Devolatilization of coal particles in a flat flame -- Experimental and modeling study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Therssen, E.; Gourichon, L.; Delfosse, L.

1995-10-01

Pulverized coals have been tested under the conditions of industrial flames, with high heating rate and high temperatures. The chars were collected after different pyrolysis times. For eight coals, the devolatilized fraction of coal has been measured, as well as those of carbon, hydrogen and nitrogen. During pyrolysis, the evolution of the texture of the grains has been studied by measurement of their microporous surface area, which undergoes a large increase, depending on coal rank. The composition of the volatiles, as deduced from the ultimate and proximate analysis of chars, showed high volatile bituminous coals to essentially produce tars withmore » an aromatic structure. Low and medium volatile bituminous coals produced light hydrocarbons on devolatilization and the char`s surface area continued increasing slowly during the whole of devolatilization, according to the slow increase of the fraction of hydrogen devolatilized. The char`s reactivity with oxygen was followed by measurements of Active Surface Area (ASA). It was shown that the ASA continuously decreases during devolatilization. Five models of devolatilization in the literature were tested and compared to the experimental results, assuming first-order reactions with respect to the remaining volatile matter. Badzioch`s model correctly fitted the experimental results and values of the rate constant obtained by computer trial and error adjustment were higher for lower ranks of the four bituminous coals. Anthony`s model also fits the measurements, provided an adjustment of the preexponential factor of activation energy for which it is shown that an infinite number of such pairs is suitable. If the model is run isothermally at the flame`s peak temperature, it also correctly fits the experimental results.« less

Adsorption behavior and mechanism of different arsenic species on mesoporous MnFe2O4 magnetic nanoparticles.

PubMed

Hu, Qingsong; Liu, Yuling; Gu, Xueyuan; Zhao, Yaping

2017-08-01

Arsenic pollution poses severe threat to human health, therefore dealing with the problem of arsenic contamination in water bodies is extremely important. The adsorption behaviors of different arsenic species, such as arsenate (As(V)), p-arsanilic acid (p-ASA), roxarsone (ROX), dimethylarsenate (DMA) from water using mesoporous bimetal oxide magnetic manganese ferrite nanoparticles (MnFe 2 O 4 ) have been detailedly investigated. The adsorbent was synthesized via a facile co-precipitation approach and recovered conveniently owing to its strong magnetic properties. The obtained MnFe 2 O 4 with large surface area and abundant hydroxyly functional groups exhibited excellent adsorption performance for As(V) and p-ASA, in contrast to ROX and DMA with the maximum adsorption capacities of As(V), p-ASA, ROX and DMA of 68.25 mg g -1 , 59.45 mg g -1 , 51.49 mg g -1 , and 35.77 mg g -1 , respectively. The Langmuir model and the pseudo-second-order kinetic model correlated satisfactorily with the adsorption thermodynamics and kinetics, and thermodynamic parameters depicted the spontaneous endothermic nature for the adsorption of different arsenic species. The adsorption mechanism of different arsenic species onto MnFe 2 O 4 nanoparticles at various pH values could be explained by surface complexation and molecular structural variations. Attenuated Total internal Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS) further proved that arsenic species were bonded to the surface of MnFe 2 O 4 through the formation of an inner-sphere complex between the arsenic acid moiety and surface metal centers. The results would help to know the interaction of arsenic species with iron-manganese minerals and the mobility of arsenic species in natural environments. Copyright © 2017 Elsevier Ltd. All rights reserved.

BOREAS RSS-2 Level-1B ASAS Image Data: At-Sensor Radiance in BSQ Format

NASA Technical Reports Server (NTRS)

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

2000-01-01

The BOREAS RSS-2 team used the ASAS instrument, mounted on the NASA C-130 aircraft, to create at-sensor radiance images of various sites as a function of spectral wavelength, view geometry (combinations of view zenith angle, view azimuth angle, solar zenith angle, and solar azimuth angle), and altitude. The level-1b ASAS images of the BOREAS study areas were collected from April to September 1994 and March to July 1996.

Effects of Average Signed Area Between Two Item Characteristic Curves and Test Purification Procedures on the DIF Detection via the Mantel-Haenszel Method

ERIC Educational Resources Information Center

Wang, Wen-Chung; Su, Ya-Hui

2004-01-01

In this study we investigated the effects of the average signed area (ASA) between the item characteristic curves of the reference and focal groups and three test purification procedures on the uniform differential item functioning (DIF) detection via the Mantel-Haenszel (M-H) method through Monte Carlo simulations. The results showed that ASA,…

AIR SCREENING ASSESSMENT (ASA) - COOK CO., IL/LAKE CO., IN

EPA Science Inventory

ASA Background and Overview - In 1995 the Chcago Legal Clinic and 11 Chicago-area community advocacy groups filed a partition under the Toxics Substances Control Act requesting that the USEPA Administrator prohibit or further regulate the emissions from eight proposed or construc...

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

PubMed

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

2017-02-07

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

Hydraulic forces contribute to left ventricular diastolic filling

PubMed Central

Maksuti, Elira; Carlsson, Marcus; Arheden, Håkan; Kovács, Sándor J.; Broomé, Michael; Ugander, Martin

2017-01-01

Myocardial active relaxation and restoring forces are known determinants of left ventricular (LV) diastolic function. We hypothesize the existence of an additional mechanism involved in LV filling, namely, a hydraulic force contributing to the longitudinal motion of the atrioventricular (AV) plane. A prerequisite for the presence of a net hydraulic force during diastole is that the atrial short-axis area (ASA) is smaller than the ventricular short-axis area (VSA). We aimed (a) to illustrate this mechanism in an analogous physical model, (b) to measure the ASA and VSA throughout the cardiac cycle in healthy volunteers using cardiovascular magnetic resonance imaging, and (c) to calculate the magnitude of the hydraulic force. The physical model illustrated that the anatomical difference between ASA and VSA provides the basis for generating a hydraulic force during diastole. In volunteers, VSA was greater than ASA during 75–100% of diastole. The hydraulic force was estimated to be 10–60% of the peak driving force of LV filling (1–3 N vs 5–10 N). Hydraulic forces are a consequence of left heart anatomy and aid LV diastolic filling. These findings suggest that the relationship between ASA and VSA, and the associated hydraulic force, should be considered when characterizing diastolic function and dysfunction. PMID:28256604

Carboxylator: incorporating solvent-accessible surface area for identifying protein carboxylation sites

NASA Astrophysics Data System (ADS)

Lu, Cheng-Tsung; Chen, Shu-An; Bretaña, Neil Arvin; Cheng, Tzu-Hsiu; Lee, Tzong-Yi

2011-10-01

In proteins, glutamate (Glu) residues are transformed into γ-carboxyglutamate (Gla) residues in a process called carboxylation. The process of protein carboxylation catalyzed by γ-glutamyl carboxylase is deemed to be important due to its involvement in biological processes such as blood clotting cascade and bone growth. There is an increasing interest within the scientific community to identify protein carboxylation sites. However, experimental identification of carboxylation sites via mass spectrometry-based methods is observed to be expensive, time-consuming, and labor-intensive. Thus, we were motivated to design a computational method for identifying protein carboxylation sites. This work aims to investigate the protein carboxylation by considering the composition of amino acids that surround modification sites. With the implication of a modified residue prefers to be accessible on the surface of a protein, the solvent-accessible surface area (ASA) around carboxylation sites is also investigated. Radial basis function network is then employed to build a predictive model using various features for identifying carboxylation sites. Based on a five-fold cross-validation evaluation, a predictive model trained using the combined features of amino acid sequence (AA20D), amino acid composition, and ASA, yields the highest accuracy at 0.874. Furthermore, an independent test done involving data not included in the cross-validation process indicates that in silico identification is a feasible means of preliminary analysis. Additionally, the predictive method presented in this work is implemented as Carboxylator (http://csb.cse.yzu.edu.tw/Carboxylator/), a web-based tool for identifying carboxylated proteins with modification sites in order to help users in investigating γ-glutamyl carboxylation.

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

PubMed

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

2017-01-06

To evaluate the effects of the non-selective, non-steroidal anti-inflammatory drug (NSAID) acetylsalicylic acid (ASA), on ex vivo embryonic kidney growth and development. Pairs of fetal mouse kidneys at embryonic day 12.5 were cultured ex vivo in increasing concentrations of ASA (0.04-0.4 mg/mL) for up to 7 d. One organ from each pair was grown in control media and was used as the internal control for the experimental contralateral organ. In some experiments, organs were treated with ASA for 48 h and then transferred either to control media alone or control media containing 10 μmol/L prostaglandin E 2 (PGE 2 ) for a further 5 d. Fetal kidneys were additionally obtained from prostaglandin synthase 2 homozygous null or heterozygous (PTGS2 -/- and PTGS2 -/+ ) embryos and grown in culture. Kidney cross-sectional area was used to determine treatment effects on kidney growth. Whole-mount labelling to fluorescently detect laminin enabled crude determination of epithelial branching using confocal microscopy. Increasing ASA concentration (0.1, 0.2 and 0.4 mg/mL) significantly inhibited metanephric growth ( P < 0.05). After 7 d of culture, exposure to 0.2 mg/mL and 0.4 mg/mL reduced organ size to 53% and 23% of control organ size respectively ( P < 0.01). Addition of 10 μmol/L PGE 2 to culture media after exposure to 0.2 mg/mL ASA for 48 h resulted in a return of growth area to control levels. Application of control media alone after cessation of ASA exposure showed no benefit on kidney growth. Despite the apparent recovery of growth area with 10 μmol/L PGE 2 , no obvious renal tubular structures were formed. The number of epithelial tips generated after 48 h exposure to ASA was reduced by 40% (0.2 mg/mL; P < 0.05) and 47% (0.4 mg/mL; P < 0.01). Finally, growth of PTGS2 -/- and PTGS2 +/- kidneys in organ culture showed no differences, indicating that PTGS2 derived PGE 2 may at best have a minor role. ASA reduces early renal growth and development but the role of prostaglandins in this may be minor.

Increased level of antibodies cross-reacting with Ves v 5 and CRISP-2 in MAR-positive patients.

PubMed

Brunner-Agten, S; Pavlovic, R; Müller, L; Horn, M P; Huber, A R; Stadler, B M; Vogel, M

2013-01-01

Anti-sperm antibodies (ASA) have been described to be involved in immunological infertility. A possible antigen for ASA is the human cysteine-rich secretory protein 2 (CRISP-2), a sperm surface protein important in sperm-oocyte interaction. Furthermore, anti-CRISP-2 antibodies were shown to decrease fertility rates in vitro. Recently, we have reported cross-reacting antibodies recognizing CRISP-2 and antigen 5 from yellow jacket venom (Ves v 5) in human serum. Here, we investigated anti-Ves v 5 and CRISP-2 antibodies in sera from two groups of donors: MAR+ and MAR- patients. A higher incidence of allergy against hymenoptera venom was found in MAR+ patients. Interestingly, affinity-purified ASA from MAR+ patients' sera reacted against both Ves v 5 and CRISP-2, leading to sperm immobilization. Immunofluorescence analysis showed that ASA bound to the sperm surface, including the head part where CRISP-2 is localized. Taken together, these results showed a higher incidence of antibodies cross-reacting with Ves v 5 and CRISP-2 in MAR+ patients. This leads to the hypothesis that MAR+ patients may have a higher risk to develop wasp allergy. Copyright © 2012 S. Karger AG, Basel.

Characterization of a novel antibiofilm effect of nitric oxide-releasing aspirin (NCX-4040) on Candida albicans isolates from denture stomatitis patients

PubMed Central

Madariaga-Venegas, Francisco; Fernández-Soto, Roberto; Duarte, Luisa Fernanda; Suarez, Nicole; Delgadillo, Daniela; Jara, José A.; Fernández-Ramires, Ricardo; Urzúa, Blanca; Molina-Berríos, Alfredo

2017-01-01

Candida albicans biofilms play a key role in denture stomatitis, one of the most common oral pathologies in elderly people. Because biofilms are highly resistant to antifungals, new pharmacological strategies are needed. Aspirin and nitric oxide-donor molecules have both shown antibiofilm effects on C. albicans, making them promising candidates for treatment. In this study, we evaluated the antifungal/antibiofilm effect of a nitric-oxide releasing aspirin (NO-ASA) on C. albicans isolates from denture stomatitis patients in vitro. Disk diffusion assays showed that while NO-ASA had no antifungal effect, the drug potentiated fluconazole inhibition zone diameters, increasing the effect of fluconazole by 20–30% (p<0.05). The effect of NO-ASA on the morphogenesis of C. albicans was evaluated using light microscopy after inducing hyphae formation. For all clinical strains assayed, 125 μM NO-ASA significantly decreased the number of filamentous cells present (p<0.01). Adhesion to abiotic surfaces, a critical event for biofilm formation, was evaluated in 96-well polystyrene plates using crystal violet assay; 125 μM NO-ASA significantly inhibited adhesion. Biofilms were observed with scanning electron microscopy (SEM) and quantified using XTT reduction assay. NO-ASA decreased biofilm formation (IC50 ranging from 300 μM to 700 μM), consistent with SEM findings of altered biofilm microarchitecture. PGE2 and carboxy-PTIO (an NO scavenger) both blocked the antibiofilm effects of NO-ASA, suggesting that the efficacy of NO-ASA may be associated with both inhibition of PGE2 synthesis and release of NO. NO-ASA is a promising novel antibiofilm agent for treating fluconazole-resistant strains of C. albicans. PMID:28493889

Characterization of a novel antibiofilm effect of nitric oxide-releasing aspirin (NCX-4040) on Candida albicans isolates from denture stomatitis patients.

PubMed

Madariaga-Venegas, Francisco; Fernández-Soto, Roberto; Duarte, Luisa Fernanda; Suarez, Nicole; Delgadillo, Daniela; Jara, José A; Fernández-Ramires, Ricardo; Urzúa, Blanca; Molina-Berríos, Alfredo

2017-01-01

Candida albicans biofilms play a key role in denture stomatitis, one of the most common oral pathologies in elderly people. Because biofilms are highly resistant to antifungals, new pharmacological strategies are needed. Aspirin and nitric oxide-donor molecules have both shown antibiofilm effects on C. albicans, making them promising candidates for treatment. In this study, we evaluated the antifungal/antibiofilm effect of a nitric-oxide releasing aspirin (NO-ASA) on C. albicans isolates from denture stomatitis patients in vitro. Disk diffusion assays showed that while NO-ASA had no antifungal effect, the drug potentiated fluconazole inhibition zone diameters, increasing the effect of fluconazole by 20-30% (p<0.05). The effect of NO-ASA on the morphogenesis of C. albicans was evaluated using light microscopy after inducing hyphae formation. For all clinical strains assayed, 125 μM NO-ASA significantly decreased the number of filamentous cells present (p<0.01). Adhesion to abiotic surfaces, a critical event for biofilm formation, was evaluated in 96-well polystyrene plates using crystal violet assay; 125 μM NO-ASA significantly inhibited adhesion. Biofilms were observed with scanning electron microscopy (SEM) and quantified using XTT reduction assay. NO-ASA decreased biofilm formation (IC50 ranging from 300 μM to 700 μM), consistent with SEM findings of altered biofilm microarchitecture. PGE2 and carboxy-PTIO (an NO scavenger) both blocked the antibiofilm effects of NO-ASA, suggesting that the efficacy of NO-ASA may be associated with both inhibition of PGE2 synthesis and release of NO. NO-ASA is a promising novel antibiofilm agent for treating fluconazole-resistant strains of C. albicans.

Largely improved the low temperature toughness of acrylonitrile-styrene-acrylate (ASA) resin: Fabricated a core-shell structure of two elastomers through the differences of interfacial tensions

NASA Astrophysics Data System (ADS)

Mao, Zepeng; Zhang, Jun

2018-06-01

The phase morphology of two elastomers (i.e., chlorinated polyethylene (CPE) and polybutadiene rubber (BR)) were devised to be a core-shell structure in acrylonitrile-styrene-acrylate (ASA) resin matrix, via the interfacial tension differences of polymer pairs. Selective extraction test and scanning electron microscopy (SEM) were utilized to verify this special phase morphology. The results demonstrated that the core-shell structure, BR core and CPE shell, significantly contributed to improve the low temperature toughness of ASA/CPE/BR ternary blends, which may be because the nonpolar BR core was segregated from polar ASA by the CPE shell. The CPE shell served dual functions: Not only did it play compatibilizing effect in the interface between BR and ASA matrix, but it also toughened the blends at 25 and 0 °C. The blends of ASA/CPE/BR (100/27/3, w/w/w) and ASA/CPE/BR (100/22/8, w/w/w) showed the peak impact strengths at about 28 and 9 kJ/m2 at 0 and -30 °C, respectively, which were higher than both that of ASA/CPE/BR (100/30/0, w/w/w) and ASA/CPE/BR (100/0/30, w/w/w). Moreover, the impact strength of ternary blends at room temperature kept at 40 kJ/m2 when BR content was lower than 10 phr. Other characterizations including contact angle measurement, dynamic mechanical thermal analysis (DMTA), morphology of impact-fractured surfaces, tensile properties, flexural properties, and Fourier transform infrared spectroscopy (FTIR) were measured as well.

Hydrophobic surface modification of TiO2 nanoparticles for production of acrylonitrile-styrene-acrylate terpolymer/TiO2 composited cool materials

NASA Astrophysics Data System (ADS)

Qi, Yanli; Xiang, Bo; Tan, Wubin; Zhang, Jun

2017-10-01

Hydrophobic surface modification of TiO2 was conducted for production of acrylonitrile-styrene-acrylate (ASA) terpolymer/titanium dioxide (TiO2) composited cool materials. Different amount of 3-methacryloxypropyl-trimethoxysilane (MPS) was employed to change hydrophilic surface of TiO2 into hydrophobic surface. The hydrophobic organosilane chains were successfully grafted onto TiO2 through Sisbnd Osbnd Ti bonds, which were verified by Fourier transformed infrared spectra and X-ray photoelectron spectroscopy. The water contact angle of the sample added with TiO2 modified by 5 wt% MPS increased from 86° to 113°. Besides, all the ASA/TiO2 composites showed significant improvement in both solar reflectance and cooling property. The reflectance of the composites throughout the near infrared (NIR) region and the whole solar wavelength is increased by 113.92% and 43.35% compared with pristine ASA resin. Simultaneously, significant drop in temperature demonstrates excellent cooling property. A maximum decrease approach to 27 °C was observed in indoor temperature test, while a decrease around 9 °C tested outdoors is achieved.

Hydration of AN Acid Anhydride: the Water Complex of Acetic Sulfuric Anhydride

NASA Astrophysics Data System (ADS)

Smith, CJ; Huff, Anna; Mackenzie, Becca; Leopold, Ken

2017-06-01

The water complex of acetic sulfuric anhydride (ASA, CH_{3}COOSO_{2}OH) has been observed by pulsed nozzle Fourier transform microwave spectroscopy. ASA is formed in situ in the supersonic jet via the reaction of SO_{3} and acetic acid and subsequently forms a complex with water during the expansion. Spectra of the parent and fully deuterated form, as well as those of the species derived from CH_{3}^{13}COOH, have been observed. The fitted internal rotation barrier of the methyl group is 219.599(21), \\wn indicating the complexation with water lowers the internal rotation barrier of the methyl group by 9% relative to that of free ASA. The observed species is one of several isomers identified theoretically in which the water inserts into the intramolecular hydrogen bond of the ASA. Aspects of the intermolecular potential energy surface are discussed.

Interaction of Aspirin (Acetylsalicylic Acid) with Lipid Membranes

PubMed Central

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

2012-01-01

We studied the interaction of Aspirin (acetylsalicylic acid) with lipid membranes using x-ray diffraction for bilayers containing up to 50 mol% of aspirin. From 2D x-ray intensity maps that cover large areas of reciprocal space we determined the position of the ASA molecules in the phospholipid bilayers and the molecular arrangement of the molecules in the plane of the membranes. We present direct experimental evidence that ASA molecules participate in saturated lipid bilayers of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) and preferably reside in the head group region of the membrane. Up to 50 mol% ASA molecules can be dissolved in this type of bilayer before the lateral membrane organization is disturbed and the membranes are found to form an ordered, 2D crystal-like structure. Furthermore, ASA and cholesterol were found to co-exist in saturated lipid bilayers, with the ASA molecules residing in the head group region and the cholesterol molecules participating in the hydrophobic membrane core. PMID:22529913

The Influence of Prolonged Acetylsalicylic Acid Supplementation-Induced Gastritis on the Neurochemistry of the Sympathetic Neurons Supplying Prepyloric Region of the Porcine Stomach.

PubMed

Palus, Katarzyna; Całka, Jarosław

2015-01-01

This experiment was designed to establish the localization and neurochemical phenotyping of sympathetic neurons supplying prepyloric area of the porcine stomach in a physiological state and during acetylsalicylic acid (ASA) induced gastritis. In order to localize the sympathetic perikarya the stomachs of both control and acetylsalicylic acid treated (ASA group) animals were injected with neuronal retrograde tracer Fast Blue (FB). Seven days post FB injection, animals were divided into a control and ASA supplementation group. The ASA group was given 100 mg/kg of b.w. ASA orally for 21 days. On the 28th day all pigs were euthanized with gradual overdose of anesthetic. Then fourteen-micrometer-thick cryostat sections were processed for routine double-labeling immunofluorescence, using primary antisera directed towards tyrosine hydroxylase (TH), dopamine β-hydroxylase (DβH), neuropeptide Y (NPY), galanin (GAL), neuronal nitric oxide synthase (nNOS), leu 5-enkephalin (LENK), cocaine- and amphetamine- regulated transcript peptide (CART), calcitonin gene-related peptide (CGRP), substance P (SP) and vasoactive intestinal peptide (VIP). The data obtained in this study indicate that postganglionic sympathetic nerve fibers supplying prepyloric area of the porcine stomach originate from the coeliac-cranial mesenteric ganglion complex (CCMG). In control animals, the FB-labelled neurons expressed TH (94.85 ± 1.01%), DβH (97.10 ± 0.97%), NPY (46.88 ± 2.53%) and GAL (8.40 ± 0.53%). In ASA group, TH- and DβH- positive nerve cells were reduced (85.78 ± 2.65% and 88.82 ± 1.63% respectively). Moreover, ASA- induced gastritis resulted in increased expression of NPY (76.59 ± 3.02%) and GAL (26.45 ± 2.75%) as well as the novo-synthesis of nNOS (6.13 ± 1.11%) and LENK (4.77 ± 0.42%) in traced CCMG neurons. Additionally, a network of CART-, CGRP-, SP-, VIP-, LENK-, nNOS- immunoreactive (IR) nerve fibers encircling the FB-positive perikarya were observed in both intact and ASA-treated animals. The results of this study indicate involvement of these neuropeptides in the development or presumably counteraction of gastric inflammation.

Pharmacological intervention against bubble-induced platelet aggregation in a rat model of decompression sickness

PubMed Central

Vallée, Nicolas; Ignatescu, Mihaela; Bourdon, Lionel

2011-01-01

Decompression sickness (DCS) with alterations in coagulation system and formation of platelet thrombi occurs when a subject is subjected to a reduction in environmental pressure. Blood platelet consumption after decompression is clearly linked to bubble formation in humans and offers an index for evaluating DCS severity in animal models. Previous studies highlighted a predominant involvement of platelet activation and thrombin generation in bubble-induced platelet aggregation (BIPA). To study the mechanism of the BIPA in DCS, we examined the effect of acetylsalicylic acid (ASA), heparin (Hep), and clopidogrel (Clo), with anti-thrombotic dose pretreatment in a rat model of DCS. Male Sprague-Dawley rats (n = 208) were randomly assigned to one experimental group treated before the hyperbaric exposure and decompression protocol either with ASA (3×100 mg·kg−1·day−1, n = 30), Clo (50 mg·kg−1·day−1, n = 60), Hep (500 IU/kg, n = 30), or to untreated group (n = 49). Rats were first compressed to 1,000 kPa (90 msw) for 45 min and then decompressed to surface in 38 min. In a control experiment, rats were treated with ASA (n = 13), Clo (n = 13), or Hep (n = 13) and maintained at atmospheric pressure for an equivalent period of time. Onset of DCS symptoms and death were recorded during a 60-min observation period after surfacing. DCS evaluation included pulmonary and neurological signs. Blood samples for platelet count (PC) were taken 30 min before hyperbaric exposure and 30 min after surfacing. Clo reduces the DCS mortality risk (mortality rate: 3/60 with Clo, 15/30 with ASA, 21/30 with Hep, and 35/49 in the untreated group) and DCS severity (neurological DCS incidence: 9/60 with Clo, 6/30 with ASA, 5/30 with Hep, and 12/49 in the untreated group). Clo reduced fall in platelet count and BIPA (−4,5% with Clo, −19.5% with ASA, −19,9% with Hep, and −29,6% in the untreated group). ASA, which inhibits the thromboxane A2 pathway, and Hep, which inhibits thrombin generation, have no protective effect on DCS incidence. Clo, a specific ADP-receptor antagonist, reduces post-decompression platelet consumption. These results point to the predominant involvement of the ADP release in BIPA but cannot differentiate definitively between bubble-induced vessel wall injury and bubble-blood component interactions in DCS. PMID:21212250

Incidence of virulence determinants in clinical Enterococcus faecalis and Enterococcus faecium isolates collected in Bulgaria.

PubMed

Strateva, Tanya; Atanasova, Daniela; Savov, Encho; Petrova, Guergana; Mitov, Ivan

2016-01-01

To evaluate the prevalence of some virulence genes among 510 clinical Enterococcus spp. isolates and to assess the association of those genes with the species, infection site, and patient group (inpatients/outpatients). Adhesins genes (aggregation substances agg and asa1 of Enterococcus faecalis and Enterococcus faecium, respectively), enterococcal surface protein (esp), endocarditis-specific antigen A (efaA), collagen-binding proteins (ace/acm)); invasins (hyaluronidase (hyl) and gelatinase (gelE)); cytotoxines (activation of cytolysin (cylA) in E. faecalis); and modulators of the host immunity and inflammation (enhanced expression pheromone (eep) in E. faecalis) were detected by polymerase chain reaction. The overall prevalence was: esp - 44.3%, agg/asa1 - 38.4%, ace/acm - 64.3%, efaA - 85.9%, eep - 69.4%, gelE - 64.3%, hyl - 25.1%, and cylA - 47.1%. E. faecalis isolates had significantly higher frequency of adhesin genes (esp and agg/asa1) and gelatinase in comparison to E. faecium. Multiple virulence genes in E. faecalis were significantly more prevalent than in E. faecium isolates. Domination of E. faecium with or without only one gene compared to the isolates of E. faecalis were found. Enterococcus spp. isolates obtained from outpatients compared to inpatients isolates had significantly higher frequency of agg/asa1, eep, gelE and cylA. Some adhesins genes (esp, agg/asa1 and efaA) had higher prevalence among the non-invasive Enterococcus spp. isolates compared to those causing invasive bacteremia, while ace/acm revealed higher dissemination in isolates causing invasive infections compared to non-invasive isolates. Most E. faecalis attaches to abiotic surfaces in hospital environment, which correlates with higher prevalence of gene encoding for virulence factors involved in biofilm formation, such as enterococcal surface protein, aggregation substance, and gelatinase. The intestinal tract is an important reservoir for opportunistic enterococcal pathogens and allows them to access infectious sites through different virulence factors, demonstrated in outpatient isolates in this study. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

A novel prediction approach for antimalarial activities of Trimethoprim, Pyrimethamine, and Cycloguanil analogues using extremely randomized trees.

PubMed

Nattee, Cholwich; Khamsemanan, Nirattaya; Lawtrakul, Luckhana; Toochinda, Pisanu; Hannongbua, Supa

2017-01-01

Malaria is still one of the most serious diseases in tropical regions. This is due in part to the high resistance against available drugs for the inhibition of parasites, Plasmodium, the cause of the disease. New potent compounds with high clinical utility are urgently needed. In this work, we created a novel model using a regression tree to study structure-activity relationships and predict the inhibition constant, K i of three different antimalarial analogues (Trimethoprim, Pyrimethamine, and Cycloguanil) based on their molecular descriptors. To the best of our knowledge, this work is the first attempt to study the structure-activity relationships of all three analogues combined. The most relevant descriptors and appropriate parameters of the regression tree are harvested using extremely randomized trees. These descriptors are water accessible surface area, Log of the aqueous solubility, total hydrophobic van der Waals surface area, and molecular refractivity. Out of all possible combinations of these selected parameters and descriptors, the tree with the strongest coefficient of determination is selected to be our prediction model. Predicted K i values from the proposed model show a strong coefficient of determination, R 2 =0.996, to experimental K i values. From the structure of the regression tree, compounds with high accessible surface area of all hydrophobic atoms (ASA_H) and low aqueous solubility of inhibitors (Log S) generally possess low K i values. Our prediction model can also be utilized as a screening test for new antimalarial drug compounds which may reduce the time and expenses for new drug development. New compounds with high predicted K i should be excluded from further drug development. It is also our inference that a threshold of ASA_H greater than 575.80 and Log S less than or equal to -4.36 is a sufficient condition for a new compound to possess a low K i . Copyright © 2016 Elsevier Inc. All rights reserved.

Central effects of acetylsalicylic acid on trigeminal-nociceptive stimuli

PubMed Central

2014-01-01

Background Acetylsalicylic acid is one of the most used analgesics to treat an acute migraine attack. Next to the inhibitory effects on peripheral prostaglandin synthesis, central mechanisms of action have also been discussed. Methods Using a standardized model for trigeminal-nociceptive stimulation during fMRI scanning, we investigated the effect of acetylsalicylic acid on acute pain compared to saline in 22 healthy volunteers in a double-blind within-subject design. Painful stimulation was applied using gaseous ammonia and presented in a pseudo-randomized order with several control stimuli. All participants were instructed to rate the intensity and unpleasantness of every stimulus on a VAS scale. Based on previous results, we hypothesized to find an effect of ASA on central pain processing structures like the ACC, SI and SII as well as the trigeminal nuclei and the hypothalamus. Results Even though we did not find any differences in pain ratings between saline and ASA, we observed decreased BOLD signal changes in response to trigemino-nociceptive stimulation in the ACC and SII after administration of ASA compared to saline. This finding is in line with earlier imaging results investigating the effect of ASA on acute pain. Contrary to earlier findings from animal studies, we could not find an effect of ASA on the trigeminal nuclei in the brainstem or within the hypothalamic area. Conclusion Taken together our study replicates earlier findings of an attenuating effect of ASA on pain processing structures, which adds further evidence to a possibly central mechanism of action of ASA. PMID:25201152

Gastric adaptation to injury by repeated doses of aspirin strengthens mucosal defence against subsequent exposure to various strong irritants in rats.

PubMed Central

Brzozowski, T; Konturek, P C; Konturek, S J; Ernst, H; Stachura, J; Hahn, E G

1995-01-01

Gastric adaptation to injury during repeated doses of acetyl salicylic acid (ASA) is a well documented finding but it is not known whether this adaptation affects the tolerance of the mucosa to other strong irritants. Gastric adaptation was induced by repeated daily doses of acidified ASA (100 mg/kg in 1.5 ml of 0.2 N HCl) given intragastrically (series A rats). Control rats with an intact stomach were given daily intragastric vehicle only (1.5 ml of 0.2 N HCl) (series B). After full adaptation to ASA (5 days), rats were challenged again with acidified ASA or, for comparison, with strong irritants such as 100% ethanol, 200 mM acidified taurocholate, or 25% NaCl for 1 hour or with water immersion and restraint for 3.5 hours. The first dose of ASA produced numerous gastric lesions and deep histological necrosis accompanied by a fall in the gastric blood flow, negligible expression of epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) or their receptors, and no evidence of mucosal proliferation. As adaptation to ASA developed, however, the areas of gastric lesions were reduced by more than 80% and there was a noticeable decrease in deep necrosis, a partial restoration of gastric blood flow, an approximately four-fold increase in EGF expression (but not in TGF alpha) and its receptors, and an appreciable increase in mucosal cell proliferation compared with vehicle treated rats. Increases in the mucosal expression of EGF receptors and the luminal content of EGF were also found in ASA adapted animals. In ASA adapted rats subsequently challenged with 100% ethanol, 200 mM TC, 25% NaCl, or stress, the area of the gastric lesions and deep histological necrosis were appreciably reduced compared with values in vehicle treated rats. This increased mucosal tolerance to strong irritants was also accompanied by the return of the gastric blood flow towards control levels and further significant increases in the mucosal expression of EGF receptors and mucosal cell proliferation. Gastric adaptation to ASA enhances the mucosal resistance to injury by strong irritants probably as a result of the restoration of the gastric blood flow and increased cell proliferation that may result from increased mucosal expression of EGF and its receptors. Images Figure 1 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:8537043

Using generalized additive mixed models to assess spatial, temporal, and hydrologic controls on bacteria and nitrate in a vulnerable agricultural aquifer.

PubMed

Mellor, Andrea F P; Cey, Edwin E

2015-11-01

The Abbotsford-Sumas aquifer (ASA) has a history of nitrate contamination from agricultural land use and manure application to soils, yet little is known about its microbial groundwater quality. The goal of this study was to investigate the spatiotemporal distribution of pathogen indicators (Escherichia coli [E. coli] and total coliform [TC]) and nitrate in groundwater, and their potential relation to hydrologic drivers. Sampling of 46 wells over an 11-month period confirmed elevated nitrate concentrations, with more than 50% of samples exceeding 10 mg-N/L. E. coli detections in groundwater were infrequent (4 of 385 total samples) and attributed mainly to surface water-groundwater connections along Fishtrap Creek, which tested positive for E. coli in every sampling event. TC was detected frequently in groundwater (70% of samples) across the ASA. Generalized additive mixed models (GAMMs) yielded valuable insights into relationships between TC or nitrate and a range of spatial, temporal, and hydrologic explanatory variables. Increased TC values over the wetter fall and winter period were most strongly related to groundwater temperatures and levels, while precipitation and well location were weaker (but still significant) predictors. In contrast, the moderate temporal variability in nitrate concentrations was not significantly related to hydrologic forcings. TC was relatively widespread across the ASA and spatial patterns could not be attributed solely to surface water connectivity. Varying nitrate concentrations across the ASA were significantly related to both well location and depth, likely due to spatially variable nitrogen loading and localized geochemical attenuation (i.e., denitrification). Vulnerability of the ASA to bacteria was clearly linked to hydrologic conditions, and was distinct from nitrate, such that a groundwater management strategy specifically for bacterial contaminants is warranted. Copyright © 2015 Elsevier B.V. All rights reserved.

Anticipatory postural adjustments and anticipatory synergy adjustments: Preparing to a postural perturbation with predictable and unpredictable direction

PubMed Central

Piscitelli, Daniele; Falaki, Ali; Solnik, Stanislaw; Latash, Mark L.

2016-01-01

We explored two aspects of feed-forward postural control, anticipatory postural adjustments (APAs) and anticipatory synergy adjustments (ASAs) seen prior to self-triggered unloading with known and unknown direction of the perturbation. In particular, we tested two main hypotheses predicting contrasting changes in APAs and ASAs. The first hypothesis predicted no major changes in ASAs. The second hypothesis predicted delayed APAs with predominance of co-contraction patterns when perturbation direction was unknown. Healthy subjects stood on the force plate and help a bar with two loads acting in the forward and backward directions. They pressed a trigger that released one of the loads causing a postural perturbation. In different series, the direction of the perturbation was either known (the same load released in all trials) or unknown (the subjects did not know which of the two loads would be released). Surface electromyograms were recorded and used to quantify APAs, synergies stabilizing center of pressure coordinate (within the uncontrolled manifold hypothesis), and ASA. APAs and ASAs were seen in all conditions. APAs were delayed and predominance of co-contraction patterns was seen under the conditions with unpredictable direction of perturbation. In contrast, no significant changes in synergies and ASAs were seen. Overall, these results show that feed-forward control of vertical posture has two distinct components, reflected in APAs and ASAs, which show qualitatively different adjustments with changes in predictability of the direction of perturbation. These results are interpreted within the recently proposed hierarchical scheme of the synergic control of motor tasks. The observations underscore the complexity of the feed-forward postural control, which involves separate changes in salient performance variables (such as coordinate of the center of pressure) and in their stability properties. PMID:27866261

Anticipatory postural adjustments and anticipatory synergy adjustments: preparing to a postural perturbation with predictable and unpredictable direction.

PubMed

Piscitelli, Daniele; Falaki, Ali; Solnik, Stanislaw; Latash, Mark L

2017-03-01

We explored two aspects of feed-forward postural control, anticipatory postural adjustments (APAs) and anticipatory synergy adjustments (ASAs) seen prior to self-triggered unloading with known and unknown direction of the perturbation. In particular, we tested two main hypotheses predicting contrasting changes in APAs and ASAs. The first hypothesis predicted no major changes in ASAs. The second hypothesis predicted delayed APAs with predominance of co-contraction patterns when perturbation direction was unknown. Healthy subjects stood on the force plate and held a bar with two loads acting in the forward and backward directions. They pressed a trigger that released one of the loads causing a postural perturbation. In different series, the direction of the perturbation was either known (the same load released in all trials) or unknown (the subjects did not know which of the two loads would be released). Surface electromyograms were recorded and used to quantify APAs, synergies stabilizing center of pressure coordinate (within the uncontrolled manifold hypothesis), and ASA. APAs and ASAs were seen in all conditions. APAs were delayed, and predominance of co-contraction patterns was seen under the conditions with unpredictable direction of perturbation. In contrast, no significant changes in synergies and ASAs were seen. Overall, these results show that feed-forward control of vertical posture has two distinct components, reflected in APAs and ASAs, which show qualitatively different adjustments with changes in predictability of the direction of perturbation. These results are interpreted within the recently proposed hierarchical scheme of the synergic control of motor tasks. The observations underscore the complexity of the feed-forward postural control, which involves separate changes in salient performance variables (such as coordinate of the center of pressure) and in their stability properties.

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

PubMed Central

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

2011-01-01

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

Nitric oxide-releasing aspirin but not conventional aspirin improves healing of experimental colitis

PubMed Central

Zwolinska-Wcislo, Malgorzata; Brzozowski, Tomasz; Ptak-Belowska, Agata; Targosz, Aneta; Urbanczyk, Katarzyna; Kwiecien, Slawomir; Sliwowski, Zbigniew

2011-01-01

AIM: To determine the effect of non-selective cyclooxygenase (COX) inhibitors, selective COX-2 inhibitors and nitric oxide (NO)-releasing aspirin in the healing of ulcerative colitis. METHODS: Rats with 2,4,6 trinitrobenzenesulfon-ic acid (TNBS)-induced colitis received intragastric (ig) treatment with vehicle, aspirin (ASA) (a non-selective COX inhibitor), celecoxib (a selective COX-2 inhibitor) or NO-releasing ASA for a period of ten days. The area of colonic lesions, colonic blood flow (CBF), myeloperoxidase (MPO) activity and expression of proinflammatory markers COX-2, inducible form of nitric oxide synthase (iNOS), IL-1β and tumor necrosis factor (TNF)-α were assessed. The effects of glyceryl trinitrate (GTN), a NO donor, and 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-​tetramethyl-1H-imidazolyl-1-oxy-3-oxide, onopotassium salt (carboxy-PTIO), a NO scavenger, administered without and with ASA or NO-ASA, and the involvement of capsaicin-sensitive afferent nerves in the mechanism of healing the experimental colitis was also determined. RESULTS: Rats with colitis developed macroscopic and microscopic colonic lesions accompanied by a significant decrease in the CBF, a significant rise in colonic weight, MPO activity and plasma IL-1β and TNF-α levels. These effects were aggravated by ASA and 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560), but not celecoxib and counteracted by concurrent treatment with a synthetic prostaglandin E2 (PGE2) analog. Treatment with NO-ASA dose-dependently accelerated colonic healing followed by a rise in plasma NOx content and CBF, suppression of MPO and downregulation of COX-2, iNOS, IL-1β and TNF-α mRNAs. Treatment with GTN, the NO donor, significantly inhibited the ASA-induced colonic lesions and increased CBF, while carboxy-PTIO or capsaicin-denervation counteracted the NO-ASA-induced improvement of colonic healing and the accompanying increase in the CBF. These effects were restored by co-treatment with calcitonin gene related peptide (CGRP) and NO-ASA in capsaicin-denervated animals. CONCLUSION: NO-releasing ASA, in contrast to ASA, COX-1 inhibitors, and SC-560, accelerated the healing of colitis via a mechanism involving NO mediated improvement of microcirculation and activation of sensory nerves releasing CGRP. PMID:22039321

Virulence and antimicrobial resistance of Enterococcus faecium isolated from water samples.

PubMed

Enayati, M; Sadeghi, J; Nahaei, M R; Aghazadeh, M; Pourshafie, M R; Talebi, M

2015-10-01

The aim of this study was to determine the incidence of Enterococcus species and six virulence factors of Enterococcus faecium which were isolated from surface water and wells. Fifteen different water samples, which were used for drinking as well as agricultural irrigation, were collected from nine private wells and surface water from six rivers located at the east of Tehran. The Ent. faecium isolates were tested for their resistance to 10 antibiotics and their virulence factors were detected using multiplex PCR for esp, acm, gelE, asa1, cylA and hyl genes. The most predominant species in 315 isolates were Ent. faecium (n = 118) followed by Enterococcus galinarom (n = 110), Enterococcus mundeti (n = 18), Enterococcus hirea (n = 37) and Enterococcus casselifelavus (n = 32). The resistance rates were observed in 41·5, 27·1, 12·7, 6·8 and 1·7% isolates for tetracycline, erythromycin, ampicillin, ciprofloxacin and chloramphenicol respectively. None of the Ent. faecium isolates were resistant to vancomycin, teicoplanin, linezolid, gentamicin and quinuspristin-dalfopristin. Virulence determinant was found in 84·7, 33·9, 16·1 and 2·5% of isolates for acm, asa1, esp, cylA respectively. None of the isolates carried hyl and gelE gene. The presence of virulence factors and antibiotic resistance indicated that water might be an important source of dissemination of virulent enterococci. Contamination of drinking or recreational water by human or animal faecal waste is a major public health threat. In this study, we determine the incidence of Enterococcus species and six virulence factors of Enterococcus faecium which were isolated from surface water and wells. Results from this study suggest that the presence of Ent. faecium in natural and well waters was found to be significant in rural areas of Tehran. Resistant to erythromycin among Ent. faecium was relatively high and the incidence of acm and asa1 among our isolates was common overall. © 2015 The Society for Applied Microbiology.

What happens when you want to talk to the animals: lessons of a career in animal bioacoustics

NASA Astrophysics Data System (ADS)

Bowles, Ann E.

2004-05-01

Animal bioacoustics (AB) is the study of sound in nonhuman animal biology. I entered the field because I was interested in the evolution of language, and I wanted to study the acoustic communication of whales and dolphins. Topics like this within the scope of AB make the discipline accessible to students and laypeople. Although career opportunities are limited (professionals declaring AB as their primary area represent only 3% of ASA membership [http://www.acoustics.org/WIA, statistics for 2000]), an interest in AB can foster entry into more marketable disciplines. It has been a particularly important avenue for bringing women into careers in traditionally male-dominated subject areas. For example, women represent 14% of the ASA membership and 12% or fewer of those declaring Underwater Acoustics, Engineering Acoustics, and Noise as their primary interest. However, 25% of those declaring AB as their primary interest are women, and AB includes all three topic areas within its scope. Unfortunately, AB is still fairly inaccessible to interested lay professionals such as educators, science writers, and environmental planners. By helping them to develop a deeper understanding of topics in AB, ASA can help them foster careers in acoustics.

Development and Validation of a Deep Neural Network Model for Prediction of Postoperative In-hospital Mortality.

PubMed

Lee, Christine K; Hofer, Ira; Gabel, Eilon; Baldi, Pierre; Cannesson, Maxime

2018-04-17

The authors tested the hypothesis that deep neural networks trained on intraoperative features can predict postoperative in-hospital mortality. The data used to train and validate the algorithm consists of 59,985 patients with 87 features extracted at the end of surgery. Feed-forward networks with a logistic output were trained using stochastic gradient descent with momentum. The deep neural networks were trained on 80% of the data, with 20% reserved for testing. The authors assessed improvement of the deep neural network by adding American Society of Anesthesiologists (ASA) Physical Status Classification and robustness of the deep neural network to a reduced feature set. The networks were then compared to ASA Physical Status, logistic regression, and other published clinical scores including the Surgical Apgar, Preoperative Score to Predict Postoperative Mortality, Risk Quantification Index, and the Risk Stratification Index. In-hospital mortality in the training and test sets were 0.81% and 0.73%. The deep neural network with a reduced feature set and ASA Physical Status classification had the highest area under the receiver operating characteristics curve, 0.91 (95% CI, 0.88 to 0.93). The highest logistic regression area under the curve was found with a reduced feature set and ASA Physical Status (0.90, 95% CI, 0.87 to 0.93). The Risk Stratification Index had the highest area under the receiver operating characteristics curve, at 0.97 (95% CI, 0.94 to 0.99). Deep neural networks can predict in-hospital mortality based on automatically extractable intraoperative data, but are not (yet) superior to existing methods.

Inhibition of Mycobacterium tuberculosis dihydrodipicolinate synthase by alpha-ketopimelic acid and its other structural analogues

PubMed Central

Shrivastava, Priyanka; Navratna, Vikas; Silla, Yumnam; Dewangan, Rikeshwer P.; Pramanik, Atreyi; Chaudhary, Sarika; Rayasam, GeethaVani; Kumar, Anuradha; Gopal, Balasubramanian; Ramachandran, Srinivasan

2016-01-01

The Mycobacterium tuberculosis dihydrodipicolinate synthase (Mtb-dapA) is an essential gene. Mtb-DapA catalyzes the aldol condensation between pyruvate and L-aspartate-beta-semialdehyde (ASA) to yield dihydrodipicolinate. In this work we tested the inhibitory effects of structural analogues of pyruvate on recombinant Mtb-DapA (Mtb-rDapA) using a coupled assay with recombinant dihydrodipicolinate reductase (Mtb-rDapB). Alpha-ketopimelic acid (α-KPA) showed maximum inhibition of 88% and IC50 of 21 μM in the presence of pyruvate (500 μM) and ASA (400 μM). Competition experiments with pyruvate and ASA revealed competition of α-KPA with pyruvate. Liquid chromatography-mass spectrometry (LC-MS) data with multiple reaction monitoring (MRM) showed that the relative abundance peak of final product, 2,3,4,5-tetrahydrodipicolinate, was decreased by 50%. Thermal shift assays showed 1 °C Tm shift of Mtb-rDapA upon binding α-KPA. The 2.4 Å crystal structure of Mtb-rDapA-α-KPA complex showed the interaction of critical residues at the active site with α-KPA. Molecular dynamics simulations over 500 ns of pyruvate docked to Mtb-DapA and of α-KPA-bound Mtb-rDapA revealed formation of hydrogen bonds with pyruvate throughout in contrast to α-KPA. Molecular descriptors analysis showed that ligands with polar surface area of 91.7 Å2 are likely inhibitors. In summary, α-hydroxypimelic acid and other analogues could be explored further as inhibitors of Mtb-DapA. PMID:27501775

Two aspects of feedforward postural control: anticipatory postural adjustments and anticipatory synergy adjustments.

PubMed

Klous, Miriam; Mikulic, Pavle; Latash, Mark L

2011-05-01

We used the framework of the uncontrolled manifold hypothesis to explore the relations between anticipatory synergy adjustments (ASAs) and anticipatory postural adjustments (APAs) during feedforward control of vertical posture. ASAs represent a drop in the index of a multimuscle-mode synergy stabilizing the coordinate of the center of pressure in preparation to an action. ASAs reflect early changes of an index of covariation among variables reflecting muscle activation, whereas APAs reflect early changes in muscle activation levels averaged across trials. The assumed purpose of ASAs is to modify stability of performance variables, whereas the purpose of APAs is to change magnitudes of those variables. We hypothesized that ASAs would be seen before APAs and that this finding would be consistent with regard to the muscle-mode composition defined on the basis of different tasks and phases of action. Subjects performed a voluntary body sway task and a quick, bilateral shoulder flexion task under self-paced and reaction time conditions. Surface muscle activity of 12 leg and trunk muscles was analyzed to identify sets of 4 muscle modes for each task and for different phases within the shoulder flexion task. Variance components in the muscle-mode space and indexes of multimuscle-mode synergy stabilizing shift of the center of pressure were computed. ASAs were seen ∼ 100-150 ms prior to the task initiation, before APAs. The results were consistent with respect to different sets of muscle modes defined over the two tasks and different shoulder flexion phases. We conclude that the preparation for a self-triggered postural perturbation is associated with two types of anticipatory adjustments, ASAs and APAs. They reflect different feedforward processes within the hypothetical hierarchical control scheme, resulting in changes in patterns of covariation of elemental variables and in their patterns averaged across trials, respectively. The results show that synergies quantified using dissimilar sets of muscle modes show similar feedforward changes in preparation to action.

Brønsted acid sites based on penta-coordinated aluminum species

NASA Astrophysics Data System (ADS)

Wang, Zichun; Jiang, Yijiao; Lafon, Olivier; Trébosc, Julien; Duk Kim, Kyung; Stampfl, Catherine; Baiker, Alfons; Amoureux, Jean-Paul; Huang, Jun

2016-12-01

Zeolites and amorphous silica-alumina (ASA), which both provide Brønsted acid sites (BASs), are the most extensively used solid acid catalysts in the chemical industry. It is widely believed that BASs consist only of tetra-coordinated aluminum sites (AlIV) with bridging OH groups in zeolites or nearby silanols on ASA surfaces. Here we report the direct observation in ASA of a new type of BAS based on penta-coordinated aluminum species (AlV) by 27Al-{1H} dipolar-mediated correlation two-dimensional NMR experiments at high magnetic field under magic-angle spinning. Both BAS-AlIV and -AlV show a similar acidity to protonate probe molecular ammonia. The quantitative evaluation of 1H and 27Al sites demonstrates that BAS-AlV co-exists with BAS-AlIV rather than replaces it, which opens new avenues for strongly enhancing the acidity of these popular solid acids.

Effects of olsalazine in the jejunum of the rat.

PubMed Central

Mohsen, A Q; Mulvey, D; Priddle, J D; Parsons, D S; Jewell, D P

1987-01-01

Olsalazine (ADS) is the azo-linked dimer of 5-aminosalicylic acid (5-ASA). It is of value for the management of patients with ulcerative colitis but may be associated with increasing diarrhoea in a few. This study examines the effect of 5-ASA and ADS on small intestinal transport systems of the rat. Krebs-Ringer-bicarbonate solution was circulated through the lumen of a jejunal segment and the appearance of fluid, glucose and lactate on the serosal surface was shown to be linear over a two hour period. Addition of 5-ASA (10 mmol/l) or ADS (5 mmol/l and 10 mmol/l) caused a significant inhibition both of fluid transport (p less than 0.001), and of the appearance of glucose (p less than 0.001) and lactate (p less than 0.001 for 5 mmol/l and 10 mmol/l ADS, p less than 0.01 for 10 mmol/l 5-ASA). The uptake of glucose by rings of rat jejunum was shown to be markedly reduced by ADS. Experiments substituting glucose with either sucrose of 2-aminoisobutyric acid showed that ADS (5 mmol/l, 10 mmol/l) also inhibited the serosal appearance of fructose and the amino acid. These results show that 5-ASA and ADS, at concentrations which could be expected in the jejunum of patients receiving therapeutic doses, are able to inhibit small intestinal transport systems. The resulting increase in load on the diseased colon could be important for the pathogenesis of diarrhoea. PMID:3570038

Synaptic Inputs Compete during Rapid Formation of the Calyx of Held: A New Model System for Neural Development

PubMed Central

Holcomb, Paul S.; Hoffpauir, Brian K.; Hoyson, Mitchell C.; Jackson, Dakota R.; Deerinck, Thomas J.; Marrs, Glenn S.; Dehoff, Marlin; Wu, Jonathan; Ellisman, Mark H.

2013-01-01

Hallmark features of neural circuit development include early exuberant innervation followed by competition and pruning to mature innervation topography. Several neural systems, including the neuromuscular junction and climbing fiber innervation of Purkinje cells, are models to study neural development in part because they establish a recognizable endpoint of monoinnervation of their targets and because the presynaptic terminals are large and easily monitored. We demonstrate here that calyx of Held (CH) innervation of its target, which forms a key element of auditory brainstem binaural circuitry, exhibits all of these characteristics. To investigate CH development, we made the first application of serial block-face scanning electron microscopy to neural development with fine temporal resolution and thereby accomplished the first time series for 3D ultrastructural analysis of neural circuit formation. This approach revealed a growth spurt of added apposed surface area (ASA) >200 μm2/d centered on a single age at postnatal day 3 in mice and an initial rapid phase of growth and competition that resolved to monoinnervation in two-thirds of cells within 3 d. This rapid growth occurred in parallel with an increase in action potential threshold, which may mediate selection of the strongest input as the winning competitor. ASAs of competing inputs were segregated on the cell body surface. These data suggest mechanisms to select “winning” inputs by regional reinforcement of postsynaptic membrane to mediate size and strength of competing synaptic inputs. PMID:23926251

Nitrates and NO-NSAIDs in Cancer Chemoprevention & Therapy: In Vitro Evidence Querying the NO Donor Functionality

PubMed Central

Dunlap, Tareisha; Abdul-Hay, Samer; Chandrasena, R. Esala P.; Hagos, Ghenet K; Sinha, Vaishali; Wang, Zhiqiang; Wang, Huali; Thatcher, Gregory R. J.

2008-01-01

Properties of the NO-ASA family of NO-donating NSAIDs (NO-NSAIDs), notably NCX 4016 (mNO-ASA) and NCX 4040 (pNO-ASA), reported in more than a hundred publications, have included positive preclinical data in cancer chemoprevention and therapy. Evidence is presented that the antiproliferative, the chemopreventive (antioxidant/electrophile response element (ARE) activation), and the anti-inflammatory activity of NO-ASA in cell cultures is replicated by X-ASA derivatives that are incapable of acting as NO donors. pBr-ASA and mBr-ASA are conisogenic with NO-ASA, but are not NO donors. The biological activity of pNO-ASA is replicated by pBr-ASA; and both pNO-ASA and pBr-ASA are bioactivated to the same quinone methide electrophile. The biological activity of mNO-ASA is replicated by mBr-ASA; mNO-ASA and mBr-ASA are bioactivated to different benzyl electrophiles. The observed activity is likely initiated by trapping of thiol biomolecules by the quinone and benzyl electrophiles, leading to depletion of GSH and modification of Cys-containing sensor proteins. Whereas all NO-NSAIDs containing the same structural “linker” as NCX 4040 and NCX 4016 are anticipated to possess activity resulting from bioactivation to electrophilic metabolites, this expectation does not extend to other linker structures. Nitrates require metabolic bioactivation to liberate NO bioactivity, which is often poorly replicated in vitro, and NO bioactivity provided by NO-NSAIDs in vivo provides proven therapeutic benefits in mitigation of NSAID gastrotoxicity. The in vivo properties of X-ASA drugs await discovery. PMID:18485921

Nitrates and NO-NSAIDs in cancer chemoprevention and therapy: in vitro evidence querying the NO donor functionality.

PubMed

Dunlap, Tareisha; Abdul-Hay, Samer O; Chandrasena, R Esala P; Hagos, Ghenet K; Sinha, Vaishali; Wang, Zhiqiang; Wang, Huali; Thatcher, Gregory R J

2008-09-01

Properties of the NO-ASA family of NO-donating NSAIDs (NO-NSAIDs), notably NCX 4016 (mNO-ASA) and NCX 4040 (pNO-ASA), reported in more than one hundred publications, have included positive preclinical data in cancer chemoprevention and therapy. Evidence is presented that the antiproliferative, the chemopreventive (antioxidant/electrophile response element (ARE) activation), and the anti-inflammatory activity of NO-ASA in cell cultures is replicated by X-ASA derivatives that are incapable of acting as NO donors. pBr-ASA and mBr-ASA are conisogenic with NO-ASA, but are not NO donors. The biological activity of pNO-ASA is replicated by pBr-ASA; and both pNO-ASA and pBr-ASA are bioactivated to the same quinone methide electrophile. The biological activity of mNO-ASA is replicated by mBr-ASA; mNO-ASA and mBr-ASA are bioactivated to different benzyl electrophiles. The observed activity is likely initiated by trapping of thiol biomolecules by the quinone and benzyl electrophiles, leading to depletion of GSH and modification of Cys-containing sensor proteins. Whereas all NO-NSAIDs containing the same structural "linker" as NCX 4040 and NCX 4016 are anticipated to possess activity resulting from bioactivation to electrophilic metabolites, this expectation does not extend to other linker structures. Nitrates require metabolic bioactivation to liberate NO bioactivity, which is often poorly replicated in vitro, and NO bioactivity provided by NO-NSAIDs in vivo provides proven therapeutic benefits in mitigation of NSAID gastrotoxicity. The in vivo properties of X-ASA drugs await discovery.

Asiago spectroscopic classification of ASAS-SN18ck, ASAS-SN18cp, ASAS-SN18cq and ASASSN-18cj

NASA Astrophysics Data System (ADS)

Tomasella, L.; Benetti, S.; Cappellaro, E.; Turatto, M.

2018-02-01

The Asiago Transient Classification Program (Tomasella et al. 2014, AN, 335, 841) reports the spectroscopic classification of ASAS-SN18ck, ASAS-SN18cp, ASAS-SN18cq and ASASSN-18cj, discovered during the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN, Shappee et al. 2014, Atel #11178).

Aspirin Allergy Desensitization in Cerebrovascular Disease

PubMed Central

Zuckerman, Scott L; Seder, David B; Tsujiura, Crystiana; Cushing, Deborah; Gallup, Holly; Mocco, J; Hanel, Richard A; Ecker, Robert D

2014-01-01

Summary Aspirin (ASA) is the mainstay of treatment in cerebrovascular and systemic vascular disease. ASA hypersensitivity can pose a challenge to achieving optimum medical management prior to and after neurointerventional treatment. Desensitization to ASA is well described in the allergy and cardiovascular literature, but there are no similar discussions specific to neurointervention. The purpose of our study was to describe our experience with ASA hypersensitivity management and review the relevant literature. Two cases of patients with symptomatic cerebrovascular disease requiring neurointervention who were successfully desensitized to their ASA hypersensitivity prior to treatment are described. The subsequent literature is reviewed. Several ASA desensitization protocols exist and have been proven to successfully treat ASA hypersensitivity and allow for ASA therapy to be safely initiated. We describe several previously published protocols. ASA desensitization is a safe and simple way to manage ASA hypersensitivity. We provide comprehensive management guidelines for the neurointerventionalist engaging in ASA desensitization. PMID:24556294

What Level 2 Products are available?

Atmospheric Science Data Center

2014-12-08

The Aerosol data (MIL2ASAE) contains aerosol optical depth, aerosol compositional model, ancillary meteorological data, and related parameters on a 17.6 km grid. The Land Surface data (MIL2ASLS) includes bihemispherical and...

Influence of the aqueous film coating process on the properties and stability of tablets containing a moisture-labile drug.

PubMed

Ruotsalainen, Mirja; Heinämäki, Jyrki; Taipale, Krista; Yliruusi, Jouko

2003-01-01

The effects of an aqueous film coating process on the morphology and storage stability of hydroxypropyl methylcellulose-coated tablets containing a moisture-labile model drug (acetylsalicylic acid, ASA) were evaluated using an instrumented side-vented tablet pan coater. Coating parameters studied were inlet air absolute humidity 5 g/m3 and 12 g/m3, spraying air pressure 100 kPa and 500 kPa, pan air temperature 35 degrees C and 55 degrees C, and coating solution flow rate 2.2 g/min and 7.8 g/min. The surface roughness of the coatings was measured with a laser profilometer and the chemical hydrolysis of the model drug ASA with an UV-spectrophotometer. The film-coated tablets were stored at 25 degrees C/60% RH and 40 degrees C/75% RH for three months. The high absolute humidity of the inlet air increased the residual water content and surface roughness of the coated tablets. Using a lower coating solution flow rate, higher spraying air pressure and pan temperature the coatings were smooth and homogeneous. In both ambient and accelerated storage conditions, the roughness of the coatings and the hydrolysis of ASA increased, but this was independent of the film coating process. Uniform and smooth hydroxypropyl methylcellulose coatings can be achieved by improved control of process parameters related to the application of the coating solution and water evaporation of the tablet surface.

Inhibitory activity of aspirin on von Willebrand factor-induced platelet aggregation.

PubMed

Homoncik, M; Jilma, B; Eichelberger, B; Panzer, S

2000-09-01

The effect of aspirin (ASA) on vWF induced platelet - platelet interaction is unknown. We therefore tested the response of platelets to von Willebrand factor (vWF) coated beads induced platelet aggregation before and after i.v. and oral ASA. 1000 mg ASA was infused to 10 healthy individuals and after a wash-out period 7 volunteers received 100 mg ASA orally over a period of 11 days. Prior to ASA and in regular intervals thereafter we tested the reactivity to vWF-coated beads to assess platelet adhesion/aggregation and the fade-out time of ASA effects on platelets. Considerable interindividual variability in response to vWF-coated beads was observed, both before ASA and after treatment with ASA. The maximal response to vWF-coated beads (Tmax), the time lag, and the slope of the curve were significantly affected by i.v. ASA, whereas 100 mg of ASA had only inconstant effect on Tmax and slope. The absolute reduction of Tmax after ASA depended on the pre-ASA level, while the percentage of the reduction was similar in all individuals. Thus, platelet aggregation induced by vWF-coated beads is impaired by ASA. Furthermore, our data indicate a large interindividual variability of the response to ASA shortly after treatment induction, which becomes more constant after prolonged treatment.

Long-distance transport of L-ascorbic acid in potato

PubMed Central

Tedone, Luigi; Hancock, Robert D; Alberino, Salvatore; Haupt, Sophie; Viola, Roberto

2004-01-01

Background Following on from recent advances in plant AsA biosynthesis there is increasing interest in elucidating the factors contributing to the L-ascorbic acid (AsA) content of edible crops. One main objective is to establish whether in sink organs such as fruits and tubers, AsA is synthesised in situ from imported photoassimilates or synthesised in source tissues and translocated via the phloem. In the current work we test the hypothesis that long-distance transport is involved in AsA accumulation within the potato tuber, the most significant source of AsA in the European diet. Results Using the EDTA exudation technique we confirm the presence of AsA in the phloem of potato plants and demonstrate a correlation between changes in the AsA content of source leaves and that of phloem exudates. Comparison of carboxyflourescein and AgNO3 staining is suggestive of symplastic unloading of AsA in developing tubers. This hypothesis was further supported by the changes in AsA distribution during tuber development which closely resembled those of imported photoassimilates. Manipulation of leaf AsA content by supply of precursors to source leaves resulted in increased AsA content of developing tubers. Conclusion Our data provide strong support to the hypothesis that long-distance transport of AsA occurs in potato. We also show that phloem AsA content and AsA accumulation in sink organs can be directly increased via manipulation of AsA content in the foliage. We are now attempting to establish the quantitative contribution of imported AsA to overall AsA accumulation in developing potato tubers via transgenic approaches. PMID:15377389

Quantitative distribution of radiolabeled 5-aminosalicylic acid enemas in patients with left-sided ulcerative colitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vitti, R.A.; Meyers, F.; Knight, L.C.

1989-11-01

Rectally administered suspensions of 5-aminosalicylic acid (5-ASA) are topically effective in treating left-sided ulcerative colitis. The extent to which the contents of these enemas are distributed to inflamed mucosal linings has not previously been determined. This study was undertaken to validate a technique for labeling 5-ASA with 99mTc and to quantitate the distribution of (99mTc)5-ASA in eight patients with left-sided ulcerative colitis. Eight patients underwent three colonic scintigraphic exams within five days, receiving a 60-ml radiolabeled 5-ASA enema into the unprepared rectum for each study, with sequential anterior abdominal images obtained for 4 hr. Activity within the rectum, sigmoid, descending,more » transverse, and ascending colon was quantitated. Over 50% of the labeled enema had advanced beyond the rectum in five of eight patients and in six of eight patients by 30 min and 60 min, respectively. The distribution of (99mTc)5-ASA was quantitatively reproducible when repeated in the same patient on different days, despite apparent visual differences. By 2 hr, the amount of the enema present within the rectum decreased significantly (P less than 0.05) compared to the initial distribution. The amount of enema present within the descending colon was increased significantly at 0.5 hr (P less than 0.05) and at 2 hr (P less than 0.01). There were no significant changes in the distribution from initial values for the sigmoid, transverse, or ascending colon at any time. In each of these cases the spread of the enema to or beyond the extent of disease was documented. In patients with left-sided ulcerative colitis, small volume (99mTc)5-ASA enemas reliably reach the area of inflammation.« less

Aspirin Enhances Osteogenic Potential of Periodontal Ligament Stem Cells (PDLSCs) and Modulates the Expression Profile of Growth Factor-Associated Genes in PDLSCs.

PubMed

Abd Rahman, Fazliny; Mohd Ali, Johari; Abdullah, Mariam; Abu Kasim, Noor Hayaty; Musa, Sabri

2016-07-01

This study investigates the effects of aspirin (ASA) on the proliferative capacity, osteogenic potential, and expression of growth factor-associated genes in periodontal ligament stem cells (PDLSCs). Mesenchymal stem cells (MSCs) from PDL tissue were isolated from human premolars (n = 3). The MSCs' identity was confirmed by immunophenotyping and trilineage differentiation assays. Cell proliferation activity was assessed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Polymerase chain reaction array was used to profile the expression of 84 growth factor-associated genes. Pathway analysis was used to identify the biologic functions and canonic pathways activated by ASA treatment. The osteogenic potential was evaluated through mineralization assay. ASA at 1,000 μM enhances osteogenic potential of PDLSCs. Using a fold change (FC) of 2.0 as a threshold value, the gene expression analyses indicated that 19 genes were differentially expressed, which includes 12 upregulated and seven downregulated genes. Fibroblast growth factor 9 (FGF9), vascular endothelial growth factor A (VEGFA), interleukin-2, bone morphogenetic protein-10, VEGFC, and 2 (FGF2) were markedly upregulated (FC range, 6 to 15), whereas pleotropin, FGF5, brain-derived neurotrophic factor, and Dickkopf WNT signaling pathway inhibitor 1 were markedly downregulated (FC 32). Of the 84 growth factor-associated genes screened, 35 showed high cycle threshold values (≥35). ASA modulates the expression of growth factor-associated genes and enhances osteogenic potential in PDLSCs. ASA upregulated the expression of genes that could activate biologic functions and canonic pathways related to cell proliferation, human embryonic stem cell pluripotency, tissue regeneration, and differentiation. These findings suggest that ASA enhances PDLSC function and may be useful in regenerative dentistry applications, particularly in the areas of periodontal health and regeneration.

Gastroduodenal mucosal defence mechanisms and the action of non-steroidal anti-inflammatory agents.

PubMed

Garner, A; Allen, A; Rowe, P H

1987-01-01

This review summarises gastroduodenal protective mechanisms, the actions of non-steroidal anti-inflammatory (NSAI) agents on mucus and HCO3 secretions, and the basis of gastric mucosal injury induced by acetylsalicylic and salicylic acids (ASA and SA). Resistance to autodigestion by acid and pepsin present in gastric juice is multifactorial involving pre-epithelial (mucus-bicarbonate barrier) and post-epithelial (blood flow, acid-base balance) factors in addition to properties of the surface cell layer per se. The latter includes mucosal re-epithelialisation, a property which appears particularly important with respect to recovery from acute injury. A range of NSAI agents (ASA, fenclofenac, ibuprofen and indomethacin) inhibit gastric HCO3 transport in isolated mucosal preparations. Inhibition of duodenal HCO3 transport has been demonstrated in response to indomethacin in vitro and in vivo. These effects on secretion can be antagonised by exogenous prostaglandins of the E series. The layer of secreted mucus gel overlying the epithelial surface is not affected by NSAI drugs in the short term. However a number of these agents have been shown to inhibit glycoprotein biosynthesis by the epithelial cells. Thus loss of this protective coat could be anticipated during chronic drug exposure since erosion of adherent mucus by luminal shear and proteolysis would not be compensated by continued secretion. Detailed analysis of the gastric mucosal injury induced by salicylates both in vitro and in vivo reveals that much of the damage previously attributed to ASA is in fact due to the metabolic product SA. In this respect it is concluded that mucosal injury caused by ASA is due to a combination of two factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Transintestinal transport mechanisms of 5-aminosalicylic acid (in situ rat intestine perfusion, Caco-2 cells) and Biopharmaceutics Classification System.

PubMed

Smetanová, Libuše; Stětinová, Věra; Kholová, Dagmar; Kuneš, Martin; Nobilis, Milan; Svoboda, Zbyněk; Květina, Jaroslav

2013-09-01

The aim of the study was 1) to estimate permeability of 5-aminosalicylic acid (5-ASA), 2) to categorize 5-ASA according to BCS (Biopharmaceutics Classification System), and 3) to contribute to determination of 5-ASA transintestinal transport and biotransformation mechanisms. The in situ rat intestine perfusion was used as an initial method to study 5-ASA transport. The amount of 5-ASA (released from tablet) transferred into portal circulation reached 5.79 ± 0.24%. During this transport, the intestinal formation of 5-ASA main metabolite (N-ac-5-ASA) occurred. N-ac-5-ASA was found in perfusate both from intestinal lumen and from v. portae. In in vitro Caco-2 monolayers, transport of 5-ASA (10-1000 µmol/l) was studied in apical-basolateral and basolateral-apical direction (iso-pH 7.4 conditions). The transport of total 5-ASA (parent drug plus intracellularly formed N-ac-5-ASA) was linear with time, concentration- and direction-dependent. Higher basolateral-apical (secretory) transport was mainly caused by higher transport of the metabolite (suggesting metabolite efflux transport). Transport of 5-ASA (only parent drug) was saturable (transepithelial carrier-mediated) at low doses, dominated by passive, paracellular process in higher doses which was confirmed by increased 5-ASA transport using Ca2+-free transport medium. The estimated low 5-ASA permeability and its low solubility enable to classify 5-ASA as BCS class IV.

Aspirin allergy desensitization in cerebrovascular disease. A report of two cases, literature review and management guide for the neurointerventionalist.

PubMed

Zuckerman, Scott L; Seder, David B; Tsujiura, Crystiana; Cushing, Deborah; Gallup, Holly; Mocco, J; Hanel, Richard A; Ecker, Robert D

2014-01-01

Aspirin (ASA) is the mainstay of treatment in cerebrovascular and systemic vascular disease. ASA hypersensitivity can pose a challenge to achieving optimum medical management prior to and after neurointerventional treatment. Desensitization to ASA is well described in the allergy and cardiovascular literature, but there are no similar discussions specific to neurointervention. The purpose of our study was to describe our experience with ASA hypersensitivity management and review the relevant literature. Two cases of patients with symptomatic cerebrovascular disease requiring neurointervention who were successfully desensitized to their ASA hypersensitivity prior to treatment are described. The subsequent literature is reviewed. Several ASA desensitization protocols exist and have been proven to successfully treat ASA hypersensitivity and allow for ASA therapy to be safely initiated. We describe several previously published protocols. ASA desensitization is a safe and simple way to manage ASA hypersensitivity. We provide comprehensive management guidelines for the neurointerventionalist engaging in ASA desensitization.

Electrochemical behavior of triflusal, aspirin and their metabolites at glassy carbon and boron doped diamond electrodes.

PubMed

Enache, Teodor Adrian; Fatibello-Filho, Orlando; Oliveira-Brett, Ana Maria

2010-08-01

The electrochemical behavior of triflusal (TRF) and aspirin (ASA), before and after hydrolysis in water and in alkaline medium using two different electrode surfaces, glassy carbon and boron doped diamond, was study by differential pulse voltammetry over a wide pH range. The hydrolysis products are 2-(hydroxyl)-4-(trifluoromethyl)-benzoic acid (HTB) for triflusal and salicylic acid (SA) for aspirin, which in vivo represent their main metabolites. The hydrolysis processes were also followed by spectrophotometry. The UV results showed complete hydrolysis after one hour for TRF and after two hours for ASA in alkaline solution. The glassy carbon electrode enables only indirect determination of TRF and ASA through the electrochemical detection of their hydrolysis products HTB and SA, respectively. The oxidation processes of HTB and SA are pH dependent and involve different numbers of electrons and protons. Moreover, the difference between the oxidation peak potential of SA and HTB was equal to 100 mV in the studied pH range from 1 to 8 due to the CF3 of the aromatic ring of HTB molecule. Due to its wider oxidation potential range, the boron doped diamond electrode was used to study the direct oxidation of TRF and ASA, as well as of their respective metabolites HTB and SA.

Human brucellosis mimicking axial spondyloarthritis: a challenge for rheumatologists when applying the 2009 ASAS criteria.

PubMed

Ye, Cong; Shen, Gui-Fen; Li, Shou-Xin; Dong, Ling-Li; Yu, Yi-Kai; Tu, Wei; Zhu, Ying-Zi; Hu, Shao-Xian

2016-06-01

Although the development of the 2009 SpA classification criteria by Assessment of SpondyloArthritis international Society (ASAS) represents an important step towards a better definition of the early disease stage particularly in axial spondyloarthritis (axSpA), the specificity of the criteria has been criticized these days. As the commonest zoonotic infection worldwide, human brucellosis can mimic a large number of diseases, including SpA. This study was performed to determine the frequency of rheumatologic manifestations in patients with brucellosis and the chance of misdiagnosing them as having axSpA in central China. The results showed that clinical manifestations of axSpA could be observed in brucellosis. Over half of patients had back pain, and one fifth of the patients with back pain were less than 45 years old at onset and had the symptom for more than 3 months. Two young males were falsely classified as suffering from axSpA according to the ASAS criteria, and one with MRI proved sacroiliitis was once given Etanercept for treatment. Therefore, differential diagnosis including human brucellosis should always be kept in mind when applying the ASAS criteria, even in traditionally non-endemic areas.

Final expanded site inspection, ammunition storage area, Anniston Army Depot, Anniston, Alabama. Final report, September 1992-November 1994

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suomela, K.D.; Highsmith, R.L.; Rapuano, K.F.

1994-11-15

An Expanded Site Inspection (ESI) was conducted at the Anniston Army Depot (ANAD) Ammunition Storage Area (ASA). The objective of this ESI was to gather the information and data necessary to determine whether there is sufficient evidence of any release of contamination that would require additional investigation. The ASA contains 1,300 ammunition storage magazines and an ammunition maintenance workshop complex which includes buildings for maintenance, demilitarization, and inspection of all types of ammunition and their components. Fifteen Solid Waste Management Units (SWMUs) were the focus of the ESI, of which 11 were recommend for further investigation. The work included amore » review of historical records, field investigations, laboratory analyses, data interpretation, and report preparation. Contamination from volatile organic compounds and semi volatile organic compounds is not a major problem at the ASA. Arsenic, beryllium, cadmium, chromium, lead, mercury, nickel, silver, vanadium, zinc, explosives, and total petroleum hydrocarbons were detected above control screening values levels in one or more of the media sampled. Nitrate/nitrite and total organic carbon were also detected above control screening values in samples of groundwater, soil, and sediment from a number of SWMUs.« less

Warfarin and Aspirin Use for Stroke Prevention Among Patients With Atrial Fibrillation: The US National Health and Wellness Survey.

PubMed

Goren, Amir; Liu, Xianchen; Gupta, Shaloo; Simon, Teresa A; Phatak, Hemant

2015-01-01

Vitamin K antagonist (VKA) and aspirin (ASA) are recommended for stroke prevention in patients with atrial fibrillation (AF). This study examined VKA and ASA use and their clinical correlates, including CHADS2 stroke risk scores, among adult patients with AF in the general population. Participants included 1290 (1.72%) adults reporting diagnosis with AF (mean age, 64.9 years; 65% men) from the 2009 US National Health and Wellness Survey, an online, self-administered, nationwide, stratified random sample survey of 75,000 adults. Antithrombotic use patterns, including VKA, ASA, VKA+ASA, and non-VKA/ASA, and their correlates were examined using logistic regressions. Respondents with AF were treated with VKA (26.6%), ASA (34.5%), VKA+ASA (15.4%), or neither (23.5%). Among those with CHADS2 ≥1, 19.3% did not report use of VKA or ASA. Among those with CHADS2 ≥2, 35.7% were treated only with ASA. Adjusting for covariates in logistic regressions, CHADS2 ≥1 was associated with VKA and/or ASA (vs. non-VKA/ASA) use (P ≤ 0.02), but CHADS2 score did not differentiate VKA versus ASA use (P > 0.4). Comorbidities were associated with ASA versus VKA use (P ≤ 0.01). Older age, male gender, married status, and obesity were each associated with use of at least one of the treatments investigated (all P < 0.05). One-in-five AF patients with CHADS2 ≥1 were untreated and more than one-third with CHADS2 ≥2 treated with only ASA for stroke prevention. Our findings suggest that although patient characteristics including CHADS2 score were associated with either VKA or ASA use, CHADS2 score was unrelated to VKA versus ASA treatment.

[Preoperative risk assessment with the ASA classification. A prospective study of morbidity and mortality in various ASA classes in 2,937 patients in general surgery].

PubMed

Menke, H; John, K D; Klein, A; Lorenz, W; Junginger, T

1992-12-01

The value of ASA classification in assessment of perioperative risk, i.e. especially postoperative morbidity, was analyzed prospectively using the data of 2937 patients. The analysis took into account the criteria validity, reliability, and sensitivity. The incidence of post-operative morbidity after elective surgery rose from 3.9% in ASA class I to 36% in ASA class IV. Mortality was 0.6% in ASA class II, whereas 9.3% died in ASA class IV. Morbidity, mortality respectively, after emergency surgery was 10.2% in ASA class II compared to 69% in class IV, mortality 1.4% compared to 21.5%. Differences between the ASA classes were confirmed (p-value < 0.05) considering separate kinds of complications and different periods. Furthermore, ASA classification was a valuable reference to length of stay and severity of necessary therapy at the ICU.

Ascorbic Acid Metabolism in Pea Seedlings. A Comparison of d-Glucosone, l-Sorbosone, and l-Galactono-1,4-Lactone as Ascorbate Precursors1

PubMed Central

Pallanca, Jane E.; Smirnoff, Nicholas

1999-01-01

l-Ascorbic acid (AsA) accumulates in pea (Pisum sativum L.) seedlings during germination, with the most rapid phase of accumulation coinciding with radicle emergence. Monodehydroascorbate reductase and dehydroascorbic acid reductase were active in the embryonic axes before AsA accumulation started, whereas AsA oxidase and AsA peroxidase activities increased in parallel with AsA. Excised embryonic axes were used to investigate the osone pathway of AsA biosynthesis, in which d-glucosone and l-sorbosone are the proposed intermediates. [U-14C]Glucosone was incorporated into AsA and inhibited the incorporation of [U-14C]glucose (Glc) into AsA. A higher d-glucosone concentration (5 mm) inhibited AsA accumulation. l-Sorbosone did not affect AsA pool size but caused a small inhibition in the incorporation of [U-14C]Glc into AsA. Oxidase and dehydrogenase activities capable of converting Glc or Glc-6-phosphate to glucosone were not detected in embryonic axis extracts. The osones are therefore unlikely to be physiological intermediates of AsA biosynthesis. l-Galactono-1,4-lactone, recently proposed as the AsA precursor (G.L. Wheeler, M.A. Jones, N. Smirnoff [1998] Nature 393: 365–369), was readily converted to AsA by pea embryonic axes. Although l-galactono-1,4-lactone did not inhibit [14C]Glc incorporation into AsA, this does not mean that it is not a precursor, because competition between endogenous and exogenous pools was minimized by its very small pool size and rapid metabolism. PMID:10364396

Bidirectional reflectance effects derived from ASAS imagery of a pecan orchard

NASA Astrophysics Data System (ADS)

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

1993-09-01

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

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

PubMed Central

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

2016-01-01

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

Genetic parameters for carcass and ultrasound traits in Hereford and admixed Simmental beef cattle: Accuracy of evaluating carcass traits.

PubMed

Su, H; Golden, B; Hyde, L; Sanders, S; Garrick, D

2017-11-01

Genetic parameters are required to evaluate carcass merit using correlated real-time ultrasound (RTU) measurements. Many registered bulls and heifers are measured using RTU before consideration for selection as parents, whereas few animals are recorded for carcass traits and those are often crossbred steers. The objective of this study was to estimate genetic parameters required for evaluating carcass merit in the American Hereford Association (AHA) and the American Simmental Association (ASA) using multivariate models and to assess accuracy of carcass trait estimated breeding values (EBV) for selection candidates. All available carcass data including carcass weight (CWT), fat thickness (FAT), longissimus muscle area (LMA), and marbling score (MRB) were provided by the AHA and the ASA along with RTU data including fat thickness (UFAT), longissimus muscle area (ULMA), and percentage of intramuscular fat (UIMF). Carcass data comprised 6,054 AHA and 9,056 ASA cattle, while RTU data in comparable numbers from close relatives comprised 6,074 AHA and 7,753 ASA cattle. Pedigrees included 33,226 AHA and 37,665 ASA animals. Fixed effects for carcass and RTU data included contemporary group, age at scan/slaughter, and major breed percentages. Restricted maximum likelihood procedures were applied to all the carcass and RTU measurements, along with birth weight to account for selection, fitting 8-trait multivariate models separately for each breed association. Heritability estimates for AHA and ASA carcass traits were 0.41 ± 0.04 and 0.25 ± 0.03 for FAT, 0.47 ± 0.04 and 0.32 ± 0.03 for LMA, 0.48 ± 0.04 and 0.43 ± 0.04 for MRB, 0.51 ± 0.04 and 0.34 ± 0.03 for CWT, and for RTU traits were 0.29 ± 0.04 and 0.37 ± 0.03 for UFAT, 0.31 ± 0.04 and 0.44 ± 0.03 for ULMA, and 0.45 ± 0.04 and 0.42 ± 0.03 for UIMF. Genetic correlations for AHA and ASA analyses between FAT and UFAT were 0.74 ± 0.08 and 0.28 ± 0.13, between LMA and ULMA were 0.81 ± 0.07 and 0.57 ± 0.10, and between MRB and UIMF were 0.54 ± 0.08 and 0.73 ± 0.07. Predictions of carcass merit using RTU measurements in Hereford cattle would be more reliable for FAT and LMA than MRB, but the reverse would be true for admixed Simmental cattle. Genetic correlations for MRB in AHA and for FAT and LMA in ASA are less than currently assumed in their national evaluations. Collection of greater numbers of carcass measurements would improve the accuracy of genetic evaluations for carcass traits in both breeds.

Size control of Au NPs supported by pH operation

NASA Astrophysics Data System (ADS)

Ichiji, Masumi; Akiba, Hiroko; Hirasawa, Izumi

2017-07-01

Au NPs are expected to become useful functional particles, as particle gun used for plant gene transfer and also catalysts. We have studied PSD (particle size distribution) control of Au NPs by reduction crystallization. Previous study found out importance of seeds policy and also feeding profile. In this paper, effect of pH in the reduction crystallization was investigated to clarify the possibility of Au NPs PSD control by pH operation and also their growth process. Au NPs of size range 10-600 nm were obtained in single-jet system using ascorbic acid (AsA) as a reducing agent with adjusting pH of AsA. Au NPs are found to grow in the process of nucleation, agglomeration, agglomeration growth and surface growth. Au NPs tend to grow by agglomeration and become larger size in lower pH regions, and to grow only by surface growth and become smaller size in higher pH regions.

[Comparative study of respiratory exchanging surfaces in birds and mammals].

PubMed

Jammes, Y

1975-01-01

Anatomical studies of the respiratory apparatus of birds show evidences for a gas exchanging tubular system (parabronchi and air capillaries); these exchanging structures are entirely dissociated from the ventilatory drive acting on the air sacs. A "cross-current" gas exchanging system (perpendicular disposition of air and blood capillaries) allow a good wash-out of carbon dioxide (PaCO2 lower than PECO2). The great efficiency of this lung is allowed by its very large diffusive surface (ASa) and by the high values of lung specific oxygen diffusing capacity (DO2/ASa) and of O2 extraction coefficient in inspired air. The ventilatory pattern of birds is characterized by a greater tidal volume and a smaller respiratory frequency than in mammals of same weight. Respiratory centers of birds receive afferences from lung stretch receptors, CO2-sensitive lung receptors and arterial chemoreceptors.

ASA24-2016

Cancer.gov

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

ASA24-2014, 2012, and 2011, all versions (no longer available)

Cancer.gov

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

Privatization of Army Lodging

DTIC Science & Technology

2008-03-25

primary point person for this initiative is ASA for Installations and Environment (ASA- I& E ). 9 * There are 11 major commands, only 1 shown on...FM&C) DCS G-8 DCS G-8 ASA (I& E ) ASA (I& E ) ASA (M&RA) ASA (M&RA) DCS G-1 DCS G-1 CIO/ G-6 CIO/ G-6 DCS G-2 DCS G-2 DCS G-3 DCS G-3 DASDAS ACSIM/ IMCOM...Army Ch of Staff Army Figure 1 – Army Stakeholders in Policy Process18 The Office of the ASA-I& E has responsibility for policy development

Aspirin desensitization in aspirin-sensitive asthma: failure to maintain a desensitized state during prolonged therapy.

PubMed

Dankner, R E; Wedner, H J

1983-11-01

A patient with a history of asthma induced by acetylsalicylic acid (ASA) was found to be ASA sensitive when orally challenged with ASA. She was successfully desensitized using incremental doses of ASA given orally and maintained on ASA or other nonsteroidal antiinflammatory (NSAI) agents for the treatment of arthritis. After 6 months of uninterrupted therapy the patient developed asthmatic symptoms that were related to ASA and NSAI drug therapy. Although desensitization may be achieved in patients with ASA-sensitive asthma, sensitivity may recur despite continuous therapy.

Regulation of tomato fruit ascorbate content is more highly dependent on fruit irradiance than leaf irradiance.

PubMed

Gautier, Hélène; Massot, Capucine; Stevens, Rebecca; Sérino, Sylvie; Génard, Michel

2009-02-01

The mechanisms involving light control of vitamin C content in fruits are not yet fully understood. The present study aimed to evaluate the impact of fruit and leaf shading on ascorbate (AsA) accumulation in tomato fruit and to determine how fruit sugar content (as an AsA precursor) affected AsA content. Cherry tomato plants were grown in a glasshouse. The control treatment (normally irradiated fruits and irradiated leaves) was compared with the whole-plant shading treatment and with leaf or fruit shading treatments in fruits harvested at breaker stage. In a second experiment, the correlation between sugars and AsA was studied during ripening. Fruit shading was the most effective treatment in reducing fruit AsA content. Under normal conditions, AsA and sugar content were correlated and increased with the ripening stage. Reducing fruit irradiance strongly decreased the reduced AsA content (-74 %), without affecting sugars, so that sugar and reduced AsA were no longer correlated. Leaf shading delayed fruit ripening: it increased the accumulation of oxidized AsA in green fruits (+98 %), whereas it decreased the reduced AsA content in orange fruits (-19 %), suggesting that fruit AsA metabolism also depends on leaf irradiance. Under fruit shading only, the absence of a correlation between sugars and reduced AsA content indicated that fruit AsA content was not limited by leaf photosynthesis or sugar substrate, but strongly depended on fruit irradiance. Leaf shading most probably affected fruit AsA content by delaying fruit ripening, and suggested a complex regulation of AsA metabolism which depends on both fruit and leaf irradiance and fruit ripening stage.

[Pharmacokinetics after oral and intravenous administration of d,l-monolysine acetylsalicylate and an oral dose of acetylsalicylic acid in healthy volunteers].

PubMed

Raschka, C; Koch, H J

2001-01-01

We studied the ASA pharmacokinetics of single doses of 500 mg and 1000 mg of D,L-lysine-monoacetylsalicylate (Lys-ASA) administered both orally (Delgesic) and 500 mg parenterally (Aspisol) as well as 500 mg acetylsalicylate (ASA, Aspirin) in 13 healthy volunteers. Blood samples were taken before and at defined times up to 48 h after application of Lys-ASA and ASA. Analysis for ASA and its metabolite salicylic acid were performed by HPLC. All concentration versus time data were presented descriptively. As far as ASA was concerned, differences were assessed by means of ANOVA according to Friedman including post hoc Wilcoxon tests for each time point. Pharmacokinetic parameters were calculated based on a one-compartment model. The concentration vs. time curves after oral intake of 500 mg of ASA and Lys-ASA differed significantly (p < 0.001). Peak serum ASA concentrations (Cmax) were 6.8 mg/l for oral Lys-ASA and 2.7 mg/l for ASA per os. The corresponding tmax-values were 14.2 and 38.0 min. Absolute bioavailabilities for 500 mg doses were 75.4 and 63.4 pour cent, respectively. After intake of 100 mg and 1000 mg oral doses of Lys-ASA Cmax was 2.7 mg/l and 15.9 mg/l, tmax being 14.2 min for the 1000 mg dose. The shortest half-life was found after i.v. injection with 7.5 min. Metabolism was fast with maximum rise of salicylic acid concentration after injection of Lys-ASS. We conclude that concerning time dimension oral administration of Lys-ASA is almost equivalent to i.v. Lys-ASA and may be an alternative for i.v. administration in cases of acute heart attacks.

Regulation of tomato fruit ascorbate content is more highly dependent on fruit irradiance than leaf irradiance

PubMed Central

Gautier, Hélène; Massot, Capucine; Stevens, Rebecca; Sérino, Sylvie; Génard, Michel

2009-01-01

Background and Aims The mechanisms involving light control of vitamin C content in fruits are not yet fully understood. The present study aimed to evaluate the impact of fruit and leaf shading on ascorbate (AsA) accumulation in tomato fruit and to determine how fruit sugar content (as an AsA precursor) affected AsA content. Methods Cherry tomato plants were grown in a glasshouse. The control treatment (normally irradiated fruits and irradiated leaves) was compared with the whole-plant shading treatment and with leaf or fruit shading treatments in fruits harvested at breaker stage. In a second experiment, the correlation between sugars and AsA was studied during ripening. Key Results Fruit shading was the most effective treatment in reducing fruit AsA content. Under normal conditions, AsA and sugar content were correlated and increased with the ripening stage. Reducing fruit irradiance strongly decreased the reduced AsA content (−74 %), without affecting sugars, so that sugar and reduced AsA were no longer correlated. Leaf shading delayed fruit ripening: it increased the accumulation of oxidized AsA in green fruits (+98 %), whereas it decreased the reduced AsA content in orange fruits (−19 %), suggesting that fruit AsA metabolism also depends on leaf irradiance. Conclusions Under fruit shading only, the absence of a correlation between sugars and reduced AsA content indicated that fruit AsA content was not limited by leaf photosynthesis or sugar substrate, but strongly depended on fruit irradiance. Leaf shading most probably affected fruit AsA content by delaying fruit ripening, and suggested a complex regulation of AsA metabolism which depends on both fruit and leaf irradiance and fruit ripening stage. PMID:19033285

Safety of aspirin desensitization in patients with reported aspirin allergy and cardiovascular disease.

PubMed

McMullan, Kathryn L; Wedner, H James

2013-01-01

Aspirin (ASA) is the drug of choice in patients with coronary artery disease for primary and secondary prevention. This poses a problem for those patients reporting hypersensitivity to this drug or class of drugs. Desensitization to ASA may be carried out safely and effectively in patients with reported ASA or nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity needing ASA for cardiac indications. Our 7-step protocol is one choice for a rapid desensitization protocol. A retrospective chart review was conducted evaluating ASA desensitization in patients with reported ASA or NSAID hypersensitivity and a cardiac indication for ASA. In 160 evaluations over 15 years, 89 desensitizations were performed in both the inpatient and outpatient setting with only 16 reactions (18%). Eleven of these 16 patients (68.7%) were able to take daily ASA. Twenty-six desensitization procedures were performed with our 7-step rapid desensitization protocol in 10 inpatients and 16 outpatients with 3 reactions (18.75% of reactions). Initial reaction to ASA involving angioedema and reacting to ASA within the past year increased the risk of having a reaction to desensitization. Desensitization may be safely performed in patients with reported ASA or NSAID hypersensitivity and a cardiac indication for ASA. Our 7-step rapid protocol may be used in both the inpatient and outpatient setting to desensitize these patients. Patients who had angioedema with ASA ingestion or a reaction to ASA within the past year are at higher risk for reaction during the desensitization protocol. The authors have no funding, financial relationships, or conflicts of interest to disclose. © 2012 Wiley Periodicals, Inc.

The Antineoplastic Effect of Nitric Oxide-Donating Acetylsalicylic Acid (NO-ASA) in Chronic Lymphocytic Leukemia (CLL) Cells is Highly Dependent on its Positional Isomerism.

PubMed

Gehrke, Iris; Razavi, Regina; Poll-Wolbeck, Simon Jonas; Berkessel, Albrecht; Hallek, Michael; Kreuzer, Karl-Anton

2011-10-01

Chronic Lymphocytic Leukemia (CLL) is not curable in patients that are not eligible for allogeneic stem cell transplantation. Therefore, new treatment options are highly desirable. Chemically modified nonsteroidal anti-inflammatory drugs (NSAIDs), such as nitric-oxide-donating acetylsalicylic acid (NO-ASA), have been described to possess antineoplastic capacity. Recently, we could demonstrate a potent apoptosis induction in primary CLL cells in vitro and tumor growth inhibition by para-NO-ASA in a xenograft mouse model. However, little is known about the impact of positional isomerism of NO-ASA on its antineoplastic capacity in CLL. Primary CLL cells were treated with the meta-or para-isomer of NO-ASA at varying concentrations and durations. Viability was assessed flow cytometrically by annexin V-FITC/PI staining and by CellTiter-Glo luminescence cell viability assay. Caspase and PARP cleavage as well as involvement of β-catenin/Lef-1 signaling was determined by immunoblotting. For caspase inhibition, BD™ ApoBlock was used. Nude mice were xenografted with JVM3 cells and treated with meta-NO-ASA, para-NO-ASA or vehicle control. The meta-isomer was entirely ineffective in inducing CLL cell apoptosis in concentrations up to 100 μM, while para-NO-ASA acted in the low micromolar range. meta-NO-ASA, in contrast to para-NO-ASA, did not alter caspase activity. While para-NO-ASA action involved inhibition of β-catenin/Lef-1 signaling, meta-NO-ASA did not show any impact on this signaling pathway. Further, meta-NO-ASA did not significantly reduce tumor growth in a CLL xenograft mouse model, while para-NO-ASA was highly potent. We conclude that positional isomerism is crucial for the antineoplastic effect of NO-ASA in CLL. It can be suggested that the para-isomer, but not the meta-isomer, generates a chemical structure which is essential for the neoplastic effect of NO-ASA.

Frequency of Atrial Septal Aneurysms in Patients with Cerebral Ischemic Events

NASA Technical Reports Server (NTRS)

Agmon, Yoram; Khandheria, Bijoy K.; Meissner, Irene; Gentile, Federico; Whisnant, Jack P.; Sicks, JoRean D.; O'Fallon, W. Michael; Covalt, Jody L.; Wiebers, David O.; Seward, James B.

1999-01-01

Background-Atrial septal aneurysm (ASA) is a putative risk factor for cardioembolism. However, the frequency of ASA in the general population has not been adequately determined. Therefore, the frequency in patients with cerebral ischemic events, compared with the frequency in the general population, is poorly defined. We sought to determine the frequency of ASA in the general population and to compare the frequency of ASA in patients with cerebral ischemic events with the frequency in the general population. Methods and Results-The frequency of ASA in the population was determined in 363 subjects, a sample of the participants in the Stroke Prevention: Assessment of Risk in a Community study (control subjects), and was compared with the frequency in 355 age- and sex-matched patients undergoing transesophageal echocardiography in search of a cardiac source of embolism after a focal cerebral ischemic event. The proportion with ASA was 7.9% in patients versus 2.2% in control subjects (P=0.002; odds ratio of ASA, 3.65; 95% CI, 1.64 to 8.13, in patients versus control subjects). Patent foramen ovale (PFO) was detected with contrast injections in 56% of subjects with ASA. The presence of ASA predicted the presence of PFO (odds ratio of PFO, 4.57; 95% CI, 2.18 to 9.57, in subjects with versus those without ASA). In 86% of subjects with ASA and cerebral ischemia, transesophageal echocardiography did not detect an alternative source of cardioembolism other than an associated PFO. Conclusions-The prevalence of ASA based on this population-based study is 2.2%. The frequency of ASA is relatively higher in patients evaluated with transesophageal echocardiography after a cerebral ischemic event. ASA is frequently associated with PFO, suggesting paradoxical embolism as a mechanism of cardioembolism. In patients with cerebral ischemia and ASA, ASA (with or without PFO) commonly is the only potential cardioembolic source detected with transesophageal echocardiography.

The Antineoplastic Effect of Nitric Oxide-Donating Acetylsalicylic Acid (NO-ASA) in Chronic Lymphocytic Leukemia (CLL) Cells is Highly Dependent on its Positional Isomerism

PubMed Central

Gehrke, Iris; Razavi, Regina; Poll-Wolbeck, Simon Jonas; Berkessel, Albrecht; Hallek, Michael; Kreuzer, Karl-Anton

2011-01-01

Background: Chronic Lymphocytic Leukemia (CLL) is not curable in patients that are not eligible for allogeneic stem cell transplantation. Therefore, new treatment options are highly desirable. Chemically modified nonsteroidal anti-inflammatory drugs (NSAIDs), such as nitric-oxide-donating acetylsalicylic acid (NO-ASA), have been described to possess antineoplastic capacity. Recently, we could demonstrate a potent apoptosis induction in primary CLL cells in vitro and tumor growth inhibition by para-NO-ASA in a xenograft mouse model. However, little is known about the impact of positional isomerism of NO-ASA on its antineoplastic capacity in CLL. Methods: Primary CLL cells were treated with the meta-or para-isomer of NO-ASA at varying concentrations and durations. Viability was assessed flow cytometrically by annexin V-FITC/PI staining and by CellTiter-Glo luminescence cell viability assay. Caspase and PARP cleavage as well as involvement of β-catenin/Lef-1 signaling was determined by immunoblotting. For caspase inhibition, BD™ ApoBlock was used. Nude mice were xenografted with JVM3 cells and treated with meta-NO-ASA, para-NO-ASA or vehicle control. Results: The meta-isomer was entirely ineffective in inducing CLL cell apoptosis in concentrations up to 100 μM, while para-NO-ASA acted in the low micromolar range. meta-NO-ASA, in contrast to para-NO-ASA, did not alter caspase activity. While para-NO-ASA action involved inhibition of β-catenin/Lef-1 signaling, meta-NO-ASA did not show any impact on this signaling pathway. Further, meta-NO-ASA did not significantly reduce tumor growth in a CLL xenograft mouse model, while para-NO-ASA was highly potent. Conclusion: We conclude that positional isomerism is crucial for the antineoplastic effect of NO-ASA in CLL. It can be suggested that the para-isomer, but not the meta-isomer, generates a chemical structure which is essential for the neoplastic effect of NO-ASA. PMID:23556096

Modeling a two-layer flow system at the subarctic, subalpine tree line during snowmelt

NASA Astrophysics Data System (ADS)

Leenders, Erica E.; Woo, Ming-Ko

2002-10-01

In the subarctic it is common to encounter a two-layer flow system consisting of a porous organic cover overlying frozen or unfrozen mineral soils with much lower hydraulic conductivities. The "simple lumped reservoir parametric," or "semidistributed land-use-based runoff processes" (SLURP), model was adapted to simulate runoff generated by such a flow system from an upland shrub land to an open woodland downslope. A subalpine site in Wolf Creek, Yukon, Canada, was subdivided into two aggregated simulation areas (ASA), each being a unit characterized by a set of parameters. The model computes the vertical water balance and flow generation from several storages, and then routes the water out of the ASA. When applied to the 1999 snowmelt season, the model simulated the very low lateral flow and a large increase in storage in the mineral soil, as was observed in the field. The model was used to assess the sensitivity of the two-layer flow system under a range of temperature, snow cover, and frost conditions. Results show that within the range of possible climatic conditions, the hydrologic system is unlikely to yield significant runoff across the subalpine tree line, but if ground ice is abundant in the soil pores, percolation will be limited and fast flow from the surface layer is enhanced.

Destructive effect of non-enzymatic glycation on catalase and remediation via curcumin.

PubMed

Mofidi Najjar, Fayezeh; Taghavi, Fereshteh; Ghadari, Rahim; Sheibani, Nader; Moosavi-Movahedi, Ali Akbar

2017-09-15

Non-enzymatic glycation of proteins is a post-translational modification that is produced by a covalent binding between reducing sugars and amino groups of lysine and arginine residues. In this paper the effect of pathological conditions, derived from hyperglycemia on bovine liver catalase (BLC) as a model protein was considered by measuring enzyme activity, reactive oxygen species (ROS) generation, and changes in catalase conformational properties. We observed that in the presence of glucose, the catalase activity gradually decreased. ROS generation was also involved in the glycation process. Thus, decreased BLC activity was partly considered as a result of ROS generation through glycation. However, in the presence of curcumin the amount of ROS was reduced resulting in increased activity of the glycated catalase. The effect of high glucose level and the potential inhibitory effect of curcumin on aggregation and structural changes of catalase were also investigated. Molecular dynamic simulations also showed that interaction of catalase with curcumin resulted in changes in accessible surface area (ASA) and pKa, two effective parameters of glycation, in potential glycation lysine residues. Thus, the decrease in ASA and increase in pKa of important lysine residues were considered as predominant factors in decreased glycation of BLC by curcumin. Copyright © 2017 Elsevier Inc. All rights reserved.

L-Ascorbic acid metabolism during fruit development in an ascorbate-rich fruit crop chestnut rose (Rosa roxburghii Tratt).

PubMed

Huang, Ming; Xu, Qiang; Deng, Xiu-Xin

2014-09-01

Chestnut rose (Rosa roxburghii Tratt) is a fruit crop that contains unusually high levels of l-ascorbic acid (AsA; ∼1300 mg 100g(-1) FW). To explore the mechanisms underlying AsA metabolism, we investigated the distribution and abundance of AsA during fruit development. We also analyzed gene expression patterns, enzyme activities, and content of metabolites related to AsA biosynthesis and recycling. AsA first accumulated during late fruit development and continued to accumulate during ripening, with the highest accumulation rate near fruit maturity. The redox state of AsA in fruit was also enhanced during late fruit development, while leaf and other tissues had much lower levels of AsA and the redox state of AsA was lower. In mature fruit, AsA was mainly distributed in the cytoplasm of the mesocarp. Correlation analysis suggested that the gene expression patterns, enzyme activities, and related metabolite concentrations involved in the l-galactose pathway showed relatively high correlations with the accumulation rate of AsA. The gene expression pattern and activity of dehydroascorbate reductase (DHAR, EC 1.8.5.1) correlated strongly with AsA concentration, possibly indicating the crucial role of DHAR in the accumulation of high levels of AsA in chestnut rose fruit. Over expression of DHAR in Arabidopsis significantly increased the reduced AsA content and redox state. This was more effective than over expression of the l-galactose pathway gene GDP-d-mannose-3,5-epimerase (EC 5.1.3.18). These findings will enhance understanding of the molecular mechanisms regulating accumulation of AsA in chestnut rose. Copyright © 2014 Elsevier GmbH. All rights reserved.

Orally given gastroprotective capsaicin does not modify aspirin-induced platelet aggregation in healthy male volunteers (human phase I examination).

PubMed

Sandor, B; Papp, J; Mozsik, Gy; Szolcsanyi, J; Keszthelyi, Zs; Juricskay, I; Toth, K; Habon, Tamas

2014-12-01

Capsaicin is a well-known component of red pepper. Recent studies have shown that capsaicin could prevent gastric ulcer provoked by various NSAID-s like acetylsalicylic acid (ASA). Primary objective of this human clinical phase I trial was to investigate whether two different doses of capsaicin co-administered with ASA could alter the inhibitory effect of ASA on platelet aggregation. 15 healthy male subjects were involved in the study and treated orally with 400 μg capsaicin, 800 μg capsaicin, 500 mg ASA, 400 μg capsaicin+500 mg ASA and 800 μg capsaicin+500 mg ASA. Blood was drawn before and 1, 2, 6 and 24 hours after the drug administration. After that epinephrine induced platelet aggregation was measured by optical aggregometry. Between treatments, volunteers had a 6-day wash-out period. Our results showed that capsaicin had no effect on platelet aggregation, while as expected, ASA monotherapy resulted in a significant and clinically effective platelet aggregation inhibition (p ≤ 0.001). The combined ASA-capsaicin therapies reached equivalent effectiveness in platelet aggregation inhibition as ASA monotherapy. Our investigation proved that capsaicin did not influence the inhibitory effect of ASA on platelet aggregation, thus the capsaicin-ASA treatment would combine the antiplatelet effect of ASA with the possible gastroprotection of capsaicin.

Inhibitory Effect of Flavonoids on the Efflux of N-Acetyl 5-Aminosalicylic Acid Intracellularly Formed in Caco-2 Cells

PubMed Central

Shin, Yoshimura; Kentaro, Kawano; Ryusuke, Matsumura; Narumi, Sugihara; Koji, Furuno

2009-01-01

N-acetyl 5-aminosalicylic acid (5-AcASA) that was intracellularly formed from 5-aminosalicylic acid (5-ASA) at 200 μM was discharged 5.3, 7.1, and 8.1-fold higher into the apical site than into the basolateral site during 1, 2, and 4-hour incubations, respectively, in Caco-2 cells grown in Transwells. The addition of flavonols (100 μM) such as fisetin and quercetin with 5-ASA remarkably decreased the apically directed efflux of 5-AcASA. When 5-ASA (200 μM) was added to Caco-2 cells grown in tissue culture dishes, the formation of 5-AcASA decreased, and, in addition, the formed 5-AcASA was found to be accumulated within the cells in the presence of such flavonols. Thus, the decrease in 5-AcASA efflux by such flavonols was attributed not only to the inhibition of N-acetyl-conjugation of 5-ASA but to the predominant cellular accumulation of 5-AcASA. Various flavonoids also had both of the effects with potencies that depend on their specific structures. The essential structure of flavonoids was an absence of a hydroxyl substitution at the C5 position on the A-ring of flavone structure for the inhibitory effect on the N-acetyl-conjugation of 5-ASA, and a presence of hydroxyl substitutions at the C3′ or C4′ position on the B-ring of flavone structure for the promoting effect on the cellular accumulation of 5-AcASA. Both the decrease in 5-AcASA apical efflux and the increase in 5-AcASA cellular accumulation were also caused by MK571 and indomethacin, inhibitors of MRPs, but not by quinidine, cyclosporin A, P-glycoprotein inhibitors, and mitoxantrone, a BCRP substrate. These results suggest that certain flavonoids suppress the apical efflux of 5-AcASA possibly by inhibiting MRPs pumps located on apical membranes in Caco-2 cells. PMID:19688110

Gene expression studies in kiwifruit and gene over-expression in Arabidopsis indicates that GDP-L-galactose guanyltransferase is a major control point of vitamin C biosynthesis.

PubMed

Bulley, Sean M; Rassam, Maysoon; Hoser, Dana; Otto, Wolfgang; Schünemann, Nicole; Wright, Michele; MacRae, Elspeth; Gleave, Andrew; Laing, William

2009-01-01

Vitamin C (L-ascorbic acid, AsA) is an essential metabolite for plants and animals. Kiwifruit (Actinidia spp.) are a rich dietary source of AsA for humans. To understand AsA biosynthesis in kiwifruit, AsA levels and the relative expression of genes putatively involved in AsA biosynthesis, regeneration, and transport were correlated by quantitative polymerase chain reaction in leaves and during fruit development in four kiwifruit genotypes (three species; A. eriantha, A. chinensis, and A. deliciosa). During fruit development, fruit AsA concentration peaked between 4 and 6 weeks after anthesis with A. eriantha having 3-16-fold higher AsA than other genotypes. The rise in AsA concentration typically occurred close to the peak in expression of the L-galactose pathway biosynthetic genes, particularly the GDP-L-galactose guanyltransferase gene. The high concentration of AsA found in the fruit of A. eriantha is probably due to higher expression of the GDP-mannose-3',5'-epimerase and GDP-L-galactose guanyltransferase genes. Over-expression of the kiwifruit GDP-L-galactose guanyltransferase gene in Arabidopsis resulted in up to a 4-fold increase in AsA, while up to a 7-fold increase in AsA was observed in transient expression studies where both GDP-L-galactose guanyltransferase and GDP-mannose-3',5'-epimerase genes were co-expressed. These studies show the importance of GDP-L-galactose guanyltransferase as a rate-limiting step to AsA, and demonstrate how AsA can be significantly increased in plants.

Microencapsulated Fluorescent Dye Penetrant.

DTIC Science & Technology

1979-07-01

Microencapsulated fluorescent dye pentrant materials were evaluated for feasibility as a technique to detect cracks on metal surfaces when applied as...a free flowing dry powder. Various flourescent dye solutions in addition to a commercial penetrant (Zyglo ZL-30) were microencapsulated and tested on

Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis.

PubMed

Feagan, Brian G; Macdonald, John K

2012-10-17

Oral 5-aminosalicylic acid (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. Previously, it was found that 5-ASA drugs in doses of at least 2 g/day, were more effective than placebo but no more effective than SASP for inducing remission in ulcerative colitis. This updated review includes more recent studies and evaluates the efficacy and safety of 5-ASA preparations used for the treatment of mild to moderately active ulcerative colitis. The primary objectives were to assess the efficacy, dose-responsiveness and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators for induction of remission in active ulcerative colitis. A secondary objective of this systematic review was to compare the efficacy and safety of once daily dosing of oral 5-ASA with conventional (two or three times daily) dosing regimens. A computer-assisted literature search for relevant studies (inception to January 20, 2012) was performed using MEDLINE, EMBASE and the Cochrane Library. Review articles and conference proceedings were also searched to identify additional studies. Studies were accepted for analysis if they were randomized controlled clinical trials of parallel design, with a minimum treatment duration of four weeks. Studies of oral 5-ASA therapy for treatment of patients with active ulcerative colitis compared with placebo, SASP or other formulations of 5-ASA were considered for inclusion. Studies that compared once daily 5-ASA treatment with conventional dosing of 5-ASA (two or three times daily) and 5-ASA dose ranging studies were also considered for inclusion. The outcomes of interest were the failure to induce global/clinical remission, global/clinical improvement, endoscopic remission, endoscopic improvement, adherence, adverse events, withdrawals due to adverse events, and withdrawals or exclusions after entry. Trials were separated into five comparison groups: 5-ASA versus placebo, 5-ASA versus sulfasalazine, once daily dosing versus conventional dosing, 5-ASA versus comparator 5-ASA, and 5-ASA dose-ranging. Placebo-controlled trials were subgrouped by dosage. SASP-controlled trials were subgrouped by 5-ASA/SASP mass ratios. Once daily versus conventional dosing studies were subgrouped by formulation. 5-ASA-controlled trials were subgrouped by common 5-ASA comparators (e.g. Asacol, Claversal, Salofalk and Pentasa). Dose-ranging studies were subgrouped by 5-ASA formulation. We calculated the relative risk (RR) and 95% confidence intervals (95% CI) for each outcome. Data were analyzed on an intention to treat basis. Forty-eight studies (7776 patients) were included. The majority of included studies were rated as low risk of bias. 5-ASA was significantly superior to placebo with regard to all measured outcome variables. Seventy-two per cent of 5-ASA patients failed to enter clinical remission compared to 85% of placebo patients (RR 0.86, 95% CI 0.81 to 0.91). A dose-response trend for 5-ASA was also observed. No statistically significant differences in efficacy were found between 5-ASA and SASP. Fifty-four per cent of 5-ASA patients failed to enter remission compared to 58% of SASP patients (RR 0.90, 95% CI 0.77 to 1.04). No statistically significant differences in efficacy or adherence were found between once daily and conventionally dosed 5-ASA. Forty-two per cent of once daily patients failed to enter clinical remission compared to 44% of conventionally dosed patients (RR 0.95, 95% CI 0.82 to 1.10). Eight per cent of patients dosed once daily failed to adhere to their medication regimen compared to 6% of conventionally dosed patients (RR 1.36, 95% CI 0.64 to 2.86). There does not appear to be any difference in efficacy among the various 5-ASA formulations. Forty-eight per cent of patients in the 5-ASA group failed to enter remission compared to 50% of patients in the 5-ASA comparator group (RR 0.94, 95% CI 0.86 to 1.03). A pooled analysis of the ASCEND (I, II and III, n = 1459 patients) studies found no statistically significant difference in clinical improvement between Asacol 4.8 g/day and 2.4 g/day used for the treatment of moderately active ulcerative colitis. Thirty-seven per cent of patients in the 4.8 g/day group failed to improve clinically compared to 41% of patients in the 2.4 g/day group (RR 0.89; 95% CI 0.78 to 1.01). Subgroup analysis indicated that patients with moderate disease may benefit from the higher dose of 4.8 g/day. One study compared (n = 123 patients) Pentasa 4 g/day to 2.25 g/day in patients with moderate disease. Twenty-five per cent of patients in the 4 g/day group failed to improve clinically compared to 57% of patients in the 2.25 g/day group (RR 0.44; 95% CI 0.27 to 0.71). A pooled analysis of two studies comparing MMX mesalamine 4.8 g/day to 2.4 g/day found no statistically significant difference in efficacy (RR 1.03, 95% CI 0.82 to 1.29). 5-ASA was generally safe and common adverse events included flatulence, abdominal pain, nausea, diarrhea, headache and worsening ulcerative colitis. There were no statistically significant differences in the incidence of adverse events between 5-ASA and placebo, once daily and conventionally dosed 5-ASA, 5-ASA and comparator 5-ASA formulation and 5-ASA dose ranging (high dose versus low dose) studies. SASP was not as well tolerated as 5-ASA. Twenty-nine percent of SASP patients experienced an adverse event compared to 15% of 5-ASA patients (RR 0.48, 95% CI 0.37 to 0.63). 5-ASA was superior to placebo and no more effective than SASP. Considering their relative costs, a clinical advantage to using oral 5-ASA in place of SASP appears unlikely. 5-ASA dosed once daily appears to be as efficacious and safe as conventionally dosed 5-ASA. Adherence does not appear to be enhanced by once daily dosing in the clinical trial setting. It is unknown if once daily dosing of 5-ASA improves adherence in a community-based setting. There do not appear to be any differences in efficacy or safety among the various 5-ASA formulations. A daily dosage of 2.4 g appears to be a safe and effective induction therapy for patients with mild to moderately active ulcerative colitis. Patients with moderate disease may benefit from an initial dose of 4.8 g/day.

Gene expression studies in kiwifruit and gene over-expression in Arabidopsis indicates that GDP-L-galactose guanyltransferase is a major control point of vitamin C biosynthesis

PubMed Central

Bulley, Sean M.; Rassam, Maysoon; Hoser, Dana; Otto, Wolfgang; Schünemann, Nicole; Wright, Michele; MacRae, Elspeth; Gleave, Andrew; Laing, William

2009-01-01

Vitamin C (L-ascorbic acid, AsA) is an essential metabolite for plants and animals. Kiwifruit (Actinidia spp.) are a rich dietary source of AsA for humans. To understand AsA biosynthesis in kiwifruit, AsA levels and the relative expression of genes putatively involved in AsA biosynthesis, regeneration, and transport were correlated by quantitative polymerase chain reaction in leaves and during fruit development in four kiwifruit genotypes (three species; A. eriantha, A. chinensis, and A. deliciosa). During fruit development, fruit AsA concentration peaked between 4 and 6 weeks after anthesis with A. eriantha having 3–16-fold higher AsA than other genotypes. The rise in AsA concentration typically occurred close to the peak in expression of the L-galactose pathway biosynthetic genes, particularly the GDP-L-galactose guanyltransferase gene. The high concentration of AsA found in the fruit of A. eriantha is probably due to higher expression of the GDP-mannose-3′,5′-epimerase and GDP-L-galactose guanyltransferase genes. Over-expression of the kiwifruit GDP-L-galactose guanyltransferase gene in Arabidopsis resulted in up to a 4-fold increase in AsA, while up to a 7-fold increase in AsA was observed in transient expression studies where both GDP-L-galactose guanyltransferase and GDP-mannose-3′,5′-epimerase genes were co-expressed. These studies show the importance of GDP-L-galactose guanyltransferase as a rate-limiting step to AsA, and demonstrate how AsA can be significantly increased in plants. PMID:19129165

Antibiotic resistance due to an unusual ColE1-type replicon plasmid in Aeromonas salmonicida.

PubMed

Vincent, Antony T; Emond-Rheault, Jean-Guillaume; Barbeau, Xavier; Attéré, Sabrina A; Frenette, Michel; Lagüe, Patrick; Charette, Steve J

2016-06-01

Aeromonas salmonicida subsp. salmonicida is a fish pathogen known to have a rich plasmidome. In the present study, we discovered an isolate of this bacterium bearing an additional unidentified small plasmid. After having sequenced the DNA of that isolate by next-generation sequencing, it appeared that the new small plasmid is a ColE1-type replicon plasmid, named here pAsa7. This plasmid bears a functional chloramphenicol-acetyltransferase-encoding gene (cat-pAsa7) previously unknown in A. salmonicida and responsible for resistance to chloramphenicol. A comparison of pAsa7 with pAsa2, the only known ColE1-type replicon plasmid usually found in A. salmonicida subsp. salmonicida, revealed that even if both plasmids share a high structural similarity, it is still unclear if pAsa7 is a derivative of pAsa2 since they showed several mutations at the nucleotide level. Transcriptomic analysis revealed that the cat-pAsa4 gene, another chloramphenicol-acetyltransferase-encoding gene, found on the large plasmid pAsa4, was significantly more transcribed than cat-pAsa7. This was correlated with a higher chloramphenicol resistance for isolates bearing pAsa4 compared with the one having pAsa7. Finally, a phylogenetic analysis showed that both CAT-pAsa4 and CAT-pAsa7 proteins were in different clusters. The clustering was supported by the identity of residues involved in the catalytic site. In addition, to give a better understanding of the large drug-resistance panel of A. salmonicida, this study reinforces the hypothesis that A. salmonicida subsp. salmonicida is a considerable reservoir for mobile genetic elements such as plasmids.

Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis.

PubMed

Cuffari, Carmen; Pierce, David; Korczowski, Bartosz; Fyderek, Krzysztof; Van Heusen, Heather; Hossack, Stuart; Wan, Hong; Edwards, Alena Y Z; Martin, Patrick

2016-01-01

Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA) use in pediatric ulcerative colitis (UC). To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA) after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC. Participants (5-17 years of age; 18-82 kg, stratified by weight) with UC received multi-matrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day) for 7 days. Blood samples were collected pre-dose on days 5 and 6. On days 7 and 8, blood and urine samples were collected and safety was evaluated. 5-ASA and Ac-5-ASA plasma and urine concentrations were analyzed by non-compartmental methods and used to develop a population pharmacokinetic model. Fifty-two subjects (21 [30 mg/kg]; 22 [60 mg/kg]; 9 [100 mg/kg]) were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose-proportional increase between 30 and 60 mg/kg/day cohorts. For 30, 60, and 100 mg/kg/day doses, mean percentages of 5-ASA absorbed were 29.4%, 27.0%, and 22.1%, respectively. Simulated steady-state exposures and variabilities for 5-ASA and Ac-5-ASA (coefficient of variation approximately 50% and 40%-45%, respectively) were similar to those observed previously in adults at comparable doses. Treatment-emergent adverse events were reported by ten subjects. Events were similar among different doses and age groups with no new safety signals identified. Children and adolescents with UC receiving multimatrix mesalamine demonstrated 5-ASA and Ac-5-ASA pharmacokinetic profiles similar to historical adult data. Multimatrix mesalamine was well tolerated across all dose and age groups. ClinicalTrials.gov Identifier: NCT01130844.

Efficacy of oral vs. topical, or combined oral and topical 5-aminosalicylates, in Ulcerative Colitis: systematic review and meta-analysis.

PubMed

Ford, Alexander C; Khan, Khurram J; Achkar, Jean-Paul; Moayyedi, Paul

2012-02-01

Efficacy of 5-aminosalicylic acids (5-ASAs) in ulcerative colitis (UC) has been studied previously in meta-analyses. However, no recent meta-analysis has studied the relative efficacies of differing routes of administration. MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through May 2011). Eligible trials recruited adults with mildly to moderately active UC, or quiescent UC, and compared oral 5-ASAs with either topical 5-ASAs or a combination of oral and topical 5-ASAs. Dichotomous data were pooled to obtain relative risk (RR) of failure to achieve remission in active UC, and RR of relapse of disease activity in quiescent UC, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. The search identified 3,061 citations, and 12 randomized controlled trials (RCTs) were eligible. Four compared topical with oral 5-ASAs in active UC remission, with an RR of no remission with topical 5-ASAs of 0.82 (95% CI=0.52-1.28). Four trials compared combined with oral 5-ASAs in active UC (RR of no remission=0.65; 95% CI=0.47-0.91; NNT=5). Three RCTs compared intermittent topical with oral 5-ASAs in preventing relapse of quiescent UC (RR=0.64; 95% CI=0.43-0.95; NNT=4), and two compared combined with oral 5-ASAs (RR of relapse=0.48; 95% CI=0.17-1.38). Combined 5-ASA therapy appeared superior to oral 5-ASAs for induction of remission of mildly to moderately active UC. Intermittent topical 5-ASAs appeared superior to oral 5-ASAs for preventing relapse of quiescent UC.

Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis.

PubMed

Wang, Yongjun; Parker, Claire E; Bhanji, Tania; Feagan, Brian G; MacDonald, John K

2016-04-21

Oral 5-aminosalicylic acid (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. Previously, it was found that 5-ASA drugs in doses of at least 2 g/day, were more effective than placebo but no more effective than SASP for inducing remission in ulcerative colitis. This updated review includes more recent studies and evaluates the efficacy and safety of 5-ASA preparations used for the treatment of mild to moderately active ulcerative colitis. The primary objectives were to assess the efficacy, dose-responsiveness and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators for induction of remission in active ulcerative colitis. A secondary objective of this systematic review was to compare the efficacy and safety of once daily dosing of oral 5-ASA with conventional (two or three times daily) dosing regimens. A computer-assisted literature search for relevant studies (inception to July 9, 2015) was performed using MEDLINE, EMBASE and the Cochrane Library. Review articles and conference proceedings were also searched to identify additional studies. Studies were accepted for analysis if they were randomized controlled clinical trials of parallel design, with a minimum treatment duration of four weeks. Studies of oral 5-ASA therapy for treatment of patients with active ulcerative colitis compared with placebo, SASP or other formulations of 5-ASA were considered for inclusion. Studies that compared once daily 5-ASA treatment with conventional dosing of 5-ASA (two or three times daily) and 5-ASA dose ranging studies were also considered for inclusion. The outcomes of interest were the failure to induce global/clinical remission, global/clinical improvement, endoscopic remission, endoscopic improvement, adherence, adverse events, withdrawals due to adverse events, and withdrawals or exclusions after entry. Trials were separated into five comparison groups: 5-ASA versus placebo, 5-ASA versus sulfasalazine, once daily dosing versus conventional dosing, 5-ASA versus comparator 5-ASA, and 5-ASA dose-ranging. Placebo-controlled trials were subgrouped by dosage. SASP-controlled trials were subgrouped by 5-ASA/SASP mass ratios. Once daily versus conventional dosing studies were subgrouped by formulation. 5-ASA-controlled trials were subgrouped by common 5-ASA comparators (e.g. Asacol, Claversal, Salofalk and Pentasa). Dose-ranging studies were subgrouped by 5-ASA formulation. We calculated the relative risk (RR) and 95% confidence intervals (95% CI) for each outcome. Data were analyzed on an intention-to-treat basis. Fifty-three studies (8548 patients) were included. The majority of included studies were rated as low risk of bias. 5-ASA was significantly superior to placebo with regard to all measured outcome variables. Seventy-one per cent of 5-ASA patients failed to enter clinical remission compared to 83% of placebo patients (RR 0.86, 95% CI 0.82 to 0.89). A dose-response trend for 5-ASA was also observed. No statistically significant differences in efficacy were found between 5-ASA and SASP. Fifty-four per cent of 5-ASA patients failed to enter remission compared to 58% of SASP patients (RR 0.90, 95% CI 0.77 to 1.04). No statistically significant differences in efficacy or adherence were found between once daily and conventionally dosed 5-ASA. Forty-five per cent of once daily patients failed to enter clinical remission compared to 48% of conventionally dosed patients (RR 0.94, 95% CI 0.83 to 1.07). Eight per cent of patients dosed once daily failed to adhere to their medication regimen compared to 6% of conventionally dosed patients (RR 1.36, 95% CI 0.64 to 2.86). There does not appear to be any difference in efficacy among the various 5-ASA formulations. Fifty per cent of patients in the 5-ASA group failed to enter remission compared to 52% of patients in the 5-ASA comparator group (RR 0.94, 95% CI 0.86 to 1.02). A pooled analysis of 3 studies (n = 1459 patients) studies found no statistically significant difference in clinical improvement between Asacol 4.8 g/day and 2.4 g/day used for the treatment of moderately active ulcerative colitis. Thirty-seven per cent of patients in the 4.8 g/day group failed to improve clinically compared to 41% of patients in the 2.4 g/day group (RR 0.89; 95% CI 0.78 to 1.01). Subgroup analysis indicated that patients with moderate disease may benefit from the higher dose of 4.8 g/day. One study compared (n = 123 patients) Pentasa 4 g/day to 2.25 g/day in patients with moderate disease. Twenty-five per cent of patients in the 4 g/day group failed to improve clinically compared to 57% of patients in the 2.25 g/day group (RR 0.44; 95% CI 0.27 to 0.71). A pooled analysis of two studies comparing MMX mesalamine 4.8 g/day to 2.4 g/day found no statistically significant difference in efficacy (RR 1.03, 95% CI 0.82 to 1.29). There were no statistically significant differences in the incidence of adverse events between 5-ASA and placebo, once daily and conventionally dosed 5-ASA, 5-ASA and comparator 5-ASA formulation and 5-ASA dose ranging (high dose versus low dose) studies. Common adverse events included flatulence, abdominal pain, nausea, diarrhea, headache and worsening ulcerative colitis. SASP was not as well tolerated as 5-ASA. Twenty-nine percent of SASP patients experienced an adverse event compared to 15% of 5-ASA patients (RR 0.48, 95% CI 0.37 to 0.63). 5-ASA was superior to placebo and no more effective than SASP. Considering their relative costs, a clinical advantage to using oral 5-ASA in place of SASP appears unlikely. 5-ASA dosed once daily appears to be as efficacious and safe as conventionally dosed 5-ASA. Adherence does not appear to be enhanced by once daily dosing in the clinical trial setting. It is unknown if once daily dosing of 5-ASA improves adherence in a community-based setting. There do not appear to be any differences in efficacy or safety among the various 5-ASA formulations. A daily dosage of 2.4 g appears to be a safe and effective induction therapy for patients with mild to moderately active ulcerative colitis. Patients with moderate disease may benefit from an initial dose of 4.8 g/day.

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

NASA Astrophysics Data System (ADS)

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

2015-02-01

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

Surgical scheduling categorization system (SSCS): A novel classification system to improve coordination and scheduling of operative cases in a tertiary pediatric medical system.

PubMed

Gantwerker, Eric A; Bannos, Cassandra; Cunningham, Michael J; Rahbar, Reza

2017-01-01

To describe a surgical categorization system to create a universal nomenclature, delineating patient complexity as a first step toward developing a true risk stratification system. Retrospective database review of all otolaryngology surgical procedures performed in a tertiary pediatric hospital system over one academic year (July 2012-June 2013). All otolaryngology surgical procedures were reviewed, encompassing 8478 procedures on 5711 patients. The attending otolaryngologist assigned surgical scheduling category (SSCS) at the time of case booking based on an institution specific guidelines. The guidelines are as follow: Category I was assigned to American Society of Anesthesiologists physical status classification (ASA) I/II patients, designating them appropriate for institution's suburban ambulatory surgery centers; Category II was ASA I/II patients with social or transportation issues; Category III was ASA I/II patients who required case coordination with other medical or surgical departments; Category IV was reserved for patients of any ASA class whom the surgeon designated to be of a higher complexity. 8478 total procedures analyzed with 7198 having complete records. 48% were Category I, 13.6% were Category II, 1.9% were Category III and 36.5% were Category IV. The ASA were 34.7% ASA I, 50% ASA II, 13.39% ASA III, and 1.9% ASA IV. Although the largest proportion of patients were ASA II (50%), 39.6% of all ASA II were Category IV. Category IV was split into 54.2% ASA II and 34% ASA III and shows that peri-operative surgical concerns were not encompassed by the ASA system. This surgical categorization system streamlines surgical scheduling in a tertiary pediatric hospital system, particularly with respect to the designation of cases as ambulatory surgery center or main operating room appropriate. The case mix complexity is also readily apparent, enhancing recognition of the coordination and attention required for the perioperative management of high complexity patients. The SSCS helps convey concerns not addressed by ASA physical status alone. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Transcriptomic analysis of genes involved in the biosynthesis, recycling and degradation of L-ascorbic acid in pepper fruits (Capsicum annuum L.).

PubMed

Alós, Enriqueta; Rodrigo, María J; Zacarías, Lorenzo

2013-06-01

Sweet pepper (Capsicum annuum L.) is widely recognized among the vegetables with high content of ascorbic acid (AsA). However, the metabolic pathways involved in the biosynthesis, recycling and degradation of AsA and their relative contribution to the concentration of AsA have not been established yet. In the present work, the expression levels of selected genes involved in the AsA biosynthesis, degradation and recycling pathways were analyzed during development and ripening of pepper fruit cv. Palermo and in mature fruit of four cultivars (Lipari, C-116, Surrentino and Italverde) with different AsA concentrations. An inverse correlation was found between the expression of the biosynthetic genes and AsA concentrations, which could indicate that a feedback mechanism regulates AsA homeostasis in pepper fruits. Interestingly, analysis of mRNA levels of ascorbate oxidase, involved in the degradation of AsA, suggests that this enzyme plays a critical role in the regulation of the AsA pool during fruit development and ripening. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Regulation of fruit ascorbic acid concentrations during ripening in high and low vitamin C tomato cultivars

PubMed Central

2012-01-01

Background To gain insight into the regulation of fruit ascorbic acid (AsA) pool in tomatoes, a combination of metabolite analyses, non-labelled and radiolabelled substrate feeding experiments, enzyme activity measurements and gene expression studies were carried out in fruits of the ‘low-’ and ‘high-AsA’ tomato cultivars ‘Ailsa Craig’ and ‘Santorini’ respectively. Results The two cultivars exhibited different profiles of total AsA (totAsA, AsA + dehydroascorbate) and AsA accumulation during ripening, but both displayed a characteristic peak in concentrations at the breaker stage. Substrate feeding experiments demonstrated that the L-galactose pathway is the main AsA biosynthetic route in tomato fruits, but that substrates from alternative pathways can increase the AsA pool at specific developmental stages. In addition, we show that young fruits display a higher AsA biosynthetic capacity than mature ones, but this does not lead to higher AsA concentrations due to either enhanced rates of AsA breakdown (‘Ailsa Craig’) or decreased rates of AsA recycling (‘Santorini’), depending on the cultivar. In the later stages of ripening, differences in fruit totAsA-AsA concentrations of the two cultivars can be explained by differences in the rate of AsA recycling activities. Analysis of the expression of AsA metabolic genes showed that only the expression of one orthologue of GDP-L-galactose phosphorylase (SlGGP1), and of two monodehydroascorbate reductases (SlMDHAR1 and SlMDHAR3) correlated with the changes in fruit totAsA-AsA concentrations during fruit ripening in ‘Ailsa Craig’, and that only the expression of SlGGP1 was linked to the high AsA concentrations found in red ripe ‘Santorini’ fruits. Conclusions Results indicate that ‘Ailsa Craig’ and ‘Santorini’ use complementary mechanisms to maintain the fruit AsA pool. In the low-AsA cultivar (‘Ailsa Craig’), alternative routes of AsA biosynthesis may supplement biosynthesis via L-galactose, while in the high-AsA cultivar (‘Santorini’), enhanced AsA recycling activities appear to be responsible for AsA accumulation in the later stages of ripening. Gene expression studies indicate that expression of SlGGP1 and two orthologues of SlMDHAR are closely correlated with totAsA-AsA concentrations during ripening and are potentially good candidates for marker development for breeding and selection. PMID:23245200

ASCORBIC ACID RETENTION AND COLOR OF STRAWBERRIES AS RELATED TO LOW-LEVEL IRRADIATION AND STORAGE TIME

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wells, C.E.; Tichenor, D.A.; Martin, D.C.

1963-01-01

Freshly picked strawberries were irradiated in a gamma source and ascorbic acid (ASA) and its oxidative breakdown products were measured at intervals during 3 to 6 months' storage. Reduced ASA, dehydroascorbic acid (DHA), diketogulonic acid (DKA), and total ASA were determined in unirradiated strawberries and in strawberries receiving 0.3 and 0.8 Mrad. Irradiation caused a significant loss of total ASA. Storage at 35 un. Concent 85% F for 180 days resulted in further losses, most of which occurred during the first 95 days. Addition of a glucose oxidase packet to atmospheric packs did not affect retention of total ASA. Amore » significant amount of reduced ASA was destroyed by irradiation, the loss being greater at the higher level used. Relatively large amounts er irradiation in the presence of almost complete retention of total ASA indicated that the degradation followed the usual pattern: reduced ASA to DHA to DKA. After 180 days storage, practically all of the reduced ASA was destroyed in air-packed irradiated samples, but comparable glucose-oxidase-packed samples retained 33 to 47% of their original reduced ASA. Measurement of the Gardner a color value revealed a significant able color variability among samples. Color losses were higher at higher doses. (H.R.D.)« less

Exploring the impact of wounding and jasmonates on ascorbate metabolism

PubMed Central

Suza, Walter P.; Avila, Carlos A.; Carruthers, Kelly; Kulkarni, Shashank; Goggin, Fiona L.; Lorence, Argelia

2010-01-01

Vitamin C (ascorbate, AsA) is the most abundant water-soluble antioxidant in plants. Ascorbate provides the first line of defense against damaging reactive oxygen species (ROS), and helps protect plant cells from many factors that induce oxidative stress, including wounding, ozone, high salinity, and pathogen attack. Plant defenses against these stresses are also dependent upon jasmonates (JAs), a class of plant hormones that promote ROS accumulation. Here, we review evidence showing that wounding and JAs influence AsA accumulation in various plant species, and we report new data from Arabidopsis and tomato testing the influence of JAs on AsA levels in wounded and unwounded plants. In both species, certain mutations that impair JA metabolism and signaling influence foliar AsA levels, suggesting that endogenous JAs may regulate steady-state AsA. However, the impact of wounding on AsA accumulation was similar in JA mutants and wild type controls, indicating that this wound response does not require JAs. Our findings also indicate that the effects of wounding and JAs on AsA accumulation differ between species; these factors both enhanced AsA accumulation in Arabidopsis, but depressed AsA levels in tomato. These results underscore the importance of obtaining data from more than one model species, and demonstrate the complexity of AsA regulation. PMID:20346686

Ascorbic acid metabolism during bilberry (Vaccinium myrtillus L.) fruit development.

PubMed

Cocetta, Giacomo; Karppinen, Katja; Suokas, Marko; Hohtola, Anja; Häggman, Hely; Spinardi, Anna; Mignani, Ilaria; Jaakola, Laura

2012-07-15

Bilberry (Vaccinium myrtillus L.) possesses a high antioxidant capacity in berries due to the presence of anthocyanins and ascorbic acid (AsA). Accumulation of AsA and the expression of the genes encoding the enzymes of the main AsA biosynthetic route and of the ascorbate-glutathione cycle, as well as the activities of the enzymes involved in AsA oxidation and recycling were investigated for the first time during the development and ripening of bilberry fruit. The results showed that the AsA level remained relatively stable during fruit maturation. The expression of the genes encoding the key enzymes in the AsA main biosynthetic route showed consistent trends with each other as well as with AsA levels, especially during the first stages of fruit ripening. The expression of genes and activities of the enzyme involved in the AsA oxidation and recycling route showed more prominent developmental stage-dependent changes during the ripening process. Different patterns of activity were found among the studied enzymes and the results were, for some enzymes, in accordance with AsA levels. In fully ripe berries, both AsA content and gene expression were significantly higher in skin than in pulp. Copyright © 2012 Elsevier GmbH. All rights reserved.

Interaction between the LMWH reviparin and aspirin in healthy volunteers

PubMed Central

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

2000-01-01

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

ASA24-Kids (no longer available)

Cancer.gov

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

Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis.

PubMed

Wang, Yongjun; Parker, Claire E; Feagan, Brian G; MacDonald, John K

2016-05-09

Oral 5-aminosalicylic (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. Previously, it was found that 5-ASA drugs were more effective than placebo but had a statistically significant therapeutic inferiority relative to SASP. This updated review includes more recent studies and evaluates the effectiveness, dose-responsiveness, and safety of 5-ASA preparations used for maintenance of remission in quiescent ulcerative colitis. The primary objectives were to assess the efficacy, dose-responsiveness and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators for maintenance of remission in quiescent ulcerative colitis. A secondary objective was to compare the efficacy and safety of once daily dosing of oral 5-ASA with conventional (two or three times daily) dosing regimens. A literature search for relevant studies (inception to 9 July 2015) was performed using MEDLINE, EMBASE and the Cochrane Library. Review articles and conference proceedings were also searched to identify additional studies. Studies were accepted for analysis if they were randomized controlled trials with a minimum treatment duration of six months. Studies of oral 5-ASA therapy for treatment of patients with quiescent ulcerative colitis compared with placebo, SASP or other 5-ASA formulations were considered for inclusion. Studies that compared once daily 5-ASA treatment with conventional dosing of 5-ASA and 5-ASA dose ranging studies were also considered for inclusion. The primary outcome was the failure to maintain clinical or endoscopic remission. Secondary outcomes included adherence, adverse events, withdrawals due to adverse events, and withdrawals or exclusions after entry. Trials were separated into five comparison groups: 5-ASA versus placebo, 5-ASA versus sulfasalazine, once daily dosing versus conventional dosing, 5-ASA versus comparator 5-ASA formulation, and 5-ASA dose-ranging. Placebo-controlled trials were subgrouped by dosage. Once daily versus conventional dosing studies were subgrouped by formulation. 5-ASA-controlled trials were subgrouped by common 5-ASA comparators (e.g. Asacol and Salofalk). Dose-ranging studies were subgrouped by 5-ASA formulation. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for each outcome. Data were analyzed on an intention-to-treat basis. Forty-one studies (8928 patients) were included. The majority of included studies were rated as low risk of bias. Ten studies were rated at high risk of bias. Seven of these studies were single-blind and three studies were open-label. However, two open-label studies and four of the single-blind studies utilized investigator performed endoscopy as an endpoint, which may protect against bias. 5-ASA was significantly superior to placebo for maintenance of clinical or endoscopic remission. Forty-one per cent of 5-ASA patients relapsed compared to 58% of placebo patients (7 studies, 1298 patients; RR 0.69, 95% CI 0.62 to 0.77). There was a trend towards greater efficacy with higher doses of 5-ASA with a statistically significant benefit for the 1 to 1.9 g/day (RR 0.65; 95% CI 0.56 to 0.76) and the > 2 g/day subgroups (RR 0.73, 95% CI 0.60 to 0.89). SASP was significantly superior to 5-ASA for maintenance of remission. Forty-eight per cent of 5-ASA patients relapsed compared to 43% of SASP patients (12 studies, 1655 patients; RR 1.14, 95% CI 1.03 to 1.27). A GRADE analysis indicated that the overall quality of the evidence for the primary outcome for the placebo and SASP-controlled studies was high. No statistically significant differences in efficacy or adherence were found between once daily and conventionally dosed 5-ASA. Twenty-nine per cent of once daily patients relapsed over 12 months compared to 31% of conventionally dosed patients (8 studies, 3127 patients; RR 0.91, 95% CI 0.82 to 1.01). Eleven per cent of patients in the once daily group failed to adhere to their medication regimen compared to 9% of patients in the conventional dosing group (6 studies, 1462 patients; RR 1.22, 95% CI 0.91 to 1.64). There does not appear to be any difference in efficacy among the various 5-ASA formulations. Forty-four per cent of patients in the 5-ASA group relapsed compared to 41% of patients in the 5-ASA comparator group (6 studies, 707 patients; RR 1.08, 95% CI 0.91 to 1.28). A pooled analysis of two studies showed no statistically significant difference in efficacy between Balsalazide 6 g and 3 g/day. Twenty-three per cent of patients in the 6 g/day group relapsed compared to 33% of patients in the 3 g/day group (216 patients; RR 0.76; 95% CI 0.45 to 2.79). One study found Balsalazide 4 g to be superior to 2 g/day. Thirty-seven per cent of patients in the 4 g/day Balsalazide group relapsed compared to 55% of patients in the 2 g/day group (133 patients; RR 0.66; 95% CI 0.45 to 0.97). One study found a statistically significant difference between Salofalk granules 3 g and 1.5 g/day. Twenty-five per cent of patients in the Salofalk 3 g/day group relapsed compared to 39% of patients in the 1.5 g/day group (429 patients; RR 0.65; 95% CI 0.49 to 0.86). Common adverse events included flatulence, abdominal pain, nausea, diarrhea, headache, dyspepsia, and nasopharyngitis. There were no statistically significant differences in the incidence of adverse events between 5-ASA and placebo, 5-ASA and SASP, once daily and conventionally dosed 5-ASA, 5-ASA and comparator 5-ASA formulations and 5-ASA dose ranging studies. The trials that compared 5-ASA and SASP may have been biased in favour of SASP because most trials enrolled patients known to be tolerant to SASP which may have minimized SASP-related adverse events. 5-ASA was superior to placebo for maintenance therapy in ulcerative colitis. However, 5-ASA had a statistically significant therapeutic inferiority relative to SASP. Oral 5-ASA administered once daily is as effective and safe as conventional dosing for maintenance of remission in quiescent ulcerative colitis. There does not appear to be any difference in efficacy or safety between the various formulations of 5-ASA. Patients with extensive ulcerative colitis or with frequent relapses may benefit from a higher dose of maintenance therapy. High dose therapy appears to be as safe as low dose and is not associated with a higher incidence of adverse events.

Silicon improves growth and alleviates oxidative stress in rice seedlings (Oryza sativa L.) by strengthening antioxidant defense and enhancing protein metabolism under arsanilic acid exposure.

PubMed

Geng, Anjing; Wang, Xu; Wu, Lishu; Wang, Fuhua; Wu, Zhichao; Yang, Hui; Chen, Yan; Wen, Dian; Liu, Xiangxiang

2018-08-30

Organoarsenic arsanilic acid (ASA) contamination of paddy soil is a serious but less concerned hazard to agriculture and health of people consuming rice as staple food, for rice is one major pathway of arsenic (As) exposure to human food. To date little research has studied the effect of ASA on biochemical process of rice. Silicon (Si) application is able to reduce the toxicities of heavy metals in numerous plants, but little information about ASA. This work investigated whether and how Si influenced alleviation of ASA toxicity in rice at biochemical level to have a better understanding of defense mechanism by Si against ASA stress. Results showed that ASA reduced rice growth, disturbed protein metabolism, increased lipid peroxidation but decreased the efficiencies of antioxidant activities compared to control plants, more severe in roots than in shoots. The addition of Si in ASA-stressed rice plants noticeably increased growth and development as well as soluble protein contents, but decreased malondialdehyde (MDA) contents in ASA-stressed rice plants, suggesting that Si did have critical roles in ASA detoxification in rice. Furthermore, increased superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) activities along with elevated glutathione (GSH) and ascorbic acid (AsA) contents implied the active involvement of ROS scavenging and played, at least in part, to Si-mediated alleviation of ASA toxicity in rice, and these changes were related to rice genotypes and tissues. The study provided physio-chemical mechanistic evidence on the beneficial effect of Si on organoarsenic ASA toxicity in rice seedlings. Copyright © 2018. Published by Elsevier Inc.

Importance of the Evaluation of N-Acetyltransferase Enzyme Activity Prior to 5-Aminosalicylic Acid Medication for Ulcerative Colitis.

PubMed

Matthis, Andrea L; Zhang, Bin; Denson, Lee A; Yacyshyn, Bruce R; Aihara, Eitaro; Montrose, Marshall H

2016-08-01

5-aminosalicylic acid (5-ASA) is a classic anti-inflammatory drug for the treatment of ulcerative colitis. N-acetyltransferase (NAT) enzymes convert 5-ASA to its metabolite N-acetyl-5-ASA, and it is unresolved whether 5-ASA or N-acetyl-5-ASA is the effective therapeutic molecule. We previously demonstrated that colonic production of N-acetyl-5-ASA (NAT activity) is decreased in dextran sulfate sodium-induced colitis. Our hypothesis is that 5-ASA is the therapeutic molecule to improve colitis, with the corollary that altered NAT activity affects drug efficacy. Since varying clinical effectiveness of 5-ASA has been reported, we also ask if NAT activity varies with inflammation in pediatric or adult patients. Acute colonic inflammation was induced in C57BL/6 NAT wild-type (WT) or knockout mice, using 3.5% dextran sulfate sodium (w/v) concurrent with 5-ASA treatment. Adult and pediatric rectosigmoid biopsies were collected from control or patients with ulcerative colitis. Tissue was analyzed for NAT and myeloperoxidase activity. Dextran sulfate sodium-induced colitis was of similar severity in both NAT WT and knockout mice, and NAT activity was significantly decreased in NAT WT mice. In the setting of colitis, 5-ASA significantly restored colon length and decreased myeloperoxidase activity in NAT knockout but not in WT mice. Myeloperoxidase activity negatively correlated with NAT activity in pediatric patients, but correlation was not observed in adult patients. Inflammation decreases NAT activity in the colon of mice and human pediatric patients. Decreased NAT activity enhances the therapeutic effect of 5-ASA in mice. A NAT activity assay could be useful to help predict the efficacy of 5-ASA therapy.

Combination of corticosteroids and 5-aminosalicylates or corticosteroids alone for patients with moderate-severe active ulcerative colitis: A global survey of physicians' practice.

PubMed

Ben-Horin, Shomron; Andrews, Jane M; Katsanos, Konstantinos H; Rieder, Florian; Steinwurz, Flavio; Karmiris, Konstantinos; Cheon, Jae Hee; Moran, Gordon William; Cesarini, Monica; Stone, Christian D; Schwartz, Doron; Protic, Marijana; Roblin, Xavier; Roda, Giulia; Chen, Min-Hu; Har-Noy, Ofir; Bernstein, Charles N

2017-04-28

To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates (5ASA) with corticosteroids (CS) versus corticosteroids alone for patients with active ulcerative colitis (UC). A cross-sectional questionnaire exploring physicians' attitude toward 5ASA + CS combination therapy vs CS alone was developed and validated. The questionnaire was distributed to gastroenterology experts in twelve countries in five continents. Respondents' agreement with stated treatment choices were assessed by standardized Likert scale. Background professional characteristics of respondents were analyzed for correlation with responses. Six hundred and sixty-four questionnaires were distributed and 349 received (52.6% response rate). Of 340 eligible respondents, 221 (65%) would continue 5ASA in a patient hospitalized for intravenous CS treatment due to a moderate-severe UC flare, while 108 (32%) would stop the 5ASA ( P < 0.001), and 11 (3%) are undecided. Similarly, 62% would continue 5ASA in an out-patient starting oral CS. However, only 140/340 (41%) would proactively start 5ASA in a hospitalized patient not receiving 5ASA before admission. Most (94%) physicians consider the safety profile of 5ASA as very good. Only 52% consider them inexpensive, 35% perceive them to be expensive and 12% are undecided. On multi-variable analysis, less years of practice and perception of a plausible additive mechanistic effect of 5ASA + CS were positively associated with the decision to continue 5ASA with CS. Despite the absence of data supporting its benefit, most gastroenterologists endorse combination of 5ASA + CS for patients with active moderate-to-severe UC. Randomized controlled trials are needed to assess if 5ASA confer any benefit for these patients.

Amino acid derivatives of 5-ASA as novel prodrugs for intestinal drug delivery.

PubMed

Clerici, C; Gentili, G; Boschetti, E; Santucci, C; Aburbeh, A G; Natalini, B; Pellicciari, R; Morelli, A

1994-12-01

In an attempt to obtain site-specific delivery of 5-ASA in the intestinal tract, we have determined the extent of absorption and metabolism of a number of novel 5-ASA derivatives, namely, (N-L-glutamyl)-amino-2-salicylic acid (1), (N-L-aspartyl)-amino-2-salicylic-acid (2), 5-aminosalicyl-L-proline-L-leucine (3), and 5-(N-L-glutamyl)-aminosalicyl-L-proline-L-leucine (4), which are selectively cleaved by intestinal brush border aminopeptidase A and carboxypeptidases. These novel prodrugs, 5-ASA, and sulfasalazine were administered to adult Fisher rats (N = 30) and to animals that had undergone prior colostomy (N = 30). Urine and feces were collected at timed intervals for 48 hr and the metabolites, 5-ASA, and N-acetyl-5-ASA were measured by high-performance liquid chromatography. The absorption and metabolism of all compounds were essentially identical in colostomized and normal animals. 5-ASA exhibited a rapid proximal intestinal absorption as evidenced by the high cumulative urinary excretion (> 65%) and low fecal excretion. Sulfasalazine, as expected, exhibited a lower urinary recovery (< 35%) and higher fecal excretion of 5-ASA and its metabolite. The novel glutamate and aspartate derivatives (1 and 2) behaved similarly to sulfasalazine, while administration of the proline-leucine derivative (3) resulted in urinary and fecal recovery values intermediate with respect to those observed with 5-ASA and sulfasalazine. 5-(N-L-Glutamyl)-aminosalicyl-L-proline-L-leucine yielded the highest fecal recovery of 5-ASA and its N-acetyl derivative, indicating a more efficient delivery to the distal bowel. Amino acid derivatives of 5-ASA appear to be potentially useful prodrugs for the site-specific delivery of 5-ASA to different regions of the intestinal tract.

Effects of clopidogrel and aspirin in combination versus aspirin alone on platelet activation and major receptor expression in patients after recent ischemic stroke: for the Plavix Use for Treatment of Stroke (PLUTO-Stroke) trial.

PubMed

Serebruany, Victor L; Malinin, Alex I; Ziai, Wendy; Pokov, Alex N; Bhatt, Deepak L; Alberts, Mark J; Hanley, Dan F

2005-10-01

Clopidogrel is widely used in patients after recent ischemic stroke; however, its ability to yield additional antiplatelet protection on top of aspirin has never been explored in a controlled study. To determine whether clopidogrel with aspirin (C+ASA) will produce more potent platelet inhibition than aspirin alone (ASA) in patients after ischemic stroke, we conducted the Plavix Use for Treatment of Stroke trial. Seventy patients after ischemic stroke were randomly assigned to C+ASA or ASA groups. Platelet studies included aggregometry; cartridge-based analyzers; expression of PECAM-1, P-selectin, GP IIb/IIIa (antigen and activity), vitronectin receptor, and formation of platelet-leukocyte microparticles by flow cytometry. Platelet tests were performed at baseline and after 30 days after randomization. There were no deaths, hospitalizations, or serious adverse events. There were no differences in the baseline platelet characteristics between C+ASA and ASA groups, or significant changes in platelet parameters in the ASA group, except diminished collagen-induced aggregation (P=0.001). In contrast, therapy with C+ASA resulted in a significant inhibition of platelet activity assessed by ADP- (P=0.00001) and collagen-induced (P=0.02) aggregation; closure time prolongation (P=0.03), and reduction of platelet activation units with Ultegra (P=0.00001); expression of PECAM-1 (P=0.01), and GP IIb/IIIa activity with PAC-1 (P=0.02) when compared with ASA group. Therapy with C+ASA also resulted in the reduced formation of platelet-leukocyte microparticles (P=0.02). Treatment with C+ASA for 1 month provides significantly greater inhibition of platelet activity than ASA alone in patients after recent ischemic stroke in the frame of the small randomized trial.

Mesalamine modulates intercellular adhesion through inhibition of p-21 activated kinase-1

PubMed Central

Khare, Vineeta; Lyakhovich, Alex; Dammann, Kyle; Lang, Michaela; Borgmann, Melanie; Tichy, Boris; Pospisilova, Sarka; Luciani, Gloria; Campregher, Christoph; Evstatiev, Rayko; Pflueger, Maren; Hundsberger, Harald; Gasche, Christoph

2013-01-01

Mesalamine (5-ASA) is widely used for the treatment of ulcerative colitis, a remitting condition characterized by chronic inflammation of the colon. Knowledge about the molecular and cellular targets of 5-ASA is limited and a clear understanding of its activity in intestinal homeostasis and interference with neoplastic progression is lacking. We sought to identify molecular pathways interfered by 5-ASA, using CRC cell lines with different genetic background. Microarray was performed for gene expression profile of 5-ASA-treated and untreated cells (HCT116 and HT29). Filtering and analysis of data identified three oncogenic pathways interfered by 5-ASA: MAPK/ERK pathway, cell adhesion and β-catenin/Wnt signaling. PAK1 emerged as a consensus target of 5-ASA, orchestrating these pathways. We further investigated the effect of 5-ASA on cell adhesion. 5-ASA increased cell adhesion which was measured by cell adhesion assay and transcellular-resistance measurement. Moreover, 5-ASA treatment restored membranous expression of adhesion molecules E-cadherin and β-catenin. Role of PAK1 as a mediator of mesalamine activity was validated in vitro and in vivo. Inhibition of PAK1 by RNA interference also increased cell adhesion. PAK1 expression was elevated in APCmin polyps and 5-ASA treatment reduced its expression. Our data demonstrates novel pharmacological mechanism of mesalamine in modulation of cell adhesion and role of PAK1 in APCmin polyposis. We propose that inhibition of PAK1 expression by 5-ASA can impede with neoplastic progression in colorectal carcinogenesis. The mechanism of PAK1 inhibition and induction of membranous translocation of adhesion proteins by 5-ASA might be independent of its known anti-inflammatory action. PMID:23146664

Mesalamine modulates intercellular adhesion through inhibition of p-21 activated kinase-1.

PubMed

Khare, Vineeta; Lyakhovich, Alex; Dammann, Kyle; Lang, Michaela; Borgmann, Melanie; Tichy, Boris; Pospisilova, Sarka; Luciani, Gloria; Campregher, Christoph; Evstatiev, Rayko; Pflueger, Maren; Hundsberger, Harald; Gasche, Christoph

2013-01-15

Mesalamine (5-ASA) is widely used for the treatment of ulcerative colitis, a remitting condition characterized by chronic inflammation of the colon. Knowledge about the molecular and cellular targets of 5-ASA is limited and a clear understanding of its activity in intestinal homeostasis and interference with neoplastic progression is lacking. We sought to identify molecular pathways interfered by 5-ASA, using CRC cell lines with different genetic background. Microarray was performed for gene expression profile of 5-ASA-treated and untreated cells (HCT116 and HT29). Filtering and analysis of data identified three oncogenic pathways interfered by 5-ASA: MAPK/ERK pathway, cell adhesion and β-catenin/Wnt signaling. PAK1 emerged as a consensus target of 5-ASA, orchestrating these pathways. We further investigated the effect of 5-ASA on cell adhesion. 5-ASA increased cell adhesion which was measured by cell adhesion assay and transcellular-resistance measurement. Moreover, 5-ASA treatment restored membranous expression of adhesion molecules E-cadherin and β-catenin. Role of PAK1 as a mediator of mesalamine activity was validated in vitro and in vivo. Inhibition of PAK1 by RNA interference also increased cell adhesion. PAK1 expression was elevated in APC(min) polyps and 5-ASA treatment reduced its expression. Our data demonstrates novel pharmacological mechanism of mesalamine in modulation of cell adhesion and role of PAK1 in APC(min) polyposis. We propose that inhibition of PAK1 expression by 5-ASA can impede with neoplastic progression in colorectal carcinogenesis. The mechanism of PAK1 inhibition and induction of membranous translocation of adhesion proteins by 5-ASA might be independent of its known anti-inflammatory action. Copyright © 2012 Elsevier Inc. All rights reserved.

Administration of melatonin protects against acetylsalicylic acid-induced impairment of male reproductive function in mice

PubMed Central

Emami, Niloufar Hedayati; Lafout, Farzaneh Mahmoudi; Mohammadghasemi, Fahimeh

2018-01-01

Objective(s): Melatonin, an important hormone secreted by the epiphysis, is a powerful anti-oxidant with a high potential to neutralize medical toxins. The goal of this study was to demonstrate the beneficial effect of melatonin on epididymal sperm and reproductive parameters in mice treated with acetylsalicylic acid (ASA). Materials and Methods: Male adult mice were divided into four treatment groups: control, ASA, melatonin, and ASA+melatonin. Mice were administered ASA (50 mg/kg, orally) and/or melatonin (10 mg/kg, intraperitoneally), or vehicle control, for 14 days. Sperm count, sperm motility, and sperm morphology were evaluated to assess fertility. A colorimetric assay was used to measure serum total antioxidant capacity (TAC). A sperm chromatin dispersion (SCD) test was used to assess sperm chromatin integrity. Sex hormone levels were measured by ELISA. Results: Compared to the control group, ASA treatment resulted in a significant decrease in sperm parameters (P<0.05), as well as a decrease in the integrity of sperm chromatin (P<0.01). ASA treatment also reduced serum testosterone and TAC levels (P<0.05). Co-administration of melatonin with ASA significantly improved epididymal sperm parameters and increased serum testosterone and TAC levels compared to the ASA-treated group. LH level was not different in the combined treatment group compared to control or ASA treatment. Conclusion: Short-term administration of ASA (50 mg/kg) has adverse effects on male reproductive function in mice. Co-administration of melatonin protects against ASA-induced impairment of male reproductive function by preventing the reduction in serum TAC and testosterone levels seen with ASA treatment alone. PMID:29456808

A spectroscopic study of phenylbutazone and aspirin bound to serum albumin in rheumatoid diseases

NASA Astrophysics Data System (ADS)

Maciążek-Jurczyk, M.; Sułkowska, A.; Bojko, B.; Równicka-Zubik, J.; Sułkowski, W. W.

2011-11-01

Interaction of phenylbutazone (PBZ) and aspirin (ASA), two drugs recommended in rheumatoid diseases (RDs), when binding to human (HSA) and bovine (BSA) serum albumins, has been studied by quenching of fluorescence and proton nuclear magnetic resonance ( 1HNMR) techniques. On the basis of spectrofluorescence measurements high affinity binding sites of PBZ and ASA on albumin as well as their interaction within the binding sites were described. A low affinity binding site has been studied by proton nuclear magnetic resonance spectroscopy. Using fluorescence spectroscopy the location of binding site in serum albumin (SA) for PBZ and ASA was found. Association constants Ka were determined for binary (i.e. PBZ-SA and ASA-SA) and ternary complexes (i.e. PBZ-[ASA]-SA and ASA-[PBZ]-SA). PBZ and ASA change the affinity of each other to the binding site in serum albumin (SA). The presence of ASA causes the increase of association constants KaI of PBZ-SA complex. Similarly, PBZ influences KaI of ASA-SA complex. This phenomenon shows that the strength of binding and the stability of the complexes increase in the presence of the second drug. The decrease of KaII values suggests that the competition between PBZ and ASA in binding to serum albumin in the second class of binding sites occurs. The analysis of 1HNMR spectral parameters i.e. changes of chemical shifts and relaxation times of the drug indicate that the presence of ASA weakens the interaction of PBZ with albumin. Similarly PBZ weakens the interaction of ASA with albumin. This conclusion points to the necessity of using a monitoring therapy owning to the possible increase of uncontrolled toxic effects.

The influence of ascorbic acid on root growth and the root apical meristem in Arabidopsis thaliana.

PubMed

Kka, Noura; Rookes, James; Cahill, David

2018-06-08

Cell division is a fundamental biological process governed by molecular networks that are initiated in the apical meristems of plants. l-ascorbic acid (AsA) commonly known as vitamin C is a crucial molecular modulator involved in cell proliferation. In this study, we used AsA application to Arabidopsis and four AsA pathway mutants to investigate the influence of AsA on the root apical meristem (RAM) and root growth. Treatment of seeds of wild-type Col-0 with AsA prior to sowing showed a significant increase in the activity of cell division of the RAM, root growth rate and root length when compared with untreated seeds. Seedlings of the AsA pathway mutant vtc1-1 showed a significant reduction in the level of AsA and a significant increase in the number of quiescent cells in the RAM when compared with Col-0. Cell proliferation was reduced in the AsA pathway mutants vtc1-1, dhar1, vtc5-1, apx1, respectively, however, root growth decreased significantly only in vtc1-1 when compared with Col-0. In addition, hydrogen peroxide (H 2 O 2 ) levels were shown to increase in the AsA pathway mutants, with the highest level of H 2 O 2 found in vtc1-1. AsA is also shown to have an indirect influence in inducing periclinal division as a reduced level was found in vtc1-1. Therefore, in this study, we found that AsA had an influence on cell proliferation and root growth and VTC1 was shown to be a key modulator of H 2 O 2 levels. These findings open the door for further studies to reveal the involvement of AsA in cell proliferation and the interaction between AsA and H 2 O 2 on cell polarity in the RAM and potentially the shoot apical meristem. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis

PubMed Central

Cuffari, Carmen; Pierce, David; Korczowski, Bartosz; Fyderek, Krzysztof; Van Heusen, Heather; Hossack, Stuart; Wan, Hong; Edwards, Alena YZ; Martin, Patrick

2016-01-01

Background Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA) use in pediatric ulcerative colitis (UC). Aim To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA) after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC. Methods Participants (5–17 years of age; 18–82 kg, stratified by weight) with UC received multi-matrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day) for 7 days. Blood samples were collected pre-dose on days 5 and 6. On days 7 and 8, blood and urine samples were collected and safety was evaluated. 5-ASA and Ac-5-ASA plasma and urine concentrations were analyzed by non-compartmental methods and used to develop a population pharmacokinetic model. Results Fifty-two subjects (21 [30 mg/kg]; 22 [60 mg/kg]; 9 [100 mg/kg]) were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose-proportional increase between 30 and 60 mg/kg/day cohorts. For 30, 60, and 100 mg/kg/day doses, mean percentages of 5-ASA absorbed were 29.4%, 27.0%, and 22.1%, respectively. Simulated steady-state exposures and variabilities for 5-ASA and Ac-5-ASA (coefficient of variation approximately 50% and 40%–45%, respectively) were similar to those observed previously in adults at comparable doses. Treatment-emergent adverse events were reported by ten subjects. Events were similar among different doses and age groups with no new safety signals identified. Conclusion Children and adolescents with UC receiving multimatrix mesalamine demonstrated 5-ASA and Ac-5-ASA pharmacokinetic profiles similar to historical adult data. Multimatrix mesalamine was well tolerated across all dose and age groups. ClinicalTrials.gov Identifier: NCT01130844. PMID:26893546

The Assignment of American Society of Anesthesiologists Physical Status Classification for Adult Polytrauma Patients: Results From a Survey and Future Considerations.

PubMed

Kuza, Catherine M; Hatzakis, George; Nahmias, Jeffry T

2017-12-01

The American Society of Anesthesiologists (ASA) physical status (PS) classification system assesses the preoperative health of patients. Previous studies demonstrated poor interrater reliability and variable ASA PS scores, especially in trauma scenarios. There are few studies that evaluated the assignment of ASA PS scores in trauma patients and no studies that evaluated ASA PS assignment in severely injured adult polytrauma patients. Our objective was to assess interrater reliability and identify sources of discrepancy among anesthesiologists and trauma surgeons in designating ASA PS scores to adult polytrauma patients. A link to an online survey containing questions assessing attitudes regarding ASA PS classification, demographic information, and 8 fictional trauma cases was e-mailed to anesthesiologists and trauma surgeons. The participants were asked to assign an ASA PS score to each scenario and explain their choice. Rater-versus-reference and interrater reliability, beyond that expected by chance, among respondents was analyzed using the Fleiss kappa analysis. A total of 349 participants completed the survey. All 8 cases had inconsistent ASA PS scores; several cases had scores ranging from I to VI and variable emergency (E) designations. Using weighted kappa (Kw) analysis for a subset of 201 respondents (101 trauma surgeons [S] and 100 anesthesiologists [A]), we found moderate (Kw = 0.63; SE = 0.024; 95% confidence interval, 0.594-0.666; P < .001) interrater-versus-reference reliability. The interrater reliability was fair (Kw = 0.43; SE = 0.037; 95% confidence interval, 0.360-0.491; P < .001). This study demonstrates fair interrater reliability beyond that expected by chance of the ASA PS scores among anesthesiologists and trauma surgeons when assessing adult polytrauma patients. Although the ASA PS is used in some trauma risk stratification models, discrepancies of ASA PS scores assigned to trauma cases exist. Future modifications of the ASA PS guidelines should aim to improve the interrater reliability of ASA PS scores in trauma patients. Further studies are warranted to determine the value of the ASA PS score as a trauma prognostic metric.

Long-term clinical outcome after alcohol septal ablation for obstructive hypertrophic cardiomyopathy: results from the Euro-ASA registry.

PubMed

Veselka, Josef; Jensen, Morten Kvistholm; Liebregts, Max; Januska, Jaroslav; Krejci, Jan; Bartel, Thomas; Dabrowski, Maciej; Hansen, Peter Riis; Almaas, Vibeke Marie; Seggewiss, Hubert; Horstkotte, Dieter; Tomasov, Pavol; Adlova, Radka; Bundgaard, Henning; Steggerda, Robbert; Ten Berg, Jurriën; Faber, Lothar

2016-05-14

The first cases of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy (HCM) were published two decades ago. Although the outcomes of single-centre and national ASA registries have been published, the long-term survival and clinical outcome of the procedure are still debated. We report long-term outcomes from the as yet largest multinational ASA registry (the Euro-ASA registry). A total of 1275 (58 ± 14 years, median follow-up 5.7 years) highly symptomatic patients treated with ASA were included. The 30-day post-ASA mortality was 1%. Overall, 171 (13%) patients died during follow-up, corresponding to a post-ASA all-cause mortality rate of 2.42 deaths per 100 patient-years. Survival rates at 1, 5, and 10 years after ASA were 98% (95% CI 96-98%), 89% (95% CI 87-91%), and 77% (95% CI 73-80%), respectively. In multivariable analysis, independent predictors of all-cause mortality were age at ASA (P < 0.01), septum thickness before ASA (P < 0.01), NYHA class before ASA (P = 0.047), and the left ventricular (LV) outflow tract gradient at the last clinical check-up (P = 0.048). Alcohol septal ablation reduced the LV outflow tract gradient from 67 ± 36 to 16 ± 21 mmHg (P < 0.01) and NYHA class from 2.9 ± 0.5 to 1.6 ± 0.7 (P < 0.01). At the last check-up, 89% of patients reported dyspnoea of NYHA class ≤2, which was independently associated with LV outflow tract gradient (P < 0.01). The Euro-ASA registry demonstrated low peri-procedural and long-term mortality after ASA. This intervention provided durable relief of symptoms and a reduction of LV outflow tract obstruction in selected and highly symptomatic patients with obstructive HCM. As the post-procedural obstruction seems to be associated with both worse functional status and prognosis, optimal therapy should be focused on the elimination of LV outflow tract gradient. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Acetylsalicylic acid-triggered 15-HETE generation by peripheral leukocytes for identifying ASA sensitivity.

PubMed

Korosec, Peter; Tisler, Ursa; Bajrovic, Nissera; Silar, Mira; Mrhar, Ales; Kosnik, Mitja

2011-10-01

Exposure to acetylsalicylic acid (ASA) may exacerbate respiratory or skin diseases or induce anaphylactoid reactions in apparently healthy individuals. We wanted to evaluate the clinical and diagnostic utility of measuring ASA-induced 15-hydroxyeicosatetraenoic acid (15-HETE) generation. We performed a prospective single-blind study with 26 subjects undergoing clinical evaluation and/or ASA provocation testing. We also included 12 control subjects. Peripheral blood leukocytes were incubated with 500 μM ASA and 15-HETE release was measured by competitive ELISA. We found that 18 subjects were ASA-tolerant and 8 were ASA-intolerant. The mean increase in 15-HETE in intolerant subjects was 34% and this was comparable to the mean increase of 30% observed in ASA-tolerant subjects. A similar mean increase was also observed in control subjects. The ROC calculation showed that the optimal diagnostic threshold would be an increase of greater than 33%. However, the sensitivity of this increase was only 63% and the specificity was 50%. Our data suggest that further studies are needed before the ASA-induced 15-HETE test can be used in clinical practice. Copyright © 2011 Elsevier Ltd. All rights reserved.

Enhanced Adsorption of p-Arsanilic Acid from Water by Amine-Modified UiO-67 as Examined Using Extended X-ray Absorption Fine Structure, X-ray Photoelectron Spectroscopy, and Density Functional Theory Calculations.

PubMed

Tian, Chen; Zhao, Jian; Ou, Xinwen; Wan, Jieting; Cai, Yuepeng; Lin, Zhang; Dang, Zhi; Xing, Baoshan

2018-03-20

p-Arsanilic acid ( p-ASA) is an emerging organoarsenic pollutant comprising both inorganic and organic moieties. For the efficient removal of p-ASA, adsorbents with high adsorption affinity are urgently needed. Herein, amine-modified UiO-67 (UiO-67-NH 2 ) metal-organic frameworks (MOFs) were synthesized, and their adsorption affinities toward p-ASA were 2 times higher than that of the pristine UiO-67. Extended X-ray absorption fine structure (EXAFS), X-ray photoelectron spectroscopy (XPS), and density functional theory (DFT) calculation results revealed adsorption through a combination of As-O-Zr coordination, hydrogen bonding, and π-π stacking, among which As-O-Zr coordination was the dominant force. Amine groups played a significant role in enhancing the adsorption affinity through strengthening the As-O-Zr coordination and π-π stacking, as well as forming new adsorption sites via hydrogen bonding. UiO-67-NH 2 s could remove p-ASA at low concentrations (<5 mg L -1 ) in simulated natural and wastewaters to an arsenic level lower than that of the drinking water standard of World Health Organization (WHO) and the surface water standard of China, respectively. This work provided an emerging and promising method to increase the adsorption affinity of MOFs toward pollutants containing both organic and inorganic moieties, via modifying functional groups based on the pollutant structure to achieve synergistic adsorption effect.

Hydrophobic folding units derived from dissimilar monomer structures and their interactions.

PubMed

Tsai, C J; Nussinov, R

1997-01-01

We have designed an automated procedure to cut a protein into compact hydrophobic folding units. The hydrophobic units are large enough to contain tertiary non-local interactions, reflecting potential nucleation sites during protein folding. The quality of a hydrophobic folding unit is evaluated by four criteria. The first two correspond to visual characterization of a structural domain, namely, compactness and extent of isolation. We use the definition of Zehfus and Rose (Zehfus MH, Rose GD, 1986, Biochemistry 25:35-340) to calculate the compactness of a cut protein unit. The isolation of a unit is based on the solvent accessible surface area (ASA) originally buried in the interior and exposed to the solvent after cutting. The third quantity is the hydrophobicity, equivalent to the fraction of the buried non-polar ASA with respect to the total non-polar ASA. The last criterion in the evaluation of a folding unit is the number of segments it includes. To conform with the rationale of obtaining hydrophobic units, which may relate to early folding events, the hydrophobic interactions are implicitly and explicitly applied in their generation and assessment. We follow Holm and Sander (Holm L, Sander C, 1994, Proteins 19:256-268) to reduce the multiple cutting-point problem to a one-dimensional search for all reasonable trial cuts. However, as here we focus on the hydrophobic cores, the contact matrix used to obtain the first non-trivial eigenvector contains only hydrophobic contracts, rather than all, hydrophobic and hydrophilic, interactions. This dataset of hydrophobic folding units, derived from structurally dissimilar single chain monomers, is particularly useful for investigations of the mechanism of protein folding. For cases where there are kinetic data, the one or more hydrophobic folding units generated for a protein correlate with the two or with the three-state folding process observed. We carry out extensive amino acid sequence order independent structural comparisons to generate a structurally non-redundant set of hydrophobic folding units for fold recognition and for statistical purposes.

Evaluation by undergraduate medical students of a role-playing training program on the management of acute states of agitation.

PubMed

Rolland, B; Fovet, T; Poissy, J; Eichholtzer, C; Lesage, M; Thomas, P; Jourdain, M

2018-04-01

Acute states of agitation (ASAs) are frequent in daily medical practice. However, training on real ASAs raises technical and ethical issues, whereas lecture-based teaching hardly addresses some educational objectives, e.g., improving relational skills and team-based coordination. Simulation-based medical education (SBME) is a promising medium to train students on managing ASAs. We have recently implemented a role-playing training module on ASAs. In this scenario, four to five students play the role of the staff, while a trained professional actor plays the agitated patient. A subsequent standardized debriefing is conducted by a senior psychiatrist. A first wave of 219 students participated in a one-session training of this ASA module in June 2015. They completed pre-session and post-session questionnaires aiming to collect "proof-of-concept" data. The pre-session questionnaire investigated: previous experience of ASA among students during their clinical training; previous participation in a role-playing SBME; and perceived knowledge of the good practice rules for managing ASAs. The post-session questionnaire investigated among the students if: they thought having been able to appropriately manage the simulated ASA; they found the SBME medium more fitted for training than real situations; they found that the SBME session faithfully reproduced a real ASA; and the session was found useful for transmitting the skills on correct management of ASA. The average level of stress induced by the training was assessed using a numerical rating scale (0-10). Two hundred and six of the 219 students completed the pre-session questionnaire (63% females; response rate 96.7%). A hundred and thirty four students played the scenario and completed the post-session questionnaire (65.7% females; response rate 100%). 38.3% of the responders reported having previously experienced a situation of ASA in their practice, and 31.1% deemed to know the good practices rules for managing an ASA. In post-session, 29.9% of the participants considered that they appropriately managed the ASA, 79.9% deemed that the role-playing session faithfully reproduced a real ASA, and 97% deemed that this SBME was more fitted and useful than a real clinical situation to improve their medical skills. Bivariate analyses revealed that the post-session responses and level of stress were not influenced by previous experience on ASA, previous participation in a SBME role-playing session, or thinking to know the rules for managing ASAs. SBME role-playing training appears a promising, realistic, and well-accepted method for teaching the management of ASA. Copyright © 2017 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

ASAS 095221-4329.8 und ASAS 123034-7703.9 - zwei R-CrB-Stern-Kandidaten aus der ASAS-Datenbank

NASA Astrophysics Data System (ADS)

Huemmerich, Stefan

2011-04-01

During an examination of ASAS Misc-type objects, the stars ASAS 095221-4329.8 GSC 07706-00560, 09:52:21.38 -43:29:40.5) and ASAS 123034-7703.9 (GSC 09416-00380, 12:30:34.22 -77:03:52.7) - both of which show semi-regular variability - were found to exhibit significant obscuration events in their V-band lightcurves. Both stars are likely to be red giants undergoing fading events, possibly of DY Per-type. However, spectroscopy of both stars is needed for a conclusive classification. The corresponding entries in the International Variable Star Index (VSX) have been revised accordingly; variability type was set to "RCB:".

Urinalysis of MMX-mesalazine as a tool to monitor 5-ASA adherence in daily IBD practice.

PubMed

Römkens, Tessa E H; Te Morsche, Rene; Peters, Wilbert; Burger, David M; Hoentjen, Frank; Drenth, Joost P H

2018-03-01

Adherence is pivotal but challenging in ulcerative colitis (UC) treatment. Many methods to assess adherence are subjective or have limitations. (Nac-)5-aminosalicylic acid (5-ASA) urinalysis by high-performance liquid chromatography (HPLC) seems feasible and reproducible in healthy volunteers. We performed a prospective study in adult quiescent UC patients to evaluate the feasibility of spot (Nac-)5-ASA urinalysis by HPLC to assess adherence in daily inflammatory bowel disease (IBD) care. Twenty-nine patients (51.7% male, mean age 52 ± 11 years) were included (median FU 9 months) and weekly spot urine samples were collected. We found large variation in spot (Nac-)5-ASA urinary excretion that was unrelated to brand, dosing schedule or dosage of 5-ASA. In conclusion, spot (Nac-)5-ASA urinalysis is not applicable to assess 5-ASA adherence in daily IBD care. © 2017 The British Pharmacological Society.

Ulcerative proctitis: a review of pharmacotherapy and management.

PubMed

Lakatos, Peter Laszlo; Lakatos, Laszlo

2008-04-01

Ulcerative proctitis (UP) is a common presentation of ulcerative colitis (UC). To summarize available literature on up-to-date management and pharmacotherapy of UP patients. Extensive Medline/Embase literature search was performed to identify relevant articles. Topical medication with rectally administered 5-aminosalicylic acid (5-ASA)/corticosteroid suppositories or enemas is effective treatment for most UP patients. Locally administered 5-ASA is more efficacious than oral compounds. The combination of topical 5-ASA and oral 5-ASA or topical steroids should be considered for escalation of treatment. Maintenance treatment is indicated in all UC cases. 5-ASA suppositories are suggested as first-line maintenance therapy if accepted by patients, although oral 5-ASA as maintenance therapy might prevent proximal extension of the disease. After re-assessment, chronically active patients refractory or intolerant to 5-ASAs and corticosteroids may require immunomodulators or biological therapy. Exceptional cases may require a proctocolectomy.

Variation of ascorbic acid concentration in fruits of cultivated and wild apples.

PubMed

Fang, Ting; Zhen, Qiaoling; Liao, Liao; Owiti, Albert; Zhao, Li; Korban, Schuyler S; Han, Yuepeng

2017-06-15

Ascorbic acid (AsA) content in mature fruits of 457 apple accessions were measured, and a great variation in AsA concentration was detected. Wild fruits showed significantly higher level of AsA than cultivated fruits. Fruit AsA content was positively correlated with malic acid content, but negatively correlated with fruit weight and soluble solid content. Thus, the difference in AsA content between the wild and cultivated fruits could be attributed to an indirect consequence of human selection for larger fruit size, less acidity, and increased sweetness during apple domestication. Additionally, AsA concentration was extremely high in fruit at the juvenile stage, but dramatically decreased at the expanding and mature stages. The expression levels of three genes controlling AsA accumulation, MdGGP1, MdDHAR3-3, and MdNAT7-2, were significantly negatively correlated with AsA contents in fruits, suggesting a feedback regulation mechanism in AsA-related gene expression. Our results could be helpful for future apple breeding. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hydrocortisone effect of arylsulfatase A in primary mouse brain cell cultures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marcelo, A.; Pieringer, R.A.

The primary goal of this study was to study the mechanism of action of hydrocortisone (HC) on arylsulfatase A (ASA) in primary cultures of cells that were dissociated from the brains of embryonic mice. Cells were cultured in a defined medium in the absence or in the presence of 3 ..mu..M HC. The specific activity of ASA in nontreated cells was 1.297 U/mg (U = ..mu..mol/hr) while the value for the HC-treated cells was 0.783 U/mg. The authors data shows that HC inhibits ASA activity in these cultures cells (p < 0.001). The determination of the ASA enzyme activity wasmore » assayed primarily with the artificial substrate p-nitrocatechol sulfate. However, the natural substrate (cerebroside /sup 35/S-sulfate) also as active and correlated linearly with the activity of p-nitrocatechol sulfate. Purified ASA was isolated from calf brains and used to generate an antibody (Ab) against ASA. The specificity of the Ab for the ASA protein of cell cultures was tested in Ouchterlony double immunodiffusion studies. The Ab was used in a competitive enzyme-linked immunosorbent assay to quantify the number of ASA molecules in the cell extracts from the embryonic mouse cell cultures. Preliminary data suggest that HC decreases the number of ASA molecules.« less

Identifying the Risk of Swallowing-Related Pulmonary Complications in Older Patients With Hip Fracture.

PubMed

Meals, Clifton; Roy, Siddharth; Medvedev, Gleb; Wallace, Matthew; Neviaser, Robert J; O'Brien, Joseph

2016-01-01

To identify and potentially modify the risk of pulmonary complications in a group of older patients with hip fracture, the authors obtained speech and language pathology consultations for these patients. Then they performed a retrospective chart review of all patients 65 years and older who were admitted to their institution between June 2011 and July 2013 with acute hip fracture, were treated surgically, and had a speech and language pathology evaluation in the immediate perioperative period. The authors identified 52 patients who met the study criteria. According to the American Society of Anesthesiologists (ASA) classification system, at the time of surgery, 1 patient (2%) was classified as ASA I, 12 patients (23%) were ASA II, 26 (50%) were ASA III, and 12 (23%) were ASA IV. Based on a speech and language pathology evaluation, 22 patients (42%) were diagnosed with dysphagia. Statistical analysis showed that ASA III status and ASA IV status were meaningful predictors of dysphagia and that dysphagia itself was a strong risk factor for pulmonary aspiration, pneumonia, and aspiration pneumonitis. Evaluation by a speech and language pathologist, particularly of patients classified as ASA III or ASA IV, may be an efficient means of averting pulmonary morbidity that is common in older patients with hip fracture. Copyright 2016, SLACK Incorporated.

Synthesis of L-ascorbic acid in the phloem

PubMed Central

Hancock, Robert D; McRae, Diane; Haupt, Sophie; Viola, Roberto

2003-01-01

Background Although plants are the main source of vitamin C in the human diet, we still have a limited understanding of how plants synthesise L-ascorbic acid (AsA) and what regulates its concentration in different plant tissues. In particular, the enormous variability in the vitamin C content of storage organs from different plants remains unexplained. Possible sources of AsA in plant storage organs include in situ synthesis and long-distance transport of AsA synthesised in other tissues via the phloem. In this paper we examine a third possibility, that of synthesis within the phloem. Results We provide evidence for the presence of AsA in the phloem sap of a wide range of crop species using aphid stylectomy and histochemical approaches. The activity of almost all the enzymes of the primary AsA biosynthetic pathway were detected in phloem-rich vascular exudates from Cucurbita pepo fruits and AsA biosynthesis was demonstrated in isolated phloem strands from Apium graveolens petioles incubated with a range of precursors (D-glucose, D-mannose, L-galactose and L-galactono-1,4-lactone). Phloem uptake of D-[U-14C]mannose and L-[1-14C]galactose (intermediates of the AsA biosynthetic pathway) as well as L-[1-14C]AsA and L-[1-14C]DHA, was observed in Nicotiana benthamiana leaf discs. Conclusions We present the novel finding that active AsA biosynthesis occurs in the phloem. This process must now be considered in the context of mechanisms implicated in whole plant AsA distribution. This work should provoke studies aimed at elucidation of the in vivo substrates for phloem AsA biosynthesis and its contribution to AsA accumulation in plant storage organs. PMID:14633288

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

PubMed

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

2011-01-01

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

ASAS definition for sacroiliitis on MRI in SpA: applicable to children?

PubMed

Herregods, Nele; Dehoorne, Joke; Van den Bosch, Filip; Jaremko, Jacob Lester; Van Vlaenderen, Joke; Joos, Rik; Baraliakos, Xenofon; Varkas, Gaëlle; Verstraete, Koenraad; Elewaut, Dirk; Jans, Lennart

2017-04-11

The Assessment of Spondyloarthritis International Society (ASAS) definition for a 'positive' Magnetic Resonance Imaging (MRI) for sacroiliitis is well studied and validated in adults, but studies about the value of this definition in children are lacking. The aim of this study is to evaluate whether the adult ASAS definition of a positive MRI of the sacroiliac joints can be applied to children with a clinical suspicion of Juvenile Spondyloarthritis (JSpA). Two pediatric musculoskeletal radiologists blinded to clinical data independently retrospectively reviewed sacroiliac (SI) joint MRI in 109 children suspected of sacroiliitis. They recorded global impression (sacroiliitis yes/no) and whether the adult ASAS definition for sacroiliitis was met at each joint. This was compared to gold-standard clinical diagnosis of JSpA. Additionally, MRI were scored according to'adapted' ASAS definitions including other features of sacroiliitis on MRI. JSpA was diagnosed clinically in 47/109 (43%) patients. On MRI, sacroiliitis was diagnosed by global assessment in 30/109 patients, of whom 14 also fulfilled ASAS criteria. No patients with negative global assessment for sacroiliitis fulfilled ASAS criteria. Sensitivity (SN) for JSpA was higher for global assessment (SN = 49%) than for ASAS definition (SN = 26%), but the ASAS definition was more specific (SP = 97% vs. 89%). Modifying adult ASAS criteria to allow bone marrow edema (BME) lesions seen on only one slice, synovitis or capsulitis, increased SN to 36%, 32% and 32% respectively, only slightly lowering SP. Including structural lesions increased SN to 28%, but lowered specificity to 95%. The adult ASAS definition for sacroiliitis has low sensitivity in children. A pediatric-specific definition of MRI-positive sacroiliitis including BME lesions visible on one slice only, synovitis and/or capsulitis may improve diagnostic utility, and increase relevance of MRI in pediatric rheumatology practice.

Fitness plus American Society of Anesthesiologists grade improve outcome prediction after endovascular aneurysm repair.

PubMed

Boult, Margaret; Cowled, Prue; Barnes, Mary; Fitridge, Robert A

2017-09-01

Although the American Society of Anesthesiologists (ASA) grade was established for statistical purposes, it is often used prognostically. However, older patients undergoing elective surgery are typically ASA III, which limits patient stratification. We look at the prognostic effect on early complications and survival of using ASA and self-reported physical fitness to stratify patients undergoing endovascular repair of abdominal aortic aneurysms. Data were extracted from a trial database. All patients were assigned a fitness level (A (fit) or B (unfit)) based on their self-reported ability to walk briskly for 1 km or climb two flights of stairs. Fitness was used to stratify ASA III patients, with fitter patients assigned ASA IIIA and less fit patients ASA IIIB. Outcomes assessed included survival, reinterventions, endoleak, all early and late complications and early operative complications. A combined ASA/fitness scale (II, IIIA, IIIB and IV) correlated with 1- and 3-year survival (1-year P = 0.001, 3-year P = 0.001) and early and late complications (P = 0.001 and P = 0.05). On its own, ASA predicted early complications (P = 0.0004) and survival (1-year P = 0.01, 3-year P = 0.01). Fitness alone was predictive for survival (1-year P = 0.001, 3-year P = 0.001) and late complications (P = 0.009). This study shows that even a superficial assessment of fitness is reflected in surgical outcomes, with fitter ASA III patients showing survival patterns similar to ASA II patients. Physicians should be alert to differences in fitness between patients in the ASA III group, despite similarities based on preexisting severe systemic disease. © 2017 Royal Australasian College of Surgeons.

Effects of clopidogrel and aspirin in combination versus aspirin alone on platelet activation and major receptor expression in diabetic patients: the PLavix Use for Treatment Of Diabetes (PLUTO-Diabetes) trial.

PubMed

Serebruany, Victor L; Malinin, Alex I; Pokov, Alex; Barsness, Gregory; Hanley, Dan F

2008-01-01

Clopidogrel is widely used in diabetic patients after vascular events; however, the ability of this thienopyridine to yield additional antiplatelet protection on top of aspirin has never been explored in a controlled study with comprehensive assessment of platelet activity. The objective of this study was to compare the antiplatelet profiles of clopidogrel + aspirin in combination (C + ASA) versus aspirin alone (ASA) in patients with type 2 diabetes mellitus. Seventy patients with documented diabetes already treated with antecedent aspirin were randomly assigned to receive C + ASA or ASA in the PLUTO-Diabetes trial. Platelet studies included adenosine diphosphate-, collagen-, and arachidonic acid-induced aggregometry; PFA-100 (Dade-Behring, Miami, FL) and Ultegra (Accumetrics, San Diego, CA) analyzers; and expression of 6 major receptors by flow cytometry at baseline and at day 30 after randomization. There were no differences in the baseline clinical and platelet characteristics between the C + ASA and ASA groups, or subsequent significant changes in platelet biomarkers in the ASA group, except for diminished collagen-induced aggregation (P = .02). In contrast, when compared with the ASA group, therapy with C + ASA resulted in significant inhibition of platelet activity assessed by adenosine diphosphate aggregation (P = .0001); closure time prolongation (P = .0003) and reduction of platelet activation units with Ultegra (P = .0001); and expression of platelet/endothelial cell adhesion molecule 1 (P = .002), glycoprotein IIb/IIIa antigen (P = .0002), and activity (P = .0001). Treatment with C + ASA for 1 month provides significantly greater inhibition of platelet activity than ASA alone in diabetic patients in this small randomized trial. However, despite dual antiplatelet regimen, diabetic patients exhibit high residual activity of some platelet biomarkers, including unaffected protease-activated receptor 1 receptor expression.

Ibudilast, a phosphodiesterase inhibitor, in combination with low-dose aspirin potently inhibits guinea pig carotid artery thrombosis without extending bleeding time and causing gastric mucosal injury.

PubMed

Matsuzawa, S; Hoshina, K; Sueyoshi, S; Miyata, Y; Manita, S; Ooie, T; Yasue, T; Sasahara, T

2012-12-01

A combination of low-dose aspirin (ASA) and a phosphodiesterase inhibitor has been clinically tried for the secondary prevention of atherothrombotic diseases. The in vivo antithrombotic property of ibudilast (CAS 50847-11-5), a phosphodiesterase 4 (PDE4) inhibitor, was evaluated in a photochemically-induced guinea pig carotid artery thrombosis model in combination with low-dose ASA. The time required to decrease the carotid artery blood flow to the reading "zero" was defined as the time to occlusion (TTO) of the artery through thrombogenesis. Each independent use of ASA (300 mg/kg, p.o.) and ibudilast (3 and 10 mg/kg, p.o.) significantly prolonged the TTO, and ASA (300 mg/kg) significantly increased bleeding time (BT) and gastric mucosal injury. A selective PDE4 inhibitor rolipram (1 and 5 mg/kg, p.o.) tended to prolong the TTO without extending BT. ASA (100 mg/kg) plus ibudilast (3 mg/kg) and ASA (100 mg/kg) plus rolipram (5 mg/kg) markedly prolonged the TTO compared with each agent alone. Interestingly, ASA (100 mg/kg) plus ibudilast (3 mg/kg) caused a longer TTO than ASA (300 mg/kg) alone, without significant extension of BT and gastric mucosal injury as observed in ASA (300 mg/kg). These results indicate that the combination of low-dose ASA and ibudilast has a more potent antithrombotic effect than ASA alone without increasing bleeding tendency and gastric mucosal injury. The potent in vivo antithrombotic effect of this combination may be brought about by an action that is associated with PDE4 inhibition of ibudilast. © Georg Thieme Verlag KG Stuttgart · New York.

Regulation of L-ascorbic acid content in strawberry fruits

PubMed Central

Cruz-Rus, Eduardo; Amaya, Iraida; Sánchez-Sevilla, José F.; Botella, Miguel A.; Valpuesta, Victoriano

2011-01-01

Plants have several L-ascorbic acid (AsA) biosynthetic pathways, but the contribution of each one to the synthesis of AsA varyies between different species, organs, and developmental stages. Strawberry (Fragaria×ananassa) fruits are rich in AsA. The pathway that uses D-galacturonate as the initial substrate is functional in ripe fruits, but the contribution of other pathways to AsA biosynthesis has not been studied. The transcription of genes encoding biosynthetic enzymes such as D-galacturonate reductase (FaGalUR) and myo-inositol oxygenase (FaMIOX), and the AsA recycling enzyme monodehydroascorbate reductase (FaMDHAR) were positively correlated with the increase in AsA during fruit ripening. Fruit storage for 72 h in a cold room reduced the AsA content by 30%. Under an ozone atmosphere, this reduction was 15%. Ozone treatment increased the expression of the FaGalUR, FaMIOX, and L-galactose-1-phosphate phosphatase (FaGIPP) genes, and transcription of the L-galactono-1,4-lactone dehydrogenase (FaGLDH) and FAMDHAR genes was higher in the ozone-stored than in the air-stored fruits. Analysis of AsA content in a segregating population from two strawberry cultivars showed high variability, which did not correlate with the transcription of any of the genes studied. Study of GalUR protein in diverse cultivars of strawberry and different Fragaria species showed that a correlation between GalUR and AsA content was apparent in most cases, but it was not general. Three alleles were identified in strawberry, but any sequence effect on the AsA variability was eliminated by analysis of the allele-specific expression. Taken together, these results indicate that FaGalUR shares the control of AsA levels with other enzymes and regulatory elements in strawberry fruit. PMID:21561953

Comparison of effects of calcium carbasalate and aspirin on gastroduodenal mucosal damage in human volunteers.

PubMed Central

Murray, F E; Hudson, N; Atherton, J C; Cole, A T; Scheck, F; Hawkey, C J

1996-01-01

Calcium carbasalate is a therapeutically active salicylate which seems to cause less gastroduodenal mucosal damage than aspirin in laboratory animals. This endoscopist-blinded, randomised, cross over trial aimed to compare acute gastric mucosal damage in 20 healthy volunteers treated with acetyl salicylic acid (ASA) (650 mg three times daily) and effervescent calcium carbasalate (ECC) (826.8 mg three times daily) bioequivalent to 650 mg ASA over a five day period. Endoscopy was performed immediately before treatment and on day 5 of each treatment. Serum salicylate, thromboxane B2, and gastric mucosal prostaglandin E2 (PGE2) concentrations were measured after endoscopy. ECC caused fewer gastric mucosal erosions than ASA. The total number of gastric erosions was 23.8 (16.1) in the ASA treated subjects compared with 9.1 (8.7) in ECC treated subjects (p = 0.004). Differences between ASA and ECC were significant for both the gastric antrum and body, and for both haemorrhagic and non-haemorrhagic erosions. The mean gastric body Lanza score for mucosal damage was lower after ECC than ASA (p = 0.003). The visual analogue score for gastric body damage was lower for ECC (16.9 mm (15.9)) than for ASA (32.7 mm (20.8)), p = 0.008. Serum salicylate concentrations were similar after both preparations (ASA: 66 (23) mg/l, versus ECC: 58 (17) mg/l, NS). Serum thromboxane B2 was similarly reduced using both preparations-97.2 (3.5)% inhibition with ASA, 95.2 (5.5)% inhibition with calcium carbasalate (NS). Suppression of gastric mucosal PGE2 synthesis was similar with both preparations (ASA: 83.4 (17.1)%; ECC 84.3 (12.9)%; NS). It is concluded that ECC causes significantly less gastroduodenal mucosal damage than ASA administered at bioequivalent doses as judged by serum salicylate, serum thromboxane, and mucosal PGE2 values. ECC may therefore be a less harmful alternative treatment to plain ASA. PMID:8566836

Microfluidic assay of platelet deposition on collagen by perfusion of whole blood from healthy individuals taking aspirin.

PubMed

Li, Ruizhi; Fries, Susanne; Li, Xuanwen; Grosser, Tilo; Diamond, Scott L

2013-08-01

Microfluidic devices can create hemodynamic conditions for platelet assays. We validated an 8-channel device in a study of interdonor response to acetylsalicylic acid (ASA, aspirin) with whole blood from 28 healthy individuals. Platelet deposition was assessed before treatment or 24 h after ingestion of 325 mg ASA. Whole blood (plus 100 μmol/L H-d-Phe-Pro-Arg-chloromethylketone to inhibit thrombin) was further treated ex vivo with ASA (0-500 μmol/L) and perfused over fibrillar collagen for 300 s at a venous wall shear rate (200 s(-1)). Ex vivo ASA addition to blood drawn before aspirin ingestion caused a reduction in platelet deposition [half-maximal inhibitory concentration (IC50) approximately 10-20 μmol/L], especially between 150 and 300 s of perfusion, when secondary aggregation mediated by thromboxane was expected. Twenty-seven of 28 individuals displayed smaller deposits (45% mean reduction; range 10%-90%; P < 0.001) from blood obtained 24 h after ASA ingestion (no ASA added ex vivo). In replicate tests, an R value to score secondary aggregation [deposition rate from 150 to 300 s normalized by rate from 60 to 150 s] showed R < 1 in only 2 of 28 individuals without ASA ingestion, with R > 1 in only 3 of 28 individuals after 500 μmol/L ASA addition ex vivo. At 24 h after ASA ingestion, 21 of 28 individuals displayed poor secondary aggregation (R < 1) without ex vivo ASA addition, whereas the 7 individuals with residual secondary aggregation (R > 1) displayed insensitivity to ex vivo ASA addition. Platelet deposition was not correlated with platelet count. Ex vivo ASA addition caused similar inhibition at venous and arterial wall shear rates. Microfluidic devices quantified platelet deposition after ingestion or ex vivo addition of aspirin.

Asiatic Acid Inhibits Pro-Angiogenic Effects of VEGF and Human Gliomas in Endothelial Cell Culture Models

PubMed Central

Kavitha, Chandagirikoppal V.; Agarwal, Chapla; Agarwal, Rajesh; Deep, Gagan

2011-01-01

Malignant gliomas are one of the most devastating and incurable tumors. Sustained excessive angiogenesis by glioma cells is the major reason for their uncontrolled growth and resistance toward conventional therapies resulting in high mortality. Therefore, targeting angiogenesis should be a logical strategy to prevent or control glioma cell growth. Earlier studies have shown that Asiatic Acid (AsA), a pentacyclic triterpenoid, is effective against glioma and other cancer cells; however, its efficacy against angiogenesis remains unknown. In the present study, we examined the anti-angiogenic efficacy of AsA using human umbilical vein endothelial cells (HUVEC) and human brain microvascular endothelial cells (HBMEC). Our results showed that AsA (5–20 µM) inhibits HUVEC growth and induces apoptotic cell death by activating caspases (3 and 9) and modulating the expression of apoptosis regulators Bad, survivin and pAkt-ser473. Further, AsA showed a dose-dependent inhibition of HUVEC migration, invasion and capillary tube formation, and disintegrated preformed capillary network. AsA also inhibited the VEGF-stimulated growth and capillary tube formation by HUVEC and HBMEC. Next, we analyzed the angiogenic potential of conditioned media collected from human glioma LN18 and U87-MG cells treated with either DMSO (control conditioned media, CCM) or AsA 20 µM (AsA20 conditioned media, AsA20CM). CCM from glioma cells significantly enhanced the capillary tube formation in both HUVEC and HBMEC, while capillary tube formation in both endothelial cell lines was greatly compromised in the presence of AsA20CM. Consistent with these results, VEGF expression was lesser in AsA20CM compared to CCM, and indeed AsA strongly inhibited VEGF level (both cellular and secreted) in glioma cells. AsA also showed dose-dependent anti-angiogenic efficacy in Matrigel plug assay, and inhibited the glioma cells potential to attract HUVEC/HBMEC. Overall, the present study clearly showed the strong anti-angiogenic potential of AsA and suggests its usefulness against malignant gliomas. PMID:21826202

Protein–DNA Interactions: The Story so Far and a New Method for Prediction

DOE PAGES

Jones, Susan; Thornton, Janet M.

2003-01-01

This review describes methods for the prediction of DNA binding function, and specifically summarizes a new method using 3D structural templates. The new method features the HTH motif that is found in approximately one-third of DNAbinding protein families. A library of 3D structural templates of HTH motifs was derived from proteins in the PDB. Templates were scanned against complete protein structures and the optimal superposition of a template on a structure calculated. Significance thresholds in terms of a minimum root mean squared deviation (rmsd) of an optimal superposition, and a minimum motif accessible surface area (ASA), have been calculated. Inmore » this way, it is possible to scan the template library against proteins of unknown function to make predictions about DNA-binding functionality.« less

The effect of flap thickness on corneal biomechanics after myopic laser in situ keratomileusis using the M-2 microkeratome

PubMed Central

Goussous, Iyad A; El-Agha, Mohamed-Sameh; Awadein, Ahmed; Hosny, Mohamed H; Ghaith, Alaa A; Khattab, Ahmed L

2017-01-01

Purpose The purpose of this study was to determine the effect of flap thickness on corneal biomechanics after myopic laser in situ keratomileusis (LASIK). Methods This is a prospective controlled non-randomized, institutional study. Patients underwent either epi-LASIK with mitomycin (advanced surface ablation [ASA]), thin-flap LASIK (90 µm head), or thick-flap LASIK (130 µm head). In ASA, the Moria Epi-K hydroseparator was used. LASIK flaps were created using the Moria M-2 mechanical microkeratome. The corneal hysteresis (CH) and corneal resistance factor (CRF) were measured preoperatively and 3 months after surgery, using the Ocular Response Analyzer®. Results Ten patients (19 eyes) underwent ASA, 11 patients (16 eyes) underwent thin-flap LASIK, and 11 patients (16 eyes) underwent thick-flap LASIK. The mean preoperative CH was 10.47±0.88, 10.52±1.4, and 11.28±1.4 mmHg (p=0.043), respectively, decreasing after surgery by 1.75±1.02, 1.66±1.00, and 2.62±1.03 mmHg (p=0.017). The mean reduction of CH per micron of central corneal ablation was 0.031, 0.023, and 0.049 mmHg/µm (p=0.005). Mean preoperative CRF was 10.11±1.28, 10.34±1.87, and 10.62±1.76 mmHg (p=0.66), decreasing after surgery by 2.33±1.35, 2.77±1.03, and 2.92±1.10 mmHg (p=0.308). The mean reduction of CRF per micron of central corneal ablation was 0.039, 0.040, and 0.051 mmHg/µm (p=0.112). Conclusion Thick-flap LASIK caused a greater reduction of CH and CRF than thin-flap LASIK and ASA, although this was statistically significant only for CH. ASA and thin-flap LASIK were found to be biomechanically similar. PMID:29200820

The effect of flap thickness on corneal biomechanics after myopic laser in situ keratomileusis using the M-2 microkeratome.

PubMed

Goussous, Iyad A; El-Agha, Mohamed-Sameh; Awadein, Ahmed; Hosny, Mohamed H; Ghaith, Alaa A; Khattab, Ahmed L

2017-01-01

The purpose of this study was to determine the effect of flap thickness on corneal biomechanics after myopic laser in situ keratomileusis (LASIK). This is a prospective controlled non-randomized, institutional study. Patients underwent either epi-LASIK with mitomycin (advanced surface ablation [ASA]), thin-flap LASIK (90 µm head), or thick-flap LASIK (130 µm head). In ASA, the Moria Epi-K hydroseparator was used. LASIK flaps were created using the Moria M-2 mechanical microkeratome. The corneal hysteresis (CH) and corneal resistance factor (CRF) were measured preoperatively and 3 months after surgery, using the Ocular Response Analyzer ® . Ten patients (19 eyes) underwent ASA, 11 patients (16 eyes) underwent thin-flap LASIK, and 11 patients (16 eyes) underwent thick-flap LASIK. The mean preoperative CH was 10.47±0.88, 10.52±1.4, and 11.28±1.4 mmHg ( p =0.043), respectively, decreasing after surgery by 1.75±1.02, 1.66±1.00, and 2.62±1.03 mmHg ( p =0.017). The mean reduction of CH per micron of central corneal ablation was 0.031, 0.023, and 0.049 mmHg/µm ( p =0.005). Mean preoperative CRF was 10.11±1.28, 10.34±1.87, and 10.62±1.76 mmHg ( p =0.66), decreasing after surgery by 2.33±1.35, 2.77±1.03, and 2.92±1.10 mmHg ( p =0.308). The mean reduction of CRF per micron of central corneal ablation was 0.039, 0.040, and 0.051 mmHg/µm ( p =0.112). Thick-flap LASIK caused a greater reduction of CH and CRF than thin-flap LASIK and ASA, although this was statistically significant only for CH. ASA and thin-flap LASIK were found to be biomechanically similar.

Effect of transdermic acetylsalicylic acid on hemostasis in healthy volunteers.

PubMed

Martínez, Adriana B; Funosas, Esteban; Maestri, Lorella; Lucena, Perla Hermida

2007-01-01

Acetylsalicylic acid (ASA) exerts an antiaggregatory effect on platelets by irreversible inhibition of the enzyme thrombocyte cyclooxigenase when it is administered orally at doses above 80 mg/day. For several years ASA has been available as a solution that can be topically applied on the skin. It is widely used by athletes and individuals with chronic rheumatic disorders. However, it has not been established to date whether the plasma levels that result from these doses of ASA affect hemostasis during odontological procedures that involve bleeding, causing platelet dysfunction. The aim of the present study was to evaluate whether topical application is capable of affecting hemostasis. Three studies were conducted: A, B y C. Each of the 3 groups included 12 healthy volunteers of both sexes. The aim of study A was to evaluate if the formulation for topical application resulted in plasma levels of ASA that resembled those observed for the oral formulation and affect hemostasis. In experiment A, plasma levels of salicylic acid (SA) were assessed for each volunteer at 30 minutes, 60 minutes, 6 hours, 12 hours and 24 hours after oral administration of a dose of 500 mg ASA. Experiment B was identical to experiment A except for the fact that ASA was topically applied employing a commercial preparation Aspirub in a predetermined area at a rate of 2 ml/day over a period of 15 days. Experiment C was designed in the same way as experiment B, for a higher dose and a longer period of time (4 ml/day over a period of 30 days). One of the volunteers exhibited detectable salicylemia that could affect hemostasis as occurs with the oral formulation. The following two studies (C1 and C2) employed doses of Aspirub of 8 and 16 ml/day respectively, over a period of 30 days. We measured biochemical parameters associated to platelet function. The dose of 8 ml/day induced moderate alterations in all the parameters related to platelet function and the daily dose of 16 ml inhibited platelet aggregation in all the volunteers involved.

Discriminative ability of commonly used indices to predict adverse outcomes after poster lumbar fusion: a comparison of demographics, ASA, the modified Charlson Comorbidity Index, and the modified Frailty Index.

PubMed

Ondeck, Nathaniel T; Bohl, Daniel D; Bovonratwet, Patawut; McLynn, Ryan P; Cui, Jonathan J; Shultz, Blake N; Lukasiewicz, Adam M; Grauer, Jonathan N

2018-01-01

As research tools, the American Society of Anesthesiologists (ASA) physical status classification system, the modified Charlson Comorbidity Index (mCCI), and the modified Frailty Index (mFI) have been associated with complications following spine procedures. However, with respect to clinical use for various adverse outcomes, no known study has compared the predictive performance of these indices specifically following posterior lumbar fusion (PLF). This study aimed to compare the discriminative ability of ASA, mCCI, and mFI, as well as demographic factors including age, body mass index, and gender for perioperative adverse outcomes following PLF. A retrospective review of prospectively collected data was performed. Patients undergoing elective PLF with or without interbody fusion were extracted from the 2011-2014 American College of Surgeons National Surgical Quality Improvement Program (NSQIP). Perioperative adverse outcome variables assessed included the occurrence of minor adverse events, severe adverse events, infectious adverse events, any adverse event, extended length of hospital stay, and discharge to higher-level care. Patient comorbidity indices and characteristics were delineated and assessed for discriminative ability in predicting perioperative adverse outcomes using an area under the curve analysis from the receiver operating characteristics curves. In total, 16,495 patients were identified who met the inclusion criteria. The most predictive comorbidity index was ASA and demographic factor was age. Of these two factors, age had the larger discriminative ability for three out of the six adverse outcomes and ASA was the most predictive for one out of six adverse outcomes. A combination of the most predictive demographic factor and comorbidity index resulted in improvements in discriminative ability over the individual components for five of the six outcome variables. For PLF, easily obtained patient ASA and age have overall similar or better discriminative abilities for perioperative adverse outcomes than numerically tabulated indices that have multiple inputs and are harder to implement in clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

Topical acetylsalicylic, salicylic acid and indomethacin suppress pain from experimental tissue acidosis in human skin.

PubMed

Steen, K H; Reeh, P W; Kreysel, H W

1995-09-01

Topically applied acetylsalicylic acid (ASA), salicylic acid (SA) and indomethacin were tested in an experimental pain model that provides direct nociceptor excitation through cutaneous tissue acidosis. In 30 volunteers, sustained burning pain was produced in the palmar forearm through a continuous intradermal pressure infusion of a phosphate-buffered isotonic solution (pH 5.2). In 5 different, double-blind, randomized cross-over studies with 6 volunteers each, the flow rate of the syringe pump was individually adjusted to result in constant pain ratings of around 20% (50% in study 4) on a visual analog scale (VAS). The painful skin area was then covered with either placebo or the drugs which had been dissolved in diethylether. In the first study on 6 volunteers, ASA (60 mg/ml) or lactose (placebo) in diethylether (10 ml) was applied, using both arms at 3-day intervals. Both treatments resulted in sudden and profound pain relief due to the cooling effect of the evaporating ether. With lactose, however, the mean pain rating was restored close to the baseline within 6-8 min while, with ASA, it remained significantly depressed for the rest of the observation period (another 20 min). This deep analgesia was not accompanied by a loss of tactile sensation. The further studies served to show that indomethacin (4.5 mg/ml) and SA (60 mg/ml) were equally effective as ASA (each 92-96% pain reduction) and that the antinociceptive effects were due to local but not systemic actions, since ASA and SA dis not reach measurable plasma levels up to 3 h after topical applications. With a higher flow rate of acid buffer producing more intense pain (VAS 50%). ASA and SA were still able to significantly reduce the ratings by 90% or 84%, respectively. On the other hand, by increasing the flow rate by a factor of 2 on average, during the period of fully developed drug effect it was possible to overcome the pain suppression, which suggests a competitive mechanism of (acetyl-) salicylic antinociception.

Acute murine colitis reduces colonic 5-aminosalicylic acid metabolism by regulation of N-acetyltransferase-2

PubMed Central

Ramírez-Alcántara, Verónica

2014-01-01

Pharmacotherapy based on 5-aminosalicylic acid (5-ASA) is a preferred treatment for ulcerative colitis, but variable patient response to this therapy is observed. Inflammation can affect therapeutic outcomes by regulating the expression and activity of drug-metabolizing enzymes; its effect on 5-ASA metabolism by the colonic arylamine N-acetyltransferase (NAT) enzyme isoforms is not firmly established. We examined if inflammation affects the capacity for colonic 5-ASA metabolism and NAT enzyme expression. 5-ASA metabolism by colonic mucosal homogenates was directly measured with a novel fluorimetric rate assay. 5-ASA metabolism reported by the assay was dependent on Ac-CoA, inhibited by alternative NAT substrates (isoniazid, p-aminobenzoylglutamate), and saturable with Km (5-ASA) = 5.8 μM. A mouse model of acute dextran sulfate sodium (DSS) colitis caused pronounced inflammation in central and distal colon, and modest inflammation of proximal colon, defined by myeloperoxidase activity and histology. DSS colitis reduced capacity for 5-ASA metabolism in central and distal colon segments by 52 and 51%, respectively. Use of selective substrates of NAT isoforms to inhibit 5-ASA metabolism suggested that mNAT2 mediated 5-ASA metabolism in normal and colitis conditions. Western blot and real-time RT-PCR identified that proximal and distal mucosa had a decreased mNAT2 protein-to-mRNA ratio after DSS. In conclusion, an acute colonic inflammation impairs the expression and function of mNAT2 enzyme, thereby diminishing the capacity for 5-ASA metabolism by colonic mucosa. PMID:24742986

Spectroscopic studies of the interaction of aspirin and its important metabolite, salicylate ion, with DNA, A·T and G·C rich sequences

NASA Astrophysics Data System (ADS)

Bathaie, S. Z.; Nikfarjam, L.; Rahmanpour, R.; Moosavi-Movahedi, A. A.

2010-12-01

Among different biological effects of acetylsalicylic acid (ASA), its anticancer property is controversial. Since ASA hydrolyzes rapidly to salicylic acid (SA), especially in the blood, interaction of both ASA and SA (as the small molecules) with ctDNA, oligo(dA·dT) 15 and oligo(dG·dC) 15, as a possible mechanism of their action, is investigated here. The results show that the rate of ASA hydrolysis in the absence and presence of ctDNA is similar. The spectrophotometric results indicate that both ASA and SA cooperatively bind to ctDNA. The binding constants ( K) are (1.7 ± 0.7) × 10 3 M -1 and (6.7 ± 0.2) × 10 3 M -1 for ASA and SA, respectively. Both ligands quench the fluorescence emission of ethidium bromide (Et)-ctDNA complex. The Scatchard plots indicate the non-displacement based quenching (non-intercalative binding). The circular dichroism (CD) spectra of ASA- or SA-ctDsNA complexes show the minor distortion of ctDNA structure, with no characteristic peaks for intercalation of ligands. Tm of ctDNA is decreased up to 3 °C upon ASA binding. The CD results also indicate more distortions on oligo(dG·dC) 15 structure due to the binding of both ASA and SA in comparison with oligo(dA·dT) 15. All data indicate the more affinity for SA binding with DNA minor groove in comparison with ASA which has more hydrophobic character.

Medical risk assessment in dentistry: use of the American Society of Anesthesiologists Physical Status Classification.

PubMed

Clough, S; Shehabi, Z; Morgan, C

2016-02-12

Medical risk assessment is essential to safe patient management and the delivery of appropriate dental care. The American Society of Anesthesiologists Physical Status (ASA PS) Classification is widely used within medicine and dentistry, but has received significant criticism. This is the first UK survey to assess the consistency of medical risk assessment in dentistry. (i) To determine the use and consistency of the ASA PS among dentists and anaesthetists. (ii) To consider the appropriateness of the ASA PS in relation to dental treatment planning and delivery of care. A cross-sectional online questionnaire was distributed to anaesthetists and dental practitioners in general practice, community and hospital dental services. Questions focused on professional backgrounds, use of the ASA PS, alternative approaches to risk assessment in everyday practice and scoring of eight hypothetical patients using ASA PS. There were 101 responses, 82 were complete. Anaesthetists recorded ASA PS score more frequently than dental practitioners and found it more useful. Inconsistencies were evident in the assignment of ASA PS scores both between and within professional groups. Many dental practitioners did not use or find ASA PS helpful, with significant inconsistencies in its use. An awareness of alternative assessment scales may be useful across settings. Accepting its limitations, it would be helpful for all dentists to be educated in ASA PS and its use in medical risk assessment, particularly in relation to conscious sedation.

Genetic evidence for the role of GDP-mannose in plant ascorbic acid (vitamin C) biosynthesis

PubMed Central

Conklin, Patricia L.; Norris, Susan R.; Wheeler, Glen L.; Williams, Elizabeth H.; Smirnoff, Nicholas; Last, Robert L.

1999-01-01

Vitamin C (l-ascorbic acid; AsA) acts as a potent antioxidant and cellular reductant in plants and animals. AsA has long been known to have many critical physiological roles in plants, yet its biosynthesis is only currently being defined. A pathway for AsA biosynthesis that features GDP-mannose and l-galactose has recently been proposed for plants. We have isolated a collection of AsA-deficient mutants of Arabidopsis thaliana that are valuable tools for testing of an AsA biosynthetic pathway. The best-characterized of these mutants (vtc1) contains ≈25% of wild-type AsA and is defective in AsA biosynthesis. By using a combination of biochemical, molecular, and genetic techniques, we have demonstrated that the VTC1 locus encodes a GDP-mannose pyrophosphorylase (mannose-1-P guanyltransferase). This enzyme provides GDP-mannose, which is used for cell wall carbohydrate biosynthesis and protein glycosylation as well as for AsA biosynthesis. In addition to genetically defining the first locus involved in AsA biosynthesis, this work highlights the power of using traditional mutagenesis techniques coupled with the Arabidopsis Genome Initiative to rapidly clone physiologically important genes. PMID:10097187

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

PubMed Central

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

2013-01-01

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

Neuroprotective effect of a new synthetic aspirin-decursinol adduct in experimental animal models of ischemic stroke.

PubMed

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

2013-01-01

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

Inhibition of cyclooxygenase-independent platelet aggregation by sodium salicylate.

PubMed

Violi, F; Alessandri, C; Praticò, D; Guzzo, A; Ghiselli, A; Balsano, F

1989-06-15

The effect of acetylsalicylic acid (ASA) on platelet aggregation (PA) and thromboxane A2 (TxA2) formation was investigated in vitro and ex vivo after 1 g or 300 mg ASA administration to healthy subjects. 50-100 microM ASA inhibited PA by single aggregating agent such as platelet aggregating factor (PAF) or epinephrine and reduced to less than or equal to 5% of control platelet TxB2 formation, but did not influence PA by epinephrine plus PAF. The latter was inhibited by increasing ASA concentration. In samples incubated with 100 microM ASA and stimulated with epinephrine plus PAF, PA could be inhibited by the addition of 100-300 microM sodium salicylate. After 300 mg-1 g ASA administration to healthy subjects, the inhibition of PA by epinephrine plus PAF was more marked by highest doses of ASA. This study suggests that aspirin inhibits PA with a cyclooxygenase-independent mechanism; this effect is mediated, at least in vitro, by salicylic acid.

GAMM's as a New Tool for Evaluating Spatiotemporal Distributions of Nitrate and Bacteria in an Agricultural Watershed

NASA Astrophysics Data System (ADS)

Cey, E. E.; Mellor, A. F.

2015-12-01

Generalized additive mixed models (GAMM's) are flexible regression models that are increasingly used in ecological and environmental studies to assess spatial and temporal trends in complex monitoring data. GAMM's hold promise for analysis of spatially and temporally correlated hydrogeologic data, but have been used only sparingly. Here we employed GAMM's to investigate the spatiotemporal distribution of pathogen indicators (E. coli and total coliform [TC]) and nitrate in the vulnerable Abbotsford-Sumas aquifer (ASA), and to explore potential relationships with hydrologic and climatic drivers, such as precipitation, streamflow, and groundwater level and temperature. A total of 46 wells sampled over a one year period showed more than 50% of samples exceeded 10 mg-N/L for nitrate. E. coli detections in groundwater were infrequent (4 of 385 total samples) and attributed mainly to surface water-groundwater connections. TC was detected frequently in groundwater (70% of samples) and the widespread TC distribution across the ASA could not be attributed solely to surface water connectivity. GAMM's showed that increased TC values in the wet season were most strongly related to groundwater temperatures and levels, while precipitation and well location were weaker (but still significant) predictors. In contrast, seasonal trends in nitrate were not significantly related to hydrologic forcings. Instead, nitrate concentrations across the aquifer were controlled by well location and depth, likely due to spatially variable nitrogen loading and localized geochemical attenuation. Major differences in nitrate and bacterial loading to the ASA were apparent in this study, and management strategies specific to each nonpoint source contaminant are recommended for improved source water protection.

Effect of acetyl salicylic acid on increased production of thromboxane after aortic graft surgery.

PubMed

Lewin, J; Swedenborg, J; Egberg, N; Vesterqvist, O; Green, K

1989-06-01

Contact between blood and foreign surfaces, e.g. vascular grafts, causes activation and release of platelets. One consequence of platelet activation is production of thromboxane A2 (TxA2). The physiological effects of TxA2, i.e. platelet aggregation and vaso-constriction are counteracted by another prostanoid, prostacyclin (PGI2). Acetylsalicylic acid (ASA) causes a longlasting inhibition of platelet TxA2 production and a more shortlasting inhibition of PGI2 production. The present study examines TxA2 and PGI2 synthesis in patients receiving synthetic arterial grafts, some of which were treated with ASA. The prostanoid synthesis was evaluated by measurement of their main urinary metabolites with gas chromatography-mass spectrometry. Platelet release was evaluated by measurements of beta-thromboglobulin (beta-TG) and the plasma coagulation by measurements of fibrinopeptide A (FPA). These compounds were also measured in urine in order to avoid artifacts caused by activation of platelets and plasma coagulation during blood sampling. Following replacement of the abdominal aorta with a synthetic vascular graft there was a marked increase in the synthesis of TxA2 and PGI2. Increased levels of beta-TG and FPA were also demonstrated. Administration of ASA on the first and second postoperative days significantly reduced the synthesis of TxA2 but caused no significant effects on the other parameters measured. It is concluded that ASA may be beneficial in the postoperative period since it counteracts TxA2 with vasoconstricting and platelet aggregating properties but leaves PGI2 with vasodilating and antiaggregating properties relatively uneffected.

The influence of the combined treatment with Vadimezan (ASA404) and taxol on the growth of U251 glioblastoma xenografts

PubMed Central

2012-01-01

Background One of the most important biological characteristics of Glioblastoma multiforme (GBM) is high vascular density. Vadimezan (ASA404, DMXAA) belongs to the class of small molecule vascular disrupting agents (VDA) that cause disruption of established tumor vessels and subsequent tumor hemorrhagic necrosis. Its selective antivascular effect is mediated by intratumoral induction of several cytokines including tumor necrosis factor-α (TNF-α), granulocyte-colony-stimulating factor (G-CSF), interleukin 6 (IL-6) and macrophage inflammatory protein 1α (MIP-1α). Preclinical studies have demonstrated that ASA404 acts synergistically with taxanes. In this study, we investigated if treatment of mice bearing U251 human glioblastoma xenografts with ASA404 and taxol may be synergistic. Therapy response was evaluated by measuring changes in tumor size and metabolic activity using 18F-FDG PET (Fluorodeoxyglucose - positron emision tomography) imaging. Methods U251 cells were inoculated s.c. in the right hind limb of NMRI-Foxn1nu athymic female nude mice. Animals were randomly assigned into 4 groups (7–9 animals/group) for treatment: control, taxol, ASA404, and ASA404 plus taxol. The animals received either a single dose of taxol (10 mg/kg), ASA404 (27.5 mg/kg), or taxol (10 mg/kg) plus ASA404 (27.5 mg/kg) administered i.p.; ASA404 was administred 24 h after the treatment with taxol. 4 and 24 h after treatment with ASA404 (28 and 48 h hours after treatment with taxol) 18 F-FDG PET scans were performed. Results The treatment with taxol did not affect the tumor growth in comparison to untreated controls. The treatment of animals with single dose ASA404 alone or in combination with taxol caused a significant delay in tumor growth. The combined treatment did not decrease the growth of the xenografts significantly more than ASA404 alone, but early changes in tumor 18 F-FDG uptake preceded subsequent growth inhibition. The tumor weights, which were determined at the end of treatment, were lower in case of combined treatment. Conclusions The treatment with ASA404 alone or in combination with taxol showed antitumoral effects in our glioblastoma model probably through destruction of blood vessels. The implications for the anticancer effect of this compound warrant further preclinical studies. 18F-FDG PET appears to be a promising tool to monitor treatment with ASA404 early in the course of therapy. PMID:22695475

The performance of different classification criteria sets for spondyloarthritis in the worldwide ASAS-COMOSPA study.

PubMed

Bakker, Pauline; Moltó, Anna; Etcheto, Adrien; Van den Bosch, Filip; Landewé, Robert; van Gaalen, Floris; Dougados, Maxime; van der Heijde, Désirée

2017-05-16

In this study, we sought to compare the performance of spondyloarthritis (SpA) classification criteria sets in an international SpA cohort with patients included from five continents around the world. Data from the (ASAS) COMOrbidities in SPondyloArthritis (ASAS-COMOSPA) study were used. ASAS-COMOSPA is a multinational, cross-sectional study with consecutive patients diagnosed with SpA by rheumatologists worldwide. Patients were classified according to the European Spondyloarthropathy Study Group (ESSG), modified European Spondyloarthropathy Study Group (mESSG), Amor, modified Amor, Assessment of SpondyloArthritis international Society (ASAS) axial Spondyloarthritis (axSpA), ASAS peripheral spondyloarthritis (pSpA) and ClASsification criteria for Psoriatic Arthritis (CASPAR) criteria. Overlap between the classification criteria sets was assessed for patients with and without back pain. Furthermore, patients fulfilling different arms of the ASAS axSpA criteria (imaging arm, clinical arm, both arms) were compared on the presence of SpA features. A total of 3942 patients (5 continents, 26 countries) were included. The mean age was 43.6 years, 65.0% were male, 56.2% were human leucocyte antigen B27-positive and 64.4% had radiographic sacroiliitis (based on modified New York criteria). Of the patients, 85.5% were classified by the ASAS SpA criteria (87.7% ASAS axSpA, 12.3% ASAS pSpA). Fulfilment of the Amor, ESSG and CASPAR criteria was present in 83.3%, 88.4% and 21.6% of patients, respectively. Of the patients with back pain (n = 3227), most were classified by all three of Amor, ESSG and ASAS axSpA criteria (71.4%). Patients fulfilling the imaging arm and the clinical arm of the ASAS axSpA criteria had similar presentations of SpA features. In patients without back pain, overlap between classification criteria sets was seen, although to a lesser extent. Most patients with a clinical diagnosis of axial SpA in the worldwide ASAS-COMOSPA study fulfil several classification criteria sets, and a substantial overlap between different criteria sets is seen, which suggests a high level of credibility of the criteria. Large inter-regional differences in the fulfilment of classification criteria were not found. Patients fulfilling the clinical arm were remarkably similar to patients fulfilling the imaging arm with respect to the presence of most SpA features.

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

PubMed

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

2017-05-10

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

Association between low-dose acetylsalicylic acid reinitiation and the risk of myocardial infarction or coronary heart disease death.

PubMed

Sáez, María E; González-Pérez, Antonio; Johansson, Saga; Himmelmann, Anders; García Rodríguez, Luis A

2016-07-01

In secondary cardiovascular prevention, discontinuation of acetylsalicylic acid (ASA) is associated with an increased risk of cardiovascular events. This study assessed the impact of ASA reinitiation on the risk of myocardial infarction and coronary heart disease death. Patients prescribed ASA for secondary cardiovascular prevention and who had had a period of ASA discontinuation of ≥90 days in 2000-2007 were identified from The Health Improvement Network (N = 10,453). Incidence of myocardial infarction/coronary heart disease death was calculated. Survival analyses using adjusted Cox proportional hazard models were performed to calculate hazard ratios and 95% confidence intervals for the risk of myocardial infarction/coronary heart disease death associated with ASA use patterns after the initial period of discontinuation. Individuals who were prescribed ASA during follow-up were considered reinitiators. The incidence of myocardial infarction/coronary heart disease death was 8.90 cases per 1000 person-years. Risk of myocardial infarction/coronary heart disease death was similar for current ASA users, who had been continuously exposed since reinitiation, and patients who had not reinitiated ASA (hazard ratio 1.27, 95% confidence interval 0.93-1.73). Among reinitiators, an additional period of ASA discontinuation was associated with increased risk of myocardial infarction/coronary heart disease death compared with no reinitiation (current users: hazard ratio 1.46, 95% confidence interval 1.13-1.90; noncurrent users: hazard ratio 1.70, 95% confidence interval 1.31-2.21). ASA reinitiation was not associated with a decreased risk of myocardial infarction/coronary heart disease death. This may be explained by confounding by indication/comorbidity, whereby higher-risk patients are more likely to reinitiate therapy. An additional period of ASA discontinuation among reinitiators was associated with an increased risk of myocardial infarction/coronary heart disease death. © The European Society of Cardiology 2015.

Release of 5-Aminosalicylic Acid (5-ASA) from Mesalamine Formulations at Various pH Levels.

PubMed

Abinusawa, Adeyinka; Tenjarla, Srini

2015-05-01

Oral formulations of 5-aminosalicylic acid (5-ASA) for treatment of ulcerative colitis have been developed to minimize absorption prior to the drug reaching the colon. In this study, we investigate the release of 5-ASA from available oral mesalamine formulations in physiologically relevant pH conditions. Release of 5-ASA from 6 mesalamine formulations (APRISO®, Salix Pharmaceuticals, Inc., USA; ASACOL® MR, Procter & Gamble Pharmaceuticals UK Ltd.; ASACOL® HD, Procter & Gamble Pharmaceuticals, USA; MEZAVANT XL®, Shire US Inc.; PENTASA®, Ferring Pharmaceuticals, Ltd., UK; SALOFALK®, Dr. Falk Pharma UK Ltd.) was evaluated using United States Pharmacopeia apparatus I and II at pH values of 1.0 (2 h), 6.0 (1 h), and 6.8 (8 h). Dissolution profiles were determined for each formulation, respectively. Of the tested formulations, only the PENTASA formulation demonstrated release of 5-ASA at pH 1.0 (48%), with 56% cumulative release after exposure to pH 6.0 and 92% 5-ASA release after 6-8 h at pH 6.8. No other mesalamine formulation showed >1% drug release at pH 1.0. The APRISO formulation revealed 36% 5-ASA release at pH 6.0, with 100% release after 3 h at pH 6.8. The SALOFALK formulation revealed 11% 5-ASA release at pH 6.0, with 100% release after 1 h at pH 6.8. No 5-ASA was released by the ASACOL MR, ASACOL HD, and MEZAVANT XL formulations at pH 6.0. At pH 6.8, the ASACOL MR and ASACOL HD formulations exhibited complete release of 5-ASA after 4 and 2 h, respectively, and the MEZAVANT XL formulation demonstrated complete 5-ASA release over 6-7 h. 5-Aminosalicylic acid release profiles were variable among various commercially available formulations. Shire Development LLC.

Ascorbate biosynthesis during early fruit development is the main reason for its accumulation in kiwi.

PubMed

Li, Mingjun; Ma, Fengwang; Liang, Dong; Li, Juan; Wang, Yanlei

2010-12-09

Ascorbic acid (AsA) is a unique antioxidant as well as an enzyme cofactor. Although it has multiple roles in plants, it is unclear how its accumulation is controlled at the expression level, especially in sink tissues. Kiwifruit (Actinidia) is well-known for its high ascorbate content. Our objective was to determine whether AsA accumulates in the fruits primarily through biosynthesis or because it is imported from the foliage. We systematically investigated AsA levels, biosynthetic capacity, and mRNA expression of genes involved in AsA biosynthesis in kiwi (A. deliciosa cv. Qinmei). Recycling and AsA localization were also monitored during fruit development and among different tissue types. Over time, the amount of AsA, with its capacity for higher biosynthesis and lower recycling, peaked at 30 days after anthesis (DAA), and then decreased markedly up to 60 DAA before declining more slowly. Expression of key genes showed similar patterns of change, except for L-galactono-1,4-lactone dehydrogenase and L-galactose-1-phosphate phosphatase (GPP). However, GPP had good correlation with the rate of AsA accumulation. The expression of these genes could be detected in phloem of stem as well as petiole of leaf and fruit. Additionally, fruit petioles had greater ascorbate amounts, although that was the site of lowest expression by most genes. Fruit microtubule tissues also had higher AsA. However, exogenous applications of AsA to those petioles did not lead to its transport into fruits, and distribution of ascorbate was cell-specific in the fruits, with more accumulation occurring in larger cells. These results suggest that AsA biosynthesis in kiwi during early fruit development is the main reason for its accumulation in the fruits. We also postulate here that GPP is a good candidate for regulating AsA biosynthesis whereas GDP-L-galactose-1-phosphate phosphorylase is not.

Inflamed site-specific drug delivery system based on the interaction of human serum albumin nanoparticles with myeloperoxidase in a murine model of experimental colitis.

PubMed

Iwao, Yasunori; Tomiguchi, Izumi; Domura, Ayaka; Mantaira, Yusuke; Minami, Akira; Suzuki, Takashi; Ikawa, Takashi; Kimura, Shin-Ichiro; Itai, Shigeru

2018-04-01

To develop a new strategy for inflamed site-specific drug delivery in the colon for the treatment of ulcerative colitis (UC), we leveraged on the interaction between myeloperoxidase (MPO) and human serum albumin (HSA) and prepared nanoparticles (HSA NPs) conjugated with 5-aminosalicylic acid (5-ASA). The 5-ASA-HSA NPs (nine molecules of 5-ASA per HSA molecule) were uniform particles with an average particle size of 190 nm, a zeta potential of --11.8 mV, and a polydispersity index of 0.35. This was considered a suitable particle characteristic to pass through the mucus layer and accumulate into the mucosa. The specific interaction between the 5-ASA-HSA NPs and MPO was observed using quartz crystal microbalance analysis in vitro. In addition, the 5-ASA-HSA NPs group containing one thousandth of the dose of the 5-ASA (75 μg/kg) showed significantly lower disease activity index values and colon weight/length ratios in UC model mice as similar to large amount of neat 5-ASA group (75 mg/kg), indicating that the therapeutic effect of the 5-ASA-HSA NP formulation was confirmed in vivo. Microscopic images of tissue sections of colon extracted from UC model mice demonstrated that HSA NPs and MPO were both localized in the colon, and this specific interaction between HSA NPs and MPO would be involved the in the therapeutic effect in vivo. Furthermore, in the 5-ASA and 5-ASA-HSA NPs groups, some inflammatory damage was observed in the colon, but the degree of damage was mild compared with the control and HSA NPs groups, suggesting mucosal repair and replacement with fibrous granulation tissue had occurred. Therefore, these data demonstrated that an HSA NP formulation has the potential to specifically deliver 5-ASA to an inflamed site where MPO is highly expressed. Copyright © 2018 Elsevier B.V. All rights reserved.

Pharmacokinetics and brain uptake in the rhesus monkey of a fusion protein of arylsulfatase a and a monoclonal antibody against the human insulin receptor.

PubMed

Boado, Ruben J; Lu, Jeff Zhiqiang; Hui, Eric K-W; Sumbria, Rachita K; Pardridge, William M

2013-05-01

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder of the brain caused by mutations in the gene encoding the lysosomal sulfatase, arylsulfatase A (ASA). It is not possible to treat the brain in MLD with recombinant ASA, because the enzyme does not cross the blood-brain barrier (BBB). In the present investigation, a BBB-penetrating IgG-ASA fusion protein is engineered and expressed, where the ASA monomer is fused to the carboxyl terminus of each heavy chain of an engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb crosses the BBB via receptor-mediated transport on the endogenous BBB insulin receptor, and acts as a molecular Trojan horse to ferry the ASA into brain from blood. The HIRMAb-ASA is expressed in stably transfected Chinese hamster ovary cells grown in serum free medium, and purified by protein A affinity chromatography. The fusion protein retains high affinity binding to the HIR, EC50 = 0.34 ± 0.11 nM, and retains high ASA enzyme activity, 20 ± 1 units/mg. The HIRMAb-ASA fusion protein is endocytosed and triaged to the lysosomal compartment in MLD fibroblasts. The fusion protein was radio-labeled with the Bolton-Hunter reagent, and the [(125) I]-HIRMAb-ASA rapidly penetrates the brain in the Rhesus monkey following intravenous administration. Film and emulsion autoradiography of primate brain shows global distribution of the fusion protein throughout the monkey brain. These studies describe a new biological entity that is designed to treat the brain of humans with MLD following non-invasive, intravenous infusion of an IgG-ASA fusion protein. Copyright © 2012 Wiley Periodicals, Inc.

Cost-Effectiveness of Proton Pump Inhibitor Co-Therapy in Patients Taking Aspirin for Secondary Prevention of Ischemic Stroke.

PubMed

Takabayashi, Nobuyoshi; Murata, Kyoko; Tanaka, Shiro; Kawakami, Koji

2015-10-01

Low-dose aspirin (ASA) is effective for secondary prevention of ischemic stroke but can increase the risks of hemorrhagic stroke, upper gastrointestinal bleeding (UGIB), and dyspepsia. Prophylactic administration of proton pump inhibitors (PPIs) reduces the risks of these digestive symptoms. We investigated the cost effectiveness of adding a PPI to ASA therapy for ischemic stroke patients in Japan. A Markov state-transition model was developed to compare the cost effectiveness of ASA monotherapy with ASA plus PPI co-therapy in patients with histories of upper gastrointestinal ulcers and ischemic stroke. The model takes into account ASA adherence rate and adverse effects due to ASA, including hemorrhagic stroke and UGIB. The analysis was performed from the perspective of healthcare payers in 2013. In the base case, total life-years by PPI co-therapy and monotherapy were 16.005 and 15.932, respectively. The difference in duration of no therapy (no ASA or PPI) between the therapies was 558.5 days, which would prevent 30.3 recurrences of ischemic stroke per 1000 person-years. The incremental cost-effectiveness ratio of PPI co-therapy relative to monotherapy was ¥1,191,665 (US$11,458) per life-year gained. In a one-way sensitivity analysis, PPI co-therapy was consistently cost effective at a willingness to pay of ¥5,000,000 (US$48,077) per life-year gained. In a probabilistic sensitivity analysis, the probability that PPI co-therapy was cost effective was 89.74% at the willingness to pay. Co-therapy with ASA plus PPI appears to be cost-effective compared with ASA monotherapy. The addition of PPI also appeared to prolong the duration of ASA therapy, thereby reducing the risk of ischemic stroke.

Patterns of separation anxiety symptoms amongst pregnant women in conflict-affected Timor-Leste: Associations with traumatic loss, family conflict, and intimate partner violence.

PubMed

Silove, D M; Tay, A K; Tol, W A; Tam, N; Dos Reis, N; da Costa, Z; Soares, C; Rees, S

2016-11-15

Adult separation anxiety (ASA) symptoms are prevalent amongst young women in low and middle-income countries and symptoms may be common in pregnancy. No studies have focused on defining distinctive patterns of ASA symptoms amongst pregnant women in these settings or possible associations with trauma exposure and ongoing stressors. In a consecutive sample of 1672 women attending antenatal clinics in Dili, Timor-Leste (96% response), we assessed traumatic events of conflict, ongoing adversity, intimate partner violence (IPV), ASA, post-traumatic stress disorder (PTSD) and severe psychological distress. Latent Class Analysis was used to identify classes of women based on their distinctive profiles of ASA symptoms, comparisons then being made with key covariates including trauma domains of conflict, intimate partner violence (IPV) and ongoing stressors. LCA yielded three classes, comprising a core ASA (4%), a limited ASA (25%) and a low symptom class (61%). The core ASA class reported exposure to multiple traumatic losses and IPV and showed a pattern of comorbidity with PTSD; the limited ASA class predominantly reported exposure to ongoing stressors and was comorbid with severe psychological distress; the low symptom class reported relatively low levels of exposure to trauma and stressors. The study is cross-sectional, cautioning against inferring causal inferences. The core ASA group may be in need of immediate intervention given the high rate of exposure to IPV amongst this class. A larger number of women experiencing a limited array of non-specific ASA symptoms may need assistance to address the immediate stressors of pregnancy. Copyright © 2016 Elsevier B.V. All rights reserved.

Baseline Oral 5-ASA Use and Efficacy and Safety of Budesonide Foam in Patients with Ulcerative Proctitis and Ulcerative Proctosigmoiditis: Analysis of 2 Phase 3 Studies

PubMed Central

Sandborn, William J.; Rubin, David T.; Harper, Joseph R.

2016-01-01

Background: Rectal budesonide foam is a second-generation corticosteroid efficacious for active mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis. This subgroup analysis examined the impact of baseline oral 5-aminosalicylic acid (5-ASA) on the efficacy and safety of budesonide foam in patients with mild to moderate ulcerative proctitis or ulcerative proctosigmoiditis. Methods: Patients received budesonide foam 2 mg/25 mL twice daily for 2 weeks, then once daily for 4 weeks, or placebo, with or without continued stable dosing of baseline oral 5-ASAs, for remission induction at week 6 (primary endpoint) in 2 identically designed, randomized, double-blind, phase 3 studies. Results: Of the 267 and 279 patients randomized to treatment with budesonide foam or placebo (pooled population), 55.1% and 55.2%, respectively, reported baseline 5-ASA use. A significantly greater percentage of patients achieved remission with budesonide foam versus placebo, either with (42.2% versus 31.8%, respectively; P = 0.03) or without (40.0% versus 14.4%; P < 0.0001) baseline 5-ASA use at week 6. A significantly greater percentage of patients achieved a Modified Mayo Disease Activity Index rectal bleeding subscale score of 0 at week 6, regardless of baseline 5-ASA use (5-ASA, 50.3% versus 35.7%; P = 0.003: no 5-ASA, 45.8% versus 19.2%; P < 0.0001). The frequency of adverse events was comparable between groups, regardless of baseline 5-ASA use. Conclusions: Budesonide foam was efficacious and safe for induction of remission of mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis in patients receiving oral 5-ASA at baseline and those who were not (Clinicaltrials.gov: NCT01008410 and NCT01008423). PMID:27416045

High Temperature Inhibits Ascorbate Recycling and Light Stimulation of the Ascorbate Pool in Tomato despite Increased Expression of Biosynthesis Genes

PubMed Central

Massot, Capucine; Bancel, Doriane; Lopez Lauri, Félicie; Truffault, Vincent; Baldet, Pierre; Stevens, Rebecca; Gautier, Hélène

2013-01-01

Understanding how the fruit microclimate affects ascorbate (AsA) biosynthesis, oxidation and recycling is a great challenge in improving fruit nutritional quality. For this purpose, tomatoes at breaker stage were harvested and placed in controlled environment conditions at different temperatures (12, 17, 23, 27 and 31°C) and irradiance regimes (darkness or 150 µmol m-2 s-1). Fruit pericarp tissue was used to assay ascorbate, glutathione, enzymes related to oxidative stress and the AsA/glutathione cycle and follow the expression of genes coding for 5 enzymes of the AsA biosynthesis pathway (GME, VTC2, GPP, L-GalDH, GLDH). The AsA pool size in pericarp tissue was significantly higher under light at temperatures below 27°C. In addition, light promoted glutathione accumulation at low and high temperatures. At 12°C, increased AsA content was correlated with the enhanced expression of all genes of the biosynthesis pathway studied, combined with higher DHAR and MDHAR activities and increased enzymatic activities related to oxidative stress (CAT and APX). In contrast, at 31°C, MDHAR and GR activities were significantly reduced under light indicating that enzymes of the AsA/glutathione cycle may limit AsA recycling and pool size in fruit pericarp, despite enhanced expression of genes coding for AsA biosynthesis enzymes. In conclusion, this study confirms the important role of fruit microclimate in the regulation of fruit pericarp AsA content, as under oxidative conditions (12°C, light) total fruit pericarp AsA content increased up to 71%. Moreover, it reveals that light and temperature interact to regulate both AsA biosynthesis gene expression in tomato fruits and AsA oxidation and recycling. PMID:24367665

Baseline Oral 5-ASA Use and Efficacy and Safety of Budesonide Foam in Patients with Ulcerative Proctitis and Ulcerative Proctosigmoiditis: Analysis of 2 Phase 3 Studies.

PubMed

Bosworth, Brian P; Sandborn, William J; Rubin, David T; Harper, Joseph R

2016-08-01

Rectal budesonide foam is a second-generation corticosteroid efficacious for active mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis. This subgroup analysis examined the impact of baseline oral 5-aminosalicylic acid (5-ASA) on the efficacy and safety of budesonide foam in patients with mild to moderate ulcerative proctitis or ulcerative proctosigmoiditis. Patients received budesonide foam 2 mg/25 mL twice daily for 2 weeks, then once daily for 4 weeks, or placebo, with or without continued stable dosing of baseline oral 5-ASAs, for remission induction at week 6 (primary endpoint) in 2 identically designed, randomized, double-blind, phase 3 studies. Of the 267 and 279 patients randomized to treatment with budesonide foam or placebo (pooled population), 55.1% and 55.2%, respectively, reported baseline 5-ASA use. A significantly greater percentage of patients achieved remission with budesonide foam versus placebo, either with (42.2% versus 31.8%, respectively; P = 0.03) or without (40.0% versus 14.4%; P < 0.0001) baseline 5-ASA use at week 6. A significantly greater percentage of patients achieved a Modified Mayo Disease Activity Index rectal bleeding subscale score of 0 at week 6, regardless of baseline 5-ASA use (5-ASA, 50.3% versus 35.7%; P = 0.003: no 5-ASA, 45.8% versus 19.2%; P < 0.0001). The frequency of adverse events was comparable between groups, regardless of baseline 5-ASA use. Budesonide foam was efficacious and safe for induction of remission of mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis in patients receiving oral 5-ASA at baseline and those who were not (Clinicaltrials.gov: NCT01008410 and NCT01008423).

High temperature inhibits ascorbate recycling and light stimulation of the ascorbate pool in tomato despite increased expression of biosynthesis genes.

PubMed

Massot, Capucine; Bancel, Doriane; Lopez Lauri, Félicie; Truffault, Vincent; Baldet, Pierre; Stevens, Rebecca; Gautier, Hélène

2013-01-01

Understanding how the fruit microclimate affects ascorbate (AsA) biosynthesis, oxidation and recycling is a great challenge in improving fruit nutritional quality. For this purpose, tomatoes at breaker stage were harvested and placed in controlled environment conditions at different temperatures (12, 17, 23, 27 and 31 °C) and irradiance regimes (darkness or 150 µmol m(-2) s(-1)). Fruit pericarp tissue was used to assay ascorbate, glutathione, enzymes related to oxidative stress and the AsA/glutathione cycle and follow the expression of genes coding for 5 enzymes of the AsA biosynthesis pathway (GME, VTC2, GPP, L-GalDH, GLDH). The AsA pool size in pericarp tissue was significantly higher under light at temperatures below 27 °C. In addition, light promoted glutathione accumulation at low and high temperatures. At 12 °C, increased AsA content was correlated with the enhanced expression of all genes of the biosynthesis pathway studied, combined with higher DHAR and MDHAR activities and increased enzymatic activities related to oxidative stress (CAT and APX). In contrast, at 31 °C, MDHAR and GR activities were significantly reduced under light indicating that enzymes of the AsA/glutathione cycle may limit AsA recycling and pool size in fruit pericarp, despite enhanced expression of genes coding for AsA biosynthesis enzymes. In conclusion, this study confirms the important role of fruit microclimate in the regulation of fruit pericarp AsA content, as under oxidative conditions (12 °C, light) total fruit pericarp AsA content increased up to 71%. Moreover, it reveals that light and temperature interact to regulate both AsA biosynthesis gene expression in tomato fruits and AsA oxidation and recycling.

Vorapaxar and optimal aspirin dose: The FDA outlook.

PubMed

Serebruany, Victor L; Fortmann, Seth D; Kim, Moo Hyun

2016-01-15

Vorapaxar, a novel thrombin PAR-1 inhibitor, approved for post-myocardial infarction, and peripheral artery disease indications has been tested in 2 major clinical trials. In the successful TRA2P, antecedent aspirin (ASA) has been used in 94% of patients, and in failed TRACER in over 96% of patients. However, both trial publications were silent on the impact of ASA dose on clinical outcomes after voraparax. We determined which ASA dose range should be used in combination with voraparax based on the TRA2P and TRACER secondary FDA review. The data suggest that for both voraparax trials, younger patients, males, and diabetics received higher ASA doses. The interactions between voraparax efficacy and ASA dose ≥ 300 mg was marginally significant by Cox regressions for TRA2P (CI=1.00-1.61; p=0.048) and strongly trended in TRACER (CI=0.98-1.47; p=0.073). Bleeding rates were overall slightly higher with voraparax than with placebo, and were the highest in patients receiving ASA dosages ≥ 300 mg. However, there were no interactions between ASA dose and GUSTO moderate/severe bleeding. In conclusion, the efficacy of voraparax in TRA2P and TRACER, was slightly worse while bleeding was substantially worse with the higher over 300 mg/day of ASA dosages. Voraparax label should recommend ASA daily use in 75 to 100mg range for concomitant use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The ASAS-SN bright supernova catalogue – I. 2013–2014

DOE PAGES

Holoien, T. W. -S.; Stanek, K. Z.; Kochanek, C. S.; ...

2016-09-12

We present basic statistics for all supernovae discovered by the All-Sky Automated Survey for SuperNovae (ASAS-SN) during its first year-and-a-half of operations, spanning 2013 and 2014. We also present the same information for all other bright (m V ≤ 17), spectroscopically confirmed supernovae discovered from 2014 May 1 through the end of 2014, providing a comparison to the ASAS-SN sample starting from the point where ASAS-SN became operational in both hemispheres. In addition, we present collected redshifts and near-UV through IR magnitudes, where available, for all host galaxies of the bright supernovae in both samples. This work represents a comprehensivemore » catalogue of bright supernovae and their hosts from multiple professional and amateur sources, allowing for population studies that were not previously possible because the all-sky emphasis of ASAS-SN redresses many previously existing biases. In particular, ASAS-SN systematically finds bright supernovae closer to the centres of host galaxies than either other professional surveys or amateurs, a remarkable result given ASAS-SN's poorer angular resolution. In conclusion, this is the first of a series of yearly papers on bright supernovae and their hosts that will be released by the ASAS-SN team.« less

Regulation of ascorbic acid metabolism by blue LED light irradiation in citrus juice sacs.

PubMed

Zhang, Lancui; Ma, Gang; Yamawaki, Kazuki; Ikoma, Yoshinori; Matsumoto, Hikaru; Yoshioka, Terutaka; Ohta, Satoshi; Kato, Masaya

2015-04-01

In the present study, the effects of red and blue LED lights on the accumulation of ascorbic acid (AsA) were investigated in the juice sacs of three citrus varieties, Satsuma mandarin, Valencia orange, and Lisbon lemon. The results showed that the blue LED light treatment effectively increased the AsA content in the juice sacs of the three citrus varieties, whereas the red LED light treatment did not. By increasing the blue LED light intensity, the juice sacs of the three citrus varieties accumulated more AsA. Moreover, continuous irradiation with blue LED light was more effective than pulsed irradiation for increasing the AsA content in the juice sacs of the three citrus varieties. Gene expression results showed that the modulation of AsA accumulation by blue LED light was highly regulated at the transcription level. The up-regulation of AsA biosynthetic genes (CitVTC1, CitVTC2, CitVTC4, and CitGLDH), AsA regeneration genes (CitMDAR1, CitMDAR2, and CitDHAR) and two GSH-producing genes (CitGR and CitchGR) contributed to these increases in the AsA content in the three citrus varieties. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Determination of the pK values of 5-aminosalicylic acid and N-acetylaminosalicylic acid and comparison of the pH dependent lipid-water partition coefficients of sulphasalazine and its metabolites.

PubMed

Allgayer, H; Sonnenbichler, J; Kruis, W; Paumgartner, G

1985-01-01

Sulphasalazine (SASP), used in the treatment of inflammatory bowel disease, is split into sulphapyridine (SP) and 5-aminosalicylic acid (5-ASA) in the colon. Lower plasma levels of SASP and 5-ASA as compared to those of SP may be due to different absorption rates from the colon because of different pK values and pH dependent lipid-water partition coefficients. In this study we determined the pK values of 5-ASA and its major metabolite, N-acetyl amino-salicylic acid (AcASA), by 13C-NMR spectroscopy and compared the pH dependent apparent benzene-water partition coefficients (Papp) of SASP, SP and 5-ASA with respect to their different plasma levels. The COOH group of 5-ASA had a pK value of 3.0, the -NH3+ group had 6.0, the -OH group 13.9; the -COOH group of AcASA had 2.7 and the -OH group 12.9; The Papp of SASP (0.042 +/- 0.004) and 5-ASA (0.059 +/- 0.01) were significantly lower than that of SP (0.092 +/- 0.03) (at pH 5.5).

Rectal 5-aminosalicylic acid for maintenance of remission in ulcerative colitis.

PubMed

Marshall, John K; Thabane, Marroon; Steinhart, A Hillary; Newman, Jamie R; Anand, Anju; Irvine, E Jan

2012-11-14

5-Aminosalicylic acid (5-ASA) is a first-line therapy for inducing and maintaining remission of mild and moderately active ulcerative colitis (UC). When the proximal margin of inflammation is distal to the splenic flexure, 5-ASA therapy can be delivered as a rectal suppository, foam or liquid enema. The primary objective was to assess the efficacy and safety of rectal 5-ASA for maintaining remission of distal UC. We searched MEDLINE (1966 to August 2012), the Cochrane Library (August 2012), abstracts from major gastroenterology meetings (1997-2011) and bibliographies of relevant publications to identify relevant studies. Eligible studies were randomized controlled trials comparing rectal 5-ASA to placebo or another active treatment for a minimum duration of six months. Symptom scores needed to be assessed in at least one study outcome. Patients had to be at least 12 years of age with disease extent less than 60 cm from the anal verge or distal to the splenic flexure, as determined by barium enema, colonoscopy or sigmoidoscopy. Patients were expected to be in remission prior to the treatment trial. Study eligibility was independently assessed by three authors. Data were extracted using standardized forms by two independent reviewers, with inter-rater agreement assessed using Cohen's Kappa and disagreements resolved by consensus. In cases where clarification of study results or methodology was needed, corresponding authors were contacted. The methodological quality of each trial was assessed by the Cochrane risk of bias tool and by a 30-point scale developed and used previously by the authors. Pooled risk ratios (RR) and corresponding 95% confidence intervals (CI) for continued clinical, endoscopic and histologic remission were estimated for comparisons between rectal 5-ASA and placebo or oral 5-ASA, and for comparisons among 5-ASA doses. Heterogeneity was assessed using the Chi(2) test and visual inspection of forest plots. If no significant heterogeneity was identified (P > 0.10 for Chi(2)) a fixed-effect model (Mantel-Haenstzel) was used. If heterogeneity was significant, a random-effects model was used. Nine studies (484 patients) met the pre-specified inclusion criteria (Kappa 1.00). Six studies were rated as low risk of bias. Three studies were rated as high risk of bias due to blinding (two open label and one single-blind). The total daily dose of rectal 5-ASA ranged from 0.5 g to 4 g, and dose frequency ranged from once to three times daily. 5-ASA was delivered as liquid enema in five studies or as a suppository in four studies. Follow-up ranged from 6 to 24 months. Rectal 5-ASA was significantly superior to placebo for maintenance of symptomatic remission over a period of 12 months.Sixty-two per cent of patients in the rectal 5-ASA group maintained symptomatic remission compared to 30% of patients in the placebo group (4 studies; 301 patients; RR 2.22, 95% CI 1.26 to 3.90; I(2) = 67%; P < 0.01). A GRADE analysis indicated that the overall quality of the evidence for the primary outcome was low due to imprecision (i.e. sparse data 144 events) and inconsistency (i.e. unexplained heterogeneity). Rectal 5-ASA was significantly superior to placebo for maintenance of endoscopic remission over a 12 month period. Seventy-five per cent of patients in the rectal 5-ASA group maintained endoscopic remission compared to 15% of patients in the placebo group (1 study; 25 patients; RR 4.88, 95% CI 1.31 to 18.18; P < 0.05). There was no statistically significant difference in the proportion of patients who experienced at least one adverse event. Sixteen per cent of patients in the rectal 5-ASA group experienced at least one adverse compared to 12% of placebo patients (2 studies; 160 patients; RR 1.35, 95% CI 0.63 to 2.89; I(2) = 0%; P = 0.44). The most commonly reported adverse events were anal irritation and abdominal pain. No statistically significant differences between rectal and oral 5-ASA were identified for either symptomatic or endoscopic remission over a period of six months. Eighty per cent of patients in the rectal 5-ASA group maintained symptomatic remission compared to 65% of patients in the oral 5-ASA group (2 studies; 69 patients; RR 1.24, 95% CI 0.92 to 1.66; I(2) = 0%; P = 0.15). A GRADE analysis indicated that the overall quality of the evidence for the primary outcome was low due to imprecision (i.e. sparse data 50 events) and high risk of bias (i.e. both studies in the pooled analysis were open label). Eighty per cent of patients in the rectal 5-ASA group maintained endoscopic remission compared to 70% of patients in the oral 5-ASA group (2 studies; 91 patients; RR 1.14, 95% CI 0.90 to 1.45; I(2) = 0%; P = 0.26). In two small trials, one comparing 2 g/day 5-ASA enemas to 4 g/day 5-ASA enemas and the other comparing 0.5 g/day 5-ASA suppositories to 1 g/day 5-ASA suppositories no dose response relationship was observed. The limited data available suggest that rectal 5-ASA is effective and safe for maintenance of remission of mild to moderately active distal UC. Well designed randomized trials are needed to establish the optimal dosing regimen for rectal 5-ASA, to compare rectal 5-ASA with rectal corticosteroids and to identify subgroups of patients who are more or less responsive to specific rectal 5-ASA regimens. The combination of oral and rectal 5-ASA appears to be more effective than either oral or rectal monotherapy for induction of remission. The efficacy of combination therapy for maintenance of remission has not been assessed and could be evaluated in future trials.

[A case of acute pancreatitis caused by 5-aminosalicylic acid suppositories in a patient with ulcerative colitis].

PubMed

Kim, Kook Hyun; Kim, Tae Nyeun; Jang, Byung Ik

2007-12-01

Oral 5-aminosalicylic acid (5-ASA) has been known as a first-choice drug for ulcerative colitis. However, hypersensitivity reactions, including pancreatitis, hepatitis, and skin rash, have been reported with 5-ASA. Topical formulations of 5-ASA like suppositories have been rarely reported to induce adverse reactions because of their limited absorption rate. We recently experienced a case of acute pancreatitis caused by 5-ASA suppositories in a patient with ulcerative colitis. A 26-year-old male was admitted with abdominal pain and diagnosed as ulcerative colitis. Acute pancreatitis occurred soon after 24 hours of treatment with oral mesalazine. Drug-induced pancreatitis was suspected and administration of mesalazine was discontinued. Then 5-ASA suppositories were started instead of oral mesalazine. Twenty-four hours after taking 5-ASA suppositories, he experienced severe abdominal pain, fever, and elevation of amylase levels. The suppositories were immediately stopped and symptoms resolved over next 48 hours. Herein, we suggest that, in patients treated with 5-ASA suppositories who complain of severe abdominal pain, drug-induced pancreatitis should be suspected.

Effects of acetylsalicylic acid on fresh weight pigment and protein content of bean leaf discs (Phaseolus vulgaris L.).

PubMed

Canakçi, S

2003-01-01

The effects of 100, 250, and 500 ppm acetylsalicylic acid solutions treatments on weight alteration, pigment and protein amounts in discs from the primary leaves of one month old bean (Phaseolus vulgaris L.) seedlings produced tinder greenhouse conditions are presented. The experiments show that: 100 ppm ASA had no significant influence (P > 0.05) but 250 and 500 ppm ASA caused an increase on weight loss (P < 0.01); ASA at higher concentrations (250 and 500 ppm), generally, caused a decrease on pigment amounts (P < 0.05-P < 0.01) but 100 ppm ASA had no considerably significant influence on them (P > 0.05), none of the ASA treatments caused a statistically significant influence on carotenoid amount (P > 0.05); 100 and 250 ppm ASA treatments did not cause a significant influence on protein amount (P > 0.05). however 500 ppm ASA treatment caused an increase on protein injury (P < 0.05). Consequently, it is supposed that wet weight loss, pigment and protein injury have somewhat increased on leaf discs. depending on the toxic effect of high acetylsalicylic acid concentrations.

Isolation of saprophytic Leptospira spp. from a selected environmental water source of Argentina.

PubMed

Scialfa, Exequiel; Grune, Sylvia; Brihuega, Bibiana; Aguirre, Pablo; Rivero, Marina

2017-11-29

Ten Leptospira spp. strains were isolated from water samples from Nievas stream, Olavarría, Buenos Aires province (Argentina). The isolates showed the typical motility and morphology of the genus Leptospira under dark field microscopy, developing in liquid EMJH medium after eight days of incubation at 13°C and 30°C. All isolates were negative by the Multiple Locus Variable Number Tandem Repeat Analysis (MLVA). Molecular identification by 16S rRNA gene sequencing identified all isolates as nonpathogenic leptospires. Four isolates showed a genetic profile identical to that of the reference strain Leptospira biflexa serovar Patoc, and six isolates revealed sequence similarities within the 97-98% range, closely related to Leptospira yanagawae and Leptospira meyeri, respectively. Strains ScialfaASA42, ScialfaASA45, ScialfaASA44, ScialfaASA47, ScialfaASA49, ScialfaASA50 and ScialfaASA51 possibly represent a novel species of the genus Leptospira. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

Overview of the ASA24® Researcher Website

Cancer.gov

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

Ueber den Nachweis von Exoplaneten in der ASAS-3 Datenbank

NASA Astrophysics Data System (ADS)

Huemmerich, Stefan; Bernhard, Klaus

2015-02-01

Under favourable circumstances, transits of known exoplanets with large amplitudes like WASP-18 b can be observed in the ASAS-3 database. An attempt to search for exoplanets using ASAS-3 data is discussed.

Tuition Assistance Program (TAP) at ASA Institute of Computer and Business Technology, Inc. Audit for 1991-1992 through 1993-1994 Academic Years. Report 95-T-5 (Revised).

ERIC Educational Resources Information Center

Maldonado, Carmen

In an audit of the records and procedures for ASA Institute of Computer and Business Technology, Inc. (ASA), the New York Office of the State Comptroller determined that ASA was overpaid $696,352 because school officials incorrectly certified certain students as eligible for Tuition Assistance Program (TAP) awards. This error was discovered using…

The ASAS-SN Catalog of Variable Stars I: The Serendipitous Survey

NASA Astrophysics Data System (ADS)

Jayasinghe, T.; Kochanek, C. S.; Stanek, K. Z.; Shappee, B. J.; Holoien, T. W.-S.; Thompson, Todd A.; Prieto, J. L.; Dong, Subo; Pawlak, M.; Shields, J. V.; Pojmanski, G.; Otero, S.; Britt, C. A.; Will, D.

2018-04-01

The All-Sky Automated Survey for Supernovae (ASAS-SN) is the first optical survey to routinely monitor the whole sky with a cadence of ˜2 - 3 days down to V≲ 17 mag. ASAS-SN has monitored the whole sky since 2014, collecting ˜100 - 500 epochs of observations per field. The V-band light curves for candidate variables identified during the search for supernovae are classified using a random forest classifier and visually verified. We present a catalog of 66,533 bright, new variable stars discovered during our search for supernovae, including 27,753 periodic variables and 38,780 irregular variables. V-band light curves for the ASAS-SN variables are available through the ASAS-SN variable stars database (https://asas-sn.osu.edu/variables). The database will begin to include the light curves of known variable stars in the near future along with the results for a systematic, all-sky variability survey.

Burr-Hole Drainage for Chronic Subdural Hematoma Under Low-Dose Acetylsalicylic Acid: A Comparative Risk Analysis Study.

PubMed

Kamenova, Maria; Nevzati, Edin; Lutz, Katharina; Dolp, Armando; Fandino, Javier; Mariani, Luigi; Soleman, Jehuda

2017-04-01

Chronic subdural hematoma (cSDH) is one of the most common neurosurgical diseases typically affecting older people. Many of these patients have coronary artery disease and receive antiplatelet therapy, usually acetylsalicylic acid (ASA). Despite growing clinical relevance, there is still a lack of data focusing on the perioperative management of such patients. The aim of this study is to compare the perioperative and postoperative bleeding and cardiovascular complication rates of patients undergoing burr-hole drainage for cSDH with and without discontinuation of low-dose ASA. Of 963 consecutive patients undergoing burr-hole drainage for cSDH, 198 (20.5%) patients were receiving low-dose ASA treatment. In 26 patients (13.1%), ASA was not discontinued (ASA group; ASA discontinuation ≤7 days); in the remaining patients (n = 172; 86.9%), ASA was discontinued at least for 7 days (control group). The primary outcome measure was recurrent cSDH that required revision surgery owing to clinical symptoms, whereas secondary outcome measures were postoperative cardiovascular and thromboembolic events, other complications, operation and hospitalization time, morbidity, and mortality. No statistically significant difference was observed between the 2 groups regarding recurrence of cSDH (P = 1). Cardiovascular event rates, surgical morbidity, and mortality did not significantly differ between patients with and without discontinuation of low-dose ASA. Given the lack of guidelines regarding perioperative management with antiplatelet therapy, our findings elucidate one issue, showing comparable recurrence rates with and without discontinuation of low-dose ASA in patients undergoing burr-hole drainage for cSDH. Copyright © 2017 Elsevier Inc. All rights reserved.

The use of prophylactic gastroprotective therapy in patients with nonsteroidal anti-inflammatory drug- and aspirin-associated ulcer bleeding: a cross-sectional study.

PubMed

Ho, C W; Tse, Y K; Wu, B; Mulder, C J J; Chan, F K L

2013-04-01

Poor adherence to gastroprotective agents (GPAs) is common among users of nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (ASA). There are little data on the utilization of GPAs among NSAID and ASA users complicated by ulcer bleeding. To study the utilization of GPA among NSAID and ASA ulcers before the onset of ulcer bleeding. We conducted a cross-sectional study to determine the exposure to NSAIDs, ASA, and GPAs within 4 weeks before endoscopically confirmed ulcer bleeding. Sensitivity analysis was performed to study how improving adherence to GPA use would reduce the risk of ulcer bleeding in high-risk users. Between 2000 and 2009, 1093 and 2277 patients had NSAID- and ASA-associated ulcer bleeding respectively. The incidence of NSAID-associated ulcer bleeding declined by 40%, whereas that of ASA-associated ulcer bleeding increased by 46%. Thirty-nine per cent of NSAID users and 75% of ASA users belonged to high ulcer risk category. Although GPA prescription rate has increased over time, only 41.6% and 30.6% of high-risk NSAID and ASA users received GPAs before ulcer bleeding respectively. Sensitivity analysis showed that if GPAs could reduce bleeding risk by 50%, improving adherence would prevent up to 35% of ulcer bleeding in high-risk users. A substantial proportion of high-risk NSAID and ASA users had not received prophylaxis with gastroprotective agents before ulcer bleeding. These bleeding episodes may be preventable with better adherence to gastroprotective agent use. © 2013 Blackwell Publishing Ltd.

High mucosal healing rates in 5-ASA-treated ulcerative colitis patients: results of a meta-analysis of clinical trials.

PubMed

Römkens, Tessa E H; Kampschreur, Milou T; Drenth, Joost P H; van Oijen, Martijn G H; de Jong, Dirk J

2012-11-01

Recently, mucosal healing (MH) is regarded as an important treatment goal in ulcerative colitis (UC). 5-Aminosalicylates (5-ASA) are the standard treatment in mild-to-moderate UC, but the effect on MH is less known. The aim of this study was to systematically review the medical literature in order to compare different preparations of 5-ASA for the effect on MH. We conducted a structured search of PubMed and the Cochrane Central Register of Controlled Trials to identify randomized controlled clinical trials with 5-ASA in UC providing data about MH. We calculated the sample size-weighted pooled proportion of patients with MH, and performed meta-analysis of head-to-head comparisons. Out of 645 hits, we included 90 treatment arms, involving 3977 patients using oral 5-ASA (granulate and tablets) and 2513 patients using rectal 5-ASA (suppositories, enema, and foam). Overall, 43,7% of 5-ASA treated patients achieved MH (oral 36,9%; rectal 50,3%). In oral studies, 49% of patients using granulate (7 treatment-arms) achieved MH compared to 34,9% using tablets (43 treatment-arms). In rectal studies the proportion of MH was 62% for suppositories (eight treatment arms), 51% for foam (nine treatment arms), and 46% for enema (23 treatment arms), respectively. 5-ASA preparations achieved MH in nearly 50% of UC patients. There were no significant differences in MH between the various 5-ASA agents, either in the oral or the rectal treatment groups. Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.

The Management of Patients with Chronic Subdural Hematoma Treated with Low-Dose Acetylsalicylic Acid: An International Survey of Practice.

PubMed

Soleman, Jehuda; Kamenova, Maria; Guzman, Raphael; Mariani, Luigi

2017-11-01

The aim of this international survey was to investigate the current management of patients undergoing surgery for chronic subdural hematoma (cSDH) treated with low-dose acetylsalicylic acid (ASA). We administered a survey via e-mail to neurosurgeons with questions relating to the surgical treatment of cSDH, emphasizing their practices with patients treated with low-dose ASA. We received 157 responses, with a response rate of 22.4%. Almost 80% of the responders discontinue ASA treatment at least 5 days before surgery and 80.7% resume treatment after 5 days or more, and 27.6% discontinue treatment for at least 30 days. The main factor influencing ASA resumption time is the indication for ASA (54.5%), and postoperative imaging is concluded in 71.7%, Postoperative thrombosis prophylaxis is administered by 60% of the responders, and 50% apply it 24 hours after surgery. Almost 95% of the responders believe that better evidence is needed for the management of patients with cSDH treated with ASA. Guidelines for these patients exist in only 24.3% of the institutes. Most neurosurgeons discontinue ASA treatment for at least 7 days in the perioperative period of surgical evacuation of cSDH, even though recent studies show that early ASA resumption might be safe. Thrombosis prophylaxis is administered by only 60%, even though patients with cSDH are at high risk of developing thromboembolic complications. Better evidence and guidelines are warranted because the incidence of patients with cSDH under the treatment of ASA is increasing. Copyright © 2017 Elsevier Inc. All rights reserved.

Budesonide for the Treatment of Ulcerative Colitis

PubMed Central

Abdalla, Maisa I.; Herfarth, Hans

2016-01-01

Introduction Budesonide is a synthetic corticosteroid characterized by enhanced topical potency and limited systemic bioavailability. Its use in ulcerative colitis (UC) was limited to rectal preparations until recently when the new oral budesonide formulation incorporating the multi-matrix system technology was introduced. The purpose of this review is to evaluate the current role of oral and rectal budesonide in managing UC patients Areas Covered In this paper, we described the chemical structure and pharmacologic characteristics of the different oral and rectal budesonide preparations, provided a summary of the published trials that evaluated the efficacy and safety of budesonide in UC, and discussed the current status of its use in this population Expert Opinion Budesonide is effective in inducing remission in a subset of patients with mild-moderate UC. Nevertheless, the current evidence suggests inferiority of oral budesonide to 5-aminosalisylates (5-ASA) and systemic steroids, whereas rectal applications are comparable to other rectal steroid preparations but still inferior to rectal 5-ASA. In clinical practice, several issues need clarification including, its exact position in the line of induction agents; the role of combining budesonide and 5-ASAs; the role of combining oral and rectal budesonide; and the role of budesonide in maintenance therapy. PMID:27157244

Budesonide for the treatment of ulcerative colitis.

PubMed

Abdalla, Maisa I; Herfarth, Hans

2016-08-01

Budesonide is a synthetic corticosteroid characterized by enhanced topical potency and limited systemic bioavailability. Its use in ulcerative colitis (UC) was limited to rectal preparations until recently when the new oral budesonide formulation incorporating the multi-matrix system technology was introduced. The purpose of this review is to evaluate the current role of oral and rectal budesonide in managing UC patients Areas covered: In this paper, we described the chemical structure and pharmacologic characteristics of the different oral and rectal budesonide preparations, provided a summary of the published trials that evaluated the efficacy and safety of budesonide in UC, and discussed the current status of its use in this population Expert opinion: Budesonide is effective in inducing remission in a subset of patients with mild-moderate UC. Nevertheless, the current evidence suggests inferiority of oral budesonide to 5-aminosalisylates (5-ASA) and systemic steroids, whereas rectal applications are comparable to other rectal steroid preparations, but still inferior to rectal 5-ASA. In clinical practice, several issues need clarification including, its exact position in the line of induction agents; the role of combining budesonide and 5-ASAs; the role of combining oral and rectal budesonide; and the role of budesonide in maintenance therapy.

Reducing AsA leads to leaf lesion and defence response in knock-down of the AsA biosynthetic enzyme GDP-D-mannose pyrophosphorylase gene in tomato plant.

PubMed

Zhang, Chanjuan; Ouyang, Bo; Yang, Changxian; Zhang, Xiaohui; Liu, Hui; Zhang, Yuyang; Zhang, Junhong; Li, Hanxia; Ye, Zhibiao

2013-01-01

As a vital antioxidant, L-ascorbic acid (AsA) affects diverse biological processes in higher plants. Lack of AsA in cell impairs plant development. In the present study, we manipulated a gene of GDP-mannose pyrophosphorylase which catalyzes the conversion of D-mannose-1-P to GDP-D-mannose in AsA biosynthetic pathway and found out the phenotype alteration of tomato. In the tomato genome, there are four members of GMP gene family and they constitutively expressed in various tissues in distinct expression patterns. As expected, over-expression of SlGMP3 increased total AsA contents and enhanced the tolerance to oxidative stress in tomato. On the contrary, knock-down of SlGMP3 significantly decreased AsA contents below the threshold level and altered the phenotype of tomato plants with lesions and further senescence. Further analysis indicated the causes for this symptom could result from failing to instantly deplete the reactive oxygen species (ROS) as decline of free radical scavenging activity. More ROS accumulated in the leaves and then triggered expressions of defence-related genes and mimic symptom occurred on the leaves similar to hypersensitive responses against pathogens. Consequently, the photosynthesis of leaves was dramatically fallen. These results suggested the vital roles of AsA as an antioxidant in leaf function and defence response of tomato.

Genetic control of ascorbic acid biosynthesis and recycling in horticultural crops

NASA Astrophysics Data System (ADS)

Mellidou, Ifigeneia; Kanellis, Angelos K.

2017-07-01

Ascorbic acid (AsA) is an essential compound present in almost all living organisms that has important functions in several aspects of plant growth and development, hormone signalling, as well as stress defense networks. In recent years, the genetic regulation of AsA metabolic pathways has received much attention due to its beneficial role in human diet. Despite the great variability within species, genotypes, tissues and developmental stages, AsA accumulation is considered to be controlled by the fine orchestration of net biosynthesis, recycling, degradation/oxidation, and/or intercellular and intracellular transport. To date, several structural genes from the AsA metabolic pathways and transcription factors are considered to significantly affect AsA in plant tissues, either at the level of activity, transcription or translation via feedback inhibition. Yet, all the emerging studies support the notion that the steps proceeding through GDP-L-galactose phosphorylase and to a lesser extent through GDP-D-mannose-3,5-epimerase are control points in governing AsA pool size in several species. In this mini review, we discuss the current consensus of the genetic regulation of AsA biosynthesis and recycling, with a focus on horticultural crops. The aspects of AsA degradation and transport are not discussed herein. Novel insights of how this multifaceted trait is regulated are critical to prioritize candidate genes for follow-up studies towards improving the nutritional value of fruits and vegetables.

5-ASA in ulcerative colitis: improving treatment compliance.

PubMed

Prantera, Cosimo; Rizzi, Marina

2009-09-21

5-Aminosalicylic acid (5-ASA) compounds are a highly effective treatment for ulcerative colitis (UC). While UC patient compliance in clinical studies is over 90%, only 40% of patients in every day life take their prescribed therapy. Adherence to medication has been emphasized recently by a Cochrane meta-analysis that has suggested that future trials of 5-ASA in UC should look at patient compliance rather than drug efficacy. Better compliance can be obtained by reducing the number of tablets and times of administration. Given that the 5-ASA formulations have different delivery systems that split the active moiety in various regions of the intestine, it is particularly important that an adequate dose of the drug arrives at the inflamed part of the colon. 5-ASA Multi matrix (MMx) is a novel, high strength (1.2 g), oral formulation designed for once-daily dosing. It releases the active moiety throughout the colon. Different studies with this compound have shown that it is as effective as 5-ASA enema in the treatment of mild-to-moderate, left-sided UC, and is comparable to a pH-dependent, delayed release 5-ASA (Asacol), even if given once daily. Recently, the effectiveness in the acute phase of UC has been confirmed also in maintenance. In conclusion, at present, 5-ASA MMx seems theoretically the best agent for maintaining patient compliance, and consequently, treatment effectiveness.

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

PubMed

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

2017-07-01

Colorectal cancer (CRC) remains the leading cause of cancer-related death in the world. Aspirin (ASA) and curcumin (CUR) are widely investigated chemopreventive candidates for CRC. However, the precise mechanisms of their action and their combinatorial effects have not been evaluated. The purpose of the present study was to determine the effect of ASA, CUR, and their combination in azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-accelerated colorectal cancer (CAC). We also aimed to characterize the differential gene expression profiles in AOM/DSS-induced tumors as well as in tumors modulated by ASA and CUR using RNA-seq. Diets supplemented with 0.02% ASA, 2% CUR or 0.01% ASA+1% CUR were given to mice from 1week prior to the AOM injection until the experiment was terminated 22weeks after AOM initiation. Our results showed that CUR had a superior inhibitory effect in colon tumorigenesis compared to that of ASA. The combination of ASA and CUR at a lower dose exhibited similar efficacy to that of a higher dose of CUR at 2%. RNA isolated from colonic tissue from the control group and from tumor samples from the experimental groups was subjected to RNA-seq. Transcriptomic analysis suggested that the low-dose combination of ASA and CUR modulated larger gene sets than the single treatment. These differentially expressed genes were situated in several canonical pathways important in the inflammatory network and liver metastasis in CAC. We identified a small subset of genes as potential molecular targets involved in the preventive action of the combination of ASA and CUR. Taken together, the current results provide the first evidence in support of the chemopreventive effect of a low-dose combination of ASA and CUR in CAC. Moreover, the transcriptional profile obtained in our study may provide a framework for identifying the mechanisms underlying the carcinogenesis process from normal colonic tissue to tumor development as well as the cancer inhibitory effects and potential molecular targets of ASA and CUR. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic and genome-wide transcriptomic analyses identify co-regulation of oxidative response and hormone transcript abundance with vitamin C content in tomato fruit.

PubMed

Lima-Silva, Viviana; Rosado, Abel; Amorim-Silva, Vitor; Muñoz-Mérida, Antonio; Pons, Clara; Bombarely, Aureliano; Trelles, Oswaldo; Fernández-Muñoz, Rafael; Granell, Antonio; Valpuesta, Victoriano; Botella, Miguel Ángel

2012-05-14

L-ascorbic acid (AsA; vitamin C) is essential for all living plants where it functions as the main hydrosoluble antioxidant. It has diverse roles in the regulation of plant cell growth and expansion, photosynthesis, and hormone-regulated processes. AsA is also an essential component of the human diet, being tomato fruit one of the main sources of this vitamin. To identify genes responsible for AsA content in tomato fruit, transcriptomic studies followed by clustering analysis were applied to two groups of fruits with contrasting AsA content. These fruits were identified after AsA profiling of an F8 Recombinant Inbred Line (RIL) population generated from a cross between the domesticated species Solanum lycopersicum and the wild relative Solanum pimpinellifollium. We found large variability in AsA content within the RIL population with individual RILs with up to 4-fold difference in AsA content. Transcriptomic analysis identified genes whose expression correlated either positively (PVC genes) or negatively (NVC genes) with the AsA content of the fruits. Cluster analysis using SOTA allowed the identification of subsets of co-regulated genes mainly involved in hormones signaling, such as ethylene, ABA, gibberellin and auxin, rather than any of the known AsA biosynthetic genes. Data mining of the corresponding PVC and NVC orthologs in Arabidopis databases identified flagellin and other ROS-producing processes as cues resulting in differential regulation of a high percentage of the genes from both groups of co-regulated genes; more specifically, 26.6% of the orthologous PVC genes, and 15.5% of the orthologous NVC genes were induced and repressed, respectively, under flagellin22 treatment in Arabidopsis thaliana. Results here reported indicate that the content of AsA in red tomato fruit from our selected RILs are not correlated with the expression of genes involved in its biosynthesis. On the contrary, the data presented here supports that AsA content in tomato fruit co-regulates with genes involved in hormone signaling and they are dependent on the oxidative status of the fruit.

Citing ASA24® Dietary Assessment Tool in Publications & Presentations

Cancer.gov

In order to show and maintain support for ASA24, documenting its use in through publications is extremely useful to the National Cancer Institute (NCI). Please cite ASA24 as follows, depending on the version used in your study.

Review on landfill leachate treatment by electrochemical oxidation: Drawbacks, challenges and future scope.

PubMed

Mandal, Pubali; Dubey, Brajesh K; Gupta, Ashok K

2017-11-01

Various studies on landfill leachate treatment by electrochemical oxidation have indicated that this process can effectively reduce two major pollutants present in landfill leachate; organic matter and ammonium nitrogen. In addition, the process is able to enhance the biodegradability index (BOD/COD) of landfill leachate, which make mature or stabilized landfill leachate suitable for biological treatment. The elevated concentration of ammonium nitrogen especially observed in bioreactor landfill leachate can also be reduced by electrochemical oxidation. The pollutant removal efficiency of the system depends upon the mechanism of oxidation (direct or indirect oxidation) which depends upon the property of anode material. Applied current density, pH, type and concentration of electrolyte, inter-electrode gap, mass transfer mode, total anode area to volume of effluent to be treated ratio, temperature, flow rate or flow velocity, reactor geometry, cathode material and lamp power during photoelectrochemical oxidation may also influence the system performance. In this review paper, past and present scenarios of landfill leachate treatment efficiencies and costs of various lab scale, pilot scale electrochemical oxidation studies asa standalone system or integrated with biological and physicochemical processes have been reviewed with the conclusion that electrochemical oxidation can be employed asa complementary treatment system with biological process for conventional landfill leachate treatment as well asa standalone system for ammonium nitrogen removal from bioreactor landfill leachate. Furthermore, present drawbacks of electrochemical oxidation process asa landfill leachate treatment system and relevance of incorporating life cycle assessment into the decision-making process besides process efficiency and cost, have been discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antibodies to pituitary surface antigens during various pituitary disease states.

PubMed

Keda, Y M; Krjukova, I V; Ilovaiskaia, I A; Morozova, M S; Fofanova, O V; Babarina, M B; Marova, E I; Pankov, Y A; Kandror, V I

2002-11-01

Autoantibodies to cell surface antigens of human somatotropinoma (ASAS), human prolactinoma (ASAP) and rat adenohypophysis (ASARA) were assayed in the serum of patients with pituitary diseases associated with GH deficiency (GHD), such as pituitary dwarfism and primary empty sella syndrome (ESS), and in the serum of patients with hyperprolactinaemia of different etiologies: idiopathic hyperprolactinaemia, prolactinoma and ESS. The investigation was carried out with a cellular variant of an ELISA. Among children with GHD, the highest percentage of antibody-positive patients was found in the group with idiopathic isolated GHD (89% of ASAS(+) patients and 30% of ASARA(+) patients vs 33.3% and 0% respectively in the group with idiopathic combined pituitary hormone deficiency, and 33.3% and 9% in patients with pituitary hypoplasia associated with isolated GHD or combined pituitary hormone deficiency). Among hyperprolactinaemic patients, the highest ASAP and ASARA frequency was observed in patients with idiopathic hyperprolactinaemia (67.7% and 41.9% respectively) where it was twice as high as in the group of patients with prolactinoma. The proportion of ASAS(+) and ASARA(+) did not differ significantly between the groups of patients with ess with or without GHD. Similarly, there was no significant difference between the number of ESS ASAP(+) and ASARA(+) patients with or without hyperprolactinaemia. The data obtained suggested that autoimmune disorders may be primary, and responsible, at least in part, for pituitary dysfunction in the cases of idiopathic isolated GHD and idiopathic hyperprolactinaemia. At the same time, the autoimmune disorders in the patients with prolactinoma or ESS are probably secondary to the organic pituitary lesion and their significance in the development of the pituitary dysfunction is obscure.

Influence of 5-aminosalicylic acid on 6-thioguanosine phosphate metabolite levels: a prospective study in patients under steady thiopurine therapy

PubMed Central

de Graaf, P; de Boer, NKH; Wong, DR; Karner, S; Jharap, B; Hooymans, PM; Veldkamp, AI; Mulder, CJJ; van Bodegraven, AA; Schwab, M

2010-01-01

Background and purpose: 5-aminosalicylate (5-ASA) raises levels of 6-thioguanine nucleotides (6-TGN), the active metabolites of thiopurines such as azathioprine (AZA). Changes in levels of each individual TGN – 6-thioguanosine mono-, di- and triphosphate (6-TGMP, 6-TGDP, 6-TGTP) – and of 6-methylmercaptopurine ribonucleotides (6-MMPR) after 5-ASA are not known. Experimental approach: Effects of increasing 5-ASA doses on AZA metabolites were investigated prospectively in 22 patients with inflammatory bowel disease in 4-week study periods. Patients started with 2 g 5-ASA daily, and then were increased to 4 g daily and followed by a washout period. Thiopurine doses remained unchanged throughout the entire study. Levels of 6-TGMP, 6-TGDP, 6-TGTP and 6-MMPR as well as of 5-ASA and N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA) were determined each study period. Key results: Median baseline levels in 17 patients of 6-TGDP, 6-TGTP and 6-MMPR were 52, 319 and 1676 pmol per 8 × 108 red blood cells respectively. After co-administration of 2 g 5-ASA daily, median 6-TGDP and 6-TGTP levels increased but median 6-MMPR levels were unchanged. Increasing 5-ASA to 4 g daily did not affect median 6-TGDP and 6-TGTP levels, but median 6-MMPR levels decreased. After discontinuation of 5-ASA, both 6-TGDP and 6-TGTP levels decreased and median 6-MMPR levels increased. The 6-TGTP/(6-TGDP+6-TGTP)-ratio did not change during the study, but 6-MMPR/6-TGN ratios decreased. Conclusions and implications: Individual 6-TGN metabolites increased after addition of 5-ASA, but 6-MMPR-levels and the 6-MMPR/6-TGN ratios decreased. Further studies are needed to decide whether this pharmacokinetic interaction would result in improvement of efficacy and/or increased risk of toxicity of AZA. PMID:20590602

Does Early Resumption of Low-Dose Aspirin After Evacuation of Chronic Subdural Hematoma With Burr-Hole Drainage Lead to Higher Recurrence Rates?

PubMed

Kamenova, Maria; Lutz, Katharina; Schaedelin, Sabine; Fandino, Javier; Mariani, Luigi; Soleman, Jehuda

2016-11-01

Antiplatelet therapy in patients with chronic subdural hematoma (cSDH) presents significant neurosurgical challenges. Given the lack of guidelines regarding perioperative management with antiplatelet therapy, it is difficult to balance the patient's increased cardiovascular risk and prevalence of cSDH. To better understand the risk and recurrence rates related to resuming low-dose acetylsalicylic acid (ASA) by evaluating our patients' resumption of low-dose ASA at various times after burr-hole drainage of the hematoma. In our retrospective study, 140 consecutive patients taking low-dose ASA undergoing surgical evacuation of cSDH were included. Data included baseline characteristics and rates of recurrence, morbidity, and mortality. A multivariate logistic regression model analyzed the association between ASA resumption time and recurrence rates. No statistically significant association was observed between early postoperative resumption of low-dose ASA and recurrence of cSDH (odds ratio, 1.01; 95% confidence interval, 1.001-1.022; P = .06). Corresponding odds ratios and risk differences for restarting ASA treatment on postoperative days 1, 7, 14, 21, 28, 35, or 42 were estimated at 1.53 and 5.9%, 1.42 and 5.1%, 1.33 and 4.1%, 1.23 and 3.2%, 1.15 and 2.2%, 1.07 and 1.1%, and 1.01 and 0.2%, respectively (P > .05). Cardiovascular event rates, surgical morbidity, and mortality did not significantly differ between patients with or without ASA therapy. Given the few published studies regarding ASA use in cranial neurosurgery, our findings elucidate one issue, showing comparable recurrence rates with early or late resumption of low-dose ASA after burr-hole evacuation of cSDH. ASA, acetylsalicylic acidCAD, coronary artery diseaseCI, confidence intervalcSDH, chronic subdural hematomaGCS, Glasgow Coma ScalemRS, modified Rankin ScaleOR, odds ratioRD, risk difference.

Protective Role of Acetylsalicylic Acid in Experimental Trypanosoma cruzi Infection: Evidence of a 15-epi-Lipoxin A4-Mediated Effect

PubMed Central

Henriquez, Natalia; Faúndez, Mario; Torres, Gloria; Castillo, Christian; Escanilla, Sebastián; Kemmerling, Ulrike; Morello, Antonio; López-Muñoz, Rodrigo A.; Maya, Juan D.

2013-01-01

Chagas' disease, produced by Trypanosoma cruzi, affects more than 8 million people, producing approximately 10,000 deaths each year in Latin America. Migration of people from endemic regions to developed countries has expanded the risk of infection, transforming this disease into a globally emerging problem. PGE2 and other eicosanoids contribute to cardiac functional deficits after infection with T. cruzi. Thus, the inhibition of host cyclooxygenase (COX) enzyme emerges as a potential therapeutic target. In vivo studies about the effect of acetylsalicylic acid (ASA) upon T. cruzi infection are controversial, and always report the effect of ASA at a single dose. Therefore, we aimed to analyze the effect of ASA at different doses in an in vivo model of infection and correlate it with the production of arachidonic acid metabolites. ASA decreased mortality, parasitemia, and heart damage in T. cruzi (Dm28c) infected mice, at the low doses of 25 and 50 mg/Kg. However, this effect disappeared when the high ASA doses of 75 and 100 mg/Kg were used. We explored whether this observation was related to the metabolic shift toward the production of 5-lipoxygenase derivatives, and although we did not observe an increase in LTB4 production in infected RAW cells and mice infected, we did find an increase in 15-epi-LXA4 (an ASA-triggered lipoxin). We also found high levels of 15-epi-LXA4 in T. cruzi infected mice treated with the low doses of ASA, while the high ASA doses decreased 15-epi-LXA4 levels. Importantly, 15-epi-LXA4 prevented parasitemia, mortality, and cardiac changes in vivo and restored the protective role in the treatment with a high dose of ASA. This is the first report showing the production of ASA-triggered lipoxins in T. cruzi infected mice, which demonstrates the role of this lipid as an anti-inflammatory molecule in the acute phase of the disease. PMID:23638194

Antioxidant Vitamin Status in the Serum and Amniotic Fluid of Women with Premature Rupture of the Fetal Membranes.

NASA Astrophysics Data System (ADS)

Barrett, Bridget M.

The purpose of this study was to examine the status of antioxidant vitamins in women with premature rupture of the fetal membranes. Specimens of blood and amniotic fluid were obtained from 80 pregnant subjects included both smokers and non-smokers during the third trimester. The concentrations of ascorbic acid (ASA), beta -carotene, retinol and alpha -tocopherol in serum and amniotic fluid were determined. The experimental group consisted of those subjects with PROM while the control subjects were those with normal pregnancy. No statistical differences were found between the PROM and control groups in retinol and vitamin E concentrations in amniotic fluid and serum. Serum ASA concentrations of PROM subjects were not different from controls, but the PROM subjects had significantly lower amniotic fluid ASA concentrations. However, in a study with fewer subjects a lower serum ASA concentration in the PROM subjects was observed. The ratio of amniotic fluid ASA concentration to ASA serum concentration was significantly lower in PROM patients than in controls in both studies. This suggests that low levels of ASA in the amniotic fluid, but not in serum is better associated with PROM. A low amniotic fluid concentration of ASA may reflect an inefficient transfer and/or increased fetal utilization. Alterations in ASA concentration in the amniotic fluid may affect the integrity of the chorioamnion leading to PROM. beta -Carotene was not found in the amniotic fluid. Serum beta-carotene levels were significantly lower in the PROM group compared to the control group. Low concentrations of beta-carotene in maternal serum in smokers not only associated with poor maternal outcome (PROM) but also compromised the fetal outcome (decreased birth weight). Maintenance of adequate serum beta-carotene concentration and amniotic fluid ASA in smokers may result in better maternal and fetal outcome. This study demonstrated that nutrition is an important factor in the prevention of PROM.

Asiatic acid induces endoplasmic reticulum stress and apoptotic death in glioblastoma multiforme cells both in vitro and in vivo

PubMed Central

Kavitha, Chandagirikoppal V.; Jain, Anil K.; Agarwal, Chapla; Pierce, Angela; Keating, Amy; Huber, Kendra M.; Serkova, Natalie J.; Wempe, Michael F.; Agarwal, Rajesh; Deep, Gagan

2014-01-01

Glioblastoma multiforme (GBM) is an untreatable malignancy. Existing therapeutic options are insufficient, and adversely affect functional and non-cancerous cells in the brain impairing different functions of the body. Therefore, there is an urgent need for additional preventive and therapeutic non-toxic drugs against GBM. Asiatic acid (AsA; 2,3,23-trihydroxy-12-ursen-28-oic acid, C30H48O5) is a natural small molecule widely used to treat various neurological disorders, and the present research investigates AsA’s efficacy against GBM both in vitro and in vivo. Results showed that AsA treatment (10–100 μM) decreased the human GBM cell (LN18, U87MG, and U118MG) viability, with better efficacy than temozolomide at equimolar doses. Orally administered AsA (30 mg/kg/day) strongly decreased tumor volume in mice when administered immediately after ectopic U87MG xenograft implantation (54% decrease, p≤0.05) or in mice with established xenografts (48% decrease, p≤0.05) without any apparent toxicity. Importantly, AsA feeding (30 mg/kg/twice a day) also decreased the orthotopic U87MG xenografts growth in nude mice as measured by magnetic resonance imaging. Using LC/MS-MS methods, AsA was detected in mice plasma and brain tissue, confirming that AsA crosses blood-brain barrier. Mechanistic studies showed that AsA induces apoptotic death by modulating the protein expression of several apoptosis regulators (caspases, Bcl2 family members, and survivin) in GBM cells. Furthermore, AsA induced ER stress (increased GRP78 and Calpain, and decreased Calnexin and IRE1α expression), enhanced free intra-cellular calcium, and damaged cellular organization in GBM cells. These experimental results demonstrate that AsA is effective against GBM, and advocate further pre-clinical and clinical evaluations of AsA against GBM. PMID:25252179

The pharmacological profile and clinical use of mesalazine (5-aminosalicylic acid).

PubMed

Klotz, U

2012-02-01

For more than 30 years mesalazine (5-aminosalicylic acid; 5-ASA) has been used for the treatment of chronic inflammatory bowel disease (IBD) especially in ulcerative colitis (UC). During this time various rectal and oral formulations have been developed. The modified drug delivery systems were designed to release sufficient 5-ASA at the sites of inflammation. Such a drug targeting strategy is needed for its topical action and especially because local concentrations in the mucosa will determine the clinical outcome. The absorbed part (20-40% of the dose) of 5-ASA is rapidly and presystemically acetylated (t1/2: 1-2.5 h; CL: 300-690 mL/min). Consequently, the systemic exposure of 5-ASA is low and adverse effects are in the range of placebo treatment. The polypotent 5-ASA has a wide spectrum of pharmacological properties and its exact mode of action is not yet clear. Recent meta-analyses of randomized placebo-controlled clinical trials provide convincing data that 5-ASA is the preferred first-line therapy for the acute treatment of mild-to-moderate UC (NNT:6) and for remission management (NNT:4). There is also some clinical benefit for patients with active Crohn's disease (NNT:7) and in the prevention of postsurgical relapse (NNT:10). There is increasing evidence that 5-ASA also has some therapeutic potential for chemoprevention of colorectal cancer, diverticular disease and irritable bowel syndrome. In all clinical studies, the side effects of 5-ASA were very low (5-10%), mild and comparable to placebo. Thus, its use is very safe and 5-ASA will remain an interesting and valuable agent. It is anticipated that more selective drug targeting, including galenic innovations and an optimized dosaging schedule, could result in some improvement of the wide use of 5-ASA. © Georg Thieme Verlag KG Stuttgart · New York.

3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets.

PubMed

Goyanes, Alvaro; Buanz, Asma B M; Hatton, Grace B; Gaisford, Simon; Basit, Abdul W

2015-01-01

The aim of this study was to explore the potential of fused-deposition 3-dimensional printing (FDM 3DP) to produce modified-release drug loaded tablets. Two aminosalicylate isomers used in the treatment of inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA, mesalazine) and 4-aminosalicylic acid (4-ASA), were selected as model drugs. Commercially produced polyvinyl alcohol (PVA) filaments were loaded with the drugs in an ethanolic drug solution. A final drug-loading of 0.06% w/w and 0.25% w/w was achieved for the 5-ASA and 4-ASA strands, respectively. 10.5mm diameter tablets of both PVA/4-ASA and PVA/5-ASA were subsequently printed using an FDM 3D printer, and varying the weight and densities of the printed tablets was achieved by selecting the infill percentage in the printer software. The tablets were mechanically strong, and the FDM 3D printing was shown to be an effective process for the manufacture of the drug, 5-ASA. Significant thermal degradation of the active 4-ASA (50%) occurred during printing, however, indicating that the method may not be appropriate for drugs when printing at high temperatures exceeding those of the degradation point. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) of the formulated blends confirmed these findings while highlighting the potential of thermal analytical techniques to anticipate drug degradation issues in the 3D printing process. The results of the dissolution tests conducted in modified Hank's bicarbonate buffer showed that release profiles for both drugs were dependent on both the drug itself and on the infill percentage of the tablet. Our work here demonstrates the potential role of FDM 3DP as an efficient and low-cost alternative method of manufacturing individually tailored oral drug dosage, and also for production of modified-release formulations. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2017-01-01

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

Standards 101: The ASA Standards program

NASA Astrophysics Data System (ADS)

Schomer, Paul

2004-05-01

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

Atlanta Streets Alive: A Movement Building a Culture of Health in an Urban Environment.

PubMed

Torres, Andrea; Steward, John; Strasser, Sheryl; Lyn, Rodney; Serna, Rebecca; Stauber, Christine

2016-02-01

Open Streets are community-based programs that promote the use of public space for physical activity (PA), recreation and socialization by closing streets temporarily to motorized vehicles, allowing access to pedestrians. The city of Atlanta hosted its first Open Streets event, Atlanta Streets Alive (ASA), in May 2010. An evaluation of the first 5 ASA events from May 2010 to May 2012 was conducted. The purpose was to learn about the characteristics of ASA participants, the influence of the event on their PA, and perceptions of safety and neighborhood social capital. ASA's evaluation had 2 components: participant counts and a participant survey. Characteristics of participation were compared among the 3 different events in which surveys were conducted using the Pearson χ2 test and F test as appropriate. The estimated participation at ASA increased from nearly 3,500 (ASA 1 to 4) to 12,520 (ASA 5). The number of events increased to 3 per year for a total of 10 events until 2014. Overall, 19.4% of participants met the weekly PA recommendation during 1 event. The expanding diversity of routes, participants, and sponsorships highlights the potential promise such programming offers in terms of establishing an urban culture of health.

[Statins and ASS for primary prevention of cardiovascular and cerebrovascular disease].

PubMed

Goltz, L; Bodechtel, U; Siepmann, T

2014-02-01

Whereas statins and acetylsalicylic acid (ASA) are considered gold standard for secondary prevention following myocardial infarction or atherotrombotic stroke, there are inconsistent data on the use of these drugs for primary prevention in patients with increased cardiovascular risk. Some meta-analyses indicated that the use of statins and ASA for primary prevention of cardiovascular disease can reduce the risk of cardiovascular events such as ischemic stroke or myocardial infarction. However, the effects of primary prevention with statins and ASA on mortality varied in the data included in these meta-analyses. Therefore the guidelines of the German College of General Practitioners and Family Physicians recommend primary prevention with statins and ASA only in those patients who have a 10-year risk of cardiovascular events which exceeds 20 %. Divergently, primary prevention with ASA is not recommended by the European Society of Cardiology. Observational studies suggested that treatment success of primary prevention with statins and ASA depends on various factors such as adherence to medication and prescription behavior of physicians. This review summarizes the current literature on primary prevention of cardiovascular events with ASA and statins. © Georg Thieme Verlag KG Stuttgart · New York.

Basophil responsiveness and clinical picture of acetylsalicylic acid intolerance.

PubMed

Korosec, Peter; Mavsar, Nusa; Bajrovic, Nissera; Silar, Mira; Mrhar, Ales; Kosnik, Mitja

2011-01-01

Exposure to acetylsalicylic acid (ASA) may exacerbate respiratory or skin diseases or induce anaphylactoid reactions in apparently healthy individuals. We wanted to evaluate specific responsiveness of basophils to ASA in correlation with the clinical picture. We performed a prospective single-blind study of 59 subjects involved in clinical evaluation and/or ASA provocation testing. Whole blood basophils were stained with anti-CD63/CD123/HLA-DR mAbs after stimulation with 0.25 or 1 mg/ml ASA. We found that 40 subjects were ASA tolerant and 19 were ASA intolerant. Both groups had comparable manifestations of asthma and/or rhinitis (13 in the tolerant and 9 in the intolerant group). Intolerant subjects showed significantly higher basophil responsiveness to ASA in comparison to tolerant subjects, which was concentration-dependent in both groups. The ratio between responses at 1 mg/ml of ASA and at baseline (activation index) was analyzed according to the clinical picture. We demonstrate that the activation index was higher only in the intolerant subjects with anaphylactoid reactions, but not in a subgroup of subjects with asthma/rhinitis. The ROC calculations show that the optimal threshold activation index was more than 2.18. The sensitivity was 80% and the specificity was 83% in the subgroup with anaphylactoid reactions. In the asthma/rhinitis subgroup, the sensitivity was 78% and the specificity was 50%. Our study demonstrates that there is a significantly higher in vitro basophil response to ASA in intolerant as compared to tolerant subjects. ROC analyses suggest that this measurement might only have a diagnostic value in subjects without asthma and/or rhinitis. Copyright © 2011 S. Karger AG, Basel.

Iron chelation as a possible mechanism for aspirin-induced malondialdehyde production by mouse liver microsomes and mitochondria.

PubMed Central

Schwarz, K B; Arey, B J; Tolman, K; Mahanty, S

1988-01-01

To investigate the possibility that lipid peroxidation is the mechanism responsible for aspirin-induced liver damage, pure neutralized acetylsalicylic acid (ASA), 0.6-90.9 mM, was added to calcium-aggregated mouse liver microsomes followed by incubation in NADPH buffer at 37 degrees C for 60 min and subsequent measurement of malondialdehyde (MDA). MDA production at ASA concentrations from 1.2 to 4.6 mM was greater than control (P less than 0.004). Peak MDA values were observed with 4.6 mM ASA, 39.58 +/- 6.73 nmol MDA/mg protein vs. 16.16 +/- 2.85 (P less than 0.004). Higher concentrations of ASA were inhibitory compared with the value at 4.6 mM (P less than 0.001). Aspirin had similar effects on MDA production by mouse liver mitochondria. MDA production with either ASA or buffer was completely suppressed by the potent iron-chelating agents desferrioxamine and alpha,alpha' dipyridyl when these were added to the microsomal preparations. Since MDA production in this system is known to be affected by iron-chelating agents (enhanced at low concentration, inhibited at higher concentration), the iron-chelating properties of ASA were investigated. Conductivity titration curves of Fe(OH)3 added to water or ASA suggested that the ASA was complexing with iron. The presence of an iron-ASA complex was established by high pressure liquid chromatographic analysis of the solution from this study. We conclude that aspirin enhances MDA production by hepatic microsomes and mitochondria via an aspirin-iron chelate and that this represents at least one mechanism by which aspirin may produce liver damage. PMID:3335633

Multiple transformation pathways of p-arsanilic acid to inorganic arsenic species in water during UV disinfection.

PubMed

Li, Suqi; Xu, Jing; Chen, Wei; Yu, Yingtan; Liu, Zizheng; Li, Jinjun; Wu, Feng

2016-09-01

p-Arsanilic acid (p-ASA) is widely used in China as livestock and poultry feed additive for promoting animal growth. The use of organoarsenics poses a potential threat to the environment because it is mostly excreted by animals in its original form and can be transformed by UV-Vis light excitation. This work examined the initial rate and efficiency of p-ASA phototransformation under UV-C disinfection lamp. Several factors influencing p-ASA phototransformation, namely, pH, initial concentration, temperature, as well as the presence of NaCl, NH4(+), and humic acid, were investigated. Quenching experiments and LC-MS were performed to investigate the mechanism of p-ASA phototransformation. Results show that p-ASA was decomposed to inorganic arsenic (including As(III) and As(V)) and aromatic products by UV-C light through direct photolysis and indirect oxidation. The oxidation efficency of p-ASA by direct photosis was about 32%, and those by HO and (1)O2 were 19% and 49%, respectively. Cleavage of the arsenic-benzene bond through direct photolysis, HO oxidation or (1)O2 oxidation results in simultaneous formation of inorganic As(III), As(IV), and As(V). Inorganic As(III) is oxidized to As(IV) and then to As(V) by (1)O2 or HO. As(IV) can undergo dismutation or simply react with oxygen to produce As(V) as well. Reactions of the organic moieties of p-ASA produce aniline, aminophenol and azobenzene derivatives as main products. The photoconvertible property of p-ASA implies that UV disinfection of wastewaters from poultry and swine farms containing p-ASA poses a potential threat to the ecosystem, especially agricultural environments. Copyright © 2016. Published by Elsevier B.V.

Effect of radical scavengers on the inactivation of papain by ascorbic acid in the presence of cupric ions.

PubMed

Kanazawa, H; Fujimoto, S; Ohara, A

1994-04-01

Incubation of papain (EC 3.4.22.2) with ascorbic acid (AsA) and Cu2+ in acetate buffer (pH 5.6) results in an irreversible loss of enzyme activity by site-specific generation of free radicals [H. Kanazawa, S. Fujimoto, A. Ohara, Biol. Pharm.Bull., 16, 11 (1993)]. In this study, the effect of some compounds, known free radical scavengers, on the relationship between the inactivation of papain by the Cu(2+)-AsA system and the oxidation of AsA was investigated. Catalase completely protected the enzyme from inactivation by the Cu(2+)-AsA system, although hydrogen peroxide (H2O2) by itself, known to be generated during the autoxidation of AsA, did not inactivate the enzyme. The oxidation of AsA was unaffected by catalase. Both thiourea and sodium thiocyanate completely protected the enzyme from inactivation, while AsA was partially oxidized only in the initial stage. In the presence of potassium iodide, both the inactivation of the enzyme and the oxidation of AsA were characterized by a rapid initial phase followed by a stable phase where no reaction took place and, subsequently, a slower phase. Histidine partially prevented the inactivation of the enzyme and the oxidation of AsA. The present results suggest that H2O2 serves as a source of secondary, highly reactive species, probably hydroxyl radicals, which are responsible for the inactivation, and that the protection from inactivation by some radical scavengers, such as thiourea, sodium thiocyanate, potassium iodide, and histidine, is based on the removal of metal ions (Cu2+ or Cu+) at the specific site of inactivation.

Synergic carcinostatic effects of ascorbic acid and hyperthermia on Ehrlich ascites tumor cell.

PubMed

Saitoh, Y; Yoshimoto, T; Kato, S; Miwa, N

2015-06-01

In this study, we evaluated the carcinostatic effects of combined ascorbic acid (AsA) and a capacitive-resistive electric transfer (CRet) hyperthermic apparatus-induced hyperthermic treatment on Ehrlich ascites tumor (EAT) cells. EAT cells were exposed to various AsA (0-10 mM) concentrations for 1 h; they subsequently underwent CRet treatment for 15 min at 42 °C. Cell viability was assessed by the WST-8 assay 24 h after the combined treatment. Reactive oxygen species involvement was evaluated using catalase and tempol; caspase-3/7 activation was determined by their fluorescent substrates; cell proliferation were estimated by time-lapse observation. The effect on the cell cycle was analyzed by flow cytometry. Combined AsA and CRet treatment synergistically suppressed cell viability compared with either treatment alone, and these synergistically carcinostatic effects were evident even at noncytotoxic concentrations of AsA alone (≤ 2 mM). The carcinostatic effects of combined AsA and CRet treatment were attenuated in a dose-dependent manner by catalase addition, but not by the superoxide anion radical scavenger tempol. Time-lapse observation revealed that combined AsA and CRet treatment activated caspase-3/7 at 10-24 h after treatment, accompanied by significant cell growth suppression. Cell cycle analysis revealed that the rate of sub-G1-phase (apoptotic) cells was drastically increased at 12 h and 24 h, and that the G2/M-phase cells gradually increased at 6-24 h after treatment. These results indicate that combined AsA and CRet treatment synergistically inhibits EAT cell growth through G2/M arrest and apoptosis induction via H2O2 generation at lower AsA concentrations; this carcinostatic effect cannot be exerted by AsA alone.

Underutilization of aspirin for primary prevention of cardiovascular disease among HIV-infected patients.

PubMed

Burkholder, Greer A; Tamhane, Ashutosh R; Salinas, Jorge L; Mugavero, Michael J; Raper, James L; Westfall, Andrew O; Saag, Michael S; Willig, James H

2012-12-01

Individuals infected with human immunodeficiency virus (HIV) are at increased risk for cardiovascular disease (CVD) events compared with uninfected persons. However, little is known about HIV provider practices regarding aspirin (ASA) for primary prevention of CVD. A cross-sectional study was conducted among patients attending the University of Alabama at Birmingham 1917 HIV Clinic during 2010 to determine the proportion receiving ASA for primary prevention of CVD and identify factors associated with ASA prescription. Ten-year risk for CVD events was calculated for men aged 45-79 and women aged 55-79. The 2009 US Preventive Services Task Force (USPSTF) guidelines were used to determine those qualifying for primary CVD prevention. Among 397 patients who qualified to receive ASA (mean age, 52.2 years, 94% male, 36% African American), only 66 (17%) were prescribed ASA. In multivariable logistic regression analysis, diabetes mellitus (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.28-5.27), hyperlipidemia (OR, 3.42; 95% CI, 1.55-7.56), and current smoking (OR, 1.87; 95% CI, 1.03-3.41) were significantly associated with ASA prescription. Odds of ASA prescription more than doubled for each additional CVD-related comorbidity present among hypertension, diabetes, hyperlipidemia, and smoking (OR, 2.13, 95% CI, 1.51-2.99). In this HIV-infected cohort, fewer than 1 in 5 patients in need received ASA for primary CVD prevention. Escalating likelihood of ASA prescription with increasing CVD-related comorbidity count suggests that providers may be influenced more by co-occurrence of these diagnoses than by USPSTF guidelines. In the absence of HIV-specific guidelines, interventions to improve HIV provider awareness of and adherence to existing general population guidelines on CVD risk reduction are needed.

Impact of aspirin on presentation and hospital outcomes in patients with acute coronary syndromes (The Global Registry of Acute Coronary Events [GRACE]).

PubMed

Spencer, Frederick A; Santopinto, Jose J; Gore, Joel M; Goldberg, Robert J; Fox, Keith A A; Moscucci, Mauro; White, Kami; Gurfinkel, Enrique P

2002-11-15

The long-term use of aspirin (ASA) reduces the risk of subsequent acute coronary syndromes in patients with coronary artery disease (CAD). It is less clear whether ASA therapy benefits patients who develop an acute coronary syndrome despite its use. Baseline characteristics, type of acute coronary syndrome, and in-hospital events were compared on the basis of previous use of ASA in 11,388 patients with and without a history of CAD presenting to 94 multinational hospitals. A total of 73.0% of patients with a history of CAD (n = 4,974) were previously on long-term ASA therapy compared with 19.4% of patients without a history of CAD (n = 6,414). After multivariate regression analysis controlling for various potentially confounding factors, patients with a history of CAD who were previously taking ASA were significantly less likely to present with ST-segment elevation myocardial infarction (MI) (adjusted odds ratio [OR] 0.52, 95% confidence intervals [CI] 0.44 to 0.61) or die during hospitalization (OR 0.69, 95% CI 0.50 to 0.95) in comparison to patients who were not taking ASA. Patients without a history of CAD and who were previously taking ASA also had a lower risk of developing ST-segment elevation MI (OR 0.35, 95% CI 0.30 to 0.40) and a trend toward a decreased hospital death rate (OR 0.77, 95% CI 0.55 to 1.07). These results demonstrate that patients with a history of CAD who present with an acute coronary syndrome despite prior ASA use have less severe clinical presentation, fewer hospital complications, and lower in-hospital death rates than patients not previously taking ASA.

Association of anti-sperm antibodies with chronic prostatitis: A systematic review and meta-analysis.

PubMed

Jiang, Yumei; Cui, Dong; Du, Yuefeng; Lu, Jun; Yang, Lin; Li, Jinmei; Zhang, Jing; Bai, Xiaojing

2016-11-01

Chronic prostatitis is a risk factor for impaired male fertility potential, and anti-sperm antibodies (ASAs) cause the autoimmune disease immune infertility, which has a negative effect on semen parameters. Current studies have investigated the ASA-positive relationship between chronic prostatitis versus normal controls, but have shown inconsistent results. Hence, we systematic searched the PubMed, EMBASE, Science Direct/Elsevier, Medline, and the Cochrane Library up to October 2015 for case-control studies that involved the ASA-positive relationship between chronic prostatitis patients versus normal controls. The meta-analysis was performed with Review Manager and Stata software. After literature search, six studies were identified, including 721 cases of chronic prostatitis and 160 normal controls. Our results illustrated a significant correlation of the ASA-positive relationship between chronic prostatitis patients versus normal controls. The combined odds ratio of the ASA-positive rate in chronic prostatitis patients and normal controls was 3.26 (1.86-5.71). There was also a significant correlation of the ASA-positive relationship between National Institutes of Health (NIH) III versus normal controls, and the combined OR was 2.46 (1.10-5.51). However, there was no significant correlation of the ASA-positive relationship between National Institutes of Health (NIH) II versus normal controls. The present study illustrates that the positive rate of ASAs in chronic prostatitis patients was significantly higher than in the control group, suggesting that chronic prostatitis has a negative effect on male reproductive function. However, studies with larger samples are needed to better illuminate the correlation between ASAs and chronic prostatitis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A randomised controlled pilot trial to evaluate and optimize the use of anti-platelet agents in the perioperative management in patients undergoing general and abdominal surgery--the APAP trial (ISRCTN45810007).

PubMed

Antolovic, D; Rakow, A; Contin, P; Ulrich, A; Rahbari, N N; Büchler, M W; Weitz, J; Koch, M

2012-02-01

Surgeons are increasingly confronted by patients on long-term low-dose acetylsalicylic acid (ASA). However, owing to a lack of evidence-based data, a widely accepted consensus on the perioperative management of these patients in the setting of non-cardiac surgery has not yet been reached. Primary objective was to evaluate the safety of continuous versus discontinuous use of ASA in the perioperative period in elective general or abdominal surgery. Fifty-two patients undergoing elective cholecystectomy, inguinal hernia repair or colonic/colorectal surgery were recruited to this pilot study. According to cardiological evaluation, non-high-risk patients who were on long-term treatment with low-dose ASA were eligible for inclusion. Patients were allocated randomly to continuous use of ASA or discontinuation of ASA intake for 5 days before until 5 days after surgery. The primary outcome was the incidence of major haemorrhagic and thromboembolic complications within 30 days after surgery. A total of 26 patients were allocated to each study group. One patient (3.8%) in the ASA continuation group required re-operation due to post-operative haemorrhage. In neither study group, further bleeding complications occurred. No clinically apparent thromboembolic events were reported in the ASA continuation and the ASA discontinuation group. Furthermore, there were no significant differences between both study groups in the secondary endpoints. Perioperative intake of ASA does not seem to influence the incidence of severe bleeding in non-high-risk patients undergoing elective general or abdominal surgery. Further, adequately powered trials are required to confirm the findings of this study.

Continuous Acetylsalicylic Acid Treatment Does Not Influence Bleeding Pattern or Outcome of Aneurysmal Subarachnoid Hemorrhage: A Matched-Pair Analysis.

PubMed

Bruder, Markus; Won, Sae-Yeon; Wagner, Marlies; Brawanski, Nina; Dinc, Nazife; Kashefiolasl, Sepide; Seifert, Volker; Konczalla, Juergen

2018-05-01

Demographic changes are leading to an aging society with a growing number of patients with cardiovascular diseases, relying on antiplatelet drugs like acetylsalicylic acid (ASA). Although antiplatelet agents are suspected to be protective not only in the cardiologic but in the neurovascular field, the alteration of the coagulating process could have a major impact on the course and outcome after rupture of intracranial aneurysms. Between June 1999 and December 2014, 1422 patients were treated for aneurysmal SAH in our institution, 144 (10.1%) with continuous ASA at the time of aneurysm rupture. A matched-pair analysis was performed. The rate of patients with continuous ASA treatment while rupture of the aneurysm is rising significantly (P < 0.01). Those patients were significantly older than patients without ASA (60 vs. 53 years, P < 0.001). ASA-treated patients more often had aneurysmal rebleeding (4.7% vs. 2.3%, P = 0.3) and treatment-related hemorrhagic complications (13.9% vs. 6.2%, P = 0.06). However, rates were not different in microsurgical or endovascular procedures (16.4% vs. 12.2%, P = 0.6). Favorable outcome (Modified Rankin Scale 0-2) was achieved in 49.3% of the ASA group and 52.1% of the control group (P = 0.7). Patients with continuous ASA treatment were significantly older than patients without ASA, but there was no difference in admission status or bleeding pattern. Outcome was not different in the matched-pair analysis. There was no statistical difference in treatment related-complication rates of microsurgical and endovascular procedures. Therefore, ASA use should not influence treatment decision of the ruptured aneurysm. Copyright © 2018 Elsevier Inc. All rights reserved.

5-Aminosalicylic acid and chemoprevention: does it work?

PubMed

Lopez, Anthony; Peyrin-Biroulet, Laurent

2013-01-01

5-Aminosalicylic acid (5-ASA)-containing drugs are the mainstay of therapy in inflammatory bowel disease (IBD). Intestinal inflammation is the main risk factor for colorectal cancer (CRC) in IBD. Hence, all drugs that are able to induce and maintain mucosal healing (MH) may prevent CRC risk in IBD. In patients with mild to moderate ulcerative colitis (UC), a recent systematic review of 5-ASA trials demonstrated that MH was achieved in nearly 50% of patients. A systematic review including 48 studies linked 5-ASA chemopreventive properties to five distinct pathways: cell cycle progression, scavenging of reactive oxygen- or nitrogen-derived metabolites, TNF-α/TGF-ss signaling, WNT/β-catenin signaling and antibacterial properties. Therefore, in addition to their overall anti-inflammatory activity on the intestinal mucosa, 5-ASA compounds have specific effects on colorectal carcinogenesis at the molecular level. In 2005, a landmark meta-analysis of observational studies found a protective association between 5-ASA and CRC or a combined end point of CRC/dysplasia in UC patients. More recently, a meta-analysis failed to identify a protective effect of 5-ASA on CRC risk in non-referral populations, but in a separate analysis of 9 clinic-based studies, the pooled odds ratio was 0.58 (95% confidence interval: 0.45-0.75), further highlighting the chemopreventive effect of 5-ASA on CRC risk. In conclusion, 5-ASA therapy may reduce CRC risk by healing the mucosa of UC patients and via specific mechanisms of action at the molecular level. Conducting a clinical trial providing the best level of evidence by comparing UC patients receiving 5-ASA treatment versus those included in a placebo arm would be unethical. © 2013 S. Karger AG, Basel.

Clinical approach on challenge and desensitization procedures with aspirin in patients with ischemic heart disease and nonsteroidal anti-inflammatory drug hypersensitivity.

PubMed

Cortellini, G; Romano, A; Santucci, A; Barbaud, A; Bavbek, S; Bignardi, D; Blanca, M; Bonadonna, P; Costantino, M T; Laguna, J J; Lombardo, C; Losappio, L M; Makowska, J; Nakonechna, A; Quercia, O; Pastorello, E A; Patella, V; Terreehorst, I; Testi, S; Cernadas, J R; Dionicio Elera, J; Lippolis, D; Voltolini, S; Grosseto, D

2017-03-01

Hypersensitivity to acetylsalicylic acid (ASA) constitutes a serious problem for subjects with coronary artery disease. In such subjects, physicians have to choose the more appropriate procedure between challenge and desensitization. As the literature on this issue is sparse, this study aimed to establish in these subjects clinical criteria for eligibility for an ASA challenge and/or desensitization. Collection and analysis of data on ASA challenges and desensitizations from 10 allergy centers, as well as consensus among the related physicians and an expert panel. Altogether, 310 subjects were assessed; 217 had histories of urticaria/angioedema, 50 of anaphylaxis, 26 of nonimmediate cutaneous eruptions, and 17 of bronchospasm related to ASA/nonsteroidal anti-inflammatory drugs (NSAID) intake. Specifically, 119 subjects had index reactions to ASA doses lower than 300 mg. Of the 310 subjects, 138 had an acute coronary syndrome (ACS), 101 of whom underwent desensitizations, whereas 172 suffered from a chronic ischemic heart disease (CIHD), 126 of whom underwent challenges. Overall, 163 subjects underwent challenges and 147 subjects underwent desensitizations; 86 of the latter had index reactions to ASA doses of 300 mg or less. Ten subjects reacted to challenges, seven at doses up to 500 mg, three at a cumulative dose of 110 mg. The desensitization failure rate was 1.4%. In patients with stable CIHD and histories of nonsevere hypersensitivity reactions to ASA/NSAIDs, an ASA challenge is advisable. Patients with an ACS and histories of hypersensitivity reactions to ASA, especially following doses lower than 100 mg, should directly undergo desensitization. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Caffeic acid phenethyl ester protects kidneys against acetylsalicylic acid toxicity in rats.

PubMed

Bozkurt, Yasar; Bozkurt, Mehtap; Turkçu, Gul; Sancaktutar, Ahmet Ali; Soylemez, Haluk; Penbegul, Necmettin; Atar, Murat; Bodakcı, Mehmet Nuri; Hatipoglu, Namık Kemal; Yuksel, Hatice; Kıbrıslı, Erkan; Yavuz, Celal

2012-01-01

The aim of this study was to investigate the protective effect of caffeic acid phenethyl ester (CAPE) on acetylsalicylic acid (ASA)-induced renal damage in rats. A total of 40 rats were randomly divided into five groups, with eight rats in each group-group 1: control, not receiving any medication; group 2: ASA (50 mg/kg/day); group 3: ASA (50 mg/kg/day) + CAPE (20 μg/kg/day); group 4: ASA (100 mg/kg/day); and group 5: ASA (100 mg/kg/day) + CAPE (20 μg/kg/day). ASA and CAPE were given via orogastric gavage for 5 days. The total oxidant status (TOS), total antioxidant capacity (TAC), and paraoxonase-1 (PON-1) activity of the blood samples and kidney tissues were determined. Histopathological examinations of the kidneys were performed using light microscopic methods. The TOS level in the serum of rats and kidney tissues given ASA (groups 2 and 4) significantly increased, but the levels of TAC and PON-1 in these tissues significantly decreased in group 4 when compared with the control rats (p < 0.05). The levels of TAC and PON-1 in the kidney tissues increased and the levels of TOS decreased in the CAPE treatment groups (groups 3 and 5) when compared with the rats in the no CAPE treatment groups (groups 2 and 4). The PON-1, TAC, and TOS values reverted to normal levels in group 5 when compared to group 4 (p < 0.05). These results were supported by histopathological observation. Oxidative stress plays an important role in ASA-induced nephrotoxicity, and CAPE may protect against ASA-induced nephrotoxicity in rats.

Asiago spectroscopic classification of ASAS-SN18ao

NASA Astrophysics Data System (ADS)

Tomasella, L.; Benetti, S.; Cappellaro, E.; Turatto, M.

2018-01-01

The Asiago Transient Classification Program (Tomasella et al. 2014, AN, 335, 841) reports the spectroscopic classification of ASAS-SN18ao (aka AT2018gm, Atel #11178) discovered during the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN, Shappee et al. 2014).

The role of ethnicity, sexual attitudes, and sexual behavior in sexual revictimization during the transition to emerging adulthood.

PubMed

Rinehart, Jenny K; Yeater, Elizabeth A; Musci, Rashelle J; Letourneau, Elizabeth J; Lenberg, Kathryn L

2014-01-01

An experience of child sexual abuse (CSA) substantially increases women's risk of adult sexual assault (ASA), but the mechanisms underlying this relationship are unclear. Previous research often has not examined the full range of ASA experiences or included the influence of ethnicity, sexual behavior, and sexual attitudes on CSA and severity of ASA. The current study utilized path analysis to explore the relationships among ethnicity, sexual attitudes, number of lifetime sexual partners, CSA, and severity of ASA in emerging adult women. Results indicated a significant relationship between CSA and more severe ASA that was partially explained by having more lifetime sexual partners. Additionally, European American women, relative to Hispanic women, reported more severe victimization, which was fully explained by more positive attitudes toward casual sex and having more lifetime sexual partners. These results have implications in the design and implementation of universal and selective prevention programs aimed at reducing ASA and revictimization among emerging adult women. © The Author(s) 2014.

The ASAS-SN catalogue of variable stars I: The Serendipitous Survey

NASA Astrophysics Data System (ADS)

Jayasinghe, T.; Kochanek, C. S.; Stanek, K. Z.; Shappee, B. J.; Holoien, T. W.-S.; Thompson, Toda A.; Prieto, J. L.; Dong, Subo; Pawlak, M.; Shields, J. V.; Pojmanski, G.; Otero, S.; Britt, C. A.; Will, D.

2018-07-01

The All-Sky Automated Survey for Supernovae (ASAS-SN) is the first optical survey to routinely monitor the whole sky with a cadence of ˜2-3 d down to V ≲ 17 mag. ASAS-SN has monitored the whole sky since 2014, collecting ˜100-500 epochs of observations per field. The V-band light curves for candidate variables identified during the search for supernovae are classified using a random forest classifier and visually verified. We present a catalogue of 66 179 bright, new variable stars discovered during our search for supernovae, including 27 479 periodic variables and 38 700 irregular variables. V-band light curves for the ASAS-SN variables are available through the ASAS-SN variable stars data base (https://asas-sn.osu.edu/variables). The data base will begin to include the light curves of known variable stars in the near future along with the results for a systematic, all-sky variability survey.

Sexual Assault Disclosure and Sexual Functioning: The Role of Trauma Symptomatology.

PubMed

Staples, Jennifer M; Eakins, Danielle; Neilson, Elizabeth C; George, William H; Davis, Kelly Cue; Norris, Jeanette

2016-10-01

Previous research has demonstrated that a history of adult sexual assault (ASA) is associated with negative outcomes, including trauma symptomatology and fear of sexual intimacy. Disclosing sexual assault might be protective against such negative outcomes. To examine the indirect effect of trauma symptomatology on the association between disclosing ASA and current sexual functioning. Participants included 652 women 21 to 30 years old with a history of ASA recruited from the community. Participants completed self-report measurements on a computer. Separate models were performed, with sexual functioning divided into sexual desire, orgasm, and pain during sex. ASA disclosure was indirectly associated with sexual orgasm and pain during sex by trauma symptomatology. However, there was no indirect effect of trauma symptomatology on the relation between ASA disclosure and sexual desire. Disclosing experiences of ASA could serve a protective function by lessening trauma symptomatology, thereby mitigating impacts on aspects of sexual functioning, such as orgasm and pain. Published by Elsevier Inc.

Aspirin Increases the Solubility of Cholesterol in Lipid Membranes

NASA Astrophysics Data System (ADS)

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

2014-03-01

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

Is There Evidence for Systematic Upcoding of ASA Physical Status Coincident with Payer Incentives? A Regression Discontinuity Analysis of the National Anesthesia Clinical Outcomes Registry.

PubMed

Schonberger, Robert B; Dutton, Richard P; Dai, Feng

2016-01-01

Modifications in physician billing patterns have been shown to occur in response to payer incentives, but the phenomenon remains largely unexplored in billing for anesthesia services. Within the field of anesthesiology, Medicare's policy not to provide additional reimbursement for higher ASA physical status scores contrasts with the practices of most private payers, and this pattern of reimbursement introduces a change in billing incentives once patients attain Medicare eligibility. We hypothesized that, coincident with the onset of widespread Medicare eligibility at age 65 years, a discontinuity in reported ASA physical status scores would be observed after controlling for the underlying trend of increasing ASA physical status scores with age. This phenomenon would manifest as a pattern of upcoding of ASA physical status scores for patients younger than 65 years that would become less common in patients age 65 years and older. Using data on age, sex, ASA physical status scores, and type of surgery from the National Anesthesia Clinical Outcomes Registry, we used a quasi-experimental regression discontinuity design to analyze whether there was evidence for a discontinuity in reported ASA physical status scores occurring at age 65 years for the nondeferrable anesthesia services accompanying hip, femur, or lower leg fracture repair. A total of 49,850 records were analyzed. In models designed to detect regression discontinuity at 65 years of age, neither the binary variable "age ≥ 65" nor the interaction term of age × age ≥ 65 was a statistically significant predictor of the outcome of ASA physical status score. The statistical inference was unchanged when ASA physical status scores were reclassified as a binary outcome (I-II vs III-V) and when different bandwidths around age 65 years were used. To test the validity of our study design for detecting regression discontinuity, simulations of the occurrence of deliberate upcoding of ASA physical status scores demonstrated the ability to detect deliberate upcoding occurring at rates exceeding 2% of eligible cases of patients younger than 65 years. We found no evidence for a significant discontinuity in the pattern of ASA physical status scores coincident with Medicare eligibility at age 65 years for the nondeferrable conditions of hip, femur, or lower leg fracture repair. Our data do not support the presence of fraudulent ASA physical status scoring among National Anesthesia Clinical Outcomes Registry contributors. If deliberate upcoding of ASA physical status scores is present in our data, the behavior is either too rare or too insensitive to the removal of payer incentives at age 65 years to be evident in the present analysis.

Quantifying Interactions of Nucleobase Atoms with Model Compounds for the Peptide Backbone and Glutamine and Asparagine Side Chains in Water.

PubMed

Cheng, Xian; Shkel, Irina A; Molzahn, Cristen; Lambert, David; Karim, Rezwana; Record, M Thomas

2018-04-17

Alkylureas display hydrocarbon and amide groups, the primary functional groups of proteins. To obtain the thermodynamic information that is needed to analyze interactions of amides and proteins with nucleobases and nucleic acids, we quantify preferential interactions of alkylureas with nucleobases differing in the amount and composition of water-accessible surface area (ASA) by solubility assays. Using an established additive ASA-based analysis, we interpret these thermodynamic results to determine interactions of each alkylurea with five types of nucleobase unified atoms (carbonyl sp 2 O, amino sp 3 N, ring sp 2 N, methyl sp 3 C, and ring sp 2 C). All alkylureas interact favorably with nucleobase sp 2 C and sp 3 C atoms; these interactions become more favorable with an increasing level of alkylation of urea. Interactions with nucleobase sp 2 O are most favorable for urea, less favorable for methylurea and ethylurea, and unfavorable for dialkylated ureas. Contributions to overall alkylurea-nucleobase interactions from interactions with each nucleobase atom type are proportional to the ASA of that atom type with proportionality constant (interaction strength) α, as observed previously for urea. Trends in α-values for interactions of alkylureas with nucleobase atom types parallel those for corresponding amide compound atom types, offset because nucleobase α-values are more favorable. Comparisons between ethylated and methylated ureas show interactions of amide compound sp 3 C with nucleobase sp 2 C, sp 3 C, sp 2 N, and sp 3 N atoms are favorable while amide sp 3 C-nucleobase sp 2 O interactions are unfavorable. Strongly favorable interactions of urea with nucleobase sp 2 O but weakly favorable interactions with nucleobase sp 3 N indicate that amide sp 2 N-nucleobase sp 2 O and nucleobase sp 3 N-amide sp 2 O hydrogen bonding (NH···O═C) interactions are favorable while amide sp 2 N-nucleobase sp 3 N interactions are unfavorable. These favorable amide-nucleobase hydrogen bonding interactions are prevalent in specific protein-nucleotide complexes.

Impact of acetylsalicylic Acid on the clinicopathological characteristics and prognosis of patients with invasive breast cancer.

PubMed

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

2014-04-01

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

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

PubMed Central

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

2013-01-01

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

Salicylate pre-treatment attenuates intensity of bronchial and nasal symptoms precipitated by aspirin in aspirin-intolerant patients.

PubMed

Nizankowska, E; Dworski, R; Soja, J; Szczeklik, A

1990-11-01

Aspirin (ASA) and other non-steroidal anti-inflammatory drugs, which are cyclooxygenase (COX) inhibitors, precipitate asthmatic attacks in ASA-intolerant patients, while sodium salicylate, hardly active on COX by itself, is well tolerated by these patients. However, salicylate moiety appears to interfere with aspirin inhibitory action on platelets and vascular COX. Such interaction, if present at the level of respiratory tract, may be of interest to pathogenesis of ASA-induced asthma. We performed a double-blind, placebo-controlled, randomized cross-over study on the effect of choline magnesium trisalicylate (CMT, trilisate) pre-treatment on ASA-induced adverse reactions in nine patients. Pulmonary function tests, nasal symptoms score, PNIF and serum salicylate levels were monitored following challenges with threshold doses of ASA. Trilisate administered at a dose of 3000 mg daily for 3 days, offered a moderate protection against ASA-induced symptoms; it diminished the severity and/or delayed the appearance of FEV1 fall. Maximal decreases in FEV1 as well as reaction intensity indexes were significantly lower (P less than 0.02 and P less than 0.002, respectively) after trilisate pre-treatment as compared to placebo. Trilisate also attenuated nasal symptoms in three out of five patients. Although the precise mechanism of the protective action of trilisate is unknown, our data support the possibility of interaction between salicylate and ASA on cyclo-oxygenase locus in the respiratory tract in ASA-intolerant patients.

Replacing the acetyl linkage in aspirin with choline and magnesium moieties reduces the occurrence of gastric mucosal injury.

PubMed

Danesh, B J; Nelson, L M; Russell, R I; Docherty, C

1987-02-01

The acetyl moiety in aspirin (acetyl salicylic acid: ASA) is considered to play a major part in the pathogenesis of ASA-induced mucosal injury. At equivalent salicylate doses and pH values, the induction of acute gastric mucosal haemorrhagic erosions in rats by ASA and choline magnesium trisalicylate (CMT), a new non-acetylated salicylate, with and without the potentiating damaging effect of taurodeoxycholic acid (TDCA) were compared. Test solutions were administered by per oral intubation to five groups of fasting Sprague-Dawley rats (n = 24). Gastric mucosa were examined after 4 hours and mucosal injury assessed by a lesion-scoring system. The incidence and severity (median lesion scores with quartiles) of the lesions were 83% and 13 (7:20) respectively for ASA (128 mg kg-1) compared with 17% and 0 (0:0) for CMT (128 mg kg-1) (P less than 0.001 and P less than 0.001). TDCA increased mucosal damage to 100% and 29 (20:34) for ASA compared with 30% and 0 (0:4) for CMT (P less than 0.001) and P less than 0.001). Serum salicylate levels (median values of 1.4 for ASA and 1.5 mmol litre-1 for CMT) were not significantly different. It is concluded that replacing the acetyl moiety in ASA with choline and magnesium moieties reduces the ASA-induced mucosal injury, without affecting blood salicylate concentrations.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-30

... strategy consistent with its current fundamental investment policy and to achieve its desired portfolio... approval of its shareholders, ASA replaced its fundamental investment policies that, among other things... SECURITIES AND EXCHANGE COMMISSION [Investment Company Act Release No. 30539; 812-13877] ASA Gold...

Nutrient and Food Group Analysis in the 2016 ASA24® System

Cancer.gov

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

Ontogenetic changes in vitamin C in selected rice varieties

USDA-ARS?s Scientific Manuscript database

Vitamin C (L-ascorbic acid, AsA) is a key antioxidant for both plants and animals. In plants, AsA is involved in several key physiological processes including photosynthesis, cell expansion, cell division, growth, flowering, and senescence. In addition, AsA is an enzyme cofactor and a regulator of...

ExSPO: A Discovery Class Apodized Square Aperture (ASA) Expo-Planet Imaging Space Telescope Concept

NASA Technical Reports Server (NTRS)

Gezari, D.; Harwit, M.; Lyon, R.; Melnick, G.; Papaliolos, G.; Ridgeway, S.; Woodruff, R.; Nisenson, P.; Oegerle, William (Technical Monitor)

2002-01-01

ExSPO is a Discovery Class (approx. 4 meter) apodized square aperture (ASA) space telescope mission designed for direct imaging of extrasolar Earth-like planets, as a precursor to TPF. The ASA telescope concept, instrument design, capabilities, mission plan and science goals are described.

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

PubMed

Fuertes Ferre, Georgina; Ferrer Gracia, Maria Cruz; Calvo Cebollero, Isabel

2015-09-21

Dual antiplatelet therapy is essential in patients undergoing percutaneous coronary intervention with stent implantation. Hypersensitivity to acetylsalicylic acid (ASA) limits treatment options. Desensitization to ASA has classically been studied in patients with respiratory tract disease. Over the last years, many protocols have been described about ASA desensitization in patients with ischemic heart disease, including acute coronary syndrome and the need for coronary stent implantation. It is important to know the efficacy and safety of ASA desensitization in these patients. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Double-blind comparative trial of indoprofen and acetylsalicylic acid in osteoarthritis.

PubMed

Katona, G

1981-01-01

The effectiveness, safety and acceptability of indoprofen (IP) and acetylsalicylic acid (ASA) were assessed in patients with osteoarthritis, in a double-blind comparative trial. Each patient received IP 600 mg/day or ASA 2100 mg/day for a four-week period; after a one-week wash-out period, the same drug was given at a higher dosage (IP 800 or ASA 2800 mg/day) for another four weeks. Seventeen patients on indoprofen and 14 on SAS completed the trial. A significant improvement was obtained with indoprofen in the different parameters measuring pain, from the first treatment period; results were similar at the end of the second period. Results with ASA, at both dosages, appeared less impressive. Two patients on indoprofen and five on ASA complained of side effects.

Lack of cross-reactivity between 5-aminosalicylic acid-based drugs: a case report and review of the literature.

PubMed

Kung, Shiang-Ju; Choudhary, Cuckoo; McGeady, Stephen J; Cohn, John R

2006-09-01

5-Aminosalicylic acid (5-ASA)-containing drugs are the mainstay of therapy in inflammatory bowel disease, but adverse reactions to these medications are relatively common. Because there may be a lack of cross-reactivity among the various 5-ASA formulations, treatment with alternative preparations is sometimes possible even after an apparent allergic reaction to a 5-ASA product. To describe a patient with a possible allergy to 2 different 5-ASA drugs who tolerated a third. A 27-year-old man with Crohn disease developed a rash while taking mesalamine (Pentasa and Asacol). Treatment with 5-ASA products was discontinued, and 6-mercaptopurine and prednisone were prescribed. He then experienced multiorgan failure secondary to herpes simplex infection, which required discontinuation of the immunosuppressive therapy. After recovery from the acute infection, he underwent successful graded challenge with balsalazide. The patient continued treatment with balsalazide for 9 months, with good control of his inflammatory bowel disease and no adverse effects. Adverse reactions to 1 or more 5-ASA medications do not necessarily preclude the use of others in the same class. A treatment algorithm for patients with adverse reactions to 5-ASA is outlined based on the case report and review of the literature.

Evaluating the feasibility of utilizing the Automated Self-administered 24-hour (ASA24) dietary recall in a sample of multiethnic older adults

PubMed Central

Ettienne-Gittens, Reynolette; Boushey, Carol J.; Au, Donna; Murphy, Suzanne P.; Lim, Unhee; Wilkens, Lynne

2016-01-01

The ASA24 is a web application which enables the collection of self-administered dietary recalls thus utilizing technology to overcome some of the limitations of traditional assessment methodologies. Older adults, particularly those from certain ethnic groups may have less access to and may be less receptive to technology. This research sought to determine the level of access to the internet as well as evaluate the feasibility of using a web-based alternative dietary data collection method in older, multiethnic adults. Participants completed three telephone administered diet recalls (n=347), and were asked to complete a one day recall via the ASA24. They were also asked to evaluate their experience with using the ASA24 system. Almost 60% of the participants reported no access to a computer or internet access, with African Americans and Latinos less likely than non-Hispanic Whites and Japanese-Americans to have access. Of those with access to the internet (n=100), 44% of the participants accessed the ASA24 system and 37% successfully launched the ASA24 program. However, most respondents preferred the traditional diet recall methodology over the ASA24. Further research is needed to investigate recruitment and use of electronic data collection methodologies in older adults. PMID:28149712

Acetylsalicylic acid (aspirin) reduces damage to reconstituted human tissues infected with Candida species by inhibiting extracellular fungal lipases

PubMed Central

Trofa, David; Agovino, Mariangela; Stehr, Frank; Schäfer, Wilhelm; Rykunov, Dmitry; Fiser, András; Hamari, Zsuzsanna; Nosanchuk, Joshua D.; Gácser, Attila

2009-01-01

A reconstituted human tissue model was used to mimic Candida albicans and Candida parapsilosis infection in order to investigate the protective effects of acetylsalicylic acid (aspirin, ASA). We found that therapeutic concentrations of ASA reduced tissue damage in the in vitro infection model. We further evaluated the lipase inhibitory effects of ASA by investigating the growth of C. albicans, C. parapsilosis and C. parapsilosis lipase negative (Δcplip1-2/Δcplip1-2) mutants in a lipid rich minimal medium supplemented with olive oil and found that a therapeutic concentration of ASA inhibited the growth of wild type fungi. The lipase inhibitors quinine and ebelactone B were also shown to reduce growth and protect against tissue damage from Candida species, respectively. A lipolytic activity assay also showed that therapeutic concentrations of ASA inhibited C. antarctica and C. cylindracea purified lipases obtained through a commercial kit. The relationship between ASA and lipase was characterized through a computed structural model of the Lipase-2 protein from C. parapsilosis in complex with ASA. The results suggest that development of inhibitors of fungal lipases could result in broad-spectrum therapeutics, especially since fungal lipases are not homologous to their human analogues. PMID:19703582

Demonstration of the analgesic efficacy and dose-response of acetylsalicylic acid with pseudoephedrine.

PubMed

Schachtel, Bernard P; Voelker, Michael; Sanner, Kathleen M; Gagney, Diana; Bey, Mary; Schachtel, Emily J; Becka, Michael

2010-12-01

To determine acute analgesia by acetylsalicylic acid (ASA) when combined with pseudoephedrine (PSE) in patients with upper respiratory tract infection (URTI), we used the sore throat pain model to measure single-dose effects of ASA 500 mg/PSE 30 mg, ASA 1000 mg/PSE 60 mg, and acetaminophen (APAP) 1000 mg/PSE 60 mg (serving as a positive control). Under double-blind, randomized, placebo-controlled conditions, 640 adult patients with confirmed acute pharyngitis and rhinosinusitis associated with URTI rated throat pain intensity and relief at intervals over 6 hours. Efficacy was demonstrated for both doses of ASA/PSE compared with placebo for all end points, including total pain relief and summed pain intensity differences, beginning at 20 minutes on both scales (all P < .05), and the efficacy of APAP/PSE compared with placebo was confirmed (P < .01). Greater differences in pain relief and intensity were also demonstrated between the higher and lower doses of ASA/PSE (P < .05), in particular, among 329 patients with severe pain, as well as between ASA 1000 mg/PSE 60 mg and APAP 1000 mg/PSE 60 mg (P < .05). No serious adverse events were reported. This study demonstrates that ASA is a well-tolerated and effective analgesic in 500- and 1000-mg doses when combined with pseudoephedrine.

Enzymatic Production of Ascorbic Acid-2-phosphate by Recombinant Acid Phosphatase.

PubMed

Zheng, Kai; Song, Wei; Sun, Anran; Chen, Xiulai; Liu, Jia; Luo, Qiuling; Wu, Jing

2017-05-24

In this study, an environmentally friendly and efficient enzymatic method for the synthesis of l-ascorbic acid-2-phosphate (AsA-2P) from l-ascorbic acid (AsA) was developed. The Pseudomonas aeruginosa acid phosphatase (PaAPase) was expressed in Escherichia coli BL21. The optimal temperature, optimal pH, K m , k cat , and catalytic efficiency of recombinant PaAPase were 50 °C, 5.0, 93 mM, 4.2 s -1 , and 2.7 mM -1 min -1 , respectively. The maximal dry cell weight and PaAPase phosphorylating activity reached 8.5 g/L and 1127.7 U/L, respectively. The highest AsA-2P concentration (50.0 g/L) and the maximal conversion (39.2%) were obtained by incubating 75 g/L intact cells with 88 g/L AsA and 160 g/L sodium pyrophosphate under optimal conditions (0.1 mM Ca 2+ , pH 4.0, 30 °C) for 10 h; the average AsA-2P production rate was 5.0 g/L/h, and the AsA-2P production system was successfully scaled up to a 7.5 L fermenter. Therefore, the enzymatic process showed great potential for production of AsA-2P in industry.

ASA grade and Charlson Comorbidity Index of spinal surgery patients: correlation with complications and societal costs.

PubMed

Whitmore, Robert G; Stephen, James H; Vernick, Coleen; Campbell, Peter G; Yadla, Sanjay; Ghobrial, George M; Maltenfort, Mitchell G; Ratliff, John K

2014-01-01

The Charlson Comorbidity Index (CCI) and the American Society of Anesthesiologists (ASA) Physical Status Classification System (ASA grade) are useful for predicting morbidity and mortality for a variety of disease processes. To evaluate CCI and ASA grade as predictors of complications after spinal surgery and examine the correlation between these comorbidity indices and the cost of care. Prospective observational study. All patients undergoing any spine surgery at a single academic tertiary center over a 6-month period. Direct health-care costs estimated from diagnosis related group and Current Procedural Terminology (CPT) codes. Demographic data, including all patient comorbidities, procedural data, and all complications, occurring within 30 days of the index procedure were prospectively recorded. Charlson Comorbidity Index was calculated from International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes and ASA grades determined from the operative record. Diagnosis related group and CPT codes were captured for each patient. Direct costs were estimated from a societal perspective using Medicare rates of reimbursement. A multivariable analysis was performed to assess the association of the CCI and ASA grade to the rate of complication and direct health-care costs. Two hundred twenty-six cases were analyzed. The average CCI score for the patient cohort was 0.92, and the average ASA grade was 2.65. The CCI and ASA grade were significantly correlated, with Spearman ρ of 0.458 (p<.001). Both CCI and ASA grade were associated with increasing body mass index (p<.01) and increasing patient age (p<.0001). Increasing CCI was associated with an increasing likelihood of occurrence of any complication (p=.0093) and of minor complications (p=.0032). Increasing ASA grade was significantly associated with an increasing likelihood of occurrence of a major complication (p=.0035). Increasing ASA grade showed a significant association with increasing direct costs (p=.0062). American Society of Anesthesiologists and CCI scores are useful comorbidity indices for the spine patient population, although neither was completely predictive of complication occurrence. A spine-specific comorbidity index, based on ICD-9-CM coding that could be easily captured from patient records, and which is predictive of patient likelihood of complications and mortality, would be beneficial in patient counseling and choice of operative intervention. Copyright © 2014 Elsevier Inc. All rights reserved.

A Performance Assessment of an Airborne Separation Assistance System Using Realistic Complex Traffic Flows

NASA Technical Reports Server (NTRS)

Smith, Jeremy C.; Bussink, Frank J. L.

2008-01-01

This paper presents the results from a study that investigates the performance of a tactical Airborne Separation Assistance System (ASAS) in en route airspace, under varying demand levels, with realistic traffic flows. The ASAS concept studied here allows flight crews of equipped aircraft to perform separation from other air traffic autonomously. This study addresses the tactical aspects of an ASAS using aircraft state data (i.e. position and velocity) to detect and resolve projected conflicts. In addition, use of a conflict prevention system helps ASAS-equipped aircraft avoid maneuvers that may cause new conflicts. ASAS-capable aircraft are equipped with satellite-based navigation and Automatic Dependent Surveillance Broadcast (ADS-B) for transmission and receipt of aircraft state data. In addition to tactical conflict detection and resolution (CD&R), a complete, integrated ASAS is likely to incorporate a strategic CD&R component with a longer look-ahead time, using trajectory intent information. A system-wide traffic flow management (TFM) component, located at the FAA command center helps aircraft to avoid regions of excessive traffic density and complexity. A Traffic Alert and Collision Avoidance System (TCAS), as used today is the system of last resort. This integrated approach avoids sole reliance on the use of the tactical CD&R studied here, but the tactical component remains a critical element of the complete ASAS. The focus of this paper is to determine to what extent the proposed tactical component of ASAS alone can maintain aircraft separation at demand levels up to three times that of current traffic. The study also investigates the effect of mixing ASAS-equipped aircraft with unequipped aircraft (i.e. current day) that do not have the capability to self-separate. Position and velocity data for unequipped aircraft needs to be available to ASASequipped. Most likely, for this future concept, state data would be available from instrument flight rules (IFR) aircraft, equipped with at least ADS-B transmission capability. The objective is to reduce the number of losses of separation to a minimum and investigate the limits of tactical-only CD&R. Thus, the objective is not, expressly, to achieve zero losses of separation with tactical ASAS because this is one component of an integrated ASAS.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xianwei, E-mail: XWang2@UAMS.edu; Lu, Jingjun; Khaidakov, Magomed

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 cardiacmore » fibroblasts challenged with Ang II. Mouse heart fibroblasts were isolated and treated with Ang II with or without ASA. As expected, Ang II induced AT1R expression, and stimulated cardiac fibroblast growth and collagen synthesis. The AT1R blocker losartan attenuated these effects of Ang II. Similarly to losartan, ASA, and its SA moiety suppressed Ang II-mediated AT1R transcription and fibroblast proliferation as well as expression of collagens and MMPs. ASA also suppressed the expression of NADPH oxidase subunits (p22{sup phox}, p47{sup phox}, p67{sup phox}, NOX2 and NOX4) and ROS generation. ASA did not affect total NF-κB p65, but inhibited its phosphorylation and activation. These observations suggest that ASA inhibits Ang II-induced NADPH oxidase expression, NF-κB activation and AT1R transcription in cardiac fibroblasts, and fibroblast proliferation and collagen expression. The critical role of NADPH oxidase activity in stimulation of AT1R transcription became apparent in experiments where ASA also inhibited AT1R transcription in cardiac fibroblasts challenged with H{sub 2}O{sub 2}. Since SA had similar effect as ASA on AT1R expression, we suggest that ASA's effect is mediated by its SA moiety. -- Highlights: ► Aspirin in therapeutic concentrations decreases mouse cardiac fibroblast growth and collagen formation. ► Aspirin decreases the transcription of angiotensin II type 1 receptor by inhibiting NADPH oxidase–NF-κB pathway. ► The inhibition of angiotensin II type 1 receptor expression may be the basis for reduction in fibroblast growth and collagen formation. ► The effects of aspirin appear to be mediated via its salicylate moiety.« less

Oil spills abatement: factors affecting oil uptake by cellulosic fibers.

PubMed

Payne, Katharine C; Jackson, Colby D; Aizpurua, Carlos E; Rojas, Orlando J; Hubbe, Martin A

2012-07-17

Wood-derived cellulosic fibers prepared in different ways were successfully employed to absorb simulated crude oil, demonstrating their possible use as absorbents in the case of oil spills. When dry fibers were used, the highest sorption capacity (six parts of oil per unit mass of fiber) was shown by bleached softwood kraft fibers, compared to hardwood bleached kraft and softwood chemithermomechanical pulp(CTMP) fibers. Increased refining of CTMP fibers decreased their oil uptake capacity. When the fibers were soaked in water before exposure to the oil, the ability of the unmodified kraft fibers to sorb oil was markedly reduced, whereas the wet CTMP fibers were generally more effective than the wet kraft fibers. Predeposition of lignin onto the surfaces of the bleached kraft fibers improved their ability to take up oil when wet. Superior ability to sorb oil in the wet state was achieved by pretreating the kraft fibers with a hydrophobic sizing agent, alkenylsuccinic anhydride (ASA). Contact angle tests on a model cellulose surface showed that some of the sorption results onto wetted fibers could be attributed to the more hydrophobic nature of the fibers after treatment with either lignin or ASA.

An assessment of the inter-rater reliability of the ASA physical status score in the orthopaedic trauma population.

PubMed

Ihejirika, Rivka C; Thakore, Rachel V; Sathiyakumar, Vasanth; Ehrenfeld, Jesse M; Obremskey, William T; Sethi, Manish K

2015-04-01

Although recent literature has demonstrated the utility of the ASA score in predicting postoperative length of stay, complication risk and potential utilization of other hospital resources, the ASA score has been inconsistently assigned by anaesthesia providers. This study tested the reliability of assignment of the ASA score classification by both attending anaesthesiologists and anaesthesia residents specifically among the orthopaedic trauma patient population. Nine case-based scenarios were created involving preoperative patients with isolated operative orthopaedic trauma injuries. The cases were created and assigned a reference score by both an attending anaesthesiologist and orthopaedic trauma surgeon. Attending and resident anaesthesiologists were asked to assign an ASA score for each case. Rater versus reference and inter-rater agreement amongst respondents was then analyzed utilizing Fleiss's Kappa and weighted and unweighted Cohen's Kappa. Thirty three individuals provided ASA scores for each of the scenarios. The average rater versus reference reliability was substantial (Kw=0.78, SD=0.131, 95% CI=0.73-0.83). The average rater versus reference Kuw was also substantial (Kuw=0.64, SD=0.21, 95% CI=0.56-0.71). The inter-rater reliability as evaluated by Fleiss's Kappa was moderate (K=0.51, p<.001). An inter-rater comparison within the group of attendings (K=0.50, p<.001) and within the group of residents were both moderate (K=0.55, p<.001). There was a significant increase in the level of inter-rater reliability from the self-reported 'very uncomfortable' participants to the 'very comfortable' participants (uncomfortable K=0.43, comfortable K=0.59, p<.001). This study shows substantial agreement strength for reliability of the ASA score among anaesthesiologists when evaluating orthopaedic trauma patients. The significant increase in inter-rater reliability based on anaesthesiologists' comfort with the ASA scoring method implies a need for further evaluation of ASA assessment training and routine use on the ground. These findings support the use of the ASA score as a statistically reliable tool in orthopaedic trauma. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Epidemiology of Anti-Sperm Antibodies Among Couples with Unexplained Infertility in North West Bank, Palestine.

PubMed

Yasin, Anas Lotfi; Yasin, Ahmad Lotfi; Basha, Walid Salim

2016-03-01

Anti sperm antibodies (ASA) can present in serum and semen and they may lead to impair the sperms function leading to infertility. The precise mechanism of generation of these antibodies is yet to be discovered. This study was performed to determine the prevalence of anti-sperm antibodies (ASA) in patients with unexplained infertility. The study was initiated also to explore the possible factors that may associate with ASA formation and how ASA status is associated with pregnancy rates after going with in vitro fertilization - intracytoplasmic sperm injection (IVF-ICSI). A cross-sectional study was conducted on 42 normal infertile couples consulting Razan Medical Center for Infertility & I.V.F. in Nablus, Palestine, from December 2012 - March 2013. Serum levels of immunoglobulins G (IgG) ASA were measured in participants (males and females) using enzyme-linked immunosorbent assay (ELISA). In addition, participants also filled a questionnaire about the presence of previous varicocele repair, inguinal hernia repair, orchitis, testicular trauma and vasectomy reversal among males and severe coitus bleeding and coitus during menses or puerperium among females. Couples were also asked about previous IVF-ICSI procedures and the outcome of the procedure in terms of either they got pregnant or not. Data was analysed using SPSS software. The prevalence of ASA was 14.3% (6/42) among all couples, 9.5% (4/42) among males and 4.8% (2/42) among females. There was no significant relationship between previous varicocele repair, previous inguinal hernia repair, or orchitis and formation of ASA (p value =0.64, 0.56, and 0.26 respectively). Previous trauma, vasovasostomy, severe coitus bleeding and coitus during menses or puerperium were not observed in any of the study sample. ASA did not seem to affect the outcome of IVF-ICSI (p-value =0.54). Prevalence of ASA in infertile couples in the north part of Palestine is similar to that obtained worldwide. ASA formation does not relate to any of the studied risk factors and does not seem to associate with pregnancy rate after IVF-ICSI. We recommend further studies using a larger sample size and including all parts of Palestine in order to generalize the obtained results.

Effects of low-dose acetylsalicylic acid and atherosclerotic vascular diseases on the outcome in patients with severe sepsis or septic shock.

PubMed

Otto, Gordon Philipp; Sossdorf, Maik; Boettel, Janina; Kabisch, Björn; Breuel, Hannes; Winning, Johannes; Lösche, Wolfgang

2013-01-01

Sepsis and its sequelae of multiple organ failure is one of the leading causes of death in the industrial countries. Several studies have shown that patients who are treated with low-dose acetyl salicylic acid (ASA) for secondary prevention of atherothrombosis may have a lower risk to develop organ failure in the case of critical illness. The benefit of ASA is probably due to an inhibition of platelet activation as well as an increase in the formation of anti-inflammatory lipoxin A4. On the other hand, the effect of ASA could be - at least partially - an indirect one, caused by atherosclerotic vascular diseases as the cause of ASA treatment. Atherosclerosis is considered as a moderate systemic inflammation and we hypothesise that this chronic condition could have an impact on the outcome in sepsis. To get more information on the benefit of ASA in critically ill patients and on possible interference with atherosclerotic vascular diseases, we analysed the medical records of 886 septic patients who were admitted to the surgical intensive care unit (ICU) of a university hospital. Logistic regression analysis indicated that patients who were treated during the ICU stay with ASA (100 mg/d) had a significantly lower mortality. Odds ratios (ORs; with 95% confidential intervals) of 0.56 (0.37-0.84) and 0.57 (0.39-0.83) were calculated for ICU and hospital mortality, respectively. In contrast, statin treatment did not have significant effect on mortality. Diagnosis of atherosclerotic vascular diseases according to ICD classification did not influence ICU mortality but lowered hospital mortality (OR = 0.71 (0.52-0.99)). Subgroup analysis provided preliminary evidence that clopidogrel when given as only anti-platelet drug may have a similar benefit as ASA, but the combination of ASA and clopidogrel failed to improve the outcome. The time course of plasma fibrinogen and procalcitonin levels indicate that ASA seems to reduce the activation of haemostasis and increase the resolution of inflammation. It is concluded that prospective interventional studies should be done to test the use of ASA as novel therapeutic approach in critically ill patients.

Acetylsalicylic acid (aspirin) test for the diagnosis of renovascular hypertension.

PubMed

Gluszek, J; Posadzy-Malaczynska, A; Tykarski, A; Pupek-Musialik, D; Gracz, M; Kara-Perz, H

1997-06-01

To determine whether the administration of acetylsalicylic acid (ASA, also known as Aspirin) differentiates patients with renovascular hypertension from those with essential hypertension, in order to provide a simple alternative to more expensive forms of diagnosis for this condition. Trial of ASA test in patients with previously diagnosed essential and renovascular hypertension. Inpatient department of an academic health sciences centre in Poznan, Poland. Forty patients with essential hypertension and 21 patients with renovascular hypertension. Patients were given an intravenous injection of ASA (10 mg/kg body weight), blood pressure was measured and blood was sampled and assayed for plasma renin activity (PRA) before and 30 minutes after the injection. ASA infusion in patients with renovascular hypertension resulted in a decrease in PRA from 15.2 (standard deviation [SD] 12.4) ng/mL per hour to 7.2 (SD 9.8) ng/mL per hour, whereas in patients with essential hypertension the initial PRA was significantly lower before ASA administration and did not change afterward. In patients with renovascular hypertension, the mean systolic, diastolic and arterial pressure decreased significantly (p < 0.001) after ASA infusion, but these did not change in patients with essential hypertension. Based on the criterion of 4 mm Hg as a detectable decrease in mean blood pressure, the sensitivity of the ASA test was 95.0% and the specificity 82.5%; its positive predictive value was 74% and its negative predictive value 97%. The precise measurement of blood pressure during the ASA test may provide a useful method of differentiating between patients with renovascular and essential hypertension.

Ascorbic Acid-A Potential Oxidant Scavenger and Its Role in Plant Development and Abiotic Stress Tolerance

PubMed Central

Akram, Nudrat A.; Shafiq, Fahad; Ashraf, Muhammad

2017-01-01

Over-production of reactive oxygen species (ROS) in plants under stress conditions is a common phenomenon. Plants tend to counter this problem through their ability to synthesize ROS neutralizing substances including non-enzymatic and enzymatic antioxidants. In this context, ascorbic acid (AsA) is one of the universal non-enzymatic antioxidants having substantial potential of not only scavenging ROS, but also modulating a number of fundamental functions in plants both under stress and non-stress conditions. In the present review, the role of AsA, its biosynthesis, and cross-talk with different hormones have been discussed comprehensively. Furthermore, the possible involvement of AsA-hormone crosstalk in the regulation of several key physiological and biochemical processes like seed germination, photosynthesis, floral induction, fruit expansion, ROS regulation and senescence has also been described. A simplified and schematic AsA biosynthetic pathway has been drawn, which reflects key intermediates involved therein. This could pave the way for future research to elucidate the modulation of plant AsA biosynthesis and subsequent responses to environmental stresses. Apart from discussing the role of different ascorbate peroxidase isoforms, the comparative role of two key enzymes, ascorbate peroxidase (APX) and ascorbate oxidase (AO) involved in AsA metabolism in plant cell apoplast is also discussed particularly focusing on oxidative stress perception and amplification. Limited progress has been made so far in terms of developing transgenics which could over-produce AsA. The prospects of generation of transgenics overexpressing AsA related genes and exogenous application of AsA have been discussed at length in the review. PMID:28491070

Dissolution of Commercially Available Mesalamine Formulations at Various pH Levels.

PubMed

Tenjarla, Srini

2015-06-01

Mesalamine (5-aminosalicylic acid; 5-ASA) is recommended first-line therapy for mild-to-moderate ulcerative colitis. Many mesalamine formulations employ a pH-dependent release mechanism designed to maximize drug release in the colon. This study compared the in vitro release of 5-ASA from six commercially available mesalamine formulations at pH levels similar to those typically encountered in the human gastrointestinal tract. The release of 5-ASA from six mesalamine formulations [Mesalazin-Kohlpharma (Kohlpharma, Germany), Mesalazin-Eurim (Eurimpharm, Germany), Mesalazina-Faes (Faes Farma, Spain), Mesalazine EC (Actavis B.V., Netherlands), Mesalazine EC 500 PCH (Pharmachemie B.V., Netherlands); multimatrix mesalamine (Shire US Inc., USA)] was monitored separately at three different pH levels [1.0 (2 h), 6.4 (1 h), and 7.2 (8 h)] using United States Pharmacopeia dissolution apparatus II. The dissolution percentage was calculated as a mean of 12 units for each formulation. At pH 1.0 and 6.4, <1 % of 5-ASA release was observed for each of the mesalamine formulations tested. At pH 7.2, complete release of 5-ASA occurred within 1 h for Mesalazine EC and Mesalazine EC 500 PCH, and within 2 h for Mesalazin-Kohlpharma, Mesalazin-Eurim, and Mesalazina-Faes; complete release of 5-ASA from multimatrix mesalamine occurred within 7 h. Little variability in rate of 5-ASA dissolution was observed between tablets of each formulation. At pH 7.2, 5-ASA release profiles were variable among the commercially available mesalamine formulations that were tested.

[A scale of perioperative satisfaction for anesthesia. II--Preliminary results].

PubMed

Pernoud, N; Colavolpe, J C; Auquier, P; Eon, B; Auffray, J P; François, G; Blache, J L

1999-10-01

To assess the patient's experience of anaesthesia in the early postoperative period, with a self-completed questionnaire (Evan). Descriptive and evaluative study. The study included 742 adults undergoing an elective surgical or non surgical procedure under anaesthesia. An Evan questionnaire with 25 questions was completed 24 hours after anaesthesia by the patient. The questionnaire explored six areas, each one being marked out from 0 to 100, as the visual analogue scale. The marks were compared with consideration of age, gender, ASA physical class, type of anaesthesia, anaesthesia duration and type of surgery. The mean global mark was 76 +/- 9 (min-max: 34-99). Marks were lower in the youngest patients, in females, in ASA 1 patients, in longest surgical procedures, especially with regard to areas belonging to "apprehension", "pain-discomfort" and "physical needs". The lowest mark was given for the "information" provided during the pre-anaesthetic evaluation. Differences in marks occurred also between surgical specialities. The Evan questionnaire is a valuable tool for assessing the patient's opinion on the perioperative period. Further studies are required to extend its use to other fields, as ambulatory surgery.

Assessment of oxidative stress indices in a marine macro brown alga Padina tetrastromatica (Hauck) from comparable polluted coastal regions of the Arabian Sea, west coast of India.

PubMed

Maharana, Dusmant; Jena, Karmabeer; Pise, Navnath M; Jagtap, Tanaji G

2010-01-01

Oxidative stress and antioxidant defence systems were assessed in a marine brown alga Padina tetrastromatica, commonly occurring from the tropics. Lipid peroxidation (LPX) and H2O2 were measured as oxidative stress markers, and antioxidant defences were measured as catalase (CAT), glutathione S-transferase (GST) and ascorbic acid (AsA), in order to understand their dissimilarity with respect to pollution levels from selective locations along the central west coast of India. A significant increased levels of LPX, H2O2, CAT and GST were observed in samples from relatively polluted localities (Colaba and Karwar) when compared to less polluted locality (Anjuna), while AsA concentration was higher in algal samples from worst polluted region of Colaba. Heavy metals such as Cd and Pb were also higher in the vicinity of polluted areas compared to reference area. Variation of oxidative stress indices in response to accumulation of heavy metals within P. tetrastromatica could be used as molecular biomarkers in assessment and monitoring environmental quality of ecologically sensitive marine habitats.

SLICER Airborne Laser Altimeter Characterization of Canopy Structure and Sub-canopy Topography for the BOREAS Northern and Southern Study Regions: Instrument and Data Product Description

NASA Technical Reports Server (NTRS)

Hall, Forrest G. (Editor); Nickeson, Jaime (Editor); Harding, D. J.; Blair, J. B.; Rabine, D. L.; Still, K. L.

2000-01-01

SLICER data were acquired in support of BOREAS at all of the TF sites in the SSA and NSA, and along transects between the study areas. Data were acquired on 5 days between 18-Jul and 30-Jul-1996. Each coverage of a tower site is typically 40 km in length, with a minimum of 3 and a maximum of 10 lines across each tower oriented in a variety of azimuths. The SLICER data were acquired simultaneously with ASAS hyperspectral, multiview angle images. The SLICER Level 3 products consist of binary files for each flight line with a data record for each laser shot composed of 13 parameters and a 600-byte waveform that is the raw record of the backscatter laser energy reflected from Earth's surface. The SLICER data are stored in a combination of ASCII and binary data files.

Interview with David Moore

ERIC Educational Resources Information Center

Rossman, Allan; Dietz, E. Jacquelin; Moor, David

2013-01-01

David Moore is Professor Emeritus of Statistics at Purdue University. He served as the first President of the International Association for Statistical Education (IASE) from 1993-1995 and as President of the American Statistical Association (ASA) in 1998. He is a Fellow of the ASA and of the IMS and was awarded the ASA's Founders Award in…

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

NASA Astrophysics Data System (ADS)

Pigulski, A.

2005-06-01

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

Veterinary Forensic Pathology of Animal Sexual Abuse.

PubMed

Stern, A W; Smith-Blackmore, M

2016-09-01

Animal sexual abuse (ASA) involves harm inflicted on animals for the purposes of human sexual gratification and includes such terms as bestiality, zoophilia, zoosadism, animal sexual assault, and others. The prevalence of ASA is not known, although it may be more common than is currently perceived. Veterinarians have the skills required to identify and document cases of ASA. This article reviews the terminology, legal definitions and forms of ASA, and its social and psychological context. An investigative approach is outlined, including an alternate light source examination; collection of swabs for DNA analysis; sampling vaginal washes, rectal washes, and toenails for trace evidence and biologic analyses; radiographic studies; and a complete forensic necropsy, including histopathology. Gross lesions identified in ASA victims include injuries to the anus, rectum, penis, scrotum, nipples, and vagina; the presence of foreign bodies; and abrasions, bruising, and other evidence of nonaccidental injury. Specialized procedures, including examination using alternate light sources and screening tests to identify human seminal fluid within samples from ASA victims, are of potential value but have not been validated for use in animals. © The Author(s) 2016.

Letter: The clinical course of patients with analgesic nephropathy.

PubMed Central

Gault, M. H.

1975-01-01

Thirty-four patients with analgesic nephropathy were followed at intervals of 1 to 3 months with measurements of creatinine clearance and serum concentration of acetylsalicylic acid (ASA) for a total of 105 patient-years. Diagnostic criteria included total consumption of at least 2 kg of phenacetin and 3 kg of ASA, compatible tissue abnormality on biopsy and evidence of papillary necrosis on an intravenous pyelogram. Nephropathy was induced by the same compound analgesic containing ASA, pehnacetin, caffeine and codeine (APC&C) in 30. Phenacetin was removed from this preparation in 1970 and replaced by an approximately equal amount of ASA (ACC). Creatinine clearance remained unchanged or improved in 11 of 15 patients who stopped taking analgesics containing phenacetin or ASA and in 10 of 11 of those who continued to take the ACC preparation. In contrast, renal function deteriorated in seven of eight patients who continued to abuse APC&C analgesics. The results suggest that phenacetin is necessary for the major nephrotoxic effect of this APC&C combination, but that ASA is not absolved of some nephrotoxicity. PMID:1139519

Clinical evidence for use of acetyl salicylic acid in control of flushing related to nicotinic acid treatment.

PubMed

Oberwittler, H; Baccara-Dinet, M

2006-06-01

Nicotinic acid (NA) is highly effective and widely used in the management of dyslipidaemia. For many patients, the side effect of flushing of the face and upper body leads to discontinuation. Flushing with NA is mediated by prostaglandins, and as acetyl salicylic acid (ASA, 'aspirin') is a highly effective inhibitor of prostaglandin synthesis, there is a rationale for its use to prevent or reduce the severity of NA-related flushing. This literature survey identified four studies specifically exploring the utility of ASA in preventing NA-related flushing in healthy volunteers. Twenty-three NA studies, where ASA was mandatory or optional within the protocol, and four studies, where background ASA therapy was reported in most participants, were also identified. Although the incidence of flushing in studies using ASA was often high, discontinuation rates due to flushing were low (mean 7.7%). This figure compares favourably with discontinuation rates with NA commonly reported in the literature (up to approximately 40%). There is good supportive evidence for the use of ASA in reducing the severity of NA-related flushing.

Applying Latent Class Analysis to Risk Stratification for Perioperative Mortality in Patients Undergoing Intraabdominal General Surgery.

PubMed

Kim, Minjae; Wall, Melanie M; Li, Guohua

2016-07-01

Perioperative risk stratification is often performed using individual risk factors without consideration of the syndemic of these risk factors. We used latent class analysis (LCA) to identify the classes of comorbidities and risk factors associated with perioperative mortality in patients presenting for intraabdominal general surgery. The 2005 to 2010 American College of Surgeons National Surgical Quality Improvement Program was used to obtain a cohort of patients undergoing intraabdominal general surgery. Risk factors and comorbidities were entered into LCA models to identify the latent classes, and individuals were assigned to a class based on the highest posterior probability of class membership. Relative risk regression was used to determine the associations between the latent classes and 30-day mortality, with adjustments for procedure. A 9-class model was fit using LCA on 466,177 observations. After combining classes with similar adjusted mortality risks, 5 risk classes were obtained. Compared with the class with average mortality risk (class 4), the risk ratios (95% confidence interval) ranged from 0.020 (0.014-0.027) in the lowest risk class (class 1) to 6.75 (6.46-7.02) in the highest risk class. After adjusting for procedure and ASA physical status, the latent classes remained significantly associated with 30-day mortality. The addition of the risk class variable to a model containing ASA physical status and surgical procedure demonstrated a significant increase in the area under the receiver operator characteristic curve (0.892 vs 0.915; P < 0.0001). Latent classes of risk factors and comorbidities in patients undergoing intraabdominal surgery are predictive of 30-day mortality independent of the ASA physical status and improve risk prediction with the ASA physical status.

Assessment of the variation in American Society of Anesthesiologists [corrected] Physical Status Classification assignment in small animal anaesthesia.

PubMed

McMillan, Matthew; Brearley, Jacqueline

2013-05-01

To evaluate the interobserver variability in the assignment of the American Society of Anesthesiologists Physical Status Classification (ASA-PSC) to compromised small animal patients amongst a group of veterinary anaesthetists. Anonymous internet survey. Hypothetical case presentations. Sixteen hypothetical small animal cases with differing degrees of physiological or patho-physiological compromise were presented as part of an internet survey. Respondents were asked to assign a single ASA-PSC to each case and also to answer a number of demographic questions. ASA-PSC scores were considered separately and then grouped as scores of I-II and III-V. Agreement was analysed using the modified kappa statistic for multiple observers. Data were then sorted into various demographic groups for further analysis. There were 144 respondents of which 60 (~42%) were anaesthesia diplomates, 24 (~17%) were post-residency (nondiploma holders), 24 (~17%) were current anaesthesia residents, 21 (~15%) were general practitioners, 12 (~8%) were veterinary nurses or technicians, and 3 (~2%) were interns. Although there was a majority agreement (>50% in a single category) in 15 of the 16 cases, ASA-PSC were spread over at least three ASA-PS classifications for every case. Overall agreement was considered only fair (κ = 0.24, mean ± SD agreement 46 ± 7%). When comparing grouped data (ASA-PSC I-II versus III-V) overall agreement remained fair (κ = 0.36, mean ± SD agreement 69 ± 19%). There was no difference in ASA-PSC assignment between any of the demographic groups investigated. This study suggests major discrepancies can occur between observers given identical information when using the ASA-PSC to categorise health status in compromised small animal patients. The significant potential for interobserver variability in classification allocation should be borne in mind when the ASA-PSC is used for clinical, scientific and statistical purposes. © 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

The Animal Sciences Academic Quadrathlon: history, current status, and recommendations.

PubMed

Kauffman, R G; Jobsis, C T; Onan, G; Day, B N

2011-07-01

The Animal Sciences Academic Quadrathlon (AQ) provides opportunities for teams of undergraduate animal and dairy science students to participate in regional American Society of Animal Science (ASAS)/American Dairy Science Association (ADSA) meetings and to collectively exhibit their knowledge and talents competitively in 4 categories: 1) solving practical, hands-on, laboratory-type problems; 2) providing written answers to essay-type questions about principles and concepts; 3) preparing and communicating orally and extemporaneously topics of current animal science interest; and 4) quickly responding to short-answer questions provided in the form of double-elimination quiz bowls. Each team is selected by winning the local AQ at their university. Overall and individual category winning teams are recognized, but team rankings are not emphasized. The ASAS/ADSA members provide leadership for organizing and conducting the AQ, and ASAS and each university provide travel expenses for students. The ultimate purpose is to stimulate academic excellence among undergraduate students and for the students to attend ASAS/ADSA regional scientific meetings to meet faculty and students and to attend scientific research presentations. The purpose of this document was to provide a history of the event and to make recommendations for its improvement. The AQ was conceived in 1967. During the next 10 yr, an ASAS committee developed procedures for a trial AQ held in 1980 at the ASAS Midwestern Section, Kansas State University-Manhattan, and in the next year the first official AQ was held at the ASAS Midwestern Section at the University of Nebraska-Lincoln. Starting in 1985, AQ programs were initiated at the other 3 ASAS sectional meetings, and an estimated 50,000 students representing 60 universities have participated in AQ programs since that time. If the AQ is to continue its improvement over time, it will greatly depend on sustained ASAS/ADSA faculty interest and support, as well as greater adherence to the original AQ procedures. © 2011 American Society of Animal Science. All rights reserved.

Underutilization of Aspirin for Primary Prevention of Cardiovascular Disease Among HIV-Infected Patients

PubMed Central

Burkholder, Greer A.; Tamhane, Ashutosh R.; Salinas, Jorge L.; Mugavero, Michael J.; Raper, James L.; Westfall, Andrew O.; Saag, Michael S.; Willig, James H.

2012-01-01

Background. Individuals infected with human immunodeficiency virus (HIV) are at increased risk for cardiovascular disease (CVD) events compared with uninfected persons. However, little is known about HIV provider practices regarding aspirin (ASA) for primary prevention of CVD. Methods. A cross-sectional study was conducted among patients attending the University of Alabama at Birmingham 1917 HIV Clinic during 2010 to determine the proportion receiving ASA for primary prevention of CVD and identify factors associated with ASA prescription. Ten-year risk for CVD events was calculated for men aged 45–79 and women aged 55–79. The 2009 US Preventive Services Task Force (USPSTF) guidelines were used to determine those qualifying for primary CVD prevention. Results. Among 397 patients who qualified to receive ASA (mean age, 52.2 years, 94% male, 36% African American), only 66 (17%) were prescribed ASA. In multivariable logistic regression analysis, diabetes mellitus (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.28–5.27), hyperlipidemia (OR, 3.42; 95% CI, 1.55–7.56), and current smoking (OR, 1.87; 95% CI, 1.03–3.41) were significantly associated with ASA prescription. Odds of ASA prescription more than doubled for each additional CVD-related comorbidity present among hypertension, diabetes, hyperlipidemia, and smoking (OR, 2.13, 95% CI, 1.51–2.99). Conclusions. In this HIV-infected cohort, fewer than 1 in 5 patients in need received ASA for primary CVD prevention. Escalating likelihood of ASA prescription with increasing CVD-related comorbidity count suggests that providers may be influenced more by co-occurrence of these diagnoses than by USPSTF guidelines. In the absence of HIV-specific guidelines, interventions to improve HIV provider awareness of and adherence to existing general population guidelines on CVD risk reduction are needed. PMID:22942209

Ascorbic acid deficiency increases endotoxin influx to portal blood and liver inflammatory gene expressions in ODS rats.

PubMed

Tokuda, Yuki; Miura, Natsuko; Kobayashi, Misato; Hoshinaga, Yukiko; Murai, Atsushi; Aoyama, Hiroaki; Ito, Hiroyuki; Morita, Tatsuya; Horio, Fumihiko

2015-02-01

The aim of this study was to determine whether ascorbic acid (AsA) deficiency-induced endotoxin influx into portal blood from the gastrointestinal tract contributes to the inflammatory changes in the liver. The mechanisms by which AsA deficiency provokes inflammatory changes in the liver were investigated in Osteogenic Disorder Shionogi (ODS) rats (which are unable to synthesize AsA). Male ODS rats (6-wk-old) were fed a diet containing sufficient (300 mg/kg) AsA (control group) or a diet without AsA (AsA-deficient group) for 14 or 18 d. On day 14, the hepatic mRNA levels of acute-phase proteins and inflammation-related genes were significantly higher in the AsA-deficient group than the control group, and these elevations by AsA deficiency were exacerbated on day 18. The serum concentrations of interleukin (IL)-1β and IL-6, which induce acute-phase proteins in the liver, were also significantly elevated on day 14 in the AsA-deficient group compared with the respective values in the control group. IL-1β mRNA levels in the liver, spleen, and lung were increased by AsA deficiency. Moreover, on both days 14 and 18, the portal blood endotoxin concentration was significantly higher in the AsA-deficient group than in the control group, and a significant correlation between serum IL-1β concentrations and portal endotoxin concentrations was found in AsA-deficient rats. In the histologic analysis of the ileum tissues, the number of goblet cells per villi was increased by AsA deficiency. These results suggest that AsA deficiency-induced endotoxin influx into portal blood from the gastrointestinal tract contributes to the inflammatory changes in the liver. Copyright © 2015 Elsevier Inc. All rights reserved.

Prevention or treatment of ARDS with aspirin: a review of preclinical models and meta- analysis of clinical studies

PubMed Central

Panka, Bernardo Amisa; de Grooth, Harm-Jan; Spoelstra–de Man, Angeliquè; Looney, Mark; Tuinman, Pieter-Roel

2016-01-01

Background The acute respiratory distress syndrome (ARDS) is a life-threating disorder that contributes significantly to critical illness. No specific pharmacological interventions directed at lung injury itself, have proven effective in improving outcome of patients with ARDS. Platelet activation was identified as a key component in ARDS pathophysiology and may provide an opportunity for preventive and therapeutic strategies. We hypothesize that use of acetyl salicylic acid (ASA) may prevent and/or attenuate lung injury. Methods We conducted a systematic review of preclinical studies and meta-analysis of clinical studies investigating the efficacy of ASA in the setting of lung injury. MEDLINE, EMBASE AND COCHRANE databases were searched. Results The literature search yielded 1314 unique articles. Fifteen pre-clinical studies and eight clinical studies fulfilled the in- and exclusion criteria. In the animal studies, the overall effect of ASA was positive, e.g. ASA improved survival and attenuated inflammation and pulmonary edema. Mechanisms of actions involved, among others, are interference with the neutrophil-platelets interaction, reduction of leukotrienes, neutrophil extracellular traps and prostaglandins. High dose ASA may be the drug of choice. A meta-analysis of 3 clinical studies showed an association between ASA use and a reduced incidence of ARDS (OR 0.59, 95% CI 0.36–0.98), albeit with substantial between-study heterogeneity. All studies had their own shortcomings in methodological quality. Conclusion This systematic review of preclinical studies and meta-analysis of clinical studies suggests a beneficial role for ASA in ARDS prevention and treatment. However, the currently available data is insufficient to justify an indication for ASA in ARDS. The body of literature does support further studies in humans. We suggest clinical trials in which the mechanisms of action of ASA in lung injury models is being evaluated to guide optimal timing and dose, before prospective randomized trials. PMID:27984533

Comparative pharmacokinetics of acetyl salicylic acid and its metabolites in children suffering from autoimmune diseases.

PubMed

Juárez Olguín, Hugo; Flores Pérez, Janett; Lares Asseff, Ismael; Loredo Abdalá, Arturo; Carbajal Rodríguez, Luis

2004-01-01

The aim of the present study was to compare the effect produced by juvenile rheumatoid arthritis (JRA) or rheumatic fever (RF) on the pharmacokinetics of acetyl salicylic acid (ASA) and its metabolites in children with autoimmune diseases (AD). A prospective, open labelled study was performed in 17 children with JRA and 17 with RF who received a single dose of 25 mg ASA/kg orally. The pharmacokinetics of ASA and its metabolites were determined. The blood and urine levels of each salicylate collected during 24 h were measured by HPLC. A group of 15 healthy teenage volunteers was included as a control group. The maximum plasma concentration, half-life time, area under the curve and the amount of salicylates excreted were statistically different between the JRA and the RF groups, as well as between the RF group and the controls, however, there were no significant differences between the JRA group and the controls. Dosage schemes must be adjusted for JRA patients, since the half life in these patients is longer than in RF patients. However, due to ample variability of pharmacokinetic parameters it is recommended that dose schemes are individualized on the type of autoimmune disease considered. Copyright 2004 John Wiley & Sons, Ltd.

Detection of platelet sensitivity to inhibitors of COX-1, P2Y1, and P2Y12 using a whole blood microfluidic flow assay

PubMed Central

Li, Ruizhi; Diamond, Scott L.

2014-01-01

BACKGROUND Microfluidic devices recreate the hemodynamic conditions of thrombosis. METHODS Whole blood inhibited with PPACK was treated ex vivo with inhibitors and perfused over collagen for 300 s (wall shear rate = 200 s−1) using a microfluidic flow assay. Platelet accumulation was measured in the presence of COX-1 inhibitor (aspirin, ASA), P2Y1 inhibitor (MRS 2179), P2Y12 inhibitor (2MeSAMP) or combined P2Y1 and P2Y12 inhibitors. RESULTS High dose ASA (500 μM), 2MeSAMP (100 μM), MRS 2179 (10 μM),or combined 2MeSAMP and MRS 2179 decreased total platelet accumulation by 27.5%, 75.6%, 77.7%, and 87.9% (p < 0.01), respectively. ASA reduced secondary aggregation rate between 150 and 300 s without effect on primary deposition rate on collagen from 60 to 150 s. In contrast, 2MeSAMP and MRS 2179 acted earlier and reduced primary deposition to collagen between 60 and 105 s and secondary aggregation between 105 and 300 s. RCOX and RP2Y (defined as a ratio of secondary aggregation rate to primary deposition rate) demonstrated 9 of 10 subjects had RCOX < 1 or RP2Y < 1 following ASA or 2MeSAMP addition, while 6 of 10 subjects had RP2Y < 1 following MRS 2179 addition. Combined MRS 2179 and 2MeSAMP inhibited primary platelet deposition rate and platelet secondary aggregation beyond that of each individual inhibitor. Receiver-Operator Characteristic area under the curve (AUC) indicated the robustness of RCOX and RP2Y to detect inhibition of secondary platelet aggregation by ASA, 2MeSAMP, and MRS 2179 (AUC of 0.874 0.966, and 0.889, respectively). CONCLUSIONS Microfluidic devices can detect platelet sensitivity to antiplatelet agents. The R-value can serve as a self-normalized metric of platelet function for a single blood sample. PMID:24365044

Evaluation of NT-proBNP concentrations during exercise in asymptomatic patients with severe high-gradient aortic stenosis.

PubMed

Dobrowolski, Piotr; Lech, Agnieszka; Klisiewicz, Anna; Hoffman, Piotr

2016-08-11

INTRODUCTION The effect of asymptomatic severe aortic stenosis (ASAS) on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels ar rest and during exercise, as well as their relevance for clinical practice remain controversial.  OBJECTIVES The aim of this study was to test the hypothesis of whether the evaluation of NT-proBNP concentrations during exercise provides additional information about the severity of aortic stenosis and left ventricular remodeling in patients with ASAS. PATIENTS AND METHODS A total of 50 patients with ASAS (mean age, 38.4 ±18.1 years) and 21 healthy subjects (mean age, 43.4 ±10.6 years) were enrolled. Rest and exercise echocardiography was performed to evaluate maximum velocity (Vmax), mean aortic gradient (AG), and aortic valve area (AVA). The left ventricular mass index (LVMI) was calculated. NT-proBNP concentrations at rest and during exercise were assessed, and the difference between the 2 values was calculated (ΔNT-proBNP). RESULTS NT-proBNP and ΔNT-proBNP levels at rest and during exercise were significantly higher in the ASAS group compared with the control group. In the ASAS group, NT-proBNP levels at rest significantly correlated with LVMI (r = 0.432; P <0.0001), AVA (r = -0.408; P <0.0001), Vmax (r = 0.375; P = 0.002), and mean AG (r = 0.257; P = 0.03). NT-proBNP levels during exercise significantly correlated with LVMI (r = 0.432; P <0.0001), mean AG (r = 0.401; P = 0.001), and AVA (r = -0.375; P = 0.001). In the multivariate logistic regression model, the factors independently associated with NT-proBNP both at rest and during exercise were age, AVA, and LVMI. CONCLUSIONS NT-proBNP levels at rest provide valuable information for identifying patients with more advanced left ventricular hypertrophy secondary to severe aortic stenosis. NT-proBNP levels during exercise do not provide new information on the severity of AS.

Aspirin alone and combined with a statin suppresses eicosanoid formation in human colon tissue.

PubMed

Gottschall, Heike; Schmöcker, Christoph; Hartmann, Dirk; Rohwer, Nadine; Rund, Katharina; Kutzner, Laura; Nolte, Fabian; Ostermann, Annika I; Schebb, Nils Helge; Weylandt, Karsten H

2018-05-01

Eicosanoids, including prostaglandins (PGs) and thromboxanes, are broadly bioactive lipid mediators and increase colon tumorigenesis possibly through chronic inflammatory mechanisms. Epidemiological and experimental data suggest that acetylsalicylic acid (ASA) helps prevent colorectal cancer (CRC), possibly through cyclooxygenase (COX)-mediated suppression of eicosanoid, particularly PGE 2 , formation. Recent studies suggest that statins prevent CRC and improve survival after diagnosis. We identified patients on ASA and/or statin treatment undergoing routine colonoscopy and measured eicosanoid levels in colonic mucosa with targeted metabolomics technology (LC-MS/MS). ASA-treated individuals (n = 27) had significantly lower tissue eicosanoid levels of most COX-derived metabolites than untreated individuals (n = 31). In contrast, COX-derived lipid metabolites tended to be higher in patients with statin treatment (n = 7) as compared with those not receiving statins (n = 24). This effect was not discernible in subjects treated with ASA and statins (n = 11): Individuals treated with both drugs showed a pronounced suppression of COX-derived eicosanoids in colon tissue, even compared with subjects treated with ASA alone. Our data from a routine clinical setting support the hypothesis that ASA and statins could inhibit CRC development via lipid mediator modification. Further studies should directly investigate the effect of dual ASA and statin treatment on colon tumorigenesis in humans. Copyright © 2018 by the American Society for Biochemistry and Molecular Biology, Inc.

Antioxidant effect of vitamin E and 5-aminosalicylic acid on acrylamide induced kidney injury in rats.

PubMed

Rajeh, Nisreen A; Al-Dhaheri, Najlaa M

2017-02-01

To explore renal toxicity caused by sub-acute exposure of acrylamide and to study the protective effect of 5-Aminosalicylic acid (5-ASA) and Vitamin E (vit-E)on Acrylamide (ACR) induced renal toxicity. Methods: This study was conducted at King Fahad Medical Research Centre, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, between August and November 2015. A total of 49 adult Wistar rats (250 ± 20g) aged 60 days were kept in a controlled environment and used in the present study. The rats were divided into 7 groups (control, ACR alone, ACR+5-ASA, ACR+vit-E, ACR+ASA+vit-E, vit-E alone, and ASA alone). After 5 days of ACR oral gavage treatment, the rats were observed for 24 hours then killed. Histopathology for the kidney and lactate dehydrogenase assay were carried out.  Results: Acrylamide produced significant pathological changes in the kidney with acute tubular necrosis in the distal tubules that could be reversed by concomitant injection of rat with 5-ASA. Together with vitamin E, 5-ASA, showed maximum renal protection. No statistically significant difference was observed in either body weights or lactate dehydrogenase activity of ACR treated rats.  Conclusion: Acrylamide exposure leads to adverse clinical pathologies of renal tubules, which were reversed by a concomitant treatment with 5-ASA and vitamin-E.

Dry Priming of Maize Seeds Reduces Aluminum Stress

PubMed Central

Alcântara, Berenice Kussumoto; Machemer-Noonan, Katja; Silva Júnior, Francides Gomes; Azevedo, Ricardo Antunes

2015-01-01

Aluminum (Al) toxicity is directly related to acidic soils and substantially limits maize yield. Earlier studies using hormones and other substances to treat the seeds of various crops have been carried out with the aim of inducing tolerance to abiotic stress, especially chilling, drought and salinity. However, more studies regarding the effects of seed treatments on the induction of Al tolerance are necessary. In this study, two independent experiments were performed to determine the effect of ascorbic acid (AsA) seed treatment on the tolerance response of maize to acidic soil and Al stress. In the first experiment (greenhouse), the AsA seed treatment was tested in B73 (Al-sensitive genotype). This study demonstrates the potential of AsA for use as a pre-sowing seed treatment (seed priming) because this metabolite increased root and shoot growth under acidic and Al stress conditions. In the second test, the evidence from field experiments using an Al-sensitive genotype (Mo17) and an Al-tolerant genotype (DA) suggested that prior AsA seed treatment increased the growth of both genotypes. Enhanced productivity was observed for DA under Al stress after priming the seeds. Furthermore, the AsA treatment decreased the activity of oxidative stress-related enzymes in the DA genotype. In this study, remarkable effects using AsA seed treatment in maize were observed, demonstrating the potential future use of AsA in seed priming. PMID:26714286

Metformin and aspirin treatment could lead to an improved survival rate for Type 2 diabetic patients with stage II and III colorectal adenocarcinoma relative to non-diabetic patients.

PubMed

De Monte, Ariella; Brunetti, Davide; Cattin, Luigi; Lavanda, Francesca; Naibo, Erica; Malagoli, Maria; Stanta, Giorgio; Bonin, Serena

2018-03-01

Metformin, the drug of choice in the treatment of type 2 diabetes mellitus (DM2), in addition to aspirin (ASA), the drug prescribed for cardioprotection of diabetic and non-diabetic patients, have an inhibitory effect on cancer cell survival. The present population-based study conducted in the province of Trieste (Italy), aimed to investigate the prevalence of DM2 in patients with colorectal adenocarcinoma (CRC) and survival for CRC in diabetic and nondiabetic patients. All permanent residents diagnosed with a CRC between 2004 and 2007 were ascertained through the regional health information system. CRC-specific and relative survival probabilities were computed for each group of patients defined by CRC stage, presence or absence of DM2 treated with metformin, and presence or absence of daily ASA therapy. A total of 515 CRC patients without DM2 and 156 with DM2 treated with metformin were enrolled in the study. At the time of CRC diagnosis, 71 (14%) nondiabetic and 39 (25%) diabetic patients were taking ASA daily. The five-year relative survival for stage III CRC was 101% [95% confidence interval (CI)=76-126] in the 18 patients with DM2 treated with metformin and ASA, 55% (95% CI=31-78) in the 23 without DM2 treated with ASA, 55% (95% CI=45-65) in the 150 without DM2 not taking ASA, and 29% (95% CI=13-45) in the 43 with DM2 treated with metformin, however not with ASA. The findings support the hypothesis of a possible inhibitory effect of metformin and ASA on CRC cells. Randomized controlled trials are required to verify this hypothesis.

High-dose ascorbic acid induces carcinostatic effects through hydrogen peroxide and superoxide anion radical generation-induced cell death and growth arrest in human tongue carcinoma cells.

PubMed

Ohwada, Ryouhei; Ozeki, Yu; Saitoh, Yasukazu

2017-01-01

High-dose ascorbic acid (AsA) treatment, known as pharmacological AsA, has been shown to exert carcinostatic effects in many types of cancer cells and in vivo tumour models. Although pharmacological AsA has potential as a complementary and alternative medicine for anticancer treatment, its effects on human tongue carcinoma have not yet been elucidated. In this study, we investigated the effect of AsA treatment on human tongue carcinoma HSC-4 cells compared with non-tumourigenic tongue epithelial dysplastic oral keratinocyte (DOK) cells. Our results show that treatment with 1 and 3 mM of AsA for 60 min preferentially inhibits the growth of human tongue carcinoma HSC-4 over DOK cells. Furthermore, AsA-induced effects were accompanied by increased intracellular oxidative stress and were repressed by treatment with a hydrogen peroxide (H 2 O 2 ) scavenger catalase and a superoxide anion radical (O 2 - ) scavenger, tempol. Time-lapse observation and thymidine analog EdU incorporation revealed that AsA treatment induces not only cell death but also suppression of DNA synthesis and cell growth. Moreover, the growth arrest was accompanied by abnormal cellular morphologies whereby cells extended dendrite-like pseudopodia. Taken together, our results demonstrate that AsA treatment can induce carcinostatic effects through induction of cell death, growth arrest, and morphological changes mediated by H 2 O 2 and O 2 - generation. These findings suggest that high-dose AsA treatment represents an effective treatment for tongue cancer as well as for other types of cancer cells.

Clinical benefits of aspirin desensitization in patients with nonsteroidal anti-inflammatory drug exacerbated respiratory disease are not related to urinary eicosanoid release and are accompanied with decreased urine creatinine.

PubMed

Makowska, Joanna S; Olszewska-Ziąber, Agnieszka; Bieńkiewicz, Barbara; Lewandowska-Polak, Anna; Kurowski, Marcin; Woźniakowski, Bartłomiej; Rotkiewicz, Arkadiusz; Kowalski, Marek L

2016-05-01

Treatment with acetylsalicylic acid (ASA) after desensitization may be a therapeutic option in patients with nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NERD). The mechanisms that lead to improvement in rhinosinusitis and asthma symptoms remain unknown. To attribute the documented clinical effects of ASA treatment of chronic rhinosinusitis and/or asthma to the release of eicosanoid metabolites in urine. Fourteen patients with NERD were successfully desensitized, and, eventually, eight patients were treated with 650 mg of ASA daily for 3 months. In addition to clinical assessments, nuclear magnetic resonance imaging and smell test were performed before and after treatment with ASA. Venous blood and urine were collected before desensitization and after 1 and 3 months of treatment. The levels of urinary leukotrienes (LT) (cysteinyl LT and LTE4) and tetranor PGDM (metabolite of prostaglandin D2) were measured by enzyme-linked immunosorbent assay. Treatment with ASA after desensitization alleviated symptoms of rhinosinusitis, improved nasal patency (mean, 50% decrease in peak nasal inspiratory flow) and sense of smell (fourfold increase in smell test score) in as early as 4 weeks. Clinical improvements were not accompanied by any change in sinonasal mucosa thickness as assessed with nuclear magnetic resonance. Urinary cysteinyl LTs, LTE4, and prostaglandin D2 metabolite remained relatively stable during ASA treatment and did not correlate with clinical improvements. Desensitization was associated with a progressive decrease of urinary creatinine. Clinical improvement in rhinosinusitis and/or asthma after ASA desensitization was not related to concentrations of urinary eicosanoid metabolites. A decrease of urinary creatinine requires further study to determine the renal safety of long-term treatment with ASA after desensitization.

Acetylsalicylic acid inhibits the pituitary response to exercise-related stress in humans.

PubMed

Di Luigi, L; Guidetti, L; Romanelli, F; Baldari, C; Conte, D

2001-12-01

Prostaglandins (PGs) modulate the activity of the hypothalamus-pituitary axis, and pituitary hormones are largely involved in the physiological responses to exercise. The purpose of this study was to analyze the effects of acetylsalicylic acid (ASA), an inhibitor of PGs synthesis, in the pituitary responses to physical stress in humans. Adrenocorticotropin (ACTH), beta-endorphin, cortisol, growth hormone (GH), and prolactin (PRL) responses to exercise were evaluated after administration of either placebo or ASA. Blood samples for hormone evaluations before (-30, -15, and 0 pre) and after (0 post, +15, +30, +45, +60, and +90 min) a 30-min treadmill exercise (75% of .VO(2max)) were taken from 12 male athletes during two exercise trials. One tablet of ASA (800 mg), or placebo, was administered two times daily for 3 d before and on the morning of each exercise-test. The results clearly show that, compared with placebo, ASA ingestion significantly blunted the increased serum ACTH, beta-endorphin, cortisol, and GH levels before exercise (anticipatory response) and was associated with reduced cortisol concentrations after exercise. Furthermore, although no differences in the GH response to exercise were shown, a significantly reduced total PRL response to stress condition was observed after ASA. ASA influences ACTH, beta-endorphin, cortisol, GH, and PRL responses to exercise-related stress in humans (preexercise activation/exercise-linked response). Even though it is not possible to exclude direct action for ASA, our data indirectly confirm a role of PGs in these responses. We have to further evaluate the nature of the preexercise endocrine activation and, because of the large use of anti-inflammatory drugs in athletes, whether the interaction between ASA and hormones might positively or negatively influence health status, performance, and/or recovery.

Comparative effects of the anti-platelet drugs, clopidogrel, ticlopidine, and cilostazol on aspirin-induced gastric bleeding and damage in rats.

PubMed

Takeuchi, Koji; Takayama, Shinichi; Izuhara, Chitose

2014-08-21

The present study compared the effects of frequently used anti-platelet drugs, such as clopidogrel, ticlopidine, and cilostazol, on the gastric bleeding and ulcerogenic responses induced by intraluminal perfusion with 25 mM aspirin acidified with 25 mM HCl (acidified ASA) in rats. The stomach was perfused with acidified ASA at a rate of 0.4 ml/min for 60 min under urethane anesthesia, and gastric bleeding was measured as the concentration of hemoglobin in the luminal perfusate, which was collected every 15 min. Clopidogrel (10-100mg/kg), ticlopidine (10-300 mg/kg), or cilostazol (3-30 mg/kg) was given p.o. 24h or 90 min before the perfusion of acidified ASA, respectively. Perfusion of the stomach with acidified ASA alone led to slight bleeding and lesions in the stomach. The pretreatment with clopidogrel, even though it did not cause bleeding or damage by itself, dose-dependently increased the gastric bleeding and ulcerogenic responses induced by acidified ASA. Ticlopidine also aggravated the severity of damage by increasing gastric bleeding, and the effects of ticlopidine at 300 mg/kg were equivalent to those of clopidogrel at 100mg/kg. In contrast, cilostazol dose-dependently decreased gastric bleeding and damage in response to acidified ASA. These results demonstrated that clopidogrel and ticlopidine, P2Y12 receptor inhibitors, increased gastric bleeding and ulcerogenic responses to acidified ASA, to the same extent, while cilostazol, a phosphodiesterase III inhibitor, suppressed these responses. Therefore, cilostazol may be safely used in dual anti-platelet therapy combined with ASA, without increasing the risk of gastric bleeding. Copyright © 2014 Elsevier Inc. All rights reserved.

Challenging the FDA black box warning for high aspirin dose with ticagrelor in patients with diabetes.

PubMed

DiNicolantonio, James J; Serebruany, Victor L

2013-03-01

Ticagrelor, a novel reversible antiplatelet agent, has a Food and Drug Administration (FDA) black box warning to avoid maintenance doses of aspirin (ASA) >100 mg/daily. This restriction is based on the hypothesis that ASA doses >100 mg somehow decreased ticagrelor's benefit in the Platelet Inhibition and Patient Outcomes (PLATO) U.S. cohort. However, these data are highly postrandomized, come from a very small subgroup in PLATO (57% of patients in the U.S. site), and make no biological sense. Moreover, the ticagrelor-ASA interaction was not significant by any multivariate Cox regression analyses. The Complete Response Review for ticagrelor indicates that for U.S. PLATO patients, an ASA dose >300 mg was not a significant interaction for vascular outcomes. In the ticagrelor-ASA >300 mg cohort, all-cause and vascular mortality were not significantly increased (hazard ratio [HR] 1.27 [95% CI 0.84-1.93], P = 0.262 and 1.39 [0.87-2.2], P = 0.170), respectively. Furthermore, for major adverse cardiovascular events (MACEs), 30-day all-cause mortality, and 30-day vascular mortality, the strongest interaction is the diabetes-ASA interaction. That is, patients who had diabetes had significantly fewer MACEs through study end (0.49 [0.34-0.63], P < 0.0001), significantly less 30-day all-cause mortality (0.33 [0.20-0.56], P < 0.0001), and significantly less 30-day vascular mortality (0.35 [0.22-0.55], P < 0.0001), respectively, when given high-dose (300-325 mg) ASA, regardless of treatment (clopidogrel or ticagrelor) assignment. The black box warning for the use of maintenance ASA doses >100 mg with ticagrelor is inappropriate for patients with diabetes and not evidence based.

Protein nitration and nitrosylation by NO-donating aspirin in colon cancer cells: Relevance to its mechanism of action

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Jennie L.; Ji, Ping; Ouyang, Nengtai

Nitric oxide-donating aspirin (NO-ASA) is a promising agent for cancer prevention. Although studied extensively, its molecular targets and mechanism of action are still unclear. S-nitrosylation of signaling proteins is emerging as an important regulatory mechanism by NO. Here, we examined whether S-nitrosylation of the NF-{kappa}B, p53, and Wnt signaling proteins by NO-ASA might explain, in part, its mechanism of action in colon cancer. NO-ASA releases significant amounts of NO detected intracellularly in HCT116 and HT-29 colon cells. Using a modified biotin switch assay we demonstrated that NO-ASA S-nitrosylates the signaling proteins p53, {beta}-catenin, and NF-{kappa}B, in colon cancer cells inmore » a time- and concentration-dependent manner. NO-ASA suppresses NF-{kappa}B binding to its cognate DNA oligonucleotide, which occurs without changes in the nuclear levels of the NF-{kappa}B subunits p65 and p50 and is reversed by dithiothreitol that reduces -S-NO to -SH. In addition to S-nitrosylation, we documented both in vitro and in vivo widespread nitration of tyrosine residues of cellular proteins in response to NO-ASA. Our results suggest that the increased intracellular NO levels following treatment with NO-ASA modulate cell signaling by chemically modifying key protein members of signaling cascades. We speculate that S-nitrosylation and tyrosine nitration are responsible, at least in part, for the inhibitory growth effect of NO-ASA on cancer cell growth and that this may represent a general mechanism of action of NO-releasing agents.« less

Sexual assault, drinking norms, and drinking behavior among a national sample of lesbian and bisexual women.

PubMed

Gilmore, Amanda K; Koo, Kelly H; Nguyen, Hong V; Granato, Hollie F; Hughes, Tonda L; Kaysen, Debra

2014-03-01

Childhood sexual abuse (CSA) and adolescent/adult sexual assault (ASA) are strongly associated with women's alcohol use and the rates of both alcohol use and sexual assault history are higher among lesbian and bisexual women than heterosexual women. Although descriptive drinking norms are one of the highest predictors of alcohol use in emerging adults, this is the first study to examine the relationship between sexual assault history, drinking norms, and alcohol use in lesbian and bisexual women. We found that CSA severity was associated with a higher likelihood of experiencing more severe alcohol-involved ASA, more severe physically forced ASA, and was indirectly associated with more drinking behavior and higher drinking norms. Additionally, more severe alcohol-involved ASA was associated with higher drinking norms and more drinking behavior, but physically forced ASA was not. These findings help explain previous contradictory findings and provide information for interventions. Published by Elsevier Ltd.

Sexual Assault, Drinking Norms, and Drinking Behavior among a National Sample of Lesbian and Bisexual Women

PubMed Central

Gilmore, Amanda K.; Koo, Kelly H.; Nguyen, Hong V.; Granato, Hollie F.; Hughes, Tonda L.; Kaysen, Debra L.

2014-01-01

Childhood sexual abuse (CSA) and adolescent/adult sexual assault (ASA) are strongly associated with women’s alcohol use and the rates of both alcohol use and sexual assault history are higher among lesbian and bisexual women than heterosexual women. Although descriptive drinking norms are one of the highest predictors of alcohol use in emerging adults, this is the first study to examine the relationship between sexual assault history, drinking norms, and alcohol use in lesbian and bisexual women. We found that CSA severity was associated with a higher likelihood of experiencing more severe alcohol-involved ASA, more severe physically forced ASA, and was indirectly associated with more drinking behavior and higher drinking norms. Additionally, more severe alcohol-involved ASA was associated with higher drinking norms and more drinking behavior, but physically forced ASA was not. These findings help explain previous contradictory findings and provide information for interventions. PMID:24360780

Molecular modeling and multispectroscopic studies of the interaction of mesalamine with bovine serum albumin

NASA Astrophysics Data System (ADS)

Shahabadi, Nahid; Fili, Soraya Moradi

2014-01-01

The interaction of mesalamine (5-aminosalicylic acid (5-ASA)) with bovine serum albumin (BSA) was investigated by fluorescence quenching, absorption spectroscopy, circular dichroism (CD) techniques, and molecular docking. Thermodynamic parameters (ΔH < 0 and ΔS 0) indicated that the hydrogen bond and electrostatic forces played the major role in the binding of 5-ASA to BSA. The results of CD and UV-vis spectroscopy showed that the binding of this drug to BSA induces some conformational changes in BSA. Displacement experiments predicted that the binding of 5-ASA to BSA is located within domain III, Sudlows site 2, that these observations were substantiated by molecular docking studies. In addition, the docking result shows that the 5-ASA in its anionic form mainly interacts with Gln-416 residue through one hydrogen bond between H atom of 5-ASA anion and the adjacent O atom of the hydroxyl group of Gln-416.

Standards 101; the ASA standards program

NASA Astrophysics Data System (ADS)

Schomer, Paul D.

2002-11-01

ASA supports the development of standards by serving as the secretariat for standards committees of the American National Standards Institute (ANSI). The program is organized through four ANSI technical committees (S1, S2, S3, and S12) and one administrative committee (ASACOS). S1 deals with physical acoustics, S2 deals with shock and vibration, S3 deals with physiological and psychological acoustics, and S12 deals with noise. ASACOS is the ASA Committee on Standards. The program has three primary tasks: (1) the development of National Standards (ANSI Standards), (2) the national adoption of an international standard (ANSI NAIS Standards), (3) providing the USA input to the development of International Standards (ISO and IEC Standards). At every level the main work is accomplished in Working Groups (WG) that are ''staffed'' by hundreds of volunteers--mainly ASA members from its various technical committees such as Noise, Physical Acoustics, Architectural Acoustics, Psychological and Physiological Acoustics, etc. Overall, the Standards Program involves more ASA members than does any other single function of the Society except meetings and it is the biggest outreach function of ASA affecting the health, welfare, and economic well-being of large segments of the population, the business and industrial community, and government at all levels.

Tandem mass spectrometry of nitric oxide and hydrogen sulfide releasing aspirins: a hint into activity behavior.

PubMed

Crestoni, Maria Elisa; Chiavarino, Barbara; Guglielmo, Stefano; Lilla, Valentina; Fornarini, Simonetta

2013-01-01

Aspirin (acetylsalicylic acid, ASA) is the most popular non-steroidal anti-inflammatory drug. However, due to its action on cyclooxygenase and its acid nature, aspirin is associated with adverse gastrointestinal effects. In an effort to minimize these side effects, NO-donor and H2S-donor ASA co-drugs have been designed and tested. Their mass spectrometric behavior is now analyzed and reported. Positive ions were obtained by electrospray ionization involving protonation or alkali metal attachment. Their dissociation processes have been studied by collision induced dissociation in a triple quadrupole instrument. High mass accuracy measurements have been recorded on a Fourier transform ion cyclotron resonance mass spectrometer. The protonated molecules dissociate by an exclusive or largely prevailing path leading to acetyloxy-substituted benzoyl cation, namely an ASA unit. The process is reminiscent of the enzymatic hydrolysis, releasing intact ASA to a large extent. Only at higher collision energy does the formal ketene loss disrupt the ASA moiety. The gas phase chemistry of protonated ASA-releasing drugs develops along elementary dissociation steps analogous to the reactive processes in complex biological environments. This notion may provide a tool for preliminary testing of new compounds.

[Effects of exogenous AsA and GSH on the growth of Dianthus chinensis seedlings exposed to Cd].

PubMed

Ding, Ji-Jun; Liu, Shi-Liang; Pan, Yuan-Zhi; Li, Li

2014-02-01

A pot experiment was carried out under greenhouse condition to investigate the effects of different concentrations (0, 20, 40, 60, 80 and 100 mg x L(-1)) of exogenous AsA, GSH on Dianthus chinensis seedlings which were stressed by 50 mg x kg(-1) Cd in the soil. The results indicated that 50 mg x kg(-1) of Cd significantly inhibited the growth of D. chinensis seedlings. An appropriate concentration of exogenous AsA significantly improved the biomass, plant height, tiller number, GAT and APX activities, and AsA and GSH contents. However, with the increase of exogenous AsA concentration, the ameliorating effect decreased and prooxidant effect occurred. Exogenous GSH could replenish the non-enzymatic antioxidants of D. chinensis seedlings, but the changes of antioxidant enzyme activities were relatively slight. The main mechanisms of GSH to alleviate Cd toxicity might be promoting root PCs synthesis, thereby reducing the Cd concentration in the seedlings. Both 35-45 mg x L(-1) exogenous AsA and 55-65 mg x L(-1) exogenous GSH could alleviate the Cd toxicity on D. chinensis seedlings, and the former was superior to the latter.

Variability in the American Society of Anesthesiologists Physical Status Classification Scale.

PubMed

Aronson, Wendy L; McAuliffe, Maura S; Miller, Ken

2003-08-01

The American Society of Anesthesiologists (ASA) Physical Status (PS) Classification is used worldwide by anesthesia providers as an assessment of the preoperative physical health of patients. This score also has been used in policy-making, performance evaluation, resource allocation, and reimbursement of anesthesia services and frequently is cited in clinical research. The purpose of this study was to assess interrater reliability and describe sources of variability among anesthesia providers in assigning ASA PS scores. A questionnaire with 10 hypothetical patients scenarios was given to 70 anesthesia providers who were asked to assign ASA PS scores in each scenario and to provide rationale for their decisions. The data were summarized and stratified according to nurse anesthetist or anesthesiologist and military or nonmilitary anesthesia providers. We hypothesized there would be no difference between any of the anesthesia provider groups in assignment of ASA PS scores. A lack of interrater reliability in assigning ASA PS scores was demonstrated. There were no significant differences between the anesthesia provider groups. There was no correlation between ASA PS scoring and years practicing or any of the other demographic variables. Several sources of variability were identified: smoking, pregnancy, nature of the surgery, potential difficult airway, and acute injury.

Comparison of the inhibitory effects of cilostazol, acetylsalicylic acid and ticlopidine on platelet functions ex vivo. Randomized, double-blind cross-over study.

PubMed

Ikeda, Y; Kikuchi, M; Murakami, H; Satoh, K; Murata, M; Watanabe, K; Ando, Y

1987-05-01

A randomized double-blind cross-over study was conducted to determine the inhibitory effects of acetylsalicylic acid (ASA), ticlopidine (TP) and cilostazol (OPC-13013; in the following briefly called CS), a new antithrombotic agent on platelet functions ex vivo. Nine patients with cerebral thrombosis were enrolled in this study. Patients were given each of the three drugs for one week in a complete cross-over design according to a randomization schedule, followed by a wash-out period with a placebo for one week. It was found that CS and TP significantly inhibited platelet aggregation induced by ADP. Collagen- and arachidonic acid-induced platelet aggregation was all inhibited by CS, TP and ASA. Duncan's multiple range test to compare the anti-platelet effects of the three drugs revealed that: CS greater than ASA and TP greater than ASA in inhibiting ADP-induced platelet aggregation and CS greater than TP and ASA greater than TP in inhibiting arachidonic acid-induced platelet aggregation. These results may suggest that CS is superior to ASA and TP in inhibiting platelet aggregation ex vivo.

Measurement of in vivo Gastrointestinal Release and Dissolution of Three Locally Acting Mesalamine Formulations in Regions of the Human Gastrointestinal Tract.

PubMed

Yu, Alex; Baker, Jason R; Fioritto, Ann F; Wang, Ying; Luo, Ruijuan; Li, Siwei; Wen, Bo; Bly, Michael; Tsume, Yasuhiro; Koenigsknecht, Mark J; Zhang, Xinyuan; Lionberger, Robert; Amidon, Gordon L; Hasler, William L; Sun, Duxin

2017-02-06

As an orally administered, locally acting gastrointestinal drug, mesalamine products are designed to achieve high local drug concentration in the gastrointestinal (GI) tract for the treatment of ulcerative colitis. The aim of this study was to directly measure and compare drug dissolution of three mesalamine formulations in human GI tract and to correlate their GI concentration with drug concentration in plasma. Healthy human subjects were orally administered Pentasa, Apriso, or Lialda. GI fluids were aspirated from stomach, duodenum, proximal jejunum, mid jejunum, and distal jejunum regions. Mesalamine (5-ASA) and its primary metabolite acetyl-5-mesalamine (Ac-5-ASA) were measured using LC-MS/MS. GI tract pH was measured from each GI fluid sample, which averaged 1.82, 4.97, 5.67, 6.17, and 6.62 in the stomach, duodenum, proximal jejunum, middle jejunum, and distal jejunum, respectively. For Pentasa, high levels of 5-ASA in solution were observed in the stomach, duodenum, proximal jejunum, mid jejunum, and distal jejunum from 1 to 7 h. Apriso had minimal 5-ASA levels in stomach, low to medium levels of 5-ASA in duodenum and proximal jejunum from 4 to 7 h, and high levels of 5-ASA in distal jejunum from 3 to 7 h. In contrast, Lialda had minimal 5-ASA levels from stomach and early small intestine. A composite appearance rate (CAR) was calculated from the deconvolution of individual plasma concentration to reflect drug release, dissolution, transit, and absorption in the GI tract. Individuals dosed with Pentasa had high levels of CAR from 1 to 10 h; individuals dosed with Apriso had low levels of CAR from 1 to 4 h and high levels of CAR from 5 to 10 h; Lialda showed minimal levels of CAR from 0 to 5 h, then increased to medium levels from 5 to 12 h, and then decreased to further lower levels after 12 h. In the colon region, Pentasa and Apriso showed similar levels of accumulated 5-ASA excreted in the feces, while Lialda showed slightly higher 5-ASA accumulation in feces. However, all three formulations showed similar levels of metabolite Ac-5-ASA in the feces. These results provide direct measurement of drug dissolution in the GI tract, which can serve as a basis for investigation of bioequivalence for locally acting drug products.

Caleb Phillips | NREL

Science.gov Websites

, Statistical Analysis and Data Mining: The ASA Data Science Journal (2017) Using GIS-Based Methods and Lidar techniques to the problem of large area coverage mapping for wireless networks. He has also done work in -4297 Dr. Caleb Phillips is a data scientist with the Computational Science Center at NREL. Caleb comes

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

PubMed

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

2008-11-01

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

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

NASA Astrophysics Data System (ADS)

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

2000-03-01

We have developed a fast-response nanometer aerosol size analyzer (nASA) that is capable of scanning 30 size channels between 3 and 100 nm in a total time of 3 s. The analyzer includes a bipolar charger (Po210), an extended-length nanometer differential mobility analyzer (Nano-DMA), and an electrometer (TSI 3068). This combination of components provides particle size spectra at a scan rate of 0.1 s per channel free of uncertainties caused by response-time-induced smearing. The nASA thus offers a fast response for aerosol size distribution measurements in high-concentration conditions and also eliminates the need for applying a de-smearing algorithm to resulting data. In addition, because of its thermodynamically stable means of particle detection, the nASA is useful for applications requiring measurements over a broad range of sample pressures and temperatures. Indeed, experimental transfer functions determined for the extended-length Nano-DMA using the tandem differential mobility analyzer (TDMA) technique indicate the nASA provides good size resolution at pressures as low as 200 Torr. Also, as was demonstrated in tests to characterize the soot emissions from the J85-GE engine of a T-38 aircraft, the broad dynamic concentration range of the nASA makes it particularly suitable for studies of combustion or particle formation processes. Further details of the nASA performance as well as results from calibrations, laboratory tests and field applications are presented below.

Effect of amorphous silica ash used as a partial replacement for cement on the compressive and flexural strengths cement mortar.

NASA Astrophysics Data System (ADS)

Usman, Aliyu; Ibrahim, Muhammad B.; Bala, Nura

2018-04-01

This research is aimed at investigating the effect of using amorphous silica ash (ASA) obtained from rice husk as a partial replacement of ordinary Portland cement (OPC) on the compressive and flexural strength of mortar. ASA was used in partial replacement of ordinary Portland cement in the following percentages 2.5 percent, 5 percent, 7.5 percent and 10 percent. These partial replacements were used to produce Cement-ASA mortar. ASA was found to contain all major chemical compounds found in cement with the exception of alumina, which are SiO2 (91.5%), CaO (2.84%), Fe2O3 (1.96%), and loss on ignition (LOI) was found to be 9.18%. It also contains other minor oxides found in cement. The test on hardened mortar were destructive in nature which include flexural strength test on prismatic beam (40mm x 40mm x 160mm) and compressive strength test on the cube size (40mm x 40mm, by using the auxiliary steel plates) at 2,7,14 and 28 days curing. The Cement-ASA mortar flexural and compressive strengths were found to be increasing with curing time and decreases with cement replacement by ASA. It was observed that 5 percent replacement of cement with ASA attained the highest strength for all the curing ages and all the percentage replacements attained the targeted compressive strength of 6N/mm2 for 28 days for the cement mortar

A Nanometer Aerosol Size Analyzer (nASA) for Rapid Measurement of High-Concentration Size Distributions

NASA Technical Reports Server (NTRS)

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

2001-01-01

We have developed a fast-response Nanometer Aerosol Size Analyzer (nASA) that is capable of scanning 30 size channels between 3 and 100 nm in a total time of 3 seconds. The analyzer includes a bipolar charger (P0210), an extended-length Nanometer Differential Mobility Analyzer (Nano-DMA), and an electrometer (TSI 3068). This combination of components provides particle size spectra at a scan rate of 0.1 second per channel free of uncertainties caused by response-time-induced smearing. The nASA thus offers a fast response for aerosol size distribution measurements in high-concentration conditions and also eliminates the need for applying a de-smearing algorithm to resulting data. In addition, because of its thermodynamically stable means of particle detection, the nASA is useful for applications requiring measurements over a broad range of sample pressures and temperatures. Indeed, experimental transfer functions determined for the extended-length Nano-DMA using the Tandem Differential Mobility Analyzer (TDMA) technique indicate the nASA provides good size resolution at pressures as low as 200 Torr. Also, as was demonstrated in tests to characterize the soot emissions from the J85-GE engine of a T38 aircraft, the broad dynamic concentration range of the nASA makes it particularly suitable for studies of combustion or particle formation processes. Further details of the nASA performance as well as results from calibrations, laboratory tests and field applications are presented.

Acetylsalicylic acid does not reduce the intraocular pressure variation in ocular hypertension or glaucoma.

PubMed

Lindén, C; Alm, A

2000-03-01

The purpose of this study was to measure if intraocular pressure (IOP) and IOP variations in patients with ocular hypertension and glaucoma are decreased by acetylsalicylic acid (ASA). The hypothesis to be tested was that short-term fluctuations in the IOP are caused by breaks of the inner wall of Schlemm's canal that are repaired by platelets inducing a cycle of breaks and repair. Furthermore, prostaglandins affect uveoscleral outflow and ASA inhibits prostaglandin biosynthesis and platelet aggregation. This implies that ASA may have complex effects on the IOP and its variations.In 28 patients with ocular hypertension or glaucoma the IOP was measured seven times during 2 hr on two succeeding days. Five hundred mg ASA or placebo was administrated orally in a masked fashion 15 hr prior to the second session. After wash-out, this procedure was repeated with a cross-over design. The same study outline was used in 28 glaucoma patients except for the cross-over design. There were no statistically significant differences in the mean IOP or in the IOP variations between the placebo treated and the ASA treated eyes in either group, and there were no significant differences between the day before and after treatment in any group. The results suggest that ASA does not affect IOP variations in a clinically significant way and that a single dose of ASA has no significant effect on mean IOP. Copyright 2000 Academic Press.

Quantifying Additive Interactions of the Osmolyte Proline with Individual Functional Groups of Proteins: Comparisons with Urea and Glycine Betaine, Interpretation of m-Values

PubMed Central

Diehl, Roger C.; Guinn, Emily J.; Capp, Michael W.; Tsodikov, Oleg V.; Record, M. Thomas

2013-01-01

To quantify interactions of the osmolyte L-proline with protein functional groups and predict its effects on protein processes, we use vapor pressure osmometry to determine chemical potential derivatives dµ2/dm3 = µ23 quantifying preferential interactions of proline (component 3) with 21 solutes (component 2) selected to display different combinations of aliphatic or aromatic C, amide, carboxylate, phosphate or hydroxyl O, and/or amide or cationic N surface. Solubility data yield µ23 values for 4 less-soluble solutes. Values of µ23 are dissected using an ASA-based analysis to test the hypothesis of additivity and obtain α-values (proline interaction potentials) for these eight surface types and three inorganic ions. Values of µ23 predicted from these α-values agree with experiment, demonstrating additivity. Molecular interpretation of α-values using the solute partitioning model yields partition coefficients (Kp) quantifying the local accumulation or exclusion of proline in the hydration water of each functional group. Interactions of proline with native protein surface and effects of proline on protein unfolding are predicted from α-values and ASA information and compared with experimental data, with results for glycine betaine and urea, and with predictions from transfer free energy analysis. We conclude that proline stabilizes proteins because of its unfavorable interactions with (exclusion from) amide oxygens and aliphatic hydrocarbon surface exposed in unfolding, and that proline is an effective in vivo osmolyte because of the osmolality increase resulting from its unfavorable interactions with anionic (carboxylate and phosphate) and amide oxygens and aliphatic hydrocarbon groups on the surface of cytoplasmic proteins and nucleic acids. PMID:23909383

Calibration correction of an active scattering spectrometer probe to account for refractive index of stratospheric aerosols

NASA Technical Reports Server (NTRS)

Pueschel, R. F.; Overbeck, V. R.; Snetsinger, K. G.; Russell, P. B.; Ferry, G. V.

1990-01-01

The use of the active scattering spectrometer probe (ASAS-X) to measure sulfuric acid aerosols on U-2 and ER-2 research aircraft has yielded results that are at times ambiguous due to the dependence of particles' optical signatures on refractive index as well as physical dimensions. The calibration correction of the ASAS-X optical spectrometer probe for stratospheric aerosol studies is validated through an independent and simultaneous sampling of the particles with impactors; sizing and counting of particles on SEM images yields total particle areas and volumes. Upon correction of calibration in light of these data, spectrometer results averaged over four size distributions are found to agree with similarly averaged impactor results to within a few percent: indicating that the optical properties or chemical composition of the sample aerosol must be known in order to achieve accurate optical aerosol spectrometer size analysis.

ASAS-SN Discovery of a Possible Galactic Nova ASASSN-18ix

NASA Astrophysics Data System (ADS)

Stanek, K. Z.; Kochanek, C. S.; Shields, J. V.; Thompson, T. A.; Chomiuk, L.; Strader, J.; Shappee, B. J.; Holoien, T. W.-S.; Prieto, J. L.; Dong, Subo; Stritzinger, M.

2018-04-01

During the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN, Shappee et al. 2014), using data from multiple ASAS-SN telescopes, we detect a new bright transient source, possibly a classical nova, but it might also be a young, large amplitude outburst of a cataclysmic variable Object RA (J2000) DEC (J2000) Gal l (deg) Gal b (deg) Disc.

Ondansetron reduces naturalistic drinking in non-treatment seeking alcohol dependent individuals with the LL 5′-HTTLPR genotype: a laboratory study

PubMed Central

Kenna, George A.; Zywiak, William H.; Swift, Robert M.; McGeary, John E.; Clifford, James S.; Shoaff, Jessica R.; Vuittonet, Cynthia; Fricchione, Samuel; Brickley, Michael; Beaucage, Kayla; Haass-Koffler, Carolina L.; Leggio, Lorenzo

2014-01-01

Background One hypothesis suggests that the differential response to ondansetron and serotonin specific re-uptake inhibitors (SSRIs) may be due to a functional polymorphism of the 5′-HTTLPR promoter region in SLC6A4, the gene that codes for the serotonin transporter (5-HTT). The LL 5′-HTTLPR genotype is postulated to be specifically sensitive to the effects of ondansetron with SS/SL 5′-HTTLPR genotypes sensitive to SSRIs. This study tests this hypothesis by matching non-treatment seeking alcohol dependent (AD) individuals with LL genotype to ondansetron and SS/SL genotypes to the SSRI sertraline, and mis-matching them assessing naturalistic and bar-laboratory alcohol drinking. Methods Seventy-seven AD individuals were randomized to one of two counterbalanced arms to receive sertraline 200mg/day or ondansetron 0.5 mg/day for three weeks followed by an alcohol self-administration experiment (ASAE), then received placebo for three weeks followed by a second ASAE. Individuals then received the alternate drug for three weeks followed by a third ASAE. Drinks per drinking day (DDD with drinks in SDUs) for 7 days prior to each ASAE and milliliters consumed during each ASAE were the primary outcomes. Results Fifty-five participants completed the study. The genotype x order interaction was significant [F(1,47) = 8.42, p = .006] for DDD. Three ANCOVAs were conducted for DDD during the week before each ASAE. Ondansetron compared to sertraline resulted in a significant reduction in DDD during the week before the first [F(1,47) = 7.64, p = .008] but not the third ASAE. There was no difference in milliliters consumed during each ASAE. Conclusion This study modestly supports the hypothesis that ondansetron may reduce DDD in AD individuals with the LL genotype as measured naturalistically. By contrast there was no support that ondansetron reduces drinking during the ASAEs or that sertraline reduces alcohol use in individuals who have SS/SL genotypes. We provide limited support that ondansetron may reduce drinking in non-treatment seeking individuals with the LL genotype. PMID:24773166

Long-term efficacy and safety of once-daily mesalazine granules for the treatment of active ulcerative colitis

PubMed Central

Böhm, Stephan Karl; Kruis, Wolfgang

2014-01-01

In 1977, 5-aminosalicylic acid (5-ASA) was discovered as a therapeutically active moiety of sulfasalazine (SASP) and was launched for topical and oral therapy of ulcerative colitis (UC) in 1984. As a first-step, delivery systems had to be developed to protect 5-ASA against absorption in the upper gastrointestinal tract, resulting in different and competing strategies (azo compounds, controlled release, and pH-dependent release). In a second step, at the beginning of the new century, coinciding with the expiration of patent protection for the first 5-ASA formulations, two component composite release mechanisms (pH-dependent and controlled release) were developed. Furthermore, the drug was formulated as granules instead of tablets, allowing higher unit strengths compared with tablets. Neither Salofalk Granu-Stix®, nor MMX 5-ASA, nor Pentasa® granules have initially been developed for once-daily (OD) dosing. A review of the achievements of 20 years of 5-ASA development has demonstrated that 5-ASA has equal efficacy compared with SASP at best, that there are no measurable differences in efficacy between various 5-ASA preparations, and that in a group of patients tolerating SASP, adverse event profiles of SASP and 5-ASA did not differ significantly, with SASP being the far cheaper substance. Therefore, drug adherence came into focus as a new goal for improving UC therapy. Although adherence is a complex and multifactorial construct, a simple dosing schedule may contribute to higher drug adherence and better efficacy of treatment. Simultaneously, the US 5-ASA market, estimated to be worth US$1.4 billion, is expected to grow continuously. Naturally, this very competitive market is not only driven by scientific progress but also by commercial interests. Thus, patents for minor changes to the formulation may serve as protection against drug companies trying to launch generic versions. Randomized controlled trials performed on OD dosing in induction of remission have demonstrated that OD administration of 5-ASA is as effective as conventional dosing in mild to moderate active UC. The three 5-ASA products MMX, Salofalk®, and Pentasa® employed in those studies so far have not shown differences in efficacy between OD and conventional dosing. No differences regarding safety outcomes have been detected between OD and conventional dosing, including incidence of adverse events, serious adverse events, or withdrawal from treatment due to an adverse event. Although the majority of patients prefer OD dosing to conventional dosing, it was not possible to detect differences in adherence between OD and multiple dose regimens in the clinical trial setting. Well-designed and controlled large-scale community-based studies are necessary to further investigate and prove the point of improved long-term adherence and treatment efficacy in OD dosing. PMID:25285021

A Performance Assessment of a Tactical Airborne Separation Assistance System using Realistic, Complex Traffic Flows

NASA Technical Reports Server (NTRS)

Smith, Jeremy C.; Neitzke, Kurt W.; Bussink, Frank J. L.

2008-01-01

This paper presents the results from a study that investigates the performance of aspects of an Airborne Separation Assistance System (ASAS) under varying demand levels using realistic traffic patterns. This study only addresses the tactical aspects of an ASAS using aircraft state data (latitude, longitude, altitude, heading and speed) to detect and resolve projected conflicts. The main focus of this paper is to determine the extent to which sole reliance on the proposed tactical ASAS can maintain aircraft separation at demand levels up to three times current traffic. The effect of mixing ASAS equipped aircraft with non-equipped aircraft that do not have the capability to self-separate is also investigated.

Rectal 5-aminosalicylic acid for induction of remission in ulcerative colitis.

PubMed

Marshall, John K; Thabane, Marroon; Steinhart, A Hillary; Newman, Jamie R; Anand, Anju; Irvine, E Jan

2010-01-20

5-Aminosalicylates (5-ASA) are considered a first-line therapy for inducing and maintaining remission of mild to moderately active ulcerative colitis (UC). When inflammation in UC is limited to the distal colon, 5-ASA can also be administered rectally as a suppository, enema or foam. A systematic review was undertaken to evaluate the efficacy of rectal 5-ASA for treating active distal UC. Electronic searches of the MEDLINE database (1966-2008), the Cochrane Central Register of Controlled Trials and the Cochrane IBD/FBD Group Specialized Trials Register were supplemented by manual reviews of reference listings and conference proceedings. Randomized trials comparing rectal 5-ASA to placebo or another active therapy were eligible for inclusion. Eligible trials enrolled patients with a distal disease margin less than 60 cm from the anal verge or distal to the splenic flexure. Trials that enrolled subjects less than 12 years of age were excluded. Eligibility was assessed by three authors. Data were extracted by two authors using standardized forms. Pooled odds ratios (POR) for inducing improvement and remission by symptomatic, endoscopic and histologic criteria were calculated using an intention to treat principle. Fixed effects models were used unless heterogeneity was encountered within groups (P < 0.10), where random effects models were used. All statistical analyses were performed using RevMan 5. Where sufficient data were available, subgroup analyses were performed for disease extent, total daily 5-ASA dose, 5-ASA formulation (enema,suppository, foam) and the type of control intervention (placebo or another active therapy). Thirty-eight studies fulfilled the inclusion criteria. Rectal 5-ASA was superior to placebo for inducing symptomatic, endoscopic and histological improvement and remission, with POR for symptomatic improvement 8.87 (8 trials, 95% CI: 5.30 to 14.83; P < 0.00001), endoscopic improvement 11.18 (5 trials, 95% CI 5.99 to 20.88; P < 0.00001), histologic improvement 7.69 (6 trials, 95% CI 3.26 to 18.12; P < 0.00001), symptomatic remission 8.30 (8 trials, 95% CI 4.28 to 16.12; P < 0.00001), endoscopic remission 5.31 (7 trials, 95% CI 3.15 to 8.92; P < 0.00001), and histologic remission 6.28 (5 trials, 95% CI 2.74 to 14.40; P < 0.0001). Rectal 5-ASA was superior to rectal corticosteroids for inducing symptomatic improvement and remission with POR 1.56 (6 trials, 95% CI 1.15 to 2.11; P = 0.004) and 1.65 (6 trials, 95% CI 1.11 to 2.45; P = 0.01), respectively. Rectal 5-ASA was not superior to oral 5-ASA for symptomatic improvement (POR 2.25; 95% CI 0.53 to 19.54; P = 0.27). Neither total daily dose nor 5-ASA formulation affected treatment response. Rectal 5-ASA should be considered a first-line therapy for patients with mild to moderately active distal UC. The optimal total daily dose and dose frequency of 5-ASA remain to be determined. Future research should define differences in efficacy among patient subgroups defined by proximal disease margin and disease activity. There is a strong need for consensus standardization of outcome measurements for clinical trials in ulcerative colitis.

Modulation of mitomycin C-induced genotoxicity by acetyl- and thio- analogues of salicylic acid.

PubMed

Pawar, Amol Ashok; Vikram, Ajit; Tripathi, Durga Nand; Padmanabhan, Shweta; Ramarao, Poduri; Jena, Gopabandhu

2009-01-01

Recent reports regarding acetylsalicylic acid (ASA) and its metabolites suggest suppressive effects against mitomycin C (MMC)-induced genotoxicity in a mice chromosomal aberration assay. Keeping this in mind, the potential anti-genotoxic effect of the thio-analogue of salicylic acid namely thio-salicylic acid (TSA) was speculated upon. The present study investigated and compared the anti-genotoxic potential of ASA and TSA. The study was performed in male swiss mice (20+/-2 g) using single-cell gel electrophoresis and a peripheral blood micronucleus assay. ASA and TSA (5, 10 or 20 mg/kg) were administered 15 minutes after MMC (1 mg/kg) once daily for 3 or 7 days. Both ASA and TSA significantly decreased the DNA damage induced by MMC as indicated by a decrease in the comet parameters in bone marrow cells and decreased frequencies of micronucleated reticulocytes in peripheral blood. The results clearly demonstrate the anti-genotoxic potential of ASA and TSA.

Molecular modeling and multispectroscopic studies of the interaction of mesalamine with bovine serum albumin.

PubMed

Shahabadi, Nahid; Fili, Soraya Moradi

2014-01-24

The interaction of mesalamine (5-aminosalicylic acid (5-ASA)) with bovine serum albumin (BSA) was investigated by fluorescence quenching, absorption spectroscopy, circular dichroism (CD) techniques, and molecular docking. Thermodynamic parameters (ΔH<0 and ΔS 0) indicated that the hydrogen bond and electrostatic forces played the major role in the binding of 5-ASA to BSA. The results of CD and UV-vis spectroscopy showed that the binding of this drug to BSA induces some conformational changes in BSA. Displacement experiments predicted that the binding of 5-ASA to BSA is located within domain III, Sudlows site 2, that these observations were substantiated by molecular docking studies. In addition, the docking result shows that the 5-ASA in its anionic form mainly interacts with Gln-416 residue through one hydrogen bond between H atom of 5-ASA anion and the adjacent O atom of the hydroxyl group of Gln-416. Copyright © 2013 Elsevier B.V. All rights reserved.

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

PubMed

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

2017-04-15

The kinetics of browning and the correlation between browning products (BPs) and pyrazine compounds were investigated by heating equimolar l-ascorbic acid (ASA)/acidic amino acids under weak alkaline conditions at 120-150°C for 10-120min. The formations of BPs and pyrazine compounds from the reaction were monitored by UV-vis and SPME-GC-FID, respectively. The formation of BPs in both ASA/l-glutamic acid and ASA/l-aspartic acid model reaction systems followed zero order reaction kinetics with activation energies (E a ) of 90.13 and 93.38kJ/mol, respectively. ASA/l-aspartic acid browned at a slightly higher rate than ASA/l-glutamic acid. The total concentration of pyrazine compounds was highly and positively correlated with that of BPs. Based on the observed kinetic data, the formation mechanisms of BPs and pyrazine compounds were proposed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Novel levan and pNIPA temperature sensitive hydrogels for 5-ASA controlled release.

PubMed

Osman, Asila; Oner, Ebru Toksoy; Eroglu, Mehmet S

2017-06-01

Levan based cross-linker was successfully synthesized and used to prepare a series of more biocompatible and temperature responsive levan/N-isopropyl acrylamide (levan/pNIPA) hydrogels by redox polymerization at room temperature. Volume phase transition temperature (VPTT) of the hydrogels were precisely determined by derivative differential scanning calorimetry (DDSC). Incorporation of levan into the pNIPA hydrogel increased the VPTT from 32.8°C to 35.09°C, approaching to body temperature. Swelling behavior and 5-aminosalicylic acid (5-ASA) release of the hydrogels were found to vary significantly with temperature and composition. Moreover, a remarkable increase in thermal stability of levan within hydrogel with increase of pNIPA content was recorded. The biocompatibility of the hydrogels were tested against mouse fibroblast L929 cell line in phosphate buffer saline (PBS, pH 7.4). The hydrogels showed increasing biocompatibility with increasing levan ratio, indicating levan enhanced the hydrogel surface during swelling. Copyright © 2017 Elsevier Ltd. All rights reserved.

Can 5-aminosalicylic acid suppository decrease the pain after rectal band ligation?

PubMed

Kayhan, Burcak; Ozer, Digdem; Akdogan, Meral; Ozaslan, Ersan; Yuksel, Osman

2008-06-14

To investigate the effect of 5-aminosalicylic acid (5-ASA) suppositories on rectal band ligation-induced pain. Sixty patients were randomized into two treatment groups. Our results showed that there was no difference between 5-ASA suppository group and the control group for pain control. 5-ASA may be an alternative treatment for hemorrhoids; however, it does not affect the rectal band ligation-induced pain.

Temporal Aspects of the Action of ASA404 (Vadimezan; DMXAA)

PubMed Central

Baguley, Bruce C; Siemann, Dietmar W

2013-01-01

ASA404, a flavonoid tumor-vascular disrupting agent (Tumor-VDA), is in clinical trial for the treatment of non-small cell lung cancer. Its action differs from both that of the tubulin binding class of Tumor-VDAs and antiangiogenic agents. In mice, ASA404 induces a sequence of changes in tumor tissue, starting within one hour with increased vascular permeability, increased endothelial apoptosis and decreased blood flow. Later effects include the release of serotonin, induction of tumor necrosis factor and other cytokines and chemokines, as well as induction of nitric oxide. This cascade of events induces sustained effects on blood flow, tumor hypoxia, vascular failure, inflammatory responses and, in some tumors, complete regression. One feature of the action of ASA404 against murine tumors is its ability to potentiate the effects of radiation and a variety of chemotherapeutic agents. The flavonoid class appears to be unique because of its dual action on vascular endothelial function and innate immunity. The translation of preclinical to clinical results demands an understanding of both the mechanisms underlying the dual effects and the species differences in ASA404 activity. Clinical trials indicate that the future of ASA404 as an effective agent relies on a deep appreciation of its cellular action. PMID:20964495

Acetyl salicylic acid inhibits Th17 airway inflammation via blockade of IL-6 and IL-17 positive feedback

PubMed Central

Moon, Hyung-Geun; Kang, Chil Sung; Choi, Jun-Pyo; Choi, Dong Sic; Choi, Hyun Il; Choi, Yong Wook; Jeon, Seong Gyu; Yoo, Joo-Yeon; Jang, Myoung Ho; Gho, Yong Song; Kim, Yoon-Keun

2013-01-01

T-helper (Th)17 cell responses are important for the development of neutrophilic inflammatory disease. Recently, we found that acetyl salicylic acid (ASA) inhibited Th17 airway inflammation in an asthma mouse model induced by sensitization with lipopolysaccharide (LPS)-containing allergens. To investigate the mechanism(s) of the inhibitory effect of ASA on the development of Th17 airway inflammation, a neutrophilic asthma mouse model was generated by intranasal sensitization with LPS plus ovalbumin (OVA) and then challenged with OVA alone. Immunologic parameters and airway inflammation were evaluated 6 and 48 h after the last OVA challenge. ASA inhibited the production of interleukin (IL)-17 from lung T cells as well as in vitro Th17 polarization induced by IL-6. Additionally, ASA, but not salicylic acid, suppressed Th17 airway inflammation, which was associated with decreased expression of acetyl-STAT3 (downstream signaling of IL-6) in the lung. Moreover, the production of IL-6 from inflammatory cells, induced by IL-17, was abolished by treatment with ASA, whereas that induced by LPS was not. Altogether, ASA, likely via its acetyl moiety, inhibits Th17 airway inflammation by blockade of IL-6 and IL-17 positive feedback. PMID:23306703

Mortality in perforated duodenal ulcer depends upon pre-operative risk: a retrospective 10-year study.

PubMed

Larkin, J O; Bourke, M G; Muhammed, A; Waldron, R; Barry, K; Eustace, P W

2010-12-01

Most patients presenting with acutely perforated duodenal ulcer undergo operation, but conservative treatment may be indicated when an ulcer has spontaneously sealed with minimal/localised peritoneal irritation or when the patient's premorbid performance status is poor. We retrospectively reviewed our experience with operative and conservative management of perforated duodenal ulcers over a 10-year period and analysed outcome according to American Society of Anesthesiologists (ASA) score. The records of all patients presenting with perforated duodenal ulcer to the Department of Surgery, Mayo General Hospital, between January 1998 and December 2007 were reviewed. Age, gender, co-morbidity, ASA-score, clinical presentation, mode of management, operative procedures, morbidity and mortality were considered. Of 76 patients included, 48 (44 operative, 4 conservative) were ASA I-III, with no mortality irrespective of treatment. Amongst 28 patients with ASA-score IV/V, mortality was 54.5% (6/11) following operative management and 52.9% (9/17) with conservative management. In patients with a perforated duodenal ulcer and ASA-score I-III, postoperative outcome is uniformly favourable. We recommend these patients have repair with peritoneal lavage performed, routinely followed postoperatively by empirical triple therapy. Given that mortality is equivalent between ASA IV/V patients whether managed operatively or conservatively, we suggest that both management options are equally justifiable.

Mediators of the Relationship Between Sexual Assault and Sexual Behaviors in College Women.

PubMed

Kelley, Erika L; Gidycz, Christine A

2017-07-01

Some research shows that sexual assault victimization is associated with increased engagement in risky sexual behavior (e.g., intercourse without use of a condom or contraceptives), whereas other research indicates sexual assault victimization is related to sexual aversion. The purpose of the current study was to examine whether posttraumatic stress symptoms, alcohol use, and sexual assertiveness mediated the relationship between adolescent/emerging adulthood sexual assault (ASA) and risky sexual behavior, and whether posttraumatic stress symptoms mediated the relationship between ASA and sexual aversion, among college women. A sample of 462 women from a Midwestern university completed online questionnaires assessing ASA, child sexual abuse (CSA), posttraumatic stress symptoms (i.e., intrusion, avoidance, hyperarousal, and dissociation), alcohol use, sexual assertiveness, risky sexual behavior, and sexual aversion. CSA was considered as a covariate in the mediation models. Results of mediation analyses showed that the relationship between ASA and risky sexual behavior with a new partner was partially mediated by greater alcohol use and lower sexual assertiveness and that the relationship between ASA and risky sexual behavior with a regular partner was partially mediated by greater alcohol use. Results of a model examining mediators of ASA and sexual aversion detected no significant mediators. Results suggest that college women with a history of ASA would benefit from psychoeducation on the effect of alcohol on sexual decision-making, as well as from sexual assertiveness skills training, to reduce potential risks associated with risky sexual behaviors, particularly with lesser known partners, including sexually transmitted infections and sexual revictimization.

Patent Foramen Ovale With Atrial Septal Aneurysm Is Strongly Associated With Migraine With Aura: A Large Observational Study.

PubMed

Snijder, Roel J R; Luermans, Justin G L M; de Heij, Albert H; Thijs, Vincent; Schonewille, Wouter J; Van De Bruaene, Alexander; Swaans, Martin J; Budts, Werner I H L; Post, Martijn C

2016-12-01

A patent foramen ovale (PFO) with atrial septal aneurysm (ASA) has been identified as a risk factor for cryptogenic stroke. Patients with migraine with aura (MA) appear to be at risk for silent brain infarction, which might be related to the presence of a PFO. However, the association between MA and PFO with ASA has never been reported. We examined this association in a large observational study. Patients (>18 years) who underwent an agitated saline transesophageal echocardiography (cTEE) at our outpatient clinics within a timeframe of 4 years were eligible to be included. Before cTEE they received a validated headache questionnaire. Two neurologists diagnosed migraine with or without aura according to the International Headache Criteria. A total of 889 patients (mean age 56.4±14.3 years, 41.7% women) were included. A PFO was present in 23.2%, an isolated ASA in 2.7%, and a PFO with ASA in 6.9%. The occurrence of migraine was 18.9%; the occurrence of MA was 8.1%. The prevalence of PFO with ASA was significantly higher in patients with MA compared to patients without migraine (18.1% vs 6.1%; OR 3.72, 95% CI 1.86-7.44, P<0.001). However, a PFO without ASA was not significantly associated with MA (OR 1.50, 95% CI 0.79-2.82, P=0.21). Interestingly, a PFO with ASA was strongly associated with MA (OR 2.71, 95% CI 1.23-5.95, P=0.01). In this large observational study, PFO with ASA was significantly associated with MA only. PFO closure studies should focus on this specific intra-atrial anomaly. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

CCD Photometry and Roche Modeling of the Eclipsing Deep Low Mass, Overcontact Binary Star System TYC 2058-753-1

NASA Astrophysics Data System (ADS)

Alton, K. B.

2018-06-01

Abstract TYC 2058-753-1 (NSVS 7903497; ASAS 165139+2255.7) is a W UMa binary system (P = 0.353205 d) which has not been rigorously studied since first being detected nearly 15 years ago by the ROTSE-I telescope. Other than the unfiltered ROTSE-I and monochromatic All Sky Automated Survey (ASAS) survey data, no multi-colored light curves (LC) have been published. Photometric data collected in three bandpasses (B, V, and Ic) at Desert Bloom Observatory in June 2017 produced six times-of-minimum for TYC 2058-753-1 which were used to establish a linear ephemeris from the first directly measured Min I epoch (HJD0). No published radial velocity data are available for this system, however, since this W UMa binary undergoes a very obvious total eclipse, Roche modeling produced a well-constrained photometric value for the mass ratio (qph = 0.103 ± 0.001). This low-mass ratio binary star system also exhibits a high degree of contact (f > 56%). There is a suggestion from the ROTSE-I and ASAS survey data as well as from the new LCs reported herein that maximum light during quadrature (Max I and Max II) is often not equal. As a result, Roche modeling of the TYC 2058-753-1 LCs was investigated with and without surface spots to address this asymmetry as well as a diagonally-aligned flat bottom during Min I that was observed in 2017.

Hyperbaric index in the primary prevention of hypertensive complications in high-risk pregnancy.

PubMed

Otero González, Alfonso; Uribe Moya, Silvia; Arenas Moncaleano, Ivan Gilberto; Borrajo Prol, María Paz; García García, María Jesús; López Sánchez, Luis

2015-01-01

Preeclampsia (PE) is a major cause of fetal morbidity and mortality. In the Western World, PE affects 2-7% of pregnancies and is responsible for 50,000 deaths annually. Early detection is a priority as it can change the clinical course, but there are no biomarkers or instrumental methods with high sensitivity and specificity. Only the hyperbaric index has a sensitivity and specificity of 99% for early identification of pregnant women at risk of developing PE, but its use is not widespread. To assess the usefulness of the hyperbaric index in the primary prevention of hypertensive pregnancy complications in a public healthcare area. This is a retrospective study of pregnancies that occurred in our area during the period 2007-2012 (N=11,784). The diagnosis was established by the hyperbaric index and pregnant women at risk were treated with ASA at night. In pregnant patients referred to the nephrology clinic (38.2%), diagnosed as high-risk for PE, and treated with 100mg ASA/night (from week 17), the incidence of PE episodes was reduced by 96.94. Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Market Survey and Analysis in Support of ASAS Computer-Based Training System Design

DTIC Science & Technology

1988-11-01

development nf a recommended strategy for incorporating CBT in the ASAS/ENSCE training system. Approach - In order to establish the state of the art and...a training system which will meet ASAS training requirements. Eleven subsystems are described in terms of their functional input to the overall...keyboard and displays used in actual operation are also used in training, maximizing the transfer effect from practice situations to actual system

Acute exposure to the biopesticide azadirachtin affects parameters in the gills of common carp (Cyprinus carpio).

PubMed

Murussi, Camila R; Costa, Maiara D; Leitemperger, Jossiele W; Flores-Lopes, Fábio; Menezes, Charlene C; Loebens, Luisa; de Avila, Luis Antonio; Rizzetti, Tiele M; Adaime, Martha B; Zanella, Renato; Loro, Vania L

2016-02-01

The biopesticide, azadirachtin (Aza) is less hazardous to the environment, but may cause several toxic effects in aquatic organisms. The Cyprinus carpio (n=12, for all concentrations) after 10days of acclimation under controlled conditions, were exposed at 20, 40, and 60μL/L of Aza during 96h. After this period, fish were anesthetized and euthanized then mucus layer and gills collected. In this study, the effects of exposure to different Aza concentrations were analysed through a set of biomarkers: Na(+)/K(+-)ATPase, lipid peroxidation (TBARS), protein carbonyl (PC), superoxide dismutase (SOD), glutathione-S-transferase (GST), catalase (CAT), glutathione peroxidase (GPx), non-protein thiols (NPSH), ascorbic acid (AsA) and histological parameters and, yet, protein and glucose concentration in the surface area of mucous layer. Na(+)K(+-)ATPase was inhibited at 40 and 60μL/L compared to control. TBARS decreased at 40μL/L compared to control. PC, SOD and GST increased at 60μL/L in comparison to control. CAT increased at 20 and 60μL/L, and GPx increased in all Aza concentrations compared to control. NPSH decreased and AsA increased in all concentrations in comparison to control. Histological analyses demonstrated an increase in the intensity of the damage with increasing Aza concentration. Alterations in histological examination were elevation and hypertrophy of the epithelial cells of the secondary filament, hypertrophy and hyperplasia of the mucous and chlorate cells and lamellar aneurism. Glucose and protein concentrations in mucus layer increased at 60μL/L compared to control. In general, we suggest that 60μL/L Aza concentration affected several parameters causing disruptions carp metabolism. Copyright © 2015 Elsevier Inc. All rights reserved.

Genome-scale characterization of RNA tertiary structures and their functional impact by RNA solvent accessibility prediction.

PubMed

Yang, Yuedong; Li, Xiaomei; Zhao, Huiying; Zhan, Jian; Wang, Jihua; Zhou, Yaoqi

2017-01-01

As most RNA structures are elusive to structure determination, obtaining solvent accessible surface areas (ASAs) of nucleotides in an RNA structure is an important first step to characterize potential functional sites and core structural regions. Here, we developed RNAsnap, the first machine-learning method trained on protein-bound RNA structures for solvent accessibility prediction. Built on sequence profiles from multiple sequence alignment (RNAsnap-prof), the method provided robust prediction in fivefold cross-validation and an independent test (Pearson correlation coefficients, r, between predicted and actual ASA values are 0.66 and 0.63, respectively). Application of the method to 6178 mRNAs revealed its positive correlation to mRNA accessibility by dimethyl sulphate (DMS) experimentally measured in vivo (r = 0.37) but not in vitro (r = 0.07), despite the lack of training on mRNAs and the fact that DMS accessibility is only an approximation to solvent accessibility. We further found strong association across coding and noncoding regions between predicted solvent accessibility of the mutation site of a single nucleotide variant (SNV) and the frequency of that variant in the population for 2.2 million SNVs obtained in the 1000 Genomes Project. Moreover, mapping solvent accessibility of RNAs to the human genome indicated that introns, 5' cap of 5' and 3' cap of 3' untranslated regions, are more solvent accessible, consistent with their respective functional roles. These results support conformational selections as the mechanism for the formation of RNA-protein complexes and highlight the utility of genome-scale characterization of RNA tertiary structures by RNAsnap. The server and its stand-alone downloadable version are available at http://sparks-lab.org. © 2016 Yang et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

[Perioperative mortality and morbidity in the year 2000 in 502 Japanese certified anesthesia-training hospitals: with a special reference to ASA-physical status--report of the Japan Society of Anesthesiologists Committee on Operating Room Safety].

PubMed

Irita, Kazuo; Kawashima, Yasuo; Tsuzaki, Koichi; Iwao, Yasuhide; Kobayashi, Tsutomu; Seo, Norimasa; Goto, Yasuyuki; Morita, Kiyoshi; Shiraishi, Yoshito; Nakao, Yasuo; Tanaka, Yoshifumi; Tosaki, Youko; Dohi, Shuji; Obara, Hidefumi

2002-01-01

Perioperative mortality and morbidity in Japan from Jan. 1 to Dec. 31, 2000 were studied retrospectively. Committee on Operating Room Safety in Japanese Society of Anesthesiologists (JSA) sent confidential questionnaires to 794 certified training hospitals of JSA and received answers from 67.6% of the hospitals. We analyzed their answers with a special reference to ASA physical status (ASA-PS). The total number of anesthesia available for this analysis was 897,733. The percentages of patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E are 38.0, 40.3, 8.5, 0.4, 4.3, 5.3, 2.5, and 0.7%, respectively. Mortality and morbidity from all kinds of causes including anesthetic management, intraoperative events, co-existing diseases, and surgical problems were as follows. The incidences of cardiac arrest (per 10,000 cases of anesthesia) were 1.11, 3.26, 12.25, 54.60, 0.77, 4.46, 21.08 and 217.75 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The incidences of critical events including cardiac arrest, severe hypotension, and severe hypoxemia were 6.89, 20.22, 62.18, 148.21, 6.71, 20.38, 106.72 and 592.21 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The mortality rates (death during anesthesia and within 7 postoperative days) after cardiac arrest were 0.26, 0.77, 3.69, 41.60, 0.00, 1.06, 9.42 and 163.31 per 10,000 cases of anesthesia in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The overall mortality rates were 0.32, 1.38, 9.75, 70.20, 0.26, 2.12, 29.15 and 353.02 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. Overall mortality and morbidity were higher in emergency anesthesia than in elective anesthesia. ASA-PS correlated well with overall mortality and morbidity, regardless of etiology. The incidences of cardiac arrest totally attributable to anesthesia were 0.23, 0.50, 1.32, 0.00, 0.00, 0.85, 2.69 and 4.95 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The incidences of all critical events totally attributable to anesthesia were 3.13, 5.56, 11.46, 5.20, 3.87, 5.94, 13.90 and 14.85 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The mortality rates after cardiac arrest totally attributable to anesthesia were 0.03, 0.03, 0.00, 0.00, 0.00, 0.21, 0.45 and 3.30 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The overall mortality rates totally attributable to anesthesia were 0.03, 0.06, 0.00, 0.00, 0.00, 0.21, 0.45 and 6.60 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The overall mortality rate totally attributable to anesthesia among patients with good physical status (ASA-PS of I, II, I E, II E) was 0.05. Anesthetic management was mainly responsible for critical events in patients with good physical status, while coexisting diseases were in those with poor physical status. Surgical problems including procedures and massive hemorrhage were the leading causes of mortality in patients with good physical status. We reconfirmed that ASA-PS is useful to predict perioperative mortality and morbidity. It also seems likely that we should make much more efforts to reduce anesthetic morbidity in patients with good physical status, and to improve preanesthetic assessment and preparation in those with poor physical status. Reducing mortality and morbidity from surgical problems is also required for improving perioperative mortality.

Monitoring ASA and P2Y12-specific platelet inhibition--comparison of conventional (single) and multiple electrode aggregometry.

PubMed

Krüger, Jan-Christopher; Meves, Saskia H; Kara, Kaffer; Mügge, Andreas; Neubauer, Horst

2014-10-01

Several platelet function test systems exist for the evaluation of the platelet inhibitory effect in patients on P2Y12 inhibitors and/or acetylsalicylic acid (ASA, aspirin) therapy. Studies comparing different available assays found only a poor correlation. The objective of the present study was to evaluate the correlation and agreement between single electrode (SEA) and multiple electrode (MEA) aggregometry. In whole blood arachidonic acid (AA) and adenosine diphosphate (ADP)-induced platelet aggregation was measured simultaneously using SEA (Chrono-Log) and MEA (Multiplate). We analyzed a total of 226 measurements taken from 58 patients on single ASA therapy or dual antiplatelet therapy with ASA and a thienopyridine. A cut-off value for clopidogrel/prasugrel high on-treatment platelet reactivity (HPR) of > 47 units (U) was chosen for MEA testing using hirudin and > 5 Ohm for SEA with citrate anticoagulated blood samples. The respective cut-off values for ASA HPR were > 30 U for the MEA assay and > 1 Ohm for SEA testing. There was a good correlation of the prevalence of thienopyridine-HPR in both whole blood assays (Spearman rank correlation coefficient r = 0.698) and a good inter-rate accordance (Cohen's Kappa statistic κ = 0.648). For AA-induced aggregation, the correlation of the results obtained was significant (r = 0.536; p < 0.001) and detecting ASA-HPR revealed a moderate (κ = 0.482) correlation between both impedance aggregometry assays. Platelet function testing using SEA and MEA provided both good accordance and correlation and therefore study results obtained by these two assays similarly enabled the detection of HPR of thienopyridine (and ASA) therapy.

Effect of rebamipide on gastric bleeding and ulcerogenic responses induced by aspirin plus clopidogrel under stimulation of acid secretion in rats.

PubMed

Takeuchi, Koji; Takayama, Shinichi; Hashimoto, Erika; Itayama, Misaki; Amagase, Kikuko; Izuhara, Chitose

2014-12-01

We examined the prophylactic effect of rebamipide on gastric bleeding induced by the perfusion of aspirin (acetylsalicylic acid [ASA]) plus clopidogrel under the stimulation of acid secretion in rats. Under urethane anesthesia, acid secretion was stimulated by the i.v. infusion of histamine (8 mg/kg/h), and the stomach was perfused with 25 mmol/L ASA at a rate of 0.4 mL/min. Gastric bleeding was evaluated as the concentration of hemoglobin in the perfusate. Clopidogrel (30 mg/kg) was given p.o. 24 h before the perfusion. Rebamipide (3-30 mg/kg) or other antiulcer drugs were given i.d. before the ASA perfusion. Slight gastric bleeding or damage was observed with the perfusion of ASA under the stimulation of acid secretion, whereas these responses were significantly increased in the presence of clopidogrel. Both omeprazole and famotidine inhibited acid secretion and prevented these responses to ASA plus clopidogrel. Rebamipide had no effect on acid secretion, but dose-dependently prevented gastric bleeding in response to ASA plus clopidogrel, with the degree of inhibition being almost equivalent to that of the antisecretory drugs, and the same effects were obtained with the gastroprotective drugs, irsogladine and teprenone. These agents also reduced the severity of gastric lesions, although the effects were less than those of the antisecretory drugs. These results suggest that the antiplatelet drug, clopidogrel, increases gastric bleeding induced by ASA under the stimulation of acid secretion, and the gastroprotective drug, rebamipide, is effective in preventing the gastric bleeding induced under such conditions, similar to antisecretory drugs. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Longterm Hydroxychloroquine Therapy and Low-dose Aspirin May Have an Additive Effectiveness in the Primary Prevention of Cardiovascular Events in Patients with Systemic Lupus Erythematosus.

PubMed

Fasano, Serena; Pierro, Luciana; Pantano, Ilenia; Iudici, Michele; Valentini, Gabriele

2017-07-01

Systemic lupus erythematosus (SLE) is associated with an increased risk of cardiovascular disease (CVD). Thromboprophylaxis with low-dose aspirin (ASA) and hydroxychloroquine (HCQ) seems promising in SLE. We investigated the effects of HCQ cumulative dosages (c-HCQ) and the possible synergistic efficacy of ASA and HCQ in preventing a first CV event (CVE) in patients with SLE. Patients consecutively admitted to our center who, at admission, satisfied the 1997 American College of Rheumatology and/or 2012 Systemic Lupus Collaborating Clinics classification criteria for SLE, and had not experienced any CVE, were enrolled. The occurrence of a thrombotic event, use of ASA, and c-HCQ were recorded. Kaplan-Meier analysis was performed to determine the c-HCQ associated with a lower incidence of CVE. Cox regression analysis served to identify factors associated with a first CVE. For the study, 189 patients with SLE were enrolled and monitored for 13 years (median). Ten CVE occurred during followup. At Kaplan-Meier analysis, the CVE-free rate was higher in ASA-treated patients administered a c-HCQ > 600 g (standard HCQ dose for at least 5 yrs) than in patients receiving ASA alone, or with a c-HCQ dose < 600 g (log-rank test chi-square = 4.01, p = 0.04). Multivariate analysis showed that antimalarials plus ASA protected against thrombosis (HR 0.041 and HR 0.047, respectively), while antiphospholipid antibodies (HR 17.965) and hypertension (HR 18.054) increased the risk of a first CVE. Our results suggest that prolonged use of HCQ plus ASA is thromboprotective in SLE and provides additional evidence for its continued use in patients with SLE.

Platelet function in whole-blood donors is impaired: the effects of painkillers.

PubMed

Curvers, Joyce; Dielis, Arne W J H; Heeremans, Judith; van Wersch, Jan W J

2007-01-01

Aspirin (ASA) or non-aspirin-like nonsteroidal anti-inflammatory drugs (NSAIDs) influence platelet (PLT) function by inhibiting cyclooxygenase enzymes. In this study, the aim was to address the use of ASA or NSAIDs before donation and the effect on PLT function. Donors were asked questions about recent use of ASA or NSAIDs. Furthermore, PLT function was evaluated by measurement of the closure time (CT) in a PLT function analyzer (PFA-100, Dade Behring) and by aggregometry (response to ADP or arachidonic acid [AA]). Of 100 questioned donors, 22 percent had used ASA (n = 4), NSAIDs (n = 6), or paracetamol (n = 12) before donation. Upon assessment of the PLT function in the PFA-100, 27 donors showed values of greater than 180 seconds, indicative of impaired PLT function. Of these, only 7 had used pain killers before donation. Furthermore, 15 of 22 users had normal CTs. Aggregation after stimulation with AA was absent in 33 PLT-rich samples. Again only 8 had reported use of ASA (3), NSAIDs (1), or paracetamol (4). Of the 22 users, 14 had normal AA aggregation responses. All donor samples showed ADP-induced aggregation, indicating PLT integrity. There was no difference between the group of donors who reported the intake of ASA or NSAIDs and the group of donors who did not with respect to the tested PLT function assays. It is concluded that there is a considerable group of donors that use PLT-influencing medication before donation. A relation between the reported use and impaired PLT function in blood donors could not be established, however. Impaired PLT function as tested may have other causes than intake of ASA or NSAIDs.

A mission-based productivity compensation model for an academic anesthesiology department.

PubMed

Reich, David L; Galati, Maria; Krol, Marina; Bodian, Carol A; Kahn, Ronald A

2008-12-01

We replaced a nearly fixed-salary academic physician compensation model with a mission-based productivity model with the goal of improving attending anesthesiologist productivity. The base salary system was stratified according to rank and clinical experience. The supplemental pay structure was linked to electronic patient records and a scheduling database to award points for clinical activity; educational, research, and administrative points systems were constructed in parallel. We analyzed monthly American Society of Anesthesiologist (ASA) unit data for operating room activity and physician compensation from 2000 through mid-2007, excluding the 1-yr implementation period (July 2004-June 2005) for the new model. Comparing 2005-2006 with 2000-2004, quarterly ASA units increased by 14% (P = 0.0001) and quarterly ASA units per full-time equivalent increased by 31% (P < 0.0001), while quarterly ASA units per anesthetizing location decreased by 10% (P = 0.046). Compared with a baseline year (2001), Instructor and Assistant Professor faculty compensation increased more than Associate Professor and Professor faculty (P < 0.001) in both pre- and postimplementation periods. There were larger compensation increases for the postimplementation period compared with preimplementation across faculty rank groupings (P < 0.0001). Academic and educational output was stable. Implementing a productivity-based faculty compensation model in an academic department was associated with increased mean supplemental pay with relatively fewer faculty. ASA units per month and ASA units per operating room full-time equivalent increased, and these metrics are the most likely drivers of the increased compensation. This occurred despite a slight decrease in clinical productivity as measured by ASA units per anesthetizing location. Academic and educational output was stable.

Allelic Variation in Paralogs of GDP-l-Galactose Phosphorylase Is a Major Determinant of Vitamin C Concentrations in Apple Fruit1[C][W][OA

PubMed Central

Mellidou, Ifigeneia; Chagné, David; Laing, William A.; Keulemans, Johan; Davey, Mark W.

2012-01-01

To identify the genetic factors underlying the regulation of fruit vitamin C (l-ascorbic acid [AsA]) concentrations, quantitative trait loci (QTL) studies were carried out in an F1 progeny derived from a cross between the apple (Malus × domestica) cultivars Telamon and Braeburn over three years. QTL were identified for AsA, glutathione, total antioxidant activity in both flesh and skin tissues, and various quality traits, including flesh browning. Four regions on chromosomes 10, 11, 16, and 17 contained stable fruit AsA-QTL clusters. Mapping of AsA metabolic genes identified colocations between orthologs of GDP-l-galactose phosphorylase (GGP), dehydroascorbate reductase (DHAR), and nucleobase-ascorbate transporter within these QTL clusters. Of particular interest are the three paralogs of MdGGP, which all colocated within AsA-QTL clusters. Allelic variants of MdGGP1 and MdGGP3 derived from the cultivar Braeburn parent were also consistently associated with higher fruit total AsA concentrations both within the mapping population (up to 10-fold) and across a range of commercial apple germplasm (up to 6-fold). Striking differences in the expression of the cv Braeburn MdGGP1 allele between fruit from high- and low-AsA genotypes clearly indicate a key role for MdGGP1 in the regulation of fruit AsA concentrations, and this MdGGP allele-specific single-nucleotide polymorphism marker represents an excellent candidate for directed breeding for enhanced fruit AsA concentrations. Interestingly, colocations were also found between MdDHAR3-3 and a stable QTL for browning in the cv Telamon parent, highlighting links between the redox status of the AsA pool and susceptibility to flesh browning. PMID:23001142

Measuring impairments of functioning and health in patients with axial spondyloarthritis by using the ASAS Health Index and the Environmental Item Set: translation and cross-cultural adaptation into 15 languages.

PubMed

Kiltz, U; van der Heijde, D; Boonen, A; Bautista-Molano, W; Burgos-Vargas, R; Chiowchanwisawakit, P; Duruoz, T; El-Zorkany, B; Essers, I; Gaydukova, I; Géher, P; Gossec, L; Grazio, S; Gu, J; Khan, M A; Kim, T J; Maksymowych, W P; Marzo-Ortega, H; Navarro-Compán, V; Olivieri, I; Patrikos, D; Pimentel-Santos, F M; Schirmer, M; van den Bosch, F; Weber, U; Zochling, J; Braun, J

2016-01-01

The Assessments of SpondyloArthritis international society Health Index (ASAS HI) measures functioning and health in patients with spondyloarthritis (SpA) across 17 aspects of health and 9 environmental factors (EF). The objective was to translate and adapt the original English version of the ASAS HI, including the EF Item Set, cross-culturally into 15 languages. Translation and cross-cultural adaptation has been carried out following the forward-backward procedure. In the cognitive debriefing, 10 patients/country across a broad spectrum of sociodemographic background, were included. The ASAS HI and the EF Item Set were translated into Arabic, Chinese, Croatian, Dutch, French, German, Greek, Hungarian, Italian, Korean, Portuguese, Russian, Spanish, Thai and Turkish. Some difficulties were experienced with translation of the contextual factors indicating that these concepts may be more culturally-dependent. A total of 215 patients with axial SpA across 23 countries (62.3% men, mean (SD) age 42.4 (13.9) years) participated in the field test. Cognitive debriefing showed that items of the ASAS HI and EF Item Set are clear, relevant and comprehensive. All versions were accepted with minor modifications with respect to item wording and response option. The wording of three items had to be adapted to improve clarity. As a result of cognitive debriefing, a new response option 'not applicable' was added to two items of the ASAS HI to improve appropriateness. This study showed that the items of the ASAS HI including the EFs were readily adaptable throughout all countries, indicating that the concepts covered were comprehensive, clear and meaningful in different cultures.

Measuring impairments of functioning and health in patients with axial spondyloarthritis by using the ASAS Health Index and the Environmental Item Set: translation and cross-cultural adaptation into 15 languages

PubMed Central

Kiltz, U; van der Heijde, D; Boonen, A; Bautista-Molano, W; Burgos-Vargas, R; Chiowchanwisawakit, P; Duruoz, T; El-Zorkany, B; Essers, I; Gaydukova, I; Géher, P; Gossec, L; Grazio, S; Gu, J; Khan, M A; Kim, T J; Maksymowych, W P; Marzo-Ortega, H; Navarro-Compán, V; Olivieri, I; Patrikos, D; Pimentel-Santos, F M; Schirmer, M; van den Bosch, F; Weber, U; Zochling, J; Braun, J

2016-01-01

Introduction The Assessments of SpondyloArthritis international society Health Index (ASAS HI) measures functioning and health in patients with spondyloarthritis (SpA) across 17 aspects of health and 9 environmental factors (EF). The objective was to translate and adapt the original English version of the ASAS HI, including the EF Item Set, cross-culturally into 15 languages. Methods Translation and cross-cultural adaptation has been carried out following the forward–backward procedure. In the cognitive debriefing, 10 patients/country across a broad spectrum of sociodemographic background, were included. Results The ASAS HI and the EF Item Set were translated into Arabic, Chinese, Croatian, Dutch, French, German, Greek, Hungarian, Italian, Korean, Portuguese, Russian, Spanish, Thai and Turkish. Some difficulties were experienced with translation of the contextual factors indicating that these concepts may be more culturally-dependent. A total of 215 patients with axial SpA across 23 countries (62.3% men, mean (SD) age 42.4 (13.9) years) participated in the field test. Cognitive debriefing showed that items of the ASAS HI and EF Item Set are clear, relevant and comprehensive. All versions were accepted with minor modifications with respect to item wording and response option. The wording of three items had to be adapted to improve clarity. As a result of cognitive debriefing, a new response option ‘not applicable’ was added to two items of the ASAS HI to improve appropriateness. Discussion This study showed that the items of the ASAS HI including the EFs were readily adaptable throughout all countries, indicating that the concepts covered were comprehensive, clear and meaningful in different cultures. PMID:27752358

Use of a Prototype Airborne Separation Assurance System for Resolving Near-Term Conflicts During Autonomous Aircraft Operations

NASA Technical Reports Server (NTRS)

Barhydt, Richard; Eischeid, Todd M.; Palmer, Michael T.; Wing, David J.

2003-01-01

NASA is currently investigating a new concept of operations for the National Airspace System, designed to improve capacity while maintaining or improving current levels of safety. This concept, known as Distributed Air/Ground Traffic Management (DAGTM), allows appropriately equipped autonomous aircraft to maneuver freely for flight optimization while resolving conflicts with other traffic and staying out of special use airspace and hazardous weather. In order to perform these tasks, pilots use prototype conflict detection, prevention, and resolution tools, collectively known as an Airborne Separation Assurance System (ASAS). While ASAS would normally allow pilots to resolve conflicts before they become hazardous, evaluation of system performance in sudden, near-term conflicts is needed in order to determine concept feasibility. An experiment was conducted in NASA Langley's Air Traffic Operations Lab to evaluate the prototype ASAS for enabling pilots to resolve near-term conflicts and examine possible operational effects associated with the use of lower separation minimums. Sixteen commercial airline pilots flew a total of 32 traffic scenarios that required them to use prototype ASAS tools to resolve close range pop-up conflicts. Required separation standards were set at either 3 or 5 NM lateral spacing, with 1000 ft vertical separation being used for both cases. Reducing the lateral separation from 5 to 3 NM did not appear to increase operational risk, as indicated by the proximity to the intruder aircraft. Pilots performed better when they followed tactical guidance cues provided by ASAS than when they didn't follow the guidance. In an effort to improve compliance rate, ASAS design changes are currently under consideration. Further studies will of evaluate these design changes and consider integration issues between ASAS and existing Airborne Collision Avoidance Systems (ACAS).

5-ASA affects cell cycle progression in colorectal cells by reversibly activating a replication checkpoint.

PubMed

Luciani, M Gloria; Campregher, Christoph; Fortune, John M; Kunkel, Thomas A; Gasche, Christoph

2007-01-01

Individuals with inflammatory bowel disease are at risk of developing colorectal cancer (CRC). Epidemiologic, animal, and laboratory studies suggest that 5-amino-salicylic acid (5-ASA) protects from the development of CRC by altering cell cycle progression and by inducing apoptosis. Our previous results indicate that 5-ASA improves replication fidelity in colorectal cells, an effect that is active in reducing mutations. In this study, we hypothesized that 5-ASA restrains cell cycle progression by activating checkpoint pathways in colorectal cell lines, which would prevent tumor development and improve genomic stability. CRC cells with different genetic backgrounds such as HT29, HCT116, HCT116(p53-/-), HCT116+chr3, and LoVo were treated with 5-ASA for 2-96 hours. Cell cycle progression, phosphorylation, and DNA binding of cell cycle checkpoint proteins were analyzed. We found that 5-ASA at concentrations between 10 and 40 mmol/L affects cell cycle progression by inducing cells to accumulate in the S phase. This effect was independent of the hMLH1, hMSH2, and p53 status because it was observed to a similar extent in all cell lines under investigation. Moreover, wash-out experiments demonstrated reversibility within 48 hours. Although p53 did not have a causative role, p53 Ser15 was strongly phosphorylated. Proteins involved in the ATM-and-Rad3-related kinase (ATR)-dependent S-phase checkpoint response (Chk1 and Rad17) were also phosphorylated but not ataxia telengectasia mutated kinase. Our data demonstrate that 5-ASA causes cells to reversibly accumulate in S phase and activate an ATR-dependent checkpoint. The activation of replication checkpoint may slow down DNA replication and improve DNA replication fidelity, which increases the maintenance of genomic stability and counteracts carcinogenesis.

Discovery and preclinical development of a novel prodrug conjugate of mesalamine with eicosapentaenoic acid and caprylic acid for the treatment of inflammatory bowel diseases.

PubMed

Kandula, Mahesh; Sunil Kumar, K B; Palanichamy, Sivanesan; Rampal, Ashok

2016-11-01

Mesalamine (5-ASA) is one of the drugs indicated as first line therapy in ulcerative colitis for induction and maintenance of remission. Sulfasalazine and formulations of 5-ASA (pH-dependent and controlled release formulations) were developed to minimize the systemic absorption and maximize the delivery of the mesalamine to colon. Although, its efficacy and safety is well documented there are approximately 30% nonresponders to 5-ASA therapy. This necessitates the need for novel therapeutic options to improve the efficacy and safety of the currently available 5-ASA therapy. CLX-103 is a novel, patented prodrug molecular conjugate of mesalamine, eicosapentaenoic acid and caprylic acid designed to offer incremental benefits over the currently approved 5-ASA formulations. Results of in vitro and in vivo studies showed that CLX-103, was stable in simulated gastric fluid, but undergoes enzymatic hydrolysis in the small/large intestines to release the active moiety. Our data also showed that the active moiety is retained in the targeted intestinal tissues (ileum and colon) over a longer period of time in relation to sulfasalazine. The in vitro data supports the observed in vivo plasma kinetics of 5-ASA characterized by longer T max , low C max after the oral administration of CLX-103. Efficacy study of CLX-103 in acute dextran sodium sulfate (DSS) mouse colitis model showed improved potency measured as Disease Activity Index (DAI) and histological scores in the colon as compared to sulfasalazine. These findings indicate that CLX-103 could offer a differentiated drug product which is more efficacious and safer than the currently approved 5-ASA formulations in the treatment of inflammatory bowel diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Patent foramen ovale and the risk of ischemic stroke in a multiethnic population.

PubMed

Di Tullio, Marco R; Sacco, Ralph L; Sciacca, Robert R; Jin, Zhezhen; Homma, Shunichi

2007-02-20

We sought to assess the risk of ischemic stroke from a patent foramen ovale (PFO) in the multiethnic prospective cohort of northern Manhattan. Patent foramen ovale has been associated with increased risk of ischemic stroke, mainly in case-control studies. The actual PFO-related stroke risk in the general population is unclear. The presence of PFO was assessed at baseline by using transthoracic 2-dimensional echocardiography with contrast injection in 1,100 stroke-free subjects older than 39 years of age (mean age 68.7 +/- 10.0 years) from the Northern Manhattan Study (NOMAS). The presence of atrial septal aneurysm (ASA) also was recorded. Subjects were followed annually for outcomes. We assessed PFO/ASA-related stroke risk after adjusting for established stroke risk factors. We detected PFO in 164 subjects (14.9%); ASA was present in 27 subjects (2.5%) and associated with PFO in 19 subjects. During a mean follow-up of 79.7 +/- 28.0 months, an ischemic stroke occurred in 68 subjects (6.2%). After adjustment for demographics and risk factors, PFO was not found to be significantly associated with stroke (hazard ratio 1.64, 95% confidence interval [CI] 0.87 to 3.09). The same trend was observed in all age, gender, and race-ethnic subgroups. The coexistence of PFO and ASA did not increase the stroke risk (adjusted hazard ratio 1.25, 95% CI 0.17 to 9.24). Isolated ASA was associated with elevated stroke incidence (2 of 8, or 25%; adjusted hazard ratio 3.66, 95% CI 0.88 to 15.30). Patent foramen ovale, alone or together with ASA, was not associated with an increased stroke risk in this multiethnic cohort. The independent role of ASA needs further assessment in appositely designed and powered studies.

ASASSN-18gq: Discovery of A Low-Luminosity Transient Towards Very Nearby ( 3.4 Mpc) Galaxy ESO 325- G?011

NASA Astrophysics Data System (ADS)

Nicholls, B.; Brimacombe, J.; Vallely, P.; Dong, Subo; Stanek, K. Z.; Kochanek, C. S.; Brown, J. S.; Shields, J.; Thompson, T. A.; Shappee, B. J.; Holoien, T. W.-S.; Prieto, J. L.; Bersier, D.; Bose, S.; Chen, Ping; Stritzinger, M.; Holmbo, S.

2018-04-01

During the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN, Shappee et al. 2014), using data from the quadruple 14-cm "Payne-Gaposchkin" telescope in Sutherland, South Africa, and the quadruple 14-cm "Cassius" and "Paczynski" telescopes in Cerro Tololo, Chile, we discovered a new transient source, most likely a supernova, in the low surface brightness galaxy ESO 325- G?011.

Effects of salinity and ascorbic acid on growth, water status and antioxidant system in a perennial halophyte

PubMed Central

Hameed, Abdul; Gulzar, Salman; Aziz, Irfan; Hussain, Tabassum; Gul, Bilquees; Khan, M. Ajmal

2015-01-01

Salinity causes oxidative stress in plants by enhancing production of reactive oxygen species, so that an efficient antioxidant system, of which ascorbic acid (AsA) is a key component, is an essential requirement of tolerance. However, antioxidant responses of plants to salinity vary considerably among species. Limonium stocksii is a sub-tropical halophyte found in the coastal marshes from Gujarat (India) to Karachi (Pakistan) but little information exists on its salt resistance. In order to investigate the role of AsA in tolerance, 2-month-old plants were treated with 0 (control), 300 (moderate) and 600 (high) mM NaCl for 30 days with or without exogenous application of AsA (20 mM) or distilled water. Shoot growth of unsprayed plants at moderate salinity was similar to that of controls while at high salinity growth was inhibited substantially. Sap osmolality, AsA concentrations and activities of AsA-dependant antioxidant enzymes increased with increasing salinity. Water spray resulted in some improvement in growth, indicating that the growth promotion by exogenous treatments could partly be attributed to water. However, exogenous application of AsA on plants grown under saline conditions improved growth and AsA dependent antioxidant enzymes more than the water control treatment. Our data show that AsA-dependent antioxidant enzymes play an important role in salinity tolerance of L. stocksii. PMID:25603966

Effect of aspirin on the contractility of aortic smooth muscle and the course of blood pressure development in male spontaneously hypertensive rats.

PubMed

Rahmani, M A; David, V; Huang, M; DeGray, G

1998-01-01

The effects of acetylsalicylic acid (ASA) on aortic smooth muscle contractility were studied in aortic rings of male SHR and WKY rats. The rats were administered two intraperitoneal injections of 10 mg/kg of ASA per week for ten weeks. Blood pressure of each rat was monitored twice weekly prior to the i.p. injections. Twenty four hours after the last injection the aortic smooth muscles were evaluated for generation of active tension in response to KCl, Phenylephrine (PE), Clonidine and Norepinephrine (NE). In another set of experiments calcium conductance was evaluated in the presence or absence of endothelium both in ASA treated and non treated animals. We report that aortic rings from ASA-treated SHR animals were more responsive to contractile agents than rings from non-treated SHR male rats. Also, the Ca2+ conductance in vitro was enhanced appreciably in SHR aortic rings denuded of their monolayer of endothelium in response to ASA treatment. No decrease in systolic blood pressure was observed in response to ASA treatment in SHR male rats. These results suggest that acetylsalicylic acid not only may modulate aortic smooth muscle contractility through the metabolites of arachidonic acid but may repair to a great extent the hypertension associated plasma membrane permeability defect of vascular myocytes.

Using animal models to evaluate the functional consequences of anesthesia during early neurodevelopment.

PubMed

Maloney, Susan E; Creeley, Catherine E; Hartman, Richard E; Yuede, Carla M; Zorumski, Charles F; Jevtovic-Todorovic, Vesna; Dikranian, Krikor; Noguchi, Kevin K; Farber, Nuri B; Wozniak, David F

2018-03-14

Fifteen years ago Olney and colleagues began using animal models to evaluate the effects of anesthetic and sedative agents (ASAs) on neurodevelopment. The results from ongoing studies indicate that, under certain conditions, exposure to these drugs during development induces an acute elevated apoptotic neurodegenerative response in the brain and long-term functional impairments. These animal models have played a significant role in bringing attention to the possible adverse effects of exposing the developing brain to ASAs when few concerns had been raised previously in the medical community. The apoptotic degenerative response resulting from neonatal exposure to ASAs has been replicated in many studies in both rodents and non-human primates, suggesting that a similar effect may occur in humans. In both rodents and non-human primates, significantly increased levels of apoptotic degeneration are often associated with functional impairments later in life. However, behavioral deficits following developmental ASA exposure have not been consistently reported even when significantly elevated levels of apoptotic degeneration have been documented in animal models. In the present work, we review this literature and propose a rodent model for assessing potential functional deficits following neonatal ASA exposure with special reference to experimental design and procedural issues. Our intent is to improve test sensitivity and replicability for detecting subtle behavioral effects, and thus enhance the translational significance of ASA models. Copyright © 2018 Elsevier Inc. All rights reserved.

Sexual assault history and its association with the use of drinking protective behavioral strategies among college women.

PubMed

Gilmore, Amanda K; Stappenbeck, Cynthia A; Lewis, Melissa A; Granato, Hollie F; Kaysen, Debra

2015-05-01

The current study examined the relationship between sexual assault history and drinking protective behavioral strategies (PBS). Given the relationship between sexual assault history and alcohol use, we hypothesized that after we controlled for drinking behavior, women with a childhood sexual abuse (CSA) history would use fewer drinking PBS than those without a CSA history. We also hypothesized that a history of adolescent/adult sexual assault (ASA) involving incapacitation and force would be associated with lower use of drinking PBS after controlling for CSA history and drinking behavior. A total of 800 undergraduate college women completed a survey online. Regression analyses indicated that the only sexual assault history type that was consistently related to all three types of drinking PBS was ASA involving incapacitation. Women with a history of incapacitated ASA were less likely to use any type of drinking PBS than women without such history. A history of other types of sexual assault (CSA, physically forced ASA, and verbally coerced ASA) was associated only with lower use of serious harm-reduction drinking PBS, such as going home with a friend or knowing the location of your drink. This was the first study to examine the relationship between different sexual assault histories and drinking PBS, and it furthers our understanding of the relationship between alcohol and sexual assault. Possible reasons for this relationship between ASA and PBS use are discussed.

Do non-steroidal anti-inflammatory drugs influence the steroid hormone milieu in male athletes?

PubMed

Di Luigi, L; Rossi, C; Sgrò, P; Fierro, V; Romanelli, F; Baldari, C; Guidetti, L

2007-10-01

Prostaglandins modulate the hypothalamus-pituitary-adrenal and -gonadal axis pathways. We explored the effects of a single course of treatment with acetylsalicylic acid (ASA), an inhibitor of prostaglandin synthesis, on the steroid milieu in athletes. Morning plasma cortisol (F), dehydroepiandrosterone sulphate, free-testosterone, testosterone (T) and their ratios were evaluated before and after the administration of either ASA or placebo in twelve male athletes, when affected by minor musculoskeletal trauma and, as control, after a five/six week wash-out in healthy conditions respectively. One tablet of ASA (800 mg), or placebo, was administered two times daily for 10 days during treatment. All the volunteers suspended exercise training during treatment. The results revealed that compared to placebo, plasma F was significantly lower after ASA treatment (p = 0.023). Furthermore, the comparison of hormone's absolute and percentage of variations (Delta and Delta%) between ASA and placebo treatment showed significant differences respectively for DeltaF (p = 0.045), for DeltaT (p = 0.047), for DeltaT/F (p = 0.042), for DeltaF% (p = 0.04) and for DeltaT% (p = 0.049). Our data suggest that in comparison to placebo, a short-term ASA treatment is able to influence the plasma steroid milieu in athletes. Due to the observed variability of the individual hormonal patterns, further research is required to substantiate these findings.

Anagrelide reduces thrombotic risk in essential thrombocythaemia vs. hydroxyurea plus aspirin.

PubMed

Dombi, Péter; Illés, Árpád; Demeter, Judit; Homor, Lajos; Simon, Zsofia; Karadi, Eva; Udvardy, Miklos; Egyed, Miklos

2017-02-01

To evaluate the reduction in thrombotic events (TE) in patients with essential thrombocythaemia (ET) treated with anagrelide versus hydroxyurea + aspirin (HU + ASA). A questionnaire was developed using 2008 WHO diagnostic criteria, and thrombotic risk factors were stratified according to Landolfi criteria. Through questionnaire completion, clinicians at Hungarian haematological centres entered data into the Hungarian MPN Registry on patients with myeloproliferative neoplasms. Based on ET registry data, TEs in anagrelide-treated patients (n = 139) were compared with HU + ASA-treated patients (n = 141). Patients were followed up for (median) 6 yr. TEs were reported in significantly fewer anagrelide-treated patients versus HU + ASA (15.1% versus 49.6%; P < 0.001). Numbers of major arterial and major venous events were similar between the groups, although there were over fivefold more minor arterial and minor venous events in the HU + ASA group (P < 0.001). While median age at diagnosis was older and length of follow-up shorter in the HU + ASA group (P < 0.05), this did not influence TE incidence; medication and TE before diagnosis only influenced TE incidence. Anagrelide significantly decreased the number of patients experiencing minor arterial and minor venous TEs versus HU + ASA over 6 yr. Risk of TE after diagnosis was significantly increased if the patient had TE before diagnosis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of dietary ascorbic acid supplementation on lipid peroxidation and the lipid content in the liver and serum of magnesium-deficient rats.

PubMed

Akiyama, Satoko; Uehara, Mariko; Katsumata, Shin-ichi; Ihara, Hiroshi; Hashizume, Naotaka; Suzuki, Kazuharu

2008-12-01

We investigated the effects of ascorbic acid (AsA) supplementation on lipid peroxidation and the lipid content in the liver and serum of magnesium (Mg)-deficient rats. Eighteen 3-week-old male Sprague-Dawley strain rats were divided into 3 groups and maintained on a control diet (C group), a low-Mg diet (D group), or a low-Mg diet supplemented with AsA (DA group) for 42 d. At the end of this period, the final body weight, weight gain, and serum Mg concentrations were significantly decreased in the Mg-deficient rats. Further, dietary AsA supplementation had no effect on the growth, serum Mg concentration, Mg absorption, and Mg retention. The serum concentration of AsA was significantly lower in the D group than in the C group but was unaltered in the DA group. The levels of phosphatidylcholine hydroperoxide (PCOOH) in the serum and of triglycerides (TGs) and total cholesterol (TC) in the serum and liver were significantly higher in the D group than in the C group. The serum PCOOH, liver TG, and liver TC levels were decreased in the DA group. These results indicate that Mg deficiency increases the AsA requirement of the body and that AsA supplementation normalizes the serum levels of PCOOH and the liver lipid content in Mg-deficient rats, without altering the Mg status.

A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study.

PubMed

Park, Won; Hrycaj, Pawel; Jeka, Slawomir; Kovalenko, Volodymyr; Lysenko, Grygorii; Miranda, Pedro; Mikazane, Helena; Gutierrez-Ureña, Sergio; Lim, MieJin; Lee, Yeon-Ah; Lee, Sang Joon; Kim, HoUng; Yoo, Dae Hyun; Braun, Jürgen

2013-10-01

To compare the pharmacokinetics (PK), safety and efficacy of innovator infliximab (INX) and CT-P13, a biosimilar to INX, in patients with active ankylosing spondylitis (AS). Phase 1 randomised, double-blind, multicentre, multinational, parallel-group study. Patients were randomised to receive 5 mg/kg of CT-P13 (n=125) or INX (n=125). Primary endpoints were area under the concentration-time curve (AUC) at steady state and observed maximum steady state serum concentration (Cmax,ss) between weeks 22 and 30. Additional PK, efficacy endpoints, including 20% and 40% improvement response according to Assessment in Ankylosing Spondylitis International Working Group criteria (ASAS20 and ASAS40), and safety outcomes were also assessed. Geometric mean AUC was 32 765.8 μgh/ml for CT-P13 and 31 359.3 μgh/ml for INX. Geometric mean Cmax,ss was 147.0 μg/ml for CT-P13 and 144.8 μg/ml for INX. The ratio of geometric means was 104.5% (90% CI 94% to 116%) for AUC and 101.5% (90% CI 95% to 109%) for Cmax,ss. ASAS20 and ASAS40 responses at week 30 were 70.5% and 51.8% for CT-P13 and 72.4% and 47.4% for INX, respectively. In the CT-P13 and INX groups more than one adverse event occurred in 64.8% and 63.9% of patients, infusion reactions occurred in 3.9% and 4.9%, active tuberculosis occurred in 1.6% and 0.8%, and 27.4% and 22.5% of patients tested positive for anti-drug antibodies, respectively. The PK profiles of CT-P13 and INX were equivalent in patients with active AS. CT-P13 was well tolerated, with an efficacy and safety profile comparable to that of INX up to week 30.

A multicenter prospective study of surgical audit systems.

PubMed

Haga, Yoshio; Ikejiri, Koji; Wada, Yasuo; Takahashi, Tadateru; Ikenaga, Masakazu; Akiyama, Noriyoshi; Koike, Shoichiro; Koseki, Masato; Saitoh, Toshihiro

2011-01-01

This study was undertaken to evaluate a modified form of Estimation of Physiologic Ability and Surgical Stress (E-PASS) for surgical audit comparing with other existing models. Although several scoring systems have been devised for surgical audit, no nation-wide survey has been performed yet. We modified our previous E-PASS surgical audit system by computing the weights of 41 procedures, using data from 4925 patients who underwent elective digestive surgery, designated it as mE-PASS. Subsequently, a prospective cohort study was conducted in 43 national hospitals in Japan from April 1, 2005, to April 8, 2007. Variables for the E-PASS and American Society of Anesthesiologists (ASA) status-based model were collected for 5272 surgically treated patients. Of the 5272 patients, we also collected data for the Portsmouth modification of Physiologic and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM) in 3128 patients. The area under the receiver operative characteristic curve (AUC) was used to evaluate discrimination performance to detect in-hospital mortality. The ratio of observed to estimated in-hospital mortality rates (OE ratio) was defined as a measure of quality. The numbers of variables required were 10 for E-PASS, 7 for mE-PASS, 20 for P-POSSUM, and 4 for the ASA status-based model. The AUC (95% confidence interval) values were 0.86 (0.79-0.93) for E-PASS, 0.86 (0.79-0.92) for mE-PASS, 0.81 (0.75-0.88) for P-POSSUM, and 0.73 (0.63-0.83) for the ASA status-based model. The OE ratios for mE-PASS among large-volume hospitals significantly correlated with those for E-PASS (R = 0.93, N = 9, P = 0.00026), P-POSSUM (R = 0.96, N = 6, P = 0.0021), and ASA status-based model (R = 0.83, N = 9, P = 0.0051). Because of its features of easy use, accuracy, and generalizability, mE-PASS is a candidate for a nation-wide survey.

A random urine test can identify patients at risk of mesalamine non-adherence: a prospective study.

PubMed

Gifford, Anne E; Berg, Anders H; Lahiff, Conor; Cheifetz, Adam S; Horowitz, Gary; Moss, Alan C

2013-02-01

Mesalamine non-adherence is common among patients with ulcerative colitis (UC), and can be difficult to identify in practice. We sought to determine whether a random urine test for salicylates could be used as a marker of 5-aminosalicylic acid (5-ASA) ingestion and identify patients at risk of non-adherence. Our aim is to determine whether measurement of salicylates in a random urine sample correlates with 5-ASA levels, and predicts an individual's risk of mesalamine non-adherence. Prospective observational study. Urinary salicylates (by colorimetry) and 5-ASA (by liquid chromatography and tandem-mass spectrometry) were measured in a random urine sample at baseline in patients and controls. Mesalamine adherence was quantified by patient self-reports at enrollment and pharmacy refills of mesalamine over 6 months. A total of 93 patients with UC taking mesalamine maintenance therapy were prospectively enrolled from the clinic. Random urine salicylate levels (by colorimetry) were highly correlated with urine 5-ASA metabolite levels (by mass spectrometry; R2=0.9). A random urine salicylate level above 15 mg/dl distinguished patients who had recently taken mesalamine from controls (area under the curve value 0.9, sensitivity 95%, specificity 77%). A significant proportion of patients (27%) who self-identified as "high adherers" by an adherence questionnaire (Morisky Medication Adherence Scale-8) had random levels of urine salicylate below this threshold. These patients were at higher risk of objectively measured non-adherence to mesalamine over the subsequent 6 months (RR: 2.7, 95% CI: 1.1-7.0). A random urine salicylate level measured in the clinic can identify patients who have not recently taken mesalamine, and who are at higher risk of longitudinal non-adherence. This test could be used to screen patients who may warrant interventions to improve adherence and prevent disease relapse.

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

PubMed

Zhou, Lin; Duan, Xingmei; Zeng, Shi; Men, Ke; Zhang, Xueyan; Yang, Li; Li, Xiang

2015-01-01

Natural product curcumin (Cur) and H2S-releasing prodrug SH-aspirin (SH-ASA) are potential anticancer agents with diverse mechanisms, but their clinical application prospects are restricted by hydrophobicity and limited efficiency. In this work, we coencapsulated SH-ASA and Cur into methoxy poly(ethylene glycol)-poly (lactide-coglycolide) (mPEG-PLGA) nanoparticles through a modified oil-in-water single-emulsion solvent evaporation process. The prepared SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles had a mean particle size of 122.3±6.8 nm and were monodispersed (polydispersity index =0.179±0.016) in water, with high drug-loading capacity and stability. Intriguingly, by treating with SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles, obvious synergistic anticancer effects on ES-2 and SKOV3 human ovarian carcinoma cells were observed in vitro, and activation of the mitochondrial apoptosis pathway was indicated. Our results demonstrated that SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles could have potential clinical advantages for the treatment of ovarian cancer.

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

PubMed Central

Zhou, Lin; Duan, Xingmei; Zeng, Shi; Men, Ke; Zhang, Xueyan; Yang, Li; Li, Xiang

2015-01-01

Natural product curcumin (Cur) and H2S-releasing prodrug SH-aspirin (SH-ASA) are potential anticancer agents with diverse mechanisms, but their clinical application prospects are restricted by hydrophobicity and limited efficiency. In this work, we coencapsulated SH-ASA and Cur into methoxy poly(ethylene glycol)-poly (lactide-coglycolide) (mPEG-PLGA) nanoparticles through a modified oil-in-water single-emulsion solvent evaporation process. The prepared SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles had a mean particle size of 122.3±6.8 nm and were monodispersed (polydispersity index =0.179±0.016) in water, with high drug-loading capacity and stability. Intriguingly, by treating with SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles, obvious synergistic anticancer effects on ES-2 and SKOV3 human ovarian carcinoma cells were observed in vitro, and activation of the mitochondrial apoptosis pathway was indicated. Our results demonstrated that SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles could have potential clinical advantages for the treatment of ovarian cancer. PMID:26316750

Anesthesiologists' familiarity with the ASA and ACS guidelines on Advance Directives in the perioperative setting.

PubMed

Nurok, Michael; Green, Douglas S T; Chisholm, Mary F; Fins, Joseph J; Liguori, Gregory A

2014-05-01

To assess anesthesiologists' familiarity with the American Society of Anesthesiologists (ASA) and American College of Surgeons (ACS) guidelines on Advance Directives in the perioperative setting. Single-center, 4-question anonymous survey. Urban academic medical center. Up to 34 subjects responded to each question. Familiarity with the ASA and ACS guidelines on Advance Directives in the perioperative setting ranged from 45% to 100%. There was inadequate familiarity with components of the ASA and ACS guidelines on advance directives in the perioperative setting. Larger studies are required to assess anesthesiologists' familiarity with national society guidelines that directly affect patient care. Future work should investigate best practices for guideline implementation, and consequences of poor adherence to national guidelines. Copyright © 2014 Elsevier Inc. All rights reserved.

The ASAS-SN Bright Supernova Catalog – II. 2015

DOE PAGES

Holoien, T. W. -S.; Brown, J. S.; Stanek, K. Z.; ...

2017-01-16

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

The ASAS-SN Bright Supernova Catalog – II. 2015

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holoien, T. W. -S.; Brown, J. S.; Stanek, K. Z.

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

Study on the interaction of the drug mesalamine with calf thymus DNA using molecular docking and spectroscopic techniques.

PubMed

Shahabadi, Nahid; Fili, Soraya Moradi; Kheirdoosh, Fahimeh

2013-11-05

The interaction of CT-DNA with the drug mesalamine (5-ASA) at physiological pH has been investigated by absorption, emission, circular dichroism (CD), cyclic voltammetry (CV), viscosity studies and molecular modeling. Thermodynamic parameters (ΔH>0 and ΔS<0) indicated that hydrogen bond and van der Waals play main roles in the binding of 5-ASA to CT-DNA. Ethidium bromide (EB) displacement studies revealed that 5-ASA did not have any effect on ethidium bromide (EB) bound DNA which is indicative of groove binding. The results obtained from experimental and molecular modeling showed that 5-ASA is a minor groove binder of DNA and preferentially binds to GC rich regions. Copyright © 2013 Elsevier B.V. All rights reserved.

Does ASA classification impact success rates of endovascular aneurysm repairs?

PubMed

Conners, Michael S; Tonnessen, Britt H; Sternbergh, W Charles; Carter, Glen; Yoselevitz, Moises; Money, Samuel R

2002-09-01

The purpose of this study was to evaluate the technical success, clinical success, postoperative complication rate, need for a secondary procedure, and mortality rate with endovascular aneurysm repair (EAR), based on the physical status classification scheme advocated by the American Society of Anesthesiologists (ASA). At a single institution 167 patients underwent attempted EAR. Query of a prospectively maintained database supplemented with a retrospective review of medical records was used to gather statistics pertaining to patient demographics and outcome. In patients selected for EAR on the basis of acceptable anatomy, technical and clinical success rates were not significantly different among the different ASA classifications. Importantly, postoperative complication and 30-day mortality rates do not appear to significantly differ among the different ASA classifications in this patient population.

Rapid degradation of p-arsanilic acid with simultaneous arsenic removal from aqueous solution using Fenton process.

PubMed

Xie, Xiande; Hu, Yuanan; Cheng, Hefa

2016-02-01

Although banned in some developed countries, p-arsanilic acid (p-ASA) is still used widely as a feed additive for swine production in many countries. With little uptake and transformation in animal bodies, nearly all the p-ASA administered to animals is excreted chemically unchanged in animal wastes, which can subsequently release the more toxic inorganic arsenic species upon degradation in the environment. For safe disposal of the animal wastes laden with p-ASA, we proposed a method of leaching the highly water-soluble p-ASA out of the manure first, followed by treatment of the leachate using the Fenton process to achieve fast oxidation of p-ASA and removal of the inorganic arsenic species released (predominantly arsenate) from solution simultaneously. The effects of solution pH, dosages of H2O2 and Fe(2+), and the presence of dissolved organic matter (DOM) on the treatment efficiency were systematically investigated. Under the optimum treatment conditions (0.53 mmol L(-1) Fe(2+), 2.12 mmol L(-1) H2O2, and initial pH of 3.0), p-ASA (10 mg-As L(-1)) could be completely oxidized to As(V) within 30 min in pure water and 4 natural water samples, and at the final pH of 4.0, the residual arsenic levels in solution phase were as low as 1.1 and 20.1-43.4 μg L(-1) in the two types of water matrixes, respectively. The presence of humic acid significantly retarded the oxidation of p-ASA by scavenging HO, and inhibited the As(V) removal through competitive adsorption on ferric hydroxide. Due to the high contents of DOM in the swine manure leachate samples (TOC at ∼500 mg L(-1)), much higher dosages of Fe(2+) (10.0 mmol L(-1)) and H2O2 (40.0 mmol L(-1)) and a longer treatment time (120 min) were required to achieve near complete oxidation of p-ASA (98.0%), while maintaining the levels of residual arsenic in the solution at <70.0 μg L(-1). The degradation pathway of p-ASA in the Fenton process was proposed based on the major degradation products detected. Together, the results demonstrate that the Fenton process is promising as an efficient, robust, and low-cost treatment method for controlling the risk of p-ASA in the animal wastes generated at factory farms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Applying Strategic Management in the Office of the Assistant Secretary of the Army for Financial Management and Comptroller (ASA(FM&C))

DTIC Science & Technology

2000-05-31

direction for the Office of the ASA (FM&C), consolidate all of the office’s subordinate organization strategic plans, and better define the roles and...responsibilities within the office of the ASA(FM&C). Mrs. McCoy directed Ms. Barbara Bonessa, Chief of the Financial Management Redesign Office, to...lead the strategic planning effort. Ms. Bonessa built a strategic planning team primarily with strategic management expertise from outside of the office of

State-of-the-Art Resources (SOAR) for Software Vulnerability Detection, Test, and Evaluation

DTIC Science & Technology

2014-07-01

preclude in-depth analysis, and widespread use of a Software -as-a- Service ( SaaS ) model that limits data availability and application to DoD systems...provide mobile application analysis using a Software - as-a- Service ( SaaS ) model. In this case, any software to be analyzed must be sent to the...tools are only available through a SaaS model. The widespread use of a Software -as-a- Service ( SaaS ) model as a sole evaluation model limits data

Evaluation of the levels of alcohol sulfates and ethoxysulfates in marine sediments near wastewater discharge points along the coast of Tenerife Island.

PubMed

Fernández-Ramos, C; Ballesteros, O; Zafra-Gómez, A; Camino-Sánchez, F J; Blanc, R; Navalón, A; Pérez-Trujillo, J P; Vílchez, J L

2014-02-15

Alcohol sulfates (AS) and alcohol ethoxysulfates (AES) are all High Production Volume and 'down-the-drain' chemicals used globally in detergent and personal care products, resulting in low levels ultimately released to the environment via wastewater treatment plant effluents. They have a strong affinity for sorption to sediments. Almost 50% of Tenerife Island surface area is environmentally protected. Therefore, determination of concentration levels of AS/AES in marine sediments near wastewater discharge points along the coast of the Island is of interest. These data were obtained after pressurized liquid extraction and liquid chromatography-tandem mass spectrometry analysis. Short chains of AES and especially of AS dominated the homologue distribution for AES. The Principal Components Analysis was used. The results showed that the sources of AS and AES were the same and that both compounds exhibit similar behavior. Three different patterns in the distribution for homologues and ethoxymers were found. Copyright © 2013 Elsevier Ltd. All rights reserved.

ASA24-Canada

Cancer.gov

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

Aspirin Desensitization in Patients With Coronary Artery Disease: Results of the Multicenter ADAPTED Registry (Aspirin Desensitization in Patients With Coronary Artery Disease).

PubMed

Rossini, Roberta; Iorio, Annamaria; Pozzi, Roberto; Bianco, Matteo; Musumeci, Giuseppe; Leonardi, Sergio; Lettieri, Corrado; Bossi, Irene; Colombo, Paola; Rigattieri, Stefano; Dossena, Cinzia; Anzuini, Angelo; Capodanno, Davide; Senni, Michele; Angiolillo, Dominick J

2017-02-01

There are limited data on aspirin (ASA) desensitization for patients with coronary artery disease. The aim of the present study was to assess the safety and efficacy of a standard rapid desensitization protocol in patients with ASA sensitivity undergoing coronary angiography. This is a prospective, multicenter, observational study including 7 Italian centers including patients with a history of ASA sensitivity undergoing coronary angiography with intent to undergo percutaneous coronary intervention. A total of 330 patients with history of ASA sensitivity with known/suspected stable coronary artery disease or presenting with an acute coronary syndrome, including ST-segment-elevation myocardial infarction were enrolled. Adverse effects to aspirin included urticaria (n=177, 53.6%), angioedema (n=69, 20.9%), asthma (n=65, 19.7%), and anaphylactic reaction (n=19, 5.8%). Among patients with urticaria/angioedema, 13 patients (3.9%) had a history of idiopathic chronic urticaria. All patients underwent a rapid ASA (5.5 hours) desensitization procedure. The desensitization procedure was performed before cardiac catheterization in all patients, except for those (n=78, 23.6%) presenting with ST-segment-elevation myocardial infarction who underwent the desensitization after primary percutaneous coronary intervention. Percutaneous coronary intervention was performed in 235 patients (71%) of the overall study population. The desensitization procedure was successful in 315 patients (95.4%) and in all patients with a history of anaphylactic reaction. Among the 15 patients (4.6%) who did not successfully respond to the desensitization protocol, adverse reactions were minor and responded to treatment with corticosteroids and antihistamines. Among patients with successful in-hospital ASA desensitization, 253 patients (80.3%) continued ASA for at least 12 months. Discontinuation of ASA in the 62 patients (19.7%) who had responded to the desensitization protocol was because of medical decision and not because of hypersensitivity reactions. A standard rapid desensitization protocol is safe and effective across a broad spectrum of patients, irrespective of the type of aspirin sensitivity manifestation, with indications to undergo coronary angiography with intent to perform percutaneous coronary intervention. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02848339. © 2017 American Heart Association, Inc.

A metabolomics strategy to explore urinary biomarkers and metabolic pathways for assessment of interaction between Danhong injection and low-dose aspirin during their synergistic treatment.

PubMed

Li, Jianping; Guo, Jianming; Shang, Erxin; Zhu, Zhenhua; Zhu, Kevin Yue; Li, Shujiao; Zhao, Buchang; Jia, Lifu; Zhao, Jing; Tang, Zhishu; Duan, Jinao

2016-07-15

The drug combination of Danhong injection (DHI) and low-dose aspirin (ASA) was frequently applied for the treatment of cardiovascular and cerebrovascular diseases. Due to the drug interactions, a lot of potential benefits and risks might exist side by side in the course of combination therapy. However, there had been no studies of interaction between DHI and ASA. Metabolomics was a powerful tool to explore endogenous biomarkers and metabolic pathways. In present study, metabolic profiling with ultra-high-performance liquid chromatography coupled to quadrupole time of flight mass spectrometry (UHPLC-QTOF/MS) coupled with multivariate statistical analysis was performed to provide insight into understanding the interaction between DHI and low-dose ASA. Eleven potential biomarkers of three types were identified and seven metabolic pathways were constructed. The results showed that the interaction between DHI and low-dose ASA during synergistic treatment indeed affected some key endogenous biomarkers and metabolic pathways, which could not happen when DHI or low-dose ASA was used alone. The quality and quantity of endogenous metabolite were both influenced by interaction between DHI and low-dose ASA. In details, the amount of flavin mononucleotide, L-2, 4-diaminobutyric acid (DABA) and 4-aminohippuric acid were significantly increased. On the contrary, the amount of 3-methyluridine, 4, 6-dihydroxyquinoline, cortolone-3-glucuronide, and serotonin were significantly decreased. Furthermore, O-phosphotyrosine, 3-methyl-2-butenal, indoxyl sulfate and dolichyl diphosphate were disappeared in urine. As to metabolic pathways, riboflavin metabolism, pentose and glucuronate interconversions, and tryptophan metabolism were all significantly influenced. The emerging alterations of biomarkers and metabolic pathways were associated with a lot of drugs and diseases based on literature researches, which might influence the co-administration of other drugs or the treatments of relevant diseases. Our paper presented some hints to uncover the mechanism of interaction between DHI and low-dose ASA, which would provide some references for application of DHI and low-dose ASA combination. Copyright © 2015 Elsevier B.V. All rights reserved.

Performance of the Automated Self-Administered 24-hour Recall relative to a measure of true intakes and to an interviewer-administered 24-h recall.

PubMed

Kirkpatrick, Sharon I; Subar, Amy F; Douglass, Deirdre; Zimmerman, Thea P; Thompson, Frances E; Kahle, Lisa L; George, Stephanie M; Dodd, Kevin W; Potischman, Nancy

2014-07-01

The Automated Self-Administered 24-hour Recall (ASA24), a freely available Web-based tool, was developed to enhance the feasibility of collecting high-quality dietary intake data from large samples. The purpose of this study was to assess the criterion validity of ASA24 through a feeding study in which the true intake for 3 meals was known. True intake and plate waste from 3 meals were ascertained for 81 adults by inconspicuously weighing foods and beverages offered at a buffet before and after each participant served him- or herself. Participants were randomly assigned to complete an ASA24 or an interviewer-administered Automated Multiple-Pass Method (AMPM) recall the following day. With the use of linear and Poisson regression analysis, we examined the associations between recall mode and 1) the proportions of items consumed for which a match was reported and that were excluded, 2) the number of intrusions (items reported but not consumed), and 3) differences between energy, nutrient, food group, and portion size estimates based on true and reported intakes. Respondents completing ASA24 reported 80% of items truly consumed compared with 83% in AMPM (P = 0.07). For both ASA24 and AMPM, additions to or ingredients in multicomponent foods and drinks were more frequently omitted than were main foods or drinks. The number of intrusions was higher in ASA24 (P < 0.01). Little evidence of differences by recall mode was found in the gap between true and reported energy, nutrient, and food group intakes or portion sizes. Although the interviewer-administered AMPM performed somewhat better relative to true intakes for matches, exclusions, and intrusions, ASA24 performed well. Given the substantial cost savings that ASA24 offers, it has the potential to make important contributions to research aimed at describing the diets of populations, assessing the effect of interventions on diet, and elucidating diet and health relations. This trial was registered at clinicaltrials.gov as NCT00978406. © 2014 American Society for Nutrition.

Comparison of Three Risk Scores to Predict Outcomes of Severe Lower Gastrointestinal Bleeding

PubMed Central

Camus, Marine; Jensen, Dennis M.; Ohning, Gordon V.; Kovacs, Thomas O.; Jutabha, Rome; Ghassemi, Kevin A.; Machicado, Gustavo A.; Dulai, Gareth S.; Jensen, Mary Ellen; Gornbein, Jeffrey A.

2014-01-01

Background & aims Improved medical decisions by using a score at the initial patient triage level may lead to improvements in patient management, outcomes, and resource utilization. There is no validated score for management of lower gastrointestinal bleeding (LGIB) unlike for upper GIB. The aim of our study was to compare the accuracies of 3 different prognostic scores (CURE Hemostasis prognosis score, Charlston index and ASA score) for the prediction of 30 day rebleeding, surgery and death in severe LGIB. Methods Data on consecutive patients hospitalized with severe GI bleeding from January 2006 to October 2011 in our two-tertiary academic referral centers were prospectively collected. Sensitivities, specificities, accuracies and area under the receiver operating characteristic (AUROC) were computed for three scores for predictions of rebleeding, surgery and mortality at 30 days. Results 235 consecutive patients with LGIB were included between 2006 and 2011. 23% of patients rebled, 6% had surgery, and 7.7% of patients died. The accuracies of each score never reached 70% for predicting rebleeding or surgery in either. The ASA score had a highest accuracy for predicting mortality within 30 days (83.5%) whereas the CURE Hemostasis prognosis score and the Charlson index both had accuracies less than 75% for the prediction of death within 30 days. Conclusions ASA score could be useful to predict death within 30 days. However a new score is still warranted to predict all 30 days outcomes (rebleeding, surgery and death) in LGIB. PMID:25599218

Discovery of 11 ASAS-SN Supernovae

NASA Astrophysics Data System (ADS)

Brimacombe, J.; Cacella, P.; Stone, G.; Fernandez, J. M.; Vallely, P.; Stanek, K. Z.; Kochanek, C. S.; Brown, J. S.; Shields, J.; Thompson, T. A.; Shappee, B. J.; Holoien, T. W.-S.; Prieto, J. L.; Bersier, D.; Dong, Subo; Bose, S.; Chen, Ping; Stritzinger, M.; Holmbo, S.; Nicholls, B.; Post, R. S.

2018-05-01

During the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN, Shappee et al. 2014), using data from 14-cm telescopes in Hawaii, Texas, South Africa, and Chile, we discovered several new transient sources.

ASA24® Researcher Instructions

Cancer.gov

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

Predicting risky sexual behavior in emerging adulthood: examination of a moderated mediation model among child sexual abuse and adult sexual assault victims.

PubMed

Littleton, Heather L; Grills, Amie E; Drum, Katherine B

2014-01-01

Although having a sexual victimization history is associated with engaging in sexual risk behavior, the mechanisms whereby sexual victimization increases risk behavior are unclear. This study examined use of sex as an affect regulation strategy as a mediator of the relationship between depressive symptoms and sexual risk behavior among 1,616 sexually active college women as well as examined having a history of child sexual abuse (CSA), adolescent/adult sexual assault (ASA), or both (CSA/ASA) as moderators. Results supported the mediated model as well as moderated mediation, where depressive symptoms were more strongly associated with use of sex as an affect regulation strategy among ASA victims, and sex as an affect regulation strategy was more strongly related to sexual risk behavior for CSA/ASA victims.

In vitro study of platelets and circulating mononuclear cells of subjects presenting an intolerance to aspirin.

PubMed

Guez, S; Gualde, N; Bezian, J H; Cabanieu, G

1992-01-01

Aspirine-sensitive asthma (ASA) is a disease defined only by clinical criteria. It is an intrinsic asthma related to a hypersensitivity to aspirin. The illness is linked to abnormalities in platelet and macrophage arachidonic acid metabolism. We assessed in vitro the platelet chemoluminescence (CL) and lymphocyte proliferative response of ASA patients. We observed that platelets from patients and control do not generate any CL in the presence of aspirin. Concerning the proliferative response of lymphocytes, the in vitro effect of aspirin depends upon the origin of the lymphocytes tested. Thus aspirin clearly enhances the proliferative response of lymphocytes from normal subjects but diminishes the thymidine uptake by lymphocytes from ASA patients. This discrepancy in the in vitro response of lymphocytes from normal subjects and patients might be useful for in vitro diagnosis of ASA.

Alcohol septal ablation in obstructive hypertrophic cardiomyopathy: four years of experience at a reference center.

PubMed

Fiarresga, António; Cacela, Duarte; Galrinho, Ana; Ramos, Ruben; de Sousa, Lídia; Bernardes, Luís; Patrício, Lino; Cruz Ferreira, Rui

2014-01-01

We describe our center's initial experience with alcohol septal ablation (ASA) for the treatment of obstructive hypertrophic cardiomyopathy. The procedure, its indications, results and clinical outcomes will be addressed, as will its current position compared to surgical myectomy. To assess the results of ASA in all patients treated in the first four years of activity at our center. We retrospectively studied all consecutive and unselected patients treated by ASA between January 2009 and February 2013. In the first four years of experience 40 patients were treated in our center. In three patients (7.5%) the intervention was repeated. Procedural success was 84%. Minor complications occurred in 7.5%. Two patients received a permanent pacemaker for atrioventricular block (6% of those without previous pacemaker). The major complication rate was 5%. There were no in-hospital deaths; during clinical follow-up (22 ± 14 months) cardiovascular mortality was 2.5% and overall mortality was 5%. The results presented reflect the initial experience of our center with ASA. The success rate was high and in line with published results, but with room to improve with better patient selection. ASA was shown to be safe, with a low complication rate and no procedure-related mortality. Our experience confirms ASA as a percutaneous alternative to myectomy for the treatment of symptomatic patients with obstructive hypertrophic cardiomyopathy refractory to medical treatment. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Palatal approach of anterior superior alveolar injection technique may not be potentially useful in periodontal procedures.

PubMed

Bhat, Pragathi Raghavendra; Acharya, Anirudh Balakrishna; Thakur, Srinath Lakshman

2016-01-01

The palatal approach of anterior superior alveolar (P-ASA) using WAND injection was reported to effectively provide a profound bilateral maxillary anesthesia of the soft tissue of anterior one-third of the palate and facial gingivae extending from canine to canine which lasted for more than an hour thus making it ideal for scaling root planing and minor periodontal procedures in the anterior maxilla. Our study suggests that the conventional P-ASA injection is of very short duration and the extent of anesthesia was not profound and consistent. This has not been reported earlier in the literature. Thirty-five cases (20 males and 15 females), who underwent scaling, root planing and minor periodontal surgical procedures such as abscess drainage, gingivectomy, and frenectomy in the maxillary anterior region in the age range of 19-45 years was assessed for the efficacy of the P-ASA injection. After the administration of the P-ASA injection, the subjective and the objective symptoms were used to evaluate the extent and duration of the anesthesia at 10, 15, and 20 min. This study suggests that the conventional P-ASA injection technique does not provide anesthesia for more than 20 min. Wilcoxon matched pairs test was used to compare the effect of anesthesia at the different time intervals and the results were found to be statistically significant ( P < 0.05). The conventional P-ASA injection technique is of very short duration and does not demonstrate effectiveness in periodontal surgery of the anterior maxilla.

Effects of acetyl salycilic acid and ibuprofen in chronic liver damage induced by CCl4.

PubMed

Chávez, Enrique; Castro-Sánchez, Luis; Shibayama, Mineko; Tsutsumi, Victor; Pérez Salazar, Eduardo; Moreno, Mario G; Muriel, Pablo

2012-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are drugs used primarily to treat inflammation, pain and fever. Their main mechanism of action is cyclooxygenase (COX) inhibition, and this enzyme has been linked to hepatotoxicity. The association of COX and liver injury has been, in part, due to the presence of COX-2 isoform in damaged liver and the possible induction of this enzyme by profibrotic molecules like Transforming Growth Factor-β (TGF-β). The aim of this work was to evaluate the effects of two of the most used NSAIDs, acetyl salicylic acid (ASA) and ibuprofen (IBP), on experimental liver fibrosis. We formed experimental groups of rats including vehicle and drug controls, damage induced by chronic CCl4 (0.4 g kg(-1) , i.p., three times per week, for 8 weeks) administration, and CCl4 plus ASA (100 mg kg(-1) , p.o., daily) or IBP (30 mg kg(-1) , p.o., daily). Both drugs showed important antifibrotic properties. They inhibited COX-2 activity, prevented oxidative stress measured as lipid peroxidation and glutathione content, and ASA inhibited partially and IBP totally increased TGF-β expression and collagen content. ASA and IBP prevented translocation of NFκB to the nucleus and, interestingly, ASA induced MMP-2 and MMP-13 whereas IBP induced MMP-2, MMP-9 and MMP-13. As a whole, these effects explain the beneficial effects of ASA and IBP on experimental liver fibrosis. Copyright © 2011 John Wiley & Sons, Ltd.

An Energy Aware Adaptive Sampling Algorithm for Energy Harvesting WSN with Energy Hungry Sensors.

PubMed

Srbinovski, Bruno; Magno, Michele; Edwards-Murphy, Fiona; Pakrashi, Vikram; Popovici, Emanuel

2016-03-28

Wireless sensor nodes have a limited power budget, though they are often expected to be functional in the field once deployed for extended periods of time. Therefore, minimization of energy consumption and energy harvesting technology in Wireless Sensor Networks (WSN) are key tools for maximizing network lifetime, and achieving self-sustainability. This paper proposes an energy aware Adaptive Sampling Algorithm (ASA) for WSN with power hungry sensors and harvesting capabilities, an energy management technique that can be implemented on any WSN platform with enough processing power to execute the proposed algorithm. An existing state-of-the-art ASA developed for wireless sensor networks with power hungry sensors is optimized and enhanced to adapt the sampling frequency according to the available energy of the node. The proposed algorithm is evaluated using two in-field testbeds that are supplied by two different energy harvesting sources (solar and wind). Simulation and comparison between the state-of-the-art ASA and the proposed energy aware ASA (EASA) in terms of energy durability are carried out using in-field measured harvested energy (using both wind and solar sources) and power hungry sensors (ultrasonic wind sensor and gas sensors). The simulation results demonstrate that using ASA in combination with an energy aware function on the nodes can drastically increase the lifetime of a WSN node and enable self-sustainability. In fact, the proposed EASA in conjunction with energy harvesting capability can lead towards perpetual WSN operation and significantly outperform the state-of-the-art ASA.

Acetyl salicylic acid protected against heat stress damage in chicken myocardial cells and may associate with induced Hsp27 expression.

PubMed

Wu, Di; Xu, Jiao; Song, Erbao; Tang, Shu; Zhang, Xiaohui; Kemper, N; Hartung, J; Bao, Endong

2015-07-01

We investigated whether acetyl salicylic acid (ASA) protects chicken myocardial cells from heat stress-mediated damage in vivo and whether the induction of Hsp27 expression is connected with this function. Pathological changes, damage-related enzyme levels, and Hsp27 expression were studied in chickens following heat stress (40 ± 1 °C for 0, 1, 2, 3, 5, 7, 10, 15, or 24 h, respectively) with or without ASA administration (1 mg/kg BW, 2 h prior). Appearance of pathological lesions such as degenerations and karyopyknosis as well as the myocardial damage-related enzyme activation indicated that heat stress causes considerable injury to the myocardial cells in vivo. Myocardial cell injury was most serious in chickens exposed to heat stress without prior ASA administration; meanwhile, ASA pretreatment acted protective function against high temperature-induced injury. Hsp27 expression was induced under all experimental conditions but was one-fold higher in the ASA-pretreated animals (0.3138 ± 0.0340 ng/mL) than in untreated animals (0.1437 ± 0.0476 ng/mL) 1 h after heat stress exposure, and such an increase was sustained over the length of the experiment. Our findings indicate that pretreatment with ASA protects chicken myocardial cells from acute heat stress in vivo with almost no obvious side effects, and this protection may involve an enhancement of Hsp27 expression. However, the detailed mechanisms underlying this effect require further investigation.

Optimizing clinical use of mesalazine (5-aminosalicylic acid) in inflammatory bowel disease

PubMed Central

Williams, Chadwick; Panaccione, Remo; Ghosh, Subrata; Rioux, Kevin

2011-01-01

Mesalazine [5-aminosalicylic acid (5-ASA)] has been used for over 30 years in the treatment of inflammatory bowel disease (IBD). It is a highly effective, safe, and well-tolerated drug for treatment of mild to moderate ulcerative colitis, which represents most patients with this disease. Recent studies of patient adherence to 5-ASA therapies in ulcerative colitis have highlighted the need for regimens that enable long-term compliance to significantly reduce the risk of troublesome and debilitating flares in the short term, and possibly colon cancer in the long term. Indeed, much of the recent innovation in clinical use of 5-ASA in colitis has come from studies of novel delivery mechanisms and simplified oral dosing schedules. These studies have provided much needed clarity on essential matters such as starting dose, dose escalation, and efficacy in terms of the ideal clinical endpoint - mucosal healing. Various manufacturers are re-evaluating their products to determine the safety and efficacy of such dosing regimens. Although once widely employed in the treatment of Crohn’s disease (CD), the accumulated body of evidence now suggests that there is a much more limited role for 5-ASA in this particular form of inflammatory bowel disease. Recent 5-ASA randomized-controlled trials, comparative studies, and outcomes research have led to refined treatment strategies and awareness for practitioners to better inform, engage and facilitate patients in optimal use of 5-ASA in inflammatory bowel disease. PMID:21765868

Preparation and adsorption characteristics for heavy metals of active silicon adsorbent from leaching residue of lead-zinc tailings.

PubMed

Lei, Chang; Yan, Bo; Chen, Tao; Xiao, Xian-Ming

2018-05-19

To comprehensively reuse the leaching residue obtained from lead-zinc tailings, an active silicon adsorbent (ASA) was prepared from leaching residue and studied as an adsorbent for copper(II), lead(II), zinc(II), and cadmium(II) in this paper. The ASA was prepared by roasting the leaching residue with either a Na 2 CO 3 /residue ratio of 0.6:1 at 700 °C for 1 h or a CaCO 3 /residue ratio of 0.8:1 at 800 °C for 1 h. Under these conditions, the available SiO 2 content of the ASA was more than 20%. The adsorption behaviors of the metal ions onto the ASA were investigated and the Langmuir, Freundlich, and Dubinin-Radushkevich isotherm models were used to analyze the adsorption isotherm. The result showed that the maximum adsorption capacities of copper(II), lead(II), cadmium(II), and zinc(II) calculated by the Langmuir model were 3.40, 2.83, 0.66, and 0.62 mmol g -1 , respectively. The FT-IR spectra of the ASA and the mean free adsorption energies indicated that ion exchange was the mechanism of copper(II), lead(II), and cadmium(II) adsorption and that chemical reaction was the mechanism of zinc(II) adsorption. These results provide a method for reusing the leaching residue obtained from lead-zinc tailings and show that the ASA is an effective adsorbent for heavy metal pollution remediation.

Computation of ground motion amplification in Kolkata megacity (India) using finite-difference method for seismic microzonation

NASA Astrophysics Data System (ADS)

Shiuly, Amit; Kumar, Vinay; Narayan, Jay

2014-06-01

This paper presents the ground motion amplification scenario along with fundamental frequency (F 0) of sedimentary deposit for the seismic microzonation of Kolkata City, situated on the world's largest delta island with very soft soil deposit. A 4th order accurate SH-wave viscoelastic finite-difference algorithm is used for computation of response of 1D model for each borehole location. Different maps, such as for F 0, amplification at F 0, average spectral amplification (ASA) in the different frequency bandwidth of earthquake engineering interest are developed for a variety of end-users communities. The obtained ASA of the order of 3-6 at most of the borehole locations in a frequency range of 0.25-10.0 Hz reveals that Kolkata City may suffer severe damage even during a moderate earthquake. Further, unexpected severe damage to collapse of multi-storey buildings may occur in localities near Hoogly River and Salt Lake area due to double resonance effects during distant large earthquakes.

Light qualities and dose influence ascorbate pool size in detached oat leaves.

PubMed

Mastropasqua, Linda; Borraccino, Giuseppe; Bianco, Laura; Paciolla, Costantino

2012-02-01

In this work, we studied the mechanism of light influence on AsA pool size in Avena sativa L. under the effects of low intensity light at different wavelengths. Exposure to low intensity light of oat leaf segments incubated in water or in l-galactono-1,4-lactone (GL), resulted in an increase in AsA content compared with the dark control. This increase was due to modulation of l-galactono-1,4-lactone dehydrogenase (GLDH; EC 1.3.2.3) light-dependent activity and was dependent on the size of the endogenous GL pool. Both blue and red light were effective in increasing AsA, and this increase depended on both exposure time and light intensity. Protein biosynthesis, photosynthesis and calcium were involved in controlling the level of light-dependent AsA. We suggest that multiple checkpoints correlated to the presence of light underlie the ascorbate pool size. The presence of a light-activated switch for the maintenance of an adequate AsA level seems to be necessary for the various tasks of scavenging reactive oxygen species, in response to the dark-light cycle which plants experience under natural conditions. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester, a polymeric colon-specific prodrug releasing 5-aminosalicylic acid and benzocaine, ameliorates TNBS-induced rat colitis.

PubMed

Nam, Joon; Kim, Wooseong; Lee, Sunyoung; Jeong, Seongkeun; Yoo, Jin-Wook; Kim, Min-Soo; Jung, Yunjin

2016-01-01

Local anesthetics have beneficial effects on colitis. Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester (Dex-5-ESA), designed as a polymeric colon-specific prodrug liberating 5-ASA and benzocaine in the large intestine, was prepared and its therapeutic activity against colitis was evaluated using a TNBS-induced rat colitis model. Dex-5-ESA liberated 5-ASA and benzocaine in the cecal contents while (bio)chemically stable in the small intestinal contents and mucosa. Oral administration of Dex-5-ESA (equivalent to 10 mg 5-ASA/kg, twice a day) alleviated colonic injury and reduced MPO activity in the inflamed colon. In parallel, pro-inflammatory mediators, COX-2, iNOS and CINC-3, elevated by TNBS-induced colitis, were substantially diminished in the inflamed colon. Dex-5-ESA was much more effective for the treatment of colitis than 5-(4-ethoxycarbonylphenylazo)salicylic acid (5-ESA) that may not deliver benzocaine to the large intestine. Our data suggest that Dex-5-ESA is a polymeric colon-specific prodrug, liberating 5-ASA and benzocaine in the target site (large intestine), probably exerting anti-colitic effects by combined action of 5-ASA and benzocaine.

Effect of chronic treatment with acetylsalicylic acid and clopidogrel on atheroprogression and atherothrombosis in ApoE-deficient mice in vivo.

PubMed

Schulz, Christian; Konrad, Ildiko; Sauer, Susanne; Orschiedt, Lena; Koellnberger, Maria; Lorenz, Reinhard; Walter, Ulrich; Massberg, Steffen

2008-01-01

Acetylsalicylic acid (ASA) and the thienopyridine clopidogrel are established anti-platelet drugs that significantly reduce secondary cardiovascular events in patients with manifest atherosclerosis. However, their impact on atherosclerotic lesion development remains controversial. Four-week-old ApoE-deficient mice were randomly assigned to four groups receiving a cholesterol diet together with either ASA (5 mg/kg), or clopidogrel (25 mg/kg), or a combination of both ASA and clopidogrel, or vehicle for 8-12 weeks. Using intravital microscopy we found that daily administration of ASA in combination with clopidogrel reduces platelet thrombus formation following rupture of atherosclerotic plaque in vivo by approximately 50%. However, therapy with ASA or clopidogrel alone, or in combination for a period of 8-12 weeks had no significant effect on adhesion of platelets to dysfunctional endothelial cells or on atherosclerotic lesion formation in the aortic root or the carotid artery. In conclusion, anti-platelet therapy is effective in reducing platelet adhesion and subsequent thrombus formation following rupture of atherosclerotic plaque in vivo. However, our data do not support a role of either drug in the primary prevention of atherosclerosis in ApoE-deficient mice.

Efficient removal of heavy metal ions from aqueous solution using salicylic acid type chelate adsorbent.

PubMed

An, Fuqiang; Gao, Baojiao; Dai, Xin; Wang, Min; Wang, Xiaohua

2011-09-15

In this study, 5-aminosalicylic acid was successfully grafted onto the poly(glycidyl methacrylate) (PGMA) macromolecular chains of PGMA/SiO(2) to obtain a novel adsorbent designated as ASA-PGMA/SiO(2). The adsorption properties of ASA-PGMA/SiO(2) for heavy metal ions were studied through batch and column methods. The experimental results showed that ASA-PGMA/SiO(2) possesses strong chelating adsorption ability for heavy metal ions, and its adsorption capacity for Cu(2+), Cd(2+), Zn(2+), and Pb(2+) reaches 0.42, 0.40, 0.35, and 0.31 mmol g(-1), respectively. In addition, pH has a great influence on the adsorption capacity in the studied pH range. The adsorption isotherm data greatly obey the Langmuir and Freundlich model. The desorption of metal ions from ASA-PGMA/SiO(2) is effective using 0.1 mol l(-1) of hydrochloric acid solution as eluent. Consecutive adsorption-desorption experiments showed that ASA-PGMA/SiO(2) could be reused almost without any loss in the adsorption capacity. Copyright © 2011 Elsevier B.V. All rights reserved.

Meta-analysis: the efficacy of rectal beclomethasone dipropionate vs. 5-aminosalicylic acid in mild to moderate distal ulcerative colitis.

PubMed

Manguso, F; Balzano, A

2007-07-01

Beclomethasone dipropionate (BDP) is a second-generation steroid with topical effects and minimal systemic activity for patients with ulcerative colitis (UC). To review all available literature to assess the efficacy of enema/foam BDP compared with enema/foam 5-aminosalicylic acid (5-ASA) in the control of left-sided mild-moderate UC. We selected randomized controlled trials of enema/foam BDP compared with enema/foam 5-ASA treatment in patients with UC. Two reviewers assessed trial quality and extracted data independently. Four trials involving 428 UC patients, 209 treated with 5-ASA (1-4 g o.d.) and 219 with BDP (3 mg o.d.), were included. Intention-to-treat analysis showed that 5-ASA induced improvement/remission of UC in 146 (69.9%) patients, while BDP in 143 (65.3%). The test for heterogeneity (Cochran Q) was not significant and Mantel-Haenszel pooled estimate of odds ratio was 1.23 (95% CI = 0.82-1.85). The results did not change when analysis was performed on a per-protocol basis. The randomized controlled trials identified in this review showed that rectal BDP has equal effect as 5-ASA to control symptoms in UC.

Biowaiver monograph for immediate-release solid oral dosage forms: acetylsalicylic acid.

PubMed

Dressman, Jennifer B; Nair, Anita; Abrahamsson, Bertil; Barends, Dirk M; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Zimmer, Markus

2012-08-01

A biowaiver monograph for acetylsalicylic acid (ASA) is presented. Literature and experimental data indicate that ASA is a highly soluble and highly permeable drug, leading to assignment of this active pharmaceutical ingredient (API) to Class I of the Biopharmaceutics Classification System (BCS). Limited bioequivalence (BE) studies reported in the literature indicate that products that have been tested are bioequivalent. Most of the excipients used in products with a marketing authorization in Europe are not considered to have an impact on gastrointestinal motility or permeability. Furthermore, ASA has a wide therapeutic index. Thus, the risks to the patient that might occur if a nonbioequivalent product were to be incorrectly deemed bioequivalent according to the biowaiver procedure appear to be minimal. As a result, the BCS-based biowaiver procedure can be recommended for approval of new formulations of solid oral dosage forms containing ASA as the only API, including both multisource and reformulated products, under the following conditions: (1) excipients are chosen from those used in ASA products already registered in International Conference on Harmonization and associated countries and (2) the dissolution profiles of the test and the comparator products comply with the BE guidance. Copyright © 2012 Wiley Periodicals, Inc.

Molecular Characterization of Virulence Genes in Vancomycin-Resistant and Vancomycin-Sensitive Enterococci

PubMed Central

Biswas, Priyanka Paul; Dey, Sangeeta; Sen, Aninda; Adhikari, Luna

2016-01-01

Background: The aim of this study was to find out the correlation between presence of virulence (gelatinase [gel E], enterococcal surface protein [esp], cytolysin A [cyl A], hyaluronidase [hyl], and aggregation substance [asa1]) and vancomycin-resistant genes (van A and van B) in enterococci, with their phenotypic expression. Materials and Methods: A total of 500 isolates (250 each clinical and fecal) were processed. Enterococci were isolated from various clinical samples and from fecal specimens of colonized patients. Various virulence determinants namely asa1, esp, hyl, gel E, and cyl were detected by phenotypic methods. Minimum inhibitory concentration (MIC) of vancomycin was determined by agar dilution method. Multiplex polymerase chain reaction (PCR) was used to detect the presence of virulence and van genes. Results: Out of all the samples processed, 12.0% (60/500) isolates carried van A or van B genes as confirmed by MIC test and PCR methods. Genes responsible for virulence were detected by multiplex PCR and at least one of the five was detected in all the clinical vancomycin-resistant enterococci (VRE) and vancomycin-sensitive enterococci (VSE). gel E, esp, and hyl genes were found to be significantly higher in clinical VRE. Of the fecal isolates, presence of gel E, esp, and asa1 was significantly higher in VRE as compared to VSE. The presence of hyl gene in the clinical VRE was found to be statistically significant (P = 0.043) as against the fecal VRE. Correlation between the presence of virulence genes and their expression as detected by phenotypic tests showed that while biofilm production was seen in 61.1% (22/36) of clinical VRE, the corresponding genes, i.e., asa1 and esp were detected in 30.5% (11/36) and 27.8% (10/36) of strains only. Conclusion: Enterococcus faecium isolates were found to carry esp gene, a phenomenon that has been described previously only for Enterococcus faecalis, but we were unable to correlate the presence of esp with their capacity to form biofilms. PMID:27013840

Metal-rich or misclassified? The case of four RR Lyrae stars

NASA Astrophysics Data System (ADS)

Molnar, L.; Juhasz, A. L.; Plachy, E.; Szabo, R.

2016-06-01

We analysed the light curve of four, apparently extremely metal-rich fundamenta-mode RR Lyrae stars. We identified two stars, MT Tel and ASAS J091803-3022.6 as RRc (first-overtone) pulsators that were misclassified as RRab ones in the ASAS survey. In the case of the other two stars, V397 Gem and ASAS J075127-4136.3, we could not decide conclusively, as they are outliers in the period-Fourier-coefficient space from the loci of both classes, but their photometric metallicities also favour the RRc classification.

All Source Analysis System (ASAS): Migration from VAX to Alpha AXP computer systems

NASA Technical Reports Server (NTRS)

Sjoholm-Sierchio, Michael J.; Friedman, Steven Z. (Editor)

1994-01-01

The Jet Propulsion Laboratory's (JPL's) experience migrating existing VAX applications to Digital Equipment Corporation's new Alpha AXP processor is covered. The rapid development approach used during the 10-month period required to migrate the All Source Analysis System (ASAS), 1.5 million lines of FORTRAN, C, and Ada code, is also covered. ASAS, an automated tactical intelligence system, was developed by the Jet Propulsion Laboratory for the U. S. Army. Other benefits achieved as a result of the significant performance improvements provided by Alpha AXP platform are also described.

De novo assembly and functional annotation of Myrciaria dubia fruit transcriptome reveals multiple metabolic pathways for L-ascorbic acid biosynthesis.

PubMed

Castro, Juan C; Maddox, J Dylan; Cobos, Marianela; Requena, David; Zimic, Mirko; Bombarely, Aureliano; Imán, Sixto A; Cerdeira, Luis A; Medina, Andersson E

2015-11-24

Myrciaria dubia is an Amazonian fruit shrub that produces numerous bioactive phytochemicals, but is best known by its high L-ascorbic acid (AsA) content in fruits. Pronounced variation in AsA content has been observed both within and among individuals, but the genetic factors responsible for this variation are largely unknown. The goals of this research, therefore, were to assemble, characterize, and annotate the fruit transcriptome of M. dubia in order to reconstruct metabolic pathways and determine if multiple pathways contribute to AsA biosynthesis. In total 24,551,882 high-quality sequence reads were de novo assembled into 70,048 unigenes (mean length = 1150 bp, N50 = 1775 bp). Assembled sequences were annotated using BLASTX against public databases such as TAIR, GR-protein, FB, MGI, RGD, ZFIN, SGN, WB, TIGR_CMR, and JCVI-CMR with 75.2 % of unigenes having annotations. Of the three core GO annotation categories, biological processes comprised 53.6 % of the total assigned annotations, whereas cellular components and molecular functions comprised 23.3 and 23.1 %, respectively. Based on the KEGG pathway assignment of the functionally annotated transcripts, five metabolic pathways for AsA biosynthesis were identified: animal-like pathway, myo-inositol pathway, L-gulose pathway, D-mannose/L-galactose pathway, and uronic acid pathway. All transcripts coding enzymes involved in the ascorbate-glutathione cycle were also identified. Finally, we used the assembly to identified 6314 genic microsatellites and 23,481 high quality SNPs. This study describes the first next-generation sequencing effort and transcriptome annotation of a non-model Amazonian plant that is relevant for AsA production and other bioactive phytochemicals. Genes encoding key enzymes were successfully identified and metabolic pathways involved in biosynthesis of AsA, anthocyanins, and other metabolic pathways have been reconstructed. The identification of these genes and pathways is in agreement with the empirically observed capability of M. dubia to synthesize and accumulate AsA and other important molecules, and adds to our current knowledge of the molecular biology and biochemistry of their production in plants. By providing insights into the mechanisms underpinning these metabolic processes, these results can be used to direct efforts to genetically manipulate this organism in order to enhance the production of these bioactive phytochemicals. The accumulation of AsA precursor and discovery of genes associated with their biosynthesis and metabolism in M. dubia is intriguing and worthy of further investigation. The sequences and pathways produced here present the genetic framework required for further studies. Quantitative transcriptomics in concert with studies of the genome, proteome, and metabolome under conditions that stimulate production and accumulation of AsA and their precursors are needed to provide a more comprehensive view of how these pathways for AsA metabolism are regulated and linked in this species.

Antimicrobial Activity of Two Garlic Species (Allium Sativum and A. Tuberosum) Against Staphylococci Infection. In Vivo Study in Rats.

PubMed

Venâncio, Paulo César; Raimundo Figueroba, Sidney; Dias Nani, Bruno; Eduardo Nunes Ferreira, Luiz; Vilela Muniz, Bruno; de Sá Del Fiol, Fernando; Sartoratto, Adilson; Antonio Ribeiro Rosa, Edvaldo; Carlos Groppo, Francisco

2017-04-01

Purpose: This study observed the effect of garlic extracts and amoxicillin against an induced staphylococcal infection model. MIC and MBC were also obtained for aqueous extracts of Allium sativum (Asa) and Allium tuberosum (Atu) against Staphylococcus aureus penicillin-sensitive (PSSA - ATCC 25923) and MRSA (ATCC 33592). Methods: Granulation tissues were induced in the back of 205 rats. After 14 days, 0.5 mL of 10 8 CFU/mL of PSSA or MRSA were injected inside tissues. After 24h, animals were divided: G1 (Control) - 0.5 mL of NaCl 0.9%; G2 - Asa 100 mg/kg or 400mg/kg; G3 - Atu 100 mg/kg or 400 mg/kg; G4 - amoxicillin suspension 50 mg/kg, considering PSSA infection; and G5 (Control) - 0.5 mL of NaCl 0.9%; G6 - Asa 400mg/kg; G7 - amoxicillin 50 mg/kg; and G8 - Asa 400 mg/kg + amoxicillin 50 mg/kg for MRSA. All treatments were administered P.O. every 6h. Animals were killed at 0, 6, 12 and 24h. Samples were spread on salt-mannitol agar. Colonies were counted after 18 h at 37 °C. Atu was not able to inhibit or kill PSSA and MRSA. Considering Asa, MIC and MBC against PSSA were 2 mg/mL and 4 mg/mL, respectively; and 16 mg/mL and 64 mg/mL against MRSA. Results: No effect was observed in vivo for control, Asa 100 mg/kg and Atu 100 mg/kg, while amoxicillin, Atu 400 mg/kg and Asa 400 mg/kg decreased PSSA counts in all-time points. No effect of any group against MRSA was observed at any time. Conclusion: Thus, A. sativum and A. tuberosum were able to reduce PSSA infection, but not MRSA infection.

Antimicrobial Activity of Two Garlic Species (Allium Sativum and A. Tuberosum) Against Staphylococci Infection. In Vivo Study in Rats

PubMed Central

Venâncio, Paulo César; Raimundo Figueroba, Sidney; Dias Nani, Bruno; Eduardo Nunes Ferreira, Luiz; Vilela Muniz, Bruno; de Sá Del Fiol, Fernando; Sartoratto, Adilson; Antonio Ribeiro Rosa, Edvaldo; Carlos Groppo, Francisco

2017-01-01

Purpose: This study observed the effect of garlic extracts and amoxicillin against an induced staphylococcal infection model. MIC and MBC were also obtained for aqueous extracts of Allium sativum (Asa) and Allium tuberosum (Atu) against Staphylococcus aureus penicillin-sensitive (PSSA - ATCC 25923) and MRSA (ATCC 33592). Methods: Granulation tissues were induced in the back of 205 rats. After 14 days, 0.5 mL of 108 CFU/mL of PSSA or MRSA were injected inside tissues. After 24h, animals were divided: G1 (Control) – 0.5 mL of NaCl 0.9%; G2 – Asa 100 mg/kg or 400mg/kg; G3 – Atu 100 mg/kg or 400 mg/kg; G4 – amoxicillin suspension 50 mg/kg, considering PSSA infection; and G5 (Control) - 0.5 mL of NaCl 0.9%; G6 – Asa 400mg/kg; G7 – amoxicillin 50 mg/kg; and G8 - Asa 400 mg/kg + amoxicillin 50 mg/kg for MRSA. All treatments were administered P.O. every 6h. Animals were killed at 0, 6, 12 and 24h. Samples were spread on salt-mannitol agar. Colonies were counted after 18 h at 37 °C. Atu was not able to inhibit or kill PSSA and MRSA. Considering Asa, MIC and MBC against PSSA were 2 mg/mL and 4 mg/mL, respectively; and 16 mg/mL and 64 mg/mL against MRSA. Results: No effect was observed in vivo for control, Asa 100 mg/kg and Atu 100 mg/kg, while amoxicillin, Atu 400 mg/kg and Asa 400 mg/kg decreased PSSA counts in all-time points. No effect of any group against MRSA was observed at any time. Conclusion: Thus, A. sativum and A. tuberosum were able to reduce PSSA infection, but not MRSA infection. PMID:28507945

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

PubMed

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

2017-11-01

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

Nitroxide derivatives of non-steroidal anti-inflammatory drugs exert anti-inflammatory and superoxide dismutase scavenging properties in A459 cells.

PubMed

Flores-Santana, Wilmarie; Moody, Terry; Chen, Weibin; Gorczynski, Michael J; Shoman, Mai E; Velázquez, Carlos; Thetford, Angela; Mitchell, James B; Cherukuri, Murali K; King, S Bruce; Wink, David A

2012-02-01

Inflammation and reactive oxygen species are associated with the promotion of various cancers. The use of non-steroidal anti-inflammatory drugs (NSAIDs) in cancer prevention treatments has been promising in numerous cancers. We report the evaluation of NSAIDs chemically modified by the addition of a redox-active nitroxide group. TEMPO-aspirin (TEMPO-ASA) and TEMPO-indomethacin (TEMPO-IND) were synthesized and evaluated in the lung cancer cell line A549. We evaluated physico-chemical properties of TEMPO-ASA and TEMPO-IND by electron paramagnetic resonance and cyclic voltammetry. Superoxide dismutase-like properties was assayed by measuring cytochrome c reduction and anti-inflammatory effects were assayed by measuring production of prostaglandin E(2) (PGE(2) ) and leukotriene B(4) (LTB(4) ). MTT proliferation assay and clonogenic assay were evaluated in the A549 lung carcinoma cell line. Maximum tolerated doses (MTD) and acute ulcerogenic index were also evaluated in in vivo. MTD were: TEMPO (140 mg·kg(-1) ), ASA (100 mg·kg(-1) ), indomethacin (5 mg·kg(-1) ), TEMPO-ASA (100 mg·kg(-1) ) and TEMPO-IND (40 mg·kg(-1) ). While TEMPO-ASA was as well tolerated as ASA, TEMPO-IND showed an eightfold improvement over indomethacin. TEMPO-IND showed markedly less gastric toxicity than the parent NSAID. Both TEMPO-ASA and TEMPO-IND inhibited production of PGE(2) and LTB(4) in A549 cells with maximum effects at 100 µg·mL(-1) or 10 µg·mL(-1) respectively. The nitroxide-NSAIDs retained superoxide scavenging capacity of the parent nitroxide and anti-inflammatory effects, inhibiting cyclooxygenase and 5-lipoxygenase enzymes. These redox-modified NSAIDs might be potential drug candidates, as they exhibit the pharmacological properties of the parent NSAID with antioxidant activity decreasing NSAID-associated toxicity. Published 2011. This article is a U.S. Government work and is in the public domain in the USA.

Dose-dependent competitive block by topical acetylsalicylic and salicylic acid of low pH-induced cutaneous pain.

PubMed

Steen, K H; Reeh, P W; Kreysel, H W

1996-01-01

In a human acid pain model, which uses continuous intradermal pressure infusion of a phosphate-buffered solution (pH 5.2) to induce localized non-adapting pain, the flow was adjusted to result in constant pain ratings of about 20% or 50% on a visual analog scale (VAS). Six volunteers in each group participated in 4 different placebo-controlled double-blind cross-over studies to measure rapidly evolving cutaneous analgesia from topically applied new ointment formulations of acetylsalicylic acid (ASA) and salicylic acid (SA) as well as of commercial ibuprofen and benzocain creams. Similar, log-linear dose-response curves were found for both ASA and SA, significant in effect at 3 g/kg and higher drug contents and reaching saturation level at 15 or 30 g/kg, respectively, which, 20 min after application, caused a mean pain suppression of 95% using ASA and 80% using SA. Half-maximal effects were achieved using 3 g/kg ASA or 15 g/kg SA. The SA action was also clearly slower to develop. With an increased flow of the acidic buffer, producing lower effective tissue pH and more intense pain, the effect of ASA and SA decreased to 73% pain suppression. A competitive mechanism of both drug effects was suggested by the fact that, with 15 g/kg ASA and SA, pain reduction could be reversed by increasing the buffer flow by a factor of 1.75, on average. Commercial ibuprofen (50 g/kg) and benzocain creams (100 g/kg) were comparably as effective as ASA and SA, but the local anesthetic caused a loss of all cutaneous sensations while the touch threshold (von Frey) under the specific analgesics was the same as under the placebo ointment. Thus, topical applications of non-steroidal anti-inflammatory drugs (NSAIDS) dissolved in different ointment formulations have proven dose-dependently effective and specific in suppressing experimental acidotic pain by a local and competitive mechanism.

Cricothyrotomy training increases adherence to the ASA difficult airway algorithm in a simulated crisis: a randomized controlled trial.

PubMed

You-Ten, Kong Eric; Bould, M Dylan; Friedman, Zeev; Riem, Nicole; Sydor, Devin; Boet, Sylvain

2015-05-01

Non-adherence to airway guidelines in a 'cannot intubate-cannot oxygenate' (CICO) crisis situation is associated with adverse patient outcomes. This study investigated the effects of hands-on training in cricothyrotomy on adherence to the American Society of Anesthesiologists difficult airway algorithm (ASA-DAA) during a simulated CICO scenario. A total of 21 postgraduate second-year anesthesia residents completed a pre-test teaching session during which they reviewed the ASA-DAA, became familiarized with the Melker cricothyrotomy kit, and watched a video on cricothyrotomy. Participants were randomized to either the intervention 'Trained' group (n = 10) (taught and practiced cricothyrotomy) or the control 'Non-Trained' group (n = 11) (no extra training). After two to three weeks, performances of the groups were assessed in a simulated CICO scenario. The primary outcome measure was major deviation from the ASA-DAA. Secondary outcome measures were (1) performance of the four categories of non-technical behaviours using the validated Anaesthetists' Non-Technical Skills scale (ANTS) and (2) time to perform specific tasks. Significantly more non-trained than trained participants (6/11 vs 0/10, P = 0.012) committed at least one major ASA-DAA deviation, including failure to insert an oral airway, failure to call for help, bypassing the laryngeal mask airway, and attempting fibreoptic intubation. ANTS scores for all four categories of behaviours, however, were similar between the groups. Trained participants called for help faster [26 (2) vs 63 (48) sec, P = 0.012] but delayed opening of the cricothyrotomy kit [130 (50) vs 74 (36) sec, P = 0.014]. Hands-on training in cricothyrotomy resulted in fewer major ASA-DAA deviations in a simulated CICO scenario. Training in cricothyrotomy may play an important role in complying with the ASA-DAA in a CICO situation but does not appear to affect non-technical behaviours such as decision-making.

In-vitro characterization of 5-aminosalicylic acid release from MMX mesalamine tablets and determination of tablet coating thickness.

PubMed

Tenjarla, Srini; Abinusawa, Adeyinka

2011-01-01

Substantial variability in gastrointestinal pH is observed in patients with ulcerative colitis (UC). We characterized the effect of pH on 5-aminosalicylic acid (5-ASA) release from MMX mesalamine tablets (Shire Pharmaceuticals Inc., Wayne, PA, USA), examined thickness/uniformity of tablet film coatings, and explored the influence of simulating altered gastrointestinal motility. Nondestructive, three-dimensional, terahertz pulse imaging (TPI) was used to characterize the film coating of three lots of MMX mesalamine tablets (n=36). Thereafter, 5-ASA release from these tablets was evaluated using United States Pharmacopeia (USP) apparatus II at pH 6.8 and 7.2. Onset of tablet film-coat breach and mean dissolution time were determined for each lot. 5-ASA release was also assessed at three different paddle rotation speeds (50, 75, and 100 rpm) at pH 7.2. The mean ± SD film-coating thickness of the three lots of MMX mesalamine tablets were 109.2 ± 16.8, 113.1 ± 19.5, and 113.8 ± 19.8 μM, respectively. At pH 6.8 (100 rpm), the onset of film-coat breach was 10-30 minutes, whereas at pH 7.2 this was observed within 10 minutes. 5-ASA release was uniform at both pH conditions, with minimal lot-to-lot variability. Complete drug release was achieved within 6 hours under both pH conditions. 5-ASA release increased in proportion with paddle speed, but remained prolonged at all speeds. 5-ASA release from MMX mesalamine is unaffected by normal variations in simulated intracolonic pH. The dissolution profile of 5-ASA from MMX mesalamine tablets may be attributed to consistent outer film coatings and the hydrogel-forming matrix that controls the drug release after dissolution of the film coating.

5-ASA Affects Cell Cycle Progression in Colorectal Cells by Reversibly Activating a Replication Checkpoint

PubMed Central

LUCIANI, M. GLORIA; CAMPREGHER, CHRISTOPH; FORTUNE, JOHN M.; KUNKEL, THOMAS A.; GASCHE, CHRISTOPH

2007-01-01

Background & Aims Individuals with inflammatory bowel disease are at risk of developing colorectal cancer (CRC). Epidemiologic, animal, and laboratory studies suggest that 5-amino-salicylic acid (5-ASA) protects from the development of CRC by altering cell cycle progression and by inducing apoptosis. Our previous results indicate that 5-ASA improves replication fidelity in colorectal cells, an effect that is active in reducing mutations. In this study, we hypothesized that 5-ASA restrains cell cycle progression by activating checkpoint pathways in colorectal cell lines, which would prevent tumor development and improve genomic stability. Methods CRC cells with different genetic backgrounds such as HT29, HCT116, HCT116p53−/−, HCT116+chr3, and LoVo were treated with 5-ASA for 2–96 hours. Cell cycle progression, phosphorylation, and DNA binding of cell cycle checkpoint proteins were analyzed. Results We found that 5-ASA at concentrations between 10 and 40 mmol/L affects cell cycle progression by inducing cells to accumulate in the S phase. This effect was independent of the hMLH1, hMSH2, and p53 status because it was observed to a similar extent in all cell lines under investigation. Moreover, wash-out experiments demonstrated reversibility within 48 hours. Although p53 did not have a causative role, p53 Ser15 was strongly phosphorylated. Proteins involved in the ATM-and-Rad3-related kinase (ATR)-dependent S-phase checkpoint response (Chk1 and Rad17) were also phosphorylated but not ataxia telengectasia mutated kinase. Conclusions Our data demonstrate that 5-ASA causes cells to reversibly accumulate in S phase and activate an ATR-dependent checkpoint. The activation of replication checkpoint may slow down DNA replication and improve DNA replication fidelity, which increases the maintenance of genomic stability and counteracts carcinogenesis. PMID:17241873

Regaining Lost Separation in a Piloted Simulation of Autonomous Aircraft Operations

NASA Technical Reports Server (NTRS)

Barhydt, Richard; Eischeid, Todd M.; Palmer, Michael T.; Wing, David J.

2002-01-01

NASA is currently investigating a new concept of operations for the National Airspace System, designed to improve capacity while maintaining or improving current levels of safety. This concept, known as Distributed Air/Ground Traffic Management (DAG-TM), allows appropriately equipped autonomous aircraft to maneuver freely for flight optimization while resolving conflicts with other traffic and staying out of special use airspace and hazardous weather. While Airborne Separation Assurance System (ASAS) tools would normally allow pilots to resolve conflicts before they become hazardous, evaluation of system performance in sudden, near-term conflicts is needed in order to determine concept feasibility. If an acceptable safety level can be demonstrated in these situations, then operations may be conducted with lower separation minimums. An experiment was conducted in NASA Langley s Air Traffic Operations Lab to address issues associated with resolving near-term conflicts and the potential use of lower separation minimums. Sixteen commercial airline pilots flew a total of 32 traffic scenarios that required them to use prototype ASAS tools to resolve close range pop-up conflicts. Required separation standards were set at either 3 or 5 NM lateral spacing, with 1000 ft vertical separation being used for both cases. Reducing the lateral separation from 5 to 3 NM did not appear to increase operational risk, as indicated by the proximity to the intruder aircraft. Pilots performed better when they followed tactical guidance cues provided by ASAS than when they didn't follow the guidance. As air-air separation concepts are evolved, further studies will consider integration issues between ASAS and existing Airborne Collision Avoidance Systems (ACAS).These types of non-normal events will require the ASAS to provide effective alerts and resolutions prior to the time that an Airborne Collision Avoidance System (ACAS) would give a Resolution Advisory (RA). When an RA is issued, a pilot must take immediate action in order to avoid a potential near miss. The Traffic Alert and Collision Avoidance System (TCAS) II currently functions as an ACAS aboard commercial aircraft. Depending on the own aircraft s altitude, TCAS only issues RA s 15-35 seconds prior to the Closest Point of Approach (CPA). Prior to an RA, DAG-TM pilots operating autonomous aircraft must rely solely on ASAS for resolution guidance. An additional area of DAG-TM concept feasibility relates to a potential reduction in separation standards. Lower separation standards are likely needed in order to improve NAS efficiency and capacity. Current separation minimums are based in large part on the capabilities of older radar systems. Safety assessments are needed to determine the feasibility of reduced separation minimums. They will give strong consideration to surveillance system performance, including accuracy, integrity, and availability. Candidate surveillance systems include Automatic Dependent Surveillance-Broadcast (ADS-B) and multi-lateration systems. Considering studies done for Reduced Vertical Separation Minimums (RVSM) operations, it is likely that flight technical errors will also be considered. In addition to a thorough evaluation of surveillance system performance, a potential decision to lower the separation standards should also take operational considerations into account. An ASAS Safety Assessment study identified improper maneuvering in response to a conflict (due to ambiguous or improper resolution commands or a pilot s failure to comply with the resolution) as a potential safety risk. If near-term conflicts with lower separation minimums were determined to be more challenging for pilots, the severity of these risks could be even greater.

The All Sky Automated Survey. Catalog of Variable Stars. IV. 18^h-24^h Quarter of the Southern Hemisphere

NASA Astrophysics Data System (ADS)

Pojmanski, G.; Maciejewski, G.

2005-03-01

In this paper we present the fourth part of the photometric data from the 9 arcdeg x 9 arcdeg ASAS camera monitoring the whole southern hemisphere in V-band. Preliminary list (based on observations obtained since January 2001) of variable stars located between RA 18^h and 24^h is released. 10311 stars brighter than V=15 mag were found to be variable (1641 eclipsing, 1116 regularly pulsating, 938 Mira-type and 6616 other stars). Light curves have been classified using the automated algorithm taking into account periods, amplitudes, Fourier coefficients of the light curves, 2MASS colors and IRAS infrared fluxes. Basic photometric properties are presented in the tables and some examples of thumbnail light curves are printed for reference. All photometric data are available over the Internet at http://www.astrouw.edu.pl/~gp/asas/asas.html or http://archive.princeton.edu/~asas

Symptoms of anxiety and associated risk and protective factors in young Asian American children.

PubMed

Huang, Keng-Yen; Cheng, Sabrina; Calzada, Esther; Brotman, Laurie Miller

2012-10-01

Anxiety is one of the most prevalent mental health problems in young children but there has been a dearth of studies focusing on Asian American children. This study examines the patterns and the predictors of childhood anxiety and related symptoms in young children in a diverse Asian American (ASA) sample (n = 101). Findings indicate that ASA children are at higher risk for anxiety, somatization, and depressive problems than their peers. Parents' level of acculturation (i.e., American identity, English competence), parental negative emotion socialization, conflicted parent-child relationship, child emotional knowledge and adaptive skills, as well as teachers' ethnic background and school class types were all associated with ASA children's anxiety. A combination of cultural, family, and school factors explained from 17 to 39 % of the variance in anxiety symptoms. Findings inform prevention services for young ASA children.

The All Sky Automated Survey. The Catalog of Variable Stars. II. 6^h-12^h Quarter of the Southern Hemisphere

NASA Astrophysics Data System (ADS)

Pojmanski, G.

2003-12-01

This paper describes the second part of the photometric data from the 9 arcdeg times 9 arcdeg ASAS camera monitoring the whole southern hemisphere in the V-band. Preliminary list of variable stars based on observations obtained since January 2001 is presented. Over 2800000 stars brighter than V=15 mag on 18000 frames were analyzed and 11357 were found to be variable (2685 eclipsing, 907 regularly pulsating, 521 Mira and 7244 other, mostly SR, IRR and LPV stars). Periodic light curves have been classified using the automated algorithm, which now takes into account IRAS infrared fluxes. Basic photometric properties are presented in the tables and some examples of thumbnail light curves are printed for reference. All photometric data are available over the INTERNET at http://www.astrouw.edu.pl/~gp/asas/asas.html or http://archive.princeton.edu/~asas.

The All Sky Automated Survey. Catalog of Variable Stars. III. 12h-18h Quarter of the Southern Hemisphere

NASA Astrophysics Data System (ADS)

Pojmanski, G.; Maciejewski, G.

2004-06-01

This paper describes the third part of the photometric data from the 9 arcdeg x 9arcdeg ASAS camera monitoring the whole southern hemisphere in V-band. Preliminary list of variable stars based on observations obtained since January 2001 is presented. Over 3200000 stars brighter than V=15 mag on 18000 frames were analyzed and 10453 were found to be variable (1718 eclipsing, 731 regularly pulsating, 849 Mira and 7155 other stars). Light curves have been classified using the improved automated algorithm, which now takes into account 2MASS colors and IRAS infrared fluxes. Basic photometric properties are presented in the tables and some examples of thumbnail light curves are printed for reference. All photometric data are available over the INTERNET at http://www.astrouw.edu.pl/\\gp/asas/asas.html or http://archive.princeton.edu/\\asas.

Symptoms of Anxiety and Associated Risk and Protective Factors in Young Asian American Children

PubMed Central

Cheng, Sabrina; Calzada, Esther; Brotman, Laurie Miller

2014-01-01

Anxiety is one of the most prevalent mental health problems in young children but there has been a dearth of studies focusing on Asian American children. This study examines the patterns and the predictors of childhood anxiety and related symptoms in young children in a diverse Asian American (ASA) sample (n = 101). Findings indicate that ASA children are at higher risk for anxiety, somatization, and depressive problems than their peers. Parents’ level of acculturation (i.e., American identity, English competence), parental negative emotion socialization, conflicted parent–child relationship, child emotional knowledge and adaptive skills, as well as teachers’ ethnic background and school class types were all associated with ASA children’s anxiety. A combination of cultural, family, and school factors explained from 17 to 39 % of the variance in anxiety symptoms. Findings inform prevention services for young ASA children. PMID:22410755

Antisperm antibodies and fertility association.

PubMed

Restrepo, B; Cardona-Maya, W

2013-10-01

To evaluate the relation between antisperm antibodies (ASA) and human fertility by reviewing the scientific literature of the last 45 years. We carried out a review of scientific literature about antisperm antibodies and infertility published in spanish or english in databases as Pubmed, Medline, Scielo, some books and another gray literature include information related to this review and that is published in the last 45 years. Infertile couples suffer infertility by immunological mechanisms mainly by the presence of antisperm antibodies ASA in blood, semen or cervicovaginal secretions; the formation of ASA in men and women may be associated with disturbance in immunomodulatory mechanisms that result in functional impairment of sperm and thus its inability to fertilize the oocyte. Immunological infertility caused by ASA is the result of interference of these antibodies in various stages of fertilization process, inhibiting the ability of interaction between sperm and oocyte. Copyright © 2012 AEU. Published by Elsevier Espana. All rights reserved.

ASA education outreach

NASA Astrophysics Data System (ADS)

Hansen, Uwe J.; Everbach, E. Carr

2003-04-01

A number of very successful Hands-on demo sessions for high school students have been a part of regular ASA meetings for some time. In addition, the Education Committee has organized a series of teacher workshops. These workshops are designed to give high school teachers relatively sophisticated tools to enhance their laboratory content. Workshops for teachers in the elementary grades prepare teachers to use music as a vehicle to introduce additional science concepts. Content and methods associated with both workshops will be discussed. Cyberspace outreach by the ASA was accelerated by the establishment of a Home Page Committee, and more recently by the On-Line Education committee, which is creating an educational website. The website provides a fun way for users to access information including acoustics information, history, demos, and links to the Technical Committee's webpages. The ASA has joined other AIP member societies in developing additional mechanisms, including road shows and nightly news spots.

Pathways from childhood abuse to prospective revictimization: depression, sex to reduce negative affect, and forecasted sexual behavior.

PubMed

Miron, Lynsey R; Orcutt, Holly K

2014-11-01

Research suggests that adverse events in childhood, such as childhood physical, sexual, and emotional abuse, confer risk for later sexual assault. Psychological distress, coping strategies, and sexual behavior may help explain the path from childhood abuse to revictimization. The present study explored how the use of sex to regulate negative affect (SRNA) operates independently, and in combination with other psychosocial factors to increase college women's (N=541) risk of experiencing prospective adult sexual assault (ASA). Sequential multiple mediator models in Mplus were used to assess the effect of three different forms of childhood abuse on prospective ASA, both independently and while controlling for other forms of childhood abuse. The indirect effect of adolescent sexual assault (AdolSA), depressive symptoms, SRNA, and participants' response to a sex-related vignette was tested using bias-corrected bootstrapping. In the full path model, childhood emotional abuse and AdolSA predicted ASA, while childhood physical and sexual abuse were directly associated with AdolSA, but not ASA. Additionally, depressive symptoms and participants' estimate of their likely behavior in a sex-related vignette directly predicted prospective ASA. Results using bootstrapping revealed that a history of childhood abuse predicted prospective ASA via diverse direct and indirect paths, as well as through a similar multiple mediator path. Overall, findings suggest that a combination of affective, coping, and sexual expectancy factors contribute to risk for revictimization in adult survivors of childhood abuse. Future research directions and targets for risk-reduction programming are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Challenges in converting an interviewer-administered food probe database to self-administration in the National Cancer Institute Automated Self-administered 24-Hour Recall (ASA24).

PubMed

Zimmerman, Thea Palmer; Hull, Stephen G; McNutt, Suzanne; Mittl, Beth; Islam, Noemi; Guenther, Patricia M; Thompson, Frances E; Potischman, Nancy A; Subar, Amy F

2009-12-01

The National Cancer Institute (NCI) is developing an automated, self-administered 24-hour dietary recall (ASA24) application to collect and code dietary intake data. The goal of the ASA24 development is to create a web-based dietary interview based on the US Department of Agriculture (USDA) Automated Multiple Pass Method (AMPM) instrument currently used in the National Health and Nutrition Examination Survey (NHANES). The ASA24 food list, detail probes, and portion probes were drawn from the AMPM instrument; portion-size pictures from Baylor College of Medicine's Food Intake Recording Software System (FIRSSt) were added; and the food code/portion code assignments were linked to the USDA Food and Nutrient Database for Dietary Studies (FNDDS). The requirements that the interview be self-administered and fully auto-coded presented several challenges as the AMPM probes and responses were linked with the FNDDS food codes and portion pictures. This linking was accomplished through a "food pathway," or the sequence of steps that leads from a respondent's initial food selection, through the AMPM probes and portion pictures, to the point at which a food code and gram weight portion size are assigned. The ASA24 interview database that accomplishes this contains more than 1,100 food probes and more than 2 million food pathways and will include about 10,000 pictures of individual foods depicting up to 8 portion sizes per food. The ASA24 will make the administration of multiple days of recalls in large-scale studies economical and feasible.

Construction of a Calibrated Probabilistic Classification Catalog: Application to 50k Variable Sources in the All-Sky Automated Survey

NASA Astrophysics Data System (ADS)

Richards, Joseph W.; Starr, Dan L.; Miller, Adam A.; Bloom, Joshua S.; Butler, Nathaniel R.; Brink, Henrik; Crellin-Quick, Arien

2012-12-01

With growing data volumes from synoptic surveys, astronomers necessarily must become more abstracted from the discovery and introspection processes. Given the scarcity of follow-up resources, there is a particularly sharp onus on the frameworks that replace these human roles to provide accurate and well-calibrated probabilistic classification catalogs. Such catalogs inform the subsequent follow-up, allowing consumers to optimize the selection of specific sources for further study and permitting rigorous treatment of classification purities and efficiencies for population studies. Here, we describe a process to produce a probabilistic classification catalog of variability with machine learning from a multi-epoch photometric survey. In addition to producing accurate classifications, we show how to estimate calibrated class probabilities and motivate the importance of probability calibration. We also introduce a methodology for feature-based anomaly detection, which allows discovery of objects in the survey that do not fit within the predefined class taxonomy. Finally, we apply these methods to sources observed by the All-Sky Automated Survey (ASAS), and release the Machine-learned ASAS Classification Catalog (MACC), a 28 class probabilistic classification catalog of 50,124 ASAS sources in the ASAS Catalog of Variable Stars. We estimate that MACC achieves a sub-20% classification error rate and demonstrate that the class posterior probabilities are reasonably calibrated. MACC classifications compare favorably to the classifications of several previous domain-specific ASAS papers and to the ASAS Catalog of Variable Stars, which had classified only 24% of those sources into one of 12 science classes.

Hemodynamic monitoring and management in patients undergoing high risk surgery: a survey among North American and European anesthesiologists.

PubMed

Cannesson, Maxime; Pestel, Gunther; Ricks, Cameron; Hoeft, Andreas; Perel, Azriel

2011-08-15

Several studies have demonstrated that perioperative hemodynamic optimization has the ability to improve postoperative outcome in high-risk surgical patients. All of these studies aimed at optimizing cardiac output and/or oxygen delivery in the perioperative period. We conducted a survey with the American Society of Anesthesiologists (ASA) and the European Society of Anaesthesiology (ESA) to assess current hemodynamic management practices in patients undergoing high-risk surgery in Europe and in the United States. A survey including 33 specific questions was emailed to 2,500 randomly selected active members of the ASA and to active ESA members. Overall, 368 questionnaires were completed, 57.1% from ASA and 42.9% from ESA members. Cardiac output is monitored by only 34% of ASA and ESA respondents (P = 0.49) while central venous pressure is monitored by 73% of ASA respondents and 84% of ESA respondents (P < 0.01). Specifically, the pulmonary artery catheter is being used much more frequently in the US than in Europe in the setup of high-risk surgery (85.1% vs. 55.3% respectively, P < 0.001). Clinical experience, blood pressure, central venous pressure, and urine output are the most widely indicators of volume expansion. Finally, 86.5% of ASA respondents and 98.1% of ESA respondents believe that their current hemodynamic management could be improved. In conclusion, these results point to a considerable gap between the accumulating evidence about the benefits of perioperative hemodynamic optimization and the available technologies that may facilitate its clinical implementation, and clinical practices in both Europe and the United States.

Pathways from Childhood Abuse to Prospective Revictimization: Depression, Sex to Reduce Negative Affect, and Forecasted Sexual Behavior

PubMed Central

Miron, Lynsey R.; Orcutt, Holly K.

2014-01-01

Research suggests that adverse events in childhood, such as childhood physical, sexual, and emotional abuse, confer risk for later sexual assault. Psychological distress, coping strategies, and sexual behavior may help explain the path from childhood abuse to revictimization. The present study explored how the use of sex to regulate negative affect (SRNA) operates independently, and in combination with other psychosocial factors to increase college women’s (N = 541) risk of experiencing prospective adult sexual assault (ASA). Sequential multiple mediator models in Mplus were used to assess the effect of three different forms of childhood abuse on prospective ASA, both independently and while controlling for other forms of childhood abuse. The indirect effect of adolescent sexual assault (AdolSA), depressive symptoms, SRNA, and participants’ response to a sex-related vignette was tested using bias-corrected bootstrapping. In the full path model, childhood emotional abuse and AdolSA predicted ASA, while childhood physical and sexual abuse were directly associated with AdolSA, but not ASA. Additionally, depressive symptoms and participants’ estimate of their likely behavior in a sex-related vignette directly predicted prospective ASA. Results using bootstrapping revealed that a history of childhood abuse predicted prospective ASA via diverse direct and indirect paths, as well as through a similar multiple mediator path. Overall, findings suggest that a combination of affective, coping, and sexual expectancy factors contribute to risk for revictimization in adult survivors of childhood abuse. Future research directions and targets for risk-reduction programming will be discussed. PMID:25455965

Lack of inhibitory effect of acetylsalicylic acid and meloxicam on whole blood platelet aggregation in cats.

PubMed

Cathcart, Curtis J; Brainard, Benjamin M; Reynolds, Lisa R; Al-Nadaf, Sami; Budsberg, Steven C

2012-02-01

To determine the effects of acetylsalicylic acid (ASA) and meloxicam on feline platelet aggregation and associated platelet thromboxane production and serotonin release. Prospective interventional study. University research facility. Eight healthy male castrated domestic short hair cats from a research colony. Oral medications were administered to 8 cats for 14 days in a randomized, placebo-controlled, crossover design. Treatment groups included: aspirin (ASA) (5 mg/kg q 48 h), meloxicam (0.05 mg/kg q 24 h), and placebo (0.5 mL of water q 24 h). Thromboxane assays (TXB(2) ) and whole blood (impedance) aggregometry (WBA) were performed on samples collected before drug administration, and on days 7, 15, and 17, using adenosine diphosphate (ADP; 10 μM) and collagen (5 μg/mL) as agonists for WBA. Serotonin release was assayed on postaggregation plasma. Oral mucosal bleeding time (OMBT) and complete blood cell counts were measured on days 0 and 15. Neither medication affected WBA at any time point. OMBT decreased in the ASA group relative to baseline. No differences were detected in WBA and OMBT baseline between any groups. No difference was detected in serotonin secretion at any time point. TXB(2) was significantly decreased in the ASA group at all times after initiation of treatment but no change was noted in the meloxicam or placebo groups. At the doses studied, neither meloxicam nor ASA had an inhibitory effect on WBA or OMBT in cats. Thromboxane concentrations were significantly decreased with ASA treatment. © Veterinary Emergency and Critical Care Society 2011.

An Energy Aware Adaptive Sampling Algorithm for Energy Harvesting WSN with Energy Hungry Sensors

PubMed Central

Srbinovski, Bruno; Magno, Michele; Edwards-Murphy, Fiona; Pakrashi, Vikram; Popovici, Emanuel

2016-01-01

Wireless sensor nodes have a limited power budget, though they are often expected to be functional in the field once deployed for extended periods of time. Therefore, minimization of energy consumption and energy harvesting technology in Wireless Sensor Networks (WSN) are key tools for maximizing network lifetime, and achieving self-sustainability. This paper proposes an energy aware Adaptive Sampling Algorithm (ASA) for WSN with power hungry sensors and harvesting capabilities, an energy management technique that can be implemented on any WSN platform with enough processing power to execute the proposed algorithm. An existing state-of-the-art ASA developed for wireless sensor networks with power hungry sensors is optimized and enhanced to adapt the sampling frequency according to the available energy of the node. The proposed algorithm is evaluated using two in-field testbeds that are supplied by two different energy harvesting sources (solar and wind). Simulation and comparison between the state-of-the-art ASA and the proposed energy aware ASA (EASA) in terms of energy durability are carried out using in-field measured harvested energy (using both wind and solar sources) and power hungry sensors (ultrasonic wind sensor and gas sensors). The simulation results demonstrate that using ASA in combination with an energy aware function on the nodes can drastically increase the lifetime of a WSN node and enable self-sustainability. In fact, the proposed EASA in conjunction with energy harvesting capability can lead towards perpetual WSN operation and significantly outperform the state-of-the-art ASA. PMID:27043559

The C2H2 zinc-finger protein SlZF3 regulates AsA synthesis and salt tolerance by interacting with CSN5B.

PubMed

Li, Ying; Chu, Zhuannan; Luo, Jinying; Zhou, Yuhong; Cai, Yujing; Lu, Yongen; Xia, Junhui; Kuang, Hanhui; Ye, Zhibiao; Ouyang, Bo

2018-06-01

Abiotic stresses are a major cause of crop loss. Ascorbic acid (AsA) promotes stress tolerance by scavenging reactive oxygen species (ROS), which accumulate when plants experience abiotic stress. Although the biosynthesis and metabolism of AsA are well established, the genes that regulate these pathways remain largely unexplored. Here, we report on a novel regulatory gene from tomato (Solanum lycopersicum) named SlZF3 that encodes a Cys2/His2-type zinc-finger protein with an EAR repression domain. The expression of SlZF3 was rapidly induced by NaCl treatments. The overexpression of SlZF3 significantly increased the levels of AsA in tomato and Arabidopsis. Consequently, the AsA-mediated ROS-scavenging capacity of the SlZF3-overexpressing plants was increased, which enhanced the salt tolerance of these plants. Protein-protein interaction assays demonstrated that SlZF3 directly binds CSN5B, a key component of the COP9 signalosome. This interaction inhibited the binding of CSN5B to VTC1, a GDP-mannose pyrophosphorylase that contributes to AsA biosynthesis. We found that the EAR domain promoted the stability of SlZF3 but was not required for the interaction between SlZF3 and CSN5B. Our findings indicate that SlZF3 simultaneously promotes the accumulation of AsA and enhances plant salt-stress tolerance. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Semi-physiologic model validation and bioequivalence trials simulation to select the best analyte for acetylsalicylic acid.

PubMed

Cuesta-Gragera, Ana; Navarro-Fontestad, Carmen; Mangas-Sanjuan, Victor; González-Álvarez, Isabel; García-Arieta, Alfredo; Trocóniz, Iñaki F; Casabó, Vicente G; Bermejo, Marival

2015-07-10

The objective of this paper is to apply a previously developed semi-physiologic pharmacokinetic model implemented in NONMEM to simulate bioequivalence trials (BE) of acetyl salicylic acid (ASA) in order to validate the model performance against ASA human experimental data. ASA is a drug with first-pass hepatic and intestinal metabolism following Michaelis-Menten kinetics that leads to the formation of two main metabolites in two generations (first and second generation metabolites). The first aim was to adapt the semi-physiological model for ASA in NOMMEN using ASA pharmacokinetic parameters from literature, showing its sequential metabolism. The second aim was to validate this model by comparing the results obtained in NONMEM simulations with published experimental data at a dose of 1000 mg. The validated model was used to simulate bioequivalence trials at 3 dose schemes (100, 1000 and 3000 mg) and with 6 test formulations with decreasing in vivo dissolution rate constants versus the reference formulation (kD 8-0.25 h (-1)). Finally, the third aim was to determine which analyte (parent drug, first generation or second generation metabolite) was more sensitive to changes in formulation performance. The validation results showed that the concentration-time curves obtained with the simulations reproduced closely the published experimental data, confirming model performance. The parent drug (ASA) was the analyte that showed to be more sensitive to the decrease in pharmaceutical quality, with the highest decrease in Cmax and AUC ratio between test and reference formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

CONSTRUCTION OF A CALIBRATED PROBABILISTIC CLASSIFICATION CATALOG: APPLICATION TO 50k VARIABLE SOURCES IN THE ALL-SKY AUTOMATED SURVEY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richards, Joseph W.; Starr, Dan L.; Miller, Adam A.

2012-12-15

With growing data volumes from synoptic surveys, astronomers necessarily must become more abstracted from the discovery and introspection processes. Given the scarcity of follow-up resources, there is a particularly sharp onus on the frameworks that replace these human roles to provide accurate and well-calibrated probabilistic classification catalogs. Such catalogs inform the subsequent follow-up, allowing consumers to optimize the selection of specific sources for further study and permitting rigorous treatment of classification purities and efficiencies for population studies. Here, we describe a process to produce a probabilistic classification catalog of variability with machine learning from a multi-epoch photometric survey. In additionmore » to producing accurate classifications, we show how to estimate calibrated class probabilities and motivate the importance of probability calibration. We also introduce a methodology for feature-based anomaly detection, which allows discovery of objects in the survey that do not fit within the predefined class taxonomy. Finally, we apply these methods to sources observed by the All-Sky Automated Survey (ASAS), and release the Machine-learned ASAS Classification Catalog (MACC), a 28 class probabilistic classification catalog of 50,124 ASAS sources in the ASAS Catalog of Variable Stars. We estimate that MACC achieves a sub-20% classification error rate and demonstrate that the class posterior probabilities are reasonably calibrated. MACC classifications compare favorably to the classifications of several previous domain-specific ASAS papers and to the ASAS Catalog of Variable Stars, which had classified only 24% of those sources into one of 12 science classes.« less

[Intra-anesthetic arterial hypotension in elderly patients during emergency surgery: what are the risk factors?

PubMed

Boubacar Ba, El Hadji; Leye, Papa Alassane; Traoré, Mamadou Mour; Ndiaye, Pape Ibrahima; Gaye, Ibrahima; Bah, Mamadou Diawo; Fall, Mamadou Lamine; Diouf, Elisabeth

2017-01-01

Emergency anesthesia in elderly patients aged 65 years and older is complex. The occurrence of intraoperative incidents and arterial hypotension is conditioned by patients' initial health status and by the quality of intraoperative management. This study aimed to determine the incidence of intra-anesthetic arterial hypotension in elderly patients during emergency surgery and to assess the involvement of certain factors in its occurrence: age, sex, patient's history, ASA class, anesthetic technique. We conducted a retrospective descriptive and analytical study in the Emergency Surgery Department at the Aristide Le Dantec University Hospital from 1 March 2014 to 28 February 2015. We collected data from 210 patients out of 224 elderly patients aged 65 years and older undergoing emergency anesthesias (10.93%). Data of 101 men and 109 women were included in the analysis, of whom 64.3% had at least one defect. Patients' preoperative status was assessed using American Society of Anesthesiology (ASA) classification: 71% of patients were ASA class 1 and 2 and 29% were ASA class 3 and 4. Locoregional anesthesia was the most practiced anesthetic technique (56.7%). 28 patients (13.33%) had intra-anesthetic arterial hypotension, of whom 16 under general anesthesia and 12 under locoregional anesthesia. It was more frequent in patients with high ASA class and a little less frequent in patients with PAH and underlying heart disease. Arterial hypotension in elderly patients during emergency surgery exposes the subject to the risk of not negligible intraoperative hypotension, especially in patients with high ASA class. Prevention is based on adequate preoperative assessment and anesthetic management.

Improving the Efficiency and Safety of Aspirin by Complexation with the Natural Polysaccharide Arabinogalactan.

PubMed

Khvostov, Mikhail V; Tolstikova, Tatjana G; Borisov, Sergey A; Zhukova, Natalja A; Dushkin, Alexander V; Chistyachenko, Yulia S; Polyakov, Nikolay E

2016-01-01

The main undesirable side effect of the aspirin is the damage to the gastrointestinal mucosa, leading to the formation of erosions, peptic ulcers, and as a result, bleeding. To overcome this problem "host-guest" complexation with natural polysaccharide arabinogalactan could be applied. The complex with a weight ratio of ASA:AG = 1:10 was prepared by solid phase method in a rotary mill. Complex was administered orally to mice or rats at doses of 250, 500 or 1000 mg/kg. The "acetic acid induced writhing" and "hot plate" tests were used as an in vivo pain models. The antiinflammatory activity was studied using "histamine swelling" test. Also, long-term (30 days) oral introduction of the complex to rats was performed and gastric mucosa damages were evaluated. In all experiments pure aspirin (ASA) was used as a control in appropriate doses. The minimal effective analgesic dose of the complex was 250 mg/kg, equivalent to 23 mg/kg of ASA, a dose in which aspirin itself was not active. The anti-inflammatory effect was found at relatively higher doses: 500 and 1000 mg/kg (46 and 92 mg/kg of ASA respectively) for the complex and only at 100 mg/kg for the ASA. Long-term introduction of the complex at doses of 250 and 500 mg/kg was safe for gastric mucosa, while ASA at the dose of 50 mg/kg showed a strong gastric mucosal damage. The effective analgesic and anti-inflammatory doses of 1:10 aspirin complex with arabinogalactan are twice less compared to pure aspirin and safer for the gastrointestinal mucosa.

Aspirin attenuation of alcohol-induced flushing and intoxication in Oriental and Occidental subjects.

PubMed

Truitt, E B; Gaynor, C R; Mehl, D L

1987-01-01

Aspirin (ASA) was tested in a group of 8 Oriental and 3 Occidental subjects who were shown in a previous study to respond to small doses of ethanol (0.06-0.25 g/kg) with facial flushing. They were compared to a similar group of 11 non-flushing Occidental subjects following a larger ethanol dose (0.37 g/kg) to determine if similar effects could be produced in less sensitive individuals. Control tests of blood ethanol and acetaldehyde (AcH) levels (calculated from breath), facial and neck skin temperatures, body sway (Romberg test), blood pressure, heart rate and 10 Subjective High Assessment Scales (SHAS-Judd, 1977) were conducted before and at 15, 30, 60 and 90 minutes after drinking ethanol as vodka in orange juice. The tests were repeated one week later one hour after receiving 0.64 gm of ASA orally. ASA produced slight changes in the early absorption of ethanol and small decreases in AcH levels in the flushing and non-flushing groups. Facial flushing was markedly reduced in the flushing group, but was slightly increased in the non-flushing Occidentals. Body sway was reduced by ASA in both groups. An alcohol-induced increase in heart rate in the flushing group was reduced with no change in blood pressure. SHAS subjective parameters were widely variable, but indicated that ASA produced reduced sleepiness and earlier relaxation in the flushing group. It is concluded that ASA can block alcohol-induced facial flushing in sensitive subjects and also reduces body sway in the Romberg test and alters some subjective feelings of alcohol intoxication.

Acceptance of the Theory of Evolution in America: Louis Agassiz vs. Asa Gray

ERIC Educational Resources Information Center

Wolfe, Elaine Claire Daughetee

1975-01-01

Provides some background information on the contributions of Louis Agassiz and Asa Gray to the history of American science as these two men disagreed concerning the ideas in Darwin's "The Orgin of Species." (PB)

5-Aminosalicylic acid prevents oxidant mediated damage of glyceraldehyde-3-phosphate dehydrogenase in colon epithelial cells

PubMed Central

McKenzie, S; Doe, W; Buffinton, G

1999-01-01

Background—Reactive oxygen and nitrogen derived species produced by activated neutrophils have been implicated in the damage of mucosal proteins including the inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the active inflammatory lesion in patients with inflammatory bowel disease (IBD). This study investigated the efficacy of currently used IBD therapeutics to prevent injury mediated by reactive oxygen and nitrogen derived species. 
Methods—GAPDH activity of human colon epithelial cells was used as a sensitive indicator of injury produced by reactive oxygen and nitrogen derived species. HCT116 cells (106/ml phosphate buffered saline; 37°C) were incubated in the presence of 5-aminosalicylic acid (5-ASA), 6-mercaptopurine, methylprednisolone, or metronidazole before exposure to H2O2, HOCl, or NO in vitro. HCT116 cell GAPDH enzyme activity was determined by standard procedures. Cell free reactions between 5-ASA and HOCl were analysed by spectrophotometry and fluorimetry to characterise the mechanism of oxidant scavenging. 
Results—GAPDH activity of HCT116 cells was inhibited by the oxidants tested: the concentration that produced 50% inhibition (IC50) was 44.5 (2.1) µM for HOCl, 379.8 (21.3) µM for H2O2, and 685.8 (103.8) µM for NO (means (SEM)). 5-ASA was the only therapeutic compound tested to show efficacy (p<0.05) against HOCl mediated inhibition of enzyme activity; however, it was ineffective against H2O2 and NO mediated inhibition of GAPDH. Methylprednisolone, metronidazole, and the thiol-containing 6-mercaptopurine were ineffective against all oxidants. Studies at ratios of HOCl:5-ASA achievable in the mucosa showed direct scavenging to be the mechanism of protection of GAPDH activity. Mixing 5-ASA and HOCl before addition to the cells resulted in significantly greater protection of GAPDH activity than when HOCl was added to cells preincubated with 5-ASA. The addition of 5-ASA after HOCl exposure did not restore GAPDH activity. 
Conclusions—Therapies based on 5-ASA may play a direct role in scavenging the potent neutrophil oxidant HOCl, thereby protecting mucosal GAPDH from oxidative inhibition. These findings suggest that strategies for the further development of new HOCl scavenging compounds may be useful in the treatment of IBD. 

 Keywords: 5-aminosalicylic acid; 6-mercaptopurine; prednisolone; metronidazole; oxidants; glyceraldehyde-3-phosphate dehydrogenase PMID:9895376

Patient survival and surgical re-intervention predictors for intracapsular hip fractures.

PubMed

González Quevedo, David; Mariño, Iskandar Tamimi; Sánchez Siles, Juan Manuel; Escribano, Esther Romero; Granero Molina, Esther Judith; Enrique, David Bautista; Smoljanović, Tomislav; Pareja, Francisco Villanueva

2017-08-01

Choosing between total hip replacement (THR) and partial hip replacement (PHR) for patients with intracapsular hip fractures is often based on subjective factors. Predicting the survival of these patients and risk of surgical re-intervention is essential to select the most adequate implant. We conducted a retrospective cohort study on mortality of patients over 70 years with intracapsular hip fractures who were treated between January 2010 and December 2013, with either PHR or THR. Patients' information was withdrawn from our local computerized database. The age-adjusted Charlson comorbidity index (ACCI) and American Society of Anesthesiologists (ASA) score were calculated for all patients. The patients were followed for 2 years after surgery. Survival and surgical re-intervention rates were compared between the two groups using a Multivariate Cox proportional hazard model. A total of 356 individuals were included in this study. At 2 years of follow-up, 221 (74.4%) of the patients with ACCI score≤7 were still alive, in contrast to only 20 (29.0%) of those with ACCI score>7. In addition, 201 (76.2%) of the patients with ASA score≤3 were still alive after 2 years, compared to 30 (32.6%) of individuals with ASA >3. Patients with the ACCI score>7, and ASA score>3 had a significant increase in all-cause 2-year mortality (adjusted hazard ratio of 3.2, 95% CI 2.2-4.6; and 3.12, 95% CI 2.2-4.5, respectively). Patients with an ASA score>3 had a quasi-significant increase in the re-intervention risk (adjusted hazard ratio 2.2, 95% CI 1.0-5.1). The sensitivity, specificity, positive predictive value and negative predictive values of ACCI in predicting 2-year mortality were 39.2%, 91.1%, 71%, and 74.4%, respectively. On the other hand, the sensitivity, specificity, positive predictive value and negative predictive values of ASA score in predicting 2-year mortality were 49.6%, 79.1%, 67.4%, and 76.1%, respectively. Both ACCI and ASA scales were able to predict the 2-year survival of patients with intracapsular hip fractures. The ASA scale was also able to predict the risk of re-intervention in these patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enhancement After Myopic Small Incision Lenticule Extraction (SMILE) Using Surface Ablation.

PubMed

Siedlecki, Jakob; Luft, Nikolaus; Kook, Daniel; Wertheimer, Christian; Mayer, Wolfgang J; Bechmann, Martin; Wiltfang, Rainer; Priglinger, Siegfried G; Sekundo, Walter; Dirisamer, Martin

2017-08-01

To report the feasibility and outcomes of surface ablation after small incision lenticule extraction (SMILE). In this retrospective evaluation of 1,963 SMILE procedures, 43 eyes (2.2%) were re-treated at three separate clinics. Of these, 40 eyes of 28 patients with a follow-up of at least 3 months were included in the analysis. During surface ablation, mitomycin C was applied for haze prevention. Spherical equivalent was -6.35 ± 1.31 diopters (D) before SMILE and -0.86 ± 0.43 D before surface ablation. Surface ablation was performed after a mean of 9.82 ± 5.27 months and resulted in a spherical equivalent of 0.03 ± 0.57 D at 3 months (P < .0001). The number of patients within ±0.50 and ±1.00 D of target refraction increased from 22.5% to 80% and from 72.5% to 92.5%, respectively. Mean uncorrected distance visual acuity (UDVA) improved from 0.23 ± 0.20 to 0.08 ± 0.15 logMAR (P < .0001); 65% of patients gained at least one line. Corrected distance visual acuity (CDVA) remained unchanged with 0.01 ± 0.07 logMAR before versus -0.01 ± 0.05 logMAR after re-treatment (P = .99). Six eyes (15.0%) lost one line of CDVA, but final CDVA was 0.00 logMAR in four and 0.10 logMAR in two of these cases. The safety and efficacy indices were 1.06 and 0.90 at 3 months, respectively. Three of the four surface ablation profiles (Triple-A, tissue-saving algorithm, and topography-guided) resulted in equally good results, whereas enhancement with the aspherically optimized profile (ASA), used in two eyes, resulted in overcorrection (+1.38 and +1.75 D). Combined with the intraoperative application of mitomycin C, surface ablation seems to be a safe and effective method of secondary enhancement after SMILE. Due to the usually low residual myopia, the ASA profile is not recommended in these cases. [J Refract Surg. 2017;33(8):513-518.]. Copyright 2017, SLACK Incorporated.

Impact of a Focused Approach for Discharge Teaching Regarding the Use of Aspirin as Anticoagulant After Joint Replacement Surgery.

PubMed

Wittig-Wells, Deborah; Higgins, Melinda; Davis, Erica; Johnson, Ifeya; Louis, Latalya; Mason, Olga; Samms-McPherson, Jacqueline; Sims, Sandra; Jacob, Ani

2015-01-01

Patient education for the use and administration of aspirin (ASA) as an anticoagulant may be deficient. To pilot a knowledge assessment tool regarding the use of aspirin (ASA) as an anticoagulant and to evaluate the impact of a focused approach for discharge teaching. One-group pretest-posttest pilot study. Convenience sample of patients hospitalized for total knee and total hip arthroplasty. Researcher developed ASA quiz. Focused education on aspirin as an anticoagulant. There was a statistically significant improvement in knowledge (Wilcoxon rank sum test Z = 3.880, p < .001).

Self-consistent-field KKR-CPA calculations in the atomic-sphere approximations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, P.P. Gonis, A.; de Fontaine, D.

1991-12-03

We present a formulation of the Korringa-Kohn-Rostoker coherent potential approximation (KKR-CPA) for the treatment of substitutionally disordered alloys within the KKR atomic-sphere approximations (ASA). This KKR-ASA-CPA represents the first step toward the implementation of a full cell potential CPA, and combines the accuracy of the KKR-CPA method with the flexibility of treating complex crystal structures. The accuracy of this approach has been tested by comparing the self-consistent-field (SCF) KKR-ASA-CPA calculations of Cu-Pd alloys with experimental results and previous SCF-KKR-CPA calculations.

General Anesthesia Time for Pediatric Dental Cases

PubMed Central

Forsyth, Anna R.; Seminario, Ana Lucia; Scott, JoAnna; Berg, Joel; Ivanova, Iskra; Lee, Helen

2012-01-01

Purpose The purpose of this study was to describe the use of operating room (OR) time for pediatric dental procedures performed under general anesthesia (GA) at a regional children’s hospital over a 2-year period. Methods A cross-sectional review of a pediatric dental GA records was performed at Seattle Children’s Hospital. Data were collected for 709 0- to 21-year-old patients from January 2008 to December 2009. Demographic data, dental and anesthesia operator types, and procedures were recorded. Utilization of OR time was analyzed. Results The mean age of patients was 7.1 years (±4.2 SD), and 58% were male. Distribution by American Society of Anesthesiology (ASA) classifications were: ASA I 226 (32%); ASA II 316 (45%); ASA III 167 (24%). Cases finished earlier than the scheduled time by an average of 14 minutes (±28). Overrun time was significantly associated with: patient age (P=.01); ASA classification (P=.006); treatment type (P<.001); number of teeth treated (P<.001); and dentist operator type (P=.005). Conclusions Overall, 73% of dental procedures under GA finished early or on time. Significant variables included patient age, medical status, treatment type and extent, and dentist operator type. Assessing factors that impact the time needed in GA may enhance efficiency for pediatric dental procedures. PMID:23211897

Recycling ground granulated blast furnace slag as cold bonded artificial aggregate partially used in self-compacting concrete.

PubMed

Gesoğlu, Mehmet; Güneyisi, Erhan; Mahmood, Swara Fuad; Öz, Hatice Öznur; Mermerdaş, Kasım

2012-10-15

Ground granulated blast furnace slag (GGBFS), a by-product from iron industry, was recycled as artificial coarse aggregate through cold bonding pelletization process. The artificial slag aggregates (ASA) replaced partially the natural coarse aggregates in production of self-compacting concrete (SCC). Moreover, as being one of the most widely used mineral admixtures in concrete industry, fly ash (FA) was incorporated as a part of total binder content to impart desired fluidity to SCCs. A total of six concrete mixtures having various ASA replacement levels (0%, 20%, 40%, 60%, and 100%) were designed with a water-to-binder (w/b) ratio of 0.32. Fresh properties of self-compacting concretes (SCC) were observed through slump flow time, flow diameter, V-funnel flow time, and L-box filling height ratio. Compressive strength of hardened SCCs was also determined at 28 days of curing. It was observed that increasing the replacement level of ASA resulted in decrease in the amount of superplasticizer to achieve a constant slump flow diameter. Moreover, passing ability and viscosity of SCC's enhanced with increasing the amount of ASA in the concrete. The maximum compressive strength was achieved for the SCC having 60% ASA replacement. Copyright © 2012 Elsevier B.V. All rights reserved.

Diagnosis and classification of autoimmune orchitis.

PubMed

Silva, C A; Cocuzza, M; Carvalho, J F; Bonfá, E

2014-01-01

Autoimmune orchitis is characterized by testis inflammation and the presence of specific antisperm antibodies (ASA). It is classified in two categories. Primary autoimmune orchitis is defined by infertility and asymptomatic orchitis associated with ASA (100%) directed to the basement membrane or seminiferous tubules in infertile men, without any systemic disease and usually asymptomatic. Secondary autoimmune orchitis is characterized by symptomatic orchitis and/or testicular vasculiti`s associated with a systemic autoimmune disease, particularly vasculitis. These patients typically demonstrate testicular pain, erythema and/or swelling. ASA in secondary autoimmune orchitis have been reported in up to 50% of patients, especially in systemic lupus erythematosus patients. The pathogenesis of primary as well as secondary autoimmune orchitis is still unknown. Although the etiology is likely to be multifactorial, testicular inflammation, infection or trauma may induce T cell response with pro-inflammatory cytokine production with a consequent blood-testis-barrier permeability alteration, ASA production and apoptosis of spermatocytes and spermatids. ASA is known to cause immobilization and/or agglutination of spermatozoa, which may block sperm-egg interaction resulting in infertility. Assisted reproduction has been used as an efficient option in primary cases and immunosuppressive therapy for secondary autoimmune orchitis, although there is no double-blind, randomized trial to confirm the efficacy of any treatment regimens for these conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

Lessons from Studies to Evaluate an Online 24-Hour Recall for Use with Children and Adults in Canada.

PubMed

Kirkpatrick, Sharon I; Gilsing, Anne M; Hobin, Erin; Solbak, Nathan M; Wallace, Angela; Haines, Jess; Mayhew, Alexandra J; Orr, Sarah K; Raina, Parminder; Robson, Paula J; Sacco, Jocelyn E; Whelan, Heather K

2017-01-31

With technological innovation, comprehensive dietary intake data can be collected in a wide range of studies and settings. The Automated Self-Administered 24-hour (ASA24) Dietary Assessment Tool is a web-based system that guides respondents through 24-h recalls. The purpose of this paper is to describe lessons learned from five studies that assessed the feasibility and validity of ASA24 for capturing recall data among several population subgroups in Canada. These studies were conducted within a childcare setting (preschool children with reporting by parents), in public schools (children in grades 5-8; aged 10-13 years), and with community-based samples drawn from existing cohorts of adults and older adults. Themes emerged across studies regarding receptivity to completing ASA24, user experiences with the interface, and practical considerations for different populations. Overall, we found high acceptance of ASA24 among these diverse samples. However, the ASA24 interface was not intuitive for some participants, particularly young children and older adults. As well, technological challenges were encountered. These observations underscore the importance of piloting protocols using online tools, as well as consideration of the potential need for tailored resources to support study participants. Lessons gleaned can inform the effective use of technology-enabled dietary assessment tools in research.

The extent and influence of Asbestos Safety Awareness training among managers who had previously commissioned an asbestos survey in their workplace buildings

PubMed Central

HICKEY, Jane; SAUNDERS, Jean; DAVERN, Peter

2015-01-01

A telephone survey was conducted among a sample of managers (n=30) in Ireland who had previously commissioned an asbestos survey in their workplace buildings. The aims of the telephone survey were to examine the extent to which managers had completed Asbestos Safety Awareness (ASA) training, and to assess how such training might influence (i) their instinctive thoughts on asbestos, and (ii) their approach to aspects of asbestos management within their buildings. Managers’ motivations for commissioning the asbestos survey were also identified. The study found that ASA-trained managers (n=11) were not significantly more likely to work in larger organisations or in organisations which operated an accredited management system. Though ASA-trained managers’ instinctive thoughts on asbestos were of a slightly poorer technical quality compared with those of non-ASA-trained managers, they were still significantly more cognisant of their responsibilities towards those of their employees at specific risk of asbestos exposure. Most managers (n=28) commissioned the asbestos survey to satisfy a pre-requisite of external contractors for commencing refurbishment/demolition work in their buildings. Given its potential to positively influence the occupational management of asbestos, the authors recommend the general promotion of suitably tailored ASA-training programmes among building managers and external contractors alike. PMID:25914070

The extent and influence of Asbestos Safety Awareness training among managers who had previously commissioned an asbestos survey in their workplace buildings.

PubMed

Hickey, Jane; Saunders, Jean; Davern, Peter

2015-01-01

A telephone survey was conducted among a sample of managers (n=30) in Ireland who had previously commissioned an asbestos survey in their workplace buildings. The aims of the telephone survey were to examine the extent to which managers had completed Asbestos Safety Awareness (ASA) training, and to assess how such training might influence (i) their instinctive thoughts on asbestos, and (ii) their approach to aspects of asbestos management within their buildings. Managers' motivations for commissioning the asbestos survey were also identified. The study found that ASA-trained managers (n=11) were not significantly more likely to work in larger organisations or in organisations which operated an accredited management system. Though ASA-trained managers' instinctive thoughts on asbestos were of a slightly poorer technical quality compared with those of non-ASA-trained managers, they were still significantly more cognisant of their responsibilities towards those of their employees at specific risk of asbestos exposure. Most managers (n=28) commissioned the asbestos survey to satisfy a pre-requisite of external contractors for commencing refurbishment/demolition work in their buildings. Given its potential to positively influence the occupational management of asbestos, the authors recommend the general promotion of suitably tailored ASA-training programmes among building managers and external contractors alike.

Biochemical study of leaf browning in minimally processed leaves of lettuce (Lactuca sativa L. var. acephala).

PubMed

Degl'Innocenti, E; Guidi, L; Pardossi, A; Tognoni, F

2005-12-28

A series of biochemical parameters, including the concentration of total ascorbic acid (ASA(tot)) and the activities of phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), and peroxidases (PODs), was investigated during cold storage (72 h at 4 degrees C in the dark) in fresh-cut (minimally processed) leaves of two lettuce (Lactuca sativa L. var. acephala) cultivars differing in the susceptibility to tissue browning: Green Salade Bowl (GSB), susceptible, and Red Salade Bowl (RSB), resistant. The two cultivars showed differences also at the biochemical level. The content in ASA(tot) increased in RSB, as a consequence of increased DHA concentration; conversely, ASA(tot) diminished in GSB, in which ASA was not detectable after 72 h of storage, thus suggesting a disappearance of ascorbate (both ASA and DHA) into nonactive forms. The antioxidant capacity (as determined by using FRAP analysis) decreased significantly during storage in RSB, while a strong increase was observed in GSB. PAL activity increased soon after processing reaching a maximum by 3 h, then it declined to a relatively constant value in RSB, while in GSB it showed a tendency to decrease in the first few hours from harvest and processing. POD activity, at least for chlorogenic acid, increased significantly during storage only in GSB.

Urinary metabolites of histamine and leukotrienes before and after placebo-controlled challenge with ASA and food additives in chronic urticaria patients.

PubMed

Di Lorenzo, G; Pacor, M L; Vignola, A M; Profita, M; Esposito-Pellitteri, M; Biasi, D; Corrocher, R; Caruso, C

2002-12-01

The recovery of mediator metabolites from urine has the potential to provide a rapid, safe, and easily available index of release of mediators. We aimed to determine urinary metabolites of both histamine and leukotrienes (LTs) in patients affected by chronic urticaria (CU). Twenty patients with CU were studied. They were selected on the basis of double-blind placebo-controlled challenge (DBPC) with acetyl salicylic acid (ASA) and food additives. Ten patients (group B) were negative to both challenges. Ten patients (group C) presented urticaria and/or the appearance of angioedema during or 24 h after challenge, with reactions to ASA (five patients) or food additives (five patients). We recruited 15 healthy volunteers as controls (group A). During a second challenge, groups B and C were challenged double-blind with a single dose of ASA, or a specific food additive, or placebo. The healthy group was challenged only with a placebo (talc capsule). Patients in groups B and C were challenged twice: with placebo (as groups B1 and C1) and with ASA (groups B2 and C2) or food additives (C2). Four samples of urine were collected; one during the night before the specific or sham challenge (baseline), and three at 2, 6 and 24 h after the challenge. Urinary methylhistamine (N-MH) and LTE4 were analyzed and normalized for urinary creatinine. For urinary N-MH at baseline, there was a significant difference only between group A and groups B1, B2, C1 and C2 (A vs. B1, P < 0.0001; A vs. B2, P < 0.0001; A vs. C1, P < 0.0001; A vs. C2, P < 0.0001). We detected a significant variation in urinary methylhistamine excretion only in group C2 after 2 h, 6 h and 24 h (P < 0.0001). However, no variations were observed in N-MH excretion rate in the other groups (A, B1, C1) after challenge with placebo, and in B2 after challenge with ASA 20 mg. For urinary LTE4 at baseline no differences were found between the mean values for the different groups. After specific challenge, only C2 patients showed significantly increased excretion rates of urinary LTE4 compared with the other groups challenged with placebo (A, B1, C1), or ASA (B2) (P < 0.0001). No significant correlation was seen between urinary LTE4 and methylhistamine excretion rate in any patients. Our results show that urinary excretion of N-MH and LTE4 is different for CU patients without ASA or food hypersensitivity, compared to those with CU with ASA or food additive hypersensitivity after specific challenge.

Clopidogrel is not associated with major bleeding complications during peripheral arterial surgery

PubMed Central

Stone, David H.; Goodney, Philip P.; Schanzer, Andres; Nolan, Brian W.; Adams, Julie E.; Powell, Richard J.; Walsh, Daniel B.; Cronenwett, Jack L.

2017-01-01

Objectives Persistent variation in practice surrounds preoperative clopidogrel management at the time of vascular surgery. While some surgeons preferentially discontinue clopidogrel citing a perceived risk of perioperative bleeding, others will proceed with surgery in patients taking clopidogrel for an appropriate indication. The purpose of this study was to determine whether preoperative clopidogrel use was associated with significant bleeding complications during peripheral arterial surgery. Methods We reviewed a prospective regional vascular surgery registry recorded by 66 surgeons from 15 centers in New England from 2003 to 2009. Preoperative clopidogrel use within 48 hours of surgery was analyzed among patients undergoing carotid endarterectomy (CEA), lower extremity bypass (LEB), endovascular abdominal aortic aneurysm repair (EVAR), and open abdominal aortic aneurysm repair (oAAA). Ruptured AAAs were excluded. Endpoints included postoperative bleeding requiring reoperation, as well as the incidence and volume of blood transfusion. Statistical analysis was performed using analysis of variance, Fisher exact, χ2, and Wilcoxon rank-sum tests. Results Over the study interval, a total of 10,406 patients underwent surgery, including 5264 CEA, 2883 LEB, 1125 EVAR, and 1134 oAAA repair. Antiplatelet use among all patients varied, with 19% (n = 2010) taking no antiplatelet agents, 69% (n = 7132) taking aspirin (ASA) alone, 2.2% (n = 229) taking clopidogrel alone, and 9.7% (n = 1017) taking both ASA and clopidogrel. Clopidogrel alone or as dual antiplatelet therapy was most frequently used prior to CEA and least frequently prior to oAAA group (CEA 16.1%, LEB 9.0%, EVAR 6.5%, oAAA 5%). Reoperation for bleeding was not significantly different among patients based on antiplatelet regimen (none 1.5%, ASA 1.3%, clopidogrel 0.9%, ASA/clopidogrel 1.5%, P = .74). When analyzed by operation type, no difference in reoperation for bleeding was seen across antiplatelet regimens. There was also no difference in the incidence of transfusion among antiplatelet treatment groups (none 18%, ASA 17%, clopidogrel 0%, ASA/clopidogrel 24%, P = .1) and none when analyzed by individual operation type. Among patients who did require transfusion, there was no significant difference in the mean number of units of packed red blood cells required (none 0.7 units, ASA 0.5 units, clopidogrel 0 units, ASA/clopidogrel 0.6 units, P = .1) or when stratified by operation type. Conclusions Patients undergoing peripheral arterial surgery in whom clopidogrel was continued either alone or as part of dual antiplatelet therapy did not have significant bleeding complications compared with patients taking no antiplatelet therapy or ASA alone at the time of surgery. These data suggest that clopidogrel can safely be continued preoperatively in patients with appropriate indications for its use, such as symptomatic carotid disease or recent drug-eluting coronary stents. PMID:21571492

Clopidogrel is not associated with major bleeding complications during peripheral arterial surgery.

PubMed

Stone, David H; Goodney, Philip P; Schanzer, Andres; Nolan, Brian W; Adams, Julie E; Powell, Richard J; Walsh, Daniel B; Cronenwett, Jack L

2011-09-01

Persistent variation in practice surrounds preoperative clopidogrel management at the time of vascular surgery. While some surgeons preferentially discontinue clopidogrel citing a perceived risk of perioperative bleeding, others will proceed with surgery in patients taking clopidogrel for an appropriate indication. The purpose of this study was to determine whether preoperative clopidogrel use was associated with significant bleeding complications during peripheral arterial surgery. We reviewed a prospective regional vascular surgery registry recorded by 66 surgeons from 15 centers in New England from 2003 to 2009. Preoperative clopidogrel use within 48 hours of surgery was analyzed among patients undergoing carotid endarterectomy (CEA), lower extremity bypass (LEB), endovascular abdominal aortic aneurysm repair (EVAR), and open abdominal aortic aneurysm repair (oAAA). Ruptured AAAs were excluded. Endpoints included postoperative bleeding requiring reoperation, as well as the incidence and volume of blood transfusion. Statistical analysis was performed using analysis of variance, Fisher exact, χ(2), and Wilcoxon rank-sum tests. Over the study interval, a total of 10,406 patients underwent surgery, including 5264 CEA, 2883 LEB, 1125 EVAR, and 1134 oAAA repair. Antiplatelet use among all patients varied, with 19% (n = 2010) taking no antiplatelet agents, 69% (n = 7132) taking aspirin (ASA) alone, 2.2% (n = 229) taking clopidogrel alone, and 9.7% (n = 1017) taking both ASA and clopidogrel. Clopidogrel alone or as dual antiplatelet therapy was most frequently used prior to CEA and least frequently prior to oAAA group (CEA 16.1%, LEB 9.0%, EVAR 6.5%, oAAA 5%). Reoperation for bleeding was not significantly different among patients based on antiplatelet regimen (none 1.5%, ASA 1.3%, clopidogrel 0.9%, ASA/clopidogrel 1.5%, P = .74). When analyzed by operation type, no difference in reoperation for bleeding was seen across antiplatelet regimens. There was also no difference in the incidence of transfusion among antiplatelet treatment groups (none 18%, ASA 17%, clopidogrel 0%, ASA/clopidogrel 24%, P = .1) and none when analyzed by individual operation type. Among patients who did require transfusion, there was no significant difference in the mean number of units of packed red blood cells required (none 0.7 units, ASA 0.5 units, clopidogrel 0 units, ASA/clopidogrel 0.6 units, P = .1) or when stratified by operation type. Patients undergoing peripheral arterial surgery in whom clopidogrel was continued either alone or as part of dual antiplatelet therapy did not have significant bleeding complications compared with patients taking no antiplatelet therapy or ASA alone at the time of surgery. These data suggest that clopidogrel can safely be continued preoperatively in patients with appropriate indications for its use, such as symptomatic carotid disease or recent drug-eluting coronary stents. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Combining the ASA Physical Classification System and Continuous Intraoperative Surgical Apgar Score Measurement in Predicting Postoperative Risk.

PubMed

Jering, Monika Zdenka; Marolen, Khensani N; Shotwell, Matthew S; Denton, Jason N; Sandberg, Warren S; Ehrenfeld, Jesse Menachem

2015-11-01

The surgical Apgar score predicts major 30-day postoperative complications using data assessed at the end of surgery. We hypothesized that evaluating the surgical Apgar score continuously during surgery may identify patients at high risk for postoperative complications. We retrospectively identified general, vascular, and general oncology patients at Vanderbilt University Medical Center. Logistic regression methods were used to construct a series of predictive models in order to continuously estimate the risk of major postoperative complications, and to alert care providers during surgery should the risk exceed a given threshold. Area under the receiver operating characteristic curve (AUROC) was used to evaluate the discriminative ability of a model utilizing a continuously measured surgical Apgar score relative to models that use only preoperative clinical factors or continuously monitored individual constituents of the surgical Apgar score (i.e. heart rate, blood pressure, and blood loss). AUROC estimates were validated internally using a bootstrap method. 4,728 patients were included. Combining the ASA PS classification with continuously measured surgical Apgar score demonstrated improved discriminative ability (AUROC 0.80) in the pooled cohort compared to ASA (0.73) and the surgical Apgar score alone (0.74). To optimize the tradeoff between inadequate and excessive alerting with future real-time notifications, we recommend a threshold probability of 0.24. Continuous assessment of the surgical Apgar score is predictive for major postoperative complications. In the future, real-time notifications might allow for detection and mitigation of changes in a patient's accumulating risk of complications during a surgical procedure.

The relationship between study findings and publication outcome in anesthesia research: a retrospective observational study examining publication bias.

PubMed

Chong, Simon W; Collins, Neil F; Wu, Christine Y; Liskaser, Grace M; Peyton, Philip J

2016-06-01

Many areas of medicine have shown bias towards the publication of studies with positive results. To estimate publication bias in the anesthesia literature, we reviewed all abstracts presented at the American Society of Anesthesiologists (ASA) annual meetings over a four-year period and compared study results (positive vs negative) with publication outcomes. This review included all abstracts from the 2001-2004 ASA annual meetings performed as randomized-controlled trials in humans. We scored their outcome results as positive or negative and assessed abstract quality using a 13-point scoring system. We then performed a systematic literature search to identify any subsequent publication of the studies and calculated the relative risk (RR) for journal publication by comparing positive vs negative studies. Of 5,918 abstracts reviewed, 1,052 met inclusion criteria, and 564 (53.6%) of the abstracts proceeded to publication. The RR for abstracts with positive results proceeding to journal publication was 1.42 (95% confidence interval, 1.22 to 1.66; P < 0.001). This result did not change significantly after adjusting for study size and abstract quality score during logistic regression modelling. There was no significant difference in the abstract quality score between positive vs negative studies or between abstracts proceeding vs not proceeding to publication. Approximately half of the ASA annual meeting abstracts proceed to publication. After adjustment for study quality and size, abstracts with positive results were more likely to proceed to journal publication than those with negative results, suggesting publication bias in the anesthesia literature.

The Peptic Ulcer Perforation (PULP) score: a predictor of mortality following peptic ulcer perforation. A cohort study.

PubMed

Møller, M H; Engebjerg, M C; Adamsen, S; Bendix, J; Thomsen, R W

2012-05-01

Accurate and early identification of high-risk surgical patients with perforated peptic ulcer (PPU) is important for triage and risk stratification. The objective of the present study was to develop a new and improved clinical rule to predict mortality in patients following surgical treatment for PPU. nationwide cohort study based on prospectively collected data. thirty-five hospitals in Denmark. a total of 2668 patients surgically treated for gastric or duodenal PPU between 1 February 2003 and 31 August 2009. 30-day mortality. We derived a new clinical prediction rule for 30-day mortality and evaluated and compared its prognostic performance with the American Society of Anaesthesiologists (ASA) and Boey scores. A total of 708 patients (27%) died within 30 days of surgery. The Peptic Ulcer Perforation (PULP) score - comprised eight variables with an adjusted odds ratio of more than 1.28: 1) age > 65 years, 2) active malignant disease or AIDS, 3) liver cirrhosis, 4) steroid use, 5) time from perforation to admission > 24 h, 6) pre-operative shock, 7) serum creatinine > 130 μM, and 8) the four levels of the ASA score (from 2 to 5). The score predicted mortality well (area under receiver operating characteristics curve (AUC) 0.83). It performed considerably better than the Boey score (AUC 0.70) and better than the ASA score alone (AUC 0.78). The PULP score accurately predicts 30-day mortality in patients operated for PPU and can assist in risk stratification and triage. © 2011 The Authors Acta Anaesthesiologica Scandinavica © 2011 The Acta Anaesthesiologica Scandinavica Foundation.

Comparison of Three Risk Scores to Predict Outcomes of Severe Lower Gastrointestinal Bleeding.

PubMed

Camus, Marine; Jensen, Dennis M; Ohning, Gordon V; Kovacs, Thomas O; Jutabha, Rome; Ghassemi, Kevin A; Machicado, Gustavo A; Dulai, Gareth S; Jensen, Mary E; Gornbein, Jeffrey A

2016-01-01

Improved medical decisions by using a score at the initial patient triage level may lead to improvements in patient management, outcomes, and resource utilization. There is no validated score for management of lower gastrointestinal bleeding (LGIB) unlike for upper gastrointestinal bleeding. The aim of our study was to compare the accuracies of 3 different prognostic scores [Center for Ulcer Research and Education Hemostasis prognosis score, Charlson index, and American Society of Anesthesiologists (ASA) score] for the prediction of 30-day rebleeding, surgery, and death in severe LGIB. Data on consecutive patients hospitalized with severe gastrointestinal bleeding from January 2006 to October 2011 in our 2 tertiary academic referral centers were prospectively collected. Sensitivities, specificities, accuracies, and area under the receiver operator characteristic curve were computed for 3 scores for predictions of rebleeding, surgery, and mortality at 30 days. Two hundred thirty-five consecutive patients with LGIB were included between 2006 and 2011. Twenty-three percent of patients rebled, 6% had surgery, and 7.7% of patients died. The accuracies of each score never reached 70% for predicting rebleeding or surgery in either. The ASA score had a highest accuracy for predicting mortality within 30 days (83.5%), whereas the Center for Ulcer Research and Education Hemostasis prognosis score and the Charlson index both had accuracies <75% for the prediction of death within 30 days. ASA score could be useful to predict death within 30 days. However, a new score is still warranted to predict all 30 days outcomes (rebleeding, surgery, and death) in LGIB.

Retrospective study of the prevalence of postanaesthetic hypothermia in dogs.

PubMed

Redondo, J I; Suesta, P; Serra, I; Soler, C; Soler, G; Gil, L; Gómez-Villamandos, R J

2012-10-13

The anaesthetic records of 1525 dogs were examined to determine the prevalence of postanaesthetic hypothermia, its clinical predictors and consequences. Temperature was recorded throughout the anaesthesia. At the end of the procedure, details coded in were: hyperthermia (>39.50°C), normothermia (38.50°C-39.50°C), slight (38.49°C-36.50°C), moderate (36.49°C-34.00°C) and severe hypothermia (<34.00°C). Statistical analysis consisted of multiple regression to identify the factors that are associated with the temperature at the end of the procedure. Before premedication, the temperature was 38.7 ± 0.6°C (mean ± sd). At 60, 120 and 180 minutes from induction, the temperature was 36.7 ± 1.3°C, 36.1 ± 1.4°C and 35.8 ± 1.5°C, respectively. The prevalence of hypothermia was: slight, 51.5 per cent (95 per cent CI 49.0 to 54.0 per cent); moderate, 29.3 per cent (27.1-31.7 per cent) and severe: 2.8% (2.0-3.7%). The variables that associated with a decrease in the temperature recorded at the end of the anaesthesia were: duration of the preanesthetic time, duration of the anaesthesia, physical condition (ASA III and ASA IV dogs showed lower temperatures than ASA I dogs), the reason for anaesthesia (anaesthesia for diagnostic procedures or thoracic surgery reduce the temperature when compared with minor procedures), and the recumbency during the procedure (sternal and dorsal recumbencies showed lower temperatures than lateral recumbency). The temperature before premedication and the body surface (BS) were associated with a higher temperature at the end of the anaesthesia, and would be considered as protective factors.

Selective Serotonergic (SSRI) Versus Noradrenergic (SNRI) Reuptake Inhibitors with and without Acetylsalicylic Acid in Major Depressive Disorder.

PubMed

Zdanowicz, Nicolas; Reynaert, Christine; Jacques, Denis; Lepiece, Brice; Dubois, Thomas

2017-09-01

Antidepressant medication efficacy remains a major research challenge. Here, we explored four questions: whether noradrenergic antidepressants are more effective than serotonergic antidepressants; whether the addition of 100 mg acetylsalicylic acid (ASA) changes antidepressant efficacy; whether the long-term efficacy differs depending on the antidepressant and the addition of ASA; and whether serum levels of brain-derived neurotrophic factor (BDNF) are clinically informative. In a two-year study, forty people with major depressive disorder were randomly assigned to groups that received an SSRI (escitalopram) or an SNRI (duloxetine), each group received concomitant ASA (100 mg) or a placebo. Sociodemographic data were recorded and patients under went regular assessments with the Hamilton depression scale (HDS) and clinical global impression (CGI) scale. Serum levels of BDNF were measured four times per year. There was no significant difference in efficacy between the two antidepressants or between antidepressant treatment with and without ASA. However, subgroup comparisons revealed that the duloxetine + ASA (DASA) subgroup showed a more rapid improvement in HDS score as early as 2 months (t=-3.114, p=0.01), in CGI score at 5 months (t=-2.119, p=0.05), and a better remission rate (χ 2 =6.296, p 0.012) than the escitalopram + placebo (EP) subgroup. Serum BDNF before treatment was also higher in the DASA subgroup than in the EP subgroup (t=3.713; p=0.002). This suggest two hypotheses: either a noradrenergic agent combined with ASA is more effective in treating depression than a serotonergic agent alone, or the level of serum BDNF before treatment is a precursor marker of the response to antidepressants. Further research is needed to test these hypotheses.

In vitro interference by acetaminophen, aspirin, and metamizole in serum measurements of glucose, urea, and creatinine.

PubMed

Luna-Záizar, Hilda; Virgen-Montelongo, María; Cortez-Álvarez, Cesar R; Ruiz-Quezada, Sandra L; Escutia-Gutiérrez, Raymundo; García-Lemus, Cuauhtémoc R; Mendizabal-Ruiz, Adriana P

2015-05-01

Here we aimed to investigate the in vitro effects of three analgesic-antipyretic drugs frequently used in clinical practice in Mexico - acetaminophen (AAP), aspirin (ASA) and metamizole (MMZ) - on serum measurements of glucose, urea, and creatinine. Each analyte was measured in a base-serum pool spiked with the drugs at subtherapeutic, therapeutic, and toxic doses. Serum glucose and urea were measured using the hexokinase/G-6PDH and urease/GLDH kinetic assays, respectively. Serum creatinine (SCr) was measured with a Jaffe procedure based on the alkaline-picrate reaction and with an enzymatic dry-chemistry system. Measurements were carried out in IL-Monarch and Vitros DT60-II analyzers, respectively. Data were analyzed by the difference-paired interference test and by ANOVA. By the kinetic Jaffe/Monarch procedure, we found positive interference by the drugs on the SCr measurements and by only ASA for urea measurement. For creatinine measurements, the total errors (TEs) were 22-51%, 18-105%, and 15-26% for AAP, ASA, and MMZ respectively, while for urea measurement the TE was 16-21% for ASA. A negative interference by MMZ on SCr (TE=-47%), but no-interference for AAP or ASA, were found via the enzymatic/DT60-II system. In vitro positive interference induced by AAP, ASA, and MMZ (via the alkaline-picrate reaction), or negative interference by MMZ (via a dry-chemistry system), on the SCr measurements highlights the importance of investigating all possible sources of variation that may alter the accuracy of the laboratory tests, in order to provide useful results for making medical decisions for optimal patient care. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Hemodynamic monitoring and management in patients undergoing high risk surgery: a survey among North American and European anesthesiologists

PubMed Central

2011-01-01

Introduction Several studies have demonstrated that perioperative hemodynamic optimization has the ability to improve postoperative outcome in high-risk surgical patients. All of these studies aimed at optimizing cardiac output and/or oxygen delivery in the perioperative period. We conducted a survey with the American Society of Anesthesiologists (ASA) and the European Society of Anaesthesiology (ESA) to assess current hemodynamic management practices in patients undergoing high-risk surgery in Europe and in the United States. Methods A survey including 33 specific questions was emailed to 2,500 randomly selected active members of the ASA and to active ESA members. Results Overall, 368 questionnaires were completed, 57.1% from ASA and 42.9% from ESA members. Cardiac output is monitored by only 34% of ASA and ESA respondents (P = 0.49) while central venous pressure is monitored by 73% of ASA respondents and 84% of ESA respondents (P < 0.01). Specifically, the pulmonary artery catheter is being used much more frequently in the US than in Europe in the setup of high-risk surgery (85.1% vs. 55.3% respectively, P < 0.001). Clinical experience, blood pressure, central venous pressure, and urine output are the most widely indicators of volume expansion. Finally, 86.5% of ASA respondents and 98.1% of ESA respondents believe that their current hemodynamic management could be improved. Conclusions In conclusion, these results point to a considerable gap between the accumulating evidence about the benefits of perioperative hemodynamic optimization and the available technologies that may facilitate its clinical implementation, and clinical practices in both Europe and the United States. PMID:21843353

Congenital bilateral absence of the vas deferens (CBAVD): Possible correlation between cystic fibrosis (CF) genotype and antisperm antibodies (ASA) phenotype

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kupchick, G.S.; Vazquez-Levin, M.H.; Nagler, H.M.

1994-09-01

A large number of CBAVD patients have been found to carry at least one known CF mutation. Several of these individuals have been shown to be compound heterozygotes. It is likely that most CBAVD cases represent the milder end of the CF spectrum. However, in a given CBAVD patient with no known mutations found (within current screening capabilities), it is not possible to conclude a CF relationship. Since CBAVD patients have been successfully treated for infertility with epididymal aspiration techniques, there are reproductive and clinical implications regarding CF. We have studied seven CBAVD patients (P{sub 1}-P{sub 7}) with regards tomore » presence and levels of ASA and their CF genotypes. An indirect immunobead binding test was used to measure ASA. ASA were found in 5/7 (71%) patients studied. High levels of IgG binding to sperm tail-tip were found in two cases (P{sub 2}, P{sub 4}); IgG binding to all sperm regions and IgA binding to sperm head were found in one case (P{sub 5}); IgM binding to tail-tip was found in two cases (P{sub 1}, P{sub 3}). Three patients (P{sub 1}, P{sub 3}, P{sub 4}) had a {triangle}F308 / ? and two (P{sub 2}, P{sub 5}) a W1282X / ? genotype. Interestingly, the two patients with no known mutation found (P{sub 6}, P{sub 7}) had negative ASA. The study of more patients could yield ASA as a potential indirect marker for relatedness of CBAVD to CF gene mutations.« less

Evaluation of whether extremely high enthesitis or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores suggest fibromyalgia and confound the anti-TNF response in early non-radiographic axial spondyloarthritis.

PubMed

Dougados, Maxime; Logeart, Isabelle; Szumski, Annette; Coindreau, Javier; Jones, Heather

2017-01-01

Differentiating between pain from spondyloarthritis (SpA) and pain from fibromyalgia is challenging. We evaluated patients with non-radiographic axial SpA (nr-axSpA) to determine the percentage of patients with extremely high enthesitis and/or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, the relationship between extreme scores and depression, and the effect of extreme scores on treatment outcomes with etanercept. Patients with nr-axSpA received double-blind etanercept 50 mg or placebo weekly and were divided into those who did vs did not have extreme scores at baseline. Extreme scores were defined as the highest quintile for enthesitis score (≥6), and/or scores ≥8 on three of five BASDAI items (excluding morning stiffness duration). Depression was assessed with the Hospital Anxiety and Depression Scale, depression subscale (HADS-D) and medication use. Week 12 outcomes included Assessment of SpondyloArthritis (ASAS) 40 and ASAS partial remission. At baseline, 35/213 (16.4%) patients met extreme enthesitis criteria, 31 (14.6%) met extreme BASDAI criteria, 12 (5.6%) met both, and 135 (63.4%) met neither. More patients with extreme scores than without met the HADS-D definition of depression: 35/68 (51.5%) vs. 27/118 (22.9%), p<0.0001. For patients with vs. without extreme scores who received etanercept, no significant difference existed in week 12 ASAS 40: 13/41 (31.7%) vs. 21/60 (35.0%), respectively, or ASAS partial remission: 8/41 (19.5%) vs. 19/60 (31.7%). Extreme enthesitis and/or BASDAI scores were associated with measurements of depression, but did not affect week 12 ASAS 40 or ASAS partial remission.

Onyx injection by direct puncture for the treatment of hypervascular spinal metastases close to the anterior spinal artery: initial experience.

PubMed

Clarençon, Frédéric; Di Maria, Federico; Cormier, Evelyne; Sourour, Nader-Antoine; Enkaoua, Eric; Sailhan, Frédéric; Iosif, Christina; Le Jean, Lise; Chiras, Jacques

2013-06-01

Presurgical devascularization of hypervascular spinal metastases has been shown to be effective in preventing major blood loss during open surgery. Most often, embolization can be performed using polyvinyl alcohol (PVA) microparticles. However, in some cases, the close relationship between the feeders of the metastases and the feeders of the anterior spinal artery (ASA) poses a risk of spinal cord ischemia when PVA microparticle embolization is performed. The authors present their early experience in the treatment of spinal metastases close to the ASA; in 2 cases they injected Onyx-18, by direct puncture, into hypervascular posterior arch spinal metastases situated close to the ASA. Two women, one 36 and the other 55 years of age, who presented with spinal lesions (at the posterior arch of C-4 and T-6, respectively) from thyroid and a kidney tumors, were sent to the authors' department to undergo presurgical embolization. After having performed a complete spinal digital subtraction angiography study, a regular angiography catheter was positioned at the ostium of the artery that mainly supplied the lesion. Then, with the patient in the left lateral decubitus position, direct puncture with 18-gauge needles of the lesion was performed using roadmap guidance. Onyx-18 was injected through the needles under biplanar fluoroscopy. Satisfactory devascularization of the lesions was obtained; the ASA remained patent in both cases. The metastases were surgically removed in both cases within the 48 hours after the embolization and major blood loss did not occur. Presurgical devascularization of hypervascular spinal metastases close the ASA by direct puncture with Onyx-18 seems to be an effective technique and appears to be safe in terms of the preserving the ASA's patency.

Factors associated with antithrombotic treatment decisions for stroke prevention in atrial fibrillation in the Stockholm region after the introduction of NOACs.

PubMed

Komen, Joris; Forslund, Tomas; Hjemdahl, Paul; Wettermark, Björn

2017-10-01

The purpose of this study was to investigate the influence of patient characteristics such as age and stroke and bleeding risks on decisions for antithrombotic treatment in patients with atrial fibrillation (AF). This was a retrospective, population-based study including AF patients initiated with either warfarin, dabigatran, rivaroxaban, apixaban, or low-dose aspirin (ASA) between March 2015 and February 2016. Multivariate models were used to calculate adjusted odds ratios (aOR) for factors associated with treatment decisions. A total of 6765 newly initiated patients were included, most with apixaban (46.4%) and least with ASA (6.7%). There were more comorbidities in patients initiated with ASA or warfarin compared to the cohort average. Patients with high stroke risks had higher chances of receiving ASA (CHA 2 DS 2 -VASc ≥5 vs 0; aOR 2.01; 95% confidence interval (CI) 1.12-3.33). Among patients receiving oral anticoagulants, patients with high bleeding risks more often received warfarin (ATRIA score 5-10 vs 0-3; aOR 1.40; CI 1.20-1.64). Among NOACs, apixaban was preferred for patients with higher stroke risks (aOR 1.78; CI 1.31-2.41), high bleeding risks (aOR 1.54; CI 1.26-1.88) and high age (age group ≥85 vs 0-65; aOR 1.84; CI 1.44-2.35). Conversely, dabigatran treatment was associated with lower ages and lower risks. High stroke and bleeding risks favored choices of warfarin or ASA. Among patients receiving NOACs, apixaban was favored for elderly and high-risk patients whereas dabigatran was used in lower risk patients. The inadvertent use of ASA, especially among those with high stroke risks, should be further discouraged.

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

PubMed

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

2015-06-11

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

Effects of administration of beta-carotene, ascorbic acid, persimmons, and pods on antioxidative ability in UV-irradiated ODS rats.

PubMed

Hosotani, Keisuke; Yoshida, Minoru; Kitagawa, Masahiro

2005-07-01

To evaluate the effects of supplementing diets with carotenoid and ascorbic acid (AsA) on the antioxidative ability of Osteogenic Disorder-Shionogi (ODS) rats, we added synthetic beta-carotene (betaC), AsA, and powders of persimmon (Ka) and pods (Po) containing betaC and AsA to the diet and obtained the following results. The urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration was low in the -betaC.AsA and +AsA groups but high in the +betaC.AsA, +Ka, and +Po groups. The thiobarbituric acid-reactive substances (TBARS) in both the liver and skin were higher in the -betaC.AsA group than in the +betaC.AsA group and were low in the +Ka and +Po groups. As antioxidant enzymes, glutathione peroxidase (GSH-Px) activity was high in the +betaC.AsA group, low in the -beta3C.AsA group in both the skin and liver, and also high in the + Ka and +Po group in the liver. Superoxide dismutase (SOD) activity was high in the -betaC.AsA group and low in the +betaC.AsA and +Ka groups in both the skin and liver. Catalase (CAT) activity in the liver was low in the -betaC.AsA, +AsA, and +betaC groups and high in the +betaC.AsA and +Po groups. These results confirmed that the administration of betaC, AsA, and persimmons and pods increases antioxidative ability in the skin and liver of ultraviolet-b(UV-B)-irradiated ODS rats.

Homologous expression of cytosolic dehydroascorbate reductase increases grain yield and biomass under paddy field conditions in transgenic rice (Oryza sativa L. japonica).

PubMed

Kim, Young-Saeng; Kim, Il-Sup; Bae, Mi-Jung; Choe, Yong-Hoe; Kim, Yul-Ho; Park, Hyang-Mi; Kang, Hong-Gyu; Yoon, Ho-Sung

2013-06-01

Dehydroascorbate reductase (DHAR, EC 1.8.5.1) maintains redox pools of ascorbate (AsA) by recycling oxidized AsA to reduced AsA. To investigate whether DHAR affects rice yield under normal environmental conditions, cDNA-encoding DHAR (OsDHAR1) was isolated from rice and used to develop OsDHAR1-overexpressing transgenic rice plants, under the regulation of a maize ubiquitin promoter. Incorporation and expression of the transgene in transgenic rice plants was confirmed by genomic polymerase chain reaction (PCR), semi-quantitative reverse transcription PCR (RT-PCR), western blot, and enzyme activity. The expression levels were at least twofold higher in transgenic (TG) rice plants than in control wild-type (WT) rice plants. In addition, OsDHAR1-overexpression in seven-independent homologous transgenic plants, as compared to WT plants, increased photosynthetic capacity and antioxidant enzyme activities under paddy field conditions, which led to an improved AsA pool and redox homeostasis. Furthermore, OsDHAR1 overexpression significantly improved grain yield and biomass due to the increase of culm and root weights and to enhance panicle and spikelet numbers in the same seven independent TG rice plants during the farming season (2010 and 2011) in South Korea. The OsDHAR protein contained the redox-active site (Cys20), as well as the conserved GSH-binding region, GSH-binding motif, glutathione-S-transferase (GST) N-terminal domain, C-terminal domain interface, and GST C-terminal domain. Therefore, our results indicate that OsDHAR1 overexpression, capable of functioning in AsA recycling, and protein folding increases environmental adaptation to paddy field conditions by the improving AsA pool and redox homeostasis, which enhances rice grain yield and biomass.

Modulation of N-glycosylation by mesalamine facilitates membranous E-cadherin expression in colon epithelial cells☆

PubMed Central

Khare, Vineeta; Lang, Michaela; Dammann, Kyle; Campregher, Christoph; Lyakhovich, Alex; Gasche, Christoph

2014-01-01

Genome wide association studies have implicated intestinal barrier function genes in the pathogenesis of ulcerative colitis. One of such loci CDH1, encoding E-cadherin, a transmembrane glycoprotein with known tumor suppressor functions, is also linked to the susceptibility to colorectal cancer. Loss of membranous E-cadherin expression is common in both colitis and cancer. We have recently demonstrated that mesalamine (5-ASA); the anti-inflammatory drug used to treat ulcerative colitis, induces membranous expression of E-cadherin and increases intercellular adhesion. Using colorectal cancer epithelial cells with aberrant E-cadherin expression, we investigated the mechanism underlying such an effect of 5-ASA. Post-translational modification of E-cadherin glycosylation was analyzed by biotin/streptavidin detection of sialylated glycoproteins. GnT-III (N-acetylglucosaminyltransferase III) expression was assessed by qRT-PCR, Western blot and immunofluorescence. GnT-III activity was analyzed by reactivity with E-4/L-4-PHA. Expression, localization and interaction of E-cadherin and β-catenin were analyzed by Western blot, immunocytochemistry and RNA interference. 5-ASA activity modulated E-cadherin glycosylation and increased both mRNA and protein levels of GnT-III and its activity as detected by increased E4-lectin reactivity. Intestinal APCMin polyps in mice showed low expression of GnT-III and 5-ASA was effective in increasing its expression. The data demonstrated that remodeling of glycans by GnT-III mediated bisect glycosylation, contributes to the membranous retention of E-cadherin by 5-ASA; facilitating intercellular adhesion. Induction of membranous expression of E-cadherin by 5-ASA is a novel mechanism for mucosal healing in colitis that might impede tumor progression by modulation of GnT-III expression. PMID:24184502

Are there any differences in the efficacy and safety of different formulations of Oral 5-ASA used for induction and maintenance of remission in ulcerative colitis? evidence from cochrane reviews.

PubMed

Feagan, Brian G; Chande, Nilesh; MacDonald, John K

2013-08-01

We systematically reviewed and compared the efficacy and safety of oral mesalamine formulations (sustained release, delayed release, and prodrugs) used for induction and maintenance of remission in ulcerative colitis. The main objective of this review was to determine if there are any differences in efficacy or safety among the oral 5-ASA drugs. A literature search in February 2013 identified all applicable randomized trials. Study quality was evaluated using the Cochrane risk of bias tool. The Grading of Recommendations Assessment, Development and Evaluation criteria were used to assess the overall quality of the evidence. Studies were subgrouped by common mesalamine comparators for meta-analysis. Studies were pooled for analysis if they compared equimolar doses of oral 5-ASA. Seventeen studies that evaluated 2925 patients were identified. The risk of bias was low for most factors, although 1 study was single blind and 3 were open label. No difference was observed between oral 5-ASA and comparator 5-ASA formulations in the proportion of patients with clinical remission (relative risk, 0.94; 95% confidence interval, 0.86-1.02), clinical improvement (relative risk, 0.89; 95% confidence interval, 0.77-1.01), or relapse at 12 months (relative risk, 1.01; 95% confidence interval, 0.80-1.28). Subgroup analyses showed no important differences in efficacy. No significant difference was demonstrated in rates of adverse events or withdrawal due to adverse events. There does not seem to be any difference in efficacy or safety among the various formulations of oral 5-ASA. Oral mesalamine is an effective and safe treatment of mild-to-moderate or quiescent ulcerative colitis regardless of the chosen formulation.

The effect of low-dose aspirin on the decreased risk of development of dyspepsia and gastrointestinal ulcers associated to cyclooxygenase-2 selective inhibitors.

PubMed

Benito-Garcia, Elizabeth; Michaud, Kaleb; Wolfe, Frederick

2007-08-01

To evaluate the risk of gastrointestinal (GI) symptoms and ulcers associated to the use of low-dose aspirin (ASA) among patients with rheumatoid arthritis (RA) and osteoarthritis (OA) treated with cyclooxygenase-2 (COX-2) drugs, to clarify the controversy in the literature. Using a longitudinal databank, a prospective study using Cox proportional hazards models was performed in patients receiving COX-2 therapy for RA or OA to examine the effect of ASA on GI events. In 4 separate analyses patients reported dyspeptic symptoms and GI ulcers at semiannual intervals for up to 3 years. Ulcers were validated by review of medical records. Among 4240 patients taking COX-2-specific inhibitors, with no ulcer at study start, the age- and sex-adjusted hazard ratios for the effect of ASA on the development of epigastric pain, heartburn, nausea, and ulcers, without these previous events, were 1.11 (95% CI 0.97-1.29), 1.00 (95% CI 0.88-1.15), 1.32 (95% CI 1.13-1.54), and 1.27 (95% CI 0.78-2.05). The use of a propensity score to account for the risk of ASA prescription showed an even lower effect of ASA among all GI variables. This risk occurs within the setting of no prior GI symptoms or GI events, and independently of the use of proton pump inhibitors, other GI drugs, other nonsteroidal antiinflammatory drugs, prednisone, or methotrexate. In actual practice, the use of low-dose ASA has a small effect on the risk of developing dyspeptic symptoms in a group of patients with rheumatic disease.

A Novel Variant in the Platelet Endothelial Aggregation Receptor-1 Gene is Associated with Increased Platelet Aggregabili

PubMed Central

Herrera-Galeano, J. Enrique; Becker, Diane M.; Wilson, Alexander F.; Yanek, Lisa R.; Bray, Paul; Vaidya, Dhananjay; Faraday, Nauder; Becker, Lewis C

2009-01-01

Objective: Platelet endothelial aggregation receptor-1 (PEAR1) is a recently identified platelet transmembrane protein that becomes activated by platelet contact. We looked for novel genetic variants in PEAR1 and studied their association with agonist-induced native platelet aggregation and with aspirin's inhibitory effect on platelets. Methods and Results: We genotyped PEAR1 for 10 single nucleotide polymorphisms (SNPs), selected for optimal gene coverage at a density of 4kb, in 1486 apparently healthy individuals from two generations of families with premature CAD. Subjects had a mean age of 45 years; 62% were white and 38% African American. Platelet aggregation to collagen, epinephrine, and ADP was measured in platelet rich plasma, at baseline and after 2 weeks of aspirin (ASA, 81 mg/day), and genotype-phenotype associations were examined separately by ethnicity using multivariable generalized linear models adjusted for covariates. The C allele of SNP rs2768759 [A/C], located in the promoter region of the gene, was common in whites and uncommon in African Americans (allele frequency 70.2% vs 17.7%). The C allele was generally associated in both ethnic groups with increased aggregation of native platelets to each agonist. Following ASA, the associations were stronger and more consistent, and remained significant when post ASA aggregation was adjusted for baseline aggregation, consistent with a relationship between the C allele and reduced platelet responsiveness to ASA. The PEAR1 SNP explained up to 6.9% of the locus specific genetic variance in African Americans and up to 2.5% of the genetic variance in whites following ASA. Conclusion: PEAR1 appears to play an important role in agonist-induced platelet aggregation and in the response to ASA in both whites and African Americans. PMID:18511696

A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study

PubMed Central

Park, Won; Hrycaj, Pawel; Jeka, Slawomir; Kovalenko, Volodymyr; Lysenko, Grygorii; Miranda, Pedro; Mikazane, Helena; Gutierrez-Ureña, Sergio; Lim, MieJin; Lee, Yeon-Ah; Lee, Sang Joon; Kim, HoUng; Yoo, Dae Hyun; Braun, Jürgen

2013-01-01

Objectives To compare the pharmacokinetics (PK), safety and efficacy of innovator infliximab (INX) and CT-P13, a biosimilar to INX, in patients with active ankylosing spondylitis (AS). Methods Phase 1 randomised, double-blind, multicentre, multinational, parallel-group study. Patients were randomised to receive 5 mg/kg of CT-P13 (n=125) or INX (n=125). Primary endpoints were area under the concentration-time curve (AUC) at steady state and observed maximum steady state serum concentration (Cmax,ss) between weeks 22 and 30. Additional PK, efficacy endpoints, including 20% and 40% improvement response according to Assessment in Ankylosing Spondylitis International Working Group criteria (ASAS20 and ASAS40), and safety outcomes were also assessed. Results Geometric mean AUC was 32 765.8 μgh/ml for CT-P13 and 31 359.3 μgh/ml for INX. Geometric mean Cmax,ss was 147.0  μg/ml for CT-P13 and 144.8 μg/ml for INX. The ratio of geometric means was 104.5% (90% CI 94% to 116%) for AUC and 101.5% (90% CI 95% to 109%) for Cmax,ss. ASAS20 and ASAS40 responses at week 30 were 70.5% and 51.8% for CT-P13 and 72.4% and 47.4% for INX, respectively. In the CT-P13 and INX groups more than one adverse event occurred in 64.8% and 63.9% of patients, infusion reactions occurred in 3.9% and 4.9%, active tuberculosis occurred in 1.6% and 0.8%, and 27.4% and 22.5% of patients tested positive for anti-drug antibodies, respectively. Conclusions The PK profiles of CT-P13 and INX were equivalent in patients with active AS. CT-P13 was well tolerated, with an efficacy and safety profile comparable to that of INX up to week 30. PMID:23687259

Adaptive-Adaptive Narrowband Subarray Beamforming

DTIC Science & Technology

1994-02-10

the ML ASA beamformer exhibits some extra noise gain. • In the presence of dominant transition band interferers, the NG ASA beamformer exhibits an...Inc., 87. [8] M. Rendas and J. Moura. Cramer-Rao bound for location systems in multipath environments. IEEE Transactions on Signal Processing, 39

32 CFR 182.5 - Responsibilities.

Code of Federal Regulations, 2014 CFR

2014-07-01

... account in the planning and execution of military training and operations. (k) The Commanders of U.S... Defense and Americas' Security Affairs (ASD(HD&ASA)), under the authority, direction, and control of the... Defense and Americas' Security Affairs (ASD(HD&ASA)),” shall develop, coordinate, recommend, and supervise...

32 CFR 185.5 - Responsibilities.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Homeland Defense and Americas' Security Affairs (ASD(HD&ASA)), under the authority, direction, and control... and Americas' Security Affairs. When carrying out this authority, the ASD(HD&ASA) shall: 19 Available... responsibilities in the matter, and Military Department Secretaries and other DoD officials as appropriate. (ii...

32 CFR 182.5 - Responsibilities.

Code of Federal Regulations, 2013 CFR

2013-07-01

... account in the planning and execution of military training and operations. (k) The Commanders of U.S... Defense and Americas' Security Affairs (ASD(HD&ASA)), under the authority, direction, and control of the... Defense and Americas' Security Affairs (ASD(HD&ASA)),” shall develop, coordinate, recommend, and supervise...

32 CFR 185.5 - Responsibilities.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Homeland Defense and Americas' Security Affairs (ASD(HD&ASA)), under the authority, direction, and control... and Americas' Security Affairs. When carrying out this authority, the ASD(HD&ASA) shall: 19 Available... responsibilities in the matter, and Military Department Secretaries and other DoD officials as appropriate. (ii...

32 CFR 185.5 - Responsibilities.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Homeland Defense and Americas' Security Affairs (ASD(HD&ASA)), under the authority, direction, and control... and Americas' Security Affairs. When carrying out this authority, the ASD(HD&ASA) shall: 19 Available... responsibilities in the matter, and Military Department Secretaries and other DoD officials as appropriate. (ii...

32 CFR 185.5 - Responsibilities.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Homeland Defense and Americas' Security Affairs (ASD(HD&ASA)), under the authority, direction, and control... and Americas' Security Affairs. When carrying out this authority, the ASD(HD&ASA) shall: 19 Available... responsibilities in the matter, and Military Department Secretaries and other DoD officials as appropriate. (ii...

32 CFR Appendix F to Part 651 - Glossary

Code of Federal Regulations, 2013 CFR

2013-07-01

.... ASA(AL&T) Assistant Secretary of the Army (Acquisition, Logistics, and Technology). ASA(FM) Assistant.../Cost Analysis. EICS Environmental Impact Computer System. EIFS Economic Impact Forecast System. EIS... Record of Non-Applicability. RSC Regional Support Command. S&T Science and Technology. SA Secretary of...

32 CFR Appendix F to Part 651 - Glossary

Code of Federal Regulations, 2012 CFR

2012-07-01

.... ASA(AL&T) Assistant Secretary of the Army (Acquisition, Logistics, and Technology). ASA(FM) Assistant.../Cost Analysis. EICS Environmental Impact Computer System. EIFS Economic Impact Forecast System. EIS... Record of Non-Applicability. RSC Regional Support Command. S&T Science and Technology. SA Secretary of...

32 CFR Appendix F to Part 651 - Glossary

Code of Federal Regulations, 2014 CFR

2014-07-01

.... ASA(AL&T) Assistant Secretary of the Army (Acquisition, Logistics, and Technology). ASA(FM) Assistant.../Cost Analysis. EICS Environmental Impact Computer System. EIFS Economic Impact Forecast System. EIS... Record of Non-Applicability. RSC Regional Support Command. S&T Science and Technology. SA Secretary of...

[A pharmaceutical of the century will be 100. A historical vignette on the introduction of acetylsalicylic acid to the market in 1899].

PubMed

Kohl, F

1999-10-15

This article describes the historic roots of acetylsalicylic acid (ASA) from the first experiments at 1800 until the introduction into the pharmaceutical market in 1899. In 1869, Hermann Kolbe enlightened the chemical structure of salicylic acid, which was used at that time as an analgetic and antipyretic drug. Because of the side effects, for example the irritation of the stomach, analytical chemists and pharmacologists searched for chemical modifications. In August 1897 Felix Hoffmann (1868-1946) was successful in acetylizing the salicylic acid to acetylsalicylic acid (ASA). Between 1897 and 1899 Kurt Witthauer (1865-1911) collected clinical data and experiences on the efficiency of ASA as an analgetic and antipyretic drug. In 1899 ASA was introduced into the pharmaceutical market as Aspirin and became soon one of the most successful drugs of its time. The indication exceeds analgesia in the mean time and to prophylaxis of myocardial ischaemia or cerebral stroke, among others.

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

PubMed

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.

Liquid chromatographic determination of L-ascorbic acid in candies and soft drinks.

PubMed

Maeda, Y; Ochi, S; Masui, T; Matubara, S

1988-01-01

The L-ascorbic acid (AsA) contents of candies and soft drinks available in the market were determined by liquid chromatography (LC). Samples are cleaned up on a disposable Sep-Pak C18 cartridge followed by reverse phase separation on an ODS column using a mobile phase of 0.1% phosphoric acid (pH 2.2). The AsA peak is detected on the basis of the UV absorption at 254 nm. The detection limit was 1 microgram/mL final concentration. Recoveries of AsA added at levels of 1-10 mg/g candy and 1-10 mg/10 mL soft drink were 99.2-101.7% with a coefficient of variation of 0.52-1.20% (n = 5). The present method allows rapid and accurate assays because it is a simple procedure compared with the official dye-titration method, and it is suitable for the routine analysis of AsA in selected candies and soft drinks.

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

PubMed Central

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

2017-01-01

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

Prevalence of enterococcus species and their virulence genes in fresh water prior to and after storm events.

PubMed

Sidhu, J P S; Skelly, E; Hodgers, L; Ahmed, W; Li, Y; Toze, S

2014-01-01

Enterococcus spp. isolates (n = 286) collected from six surface water bodies in subtropical Brisbane, Australia, prior to and after storm events, were identified to species level and tested for the presence of seven clinically important virulence genes (VGs). Enterococcus faecalis (48%), Enterococcus faecium (14%), Enterococcus mundtii (13%), and Enterococcus casseliflavus (13%) were frequently detected at all sites. The frequency of E. faecium occurrence increased from 6% in the dry period to 18% after the wet period. The endocarditis antigen (efaA), gelatinase (gelE), collagen-binding protein (ace), and aggregation substance (asa1) were detected in 61%, 43%, 43%, and 23% of Enterococcus isolates, respectively. The chances of occurrence of ace, gelE, efaA, and asa1 genes in E. faecalis were found to be much higher compared to the other Enterococcus spp. The observed odds ratio of occurrence of ace and gelE genes in E. faecalis was much higher at 7.96 and 6.40 times, respectively. The hyl gene was 3.84 times more likely to be detected in E. casseliflavus. The presence of multiple VGs in most of the E. faecalis isolates underscores the importance of E. faecalis as a reservoir of VGs in the fresh water aquatic environment. Consequently, if contaminated surface water is to be used for production of potable and nonpotable water some degree of treatment depending upon intended use such as detention in basins prior to use or chlorination is required.

A validation study of the Automated Self-Administered 24-Hour Dietary Recall for Children (ASA24-Kids) among 9 to 11-year-old youth

PubMed Central

Diep, Cassandra S.; Hingle, Melanie; Chen, Tzu-An; Dadabhoy, Hafza R.; Beltran, Alicia; Baranowski, Janice; Subar, Amy F.; Baranowski, Tom

2015-01-01

Background Valid methods of diet assessment are important for nutrition research and practice but can be difficult with children. Objective To validate ASA24-Kids-2012, a self-administered web-based 24-hour dietary recall (24hDR) among 9-11-year-old children, in two sites. Design Quasi-experimental Participants/setting In one site, trained staff observed and recorded foods and drinks consumed by children (n=38) during school lunch. The next day, the observed children completed both ASA24-Kids-2012 and an interviewer-administered 24hDR in a randomized order. Procedures in a second site (n=31) were similar, except observations occurred during dinner in a community location. Statistical analyses Foods were classified as matches (reported and consumed), intrusions (reported, but not consumed), or omissions (not reported, but consumed) for each participant. Rates of matches, intrusions, and omissions were calculated. Rates were compared between each recall method using repeated measures analysis of covariance. For matched foods, the authors determined correlation coefficients between observed and reported serving sizes. Results Match, intrusion, and omission rates between ASA24-Kids-2012 and observed intakes in site 1 were 37%, 27%, and 35%, respectively. Comparable rates for interviewer-administered 24hDRs were 57%, 20%, and 23%, respectively. In site 2, match, intrusion, and omission rates between ASA24-Kids-2012 and observed intakes were 53%, 12%, and 36%, respectively, vs. 76% matches, 9% intrusions, and 15% omissions for interviewer-administered 24hDRs. The relationship strength between reported and observed serving sizes for matched foods was 0.18 in site 1 and 0.09 in site 2 for ASA24-Kids-2012, and 0.46 in site 1 and 0.11 in site 2 for interviewer-administered 24hDRs. Conclusions ASA24-Kids-2012 was less accurate than interviewer-administered 24hDRs when compared to observed intakes, but both performed poorly. Additional research should assess the age at which children can complete recalls without the help of a parent or guardian, as well as to elucidate under which circumstances recalls can reasonably be used among children. PMID:25887784

Surgical septal myectomy or alcohol septal ablation: which approach offers better outcomes for patients with hypertrophic obstructive cardiomyopathy?

PubMed

Poon, Shi Sum; Field, Mark; Gupta, Dhiraj; Cameron, Duke

2017-06-01

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether surgical septal myectomy (SM) is more beneficial than alcohol septal ablation (ASA) in patients with hypertrophic obstructive cardiomyopathy. Altogether 218 articles were found using the reported search, of which 15 studies represented the best evidence to answer the clinical question. There were 14 observational studies and 1 meta-analysis study. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these articles are tabulated. Surgical SM was generally performed in younger patients whereas percutaneous ASA was favoured in patients with advanced age and significant co-morbidities. In a large study comprising 716 patients, the reduction of median residual left ventricular outflow tract (LVOT) gradient at 3 months was comparable after ASA (102 ± 52-10 mmHg) and SM (92 ± 39-9 mmHg). The New York Heart Association (NYHA) functional class and symptomatic improvement for either approach was comparable. Findings from the meta-analysis study showed that patients who underwent ASA had a higher incidence of post-procedure device implantation (odds ratio 3.09; P < 0.00001), as reported in 6 other studies. The risk of permanent pacemaker insertion during follow-up (FU) varied between 2.4-12.5% in SM and 1.7-22.0% in ASA. Isolated surgical myectomy and ASA are safe and effective in abolishing outflow obstruction, although the resolution of LVOT pressure gradient is more complete with surgery. The post-procedural and late mortality rates between the 2 groups are consistently low and comparable in carefully selected patients. Nonetheless, ASA is associated with the increased likelihood of complications such as permanent pacemaker implantation, early sustained-VT and VF, and re-intervention. Overall, when performed by experienced cardiologists and surgeons, both techniques are safe and effective in most cases and therefore treatment should be offered based on patient choice. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Analysis of HLA-B15 and HLA-B27 in spondyloarthritis with peripheral and axial clinical patterns

PubMed Central

Londono, John; Santos, Ana Maria; Peña, Paola; Calvo, Enrique; Espinosa, Luis R; Reveille, John D; Vargas-Alarcon, Gilberto; Jaramillo, Carlos A; Valle-Oñate, Rafael; Avila, Mabel; Romero, Consuelo; Medina, Juan F

2015-01-01

Objective Human leucocyte antigen (HLA) B27 and HLA-B15 are associated with spondyloarthritis (SpA). Recent Assessment of SpondyloArthritis international Society (ASAS) criteria emphasise a distinction between SpA with axial and peripheral patterns. We analysed whether HLA-A, HLA-B and HLA-DRB1 alleles could associate with these patterns. Methods We studied 100 healthy individuals and 178 patients with SpA according to European Spondyloarthropathy Study Group (ESSG) criteria. Patients were then classified according to ASAS criteria, the axial spondyloarthritis pattern (axSpA) being defined by ascertained sacroiliitis and the peripheral pattern (pSpA) by enthesitis and/or arthritis in extremities. A combined ax/p pattern was also considered. Results Only HLA-B27 and HLA-B15 alleles were associated with SpA. ASAS criteria for axSpA were met in 152 patients (12 with isolated axSpA and 140 with a combined ax/p patterns). When the ASAS peripheral criteria were applied, 161 patients met these criteria (13 with isolated pSpA and 148 with a combined ax/p pattern). HLA-B27 was found in 83% of patients with axSpA and 43% of ax/pSpA patients according to axASAS. HLA-B27 occurred in 7% controls but not in any patient with isolated pSpA. HLA-B15 was encountered in 31% of patients with isolated pSpA and 20% of ax/pSpA patients according to pASAS criteria. Moreover, 2 healthy controls, but none of our patients with isolated axSpA were positive for HLA-B15. Conclusions Our data suggest that the presence of HLA-B15 favours the development of isolated/combined peripheral rather than isolated axSpA, while HLA-B27 promotes an isolated/combined axial disease and excludes a peripheral pattern. HLA-B15 should be considered in addition to HLA-B27 when diagnosing patients with SpA according to ASAS criteria. PMID:26560062

Exercise-induced changes in left ventricular global longitudinal strain in asymptomatic severe aortic stenosis.

PubMed

Lech, Agnieszka K; Dobrowolski, Piotr P; Klisiewicz, Anna; Hoffman, Piotr

2017-01-01

The management of patients with asymptomatic severe aortic stenosis (ASAS) is still under discussion. Therefore, it is advisable to search for the parameters of early damage to left ventricular (LV) function. The aim of the study was to assess exercise-induced changes in LV global longitudinal strain (GLS) in ASAS. The ASAS group consisted of 50 patients (26 women and 24 men, aged 38.4 ± 18.1 years) meeting the echocardiographic criteria of severe aortic stenosis (AVA < 1 cm², AVAI < 0.6 cm²/m², Vmax > 4 m/s, mean aortic gradient > 40 mm Hg), with normal LV ejection fraction (LVEF ≥ 55%) and sinus rhythm on electrocardiogram, and without significant concomitant valvular heart diseases. The control group consisted of 21 people matched for age and sex. Echocardiographic examinations and echocardiographic stress tests with the assessment of GLS using the speckle tracking imaging were performed. The ASAS group was characterised by statistically significantly higher LV mass index (LVMI) and higher LVEF. GLS values at rest in both groups were within normal limits but were significantly higher in the control group (-18.9 ± 2.4% vs. -20.7 ± 1.7%, p = 0.006). An increase in GLS at peak exercise in both groups was observed, lower in the ASAS group (the difference was not statistically significant: -0.8 ± 3.0% vs. -2.2 ± 3.1%, p = 0.086). Changes in GLS during exercise (ΔGLS) did not correlate with the parameters of the severity of aortic stenosis. In the multivariate model, LVMI proved to be a factor associated with GLS at rest and during exercise. In patients with ASAS, GLS is a non-invasive marker of an early stage of LV myocardial damage associated with myocardial hypertrophy. An increase in GLS during exercise in the ASAS group, smaller than in the control group, indicates a preserved functional reserve of the LV myocardium but smaller than in healthy individuals. The assessment of the clinical usefulness of exercise-induced changes in GLS requires further research.

Efficacy and Safety of Oral Beclomethasone Dipropionate in Ulcerative Colitis: A Systematic Review and Meta-Analysis.

PubMed

Manguso, Francesco; Bennato, Raffaele; Lombardi, Giovanni; Riccio, Elisabetta; Costantino, Giuseppe; Fries, Walter

2016-01-01

We performed a systematic review and meta-analysis of all the available evidence comparing efficacy and safety of oral prolonged released beclomethasone dipropionate (BDP) to active oral controls in patients with mild-to-moderate ulcerative colitis (UC). A subgroup-analysis compared the effectiveness of BDP and 5-ASA. Literature research was performed in different databases, as well as manual search to identify abstracts from international meetings with data not included in extensive publications. Experts in the field and companies involved in BDP development and manufacture were contacted to identify unpublished studies used for registration purposes. Dichotomous data were pooled to obtain odds ratio meta-analysis. Five randomized controlled trials that compared oral BDP 5mg/day vs. all oral active controls in treating UC were identified as eligible. Efficacy and safety have been addressed after 4-week treatment period. One study evaluated efficacy and safety of BDP vs. prednisone and 4 of BDP vs. 5-ASA. Treatment with oral BDP 5 mg/day induces a significant better clinical response compared to oral 5-ASA (OR 1.86, 95% CI = 1.23-2.82, P = 0.003). The effect is detectable even when the comparison to prednisone is added (OR 1.41, 95% CI = 1.03-1.93, P = 0.03). Data on remission indicate that the potential clinical efficacy of BDP may be better than 5-ASA (OR 1.55, 95% CI = 1.00-2.40, P = 0.05). This difference is lost when the comparison with prednisone is added (OR 1.30, 95% CI = 0.76-2.23, P = 0.34). The safety analysis showed no differences between BDP and 5-ASA (OR 0.55, 95% CI = 0.24-1.27, P = 0.16). The lack of difference is maintained even when the study with prednisone is added (OR 0.67, 95% CI = 0.44-1.01, P = 0.06). However, the trend of difference is clear and indicates a more favourable safety profile of BDP compared to 5-ASA and PD. Oral prolonged release BDP showed a superior efficacy vs. oral 5-ASA in inducing clinical improvement of mild-to-moderate UC with a similar safety profile.

Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos.

PubMed

Bolnick, Alan; Abdulhasan, Mohammed; Kilburn, Brian; Xie, Yufen; Howard, Mindie; Andresen, Paul; Shamir, Alexandra M; Dai, Jing; Puscheck, Elizabeth E; Rappolee, Daniel A

2016-08-01

The purpose of the present study is to test whether metformin, aspirin, or diet supplement (DS) BioResponse-3,3'-Diindolylmethane (BR-DIM) can induce AMP-activated protein kinase (AMPK)-dependent potency loss in cultured embryos and whether metformin (Met) + Aspirin (Asa) or BR-DIM causes an AMPK-dependent decrease in embryonic development. The methods used were as follows: culture post-thaw mouse zygotes to the two-cell embryo stage and test effects after 1-h AMPK agonists' (e.g., Met, Asa, BR-DIM, control hyperosmotic stress) exposure on AMPK-dependent loss of Oct4 and/or Rex1 nuclear potency factors, confirm AMPK dependence by reversing potency loss in two-cell-stage embryos with AMPK inhibitor compound C (CC), test whether Met + Asa (i.e., co-added) or DS BR-DIM decreases development of two-cell to blastocyst stage in an AMPK-dependent (CC-sensitive) manner, and evaluate the level of Rex1 and Oct4 nuclear fluorescence in two-cell-stage embryos and rate of two-cell-stage embryo development to blastocysts. Met, Asa, BR-DIM, or hyperosmotic sorbitol stress induces rapid ~50-85 % Rex1 and/or Oct4 protein loss in two-cell embryos. This loss is ~60-90 % reversible by co-culture with AMPK inhibitor CC. Embryo development from two-cell to blastocyst stage is decreased in culture with either Met + Asa or BR-DIM, and this is either >90 or ~60 % reversible with CC, respectively. These experimental designs here showed that Met-, Asa-, BR-DIM-, or sorbitol stress-induced rapid potency loss in two-cell embryos is AMPK dependent as suggested by inhibition of Rex1 and/or Oct4 protein loss with an AMPK inhibitor. The DS BR-DIM or fertility drugs (e.g., Met + Asa) that are used to enhance maternal metabolism to support fertility can also chronically slow embryo growth and block development in an AMPK-dependent manner.

American Women and American Studies.

ERIC Educational Resources Information Center

Chmaj, Betty E.

The American Studies Association (ASA) is an interprofessional group, representing a cross-section of persons from American literature, American history, the social sciences, philosophy, archeology, Black Studies, Urban Studies, American Studies, and others. This document by the ASA Commission on the Status of Women includes: (1) a report of the…

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

PubMed

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

2015-12-01

We recently reported the synthesis of NOSH-aspirin, a novel hybrid that releases both nitric oxide (NO) and hydrogen sulfide (H2S). In NOSH-aspirin, the two moieties that release NO and H2S are covalently linked at the 1, 2 positions of acetyl salicylic acid, i.e. ortho-NOSH-aspirin (o-NOSH-aspirin). In the present study, we compared the effects of the positional isomers of NOSH-ASA (o-NOSH-aspirin, m-NOSH-aspirin and p-NOSH-aspirin) to that of aspirin on growth of HT-29 and HCT 15 colon cancer cells, belonging to the same histological subtype, but with different expression of cyclooxygenase (COX) enzymes; HT-29 express both COX-1 and COX-2, whereas HCT 15 is COX-null. We also analyzed the effect of these compounds on proliferation and apoptosis in HT-29 cells. Since the parent compound aspirin, inhibits both COX-1 and COX-2, we also evaluated the effects of these compounds on COX-1 and COX-2 enzyme activities and also performed modeling of the interactions between the positional isomers of NOSH-aspirin and COX-1 and COX-2 enzymes. We observed that the three positional isomers of NOSH aspirin inhibited the growth of both colon cancer cell lines with IC50s in the nano-molar range. In particular in HT-29 cells the IC50s for growth inhibition were: o-NOSH-ASA, 0.04±0.011 µM; m-NOSH-ASA, 0.24±0.11 µM; p-NOSH-ASA, 0.46±0.17 µM; and in HCT 15 cells the IC50s for o-NOSH-ASA, m-NOSH-ASA, and p-NOSH-ASA were 0.062 ±0.006 µM, 0.092±0.004 µM, and 0.37±0.04 µM, respectively. The IC50 for aspirin in both cell lines was >5mM at 24h. The reduction of cell growth appeared to be mediated through inhibition of proliferation, and induction of apoptosis. All 3 positional isomers of NOSH-aspirin preferentially inhibited COX-1 over COX-2. These results suggest that the three positional isomers of NOSH-aspirin have the same biological actions, but that o-NOSH-ASA displayed the strongest anti-neoplastic potential. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Effects of acetylic salicylic acid and pentoxifylline on the efficacy of intravesical BCG therapy in orthotopic murine bladder cancer (MB49).

PubMed

Günther, J H; Frambach, M; Deinert, I; Brandau, S; Jocham, D; Böhle, A

1999-05-01

Intravesical immunotherapy with bacillus Calmette-Guerin (BCG), which has become the gold standard in the adjuvant treatment of superficial bladder cancer, is hampered by local side effects. Anti-inflammatory drugs may be helpful, but as an undesired side effect, therapeutic efficacy of BCG might be impaired. Therefore, we investigated the effects of anti-inflammatory drugs on the efficacy of intravesical BCG in an animal model. Syngenic tumor cells were implanted into the bladders of 75 mice according to our modification of the method. Mice were randomized to 5 groups with 15 animals each and treated with phosphate buffered saline (PBS), group 1; BCG, group 2; BCG + acetylic salicylic acid (ASA), group 3; BCG + pentoxifylline (POF), group 4; autoclaved BCG (aBCG), group 5. Intravesical instillation of 1.35 mg. BCG was initiated one day after tumor inoculation and repeated in weekly intervals for 4 instillations altogether. ASA and POF in doses of 200 mg./kg. and 150 mg./kg., respectively, were given continuously with the drinking water starting at the first instillation. Autoclaved BCG served as control for the importance of viability and was given at the same dose as viable BCG. Mice were monitored for survival, gross hematuria and body weight and after 28 days evaluated for bladder weight and tumor occurrence. Autoclaved BCG and PBS had no effect on tumor growth, whereas animals treated with viable BCG alone and in combination with POF and ASA, respectively, showed a significant reduction in bladder weight: PBS, 248 mg.; BCG, 140 mg. (p = 0.0009); BCG + ASA, 123 mg. (p = 0.0001); BCG + POF, 145 mg. (p = 0.0004); autoclaved BCG, 283 mg. (p = 0.21). Mice treated with BCG, BCG + ASA and BCG + POF showed a significantly higher proportion of survival until day 28 as compared to PBS alone. Autoclaved BCG had no therapeutic efficacy (Kaplan-Meier method/log rank test: BCG, p = 0.0053; BCG + ASA, p = 0.0044; BCG + POF, p = 0.0027; aBCG, p = 0.33). No significant differences among the 3 groups treated with viable BCG, with or without anti-inflammatory drugs, regarding bladder weight and survival were detectable. The efficacy of BCG therapy in murine orthotopic bladder cancer is dependent on BCG viability and is not compromised by ASA or POF. Clinical trials to evaluate the efficacy of routine ASA or POF to reduce BCG side effects in patients, using self-assessment criteria, should be initiated.

Efficacy and Safety of Beclomethasone Dipropionate versus 5-Aminosalicylic Acid in the Treatment of Ulcerative Colitis: A Systematic Review and Meta-Analysis.

PubMed

Zhao, Xin; Li, Nan; Ren, YiMing; Ma, Tao; Wang, ChunLi; Wang, Jun; You, ShengYi

2016-01-01

Ulcerative colitis (UC) is a chronic and remitting inflammatory disease that is characterized by chronic idiopathic inflammation of the colon and bloody diarrhea. Currently drug treatment is the main intervention for patients with mild to moderate UC. Mesalazine (5-ASA) and beclomethasone dipropionate (BDP) have been widely used for the treatment of UC and have yielded satisfactory results. This study compared the effectiveness of 5-ASA and BDP in the treatment of UC. The PubMed, Medline, SinoMed, Embase, and Cochrane Librinary databases were searched for eligible studies. Data were extracted by two of the coauthors independently and were analyzed using RevMan statistical software, version 5.3. Weighted mean differences (WMDs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool was used to assess the risk of bias. Seven randomized controlled trials that compared BDP with 5-ASA in treating UC were identified as eligible. The methodological quality of the trials ranged from low to moderate. A pooled analysis of effectiveness based on the Disease Activity Index (DAI) or other assessment method after treatment revealed that in the treatment of UC, there are no obvious differences between BDP and 5-ASA in inducing remission and clinical improvement (OR = 0.76, 95% CI = 0.56-1.03, P = 0.08). The total numbers of adverse events associated with BDP and 5-ASA treatments for UC were similar (OR = 1.21, 95% CI = 0.71-2.09, P = 0.48). The safety profiles for these two drugs are good. According to subgroup-analysis, we found no obvious differences of clinical efficacy between BDP and 5-ASA no matter oral or enema administration was used in the treatment of UC. A sensitivity analysis demonstrated the stability of the pooled results. During induction treatment of mild to moderate UC, there is no obvious difference between the two groups with respect to remission and clinical improvement. Given that the upper confidence limit for the OR barely exceeds 1.0 and that the p-value is close to 0.05 for this primary efficacy outcome as well as that the horizontal block lies to the left of the vertical line, it indicates that the clinical efficacy of BDP may be better than 5-ASA. However, taking into account that BDP has the risk of hypothalamic-pituitary-adrenal axis (HPA) suppression, 5-ASA has a potential advantage of safety in the treatment of mild to moderate UC.

Immediate Reactions to More Than 1 NSAID Must Not Be Considered Cross-Hypersensitivity Unless Tolerance to ASA Is Verified.

PubMed

Pérez-Alzate, D; Cornejo-García, J A; Pérez-Sánchez, N; Andreu, I; García-Moral, A; Agúndez, J A; Bartra, J; Doña, I; Torres, M J; Blanca, M; Blanca-López, N; Canto, G

Individuals who develop drug hypersensitivity reactions (DHRs) to chemically unrelated nonsteroidal anti-inflammatory drugs (NSAIDs) are considered cross-hypersensitive. The hallmark for this classification is that the patient presents a reaction after intake of or challenge with acetylsalicylic acid (ASA). Whether patients react to 2 or more NSAIDs while tolerating ASA remains to be studied (selective reactions, SRs). Objective: To identify patients with SRs to 2 or more NSAIDs including strong COX-1 inhibitors. Patients who attended the Allergy Service of Hospital Infanta Leonor, Madrid, Spain with DHRs to NSAIDs between January 2011 and December 2014 were evaluated. Those with 2 or more immediate reactions occurring in less than 1 hour after intake were included. After confirming tolerance to ASA, the selectivity of the response to 2 or more NSAIDs was demonstrated by in vivo and/or in vitro testing or by controlled administration. From a total of 203 patients with immediate DHRs to NSAIDs, 16 (7.9%) met the inclusion criteria. The patients presented a total of 68 anaphylactic or cutaneous reactions (mean [SD], 4.2 [2.1]). Most reactions were to ibuprofen and other arylpropionic acid derivatives and to metamizole. Two different NSAIDs were involved in 11 patients and 3 in 5 patients. Patients with NSAID-induced anaphylaxis or urticaria/angioedema should not be considered cross-hypersensitive unless tolerance to ASA is verified.

Leishmania infantum Asparagine Synthetase A Is Dispensable for Parasites Survival and Infectivity.

PubMed

Faria, Joana; Loureiro, Inês; Santarém, Nuno; Macedo-Ribeiro, Sandra; Tavares, Joana; Cordeiro-da-Silva, Anabela

2016-01-01

A growing interest in asparagine (Asn) metabolism has currently been observed in cancer and infection fields. Asparagine synthetase (AS) is responsible for the conversion of aspartate into Asn in an ATP-dependent manner, using ammonia or glutamine as a nitrogen source. There are two structurally distinct AS: the strictly ammonia dependent, type A, and the type B, which preferably uses glutamine. Absent in humans and present in trypanosomatids, AS-A was worthy of exploring as a potential drug target candidate. Appealingly, it was reported that AS-A was essential in Leishmania donovani, making it a promising drug target. In the work herein we demonstrate that Leishmania infantum AS-A, similarly to Trypanosoma spp. and L. donovani, is able to use both ammonia and glutamine as nitrogen donors. Moreover, we have successfully generated LiASA null mutants by targeted gene replacement in L. infantum, and these parasites do not display any significant growth or infectivity defect. Indeed, a severe impairment of in vitro growth was only observed when null mutants were cultured in asparagine limiting conditions. Altogether our results demonstrate that despite being important under asparagine limitation, LiAS-A is not essential for parasite survival, growth or infectivity in normal in vitro and in vivo conditions. Therefore we exclude AS-A as a suitable drug target against L. infantum parasites.

Subchorionic hematomas are increased in early pregnancy in women taking low-dose aspirin.

PubMed

Truong, Ashley; Sayago, M Mercedes; Kutteh, William H; Ke, Raymond W

2016-05-01

To determine the frequency of subchorionic hematomas (SCH) in first-trimester ultrasound examinations of patients with infertility and recurrent pregnancy loss (RPL) and in patients from a general obstetric population. To determine if the method of assisted reproduction utilized or the use of anticoagulants, such as heparin and aspirin (ASA), influenced frequency of SCH. Prospective, cohort study. Fertility clinic and general obstetrics clinic. Five hundred and thirty-three women who were pregnant in the first-trimester. Not applicable. Frequencies of subchorionic hematomas in women based on diagnosis, use of anticoagulants, and fertility treatment. SCH were identified in 129/321 (40.2%) in the study group compared to 23/212 (10.9%) in the control group. Fertility diagnosis and the use of heparin did not appear to affect the frequency of SCH in the first trimester; however, SCH occurred at an almost four-fold increase in patients taking ASA compared to those not taking ASA, regardless of fertility diagnosis or method of fertility treatment. The use of ASA may be associated with an increased risk of developing a SCH during the first trimester. The increased frequencies of SCH in pregnancies of patients attending a fertility clinic compared to women from a general obstetrical practice was highly correlated with the use of ASA. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

A novel MYB Transcription Factor regulates AsA synthesis and effects cold tolerance.

PubMed

Xing, Caihua; Liu, Yue; Zhao, Liangyi; Zhang, Shaoling; Huang, Xiaosan

2018-06-21

Dehydroascorbate reductase (DHAR) plays an important role in stress responses, but the transcriptional regulation of DHAR in response to abiotic stress is still poorly understood. In this study, we isolated a novel R2R3-type MYB transcription factor from Pyrus betulaefolia by yeast one-hybrid screening, designated as PbrMYB5. PbrMYB5 was localized in the nucleus and could bind specifically to the promoter of PbrDHAR2. PbrMYB5 was greatly induced by cold and salt, but slightly by dehydration. Overexpression of PbrMYB5 in tobacco conferred enhanced tolerance to chilling stresses, whereas down-regulation of PbrMYB5 in Pyrus betulaefolia by virus-induced gene silencing (VIGS) resulted in elevated chilling sensitivity. Transgenic tobacco exhibited higher expression levels of DHAR2 and accumulated larger amount of AsA than the WT plants. VIGS of PbrMYB5 in Pyrus betulaefolia down-regulated PbrDHAR2 abundance and decreased AsA level, accompanied by an increased sensitivity to the chilling stress. Taken together, these results demonstrated that PbrMYB5 is an activator of AsA biosynthesis and may play a positive role in chilling tolerance, at least in part, due to the modulation of AsA synthesis by regulating the PbrDHAR2 expression. This article is protected by copyright. All rights reserved.

Oral 5-Aminosalicylate, Mesalamine Suppository, and Mesalamine Enema as Initial Therapy for Ulcerative Proctitis in Clinical Practice with Quality of Care Implications.

PubMed

Richter, James M; Arshi, Nabeela K; Oster, Gerry

2016-01-01

Background. Ulcerative proctitis (UP) is typically treated initially with oral 5-aminosalicylate ("5-ASA"), mesalamine suppository, or mesalamine enema ("UP Rx"). Little is known about their effectiveness in practice. Methods. Using a US health insurance database, we identified new-onset UP patients between January 1, 2005, and December 31, 2007, based on the following: (1) initiation of UP Rx; (2) endoscopy in prior 30 days resulting in diagnosis of UP; and (3) no prior encounters for ulcerative colitis or Crohn's disease. We examined the incidence of therapy escalation and total costs in relation to initial UP Rx. Results. We identified 548 patients: 327 received mesalamine suppository, 138 received oral 5-ASA, and 83 received mesalamine enema, as initial UP Rx. One-third receiving oral 5-ASA experienced therapy escalation over 12 months, 21% for both mesalamine suppository and enema. Mean cumulative total cost of UP Rx over 12 months was $1552, $996, and $986 for patients beginning therapy with oral 5-ASA, mesalamine enema, and mesalamine suppository, respectively. Contrary to expert recommendations the treatments were often not continued prophylactically. Conclusions. Treatment escalation was common, and total costs of therapy were higher, in patients who initiated treatment with oral 5-ASA. Further study is necessary to assess the significance of these observations.

Speech and neurology-chemical impairment correlates

NASA Astrophysics Data System (ADS)

Hayre, Harb S.

2002-05-01

Speech correlates of alcohol/drug impairment and its neurological basis is presented with suggestion for further research in impairment from poly drug/medicine/inhalent/chew use/abuse, and prediagnosis of many neuro- and endocrin-related disorders. Nerve cells all over the body detect chemical entry by smoking, injection, drinking, chewing, or skin absorption, and transmit neurosignals to their corresponding cerebral subsystems, which in turn affect speech centers-Broca's and Wernick's area, and motor cortex. For instance, gustatory cells in the mouth, cranial and spinal nerve cells in the skin, and cilia/olfactory neurons in the nose are the intake sensing nerve cells. Alcohol depression, and brain cell damage were detected from telephone speech using IMPAIRLYZER-TM, and the results of these studies were presented at 1996 ASA meeting in Indianapolis, and 2001 German Acoustical Society-DEGA conference in Hamburg, Germany respectively. Speech based chemical Impairment measure results were presented at the 2001 meeting of ASA in Chicago. New data on neurotolerance based chemical impairment for alcohol, drugs, and medicine shall be presented, and shown not to fully support NIDA-SAMSHA drug and alcohol threshold used in drug testing domain.

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

NASA Astrophysics Data System (ADS)

Bernhard, Klaus; Huemmerich, Stefan

2016-02-01

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

ASAS-SN Confirmation of the Bright Microlensing Event TCP J05074264+2447555

NASA Astrophysics Data System (ADS)

Jayasinghe, T.; Dong, Subo; Stanek, K. Z.; Kochanek, C. S.; Thompson, T. A.; Prieto, J. L.; Shappee, B. J.; Holoien, T. W.-S.

2017-11-01

The transient TCP J05074264+2447555 was first discovered by T. Kojima on UT 2017-10-25.688. The ASAS-SN Sky Patrol light curve (Shappee et al. 2014; Kochanek et al. 2017) and follow-up spectroscopy (ATel #10919) suggested this to be a probable microlensing event.

Asa Grant Hilliard III: Scholar Supreme

ERIC Educational Resources Information Center

Watkins, William H.

2008-01-01

This integrative review uses two of Asa Grant Hilliard's books, "SBA: The Reawakening of the African Mind" and "The Maroon Within Us: Selected Essays on African American Community Socialization", to discuss aspects of his scholarly legacy in teaching, history, and psychology. His scholarship is provocative. Hilliard rejected the supremacy of the…

Asa Wright Nature Center, Like Another World.

ERIC Educational Resources Information Center

Trimm, Wayne

1983-01-01

The Asa Wright Nature Center, on the Caribbean island of Trinidad, offers a diversity of wildlife species: 108 mammals, 400 birds, 55 reptiles, 25 amphibians, and over 600 butterflies. Learning opportunities include art and photography instruction, lectures, interpretive nature walks, annual resident seminars, and a two-day trip to Tobago. (MH)

Review and status of sonic boom penetration into the ocean.

PubMed

Sparrow, Victor W

2002-01-01

Since the 1970 Sonic Boom Symposium, held at the ASA's 80th meeting in Houston, TX, substantial progress has been made in understanding the penetration of sonic booms into the ocean. The state of the art at that time was documented by J. C. Cook, T. Goforth, and R. K. Cook [J. Acoust. Soc. Am. 51, 729-741 (1972)]. Since then, additional experiments have been performed which corroborate Cook's and Sawyers' theory for sonic boom penetration into a flat ocean surface. In addition, computational simulations have validated that theory and extended the work to include arbitrarily shaped waveforms penetrating flat ocean surfaces. Further numerical studies have investigated realistic ocean surfaces including large-scale ocean swell. Research has also been performed on the effects of ocean inhomogeneities due to bubble plumes. This paper provides a brief overview of these developments.

Advanced Sensors and Applications Study (ASAS)

NASA Technical Reports Server (NTRS)

Chism, S. B.; Hughes, C. L.

1976-01-01

The present EOD requirements for sensors in the space shuttle era are reported with emphasis on those applications which were deemed important enough to warrant separate sections. The application areas developed are: (1) agriculture; (2) atmospheric corrections; (3) cartography; (4) coastal studies; (5) forestry; (6) geology; (7) hydrology; (8) land use; (9) oceanography; and (10) soil moisture. For each application area. The following aspects were covered: (1) specific goals and techniques, (2) individual sensor requirements including types, bands, resolution, etc.; (3) definition of mission requirements, type orbits, coverages, etc.; and (4) discussion of anticipated problem areas and solutions. The remote sensors required for these application areas include; (1) camera systems; (2) multispectral scanners; (3) microwave scatterometers; (4) synthetic aperture radars; (5) microwave radiometers; and (6) vidicons. The emphasis in the remote sensor area was on the evaluation of present technology implications about future systems.

Integration of Coastal Ocean Dynamics Application Radar (CODAR) and Short-Term Predictive System (STPS): Surface Current Estimates into the Search and Rescue Optimal Planning System (SAROPS)

DTIC Science & Technology

2005-11-01

walk (Markovian in position) techniques to perform these simulations ( Breivik et al, 2004; Spaulding and Howlett, 1996; Spaulding and Jayko, 1991; ASA...studies. Model 1 is used in most search and rescue models to make trajectory predictions ( Breivik et al, 2004; Spaulding and Howlett, 1996; Spaulding...ocean gyres: Part II hierarchy of stochastic models, Journal of Physical Oceanography, Vol. 32, 797-830. March 2002. Breivik , O., A. Allen, C. Wettre

Comparison of the effect of aspirin and choline magnesium trisalicylate on thromboxane biosynthesis in human platelets: role of the acetyl moiety.

PubMed

Danesh, B J; McLaren, M; Russell, R I; Lowe, G D; Forbes, C D

1989-01-01

Parameters of platelet thromboxane biosynthesis were measured 24 h after ingestion of equivalent salicylate doses (500 mg) of aspirin (ASA) and choline magnesium trisalicylate (CMT), a non-acetylated salicylate. In random order, 10 healthy volunteers received these drugs on 2 separate days, 2 weeks apart. While ASA significantly prolonged bleeding time, and decreased plasma thromboxane generation and serum thromboxane B2 levels, CMT failed to produce such effects. Thus CMT, which lacks an acetyl moiety in its structure, has no inhibitory effect on platelet thromboxane biosynthesis, and may therefore be considered safer than ASA for therapeutic use, when inhibition of platelet function can be hazardous.

Efficacy and safety of a non-acetylated salicylate, choline magnesium trisalicylate, in the treatment of rheumatoid arthritis.

PubMed

Rothwell, K G

1983-01-01

The results of three double-blind, multicentre trials are reviewed to compare the efficacy of acetysalicylic acid (ASA) and a non-acetylated salicylate, choline magnesium trisalicylate (CMT), in the treatment of rheumatoid arthritis. In each trial, patients were randomly assigned to receive comparable doses of salicylate as either ASA or CMT. Mean values for clinical indicators of rheumatoid arthritis (number of painful joints, articular index, number of swollen joints, swelling index, duration of morning stiffness) showed similar or greater improvement among groups of patients receiving CMT, compared to those receiving ASA. In addition, the incidence of gastro-intestinal side-effects was lower among patients receiving CMT.

Development of an Aerosol Opacity Retrieval Algorithm for Use with Multi-Angle Land Surface Images

NASA Technical Reports Server (NTRS)

Diner, D.; Paradise, S.; Martonchik, J.

1994-01-01

In 1998, the Multi-angle Imaging SpectroRadiometer (MISR) will fly aboard the EOS-AM1 spacecraft. MISR will enable unique methods for retrieving the properties of atmospheric aerosols, by providing global imagery of the Earth at nine viewing angles in four visible and near-IR spectral bands. As part of the MISR algorithm development, theoretical methods of analyzing multi-angle, multi-spectral data are being tested using images acquired by the airborne Advanced Solid-State Array Spectroradiometer (ASAS). In this paper we derive a method to be used over land surfaces for retrieving the change in opacity between spectral bands, which can then be used in conjunction with an aerosol model to derive a bound on absolute opacity.

Interview with Jessica Utts

ERIC Educational Resources Information Center

Rossman, Allan; Utts, Jessica

2014-01-01

This article offers a transcript of author Allan Rossman's interview with Jessica Utts, Professor and Chair of Statistics at the University of California-Irvine. Utts is also a Fellow of the American Statistical Association and a recipient of a Founders Award from ASA. Additionally, she has been elected as President of ASA for the year 2016. The…

Collaborative Project on Serving Linguistically Diverse Seniors. Final Report.

ERIC Educational Resources Information Center

Burt, Miriam

In 2002, the Center for Applied Linguistics (CAL) collaborated with the Senior Service Association (SSA) and the American Society on Aging (ASA) on a two-phase project to improve the effectiveness of ASA's sub-grantees in serving linguistically and culturally diverse populations. SSA provides subsidized employment for low-income seniors and funds…

ASAS-SN Discovery of a Bright Be Star Undergoing a Possible Outburst

NASA Astrophysics Data System (ADS)

Jayasinghe, T.; Stanek, K. Z.; Kochanek, C. S.; Thorstensen, J.; Rupert, J.; Prieto, J. L.; Shields, J. V.; Thompson, T. A.; Holoien, T. W.-S.; Shappee, B. J.; Dong, Subo

2017-09-01

As part of an ongoing effort by ASAS-SN project (Shappee et al. 2014; Kochanek et al. 2017) to characterize and catalog all bright variable stars (e.g., Jayasinghe et al. 2017, ATel #10634, #10677), we report the discovery of a bright Be star undergoing a possible outburst.

Discovery of Eight ASAS-SN Supernovae

NASA Astrophysics Data System (ADS)

Brimacombe, J.; Carballo, J. G.; Farfan, R. G.; Koff, R. A.; Stone, G.; Vallely, P.; Stanek, K. Z.; Brown, J. S.; Kochanek, C. S.; Shields, J.; Thompson, T. A.; Shappee, B. J.; Holoien, T. W.-S.; Prieto, J. L.; Bersier, D.; Dong, Subo; Bose, S.; Chen, Ping

2017-11-01

During the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN, Shappee et al. 2014), using data from the quadruple 14-cm "Brutus" telescope in Haleakala, Hawaii, the quadruple 14-cm "Leavitt" telescope in Fort Davis, Texas, and the quadruple 14-cm "Cassius" and "Paczynski" telescopes in Cerro Tololo, Chile, we discovered several new transient sources.

Discovery of Nine ASAS-SN Supernovae

NASA Astrophysics Data System (ADS)

Brimacombe, J.; Cacella, P.; Carballo, J. G.; Farfan, R. G.; Koff, R. A.; Nicholls, B.; Post, R. S.; Stone, G.; Vallely, P.; Stanek, K. Z.; Brown, J. S.; Kochanek, C. S.; Shields, J. V.; Thompson, T. A.; Shappee, B. J.; Holoien, T. W.-S.; Prieto, J. L.; Bersier, D.; Dong, Subo; Bose, S.; Chen, Ping; Conseil, E.

2017-11-01

During the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN, Shappee et al. 2014), using data from the quadruple 14-cm "Brutus" telescope in Haleakala, Hawaii, the quadruple 14-cm "Leavitt" telescope in Fort Davis, Texas, and the quadruple 14-cm "Cassius" and "Paczynski" telescopes in Cerro Tololo, Chile, we discovered several new transient sources.

Discovery of Eleven ASAS-SN Supernovae

NASA Astrophysics Data System (ADS)

Brimacombe, J.; Conseil, E.; Stone, G.; Koff, R. A.; Vallely, P.; Stanek, K. Z.; Brown, J. S.; Kochanek, C. S.; Shields, J.; Thompson, T. A.; Shappee, B. J.; Holoien, T. W.-S.; Prieto, J. L.; Bersier, D.; Dong, Subo; Bose, S.; Chen, Ping; Kiyota, S.

2017-12-01

During the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN, Shappee et al. 2014), using data from the quadruple 14-cm "Brutus" telescope in Haleakala, Hawaii, the quadruple 14-cm "Leavitt" telescope in Fort Davis, Texas, and the quadruple 14-cm "Cassius" and "Paczynski" telescopes in Cerro Tololo, Chile, we discovered several new transient sources.

Discovery of Three ASAS-SN Supernovae

NASA Astrophysics Data System (ADS)

Brimacombe, J.; Kiyota, S.; Vallely, P.; Stanek, K. Z.; Brown, J. S.; Kochanek, C. S.; Shields, J.; Thompson, T. A.; Shappee, B. J.; Holoien, T. W.-S.; Prieto, J. L.; Bersier, D.; Dong, Subo; Bose, S.; Chen, Ping; Koff, R. A.; Nicholls, B.

2017-12-01

During the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN, Shappee et al. 2014), using data from the quadruple 14-cm "Brutus" telescope in Haleakala, Hawaii, the quadruple 14-cm "Leavitt" telescope in Fort Davis, Texas, and the quadruple 14-cm "Cassius" and "Paczynski" telescopes in Cerro Tololo, Chile, we discovered several new transient sources.

Prognostic indices of perioperative outcome following transperitoneal laparoscopic adrenalectomy.

PubMed

Kiziloz, Halil; Meraney, Anoop; Dorin, Ryan; Nip, Jonathan; Kesler, Stuart; Shichman, Steven

2014-08-01

We sought to identify preoperative patient and tumor characteristics that may be useful prognostic indicators of postsurgical outcome in patients undergoing laparoscopic adrenalectomy (LA). Data from 92 patients who underwent 93 transabdominal LA procedures between 2006-2012 were retrieved. Patients were stratified based on estimated blood loss (EBL), length of stay (LOS), and perioperative complications. Interdependencies between surgical outcome and patient demographics, tumor characteristics, comorbidities, and Charlson Comorbidity Index (CCI) were statistically analyzed. The predictive capacity of each index was assessed using receiver operating characteristic curves. Neither age, gender, tumor laterality, body mass index, American Society of Anesthesiologists (ASA) score, nor CCI predicted the occurrence of perioperative complications. EBL was significantly associated with increased age, tumor size, ASA score, and CCI, whereas prolonged LOS was associated with higher ASA score. Tumor size was related, although not significantly, to LOS and perioperative complications. Tumors ≥7.5 cm in diameter were significantly associated with worse perioperative outcomes. LA for adrenal lesions demonstrated reasonable complication rates and perioperative outcomes. Tumor size, CCI, and ASA score are predictive of increased EBL and LOS.

Preoperative predictive model of recovery of urinary continence after radical prostatectomy.

PubMed

Matsushita, Kazuhito; Kent, Matthew T; Vickers, Andrew J; von Bodman, Christian; Bernstein, Melanie; Touijer, Karim A; Coleman, Jonathan A; Laudone, Vincent T; Scardino, Peter T; Eastham, James A; Akin, Oguz; Sandhu, Jaspreet S

2015-10-01

To build a predictive model of urinary continence recovery after radical prostatectomy (RP) that incorporates magnetic resonance imaging (MRI) parameters and clinical data. We conducted a retrospective review of data from 2,849 patients who underwent pelvic staging MRI before RP from November 2001 to June 2010. We used logistic regression to evaluate the association between each MRI variable and continence at 6 or 12 months, adjusting for age, body mass index (BMI) and American Society of Anesthesiologists (ASA) score, and then used multivariable logistic regression to create our model. A nomogram was constructed using the multivariable logistic regression models. In all, 68% (1,742/2,559) and 82% (2,205/2,689) regained function at 6 and 12 months, respectively. In the base model, age, BMI and ASA score were significant predictors of continence at 6 or 12 months on univariate analysis (P < 0.005). Among the preoperative MRI measurements, membranous urethral length, which showed great significance, was incorporated into the base model to create the full model. For continence recovery at 6 months, the addition of membranous urethral length increased the area under the curve (AUC) to 0.664 for the validation set, an increase of 0.064 over the base model. For continence recovery at 12 months, the AUC was 0.674, an increase of 0.085 over the base model. Using our model, the likelihood of continence recovery increases with membranous urethral length and decreases with age, BMI and ASA score. This model could be used for patient counselling and for the identification of patients at high risk for urinary incontinence in whom to study changes in operative technique that improve urinary function after RP. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Granulocyte-colony stimulating factor in the prevention of postoperative infectious complications and sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). Protocol for a controlled clinical trial developed by consensus of an international study group. Part two: design of the study.

PubMed

Bauhofer, A; Lorenz, W; Stinner, B; Rothmund, M; Koller, M; Sitter, H; Celik, I; Farndon, J R; Fingerhut, A; Hay, J M; Lefering, R; Lorijn, R; Nyström, P O; Schäfer, H; Schein, M; Solomkin, J; Troidl, H; Volk, H D; Wittmann, D H; Wyatt, J

2001-04-01

Presentation of a new type of a study protocol for evaluation of the effectiveness of an immune modifier (rhG-CSF, filgrastim): prevention of postoperative infectious complications and of sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). This part describes the design of the randomised, placebo controlled, double-blinded, single-centre study performed at an university hospital (n = 40 patients for each group). The trial design includes the following elements for a prototype protocol: * The study population is restricted to patients with colorectal cancer, including a left sided resection and an increased perioperative risk (ASA 3 and 4). * Patients are allocated by random to the control or treatment group. * The double blinding strategy of the trial is assessed by psychometric indices. * An endpoint construct with quality of life (EORTC QLQ-C30) and a recovery index (modified Mc Peek index) are used as primary endpoints. Qualitative analysis of clinical relevance of the endpoints is performed by both patients and doctors. * Statistical analysis uses an area under the curve (AUC) model for improvement of quality of life on leaving hospital and two and six months after operation. A confirmatory statistical model with quality of life as the first primary endpoint in the hierarchic test procedure is used. Expectations of patients and surgeons and the negative affect are analysed by social psychological scales. This study design differs from other trials on preoperative prophylaxis and postoperative recovery, and has been developed to try a new concept and avoid previous failures.

Coastal Area Tactical-mapping System (CATS)

DTIC Science & Technology

2007-09-30

file (I.STD) file. A direct comparison to the timetag of the scanner index wedge times should then yield the shot number that corresponds to the...output of 4 relevant timing files. They are as follows: A.STD: The time at which the A-Scan Wedge index mark was detected. This is recorded as...a coarse time (seconds) and a fine time (microseconds). B.STD: The time at which the B-Scan Wedge index mark was detected. This is recorded as a