Kingdom). Dept. of Chemistry

2002-05-01

Methyl salicylate is one of a number of semiochemicals, signal molecules, emitted by herbivore-infested plants. These signal molecules attract predators of the herbivore, and the chemicals thus act indirectly as part of the defence mechanism of the plant. Previous studies have shown that ozone damage to plants can also elicit the emission of signal molecules. The fate of these signal molecules in the atmosphere is not known. Preliminary studies have been undertaken to examine the atmospheric chemistry of methyl salicylate for the first time. Rate coefficients for the reaction of methyl salicylate with atomic chlorine and with ozone have been determined; the values are (2.8()+-(0.3)x10{sup -12} and )approx4x10{sup -21} cm{sup 3} molecule{sup -1} s{sup -1}. These results suggest that neither reaction with atomic chlorine nor reaction with ozone will provide important loss routes for methyl salicylate in the atmosphere. The possible importance of photolysis of methyl salicylate in the atmosphere is considered. (Author)

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

Science.gov (United States)

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

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

Expression of immediate-early genes in the inferior colliculus and auditory cortex in salicylate-induced tinnitus in rat

Directory of Open Access Journals (Sweden)

S.S. Hu

2014-03-01

Full Text Available Tinnitus could be associated with neuronal hyperactivity in the auditory center. As a neuronal activity marker, immediate-early gene (IEG expression is considered part of a general neuronal response to natural stimuli. Some IEGs, especially the activity-dependent cytoskeletal protein (Arc and the early growth response gene-1 (Egr-1, appear to be highly correlated with sensory-evoked neuronal activity. We hypothesize, therefore, an increase of Arc and Egr-1 will be observed in a tinnitus model. In our study, we used the gap prepulse inhibition of acoustic startle (GPIAS paradigm to confirm that salicylate induces tinnitus-like behavior in rats. However, expression of the Arc gene and Egr-1 gene were decreased in the inferior colliculus (IC and auditory cortex (AC, in contradiction of our hypothesis. Expression of N-methyl d-aspartate receptor subunit 2B (NR2B was increased and all of these changes returned to normal 14 days after treatment with salicylate ceased. These data revealed long-time administration of salicylate induced tinnitus markedly but reversibly and caused neural plasticity changes in the IC and the AC. Decreased expression of Arc and Egr-1 might be involved with instability of synaptic plasticity in tinnitus.

Beyond COX-1: the effects of aspirin on platelet biology and potential mechanisms of chemoprevention.

Science.gov (United States)

Ornelas, Argentina; Zacharias-Millward, Niki; Menter, David G; Davis, Jennifer S; Lichtenberger, Lenard; Hawke, David; Hawk, Ernest; Vilar, Eduardo; Bhattacharya, Pratip; Millward, Steven

2017-06-01

After more than a century, aspirin remains one of the most commonly used drugs in western medicine. Although mainly used for its anti-thrombotic, anti-pyretic, and analgesic properties, a multitude of clinical studies have provided convincing evidence that regular, low-dose aspirin use dramatically lowers the risk of cancer. These observations coincide with recent studies showing a functional relationship between platelets and tumors, suggesting that aspirin's chemopreventive properties may result, in part, from direct modulation of platelet biology and biochemistry. Here, we present a review of the biochemistry and pharmacology of aspirin with particular emphasis on its cyclooxygenase-dependent and cyclooxygenase-independent effects in platelets. We also correlate the results of proteomic-based studies of aspirin acetylation in eukaryotic cells with recent developments in platelet proteomics to identify non-cyclooxygenase targets of aspirin-mediated acetylation in platelets that may play a role in its chemopreventive mechanism.

The effect of aspirin on blood loss and transfusion requirements in patients with femoral neck fractures.

LENUS (Irish Health Repository)

Manning, Brian J

2012-02-03

Although it is widely accepted that aspirin will increase the risk of intra- and post-operative bleeding, clinical studies have not consistently supported this assumption. We aimed to assess the effect of pre-operative aspirin on blood loss and transfusion requirements in patients undergoing emergency fixation of femoral neck fractures. A prospective case-control study was undertaken in patients presenting with femoral neck fractures. Parameters recorded included intra-operative blood loss, post-operative blood loss, transfusion requirements and peri-operative reduction in haemoglobin concentration. Of 89 patients presenting with femoral neck fractures 32 were on long-term aspirin therapy. Pre-operative aspirin ingestion did not significantly affect peri-operative blood loss, or change in haemoglobin concentration or haematocrit. However those patients taking aspirin pre-operatively had a significantly lower haemoglobin concentration and haematocrit and were more likely to be anaemic at presentation than those who were not receiving aspirin. Patients taking aspirin were also more likely to receive blood transfusion post-operatively.

Is aspirin still the drug of choice for management of patients with peripheral arterial disease?

Science.gov (United States)

Poredos, Pavel; Jezovnik, Mateja K

2013-03-01

Antiplatelet drugs represent one of the basic options for management of patients with different atherosclerotic diseases. Aspirin is the oldest and most often prescribed antiplatelet drug. The efficacy of aspirin depends on the clinical characteristics of the treated population and probably also on the type or location of atherosclerotic disease. It seems that it is most effective in coronary patients with clinically unstable disease, less effective in prevention of cerebrovascular incidents, and its efficacy is uncertain in peripheral artery disease (PAD) patients. One of the first meta-analyses (Antithrombotic Trialists' Collaboration - ATC) indicated that antiplatelet drugs also significantly reduce cardiovascular events in patients with PAD. However, only one third of the PAD patients included were treated with aspirin, while the rest received other anti-platelet drugs. The latest ATC meta-analysis of randomized control trials of aspirin therapy involving patients with diabetes and PAD demonstrated no benefit of aspirin in reducing cardiovascular events. Also in patients with preclinical PAD (pathological ankle brachial index) aspirin did not result in a significant reduction of vascular events. The new anti-platelet drugs prasugrel, ticagrelor and picotamide seem to be more effective than aspirin in PAD patients, particularly in diabetic patients with PAD. In conclusion, antiplatelet drugs are effective in prevention of cardiovascular events in different atherosclerotic diseases, including PAD. However, recent studies indicated that in PAD patients aspirin is less effective than in coronary artery disease. New anti-platelet drugs showed marginal superiority over aspirin without definite advantages. Aspirin thus remains the first line of antiplatelet drug for secondary prevention of cardiovascular events in PAD patients and clopidogrel as its effective alternative. Further, new studies on PAD patients are necessary to better define the role of anti

Induction of lung lesions in Wistar rats by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and its inhibition by aspirin and phenethyl isothiocyanate

International Nuclear Information System (INIS)

Ye, Bo; Zhang, Yu-Xia; Yang, Fei; Chen, Hong-Lei; Xia, Dong; Liu, Ming-Qiu; Lai, Bai-Tang

2007-01-01

The development of effective chemopreventive agents against cigarette smoke-induced lung cancer could be greatly facilitated by suitable laboratory animal models, such as animals treated with the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In the current study, we established a novel lung cancer model in Wistar rats treated with NNK. Using this model, we assessed the effects of two chemopreventive agents, aspirin and phenethyl isothiocyanate (PEITC), on tumor progression. First, rats were treated with a single-dose of NNK by intratracheal instillation; control rats received iodized oil. The animals were then sacrificed on the indicated day after drug administration and examined for tumors in the target organs. PCNA, p63 and COX-2 expression were analyzed in the preneoplastic lung lesions. Second, rats were treated with a single-dose of NNK (25 mg/kg body weight) in the absence or presence of aspirin and/or PEITC in the daily diet. The control group received only the vehicle in the regular diet. The animals were sacrificed on day 91 after bronchial instillation of NNK. Lungs were collected and processed for histopathological and immunohistochemical assays. NNK induced preneoplastic lesions in lungs, including 33.3% alveolar hyperplasia and 55.6% alveolar atypical dysplasia. COX-2 expression increased similarly in alveolar hyperplasia and alveolar atypical dysplasia, while PCNA expression increased more significantly in the latter than the former. No p63 expression was detected in the preneoplastic lesions. In the second study, the incidences of alveolar atypical dysplasia were reduced to 10%, 10% and 0%, respectively, in the aspirin, PEITC and aspirin and PEITC groups, compared with 62.5% in the carcinogen-treated control group. COX-2 expression decreased after dietary aspirin or aspirin and PEITC treatment. PCNA expression was significantly reduced in the aspirin and PEITC group. (1) A single dose of 25 mg/kg body weight

Effect of Prior Aspirin Treatment on Patients With Acute Coronary Syndromes: Insights From the PROSPECT Study.

Science.gov (United States)

Brener, Sorin J; Maehara, Akiko; Mintz, Gary S; Weisz, Giora; de Bruyne, Bernard; Serruys, Patrick W; Stone, Gregg W

2015-12-01

Prior aspirin treatment is considered a risk factor for adverse outcomes in acute coronary syndrome (ACS) patients. The relationships between aspirin pretreatment and findings on quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS), as well as clinical outcomes, are not well understood. In the PROSPECT trial, QCA and triple-vessel IVUS imaging were performed after successful percutaneous coronary intervention (PCI) of the culprit lesion(s) in ACS patients. We compared patients receiving aspirin within 7 days of enrollment to those naive to aspirin. Propensity score matching was performed to adjust for differences in baseline characteristics. Aspirin-pretreated patients (n = 236; 35%) were older and more likely to have known coronary disease than those without pretreatment (P≤.01 for all). Pretreated patients had more untreated non-culprit lesions with angiographic and IVUS characteristics predictive of future events (53.1% vs 38.6%; PPROSPECT trial, aspirin pretreatment identifies an older population with more advanced coronary disease. Aspirin pretreatment was not an independent predictor of MACE in ACS patients treated with an early invasive strategy. The extent to which aspirin pretreatment is a risk factor for adverse events after PCI in ACS should be revisited.

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.

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

International Nuclear Information System (INIS)

Li, Xiaofei; Zhu, Yanshuang; He, Huabin; Lou, Lianqing; Ye, Weiwei; Chen, Yongxin; Wang, Jinghe

2013-01-01

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

Monosialotetrahexosylganglioside Inhibits the Expression of p-CREB and NR2B in the Auditory Cortex in Rats with Salicylate-Induced Tinnitus.

Science.gov (United States)

Song, Rui-Biao; Lou, Wei-Hua

2015-01-01

This study investigated the effects of monosialotetrahexosylganglioside (GM1) on the expression of N-methyl-D-aspartate receptor subunit 2B (NR2B) and phosphorylated (p)-cyclic AMP response element-binding protein (CREB) in the auditory cortex of rats with tinnitus. Tinnitus-like behavior in rats was tested with the gap prepulse inhibition of acoustic startle paradigm. We then investigated the NR2B mRNA and protein and p-CREB protein levels in the auditory cortex of tinnitus rats compared with normal rats. Rats treated for 4 days with salicylate exhibited tinnitus. NR2B mRNA and protein and p-CREB protein levels were upregulated in these animals, with expression returning to normal levels 14 days after cessation of treatment; baseline levels of NR2B and p-CREB were also restored by GM1 administration. These data suggest that chronic salicylate administration induces tinnitus via upregulation of p-CREB and NR2B expression, and that GM1 can potentially be used to treat tinnitus.

Aspirin degradation in surface-charged TEMPO-oxidized mesoporous crystalline nanocellulose.

Science.gov (United States)

Carlsson, Daniel O; Hua, Kai; Forsgren, Johan; Mihranyan, Albert

2014-01-30

TEMPO-mediated surface oxidation of mesoporous highly crystalline Cladophora cellulose was used to introduce negative surface charges onto cellulose nanofibrils without significantly altering other structural characteristics. This enabled the investigation of the influence of mesoporous nanocellulose surface charges on aspirin chemical stability to be conducted. The negative surface charges (carboxylate content 0.44±0.01 mmol/g) introduced on the mesoporous crystalline nanocellulose significantly accelerated aspirin degradation, compared to the starting material which had significantly less surface charge (0.06±0.01 mmol/g). This effect followed from an increased aspirin amorphisation ability in mesopores of the oxidized nanocellulose. These results highlight the importance of surface charges in formulating nanocellulose for drug delivery. Copyright © 2013 Elsevier B.V. All rights reserved.

Transport of salicylate in proximal tubule (S2 segment) isolated from rabbit kidney

International Nuclear Information System (INIS)

Schild, L.; Roch-Ramel, F.

1988-01-01

The secretory and the reabsorptive transport of salicylate was studied in the isolated and perfused rabbit proximal tubule (S 2 segment). Salicylate secretion (J sal b→l ) fulfilled the criteria for a carrier-mediated transport system: J sal b→l was saturable, was reversibly inhibited by probenecid, and occurred against a concentration gradient. The K m and V max for this secretory transport were 80 μM and 3,200 fmol·min -1 ·mm -1 , respectively. At luminal pH of 7.4 and 6.6, salicylate reabsorption (J sal l→b ) was low. J sal l→b was stimulated by increasing the bath Pco 2 or by removing basolateral HCO 3 - ; J sal l→b was inhibited by ethoxyzolamide and by SITS in the bath. The results indicate that salicylate reabsorption depends on H + secretion, consistent with reabsorption by simple nonionic diffusion. When salicylate was present in the lumen only, J sal l→b increased after inhibition of the secretory transport by adding ouabain or probenecid in the bath or by lowering the bath temperature. These results are compatible with luminal recycling of salicylate, and suggest the presence of a mediated secretory transporter located at the luminal membrane

Effect of addition of clopidogrel to aspirin on subdural hematoma: meta-analysis of randomized clinical trials.

Science.gov (United States)

Bakheet, Majid F; Pearce, Lesly A; Hart, Robert G

2015-06-01

Clopidogrel combined with aspirin is routinely prescribed after coronary artery stenting, in patients with acute coronary syndromes, and recently to prevent stroke in patients with acute minor ischemic stroke and TIA. Subdural hematomas are an important complication of antithrombotic treatment, but the risk associated with clopidogrel plus aspirin has not been previously defined. To quantify the risk of subdural hematoma associated with dual antiplatelet therapy with clopidogrel plus aspirin. Randomized clinical trials comparing clopidogrel plus aspirin with aspirin alone were identified by searching the Cochrane Central Register of Controlled Trials from 1990 to 2014, and restricted to those with more than 7 days of treatment. Two reviewers independently extracted data about subdural hematomas. Of 24 randomized trials testing clopidogrel added to aspirin, results for subdural hematoma were available for 11 trials, of which eight did not identify any subdural hematomas. The three trials reporting subdural hematomas were double-blind and included patients with recent lacunar stroke, acute coronary syndromes or atrial fibrillation with a total of 23,136 patients (mean age 66 years) and reported 39 subdural hematomas during a mean follow-up 2.1 years per patient. Clopidogrel plus aspirin was associated with a significantly increased risk of subdural hematoma compared with aspirin alone (risk ratio 2.0, 95% CI 1.0, 3.8; P = 0.04; fixed effects model; I2 for heterogeneity of 0%, P = 0.51). The average absolute incidence of subdural hematoma averaged 1.1 (95% CI 0.7,1.6) per 1000 patient - years among those assigned clopidogrel plus aspirin in 11 randomized trials. The absolute rate of subdural hematoma during dual antiplatelet therapy is low, averaging 1.1 per 1000 patient-years. Chronic treatment with clopidogrel plus aspirin significantly increases the risk of subdural hematoma compared with aspirin alone. © 2014 World Stroke Organization.

Effect of salicylic acid on the growth photosynthesis and carbohydrate metabolism in salt stressed maize plants

International Nuclear Information System (INIS)

Moussa, H.R.; Khodary, S.E.A.

2003-01-01

Aqueous solutions of salicylic acid as a spray to Na CI-treated corn (Zea mays L,) significantly increased the growth of shoots and roots as measured after seven days of treatment. Spraying of salicylic acid caused significant increases in the activity of both ribulose 1,5 bisphosphate carboxylase (rubisco) enzyme and photosynthetic pigments. Moreover, salicylic acid treatment induced high values of soluble carbohydrate fractions in salt stressed plants as compared with salicylic acid treated samples. These data suggest that salicylic acid might improve the growth pattern of NaCl-treated maize plants via increasing the rate of photosynthesis and carbohydrate metabolism

Effects of Ramadan fasting on aspirin resistance in type 2 diabetic patients.

Science.gov (United States)

Bouida, Wahid; Beltaief, Kaouthar; Baccouche, Houda; Sassi, Mouna; Dridi, Zohra; Trabelsi, Imen; Laaouiti, Kamel; Chakroun, Taher; Hellara, Ilhem; Boukef, Riadh; Sakly, Nabil; Hassine, Mohsen; Added, Faouzi; Razgallah, Rabie; Najjar, Fadhel; Nouira, Semir

2018-01-01

Ramadan fasting (RF) may affect aspirin resistance. We conducted this study in patients with cardiovascular risk (CVR) factors to assess the effect of RF on aspirin resistance and explore whether type 2 diabetes mellitus (DM) would influence this effect. A total of 177 stable patients with ≥2 CVR factors were recruited. All patients observed RF and were taking aspirin. Physical exam and standard biological tests including glycaemia and serum lipids data were performed before Ramadan (Pre-R), at the last week of Ramadan (R) and four weeks after the end of Ramadan (Post-R). In the same visits caloric intake was calculated and platelet reactivity to aspirin was assessed using Verify Now point-of-care assay. In the overall population, there was no significant change in absolute aspirin reaction unit (ARU) values and in metabolic parameters. In DM patients (n = 127), ARU change from Pre-R values was+19.7 (p = 0.01) and +14.4 (p = 0.02) respectively at R and Post-R. During Ramadan, glycaemia, triglycerides, and cholesterol levels increased significantly and returned to Pre-R values thereafter. These changes were not observed in non-DM patients. During RF aspirin resistance increased only in DM patients. This effect persisted one month after Ramadan. Simultaneous alteration of glycemic control and increase of serum lipids levels could potentially be a favorable factor. The protocol was registered at clinicaltrials.gov under: NCT02720133.

Effects of Ramadan fasting on aspirin resistance in type 2 diabetic patients

Science.gov (United States)

Bouida, Wahid; Beltaief, Kaouthar; Baccouche, Houda; Sassi, Mouna; Dridi, Zohra; Trabelsi, Imen; Laaouiti, Kamel; Chakroun, Taher; Hellara, Ilhem; Boukef, Riadh; Sakly, Nabil; Hassine, Mohsen; Added, Faouzi; Razgallah, Rabie; Najjar, Fadhel; Nouira, Semir

2018-01-01

Aims Ramadan fasting (RF) may affect aspirin resistance. We conducted this study in patients with cardiovascular risk (CVR) factors to assess the effect of RF on aspirin resistance and explore whether type 2 diabetes mellitus (DM) would influence this effect. Methods A total of 177 stable patients with ≥2 CVR factors were recruited. All patients observed RF and were taking aspirin. Physical exam and standard biological tests including glycaemia and serum lipids data were performed before Ramadan (Pre-R), at the last week of Ramadan (R) and four weeks after the end of Ramadan (Post-R). In the same visits caloric intake was calculated and platelet reactivity to aspirin was assessed using Verify Now point-of-care assay. Results In the overall population, there was no significant change in absolute aspirin reaction unit (ARU) values and in metabolic parameters. In DM patients (n = 127), ARU change from Pre-R values was+19.7 (p = 0.01) and +14.4 (p = 0.02) respectively at R and Post-R. During Ramadan, glycaemia, triglycerides, and cholesterol levels increased significantly and returned to Pre-R values thereafter. These changes were not observed in non-DM patients. Conclusions During RF aspirin resistance increased only in DM patients. This effect persisted one month after Ramadan. Simultaneous alteration of glycemic control and increase of serum lipids levels could potentially be a favorable factor. Study registration The protocol was registered at clinicaltrials.gov under: NCT02720133. PMID:29529091

RESPONSE OF SPECKLED SPUR-FLOWER TO SALINITY STRESS AND SALICYLIC ACID TREATMENT

Directory of Open Access Journals (Sweden)

Piotr Salachna

2015-11-01

Full Text Available One of the limitations to using ornamental plants in green areas is too high salinity and alkalization of the soil. The adverse effect of salinity on plant growth and development may be effectively reduced by application of salicylic acid. Plectranthus ciliatus is an attractive bed plant with ornamental leaves, recommended for growing in containers, hanging baskets, or sunny borders. The aim of this study was to investigate the response of P. ciliatus to salicylic acid and calcium chloride. The plants were grown in pots in a glasshouse and were sprayed with solution of 0.5 mM salicylic acid and watered with 200 mM calcium chloride. The application of salicylic acid resulted in an increased weight of the aboveground parts, higher stomatal conductance and leaf greenness index and enhanced leaf content of nitrogen, potassium, iron and zinc. Salinity-exposed plants were characterized by reduced weight, stomatal conductance and leaf greenness index. Salt stress caused also a drop in leaf content of nitrogen, potassium and iron, and an increase in calcium, sodium, chlorine, copper and manganese concentration. Salicylic acid seemed to relieve salinity-mediated plant stress.

Continuous Aspirin Use Does Not Increase Bleeding Risk of Split-Thickness Skin Transplantation Repair to Chronic Wounds.

Science.gov (United States)

Sun, Yanwei; Wang, Yibing; Li, Liang; Zhang, Zheng; Wang, Ning; Wu, Dan

Discontinuation of aspirin therapy before cutaneous surgery may cause serious complications. The aim of this prospective study was to evaluate the bleeding risk of split-thickness skin transplantation repair to chronic wounds in patients on aspirin therapy. A total of 97 patients who underwent split-thickness skin transplantation surgery of chronic wounds during a 2-year period were enrolled. They were categorized on the basis of aspirin therapies. The primary outcome was postoperative bleeding and bleeding complications. Univariate analysis was performed to examine the association between aspirin and bleeding complications. Among the 26 patients taking aspirin continuously in group A, there were 5 bleeding complications (19.23%). Among the 55 nonusers in group B, there were 10 bleeding complications (18.18%). Among the 16 discontinuous patients in group C, there were 3 bleeding complications (18.75%). No statistical differences were found among the groups ( P = .956). Univariate analysis showed that continuous aspirin use was not significantly associated with bleeding complications (odds ratio, 0.933; 95% confidence interval, 0.283-3.074; P = .910 in the aspirin and control groups) and that discontinuous aspirin use was not significantly associated with bleeding complications (odds ratio, 0.963; 95% confidence interval, 0.230-4.025; P = .959 in the aspirin and control groups; odds ratio, 0.969; 95% confidence interval, 0.198-4.752; P = .969 in the aspirin and discontinuous groups). Continuous aspirin use does not produce an additional bleeding risk in patients who undergo split-thickness skin transplantation repair of chronic wounds.

Chemotherapeutic potential of diazeniumdiolate-based aspirin prodrugs in breast cancer.

Science.gov (United States)

Basudhar, Debashree; Cheng, Robert C; Bharadwaj, Gaurav; Ridnour, Lisa A; Wink, David A; Miranda, Katrina M

2015-06-01

Diazeniumdiolate-based aspirin prodrugs have previously been shown to retain the anti-inflammatory properties of aspirin while protecting against the common side effect of stomach ulceration. Initial analysis of two new prodrugs of aspirin that also release either nitroxyl (HNO) or nitric oxide (NO) demonstrated increased cytotoxicity toward human lung carcinoma cells compared to either aspirin or the parent nitrogen oxide donor. In addition, cytotoxicity was significantly lower in endothelial cells, suggesting cancer-specific sensitivity. To assess the chemotherapeutic potential of these new prodrugs in treatment of breast cancer, we studied their effect both in cultured cells and in a nude mouse model. Both prodrugs reduced growth of breast adenocarcinoma cells more effectively than the parent compounds while not being appreciably cytotoxic in a related nontumorigenic cell line (MCF-10A). The HNO donor also was more cytotoxic than the related NO donor. The basis for the observed specificity was investigated in terms of impact on metabolism, DNA damage and repair, apoptosis, angiogenesis and metastasis. The results suggest a significant pharmacological potential for treatment of breast cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Browse Title Index

African Journals Online (AJOL)

Items 1 - 50 of 140 ... ... the gut of household cockroaches in and around University Of Ibadan, Abstract ... disinfectant formulations against clinical isolates of Staphyloccocus ... of aspirin and salicylic acid in healthy human volunteers, Abstract.

Reprint of: Aspirin use and early age-related macular degeneration: a meta-analysis.

Science.gov (United States)

Kahawita, Shyalle K; Casson, Robert J

2015-06-01

The aim of this review was to evaluate the evidence for an association between Aspirin use and early age-related macular degeneration (ARMD). A literature search was performed in 5 databases with no restrictions on language or date of publication. Four studies involving 10292 individuals examining the association between aspirin and ARMD met the inclusion criteria. Meta-analysis was carried out by Cochrane Collaboration Review Manager 5.2 software (Cochrane Collaboration, Copenhagen, Denmark). The pooled odd ratios showed that Aspirin use was associated with early ARMD (pooled odds ratio 1.43, 95% CI 1.09-1.88). There is a small but statistically significant association between Aspirin use and early ARMD, which may warrant further investigation. Copyright © 2015. Published by Elsevier Inc.

Thermodynamics of cosolvent action: phenacetin, salicylic acid and probenecid.

Science.gov (United States)

Peña, M A; Escalera, B; Reíllo, A; Sánchez, A B; Bustamante, P

2009-03-01

The solubility of phenacetin, salicylic acid, and probenecid in ethanol-water and ethanol-ethyl acetate mixtures at several temperatures (15-40 degrees C) was measured. The solubility profiles are related to medium polarity changes. The apparent thermodynamic magnitudes and enthalpy-entropy relationships are related to the cosolvent action. Salicylic acid and probenecid show a single peak against the solubility parameter delta(1) of both solvent mixtures, at 40% (delta(1) = 21.70 MPa(1/2)) and 30% (delta(1) = 20.91 MPa(1/2)) ethanol in ethyl acetate, respectively. Phenacetin displays two peaks at 60% ethanol in ethyl acetate (23.30 MPa(1/2)) and 90% ethanol in water (delta(1) = 28.64 MPa(1/2)). The apparent enthalpies of solution display a maximum at 30% (phenacetin and salicylic acid) and 40% (probenecid) ethanol in water, respectively. Two different mechanisms, entropy at low ethanol ratios, and enthalpy at high ethanol ratios control the solubility enhancement in the aqueous mixture. In the nonaqueous mixture (ethanol-ethyl acetate) enthalpy is the driving force throughout the whole solvent composition for salicylic acid and phenacetin. For probenecid, the dominant mechanism shifts from entropy to enthalpy as the ethanol in ethyl acetate concentration increases. The enthalpy-entropy compensation plots corroborate the different mechanisms involved in the solubility enhancement by cosolvents. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

The Italian contributions to the history of salicylates

Directory of Open Access Journals (Sweden)

Giampiero Pasero

2011-09-01

Full Text Available It is well-known that the modern history of salicylates began in 1899 when the compound acetylsalicylic acid was registered and introduced commercially as “aspirin” by the Bayer Company of Germany. As a matter of fact, however, remedies made from willow bark had been used to treat fever and rheumatic complaints at least since 1763, when Edward Stone described their efficacy against malarian fever. A number of Italian scientists made significant contributions during the long period of research leading up to the synthesis of acetylsalicylic acid and its widespread use in rheumatic diseases. In this paper we will review the contributions of some of these researchers, beginning with Bartolomeo Rigatelli, who in 1824 used a willow bark extract as a therapeutic agent, denominating it “salino amarissimo antifebbrile” (very bitter antipyretic salt. In the same year, Francesco Fontana described this natural compound, giving it the name “salicina” (salicin. Two other Italian chemists added considerably to current knowledge of the salicylates: Raffaele Piria in 1838, while working as a research fellow in Paris, extracted the chemical compound salicylic acid, and Cesare Bertagnini in 1855 published a detailed description of the classic adverse event associated with salicylate overdoses – tinnitus – which he studied by deliberately ingesting excessive doses himself. Bertagnini and above all Piria also played conspicuous roles in the history of Italy during the period of the Italian Risorgimento, participating as volunteers in the crucial battle of Curtatone and Montanara during the first Italian War of Independence.

Role of mycorrhizal fungi and salicylic acid in salinity tolerance of ...

African Journals Online (AJOL)

Most researchers showed that inoculation of plants with mycorrhizal fungi and using salicylic acid increase tolerance of plants due to salinity. In this study, the effect of mycorrhizal fungi, including Glomus mosseae, Glomus intraradices, and salicylic acid (0.2 mM) on tolerance of green basil (Ocimum basilicum L.) to salinity ...

Chemical and Pharmacological Properties of Diflunisal.

Science.gov (United States)

Shen, T Y

1983-03-01

Diflunisal, 5-(2',4'-difluorophenyl) salicylic acid, was discovered as a potent antiinflammatory analgesic agent after an extensive investigation of more than 500 salicylic acid analogs. The addition of a difluorophenyl substituent at the C 5 position of salicylic acid yielded a new molecule with much improved lipophilicity, a longer duration of action, and a molecular configuration that is optimal for greater antiinflammatory and analgesic activities. The difluorophenyl group is metabolically stable; the acyl and phenolic glucuronides of the intact diflunisal are major urinary metabolites. The absence of an O-acetyl group in this novel salicylate analog circumvents the well-known in vivo acylation potential of aspirin and renders diflunisal a reversible cyclooxygenase inhibitor with a secondary oxygen radical scavenging effect. In a variety of analgesic, acute, and chronic antiinflammatory models, diflunisal is active at 10 mg/kg, approximately 5 to 10 times more potent than aspirin. It has a relatively low potential to cause gastrointestinal irritation as indicated by the lack of acute effect on the integrity of gastric mucosal barrier, no change of intragastric potential, and no disturbance of prostaglandin production by the gastric tissue. Diflunisal holds promise as a new clinically useful analgesic and antiinflammatory drug with good tolerance and a long duration of action. 1983 Pharmacotherapy Publications Inc.

Low-dose aspirin, non-steroidal anti-inflammatory drugs, selective COX-2 inhibitors and breast cancer recurrence

DEFF Research Database (Denmark)

Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P

2016-01-01

BACKGROUND: Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and selective COX-2 inhibitors may improve outcomes in breast cancer patients. We investigated the association of aspirin, NSAIDs, and use of selective COX-2 inhibitors with breast cancer recurrence. METHODS: We identified incident...... stage I-III Danish breast cancer patients in the Danish Breast Cancer Cooperative Group registry, who were diagnosed during 1996-2008. Prescriptions for aspirin (>99% low-dose aspirin), NSAIDs, and selective COX-2 inhibitors were ascertained from the National Prescription Registry. Follow-up began....... RESULTS: We identified 34,188 breast cancer patients with 233,130 person-years of follow-up. Median follow-up was 7.1 years; 5,325 patients developed recurrent disease. Use of aspirin, NSAIDs, or selective COX-2 inhibitors was not associated with the rate of recurrence (HRadjusted aspirin = 1.0, 95% CI...

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 PFA-100 method and optical platelet aggregation was found. Within...

Stability testing of extemporaneous preparation of methyl salicylate ointment

Directory of Open Access Journals (Sweden)

H A Makeen

2018-01-01

Results: The shelf life (t90% of extemporaneously prepared methyl salicylate ointment was found to be 131 days at room temperature (25°C ± 5°C and 176 days in the refrigerator (2°C–8°C. Conclusion: The methyl salicylate present in extemporaneous ointment preparation is fairly stable at cool temperatures but shows faster degradation at higher temperature conditions. Therefore, it is recommended that an expiry date of 4 months can be safely mentioned when stored in cool.

A prospective study of aspirin use and the risk of gastrointestinal bleeding in men.

Directory of Open Access Journals (Sweden)

Edward S Huang

2010-12-01

Full Text Available Data regarding the influence of dose and duration of aspirin use on risk of gastrointestinal bleeding are conflicting.We conducted a prospective cohort study of 32,989 men enrolled in the Health Professionals Follow-up Study (HPFS in 1994 who provided biennial aspirin data. We estimated relative risk of major gastrointestinal bleeding requiring hospitalization or a blood transfusion.During 14 years of follow-up, 707 men reported an episode of major gastrointestinal bleeding over 377,231 person-years. After adjusting for risk factors, regular aspirin use (≥2 times/week had a multivariate relative risk (RR of gastrointestinal bleeding of 1.32 (95% confidence interval [CI], 1.12-1.55 compared to non-regular use. The association was particularly evident for upper gastrointestinal bleeding (multivariate RR, 1.49; 95% CI, 1.16-1.92. Compared to men who denied any aspirin use, multivariate RRs of upper gastrointestinal bleeding were 1.05 (95% CI 0.71-1.52 for men who used 0.5-1.5 standard tablets/week, 1.31 (95% CI 0.88-1.95 for 2-5 aspirin/week, 1.63 (95% CI, 1.15-2.32 for 6-14 aspirin/week and 2.40 (95% CI, 1.10-5.22 for >14 aspirin/week (P(trend<0.001. The relative risk also appeared to be dose-dependent among short-term users <5 years; P(trend<.001 and long-term users (≥5 years; P(trend = 0.015. In contrast, after controlling for dose, increasing duration of use did not appear to be associated with risk (P(trend = 0.749.Regular aspirin use increases the risk of gastrointestinal bleeding, especially from the upper tract. However, risk of bleeding appears to be more strongly related to dose than to duration of use. Risk of bleeding should be minimized by using the lowest effective dose among short-term and long-term aspirin users.

Aspirin mono-therapy continuation does not result in more bleeding after knee arthroplasty.

Science.gov (United States)

Schwab, Pierre-Emmanuel; Lavand'homme, Patricia; Yombi, JeanCyr; Thienpont, Emmanuel

2017-08-01

Current clinical practice guidelines sometimes still recommend stopping aspirin five to seven days before knee arthroplasty surgery. Literature regarding multimodal blood management and continuation of anti-platelet therapy in this type of surgery is scant. The study hypothesis was that knee arthroplasty under low-dose aspirin mono-therapy continuation does not cause more total blood loss than knee arthroplasty performed without aspirin. Blood loss would be measured by haemoglobin (Hb) and haematocrit (HTC) levels drop at day 2 or day 4 for patients who benefit from multimodal bleeding control measures. A database of all patients undergoing knee arthroplasty between 2006 and 2014 was analysed. Demographic, surgical and complete blood workup data were collected. A retrospective comparison study analysed both groups in terms of blood loss, by mean calculated blood loss as haemoglobin or haematocrit drop between the preoperative Nadir value and the postoperative day 2 and 4 value. A group of 198 (44 UKA and 154 TKA) patients underwent surgery without interrupting their aspirin therapy for cardiovascular prevention. Mean (SD) age was 71 (8) and the mean (SD) BMI was 29 (5.5) kg/m 2 . The control group consisted of 403 (102 UKA and 301 TKA) patients who were not under aspirin, or any other anti-platelet agent. Mean (SD) age was 65 (10) (p aspirin mono-therapy for cardiovascular prevention. III.

Superficial chemical peeling with salicylic acid in facial dermatoses

International Nuclear Information System (INIS)

Bari, A.U.; Iqbal, Z.; Rahman, S.B.

2007-01-01

To determine the effectiveness of salicylic acid chemical peeling in common dermatological conditions affecting face in people with predominant Fitzpatrick skin type IV and V. A total of 167 patients of either gender, aged between 13 to 60 years, having some facial dermatoses (melasma, acne vulgaris, postinflammatory hyperpigmentations, freckles, fine lines and wrinkles, post-inflammatory scars, actinic keratoses, and plane facial warts) were included. A series of eight weekly hospital based peeling sessions was conducted in all patients under standardized conditions with 30% salicylic acid. Clinical improvement in different disorders was evaluated by change in MASI score, decrease in the size of affected area and % reduction in lesions count. McNemar test was applied for data analysis. Majority of the patients showed moderate to excellent response. There was 35% to 63% improvement (p< 0.05) in all dermatoses. Significant side effects, as feared in Asian skins were not observed. Chemical peeling with salicylic acid is an effective and safe treatment modality in many superficial facial dermatoses. (author)

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.

Synthesis and characterization of a glycerol salicylate resin for bioactive root canal sealers.

Science.gov (United States)

Portella, F F; Santos, P D; Lima, G B; Leitune, V C B; Petzhold, C L; Collares, F M; Samuel, S M W

2014-04-01

To develop and characterize a salicylate resin with potential use in bioactive endodontic sealers. Methyl salicylate, glycerol and titanium isopropoxide were added in a closed system for the transesterification reaction. The resin obtained was characterized by proton nuclear magnetic resonance spectroscopy (1H NMR) and size exclusion chromatography (SEC). To verify the applicability of the resin to the development of endodontic sealers, experimental cements were prepared by mixing glycerol salicylate resin, calcium hydroxide and methyl salicylate in the ratios of 2 : 1 : 1, 1 : 2 : 1, 1 : 1 : 2, 1 : 1 : 1, 4 : 1 : 1, 1 : 4 : 1 and 1 : 1 : 4. Setting times were measured according to ISO 6876. Features of the hardening reaction were described by micro-RAMAN spectroscopy. The transesterification reaction had a 72% efficiency. The (1) H NMR analysis revealed the presence of the expected functional groups (hydroxyls and aromatic rings), and the SEC confirmed the molar mass of the resin produced. The setting times of experimental sealers ranged from 70 min (ratio 1 : 1 : 1) to 490 min (ratio 1 : 1 : 4). The conversion of the salicylic groups (1 613 cm(-1) ) to salicylate salt (1 543 cm(-1) ) and the reduction in calcium hydroxide peaks (1084 and 682 cm(-1) ) were confirmed by micro-RAMAN spectroscopy, which showed the calcium chelation by the resin. The new glycerol salicylate resin was successfully synthesized and revealed a potential application in the development of endodontic sealers. © 2013 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Is clopidogrel superior to aspirin in secondary prevention of vascular disease?

Directory of Open Access Journals (Sweden)

Algra Ale

2000-11-01

Full Text Available Abstract The cornerstone in clinical evidence of the relative efficacy of thienopyridines (clopidogrel, ticlopidine versus aspirin in the secondary prevention of vascular disease is the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events trial. This trial showed a modest benefit in the reduction of vascular events by clopidogrel. The results differed according to qualifying disorder: myocardial infarction, -3.7%; ischaemic stroke, +7.3%; and peripheral arterial disease, +23.8% (P = 0.042. Similar results were found for ticlopidine after brain ischaemia. The safety of clopidogrel appears to be similar to that of aspirin and better than that of ticlopidine. However, the recent report of thrombotic thrombocytopenic purpura in association with clopidogrel causes concern.

Effects of Low-Dose Aspirin and Fish Oil on Platelet Function and NF-kappaB in Adults with Diabetes Mellitus

Science.gov (United States)

Block, Robert C; Abdolahi, Amir; Smith, Brian; Meednu, N; Thevenet-Morrison, Kelly; Cai, Xueya; Cui, Huadong; Mousa, Shaker; Brenna, J. Thomas; Georas, S

2013-01-01

SUMMARY Introduction Many diabetics are insensitive to aspirin’s platelet anti-aggregation effects. The possible modulating effects of coadministration of aspirin and fish oil in subjects with diabetes are poorly characterized. Participants and Methods Thirty adults with type 2 diabetes mellitus were treated with aspirin 81 mg/d for 7 days, then with fish oil 4g/day for 28 days, then the combination of fish oil and aspirin for another 7 days. Results Aspirin alone and in combination with fish oil reduced platelet aggregation in most participants. Five of 7 participants classified as aspirin insensitive 1 week after daily aspirin ingestion were sensitive after the combination. Although some platelet aggregation measures correlated positively after aspirin and fish oil ingestion alone and (in combination) in all individuals, correlation was only observed in those who were aspirin insensitive after ingestion of the combination. Conclusions Co-adminstration of aspirin and fish oil may reduce platelet aggregation more than aspirin alone in adults with diabetes mellitus. PMID:23664596

Aspirin and the Primary Prevention of Cardiovascular Diseases: An Approach Based on Individualized, Integrated Estimation of Risk.

Science.gov (United States)

Volpe, Massimo; Battistoni, Allegra; Gallo, Giovanna; Coluccia, Roberta; De Caterina, Raffaele

2017-09-01

While the use of aspirin in the secondary prevention of cardiovascular (CVD) is well established, aspirin in primary prevention is not systematically recommended because the absolute CV event reduction is similar to the absolute excess in major bleedings. Recently, emerging evidence suggests the possibility that the assumption of aspirin, may also be effective in the prevention of cancer. By adding to the CV prevention benefits the potential beneficial effect of aspirin in reducing the incidence of mortality and cancer could tip the balance between risks and benefits of aspirin therapy in the primary prevention in favour of the latter and broaden the indication for treatment with in populations at average risk. While prospective and randomized study are currently investigating the effect of aspirin in prevention of both cancer and CVD, clinical efforts at the individual level to promote the use of aspirin in global (or total) primary prevention could be already based on a balanced evaluation of the benefit/risk ratio.

Mathematical modeling of complexing in the scandium-salicylic acid-isoamyl alcohol system

International Nuclear Information System (INIS)

Evseev, A.M.; Smirnova, N.S.; Fadeeva, V.I.; Tikhomirova, T.I.; Kir'yanov, Yu.A.

1984-01-01

Mathematical modeling of an equilibrium multicomponent physicochemical system for extraction of Sc salicylate complexes by isoamyl alcohol was conducted. To calculate the equilibrium concentrations of Sc complexes different with respect to the content and composition, the system of nonlinear algebraic mass balance equations was solved. Experimental data on the extraction of Sc salicylates by isoamyl alcohol versus the pH of the solution at a constant Sc concentration and different concentration of salicylate-ions were used for construction of the mathematical model. The stability constants of ScHSal 2+ , Sc(HSal) 3 , ScOH(HSal) 2 , ScoH(HSal) 2 complexes were calculated

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.

Salicylic acid-independent plant defence pathways

NARCIS (Netherlands)

Pieterse, C.M.J.; Loon, L.C. van

1999-01-01

Salicylic acid is an important signalling molecule involved in both locally and systemically induced disease resistance responses. Recent advances in our understanding of plant defence signalling have revealed that plants employ a network of signal transduction pathways, some of which are

Comparison of aspirin renogram and captopril renogram in the diagnosis of renovascular hypertension

International Nuclear Information System (INIS)

Dabiri Oskoie, S.; Argani, H.

2002-01-01

Renal artery stenosis is the most common cause of secondary hypertension. Preliminary data indicate that aspirin renography with hippurate may be more sensitive for detection renal artery stenosis. In this study 20 patients with known or suspected renal artery stenosis underwent aspirin renography (20 mg/kg orally 1 hour before injection of radiotracer) and captopril renography (50 mg orally) with 99 Tc-DTPA. Renal angiography was performed in all patients. Of the 20 patients enrolled, 11 had unilateral renal artery stenosis on angiography. Captopril renography was positive in 10 patients (915 sensitivity and 90% specificity). Aspirin renogram showed 9 patients with renal artery stenosis correctly (81.85 sensitivity and 100% specificity). Our data suggest that aspirin renography with 99 Tc-DTPA has comparable sensitivity with captopril in detection of unilateral renal artery stenosis

Microautoradiography of /sup 14/C-salicylic acid in the skin of guinea-pig

Energy Technology Data Exchange (ETDEWEB)

Washitake, M; Ozawa, Y; Anmo, T; Tanaka, I [Taisho Pharmaceutical Co. Ltd., Tokyo (Japan). Research Lab.

1974-07-01

The concentration of salicylic acid in guinea-pig skin was examined by microautoradiography. The retention of salicylic acid in the stratum corneum was observed. It was considered that the rate of transfer of the drug into the stratum corneum was small and that the stratum corneum became the barrier for permeability of the skin. The distribution of salicylic acid in other parts of the skin was uniform and no retention of the drug in any special parts was observed. The plasma level showed less percutaneous absorption of the drug when it was applied as liquid paraffin solution than when it was applied as an aqueous solution. The amount of salicylic acid absorbed from damaged skin was extremely large and, in this case, disappearance of the drug from the skin was fast.

Aspirin use and head and neck cancer survival: an observational study of 11,623 person-years follow-up.

Science.gov (United States)

Kim, Shin-Ae; Roh, Jong-Lyel; Kim, Sung-Bae; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

2018-02-01

Acetylsalicylic acid (aspirin) and non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risks for certain human cancers. However, the effects of aspirin and NSAIDs on head and neck squamous cell carcinoma (HNSCC) remain controversial, and the prognostic effects of these drugs in patients with HNSCC are largely unknown. This study examined the clinical impact of aspirin and NSAIDs on disease recurrence and survival in patients with HNSCC. This study analysed a cohort of 1392 consecutive patients who received definitive treatment for previously untreated HNSCC at our tertiary referral center. Aspirin or NSAID use was considered positive if the patients were receiving aspirin or NSAID medication from HNSCC diagnosis to at least 1 year after treatment initiation. Cox proportional hazard models were utilised to determine the association of aspirin and/or NSAID use with recurrence, survival, and second primary cancer occurrence. Of 1392 patients, 81 (5.8%) and 89 (6.4%) received post-diagnosis treatment with aspirin and NSAIDs, respectively. After controlling for clinical factors, aspirin and NSAIDs were not significantly associated with recurrence, survival, or second cancer occurrence (P > 0.05). The cumulative dose of aspirin or NSAIDs did not alter survival outcomes (P > 0.05). Our data illustrated that the use of aspirin or NSAIDs has no effect on survival or recurrence in patients with HNSCC.

Aspirin acetylates multiple cellular proteins in HCT-116 colon cancer cells: Identification of novel targets.

Science.gov (United States)

Marimuthu, Srinivasan; Chivukula, Raghavender S V; Alfonso, Lloyd F; Moridani, Majid; Hagen, Fred K; Bhat, G Jayarama

2011-11-01

Epidemiological and clinical observations provide consistent evidence that regular intake of aspirin may effectively inhibit the occurrence of epithelial tumors; however, the molecular mechanisms are not completely understood. In the present study, we determined the ability of aspirin to acetylate and post-translationally modify cellular proteins in HCT-116 human colon cancer cells to understand the potential mechanisms by which it may exerts anti-cancer effects. Using anti-acetyl lysine antibodies, here we demonstrate that aspirin causes the acetylation of multiple proteins whose molecular weight ranged from 20 to 200 kDa. The identity of these proteins was determined, using immuno-affinity purification, mass spectrometry and immuno-blotting. A total of 33 cellular proteins were potential targets of aspirin-mediated acetylation, while 16 were identified as common to both the control and aspirin-treated samples. These include enzymes of glycolytic pathway, cytoskeleton proteins, histones, ribosomal and mitochondrial proteins. The glycolytic enzymes which were identified include aldolase, glyceraldehyde-3-phosphate dehydrogenase, enolase, pyruvate kinase M2, and lactate dehydrogenase A and B chains. Immunoblotting experiment showed that aspirin also acetylated glucose-6-phosphate dehydrogenase and transketolase, both enzymes of pentose phosphate pathway involved in ribonucleotide biosynthesis. In vitro assays of these enzymes revealed that aspirin did not affect pyruvate kinase and lactate dehydrogenase activity; however, it decreased glucose 6 phosphate dehydrogenase activity. Similar results were also observed in HT-29 human colon cancer cells. Selective inhibition of glucose-6-phosphate dehydrogenase may represent an important mechanism by which aspirin may exert its anti-cancer effects through inhibition of ribonucleotide synthesis.

Fate of [14C] warfarin in guinea-pigs: effect of a concomitant single dose of salicylate

International Nuclear Information System (INIS)

Wong, L.T.; Solomonraj, G.; Thomas, B.H.

1978-01-01

When a single dose of sodium salicylate (177.8 mg kg -1 , by mouth) was given with [ 14 C] warfarin (1 mg kg -1 , i.p.) to guinea-pigs, the salicylate depressed the blood concentrations of 14 C for 6 h. At 1 h, salicylate increased the distribution of 14 C in the liver and brain, but at 1 and 6 h it was decreased in the blood and kidney. A significant portion of the 14 C was excreted into the bile, but was subject to enterohepatic circulation and then excreted by the kidney. There was an enhancement of the biliary elimination of 14 C in the first 5 h after salicylate and a decrease in 14 C concentration in blood; the proportion of warfarin to its metabolites excreted in the urine and bile was unchanged. Salicylate displaced serum protein bound [ 14 C] warfarin in vitro. Salicylate increases the initial biliary elimination of warfarin by displacing some of that bound to plasma protein. This facilitated uptake of warfarin by the liver where it was metabolized. This effect of salicylate did not modify the hypoprothrombinaemia produced by warfarin. (author)

Aspirin exposure reveals novel genes associated with platelet function and cardiovascular events.

Science.gov (United States)

Voora, Deepak; Cyr, Derek; Lucas, Joseph; Chi, Jen-Tsan; Dungan, Jennifer; McCaffrey, Timothy A; Katz, Richard; Newby, L Kristin; Kraus, William E; Becker, Richard C; Ortel, Thomas L; Ginsburg, Geoffrey S

2013-10-01

The aim of this study was to develop ribonucleic acid (RNA) profiles that could serve as novel biomarkers for the response to aspirin. Aspirin reduces death and myocardial infarction (MI), suggesting that aspirin interacts with biological pathways that may underlie these events. Aspirin was administered, followed by whole-blood RNA microarray profiling, in a discovery cohort of healthy volunteers (HV1) (n = 50) and 2 validation cohorts of healthy volunteers (HV2) (n = 53) and outpatient cardiology patients (OPC) (n = 25). Platelet function was assessed using the platelet function score (PFS) in HV1 and HV2 and the VerifyNow Aspirin Test (Accumetrics, Inc., San Diego, California) in OPC. Bayesian sparse factor analysis identified sets of coexpressed transcripts, which were examined for associations with PFS in HV1 and validated in HV2 and OPC. Proteomic analysis confirmed the association of validated transcripts in platelet proteins. Validated gene sets were tested for association with death or MI in 2 patient cohorts (n = 587 total) from RNA samples collected at cardiac catheterization. A set of 60 coexpressed genes named the "aspirin response signature" (ARS) was associated with PFS in HV1 (r = -0.31, p = 0.03), HV2 (r = -0.34, Bonferroni p = 0.03), and OPC (p = 0.046). Corresponding proteins for the 17 ARS genes were identified in the platelet proteome, of which 6 were associated with PFS. The ARS was associated with death or MI in both patient cohorts (odds ratio: 1.2 [p = 0.01]; hazard ratio: 1.5 [p = 0.001]), independent of cardiovascular risk factors. Compared with traditional risk factors, reclassification (net reclassification index = 31% to 37%, p ≤ 0.0002) was improved by including the ARS or 1 of its genes, ITGA2B. RNA profiles of platelet-specific genes are novel biomarkers for identifying patients who do not respond adequately to aspirin and who are at risk for death or MI. Copyright © 2013 American College of Cardiology Foundation. Published by

Dermal morphological changes following salicylic acid peeling and microdermabrasion.

Science.gov (United States)

Abdel-Motaleb, Amira A; Abu-Dief, Eman E; Hussein, Mahmoud Ra

2017-12-01

Microdermabrasion and chemical peeling are popular, inexpensive, and safe methods for treatment of some skin disorders and to rejuvenate skin. To study the alterations of the dermal connective tissue following salicylic acid peeling and microdermabrasion. Twenty patients were participated in our study. All participants underwent facial salicylic acid 30% peel or microdermabrasion (10 cases in each group) weekly for 6 weeks. Punch biopsies were obtained from the clinically normal skin of the right postauricular region 1 week before treatment (control group). Other punch skin biopsies were obtained 1 week after the end of the treatments from the left postauricular area. This region was treated in a similar way to the adjacent lesional skin (treated group). We used routine histological techniques (H&E stain), special stains (Masson trichrome and orcein stains), and image analyzer to study the alterations of the dermal connective tissues. Our study demonstrates variations in the morphological changes between the control and the treated groups, and between chemical peels and microdermabrasion. Both salicylic acid 30% and microdermabrasion were associated with thickened epidermal layer, shallow dermal papillae, dense collagen, and elastic fibers. There was a significant increase among those treated sites vs control regarding epidermal thickness and collagen thickness. Also, there was a highly statistically significant increase among those treated with salicylic acid vs microdermabrasion regarding the epidermal, collagen, and elastin thickness. Both methods stimulate the repair process. The mechanisms underlying these variations are open for further investigations. © 2017 Wiley Periodicals, Inc.

Aspirin suppresses the abnormal lipid metabolism in liver cancer cells via disrupting an NFκB-ACSL1 signaling

International Nuclear Information System (INIS)

Yang, Guang; Wang, Yuan; Feng, Jinyan; Liu, Yunxia; Wang, Tianjiao; Zhao, Man; Ye, Lihong; Zhang, Xiaodong

2017-01-01

Abnormal lipid metabolism is a hallmark of tumorigenesis. Hence, the alterations of metabolism enhance the development of hepatocellular carcinoma (HCC). Aspirin is able to inhibit the growth of cancers through targeting nuclear factor κB (NF-κB). However, the role of aspirin in disrupting abnormal lipid metabolism in HCC remains poorly understood. In this study, we report that aspirin can suppress the abnormal lipid metabolism of HCC cells through inhibiting acyl-CoA synthetase long-chain family member 1 (ACSL1), a lipid metabolism-related enzyme. Interestingly, oil red O staining showed that aspirin suppressed lipogenesis in HepG2 cells and Huh7 cells in a dose-dependent manner. In addition, aspirin attenuated the levels of triglyceride and cholesterol in the cells, respectively. Strikingly, we identified that aspirin was able to down-regulate ACSL1 at the levels of mRNA and protein. Moreover, we validated that aspirin decreased the nuclear levels of NF-κB in HepG2 cells. Mechanically, PDTC, an inhibitor of NF-κB, could down-regulate ACSL1 at the levels of mRNA and protein in the cells. Functionally, PDTC reduced the levels of lipid droplets, triglyceride and cholesterol in HepG2 cells. Thus, we conclude that aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling. Our finding provides new insights into the mechanism by which aspirin inhibits abnormal lipid metabolism of HCC. Therapeutically, aspirin is potentially available for HCC through controlling abnormal lipid metabolism. - Highlights: • Aspirin inhibits the levels of liquid droplets, triglyceride and cholesterol in HCC cells. • Aspirin is able to down-regulate ACSL1 in HCC cells. • NF-κB inhibitor PDTC can down-regulate ACSL1 and reduces lipogenesis in HCC cells. • Aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling.

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

International Nuclear Information System (INIS)

Sung, Jin Young; Choi, Hyoung Chul

2011-01-01

Highlights: → Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. → Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. → Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. → Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. → 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.

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.

Frequency and severity of reactions to a 325-mg aspirin dose during desensitization.

Science.gov (United States)

Schuler, Charles F; Baldwin, James L; Baptist, Alan P

2017-03-01

The frequency with which patients with aspirin-exacerbated respiratory disease (AERD) react to 325 mg of aspirin during aspirin desensitization, or fail to react at all, is not fully known. To determine the rate and type of reaction at 325 mg of aspirin during desensitization. A retrospective study of 104 patients who underwent aspirin desensitization from 2010 to 2016 was performed. A standard desensitization protocol (starting at 20-40 mg, progressing through 325 mg, and extinguishing reactions by dose repetition) was used. Reactions were defined by upper respiratory tract symptoms, lower respiratory tract symptoms, and/or forced expiratory volume in 1 second decrease of 15% or greater. Patients who did and did not react were compared by logistic regression. Eighty-four patients reacted (81%) and 20 did not (19%). Seventy-seven patients who had a provoking reaction at 162 mg of aspirin or less subsequently extinguished their reactions before they reached a dose of 325 mg and had no problems at that dose; one subsequent 325-mg reaction occurred during a protocol violation. One initial provoking reaction to 325 mg occurred. Both 325-mg reactions were mild, and neither met the forced expiratory volume in 1 second criterion for a clinically meaningful change. The remaining 5 patients could not complete the protocol because of persistent reactions or social reasons. Reactors were more likely to have had asthma for more than 10 years than nonreactors (odds ratio, 3.2; 95% confidence interval, 1.0-10.3; P = .05). During aspirin desensitization for AERD, provoking reactions at the 325-mg dose are rare (1%) and mild. Patients who react at 162 mg or less and extinguish their reactions may be able to administer the 325-mg dose at home. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Thiamin and Salicylic Acid as Biological Alternatives for Controlling Broad Bean Rot Disease

International Nuclear Information System (INIS)

AlHakimi, A.M.A; Alghalibi, Saeed M.S

2007-01-01

The interactive effects of fungi (Fusarium solani and Rhizoctonia solani) infection and thiamin or salicylic acid on growth rate, membrane stability, K+ efflux, UV-absorbing metabolites, photosynthetic pigments, cell wall components and lipid fractions of broad bean plants (30-day-old) were studied. Fungal infection induced a reduction in growth rate, membrane stability and content of photosynthetic pigments. Application of thiamin or salicylic acid increased growth rate, membrane stability and content of photosynthetic pigments. The K+ efflux and the leakage of UV-absorbing metabolites were stimulated with fungal infection. However, thiamin and salicylic acid treatment partially retarded the stimulatory effect on leakage of K+ and UV-absorbing metabolites of fungal infected plants. Fungal infection produced a reduction in the content of pectin and cellulose, total lipid, glycolipids and sterols fraction of shoots and roots and phospholipids of roots. On the other hand, the contents of hemicellulose and lignin of shoots and roots and phospholipids of shoots were stimulated by fungal infection. Soaking seeds in thiamin or salicylic acid counteracts partially or completely the adverse effect of fungal infection on pectin and cellulose composition, total lipid, glycolipids and sterols of either shoots or roots. On the other side, thiamin or salicylic acid treatments retarded the phospholipids accumulation in shoots of infected plants, and in roots the phospholipids accumulation was partially or completely alleviated. The content of hemicellulose and lignin of shoots and roots were antagonistically lowered by the application of thiamin or salicylic acid. (author)

Promising psyllium-based composite containing TiO2 nanoparticles as aspirin-carrier matrix

Directory of Open Access Journals (Sweden)

Marcela-Corina Rosu

2014-06-01

Full Text Available Composite nanomaterials represent a new trend in the biomedical field. Coupling inorganic/organic constituents with non-toxicity/biocompatibility properties leads to develop the new systems having special characteristics that can be used in various bio-applications. This paper describes the preparation and characterization of psyllium-based composites containing TiO2 nanoparticles in order to develop new therapeutic strategies for aspirin drug delivery. The structural characteristics of obtained materials were investigated by FTIR spectroscopy. The UV–vis spectrophotometric analysis was performed to evaluate the aspirin release behavior under different pH conditions at 37 °C. Combining psyllium (as an excellent source of fiber with TiO2 inorganic unit (as vehicle of aspirin it was found that polymeric-TiO2 networks have promising potential for controlled aspirin release as therapeutic agent.

Effects of salicylates and aminoglycosides on spontaneous otoacoustic emissions in the Tokay gecko.

Science.gov (United States)

Stewart, C E; Hudspeth, A J

2000-01-04

The high sensitivity and sharp frequency discrimination of hearing depend on mechanical amplification in the cochlea. To explore the basis of this active process, we examined the pharmacological sensitivity of spontaneous otoacoustic emissions (SOAEs) in a lizard, the Tokay gecko. In a quiet environment, each ear produced a complex but stable pattern of emissions. These SOAEs were reversibly modulated by drugs that affect mammalian otoacoustic emissions, the salicylates and the aminoglycoside antibiotics. The effect of a single i.p. injection of sodium salicylate depended on the initial power of the emissions: ears with strong control SOAEs displayed suppression at all frequencies, whereas those with weak control emissions showed enhancement. Repeated oral administration of acetylsalicylic acid reduced all emissions. Single i.p. doses of gentamicin or kanamycin suppressed SOAEs below 2.6 kHz, while modulating those above 2.6 kHz in either of two ways. For ears whose emission power at 2.6-5.2 kHz encompassed more than half of the total, individual emissions displayed facilitation as great as 35-fold. For the remaining ears, emissions dropped to as little as one-sixth of their initial values. The similarity of the responses of reptilian and mammalian cochleas to pharmacological intervention provides further evidence for a common mechanism of cochlear amplification.

Contemporary Reflections on the Safety of Long-Term Aspirin Treatment for the Secondary Prevention of Cardiovascular Disease

Science.gov (United States)

Fanaroff, Alexander C.; Roe, Matthew T.

2018-01-01

Aspirin has been the cornerstone of therapy for the secondary prevention treatment of patients with cardiovascular disease since landmark trials were completed in the late 1970s and early 1980s that demonstrated the efficacy of aspirin for reducing the risk of ischemic events. Notwithstanding the consistent benefits demonstrated with apirin for both acute and chronic cardiovascular disease, there are a number of toxicities associated with aspirin that have been showcased by recent long-term clinical trials that have included an aspirin monotherapy arm. As an inhibitor of cyclooxygenase, aspirin impairs gastric mucosal protective mechanisms. Prior trials have shown that up to 15–20% of patients developed gastrointestinal symptoms with aspirin monotherapy and roughly 1% of patients per year had a clinically significant bleeding event, including 1 in 1000 patients who suffered an intracranial or fatal bleed. These risks have been shown to be compounded for patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI), who are also treated with other anti-thrombotic agents during the acute care/procedural period, as well as for an extended time period afterwards. Given observations of substantial increases in bleeding rates from many prior long-term clinical trials that have evaluated aspirin together with other oral platelet inhibitors or oral anti-coagulants, the focus of contemporary research has pivoted towards tailored anti-thrombotic regimens that attempt to either shorten the duration of exposure to aspirin or replace aspirin with an alternative anti-thrombotic agent. While these shifts are occurring, the safety profile of aspirin when used for the secondary prevention treatment of patients with established cardiovascular disease deserves further consideration. PMID:27028617

Aspirin resistance may be identified by miR-92a in plasma combined with platelet distribution width

DEFF Research Database (Denmark)

Binderup, Helle Glud; Houlind, Kim; Madsen, Jonna Skov

2016-01-01

OBJECTIVE: Aspirin is a widely used drug for prevention of thrombotic events in cardiovascular patients, but approximately 25% of patients experience insufficient platelet inhibition due to aspirin, and remain in risk of cardiovascular events. This study aimed to investigate the value...... of circulating miR-92a and platelet size as biomarkers of the individual response to aspirin therapy. METHODS: Blood samples were collected from 50 healthy blood donors without antithrombotic medication and 50 patients with intermittent claudication on daily aspirin therapy. Based on results from the arachidonic...... acid stimulated aggregation test on Multiplate®analyzer (ASPItest), patients were defined as aspirin resistant (n=10) or aspirin responders (n=40). Plasma levels of miR-92a were evaluated by RT-qPCR analysis and platelet distribution width (PDW) was used to assess platelet size variability. Receiver...

Preclinical pharmacokinetic evaluation and metabolites identification of methyl salicylate-2-O-β-d-lactoside in rats using LC-MS/MS and Q-TOF-MS methods.

Science.gov (United States)

Zhang, Dan; Huang, Chao; Xin, Wenyu; Ma, Xiaowei; Zhang, Weiku; Zhang, Tiantai; Du, Guanhua

2015-05-10

Methyl salicylate-2-O-β-d-lactoside (MSL) is a natural salicylate derivative from the traditional Chinese medicine of Gaultheria yunnanensis (Franch.) Rehder (G. yunnanensis). As a non-steroidal anti-inflammatory drug (NSAID), MSL exerts a significant anti-arthritis effect but hardly has any gastrointestinal toxicity. In this paper, the pharmacokinetics, distribution, excretion and identification of MSL and its metabolites are described following rat oral and intravenous administration. The biological samples were quantified by UPLC-MS/MS and the metabolites in urine and feces were identified by using Q-TOF-MS. These results will support future investigations leading to clinical development of this drug. Copyright © 2015 Elsevier B.V. All rights reserved.

AN EXPERIMENTAL COMPARATIVE STUDY OF ANALGESIC ACTIVITY OF CURCUMA: AMADA (MANGO - GINGER WITH CONVENTIONAL NSAID ASPIRIN IN MALE ALBINO WISTAR RATS

Directory of Open Access Journals (Sweden)

Shanmukananda

2015-09-01

Amada increases the latency period of pain ( R eaction time. In the Tail immersion test the test drug significantly (P <0.001 reduced pain at 30 min when compared to the standard drug Aspirin at 60 min of oral administration. INTERPRETATION AND CONCLUSION : We can conclude that, Curcuma Amada possess analgesic activity which can be explained by animal models of pain. Probably, it acts by peripheral and central mechanisms. The combination of Curcuma Amada and Aspirin is synergistic

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.

Functional Characterization of Salicylic Acid Carboxyl Methyltransferase from Camellia sinensis, Providing the Aroma Compound of Methyl Salicylate during the Withering Process of White Tea.

Science.gov (United States)

Deng, Wei-Wei; Wang, Rongxiu; Yang, Tianyuan; Jiang, Li'na; Zhang, Zheng-Zhu

2017-12-20

Methyl salicylate (MeSA) is one of the volatile organic compounds (VOCs) that releases floral scent and plays an important role in the sweet flowery aroma of tea. During the withering process for white tea producing, MeSA was generated by salicylic acid carboxyl methyltransferase (SAMT) with salicylic acid (SA), and the specific floral scent was formed. In this study, we first cloned a CsSAMT from tea leaves (GenBank accession no. MG459470) and used Escherichia coli and Saccharomyces cerevisiae to express the recombinant CsSAMT. The enzyme activity in prokaryotic and eukaryotic expression systems was identified, and the protein purification, substrate specificity, pH, and temperature optima were investigated. It was shown that CsSAMT located in the chloroplast, and the gene expression profiles were quite different in tea organs. The obtained results might give a new understanding for tea aroma formation, optimization, and regulation and have great significance for improving the specific quality of white tea.

The Long-Term Benefits of Increased Aspirin Use by At-Risk Americans Aged 50 and Older.

Directory of Open Access Journals (Sweden)

David B Agus

Full Text Available The usefulness of aspirin to defend against cardiovascular disease in both primary and secondary settings is well recognized by the medical profession. Multiple studies also have found that daily aspirin significantly reduces cancer incidence and mortality. Despite these proven health benefits, aspirin use remains low among populations targeted by cardiovascular prevention guidelines. This article seeks to determine the long-term economic and population-health impact of broader use of aspirin by older Americans at higher risk for cardiovascular disease.We employ the Future Elderly Model, a dynamic microsimulation that follows Americans aged 50 and older, to project their lifetime health and spending under the status quo and in various scenarios of expanded aspirin use. The model is based primarily on data from the Health and Retirement Study, a large, representative, national survey that has been ongoing for more than two decades. Outcomes are chosen to provide a broad perspective of the individual and societal impacts of the interventions and include: heart disease, stroke, cancer, life expectancy, quality-adjusted life expectancy, disability-free life expectancy, and medical costs. Eligibility for increased aspirin use in simulations is based on the 2011-2012 questionnaire on preventive aspirin use of the National Health and Nutrition Examination Survey. These data reveal a large unmet need for daily aspirin, with over 40% of men and 10% of women aged 50 to 79 presenting high cardiovascular risk but not taking aspirin. We estimate that increased use by high-risk older Americans would improve national life expectancy at age 50 by 0.28 years (95% CI 0.08-0.50 and would add 900,000 people (95% CI 300,000-1,400,000 to the American population by 2036. After valuing the quality-adjusted life-years appropriately, Americans could expect $692 billion (95% CI 345-975 in net health benefits over that period.Expanded use of aspirin by older Americans with

The Long-Term Benefits of Increased Aspirin Use by At-Risk Americans Aged 50 and Older.

Science.gov (United States)

Agus, David B; Gaudette, Étienne; Goldman, Dana P; Messali, Andrew

2016-01-01

The usefulness of aspirin to defend against cardiovascular disease in both primary and secondary settings is well recognized by the medical profession. Multiple studies also have found that daily aspirin significantly reduces cancer incidence and mortality. Despite these proven health benefits, aspirin use remains low among populations targeted by cardiovascular prevention guidelines. This article seeks to determine the long-term economic and population-health impact of broader use of aspirin by older Americans at higher risk for cardiovascular disease. We employ the Future Elderly Model, a dynamic microsimulation that follows Americans aged 50 and older, to project their lifetime health and spending under the status quo and in various scenarios of expanded aspirin use. The model is based primarily on data from the Health and Retirement Study, a large, representative, national survey that has been ongoing for more than two decades. Outcomes are chosen to provide a broad perspective of the individual and societal impacts of the interventions and include: heart disease, stroke, cancer, life expectancy, quality-adjusted life expectancy, disability-free life expectancy, and medical costs. Eligibility for increased aspirin use in simulations is based on the 2011-2012 questionnaire on preventive aspirin use of the National Health and Nutrition Examination Survey. These data reveal a large unmet need for daily aspirin, with over 40% of men and 10% of women aged 50 to 79 presenting high cardiovascular risk but not taking aspirin. We estimate that increased use by high-risk older Americans would improve national life expectancy at age 50 by 0.28 years (95% CI 0.08-0.50) and would add 900,000 people (95% CI 300,000-1,400,000) to the American population by 2036. After valuing the quality-adjusted life-years appropriately, Americans could expect $692 billion (95% CI 345-975) in net health benefits over that period. Expanded use of aspirin by older Americans with elevated risk

Clopidogrel plus long-term aspirin after femoro-popliteal stenting. The CLAFS project: 1- and 2-year results

Energy Technology Data Exchange (ETDEWEB)

Strecker, Ernst-Peter K.; Boos, Irene B.L.; Goettmann, Dieter; Vetter, Sylvia [Department of Imaging, Interventional Radiology, and Nuclear Medicine, Diakonissen Hospital, Diakonissenstrasse 28, 76199, Karlsruhe (Germany)

2004-02-01

The aim of this study was to determine the patency rate after femoro-popliteal stenting followed by oral clopidogrel plus long-term aspirin. In a prospective trial, 31 patients with a total of 33 femoro-popliteal artery lesions (21 stenoses, 12 occlusions; 24 femoral, 9 popliteal) were treated with flexible tantalum stents after unsuccessful percutaneous transluminal angioplasty (PTA) preceded by local fibrinolysis in 5 of 12 patients with total occlusion. Post-interventionally, oral aspirin 100 mg was started simultaneously for the long term and was combined with an oral loading dose of 300 mg clopidogrel, followed by 75 mg clopidogrel daily for 28 days. Patients were followed for at least 12 months (maximum 34 months) by clinical examination, Doppler pressure measurement, color and duplex sonography, and angiography in case of suspicion of restenosis. In a retrospective analysis, the results were compared with those of historical groups of patients having received aspirin only (41 patients) or a long-term high-dose low molecular weight heparin (LMWH)+aspirin treatment (42 patients). Three small puncture aneurysms were treated successfully by conservative means and were categorized as minor bleeding complication. Cumulative primary patency rate (PPR) was 76{+-}7.5% (1 year), and 70{+-}9.6% (2 years) in the clopidogrel+aspirin group, thus being tendentiously better than in the aspirin-only group showing 75{+-}4.6% (1 year), and 50{+-}8.1% (2 years). Long-term high-dose LMWH+aspirin treatment showed 87{+-}5.8% (1 year), and 72{+-}9.1% (2 years), thus being superior to the other treatment regimes, with a statistically significant difference (p<0.05) between the LMWH+aspirin and the aspirin group. Clopidogrel plus aspirin is a safe medication regimen and may be effective in the prevention of early stent thrombosis. Mid- and long-term patency rate seems to be intermediate as compared with other therapeutic regimens. The LMWH+aspirin seems to be superior compared with

Clopidogrel plus long-term aspirin after femoro-popliteal stenting. The CLAFS project: 1- and 2-year results

International Nuclear Information System (INIS)

Strecker, Ernst-Peter K.; Boos, Irene B.L.; Goettmann, Dieter; Vetter, Sylvia

2004-01-01

The aim of this study was to determine the patency rate after femoro-popliteal stenting followed by oral clopidogrel plus long-term aspirin. In a prospective trial, 31 patients with a total of 33 femoro-popliteal artery lesions (21 stenoses, 12 occlusions; 24 femoral, 9 popliteal) were treated with flexible tantalum stents after unsuccessful percutaneous transluminal angioplasty (PTA) preceded by local fibrinolysis in 5 of 12 patients with total occlusion. Post-interventionally, oral aspirin 100 mg was started simultaneously for the long term and was combined with an oral loading dose of 300 mg clopidogrel, followed by 75 mg clopidogrel daily for 28 days. Patients were followed for at least 12 months (maximum 34 months) by clinical examination, Doppler pressure measurement, color and duplex sonography, and angiography in case of suspicion of restenosis. In a retrospective analysis, the results were compared with those of historical groups of patients having received aspirin only (41 patients) or a long-term high-dose low molecular weight heparin (LMWH)+aspirin treatment (42 patients). Three small puncture aneurysms were treated successfully by conservative means and were categorized as minor bleeding complication. Cumulative primary patency rate (PPR) was 76±7.5% (1 year), and 70±9.6% (2 years) in the clopidogrel+aspirin group, thus being tendentiously better than in the aspirin-only group showing 75±4.6% (1 year), and 50±8.1% (2 years). Long-term high-dose LMWH+aspirin treatment showed 87±5.8% (1 year), and 72±9.1% (2 years), thus being superior to the other treatment regimes, with a statistically significant difference (p<0.05) between the LMWH+aspirin and the aspirin group. Clopidogrel plus aspirin is a safe medication regimen and may be effective in the prevention of early stent thrombosis. Mid- and long-term patency rate seems to be intermediate as compared with other therapeutic regimens. The LMWH+aspirin seems to be superior compared with CLAFS

Low-Dose Aspirin Use and Cognitive Function in Older Age: A Systematic Review and Meta-analysis.

Science.gov (United States)

Veronese, Nicola; Stubbs, Brendon; Maggi, Stefania; Thompson, Trevor; Schofield, Patricia; Muller, Christoph; Tseng, Ping-Tao; Lin, Pao-Yen; Carvalho, André F; Solmi, Marco

2017-08-01

To investigate whether low-dose aspirin (aspirin was not associated with onset of dementia or cognitive impairment (5 studies, N = 26,159; OR = 0.82, 95% CI = 0.55-1.22, P = .33, I 2 = 67%). In three RCTs (N = 10,037; median follow-up 5 years), the use of low-dose aspirin was not associated with significantly better global cognition (SMD=0.005, 95% CI=-0.04-0.05, P = .84, I 2 = 0%) in individuals without dementia. Adherence was lower in participants taking aspirin than in controls, and the incidence of adverse events was higher. This review found no evidence that low-dose aspirin buffers against cognitive decline or dementia or improves cognitive test scores in RCTs. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

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

NARCIS (Netherlands)

CHEUNG, PK; VISSER, J; BAKKER, WW

1994-01-01

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

Magical mystery tour: Salicylic acid signalling

Czech Academy of Sciences Publication Activity Database

Janda, Martin; Ruelland, E.

2015-01-01

Roč. 114, Special Issue (2015), s. 117-128 ISSN 0098-8472 R&D Projects: GA ČR(CZ) GAP501/11/1654 Institutional support: RVO:61389030 Keywords : Salicylic acid (SA) * NPR1 * SA overaccumulating mutants Subject RIV: ED - Physiology Impact factor: 3.712, year: 2015

Cumulative inhibitory effect of low-dose aspirin on vascular prostacyclin and platelet thromboxane production in patients with atherosclerosis.

Science.gov (United States)

Weksler, B B; Tack-Goldman, K; Subramanian, V A; Gay, W A

1985-02-01

The relationship between the antithrombotic and antiplatelet effects of aspirin is complex, since aspirin influences other systems that protect against thrombosis as well as inhibiting platelet function. We investigated possible cumulative effects of low-dose aspirin on vascular production of prostacyclin in patients with documented atherosclerotic cardiovascular disease. Candidates for coronary artery vein graft bypass ingested 20 mg of aspirin daily during the week before surgery, and platelet aggregation, platelet formation of thromboxane A2 (TXA2), aortic and saphenous vein production of prostacyclin (PGI2), and hemostatic status were measured at the time of the bypass surgery. Low-dose aspirin markedly inhibited platelet aggregation responses and reduced TXA2 generation by greater than 90%, effects similar to those observed with much higher doses of aspirin. Both aortic and saphenous vein production of PGI2 were inhibited by 50% compared with PGI2 produced by vascular tissues of control subjects who received no aspirin preoperatively (51 +/- 10 pg 6-keto-PGF1 alpha/mg aortic wet weight [mean +/- SEM] in aspirin-treated subjects vs 130 +/- 16 pg/mg in control subjects, and 71 +/- 8 pg/mg saphenous vein wet weight vs 131 +/- 17 pg/mg). Blood loss at surgery was not significantly increased by preoperative low-dose aspirin as measured by chest tube drainage (754 +/- 229 ml in aspirin-treated subjects vs 645 +/- 271 ml in control subjects), hematocrit nadir (31.2 +/- 1.9% vs 31.8 +/- 1.7%), or transfusions (2.2 +/- 1.3 units of red blood cells vs 2.2 +/- 1.7 units).(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin suppresses the abnormal lipid metabolism in liver cancer cells via disrupting an NFκB-ACSL1 signaling.

Science.gov (United States)

Yang, Guang; Wang, Yuan; Feng, Jinyan; Liu, Yunxia; Wang, Tianjiao; Zhao, Man; Ye, Lihong; Zhang, Xiaodong

2017-05-06

Abnormal lipid metabolism is a hallmark of tumorigenesis. Hence, the alterations of metabolism enhance the development of hepatocellular carcinoma (HCC). Aspirin is able to inhibit the growth of cancers through targeting nuclear factor κB (NF-κB). However, the role of aspirin in disrupting abnormal lipid metabolism in HCC remains poorly understood. In this study, we report that aspirin can suppress the abnormal lipid metabolism of HCC cells through inhibiting acyl-CoA synthetase long-chain family member 1 (ACSL1), a lipid metabolism-related enzyme. Interestingly, oil red O staining showed that aspirin suppressed lipogenesis in HepG2 cells and Huh7 cells in a dose-dependent manner. In addition, aspirin attenuated the levels of triglyceride and cholesterol in the cells, respectively. Strikingly, we identified that aspirin was able to down-regulate ACSL1 at the levels of mRNA and protein. Moreover, we validated that aspirin decreased the nuclear levels of NF-κB in HepG2 cells. Mechanically, PDTC, an inhibitor of NF-κB, could down-regulate ACSL1 at the levels of mRNA and protein in the cells. Functionally, PDTC reduced the levels of lipid droplets, triglyceride and cholesterol in HepG2 cells. Thus, we conclude that aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling. Our finding provides new insights into the mechanism by which aspirin inhibits abnormal lipid metabolism of HCC. Therapeutically, aspirin is potentially available for HCC through controlling abnormal lipid metabolism. Copyright © 2017. Published by Elsevier Inc.

Quantifying solubility enhancement due to particle size reduction and crystal habit modification: case study of acetyl salicylic acid.

Science.gov (United States)

Hammond, Robert B; Pencheva, Klimentina; Roberts, Kevin J; Auffret, Tony

2007-08-01

The poor solubility of potential drug molecules is a significant problem in the design of pharmaceutical formulations. It is well known, however, that the solubility of crystalline materials is enhanced when the particle size is reduced to submicron levels and this factor can be expected to enhance drug product bioavailability. Direct estimation of solubility enhancement, as calculated via the Gibbs-Thompson relationship, demands reasonably accurate values for the particle/solution interfacial tension and, in particular, its anisotropy with respect to the crystal product's habit and morphology. In this article, an improved, more molecule-centered, approach is presented towards the calculation of solubility enhancement factors in which molecular modeling techniques are applied, and the effects associated with both crystal habit modification and solvent choice are examined. A case study for facetted, acetyl salicylic acid (aspirin) crystals in equilibrium with saturated aqueous ethanol solution reveals that their solubility will be enhanced in the range (7-58%) for a crystal size of 0.02 microm, with significantly higher enhancement for crystal morphologies in which the hydrophobic crystal faces are more predominant than the hydrophilic faces and for solvents in which the solubility is smaller. (c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.

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