Sample records for abortifacient agents nonsteroidal

  1. The first finding of Neospora caninum and the occurrence of other abortifacient agents in sheep in Slovakia.

    Spilovská, S; Reiterová, K; Kovácová, D; Bobáková, M; Dubinský, P


    Neosporosis is an infection of animals caused by an intracellular coccidian parasite, Neospora caninum, closely related to Toxoplasma gondii. The parasite is one of important abortifacient agents of bovine abortions worldwide. The aim of the study was to detect the prevalence of anti-Neospora antibodies in dairy aborting sheep from two eastern Slovak regions and to compare it with the occurrence of other potential abortifacient agents. Sera of 382 sheep, mainly the Improved Valachian and Merino breed, were tested for the presence of anti-Neospora and anti-Toxoplasma antibodies by ELISA, anti-Leptospira sp. by micro-agglutination-assay and anti-Chlamydophila antibodies using the complement fixation test. The mean seroprevalence of N. caninum was 3.7% and of T. gondii, 24.3%. This phenomenon of higher susceptibility of sheep to T. gondii is in the opposite of N. caninum infection in cattle. Anti-Leptospira antibodies were observed in 2.9% of serum samples with titres from 800 to 1600, whereas IgG antibodies against Chlamydophila abortus were found in 13.6% with titres from 64 to 1024. Half of N. caninum positive sera were simultaneously positive for T. gondii and one sample for C. abortus. From examined abortifacient agents the most important, from the frequency point of view, were toxoplasmosis (24.3%) and chlamydiosis (13.6%). No significant association between the frequencies of the abortions and mean seroprevalence of the abortifacient agents in Kosice region was determined. Likewise, no significant differences between the mean seroprevalence of neosporosis and toxoplasmosis in the two regions were detected. The first survey of neosporosis in aborting sheep from eastern Slovakia revealed a low prevalence resulting in a lower impact on reproduction losses in these small ruminants.

  2. [Hematotoxic lesions caused by non-steroidal antirheumatic agents].

    Stobbe, H; Hüge, W


    Among the lesions of haematopoiesis conditioned by medicaments the lesions by non-steroidal antirheumatic drugs occupy the first place. They get their significance by the fact that they are not so infrequently irreparable and thus show an unfavourable prognosis. On principle in pathogenetic respect lesions by immunologic reactions which vastly do not depend on the dosage, are to be demarcated from the toxically conditioned side-effects which depend on dosage. Conditioned by drugs aplastic syndromes of the bone marrow are not in every case strongly depending on dosage. For this is to be assumed an individual, particular sensitivity of the haematopoietic stem cells (stem cell defect). Of the anti-rheumatic drugs used for the basic therapy chloroquine derivations, gold, D-penicillamine, immunosuppressives and levamisol may effect disturbances of the haematopoiesis, for which facts are examples are given. This concerns also the symptomatically acting antirheumatic drugs. An overestimation of rare side-effects of drugs should not block the application of certain medicaments, however, they should be given only in such a high dosage as it is necessary. In combinations of antirheumatic drugs every individual drug is considered as causative factor. Interactions are particularly be taken into consideration. Control programmes, particularly with certain laboratory parameters, give the early recognition of side-effects and render possible to avoid severe effects.

  3. Synthetic anabolic agents: steroids and nonsteroidal selective androgen receptor modulators.

    Thevis, Mario; Schänzer, Wilhelm


    The central role of testosterone in the development of male characteristics, as well as its beneficial effects on physical performance and muscle growth, has led to the search for synthetic alternatives with improved pharmacological profiles. Hundreds of steroidal analogs have been prepared with a superior oral bioavailability, which should also possess reduced undesirable effects. However, only a few entered the pharmaceutical market due to severe toxicological incidences that were mainly attributed to the lack of tissue selectivity. Prominent representatives of anabolic-androgenic steroids (AAS) are for instance methyltestosterone, metandienone and stanozolol, which are discussed as model compounds with regard to general pharmacological aspects of synthetic AAS. Recently, nonsteroidal alternatives to AAS have been developed that selectively activate the androgen receptor in either muscle tissue or bones. These so-called selective androgen receptor modulators (SARMs) are currently undergoing late clinical trials (IIb) and will be prohibited by the World Anti-Doping Agency from January 2008. Their entirely synthetic structures are barely related to steroids, but particular functional groups allow for the tissue-selective activation or inhibition of androgen receptors and, thus, the stimulation of muscle growth without the risk of severe undesirable effects commonly observed in steroid replacement therapies. Hence, these compounds possess a high potential for misuse in sports and will be the subject of future doping control assays.

  4. Non-steroidal anti-inflammatory drugs-induced small intestinal injury and probiotic agents

    Mario Guslandi


    Intestinal bacteria play a role in the development of non-steroidal anti-inflammatory drugs (NSAID)-induced small intestinal injury.Agents such as probiotics,able t omodify the gut ecology,might theoretically be useful in preventing small intestinal damage induced by NSAIDs.The clinical studies available so far do suggest that some probiotic agents can be effective in this respect.

  5. Nonsteroidal Anti-Inflammatory Agents in the Treatment of Asthma in Children

    Pierre Gaudreault


    Full Text Available The increasing scientific information clearly demonstrates the important role of inflammation in asthma. This evidence has led physicians to focus their treatment on the elimination of inflammation instead of working solely against bronchoconstriction. Steroids and nonsteroidal agents are currently used to prevent this inflammatory component. This paper focuses only on nonstcroidal anti-inflammatory agents such as sodium cromoglycate, nedocromil sodium and ketotifen and their use in pediatric asthma. The discussion on each medication addresses its mechanism of action, the evidence concerning its efficacy in pediatrics (ie, clinical pharmacology, acute bronchial challenge, late asthmatic response, bronchial hyperrcactivity, clinical efficacy and the pediatric dose.

  6. Effects of some nonsteroidal anti-inflammatory agents on experimental radiation pneumonitis

    Gross, N.J.; Holloway, N.O.; Narine, K.R. (Medical Radiology Service, Hines VA Hospital, Maywood, IL (United States))


    Corticosteroids have previously been found to be protective against the mortality of radiation pneumonitis in mice, even when given well after lethal lung irradiation. The authors explored the possibility that this effect was due to their well-known anti-inflammatory actions by giving various nonsteroidal inhibitors of arachidonate metabolism to groups of mice that had received 19 Gy to the thorax (bilaterally). Treatments of four cyclooxygenase inhibitors, one lipoxygenase inhibitor, and one leukotriene receptor antagonist, given by various routes in various doses, were commenced 10 weeks after irradiation or sham irradiation and continued throughout the period when death from radiation pneumonitis occurs, 11-26 weeks after irradiation. Each of the treatments had the appropriate effect on arachidonate metabolism in the lungs as assessed by LTB4 and PGE2 levels in lung lavage fluid. The principal end point was mortality. The 5-lipoxygenase inhibitor diethylcarbamazine and the LTD4/LTE4 receptor antagonist LY 171883 markedly reduced mortality in dose-response fashion. The effects of cyclooxygenase inhibitors were divergent; piroxicam and ibuprofen were marginally protective, indomethacin in all doses accelerated mortality, and aspirin reduced mortality in a dose-response fashion. These results suggest that the protective effect of corticosteroids in radiation pneumonitis can be tentatively attributed to their anti-inflammatory actions, and that nonsteroidal anti-inflammatory agents, particularly those that affect lipoxygenase products, may offer equal or better protection than corticosteroids against mortality due to radiation pneumonitis.

  7. Cardiovascular pharmacogenetics of anti-thrombotic agents and non-steroidal anti-inflammatory drugs.

    Stitham, J; Vanichakarn, P; Ying, L; Hwa, J


    The use of antithrombotic agents, particularly antiplatelet drugs like aspirin and clopidogrel, has been instrumental in decreasing the risk for adverse cardiovascular events across a wide range of patients. However, despite the established benefits, the use of these medications remains suboptimal. There is a high degree of inter-individual variation in response to these treatments, whereby patients experience occlusive thromboembolic events, in spite of maintaining an appropriate treatment regimen. This has lead to the notion of antithrombotic "resistance" or "poor responders", which has been a growing concern amongst clinicians and other healthcare providers. Compounding this matter even further, reports of increased cardiovascular risk associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen, have revealed additional and unforeseen contributors to myocardial infarction and stroke. With all medications, striking a balance between the potential risks and benefits seems more art than science at times. However, given their widespread use and critical cardiovascular implications, further emphasis has been placed on understanding factors influencing antithrombotic and NSAID therapies. A major aim in cardiovascular pharmacogenetics is the discovery of genetic biomarkers that will allow for prospective screening and individualized prediction of drug efficacy and adverse reactions for these medications (both alone and together) within the context of cardiovascular disease.

  8. Progress with contraceptives and abortifacients.

    Macpherson, A


    In Canada and most other comparatively rich countries, the total fertility rate (TFR) declined from approximately 2.5 in 1970 to 1.6-1.9 in 1990. The reduction was even greater in some countries such as China, Korea, Singapore, Mauritius, Barbados, Cuba, Guadeloupe, and Puerto Rico. TFR, however, has fallen little, if at all, in many poor countries; it remains at 8.1 in Kenya and has increased from already previously high levels in Somalia, Benin, Malawi, and Rwanda. The use of contraception has been instrumental in reducing fertility. An estimated 70% of married women in rich countries use contraceptives, and a larger proportion in Eastern Asia, but only less than 15% in Africa. Education for women generally increases the level of contraceptive use. Rates, however, depend upon the degree of both acceptance and availability. An estimated 20% of births in developing countries are unwanted, so it would seem that greater availability and variety of contraceptives could lead to reductions in fertility. Research into better contraceptive technology is frustrated by paternalism, most organized religions, concern over possible future legal liability, and fear of adverse health side effects, especially in North America. Depo-Provera and RU-486, for example, have yet to be licensed in Canada for use as contraceptive agents. Research nonetheless moves forward. A vaccine against pregnancy is reportedly being developed which may be available before the turn of the century. Clinical trials have been held, and the vaccine has been found to be effective in most women, lacking in side effects, and reversible. The prototype requires a series of injections. Elsewhere, the Alza Corporation of California is working on a transdermal patch to control fertility, while some success has been reported in trials of testosterone, alone or combined with a gonadotropin-releasing hormone, to suppress sperm production in men.

  9. [Protection by zinc acexamate against gastric lesions induced by non-steroid anti-inflammatory agents].

    Navarro, C; Bravo, L; Bulbena, O


    The ability of different non-steroidal anti-inflammatory drugs (diclofenac, indomethacin, ketoprofen, naproxen and piroxicam) to inhibit gastric prostaglandin E2 production in the rat was compared with their damaging potential on gastric mucosa. The influence of treatment with zinc acexamate (ZAC) on these two parameters was also determined. ZAC treatment significantly decreased the degree of gastric damage elicited by all the antiinflammatories tested. The experimental data confirm the complexity of the gastrolesive effect exerted by anti-inflammatory drugs and that only part of such effect would be related with their inhibition of prostaglandin synthesis. These results indicate that the gastroprotection of ZAC does not exclusively depend on the effect on the synthesis of prostaglandins by the gastric mucosa, yet it can additionally be exerted through alternative mechanisms.

  10. Abortifacient and antioxidant activities of different extracts of Musa rosacea

    M. Srikanth; T. Rajananda Swamy; T. Mallikarjuna Rao; B. Ganga Rao


    Objective: To evaluate abortifacient and antioxidant activity of Musa rosacea (M. rosacea).Methods:Abortifacient activity was evaluated in rats, compared with standard drug (Mifepristone) and antioxidant activity was evaluated by using three free radicals (Superoxide, Hydroxyl and DPPH). Results: The extracts showed preimplantation loss, postimplantation loss of implantations and decreased the survival ration of foetuses. Among all extracts hydroalcoholic extract showed better activity. The selected plant extracts showed concentration dependent percentage inhibition of free radicals. Among four extracts hydroalcoholic extract showed better activity with IC50 values on superoxide, hydroxyl and DPPH radicals were 180 µg, 218 µg and 116 µg. Conclusion:From the results obtained during the study it could be concluded that M. rosacea extracts have abortifacient and antioxidant components and the results support its folklore usage as abortifacient plant. Further is necessary for isolation and characterization of bioactive molecules which are responsible for these activities.

  11. Steroid Injection and Nonsteroidal Anti-inflammatory Agents for Shoulder Pain

    Sun, Yaying; Chen, Jiwu; Li, Hong; Jiang, Jia; Chen, Shiyi


    Abstract Advantages and possible risks associated with steroid injection compared with nonsteroidal anti-inflammatory drugs (NSAIDs) for shoulder pain are not fully understood. To compare the efficiency and safety of steroid injection versus NSAIDs for patients with shoulder pain. PubMed, Embase, and the Cochrane Library were searched through July 2015. Study eligibility criteria, participants, and interventions: randomized controlled trials (RCTs) that assessed steroid injection versus NSAIDs for patients with shoulder pain. Study appraisal and synthesis methods: predefined primary efficacy outcome was functional improvement; and secondary efficacy outcomes included pain relief and complications. Relative risks (RRs) and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model accounting for clinical heterogeneity. Eight RCTs involving 465 participants were included in the meta-analysis. Five trials compared steroid injection with oral NSAIDs, and 3 compared steroids injection with NSAIDs injection. Compared with steroid injection, oral NSAIDs were less effective in 4 or 6 weeks for functional improvement (SMD 0.61; 95% CI, 0.08–1.14; P = 0.01), while there was no significant difference in pain relief (SMD 0.45; 95% CI, −0.50–1.40; P shoulder pain were included, detailed intervention protocols were inconsistent across studies, and some estimated data were input into comparison while some data were lost, which could exert an influence on pooled results. Steroid injection, compared with oral NSAIDs, provides slightly more improvement in shoulder function without superiority in pain relief or risk of complications at 4 to 6 weeks. Treatment decision should be made based on diseases. NSAIDs injection might be a treatment method for shoulder pain. PMID:26683932

  12. Marketed nonsteroidal anti-inflammatory agents, antihypertensives, and human immunodeficiency virus protease inhibitors: as-yet-unused weapons of the oncologists' arsenal.

    Papanagnou, Panagiota; Baltopoulos, Panagiotis; Tsironi, Maria


    Experimental data indicate that several pharmacological agents that have long been used for the management of various diseases unrelated to cancer exhibit profound in vitro and in vivo anticancer activity. This is of major clinical importance, since it would possibly aid in reassessing the therapeutic use of currently used agents for which clinicians already have experience. Further, this would obviate the time-consuming process required for the development and the approval of novel antineoplastic drugs. Herein, both pre-clinical and clinical data concerning the antineoplastic function of distinct commercially available pharmacological agents that are not currently used in the field of oncology, ie, nonsteroidal anti-inflammatory drugs, antihypertensive agents, and anti-human immunodeficiency virus agents inhibiting viral protease, are reviewed. The aim is to provide integrated information regarding not only the molecular basis of the antitumor function of these agents but also the applicability of the reevaluation of their therapeutic range in the clinical setting.

  13. Abortifacient activity of a medicinal plant "moringa oleifera" in rats.

    Sethi, N; Nath, D; Shukla, S C; Dyal, R


    Dried powder of leaf extract of common Indian plant Moringa Oleifera of Moringaceae family was tested experimentally in albino rats in our laboratory for its antifertility activity. Cant per cent abortifacient activity was found when administered orally in aqueous solution at dose of 175 mg/kg body weight daily to Charles foster strain albino rats from days 5-10 post mated.

  14. Marketed nonsteroidal anti-inflammatory agents, antihypertensives, and human immunodeficiency virus protease inhibitors: as-yet-unused weapons of the oncologists’ arsenal

    Papanagnou P


    Full Text Available Panagiota Papanagnou,1 Panagiotis Baltopoulos,2 Maria Tsironi1 1Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, Sparta, 2Department of Sports Medicine and Biology of Physical Activity, Faculty of Physical Education and Sport Science, National and Kapodistrian University of Athens, Athens, Greece Abstract: Experimental data indicate that several pharmacological agents that have long been used for the management of various diseases unrelated to cancer exhibit profound in vitro and in vivo anticancer activity. This is of major clinical importance, since it would possibly aid in reassessing the therapeutic use of currently used agents for which clinicians already have experience. Further, this would obviate the time-consuming process required for the development and the approval of novel antineoplastic drugs. Herein, both pre-clinical and clinical data concerning the antineoplastic function of distinct commercially available pharmacological agents that are not currently used in the field of oncology, ie, nonsteroidal anti-inflammatory drugs, antihypertensive agents, and anti-human immunodeficiency virus agents inhibiting viral protease, are reviewed. The aim is to provide integrated information regarding not only the molecular basis of the antitumor function of these agents but also the applicability of the reevaluation of their therapeutic range in the clinical setting. Keywords: repositioning, tumorigenesis, pleiotropy, exploitation

  15. Determination of Quinolones and Nonsteroidal anti-Inflammatory Agents in Animal Tissues and Bovine Milk by Microwave-assisted Extraction High Performance Liquid Chromatography

    ZHOU Xi-Liu; DING Lan; JIN Hai-Yan; LIU Miao; CHENG Jian-Hua; WU Xiu-Feng; ZHAI Yu-Juan; SUN Yan-Tao; ZHANG Han-Qi; YU Yong; WANG Xiu-Pin


    A rapid,specific microwave-assisted extraction high performance liquid chromatography is described for assaying three quinolones(fleroxacin,lomefloxacin and sparfloxacin)and two nonsteroidal anti-inflammatory agents(ketoprofen and ibuprofen)in samples of sheep liver,bovine muscle and milk.The optimal microwave-assisted extraction conditions such as extraction temperature(40 ℃),extraction time(6 min),solvent volume(10 mL)and solvent(acetonitrile)were determined by an orthogonal experiment.Recoveries were 60.0%-107% in the concentration range 0.25-0.75 μg·g with good precision(< 11%)from three varieties of spiked animal samples.

  16. [Effect of a non-steroidal anti-inflammatory agent, tolmetin sodium on exudative inflammation in experimental animals (author's transl)].

    Nakamura, H; Yokoyama, Y; Motoyoshi, S; Ishii, K; Shimizu, M


    Effect of tolmetin sodium(Tol) on acute and subacute exudative inflammation was tested in experimental animals. Tol had a potent inhibitory activity (ED50 = 0.75 mg/kg, p.o.) on the increased vascular permeability induced by acetic acid in mice, and the potency was about 0.4 times that of indomethacin (Ind), and 6-93 times that of ibuprofen (Ibu), phenylbutazone(Phe) and aspirin(Asp). The inhibitory activity of Tol(ED50 = 18.2 mg/kg, p.o.) on UV-induced erythema in guinea pigs was about 0.3 times that of Ind. A recovery of the hind paw edema of rats, produced by a mixture of kaolin and carrageenin, was promoted by oral administration of Tol(2.5 approximately 20 mg/kg x 5/2 days). Tol(80 mg/kg/day, p.o.) showed a significant activity in inhibiting the exudation caused by croton oil in rats, and the activity was about 0.025 times that of Ind and greater than that of Ibu, Phe and Asp. Tol(100-800 microgram/ml) inhibited in a dose-dependent manner the phytohemagglutinin-induced blast transformation of cultured lymphocytes from rat thymus, as did salicylic acid. In vitro, Tol showed a potent activity similar to that of Ibu and Phe in preventing the denaturation of bovine serum albumin and the lysis of rat erythrocytes. From these results, it is suggested that Tol has a particularly potent inhibitory activity on acute exudative inflammation, and the mode of action may be attributed to a mechanism similar to that seen with other acidic non-steroidal anti-inflammatory drugs.

  17. The efficacy and tolerability of the slow-acting combined agent glucosamine and chondroitin sulfate in gonarthrosis patients tacking no nonsteroidal anti-inflammatory drugs

    A. P. Rebrov


    Full Text Available Objective: to evaluate the efficacy and tolerability of the combined symptomatic slow-acting combined agent Theraflex in gonarthrosis patients untreated with nonsteroidal antiinflammatory drugs (NSAIDs.Patients and methods. The investigation enrolled 84 patients (78 women and 6 men aged 55.23±7.36 years with knee arthritis lasting 6.2±0.98 years who were blindly randomized into 2 groups. A study group took Theraflex (chondroitin sulfate 400 mg and glucosamine sulfate 500 mg with or without acetaminophen. A comparison group received acetaminophen only. At baseline and 3 and 6 months after treatment, the investigators assessed changes in the magnitude of osteoarthritis (OA using WOMAC and Lequen's indices, evaluated the therapeutic efficiency rated by a patient and a physician according to the visual analogue scale, and took into account adverse reactions (AR.Results. All the patients taking Theraflex for 6 months showed a positive effect in substantially lowering WOMAC and Lequen's indices and reducing pain and needs for analgesics as compared to both the values at baseline and those obtained in the patients receiving acetaminophen only.Conclusion. In osteoarthritis patients untreated with NSAIDs, Theraflex treatment was associated with a reduction in pain syndrome and stiffness and with better function and lower needs for analgesics. Six-month Theraflex therapy did not cause serious ARs, as well as in patients having controlled gastrointestinal and renal diseases and hypertension

  18. In Vitro Interactions between Non-Steroidal Anti-Inflammatory Drugs and Antifungal Agents against Planktonic and Biofilm Forms of Trichosporon asahii.

    Suteng Yang

    Full Text Available Increasing drug resistance has brought enormous challenges to the management of Trichosporon spp. infections. The in vitro antifungal activities of non-steroidal anti-inflammatory drugs (NSAIDs against Candida spp. and Cryptococcus spp. were recently discovered. In the present study, the in vitro interactions between three NSAIDs (aspirin, ibuprofen and diclofenac sodium and commonly used antifungal agents (fluconazole, itraconazole, voriconazole, caspofungin and amphotericin B against planktonic and biofilm cells of T. asahii were evaluated using the checkerboard microdilution method. The spectrophotometric method and the XTT reduction assay were used to generate data on biofilm cells. The fractional inhibitory concentration index (FICI and the ΔE model were compared to interpret drug interactions. Using the FICI, the highest percentages of synergistic effects against planktonic cells (86.67% and biofilm cells (73.33% were found for amphotericin B/ibuprofen, and caspofungin/ibuprofen showed appreciable percentages (73.33% for planktonic form and 60.00% for biofilm as well. We did not observe antagonism. The ΔE model gave consistent results with FICI (86.67%. Our findings suggest that amphotericin B/ibuprofen and caspofungin/ibuprofen combinations have potential effects against T. asahii. Further in vivo and animal studies to investigate associated mechanisms need to be conducted.



    Dried powder of leaf extract of common Indian plant Moringa Oleifera of Moringaceae family was tested experimentally in albino rats in our laboratory for its antifertility activity. Cant per cent abortifacient activity was found when administered orally in aqueous solution at dose of 175 mg/kg body weight daily to Charles foster strain albino rats from days 5-10 post mated.

  20. [The effect of steroidal and nonsteroidal anti-inflammatory agents on the ultrastructure of chondrocytes in the rat. Electron microscope and morphometric study].

    Annefeld, M; Raiss, R; Cleres, C


    In order to obtain indications regarding the different influences of antiinflammatory drugs on the articular cartilage, the effects of a steroidal drug (dexamethasone) and of nonsteroidal antiinflammatory substances (indometacin and phenylbutazone) on the ultrastructure of the chondrocyte were examined in comparison with tiaprofenic acid (Surgam). Using an equiefficient dosage of the active principles, referred to the ED50 in the model of adjuvant arthritis in the rat, the synthetic apparatus of the chondrocytes was stimulated by tiaprofenic acid while it was diminished by indometacin and phenylbutazone and particularly by dexamethasone.

  1. Antiovulatory and abortifacient effects of Areca catechu (betel nut in female rats

    Shrestha Jyoti


    Full Text Available Objectives : To study the antiovulatory and abortifacient effects of ethanolic extract of Areca catechu in female rats. Materials and Methods : For antiovulatory effect, ethanolic extract of A. catechu at 100 and 300 mg/kg doses was administered orally for 15 days. Vaginal smears were examined daily microscopically for estrus cycle. Rats were sacrificed on 16 th day. Ovarian weight, cholesterol estimation, and histopathological studies were done. Abortifacient activity was studied in rats at 100 and 300 mg/kg doses administered orally from 6 th to 15 th day of pregnancy. Rats were laparotomised on 19 th day. The number of implantation sites and live fetuses were observed in both horns of the uterus. Results : The extract of A. catechu showed a significant decrease in the duration of estrus at 100 mg/kg (P = 0.015 and 300 mg/kg doses (P = 0.002 as compared with control. Metestrus phase was also significantly reduced at 100 mg/kg (P = 0.024 and 300 mg/kg doses (P = 0.002. There was a significant increase in proestrus (P < 0.001 phase. However, diestrus phase was unchanged. Histopathological study of the ovaries showed mainly primordial, primary, and secondary follicles in the test groups as compared to control. There was also a significant (P = 0.002 decrease in ovarian weight and a significant (P = 0.021 increase in ovarian cholesterol level at 100 mg/kg dose. In the study to evaluate abortifacient effect, the mean percentage of abortion with 100 and 300 mg/kg doses were 75.5% and 72.22%, respectively, which was significantly (P = 0.008 and P = 0.006, respectively increased when compared with control. Conclusion : The ethanolic extract of A. catechu at doses of 100 and 300 mg/kg has antiovulatory and abortifacient effects.

  2. Micropropagation and non-steroidal anti-inflammatory and anti-arthritic agent boswellic acid production in callus cultures of Boswellia serrata Roxb.

    Nikam, Tukaram D; Ghorpade, Ravi P; Nitnaware, Kirti M; Ahire, Mahendra L; Lokhande, Vinayak H; Chopra, Arvind


    Micropropagation through cotyledonary and leaf node and boswellic acid production in stem callus of a woody medicinal endangered tree species Boswellia serrata Roxb. is reported. The response for shoots, roots and callus formation were varied in cotyledonary and leafy nodal explants from in vitro germinated seeds, if inoculated on Murshige and Skoog's (MS) medium fortified with cytokinins and auxins alone or together. A maximum of 8.0 ± 0.1 shoots/cotyledonary node explant and 6.9 ± 0.1 shoots/leafy node explants were produced in 91 and 88 % cultures respectively on medium with 2.5 μM 6-benzyladenine (BA) and 200 mg l(-1) polyvinylpyrrolidone (PVP). Shoots treated with 2.5 μM IBA showed the highest average root number (4.5) and the highest percentage of rooting (89 %). Well rooted plantlets were acclimatized and 76.5 % of the plantlets showed survival upon transfer to field conditions. Randomly amplified polymorphic DNA (RAPD) analysis of the micropropagated plants compared with mother plant revealed true-to-type nature. The four major boswellic acid components in calluses raised from root, stem, cotyledon and leaf explants were analyzed using HPLC. The total content of four boswellic acid components was higher in stem callus obtained on MS with 15.0 μM IAA, 5.0 μM BA and 200 mg l(-1) PVP. The protocol reported can be used for conservation and exploitation of in vitro production of medicinally important non-steroidal anti-inflammatory metabolites of B. serrata.

  3. Nonsteroid Anti-inflammatory Drugs and Kidney

    Yaşar Yıldırım; Zülfükar Yılmaz; A. Veysel Kara1; et al.,


    Non-steroidal anti-inflammatory drugs (NSAIDs) are often used in the treatment of chronic and acute pain and inflammation as an analgesic and anti-inflammatory agent. They inhibit the synthesis of prostaglandins which have influence on glomerular capillaries, vasa recta and tubular functions. They lead to significant complications such as hyperkalemia, hyponatremia, edema and hypertension. Usage of NSAIDs is a risk factor for acute kidney injury in some conditions such as advanced age, dehydr...

  4. Nonsteroidal, antiinflammatory drug-induced gastrointestinal injuries and related adverse reactions: Epidemiology, pathogenesis and management

    Al Mofleh Ibrahim


    Full Text Available A large proportion of the population all over the world consumes acetylsalicylic acid (ASA: aspirin or other nonsteroidal, antiinflammatory drugs (NSAIDs. This is associated with a considerable morbidity and mortality. Elderly patients, patients with prior history of peptic ulcer disease (PUD or its complications, those who require high doses of NSAIDs and those undergoing concomitant therapy with corticosteroids or anticoagulants, are at particularly high risk of developing gastroduodenal injuries and related adverse reactions. Gastroduodenal mucosal injuries induced by NSAIDs vary from subtle microscopic to gross macroscopic changes including ulcers. These injuries are induced by both topical and systemic actions of NSAIDs. Inhibition of gastroduodenal cyclooxygenase (COX enzyme by NSAIDs is considered to be a major pathogenetic factor. Reactive oxygen species (ROS appear also to play a significant role in the pathogenesis of mucosal injury. Withdrawal of NSAIDs is preferably the first therapeutic option; however, it is not feasible in the majority of patients. Therefore, several drugs including antisecretory drugs (ASDs-proton pump inhibitors and Histamine-2 receptor antagonists and misoprostol, a prostaglandin analog are used for the prevention and treatment of NSAID-induced gastroduodenal injuries. Among ASDs, proton pump inhibitors (PPIs are the most commonly used drugs. The antiulcerogenic effect of PPIs is similar to that of misoprostol and superior to standard doses of histamine-2 receptor antagonists (H2-RAs. The adverse effects of m,isoprostol such as diarrhea, abdominal pain, nausea, flatulence, headache, dyspepsia, vomiting, constipation, abortifacient and teratogenicity limit its general use. Aside from their antisecretory action, PPIs also possess an antioxidative effect. PPI maintenance is recommended in chronic NSAID treatment in those with an increased risk of complications and is more effective than Helicobacter pylori

  5. Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti-cholinergic agent against skin injury induced by sulfur mustard

    Chang, Yoke-Chen; Wang, James D.; Hahn, Rita A.; Gordon, Marion K.; Joseph, Laurie B. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Heck, Diane E. [Department of Environmental Science, New York Medical College, Valhalla, NY (United States); Heindel, Ned D. [Department of Chemistry, Lehigh University, Bethlehem, PA (United States); Young, Sherri C. [Department of Chemistry, Muhlenberg College, Allentown, PA (United States); Sinko, Patrick J. [Department of Pharmaceutics, Rutgers University, Piscataway, NJ (United States); Casillas, Robert P. [MRIGlobal, Kansas City, MO (United States); Laskin, Jeffrey D. [Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Gerecke, Donald R., E-mail: [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States)


    Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 h post-SM exposure. After 96 h, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermal–epidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure. - Highlights: • Bifunctional anti-inflammatory prodrug (NDH4338) tested on SM exposed mouse skin • The prodrug NDH4338 was designed to target COX2 and acetylcholinesterase. • The application of NDH4338 improved cutaneous wound repair after SM induced injury. • NDH4338 treatment demonstrated a reduction in COX2 expression on SM injured skin. • Changes of skin repair

  6. Review article : the potential of combinational regimen with non-steroidal anti-inflammatory drugs in the chemoprevention of colorectal cancer

    Jalving, M; Koornstra, JJ; De Jong, S; De Vries, EGE; Kleibeuker, JH


    Non-steroidal anti-inflammatory drugs are chemopreventive agents in colorectal cancer. Non-steroidal anti-inflammatory drugs do not, however, offer complete protection against adenoma and carcinoma development. There is increasing interest in combining non-steroidal anti-inflammatory drugs with agen

  7. Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-kappaB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation.

    Takada, Yasunari; Bhardwaj, Anjana; Potdar, Pravin; Aggarwal, Bharat B


    Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin have been shown to suppress transcription factor NF-kappaB, which controls the expression of genes such as cyclooxygenase (COX)-2 and cyclin D1, leading to inhibition of proliferation of tumor cells. There is no systematic study as to how these drugs differ in their ability to suppress NF-kappaB activation and NF-kappaB-regulated gene expression or cell proliferation. In the present study, we investigated the effect of almost a dozen different commonly used NSAIDs on tumor necrosis factor (TNF)-induced NF-kappaB activation and NF-kappaB-regulated gene products, and on cell proliferation. Dexamethasone, an anti-inflammatory steroid, was included for comparison with NSAIDs. As indicated by DNA binding, none of the drugs alone activated NF-kappaB. All compounds inhibited TNF-induced NF-kappaB activation, but with highly variable efficacy. The 50% inhibitory concentration required was 5.67, 3.49, 3.03, 1.25, 0.94, 0.60, 0.38, 0.084, 0.043, 0.027, 0.024, and 0.010 mM for aspirin, ibuprofen, sulindac, phenylbutazone, naproxen, indomethacin, diclofenac, resveratrol, curcumin, dexamethasone, celecoxib, and tamoxifen, respectively. All drugs inhibited IkappaBalpha kinase and suppressed IkappaBalpha degradation and NF-kappaB-regulated reporter gene expression. They also suppressed NF-kappaB-regulated COX-2 and cyclin D1 protein expression in a dose-dependent manner. All compounds inhibited the proliferation of tumor cells, with 50% inhibitory concentrations of 6.09, 1.12, 0.65, 0.49, 1.01, 0.19, 0.36, 0.012, 0.016, 0.047, 0.013, and 0.008 mM for aspirin, ibuprofen, sulindac, phenylbutazone, naproxen, indomethacin, diclofenac, resveratrol, curcumin, dexamethasone, celecoxib, and tamoxifen, respectively. Overall these results indicate that aspirin and ibuprofen are least potent, while resveratrol, curcumin, celecoxib, and tamoxifen are the most potent anti-inflammatory and antiproliferative agents of those we

  8. A comparison of the metabolism of the abortifacient compounds from Ponderosa pine needles in conditioned versus naive cattle.

    Welch, K D; Gardner, D R; Pfister, J A; Panter, K E; Zieglar, J; Hall, J O


    Isocupressic acid (ICA) is the abortifacient compound in ponderosa pine (Pinus ponderosa L.) needles, which can cause late-term abortions in cattle (Bos taurus). However, cattle rapidly metabolize ICA to agathic acid (AGA) and subsequent metabolites. When pine needles are dosed orally to cattle, no ICA is detected in their serum, whereas AGA is readily detected. Recent research has demonstrated that AGA is also an abortifacient compound in cattle. The observation has been made that when cattle are dosed with labdane acids for an extended time, the concentration of AGA in serum increases for 1 to 2 d but then decreases to baseline after 5 to 6 d even though they are still being dosed twice daily. Therefore, in this study we investigated whether cattle conditioned to pine needles metabolize ICA, and its metabolites, faster than naïve cattle. Agathic acid was readily detected in the serum of naïve cattle fed ponderosa pine needles, whereas very little AGA was detected in the serum of cattle conditioned to pine needles. We also compared the metabolism of ICA in vitro using rumen cultures from pine-needle-conditioned and naïve cattle. In the rumen cultures from conditioned cattle, AGA concentrations were dramatically less than rumen cultures from naïve cattle. Thus, an adaptation occurs to cattle conditioned to pine needles such that the metabolism AGA by the rumen microflora is altered.

  9. Genotoxic potential of nonsteroidal hormones

    Topalović Dijana


    Full Text Available Hormones are cellular products involved in the regulation of a large number of processes in living systems, and which by their actions affect the growth, function and metabolism of cells. Considering that hormones are compounds normally present in the organism, it is important to determine if they can, under certain circumstances, lead to genetic changes in the hereditary material. Numerous experimental studies in vitro and in vivo in different systems, from bacteria to mammals, dealt with the mutagenic and genotoxic effects of hormones. This work presents an overview of the research on genotoxic effects of non­steroidal hormones, although possible changes of genetic material under their influence have not still been known enough, and moreover, investigations on their genotoxic influence have given conflicting results. The study results show that mechanisms of genotoxic effect of nonsteroidal hormones are manifested through the increase of oxidative stress by arising reactive oxygen species. A common mechanism of ROS occurence in thyroid hormones and catecholamines is through metabolic oxidation of their phenolic groups. Manifestation of insulin genotoxic effect is based on production of ROS by activation of NADPH isophorms, while testing oxytocin showed absence of genotoxic effect. Considering that the investigations on genotoxicity of nonsteroidal hormones demonstrated both positive and negative results, the explanation of this discordance involve limitations of test systems themselves, different cell types or biological species used in the experiments, different level of reactivity in vitro and in vivo, as well as possible variations in a tissue-specific expression. Integrated, the provided data contribute to better understanding of genotoxic effect of nonsteroidal hormones and point out to the role and mode of action of these hormones in the process of occurring of effects caused by oxidative stress. [Projekat Ministarstva nauke Republike

  10. Nonsteroid Anti-inflammatory Drugs and Kidney

    Yaşar Yıldırım1


    Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs are often used in the treatment of chronic and acute pain and inflammation as an analgesic and anti-inflammatory agent. They inhibit the synthesis of prostaglandins which have influence on glomerular capillaries, vasa recta and tubular functions. They lead to significant complications such as hyperkalemia, hyponatremia, edema and hypertension. Usage of NSAIDs is a risk factor for acute kidney injury in some conditions such as advanced age, dehydration, vomiting, diuretics, ACE/ARB therapy, heart failure, nephrotic syndrome, cirrhosis and chronic kidney disease. Acute interstitial nephritis is not dependent on the drug dose and it is characterized by immunological inflammatory reaction and a decrease in creatinine clearance. Besides the classical findings, glomerules can be involved and minimal change disease or membranous glomerulonephritis can develop. Analgesic nephropathy is characterized by interstitial nephritis and papillary necrosis. Metabolites of NSAIDs are accumulated in renal medulla which has lowest oxygen pressure in kidney and they disrupt the renal parencymal perfusion by vasoconstriction. Respectively, papillar necrosis, glomerular sclerosis, interstitial fibrosis and cortical atrophy can develop insidiously.

  11. Fusobacterium necrophorum determined as abortifacient in sheep by laser capture microdissection and fluorescence in situ hybridization

    Boye, Mette; Aalbæk, Bent; Agerholm, Jørgen S.


    at late pregnancy by a technique that combines laser capture microdissection (LCM) and fluorescent in situ hybridization (LCM-FISH). Cultural bacteriological examination had failed to identify an infectious agent but by histological examination, large colonies of bacteria associated with tissue......Fluorescent in situ hybridization (FISH) has been extensively used for identification of individual microbial cells within their natural environment. The present work describes the identification of Fusobacterium necrophorum in formalin-fixed tissue samples from three sets of ovine twins aborted......RNA-targeting oligonucleotide probe specific for F. necrophorum was used in a FISH assay. In situ hybridization showed a high density of F. necrophorum in all examined tissue sections. Simultaneous probing with a general bacterial probe EUB338 and the specific probe for F. necrophorum showed that no other bacteria could...

  12. Nonsteroidal Anti-Inflammatory Drug-Induced Gastroduodenal Bleeding: Risk Factors and Prevention Strategies


    Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely prescribed medications in the World. A frequent complication of NSAID use is gastroduodenal bleeding. Risk factors for gastroduodenal bleeding while on NSAID therapy are age, prior peptic ulcer and co-medication with anti-platelet agents, anticoagulants, glucocorticosteroids and selective serotonin-reuptake inhibitors (SSRI). Prevention strategies for at-risk patients include the use of the lowest effective dose of NSAIDs, co-t...

  13. [Myocarditis in a cachectic female, nonsteroidal anti-inflammatory drugs abuser, in a course of progressive systemic sclerosis].

    Wozakowska-Kapłon, Beata; Gorczyca, Iwona; Maciejowska-Roge, Maria


    A case of 70-year-old cachectic female, nonsteroid anti-inflammatory drugs abuser, with progressive systemic sclerosis, who was admitted to our hospital due to joint pain and fatigue is presented. During hospitalisation the patient developed symptoms of acute myocarditis. Angiography of coronary arteries did not reveal narrowing of the vessels. Alimentary supplementation and therapy for heart failure (diuretics, vasodilators, angiotensin-converting enzyme inhibitor and beta-blocker) were used. In repeated echocardiography examinations ejection fraction systematically improved and hemodynamic stabilisation was obtained. Scleroderma, malnutrition, toxicity of nonsteroid anti-inflammatory drugs and infectious agents were considered as a cause of myocarditis.

  14. The Epidemiology of Nonsteroidal Anti-Inflammatory Drugs

    Jerry Tenenbaum


    Full Text Available Nonsteroidal anti-inflammatory drug (NSAID use has increased dramatically in the past two decades. A large proportion of the elderly population (more than 65 years of age holds a current or recent NSAID prescription, accounting for approximately 90% of all NSAID prescriptions. Despite studies that advise finding alternatives for NSAIDs for the management of osteoarthritis, physicians often prescribe NSAIDs first for such common musculoskeletal conditions. Despite being identified as risk factors for gastrointestinal complications, the simultaneous use of two NSAIDs and the coadministration of NSAIDs with corticosteroids and with coumadin continue to occur. The point prevalence of NSAID-induced ulcers is 10% to 30%, and 15% to 35% of all peptic ulcer complications are caused by NSAIDs. The increased risk of gastrointestinal complications when NSAIDs are used is 3% to 5%. This risk increases with other identified risk factors (eg, older age, previous gastrointestinal history, comorbid diseases and poor health. Gastrointestinal causes of hospitalization (eg, gastrointestinal hemorrhage and perforation and death have increased in parallel to increased NSAID use. ‘Antiulcer’ agents are prescribed twice as often in NSAID users, and the economic impact (eg, diagnostic tests and hospitalization is that about one-third of the arthritis budget has been dedicated to deal with gastrointestinal side effects of NSAIDs. Misoprostol and omeprazole have been shown to be cytoprotective for the gastroduodenal mucosa when NSAIDs are used, and misoprostol has been shown to reduce the risk of gastroduodenal ulcer complications. Economic evaluations have suggested that these agents are a cost effective means of dealing with such NSAID-associated problems. Although no NSAID is totally safe, a number of studies have demonstrated that NSAIDs may be ranked according to relative gastrointestinal toxicity. The role of Helicobacter pylori in NSAID-associated problems


    N. A. Shostak


    Full Text Available The paper shows the basic mechanisms of action of nonsteroidal antinflammatory drugs (NSAID and their classification. It considers riskfactors for NSAID gastropathy and the possibilities of its treatment, prevention in the context of modern medicine.

  16. Nonsteroidal Anti-Inflammatory Drugs: Adverse Effects and Their Prevention

    Vonkeman, Harald E.; Laar, van de Mart A.F.J.


    Objectives: To discuss nonsteroidal anti-inflammatory drugs (NSAIDs), their history, development, mode of action, toxicities, strategies for the prevention of toxicity, and future developments. - Methods: Medline search for articles published up to 2007, using the keywords acetylsalicylic acid, asp

  17. Ketorolac: a parenteral nonsteroidal antiinflammatory drug.

    Resman-Targoff, B H


    Ketorolac tromethamine is a pyrrolo-pyrrole nonsteroidal antiinflammatory drug (NSAID) with potent analgesic effects when administered intramuscularly for the treatment of acute pain. Ketorolac is well absorbed and has a rapid onset of action. Maximum plasma concentrations are achieved in 45-50 minutes and peak analgesic effects in about one to two hours following intramuscular injection. Ketorolac is more than 99 percent bound to plasma proteins and has a mean apparent volume of distribution of 0.11-0.25 L/kg. About 91 percent of a dose is excreted in urine, mostly as inactive metabolites, and approximately 6 percent is eliminated in feces. The elimination half-life, approximately four to six hours, increases in elderly patients and those with renal impairment. Its analgesic effectiveness was similar or superior to that of morphine, meperidine, or pentazocine in single-dose studies of patients with postoperative pain or renal colic and greater than that of placebo in patients with chronic cancer pain. The adverse effects are generally mild to moderate, self-limiting, and similar to those seen with other prostaglandin inhibitors. Ketorolac has a reversible inhibitory effect on platelet aggregation. It can cause dose-related gastric ulcerations, even when administered parenterally. Ketorolac is a promising parenteral alternative to oral NSAIDs and a nonnarcotic alternative to opioid analgesics. Additional multiple-dose studies are needed to more clearly define its place in therapy.

  18. Nonsteroidal Anti-Inflammatory Drug-Induced Gastroduodenal Bleeding: Risk Factors and Prevention Strategies

    Thomas Wex


    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are the most widely prescribed medications in the World. A frequent complication of NSAID use is gastroduodenal bleeding. Risk factors for gastroduodenal bleeding while on NSAID therapy are age, prior peptic ulcer and co-medication with anti-platelet agents, anticoagulants, glucocorticosteroids and selective serotonin-reuptake inhibitors (SSRI. Prevention strategies for at-risk patients include the use of the lowest effective dose of NSAIDs, co-therapy with proton-pump inhibitors and/or the use of a COX-2 selective agent. Treatment of Helicobacter pylori infection is beneficial for primary prophylaxis of NSAID-induced gastroduodenal bleeding in NSAID-naive patients. For patients with cardiovascular risk factors requiring NSAIDs, naproxen should be selected. In very high risk patients for both gastrointestinal and cardiovascular complications NSAID therapy should be avoided altogether.

  19. Non-steroidal anti-inflammatory drug use and the risk of Parkinson's disease

    Manthripragada, Angelika D; Schernhammer, Eva S; Qiu, Jiaheng;


    Experimental evidence supports a preventative role for non-steroidal anti-inflammatory drugs (NSAIDs) in Parkinson's disease (PD).......Experimental evidence supports a preventative role for non-steroidal anti-inflammatory drugs (NSAIDs) in Parkinson's disease (PD)....

  20. Bromfenac (Broksinak — a new word in the nonsteroidal antiinflamatory drug (literature review

    E. A. Spiridonov


    Full Text Available Eye inflammation can be caused by different factors — allergies, infection, trauma (including surgery. It can have severe complications, last even after elimination the reason and cause the visual impairment as an outcome. Two main classes of anti-inflammatory agents (corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs are used for the prevention and relief of the inflammatory process. Along with the fact that corticosteroids are the «gold standard» treatment of inflammation in ophthalmology, they have a number of serious side effects such as increasing of intraocular pressure and the risk of developing glaucoma, cataracts, activation of bacterial, viral infection and herpes. The positive effects of NSAIDs in comparison with corticosteroids are stable intraocular pressure (IOP, analgesic effect and reduce the risk of secondary infection. The three classes of NSADs are currently used in ophthalmology. They are phenylacetic acid (diclofenac and bromfenac nepafenak, indole acetic acid (indomethacin and geteroariluksunoy acid (ketorolac. The last synthesized NSAIDs for ophthalmology are amfenac and bromfenac. Bromfenac is effective for the relief of the inflammatory symptoms of and fully complies with the requirements for the ideal anti-inflammatory drugs such as good a penetration ability, creating a sufficient concentration inside the eye, the activity of cyclooxygenase, inhibiting the progress of macular edema, a good analgesic effect, minimal toxicity, comfort of use patients. Bromfenac is the only nonsteroidal antiinflammatory drugs, which is applied once a day and has a pronounced anti-inflammatory action.




    The nonsteroidal anti-inflammatory drugs (NSAIDs) are very commonly prescribed, especially in the elderly population. In many countries more than 10 different NSAIDs are available. As the older pyrazole compounds like phenylbutazone, oxyphenbutazone and azapropazone are most prone to pharmacokinetic

  2. Non-steroidal anti-inflammatory drugs in prevention of gastric cancer

    Yun Dai; Wei-Hong Wang


    Non-steroidal anti-inflammatory drugs (NSAIDs)including cyclooxygenase 2 (COX-2) selective inhibitors,are potential agents for the chemoprevention of gastric cancer. Epidemiological and experimental studies have shown that NSAID use is associated with a reduced risk of gastric cancer although many questions remain unanswered such as the optimal dose and duration of treatment. The possible mechanisms for the suppressor effect of NSAIDs on carcinogenesis are the ability to induce apoptosis in epithelial cells and regulation of angiogenesis. Both COX-dependent and COX-independent pathways have a role in the biological activity of NSAIDs. Knowledge of how NSAIDs prevent neoplastic growth will greatly aid the design of better chemopreventive drugs and novel treatments for gastric cancer.

  3. Consumo de antiinflamatorios no esteroideos en atención primaria en Costa Rica: evolución y variabilidad geográfica Consumption of nonsteroidal anti-inflammatory agents in primary care in Costa Rica: changing patterns and geographical variability

    Melvin Morera Salas


    Full Text Available Objetivo: Conocer la evolución y la variabilidad en el consumo de los antiinflamarios no esteroideos clásicos (AINE en las áreas de salud de Costa Rica durante el período 2000-2005. Métodos: Se estudiaron los siguientes medicamentos: ibuprofeno, indometacina, penicilamina, sulindaco, tenoxican y diclofenaco sódico. Se utilizó como medida de consumo la dosis diaria definida por 1.000 habitantes y día (DHD, y en el análisis de variabilidad el coeficiente de variación ponderado por el tamaño de población (CVw, el rango extremo, el rango interpercentil, los gráficos de puntos y los mapas con categorías de consumo. Resultados: En el período 2000-2005 el consumo de los AINE creció un 48% y el coste anual se incrementó un 184%. Los medicamentos de mayor consumo y participación en el gasto fueron sulindaco e indometacina. El consumo de los AINE varió entre 0,1 y 60,39 DHD según las áreas de salud, con un CVw del 66,38%. Los medicamento con mayor variabilidad fueron penicilamina (CVw del 449,89% y tenoxican (CVw del 315,26%. Conclusiones: Hay un patrón geográfico diferenciado en el consumo de AINE en el país, y tasas muy diferentes dentro de una misma región. Dos posibles factores asociados a esta variabilidad, según los resultados obtenidos, son la oferta de servicios médicos y el porcentaje de población mayor de 65 años adscrita al área de salud.Objective: To determine changing patterns and variability in consumption of classic nonsteroidal anti-inflammatory drugs (NSAIDs among the health areas in Costa Rica between 2000 and 2005. Methods: The drugs studied were ibuprofen, indomethacin, penicillamine, sulindac, tenoxicam, and diclofenac sodium. To measure consumption, we used the defined daily dose per 1,000 inhabitants per day (DID. To analyze variability, the coefficient of variation weighed by the population size (CVw, extremal ratio, interquartile ratio, dot plot and map graphs were used. Results: From 2000-2005, NSAID

  4. Hepatic manifestations of non-steroidal inflammatory bowel disease therapy

    Robert; Hirten; Keith; Sultan; Ashby; Thomas; David; E; Bernstein


    Inflammatory bowel disease(IBD) is composed of Crohn’s disease and ulcerative colitis and is manifested by both bowel-related and extraintestinal manifestations. Recently the number of therapeutic options available to treat IBD has dramatically increased, with each new medication having its own mechanism of action and side effect profile. A complete understanding of the hepatotoxicity of these medications is important in order to distinguish these complications from the hepatic manifestations of IBD. This review seeks to evaluate the hepatobiliary complications of non-steroid based IBD medications and aide providers in the recognition and management of these side-effects.

  5. Characterization of a novel non-steroidal glucocorticoid receptor antagonist

    Li, Qun-Yi; Zhang, Meng [The National Center for Drug Screening, Shanghai (China); State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China); Hallis, Tina M.; DeRosier, Therese A. [Cell Systems Division, Invitrogen, Madison, WI (United States); Yue, Jian-Min; Ye, Yang [State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China); Mais, Dale E. [The National Center for Drug Screening, Shanghai (China); MPI Research, Mattawan, MI (United States); Wang, Ming-Wei, E-mail: [The National Center for Drug Screening, Shanghai (China); State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China)


    Selective antagonists of the glucocorticoid receptor (GR) are desirable for the treatment of hypercortisolemia associated with Cushing's syndrome, psychic depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327, a non-steroidal small molecule with potent binding affinity to GR (K{sub i} = 13.2 nM), was identified in a high-throughput screening effort. As a full GR antagonist, NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes involved in hepatic gluconeogenesis, but has a minimal effect on matrix metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene. Interestingly, the compound recruits neither coactivators nor corepressors to the GR complex but competes with glucocorticoids for the interaction between GR and a coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation, but significantly blocks Dex-induced GR transportation to the nucleus, and thus appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal compound, NC3327, may represent a new class of GR antagonists as potential therapeutics for a variety of cortisol-related endocrine disorders.

  6. Prescription monitoring of management pattern of osteoarthritis with non-steroidal antiinflammatory drugs at PUHC, Chandigarh in India

    Bishnoi M


    Full Text Available The present prospective study was conducted in order to establish the drug-prescription trend of non-steroidal antiinflammatory drugs in the management pattern of osteoarthritis at Panjab University Health Centre, Chandigarh, India. The study was carried out in between the months of November 2003 and March 2004. Data was collected from outpatients who visited Panjab University Health Centre. WHO based prescription-auditing performa was used for data collection. Demographic analysis of this prospective and observational study revealed that out of 84 patients most were females (63.1% and maximum patients were in the age group of 40-60 (59.5%. Most of the patients at Panjab University Health Centre had primary generalized Osteoarthritis with the back (50% being the site most commonly affected followed by knee (45.23% and hips (14.3%. Pain and joint stiffness was the common feature of the clinical presentation. Non-Steroidal Antiinflammatory Drugs were mostly prescribed during the observation period predominantly for pain relief. The most commonly prescribed agents were nimesulide, paracetamol, diclofenac and ibuprofen. Mostly the drugs were administered in the tablet form (86.05% with least use of gels/creams and capsules. The use of non-drug therapies including physiotherapy and exercise was least found. The present study represents the current prescribing trend of non-steroidal antiinflammatory drugs for osteoarthritis at Panjab University Health Centre and it also suggested that there is still considerable scope for improvement, particularly in prescribing non-drug therapies and improving dispensing habits.

  7. Effect of nonsteroidal antiinflammatory drugs on the C-reactive protein level in rheumatoid arthritis

    Tarp, Simon; Bartels, Else M; Bliddal, Henning;


    To evaluate the effects of oral nonsteroidal antiinflammatory drugs (NSAIDs) on C-reactive protein (CRP) levels in rheumatoid arthritis (RA) patients, with a prespecified focus on the different NSAIDs.......To evaluate the effects of oral nonsteroidal antiinflammatory drugs (NSAIDs) on C-reactive protein (CRP) levels in rheumatoid arthritis (RA) patients, with a prespecified focus on the different NSAIDs....

  8. Nonsteroidal Anti-Inflammatory Drugs and the Kidney

    Walter H. Hörl


    Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs inhibit the isoenzymes COX-1 and COX-2 of cyclooxygenase (COX. Renal side effects (e.g., kidney function, fluid and urinary electrolyte excretion vary with the extent of COX-2-COX-1 selectivity and the administered dose of these compounds. While young healthy subjects will rarely experience adverse renal effects with the use of NSAIDs, elderly patients and those with co-morbibity (e.g., congestive heart failure, liver cirrhosis or chronic kidney disease and drug combinations (e.g., renin-angiotensin blockers, diuretics plus NSAIDs may develop acute renal failure. This review summarizes our present knowledge how traditional NSAIDs and selective COX-2 inhibitors may affect the kidney under various experimental and clinical conditions, and how these drugs may influence renal inflammation, water transport, sodium and potassium balance and how renal dysfunction or hypertension may result.

  9. Non-steroidal anti-inflammatory drugs and hypertension.

    Zheng, Liuying; Du, Xinping


    Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used to alleviate pain of the patients who suffer from inflammatory conditions like rheumatoid arthritis, osteoarthritis, and other painful conditions like gout. This class of drugs works by blocking cyclooxgenases which in turn block the prostaglandin production in the body. Most often, NSAIDs and antihypertensive drugs are used at the same time, and their use increases with increasing age. Moreover, hypertension and arthritis are common in the elderly patients requiring pharmacological managements. An ample amount of studies put forth evidence that NSAIDs reduce the efficiency of antihypertensive drugs plus aggravate pre-existing hypertension or make the individuals prone to develop high blood pressure through renal dysfunction. This review will help doctors to consider the effects and risk factors of concomitant prescription of NSAIDs and hypertensive drugs.

  10. Prodrugs of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs, More Than Meets the Eye: A Critical Review

    Amjad M. Qandil


    Full Text Available The design and the synthesis of prodrugs for nonsteroidal anti-inflammatory drugs (NSAIDs have been given much attention by medicinal chemists, especially in the last decade. As a therapeutic group, NSAIDs are among the most widely used prescribed and over the counter (OTC medications. The rich literature about potential NSAID prodrugs clearly shows a shift from alkyl, aryalkyl or aryl esters with the sole role of masking the carboxylic acid group, to more elaborate conjugates that contain carefully chosen groups to serve specific purposes, such as enhancement of water solubility and dissolution, nitric oxide release, hydrogen sulfide release, antioxidant activity, anticholinergic and acetylcholinesterase inhibitory (AChEI activity and site-specific targeting and delivery. This review will focus on NSAID prodrugs that have been designed or were, later, found to possess intrinsic pharmacological activity as an intact chemical entity. Such intrinsic activity might augment the anti-inflammatory activity of the NSAID, reduce its side effects or transform the potential therapeutic use from classical anti-inflammatory action to something else. Reports discussed in this review will be those of NO-NSAIDs, anticholinergic and AChEI-NSAIDs, Phospho-NSAIDs and some miscellaneous agents. In most cases, this review will cover literature dealing with these NSAID prodrugs from the year 2006 and later. Older literature will be used when necessary, e.g., to explain the chemical and biological mechanisms of action.

  11. The side effect profile of nonsteroidal anti-inflammatory drugs for rheumatic

    T A Raskina


    Full Text Available Objective: to study the side effect profile of nonsteroidal anti-inflammatory drugs (NSAIDs in patients with rheumatic diseases (RD. Subjects and methods. The study enrolled 373 patients (301 women and 72 men with RD, the mean age of whom was 58.9±1.3 years; the duration of the disease was 6.1±0.7 years. This study was cross-sectional and randomized, by applying a questionnaire for the estimation of the NSAID side effect profile, developed at the Research Institute of Rheumatology, Russian Academy of Medical Sciences. Results and discussion. NSAIDs are an effective agent for the symptomatic treatment of pain and inflammation in most RDs. More than 50% of the patients with RD reported unpleasant sensations in the digestive system. Dyspepsia was present in the absolute majority of RD patients (77.7% of the patients with rheumatoid arthritis; 100% of those with ankylosing spondylitis; 47.8% of those with osteoarthosis who had taken for more than a year

  12. The side effect profile of nonsteroidal anti-inflammatory drugs for rheumatic

    T A Raskina


    Full Text Available Objective: to study the side effect profile of nonsteroidal anti-inflammatory drugs (NSAIDs in patients with rheumatic diseases (RD. Subjects and methods. The study enrolled 373 patients (301 women and 72 men with RD, the mean age of whom was 58.9±1.3 years; the duration of the disease was 6.1±0.7 years. This study was cross-sectional and randomized, by applying a questionnaire for the estimation of the NSAID side effect profile, developed at the Research Institute of Rheumatology, Russian Academy of Medical Sciences. Results and discussion. NSAIDs are an effective agent for the symptomatic treatment of pain and inflammation in most RDs. More than 50% of the patients with RD reported unpleasant sensations in the digestive system. Dyspepsia was present in the absolute majority of RD patients (77.7% of the patients with rheumatoid arthritis; 100% of those with ankylosing spondylitis; 47.8% of those with osteoarthosis who had taken for more than a year

  13. Sulindac, a non-steroidal anti-inflammatory drug, mediates breast cancer inhibition as an immune modulator.

    Yin, Tao; Wang, Guoping; Ye, Tinghong; Wang, Yongsheng


    The cooperation of adaptive immunity with pharmacologic therapy influences cancer progression. Though non-steroidal anti-inflammatory drugs (NSAIDs) have a long history of cancer prevention, it is unclear whether adaptive immune system affects the action of those drugs. In present study, we revealed a novel immunological mechanism of sulindac. Our data showed that sulindac had substantial efficacy as a single agent against 4T1 murine breast cancer and prolonged the survival of tumor-bearing mice. However, in the athymic nude mice, sulindac treatment was ineffective. Further in vivo T cell subsets depletion experiments showed that CD8+ T lymphocytes deficiency reversed the anti-tumor effect of sulindac. In addition, sulindac significantly reduced M2 macrophages recruitment, cancer-related inflammation and tumor angiogenesis. Our results advance our understanding of the mechanisms of NSAIDs, and more importantly, this will provide insight into rational drug design or antitumor immunotherapy.


    FANGRui-Ying; ZHOUHui-Jun; YANGBao-Zhu; LIUHe-Chu; XUJian-Hua; LOUYi-Jia; ZHANGYuan-Pei


    DL-111-IT (3-ethylpheny1-5- (3-methoxyphenyl) -1, 2, 4-triazole) is highly effective for terminating early pregnancy in several species of animals without delayoel embryotoxic and teratogenic effects on the secondary embryo in rats. The present paper is a toxicological study of DI-111-IT.

  15. Isobolographic analysis of the antinociceptive interactions of clonidine with nonsteroidal anti-inflammatory drugs.

    Miranda, H F; Pinardi, G


    The present study was undertaken to characterize the interactions between nonsteroidal anti-inflammatory drugs and the alpha(2)-adrenoceptor agonist clonidine in an acute nociceptive test. The writhing test was selected as a model of acute visceral pain. Isobolograms were constructed to assess the interactions of clonidine and each nonsteroidal anti-inflammatory drugs, when coadministered intraperitoneally and intrathecally (i.t.). The simultaneous intraperitoneal administration of fixed ratios of ED(50) fractions of all nonsteroidal anti-inflammatory drugs (naproxen, piroxicam, paracetamol, dipyrone or metamizol and nimesulide) combined with clonidine resulted in synergistic interactions. The same combinations administered intrathecally were additive. The synergistic interactions between systemic nonsteroidal anti-inflammatory drugs and clonidine may involve supraspinal mechanisms.

  16. Non-steroidal Anti-inflammatory Drugs in Raptors

    Oaks, J. Lindsay; Meteyer, Carol U.; Miller, R. Eric; Fowler, Murray E.


    The use of analgesia has become standard, and appropriate, practice in avian medicine. As in mammals, pain control in avian patients is usually accomplished with opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) used singly or in combination for a multimodal approach. Despite their usefulness, widespread use, and relative safety in clinical use, few controlled studies in birds have been conducted on efficacy, safety, and dosing. The guidelines for the use of NSAIDs in raptors and other birds have mainly been empirical. More recently, NSAIDs in free-living raptors have emerged as a major conservation issue with the discovery that diclofenac sodium was responsible for the population crash of three species of Gyps vultures in southern Asia. In this context, residues of veterinary NSAIDs in domestic animals are now considered environmental contaminants that can be significantly toxic to vultures and possibly other avian scavengers. Ironically, the disaster with Asian vultures has led to a considerable body of research on NSAIDs in raptors to the benefit of clinicians who now have scientific information available to help assess dosing, safety, toxicity, and pharmacokinetics of NSAIDs in their raptor patients.

  17. Topical nonsteroidal anti-inflammatory drugs for osteoarthritis.

    Barthel, H Richard; Axford-Gatley, Robert A


    Nonsteroidal anti-inflammatory drugs (NSAIDs) are mainstays of the treatment of osteoarthritis (OA) but have dose- and age-related risks of gastrointestinal, cardiovascular, and renal adverse events (AEs). As a result, US and international guidelines recommend caution when prescribing oral NSAIDs, particularly in older patients and those with significant comorbidities. For OA of the hands and knees, topical NSAIDs provide efficacy similar to oral NSAIDs, with far less systemic distribution. Treatment-related cardiovascular, renal, and other serious AEs with topical NSAIDs have not been reported. At present, only 2 topical NSAIDs are approved in the United States for the treatment of OA: diclofenac sodium 1% gel for hand or knee OA and diclofenac sodium 1.5% in 45.5% dimethylsulfoxide solution for knee OA. Clinical trial data for these products have demonstrated efficacy superior to placebo or similar to oral diclofenac with AE profiles similar to placebo, except for application site reactions. In large double-blind trials, gastrointestinal AEs were infrequent and did not include ulcers, perforations, or bleeding. The purpose of this brief review is to examine the data from controlled double-blind trials evaluating the use of topical NSAIDs in patients with OA. Articles included were identified via a search of PubMed covering the period from January 1, 2005 through March 31, 2010. Reference lists from OA treatment guidelines and meta-analyses were reviewed for additional citations of importance.

  18. Safety of Etoricoxib, Celecoxib, and Nonselective Nonsteroidal Antiinflammatory Drugs in Ankylosing Spondylitis and Other Spondyloarthritis Patients

    Kristensen, L E; Jakobsen, A K; Askling, J


    OBJECTIVE: Safety data regarding the use of etoricoxib and other nonsteroidal antiinflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather limited. Our objective was to estimate and compare rates of gastrointestinal, renovascular, and cardio......OBJECTIVE: Safety data regarding the use of etoricoxib and other nonsteroidal antiinflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather limited. Our objective was to estimate and compare rates of gastrointestinal, renovascular...

  19. Topical Nonsteroidal Anti-Inflammatory Drugs: The Importance of Drug, Delivery, and Therapeutic Outcome.

    Barkin, Robert L


    Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of pain associated with a variety of indications, including arthritic conditions, but their usefulness is often limited by dose-dependent adverse events (AEs), such as gastrointestinal disturbances, cardiovascular events, and renal toxicity. The risk of such effects could be reduced by the use of topical formulations, which offer the potential to deliver analgesic concentrations locally, at the site of inflammation, while minimizing systemic concentrations. The topical preparations currently approved in the United States are diclofenac sodium 1.5% topical solution (containing dimethyl sulfoxide as a penetration enhancer), diclofenac sodium gel 1%, and a diclofenac hydroxyethylpyrrolidine 1.3% patch. Each of these topical NSAIDs provide drug delivery to subcutaneous tissues for the management of pain associated with osteoarthritis or soft-tissue injuries. Furthermore, these formulations are not significantly associated with the systemic AEs associated with oral NSAIDs; the most common AEs associated with topical formulations are local skin reactions, which are usually mild and self-limiting. Other topical NSAID preparations approved in the European Union include ibuprofen creams and gels, ketoprofen gel, felbinac gel and cutaneous foam, and piroxicam gel. Meta-analyses have confirmed the efficacy and safety of these preparations. However, it is important to recognize that pharmacokinetic absorption from topical formulations can vary markedly, even between different formulations of the same drug, depending on the agent, the underlying disorder, and the site of application. It is therefore essential to consider the patient, the drug, and the drug delivery mechanism when selecting a topical NSAID preparation.

  20. The problem in the evaluation of the efficacy and safety of nonsteroidal anti-inflammatory drugs

    N. V. Chichasova


    Full Text Available The review gives data on the safety of nimesulide used for the treatment of chronic joint diseases. The first-line treatment at its any stage for joint diseases is nonsteroidal anti-inflammatory drugs (NSAIDs. Questions have recently arisen of the safety of nimesulide; however, epidemiological findings and clinical experience confirm a positive benefit/risk profile of nimesulide in the treatment of acute pain. The International Consensus Meeting (Vienna, 2014 noted that the risk of severe adverse hepatic NSAID reactions was low and the rate of liver damage associated with nimesulide was completely similar to that observed with other NSAIDs. There are data available in the literature on the rate of serious adverse liver reactions to different NSAIDs and paracetamol. The rate of such reactions to all NSAIDs per million patientyears was 1.55 and that to nimesulide was 1.88. The members of the International Consensus Group concluded that nimesulide, if properly used, remained a valuable and safe drug for the treatment of various conditions, characterized by the presence of acute inflammatory pain, by virtue of the rapid onset of analgesic action and an evidence-based positive benefit/risk profile. The long successful experience with nimesulide in our country suggests that the agent may be successfully used to treat chronic and acute pain (including dysmenorrhea in a daily dose of 200 mg/day. The safety profile of the drug is quite satisfactorily for all adverse reactions typical of NSAIDs, including its negative effect on the liver.

  1. The synovial prostaglandin system in chronic inflammatory arthritis: differential effects of steroidal and nonsteroidal anti-inflammatory drugs

    Bombardieri, S.; Cattani, P.; Ciabattoni, G.; Di Munno, O.; Pasero, G.; Patrono, C.; Pinca, E.; Pugliese, F.


    1 The present study was undertaken to characterize the spectrum of arachidonic acid metabolites present in synovial effusions of patients with rheumatoid or psoriatic arthritis, and to compare changes in their concentration following a short-term treatment with 6α-methyl-prednisolone (6-MeP: 4-8 mg/day) or indoprofen (1.2 g/day), a nonsteroidal anti-inflammatory agent with proven synovial prostaglandin inhibitory effect. 2 Measurements of prostaglandin E2 (PGE2), thromboxane (TX) B2, 6-keto-PGF1α and PGF2α were performed by radioimmunoassay techniques in synovial effusions obtained from 23 patients, and validated by thin-layer chromatographic analysis of the extracted immunoreactivity. 3 PGE2 and TXB2 accounted for more than 60% of the total immunoreactivity in untreated patients. The absence of any constant ratio between the different arachidonic acid metabolites detected in synovial fluid is consistent with a heterogeneous cellular origin of these compounds. 4 Indoprofen treatment was associated with a consistent reduction of synovial prostaglandin and thromboxane concentrations, ranging from 36% in the case of 6-keto-PGF1α to 90% in the case of PGE2. 5 In contrast, 6-MeP caused opposite changes on different metabolites originating via the cyclo-oxygenase pathway. Thus, 6-keto-PGF1α concentrations were reduced by 35%, PGF2α concentrations were increased by 30%, while PGE2 and TXB2 were unchanged following 6-MeP. 6 Although the mechanism(s) underlying the failure of 6-MeP to reduce synovial PGE2 and TXB2 levels are uncertain, the results of the present study clearly indicate that therapeutic doses of steroidal and nonsteroidal anti-inflammatory drugs cause quite distinct changes in arachidonic acid metabolism, which might be relevant to their specific therapeutic actions and side-effects. PMID:6895043

  2. Use of non-steroidal anti-inflammatory drugs in pregnancy: impact on the fetus and newborn.

    Antonucci, Roberto; Zaffanello, Marco; Puxeddu, Elisabetta; Porcella, Annalisa; Cuzzolin, Laura; Pilloni, Maria Dolores; Fanos, Vassilios


    Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed in pregnancy to treat fever, pain and inflammation. Indications for chronic use of these agents during pregnancy are inflammatory bowel or chronic rheumatic diseases. Since the seventies, NSAIDs have been used as effective tocolytic agents: indomethacin has been the reference drug, delaying delivery for at least 48 hours and up to 7-10 days. Additionally, self-medication with NSAIDs is practiced by pregnant women. NSAIDs given to pregnant women cross the placenta and may cause embryo-fetal and neonatal adverse effects, depending on the type of agent, the dose and duration of therapy, the period of gestation, and the time elapsed between maternal NSAID administration and delivery. These effects derive from the action mechanisms of NSAIDs (mainly inhibition of prostanoid activity) and from the physiological changes in drug pharmacokinetics occurring during pregnancy. Increased risks of miscarriage and malformations are associated with NSAID use in early pregnancy. Conversely, exposure to NSAIDs after 30 weeks' gestation is associated with an increased risk of premature closure of the fetal ductus arteriosus and oligohydramnios. Fetal and neonatal adverse effects affecting the brain, kidney, lung, skeleton, gastrointestinal tract and cardiovascular system have also been reported after prenatal exposure to NSAIDs. NSAIDs should be given in pregnancy only if the maternal benefits outweigh the potential fetal risks, at the lowest effective dose and for the shortest duration possible. This article discusses in detail the placental transfer and metabolism of NSAIDs, and the adverse impact of prenatal NSAID exposure on the offspring.

  3. The non-steroidal anti-inflammatory drug niflumic acid inhibits Candida albicans growth.

    Baker, Andrew; Northrop, Frederick D; Miedema, Hendrik; Devine, Gary R; Davies, Julia M


    The non-steroidal anti-inflammatory drug niflumic acid was found to inhibit growth of the yeast form of Candida albicans. Niflumic acid inhibited respiratory oxygen uptake and it is hypothesised that this was achieved by cytosolic acidification and block of glycolysis. Inhibitory concentrations are compatible with current practice of topical application.

  4. Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer's disease?

    Andersen, K; Launer, L J; Ott, A


    Based on reports that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the risk for Alzheimer's disease (AD), we studied the cross-sectional relation between NSAID use and the risk for AD in a population-based study of disease and disability in older people. After controlling...

  5. Nonsteroidal anti-inflammatory drugs for low back pain - An updated Cochrane review

    Roelofs, Pepijn D. D. M.; Deyo, Rick A.; Koes, Bart W.; Scholten, Rob J. P. M.; van Tulder, Maurits W.


    Study Design. A systematic review of randomized controlled trials. Objectives. To assess the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors in the treatment of nonspecific low back pain and to assess which type of NSAID is most effective. Summary of Background Data. NS

  6. Non-steroidal anti-inflammatory drugs and molecular carcinogenesis of colorectal carcinomas

    Huls, G; Koornstra, JJ; Kleibeuker, JH


    Context Colorectal cancer is the second most common cause of cancer-related mortality in the west. The high incidence and mortality make effective prevention an important public-health and economic issue. Non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit colorectal-carcinogenesis and are am

  7. Non-steroidal anti-inflammatory drugs for chronic low back pain

    W.T.M. Enthoven (Wendy); P.D.D.M. Roelofs; R.A. Deyo (Richard); M.W. van Tulder (Maurits); B.W. Koes (Bart)


    textabstractBackground: Chronic back pain is an important health problem. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat people with low back pain, especially people with acute back pain. Short term NSAID use is also recommended for pain relief in people with chronic back pa

  8. Effects of dietary anticarcinogens and nonsteroidal anti-inflammatory drugs on rat gastrointestinal UDP-glucuronosyltransferases.

    Logt, E.M.J. van der; Roelofs, H.M.J.; Lieshout, E.M.M. van; Nagengast, F.M.; Peters, W.H.M.


    BACKGROUND: Dietary compounds or nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce cancer rates. Elevation of phase II detoxification enzymes might be one of the mechanisms leading to cancer prevention. We investigated the effects of dietary anticarcinogens and NSAIDs on rat gastrointestinal

  9. Pharmacological agents and impairment of fracture healing: what is the evidence?

    Pountos, I.; Georgouli, T.; Blokhuis, T.J.; Pape, H.C.; Giannoudis, P.V.


    Bone healing is an extremely complex process which depends on the coordinated action of several cell lineages on a cascade of biological events, and has always been a major medical concern. The use of several drugs such as corticosteroids, chemotherapeutic agents, non-steroidal anti-inflammatory dru

  10. Suppression of Rapidly Progressive Mouse Glomerulonephritis with the Non-Steroidal Mineralocorticoid Receptor Antagonist BR-4628.

    Frank Y Ma

    Full Text Available Steroidal mineralocorticoid receptor antagonists (MRAs are effective in the treatment of kidney disease; however, the side effect of hyperkalaemia, particularly in the context of renal impairment, is a major limitation to their clinical use. Recently developed non-steroidal MRAs have distinct characteristics suggesting that they may be superior to steroidal MRAs. Therefore, we explored the benefits of a non-steroidal MRA in a model of rapidly progressive glomerulonephritis.Accelerated anti-glomerular basement membrane (GBM glomerulonephritis was induced in groups of C57BL/6J mice which received no treatment, vehicle or a non-steroidal MRA (BR-4628, 5mg/kg/bid from day 0 until being killed on day 15 of disease. Mice were examined for renal injury.Mice with anti-GBM glomerulonephritis which received no treatment or vehicle developed similar disease with severe albuminuria, impaired renal function, glomerular tuft damage and crescents in 40% of glomeruli. In comparison, mice which received BR-4628 displayed similar albuminuria, but had improved renal function, reduced severity of glomerular tuft lesions and a 50% reduction in crescents. The protection seen in BR-4628 treated mice was associated with a marked reduction in glomerular macrophages and T-cells and reduced kidney gene expression of proinflammatory (CCL2, TNF-α, IFN-γ and profibrotic molecules (collagen I, fibronectin. In addition, treatment with BR-4626 did not cause hyperkalaemia or increase urine Na+/K+ excretion (a marker of tubular dysfunction.The non-steroidal MRA (BR-4628 provided substantial suppression of mouse crescentic glomerulonephritis without causing tubular dysfunction. This finding warrants further investigation of non-steroidal MRAs as a therapy for inflammatory kidney diseases.

  11. Distal bowel selectivity in the chemoprevention of experimental colon carcinogenesis by the non-steroidal anti-inflammatory drug nabumetone.

    Roy, H K; Karolski, W J; Ratashak, A


    Use of non-steroidal anti-inflammatory drugs (NSAIDs) for chemoprevention of colon cancer has been hindered by their potential gastro-intestinal toxicity. Nabumetone, which is approximately 10 to 36 times safer than conventional NSAIDs, was evaluated in 2 models of experimental colon carcinogenesis. In azoxymethane (AOM)-treated Fisher 344 rats, nabumetone caused dose-dependent inhibition of aberrant crypt foci (ACF), with 750 and 1,500 ppm resulting in 15% and 37% reductions, respectively (p nabumetone, with 900 ppm suppressing approximately half of the intestinal tumors. Interestingly, inhibition of intermediate biomarkers in both models was markedly greater in the distal than the proximal bowel. To mechanistically evaluate this regional selectivity, we assessed cyclo-oxygenase-2 (COX-2) expression in the uninvolved mucosa and demonstrated a 3- to 4-fold excess in the distal relative to the proximal bowel in both MIN mice and AOM-treated rats. We then investigated another putative NSAID target, peroxisome proliferator-activated receptor-delta (PPAR-delta) and demonstrated up-regulation during AOM-induced colonic tumorigenesis. Furthermore, in pre-neoplastic mucosa, there was a 3-fold excess of PPAR-delta in the distal colon. We demonstrate that nabumetone is an effective protective agent in both experimental models of colon carcinogenesis. The striking distal predilection of nabumetone may be, at least partially, explained by distal bowel over-expression of COX-2 and PPAR-delta.

  12. Chemopreventive action of non-steroidal anti-inflammatory drugs on the inflammatory pathways in colon cancer.

    Ghanghas, Preety; Jain, Shelly; Rana, Chandan; Sanyal, S N


    Non-steroidal anti-inflammatory drugs (NSAIDs) are emerging as novel chemopreventive agents against a variety of cancers owing to their capability in blocking the tumor development by cellular proliferation and by promoting apoptosis. Inflammation is principal cause of colon carcinogenesis. A missing link between inflammation and cancer could be the activation of NF-κB, which is a hallmark of inflammatory response, and is commonly detected in malignant tumors. Therefore, targeting pro-inflammatory cyclooxygenase enzymes and transcription factors will be profitable as a mechanism to inhibit tumor growth. In the present study, we have studied the role of various pro-inflammatory enzymes and transcription factors in the development of the 1,2-dimethylhydrazine dihydrochloride (DMH)-induced colorectal cancer and also observed the role of three NSAIDs, viz., Celecoxib, Etoricoxib and Diclofenac. Carcinogenic changes were observed in morphological and histopathological studies, whereas protein regulations of various biomolecules were identified by immunofluorescence analysis. Apoptotic studies was done by TUNEL assay and Hoechst/PI co-staining of the isolated colonocytes. It was found that DMH-treated animals were having an over-expression of pro-inflammatory enzymes, aberrant nuclear localization of activated cell survival transcription factor, NF-κB and suppression of anti-inflammatory transcription factor PPAR-γ, thereby suggesting a marked role of inflammation in the tumor progression. However, co-administration of NSAIDs has significantly reduced the inflammatory potential of the growing neoplasm.

  13. Host modulation by therapeutic agents

    Sugumari Elavarasu


    Full Text Available Periodontal disease susceptible group present advanced periodontal breakdown even though they achieve a high standard of oral hygiene. Various destructive enzymes and inflammatory mediators are involved in destruction. These are elevated in case of periodontal destruction. Host modulation aims at bringing these enzymes and mediators to normal level. Doxycycline, nonsteroidal anti-inflammatory drugs (NSAIDs, bisphosphonates, nitrous oxide (NO synthase inhibitors, recombinant human interleukin-11 (rhIL-11, omega-3 fatty acid, mouse anti-human interleukin-6 receptor antibody (MRA, mitogen-activated protein kinase (MAPK inhibitors, nuclear factor-kappa B (NF-kb inhibitors, osteoprotegerin, and tumor necrosis factor antagonist (TNF-α are some of the therapeutic agents that have host modulation properties.

  14. The nonsteroidal anti-inflammatory drug, nabumetone, differentially inhibits beta-catenin signaling in the MIN mouse and azoxymethane-treated rat models of colon carcinogenesis.

    Roy, Hemant K; Karolski, William J; Wali, Ramesh K; Ratashak, Anne; Hart, John; Smyrk, Thomas C


    The mechanisms through which beta-catenin signaling is inhibited during colorectal cancer chemoprevention by nonsteroidal anti-inflammatory agents is incompletely understood. We report that nabumetone decreased uninvolved intestinal mucosal beta-catenin levels in the MIN mouse with a concomitant increase in glycogen synthase kinase (GSK)-3beta levels, an enzyme that targets beta-catenin for destruction. However, in the azoxymethane-treated rat, where beta-catenin is frequently rendered GSK-3beta-insensitive, nabumetone failed to alter beta-catenin levels but did decrease beta-catenin nuclear localization and transcriptional activity as gauged by cyclin D1. In conclusion, we demonstrate that the differential mechanisms for beta-catenin suppression may be determined, at least partly, by GSK-3beta.

  15. Appearance of attenuated intestinal polyposis during chronic non-steroidal anti-inflammatory drugs use

    Hugh; James; Freeman


    Aspirin and non-steroidal anti-inflammatory drugs (NSAIDS) may prevent sporadic colonic neoplasia and reduce the polyp burden in familial adenomatous polyposis. A 41-year-old pharmacologist with no family history of intestinal polyps or cancer chronically consumed daily aspirin and other non-steroidal anti-inflammatory drugs for decades despite recurrent and multiple gastric ulcers. A cancerous polyp in the colon was endoscopically resected. Over the next 2 decades, almost 50 adenomatous polyps were removed from the rest of his colon and duodenum, typical of an attenuated form of adenomatous polyposis. Chronic and habitual use of aspirin or NSAIDS may have important significance in delaying the appearance of adenomas. The observations here emphasize the important implications for clinical risk assessment in screening programs designed to detect or prevent colon cancer.

  16. Use of nonsteroidal anti-inflammatory drugs among healthy people and specific cerebrovascular safety

    Fosbøl, Emil L; Olsen, Anne-Marie Schjerning; Olesen, Jonas Bjerring


    stroke). RESULTS: We selected 1,028,437 healthy individuals (median age 39 years). At least one nonsteroidal anti-inflammatory drug was claimed by 44·7% of the study population, and the drugs were generally used for a short period of time and in low doses. High-dose ibuprofen and diclofenac were...... associated with increased risk of ischemic stroke [hazard ratio 2·15 (95% confidence interval 1·66-2·79) and 2·37 (confidence interval 1·99-2·81), respectively]. Diclofenac was also associated with increased risk of hemorrhagic stroke and so was naproxen [hazard ratio 2·15 (confidence interval 1......·35-3·42)]. CONCLUSIONS: In healthy individuals, use of commonly available nonsteroidal anti-inflammatory drugs such as ibuprofen, diclofenac, and naproxen was associated with increased risk of stroke....

  17. Helicobacter pylori and risk of ulcer bleeding among users of nonsteroidal anti-inflammatory drugs: a case-control study

    Aalykke, C; Lauritsen, Jens; Hallas, J


    Peptic ulcer complications related to use of nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most common serious adverse drug reactions. Whether Helicobacter pylori infection potentiates this gastrointestinal toxicity of NSAIDs is still unresolved. In this study, we investigated...

  18. Nonsteroidal anti-inflammatory drugs as adjuncts in the management of periodontal diseases and peri-implantitis.

    Salvi, G E; Williams, R C; Offenbacher, S


    For the past three decades, prostaglandin E2 and other arachidonic acid metabolites have been recognized as important proinflammatory mediators in bone resorption and various forms of periodontal disease. Nonsteroidal anti-inflammatory drugs are chemical compounds that selectively inhibit the synthesis of metabolites of the cyclooxygenase pathway, thereby blocking the production of prostaglandins, thromboxane, and prostacyclin. Inhibiting prostaglandin E2 synthesis with nonsteroidal anti-inflammatory drugs has been unequivocally shown in both animal and human studies to be of primary therapeutic efficacy. Recent lines of nonsteroidal anti-inflammatory drugs research have focused on the development of daily topical administration forms such as gels, toothpastes, and rinses. Furthermore, new studies have implicated prostaglandin E2 in the peri-implantitis process, opening the possibility to manage failing implants with topical nonsteroidal anti-inflammatory drug delivery systems.

  19. Lithium Toxicity in the Setting of Nonsteroidal Anti-Inflammatory Medications

    Syed Hassan


    Full Text Available Lithium toxicity is known to affect multiple organ systems, including the central nervous system. Lithium levels have been used in the diagnosis of toxicity and in assessing response to management. There is evidence that nonsteroidal anti-inflammatory medications (NSAIDs can increase lithium levels and decrease renal lithium clearance. We present a case of lithium toxicity, which demonstrates this effect and also highlights the fact that lithium levels do not correlate with clinical improvement, especially the neurological deficit.

  20. New insights into the use of currently available non-steroidal anti-inflammatory drugs

    Brune K; Patrignani P


    Kay Brune,1 Paola Patrignani2 1Department of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany; 2Department of Neuroscience, Imaging and Clinical Sciences, Center of Excellence on Aging, G d’Annunzio University, Chieti, Italy Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs), which act via inhibition of the cyclooxygenase (COX) isozymes, were discovered more than 100 years ago. They remain a key compon...

  1. Effect of nonsteroidal anti-inflammatory drugs on glycogenolysis in isolated hepatocytes.

    Brass, E. P.; Garrity, M. J.


    E-series prostaglandins have previously been demonstrated to inhibit hormone-stimulated glycogenolysis when added to isolated hepatocytes of the rat. In the present study, the effect of nonsteroidal anti-inflammatory drugs, which inhibit cyclo-oxygenase activity, on glycogenolysis was examined in the hepatocyte model. Ibuprofen (80 microM), indomethacin (50 microM) and meclofenamate (60 microM) all increased rates of glycogenolysis when added under basal conditions. In contrast, piroxicam (50...


    Vladimir Vasilyevich Badokin


    Full Text Available The paper presents the current views of the effects of nonsteroidal anti-inflammatory drugs on the mechanisms of development of inflammation in osteoarthrosis and their action on the metabolism of chondrocytes and extracellular substance of the articular cartilage. It also gives the results of numerous studies of the efficacy and safety of meloxicam in osteoarthrosis and the data supporting its chondroprotective properties


    Vladimir Vasilyevich Badokin


    Full Text Available The paper presents the current views of the effects of nonsteroidal anti-inflammatory drugs on the mechanisms of development of inflammation in osteoarthrosis and their action on the metabolism of chondrocytes and extracellular substance of the articular cartilage. It also gives the results of numerous studies of the efficacy and safety of meloxicam in osteoarthrosis and the data supporting its chondroprotective properties

  4. Are perioperative nonsteroidal anti-inflammatory drugs ulcerogenic in the short term?

    Kehlet, H; Dahl, J B


    It is well documented that long term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk of peptic ulcer and that gastroduodenal mucosal erosions can be demonstrated in volunteers within 1 week of treatment initiation. However, long term studies in nonsurgical patients...... have not documented gastroduodenal complications within the first week of treatment. Cumulative data from controlled studies of perioperative (> or = 48 hours and perforation) within...

  5. What does a study of nonsteroidal anti-inflammatory drug sales statistics give the Russian Federation?

    Viktoriya Georgievna Barskova


    Full Text Available The paper analyzes the data obtained by Pharmexpert on the sales of nonsteroidal anti-inflammatory drugs in the Russian Federation. Ibuprofen, ketorolac, diclofenac, and nimesulide are sales leaders. Possible reasons for the popularity of a number of medications and whether it is expedient to use intramuscular formulations are considered. The WHO data on indi-cations for and contraindications to the use of injectable dosage form are given.

  6. Non-steroidal anti-inflammatory drugs(NSAIDs and physiotherapy - a selective review

    P. van der Bijl


    Full Text Available This paper presents a selective review on the non-steroidal anti-inflammatory drugs (NSAIDs. These drugs,which form the mainstay of treatment of a variety of musculoskeletal and rheumatic conditions, may facilitate the efficacy of and compliance with physiotherapy treatment.  Their mechanisms of action, adverse effects, various routes of administration, eg systemic versus topical, and the role that these drugs may play in physiotherapy practice  are discussed.

  7. Non-steroidal anti-inflammatory drugs and ulcer complications: a risk factor analysis for clinical decision-making

    Hansen, J M; Hallas, J; Lauritsen, Jens;


    Use of non-steroidal anti-inflammatory drugs (NSAIDs) is recognized as an important cause of peptic ulcer complications. The aim of this nested case-control study was to identify risk factors for NSAID-related ulcer complications.......Use of non-steroidal anti-inflammatory drugs (NSAIDs) is recognized as an important cause of peptic ulcer complications. The aim of this nested case-control study was to identify risk factors for NSAID-related ulcer complications....

  8. Cyclo-oxygenase-2 inhibitors or nonselective NSAIDs plus gastroprotective agents: What to prescribe in daily clinical practice?

    G.M.C. Masclee (Gwen); V.E. Valkhoff (Vera); E.M. van Soest; R. Schade (René); G. Mazzaglia (Giampiero); M. Molokhia (Mariam); G. Trifiro (Gianluca); J.L. Goldstein; S. Hernández-Díaz (Sonia); E.J. Kuipers (Ernst); M.C.J.M. Sturkenboom (Miriam)


    textabstractBackground Two strategies for prevention of upper gastrointestinal (UGI) events for nonselective nonsteroidal anti-inflammatory drug (nsNSAID) users are replacement of the nsNSAID by a cyclo-oxygenase-2-selective inhibitor (coxib) or co-prescription of a gastroprotective agent (GPA). Aim

  9. Combinatorial effect of non-steroidal anti-inflammatory drugs and NF-κB inhibitors in ovarian cancer therapy.

    Luiz F Zerbini

    Full Text Available Several epidemiological studies have correlated the use of non-steroidal anti-inflammatory drugs (NSAID with reduced risk of ovarian cancer, the most lethal gynecological cancer, diagnosed usually in late stages of the disease. We have previously established that the pro-apoptotic cytokine melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24 is a crucial mediator of NSAID-induced apoptosis in prostate, breast, renal and stomach cancer cells. In this report we evaluated various structurally different NSAIDs for their efficacies to induce apoptosis and mda-7/IL-24 expression in ovarian cancer cells. While several NSAIDs induced apoptosis, Sulindac Sulfide and Diclofenac most potently induced apoptosis and reduced tumor growth. A combination of these agents results in a synergistic effect. Furthermore, mda-7/IL-24 induction by NSAIDs is essential for programmed cell death, since inhibition of mda-7/IL-24 by small interfering RNA abrogates apoptosis. mda-7/IL-24 activation leads to upregulation of growth arrest and DNA damage inducible (GADD 45 α and γ and JNK activation. The NF-κB family of transcription factors has been implicated in ovarian cancer development. We previously established NF-κB/IκB signaling as an essential step for cell survival in cancer cells and hypothesized that targeting NF-κB could potentiate NSAID-mediated apoptosis induction in ovarian cancer cells. Indeed, combining NSAID treatment with NF-κB inhibitors led to enhanced apoptosis induction. Our results indicate that inhibition of NF-κB in combination with activation of mda-7/IL-24 expression may lead to a new combinatorial therapy for ovarian cancer.

  10. Synthesis and biological evaluation of a fluorine-18-labeled nonsteroidal androgen receptor antagonist, N-(3-[{sup 18}F]fluoro-4-nitronaphthyl)-cis-5-norbornene-endo-2,3-dicarboxylic imide

    Parent, Ephraim E. [Department of Chemistry, University of Illinois, Urbana, IL 61801 (United States); Dence, Carmen S. [Washington University School of Medicine, St. Louis, MO 63110 (United States); Sharp, Terry L. [Washington University School of Medicine, St. Louis, MO 63110 (United States); Welch, Michael J. [Washington University School of Medicine, St. Louis, MO 63110 (United States); Katzenellenbogen, John A. [Department of Chemistry, University of Illinois, Urbana, IL 61801 (United States)]. E-mail:


    Introduction: Androgen receptor (AR), which is overexpressed in most prostate cancers, is the target of androgen ablation and antiandrogen therapies: it is also the target for the receptor-mediated imaging of AR-positive prostate cancer using radiolabeled ligands. Previous AR imaging agents were based on a steroidal core labeled with fluorine. To develop a novel class of nonsteroidal imaging agents, with binding and pharmacological characteristics that are more similar to those of clinically used AR antagonists, we synthesized N-(3-fluoro-4-nitronaphthyl)-cis-5-norbornene-endo-2,3-dicarboxylic imide (3-F-NNDI), an analog of recently reported AR antagonist ligands. Methods: 3-F-NNDI was synthesized in six steps starting with 1-nitronaphthalene, with fluorine incorporation as the final step. The labeling of 3-F-NNDI with fluorine-18 was achieved through a novel, extremely mild, S{sub N}Ar displacement reaction of an o-nitro-activated arene trimethylammonium salt, and 3-[{sup 18}F]F-NNDI was prepared in high specific activity. Results and Discussion: 3-F-NNDI was found to have an AR-binding affinity similar to that of its parent compound. In vitro assays demonstrated high stability of the labeled compound under physiological conditions in buffer and in the blood. Androgen target tissue uptake in diethylstilbestrol-pretreated male rats, however, was minimal, probably because of extensive metabolic defluorination the radiolabeled ligand. Conclusions: This study is part of our first look at a novel class of nonsteroidal AR antagonists as positron emission tomography (PET) imaging agents that are alternatives to steroidal AR agonist-based imaging agents. Although 3-[{sup 18}F]F-NNDI has significant affinity for AR, it showed limited promise as a PET imaging agent because of its poor target tissue distribution properties.

  11. A general procedure for isotopic (deuterium) labelling of non-steroidal antiinflammatory 2-arylpropionic acids

    Castell, J.V. (Valencia Univ. Hospital (Spain). Centro de Investigacion); Martinez, L.A. (Valencia Univ. Hospital (Spain). Centro de Investigacion Universidad Politecnica de Valencia (Spain). Dept. de Quimica); Miranda, M.A.; Tarrega, Pilar (Universidad Politecnica de Valencia (Spain). Dept. de Quimica)


    Alkaline treatment of nonsteroidal antiinflammatory 2-arylpropionic acids in deuterium oxide led in all cases to isotopic exchange of the proton located at the [alpha]-position of the side chain. Monodeuteration was observed in the case of carprofen, ibuprofen, ketoprofen, fenoprofen, flurbiprofen and naproxen. Additional exchange of one or two protons of the heterocyclic ring occurred in indoprofen, suprofen and tiaprofenic acid. The isotopic labelling survived under the conditions required to perform in vitro photoallergic studies (photolysis in non-deuterated aqueous media). (Author).

  12. Non-Steroidal Anti-Inflammatory Drugs, Variation in Inflammatory Genes, and Aggressive Prostate Cancer

    John S. Witte


    Full Text Available Increasing evidence suggests that prostatic inflammation plays a key role in the development of prostate cancer. It remains controversial whether non-steroidal anti-inflammatory drugs (NSAIDs reduce the risk of prostate cancer. Here, we investigate how a previously reported inverse association between NSAID use and the risk of aggressive prostate cancer is modulated by variants in several inflammatory genes. We found that NSAIDs may have differential effects on prostate cancer development, depending on one’s genetic makeup. Further study of these inflammatory pathways may clarify the mechanisms through which NSAIDs impact prostate cancer risk.

  13. Regioselective enzymatic synthesis of non-steroidal anti-inflammatory drugs containing glucose in organic media.

    Wang, Na; Liu, Bo Kai; Wu, Qi; Wang, Jun Liang; Lin, Xian Fu


    Enzymatic transesterification of glucose with the vinyl ester of non-steroidal anti-inflammatory drugs (NSAIDs) was in organic media performed for synthesis of novel NSAIDs-glucose conjugates. Glucose was regioselectively acylated at the 6-hydroxyl group. The indomethacin-glucose conjugate and ketoprofen-glucose conjugate were produced by the catalysis of alkaline protease from Bacillus subtilis in the respective yields of 42% (over 48 h) and 63% (over 40 h). The etodolac-glucose conjugate was obtained in 26% yield (over 144 h) by lipase from Candida antarctica.

  14. Synthesis, structure-activity relationships, and characterization of novel nonsteroidal and selective androgen receptor modulators.

    Schlienger, Nathalie; Lund, Birgitte W; Pawlas, Jan; Badalassi, Fabrizio; Bertozzi, Fabio; Lewinsky, Rasmus; Fejzic, Alma; Thygesen, Mikkel B; Tabatabaei, Ali; Bradley, Stefania Risso; Gardell, Luis R; Piu, Fabrice; Olsson, Roger


    Herein we describe the discovery of ACP-105 (1), a novel and potent nonsteroidal selective androgen receptor modulator (SARM) with partial agonist activity relative to the natural androgen testosterone. Compound 1 was developed from a series of compounds found in a HTS screen using the receptor selection and amplification technology (R-SAT). In vivo, 1 improved anabolic parameters in a 2-week chronic study in castrated male rats. In addition to compound 1, a number of potent antiandrogens were discovered from the same series of compounds whereof one compound, 13, had antagonist activity at the AR T877A mutant involved in prostate cancer.

  15. Do the pharmacodynamics of the nonsteroidal anti-inflammatory drugs suggest a role in the management of postoperative pain?

    Mather, L E


    Until recently, nonsteroidal anti-inflammatory drugs (NSAIDs) were regarded as weak analgesic agents with a potent antiplatelet effect that severely limited their perioperative usefulness. However, the recent development of injectable NSAIDs has stimulated a re-evaluation of the potential role of this class of drugs in postoperative pain management. In general surgery, NSAIDs have been shown to be effective analgesics when administered after surgery, as judged by either a reduction in pain scores and/or by an opioid sparing effect. Parenteral NSAIDs alone, notably ketorolac and diclofenac, may be adequate or even preferred analgesic agents after minor surgery. In dental surgery, NSAIDs produce greater initial analgesia than steroids, although the latter produce greater suppression of swelling and less functional loss. NSAID pretreatment results in only modest suppression of swelling compared with placebo. These data suggest that the acute analgesic effects of NSAIDs in oral surgery and probably other models result from suppression of a nociceptive process, rather than a generalised anti-inflammatory effect. This view challenges the traditional association between inhibition of prostaglandin synthesis and the therapeutic effects of these drugs. The variety of NSAIDs leads to a range in half-lives from short, e.g. diclofenac (1 h), intermediate, e.g. ketorolac (5h), to long, e.g. tenoxicam (60h), which has implications for both convenience of the dosage regimen and drug accumulation. For some racemic NSAIDs (e.g. ibuprofen), metabolic 'activation' of the inactive R-enantiomer to the active S-enantiomer occurs. Renal dysfunction may increase both the plasma concentration and body residence time of NSAIDs, thereby increasing the risk of adverse effects. The concomitant effects of anaesthesia have not yet been studied. The principal concern regarding the use of perioperative NSAIDs is the risk of decreased haemostasis and wound healing. Although it has been found that

  16. Consumption and awareness of students about nonsteroidal anti-inflammatory drugs

    Wawryk-Gawda Ewelina


    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are used by millions of people worldwide to neutralize pain that is of different origin, as well as to treat fever and inflammation. However, NSAIDs misuse/overuse can induce many adverse effects and some potentially serious complications. The aim of the our study was to ascertain young people’s knowledge about non-steroidal anti-inflammatory drugs. The research tool was a questionnaire. This study was carried out among students of the Medical University in Lublin, and it involved 236 persons of an average age of 20 years. The questions were intended to assess the frequency of NSAIDs use and the general knowledge that is held with respect to them. The results of this work show that more than 77% of the respondents confirmed that they use NSAIDs. Our results revealed no statistical correlation between the place of living or origin and the use of this drug. Hence, it can be said that while young adults quite often use NSAIDs, their knowledge about the dangers associated with the use of NSAIDs is low. Therefore, it is necessary to more intensively disseminate knowledge on the potential adverse effects of NSAID utilization.

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

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


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

  18. [Uricosuric agent].

    Ohno, Iwao


    Urate lowering treatment is indicated in patients with recurrent acute attacks, tophi, gouty arthropathy, radiographic changes of gout, multiple joint involvement, or associated uric acid nephrolithiasis. Uricosuric agents like benzbromarone and probenecid are very useful to treat hyperuricemia as well as allopurinol (xanthine oxidase inhibitor). Uricosuric agents act the urate lowering effect through blocking the URAT1, an urate transporter, in brush border of renal proximal tubular cells. In order to avoid the nephrotoxicity and urolithiasis due to increasing of urinary urate excretion by using uricosuric agents, the proper urinary tract management (enough urine volume and correction of aciduria) should be performed.

  19. Antibiotic Agents

    ... Superbugs and Drugs" Home | Contact Us General Background: Antibiotic Agents What is an antibacterial and how are ... with the growth and reproduction of bacteria. While antibiotics and antibacterials both attack bacteria, these terms have ...

  20. Vasoactive Agents

    Husedzinovic, Ino; Bradic, Nikola; Goranovic, Tanja


    This article is a short review of vasoactive drugs which are in use in todays clinical practice. In the past century, development of vasoactive drugs went through several phases. All of these drugs are today divided into several groups, depending on their place of action, pharmacological pathways and/or effects on target organ or organ system. Hence, many different agents are today in clinical practice, we have shown comparison between them. These agents provide new directions in the treatmen...

  1. Chemoprevention by nonsteroidal anti-inflammatory drugs eliminates oncogenic intestinal stem cells via SMAC-dependent apoptosis

    Qiu, W.; Wang, X.; Leibowitz, B.; Liu, H.; Barker, N.; Okada, H.; Oue, N.; Yasui, W.; Clevers, H.; Schoen, R.E.; Yu, J.; Zhang, L.


    Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac effectively prevent colon cancer in humans and rodent models. However, their cellular targets and underlying mechanisms have remained elusive. We found that dietary sulindac induced apoptosis to remove the intestinal stem cells with nucl

  2. Renal targeting of a non-steroidal antiinflammatory drug : effects on renal prostaglandin synthesis in the rat

    Haas, M; Moolenaar, F; Meijer, DKF; de Jong, PE; de Zeeuw, D


    1, Renal specific targeting of the non-steroidal anti-inflammatory drug naproxen was obtained by coupling to the low-molecular-mass protein lysozyme. A previous study showed that conjugation to lysozyme resulted in a 70-fold increase of naproxen accumulation in the kidney with a subsequent renal rel

  3. Blødende peptisk ulcus. Helicobacter pylori -praevalens og forbrug af non-steroide antiinflammatoriske stoffer/acetylsalicylsyre

    Vestergaard, Anders; Bredahl, Kim; de Muckadell, Ove B Schaffalitzky


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

  4. Exacerbation of inflammatory bowel disease by nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors:Fact or fiction?

    Mario Guslandi


    The existence of a possible link between inflammatory bowel disease (IBD) and nonsteroidal anti-inflammatory drugs (NSAIDs) has been repeatedly suggested. Recently, a few studies have addressed the issue of a possible,similar effect by selective cyclooxygenase-2 inhibitors (COXIBs). The present article reviews the available scientific evidence for this controversial subject.

  5. [Inotropic agents].

    Sasayama, Shigetake


    Depression of myocardial contractility plays an important role in the development of heart failure and many inotropic agents were developed to improve the contractile function of the failing heart. Agents that increase cyclic AMP, either by increasing its synthesis or reducing its degradation, exerted dramatic short-term hemodynamic benefits, but these acute effects were not extrapolated into long-term improvement of the clinical outcome of heart failure patients. Administration of these agents to an energy starved failing heart would be expected to increase myocardial energy use and could accelerate disease progression. The role of digitalis in the management of heart failure has been controversial, however, the recent large scale clinical trial has ironically proved that digoxin reduced the rate of hospitalization both overall and for worsening heart failure. More recently, attention was paid to other inotropic agents that have a complex and diversified mechanism. These agents have some phosphodiesterase-inhibitory action but also possess additional effects, including cytokine inhibitors, immunomodulators, or calcium sensitizers. In the Western Societies these agents were again shown to increase mortality of patients with severe heart failure in a dose dependent manner with the long-term administration. However, it may not be the case in the Japanese population in whom mortality is relatively low. Chronic treatment with inotropic agent may be justified in Japanese, as it allows optimal care in the context of relief of symptoms and an improved quality of life. Therefore, each racial group should obtain specific evidence aimed at developing its own guidelines for therapy rather than translating major guidelines developed for other populations.

  6. Coordination Polymers Derived from Non-Steroidal Anti-Inflammatory Drugs for Cell Imaging and Drug Delivery.

    Paul, Mithun; Dastidar, Parthasarathi


    A new series of Mn(II) coordination polymers, namely, [{Mn(L)(H2 O)2 }⋅2 Nap]∞ (CP1), [{Mn(L)(Ibu)2 (H2 O)2 }]∞ (CP2), [{Mn(L)(Flr)2 (H2 O)2 }]∞ (CP3), [{Mn(L)(Ind)2 (H2 O)2 }⋅H2 O]∞ (CP4), [{Mn2 (L)2 (μ-Flu)4 (H2 O)}⋅L]∞ (CP5), [{Mn2 (L)2 (μ-Tol)4 (H2 O)2 }]∞ (CP6) and [{Mn2 (L)2 (μ-Mef)4 (H2 O)2 }]∞ (CP7) (Nap=naproxen, Ibu=ibuprofen, Flr=flurbiprofen, Ind=indometacin, Flu=flufenamic acid, Tol=tolfenamic acid and Mef=mefenamic acid) derived from various non-steroidal anti-inflammatory drugs (NSAIDs) and the organic linker 1,2-bis(4-pyridyl)ethylene (L) have been synthesized with the aim of being used for cell imaging and drug delivery. Single-crystal X-ray diffraction (SXRD) studies revealed that the NSAID molecules were part of the coordination polymeric network either through coordination to the metal center (in the majority of the cases) or through hydrogen bonding. Remarkably, all the Mn(II) coordination polymers were found to be soluble in DMSO, thereby making them particularly suitable for the desired biological applications. Two of the coordination polymers (namely, CP1 and CP3) reported herein, were found to be photoluminescent both in the solid as well as in the solution state. Subsequent experiments (namely, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), and PGE2 (prostaglandin E2 ) assays) established their biocompatibility and anti-inflammatory response. In vitro studies by using a macrophage cell line (i.e., RAW 264.7) revealed that both CP1 and CP3 were excellent cell imaging agents. Finally, biodegradability studies under simulated physiological conditions in phosphate-buffered saline (PBS) at pH 7.6 showed that slow and sustained release of the corresponding NSAID was indeed possible from both CP1 and CP3.

  7. Nonsteroidal anti-inflammatory drug use and breast cancer risk: a Danish cohort study

    Friis, Søren; Thomassen, Lars; Sørensen, Henrik T


    Epidemiologic studies investigating the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on breast cancer have yielded conflicting results. We examined the association between use of aspirin and nonaspirin NSAIDs and breast cancer risk among 28 695 women in the Danish Diet, Cancer...... and Health cohort. Information on NSAID and paracetamol use was obtained from a self-administered questionnaire completed at baseline (1993-1997) and updated through 2003 using a nationwide prescription database. Detailed information on breast cancer incidence and tumour characteristics was obtained from...... nationwide health registers. Cox proportional hazards regression was used to compute incidence rate ratios (RRs) and 95% confidence intervals (CIs). We identified 847 breast cancer cases over an average follow-up period of 7.5 years. Any NSAID use at baseline was associated with an increased incidence...

  8. Use of nonsteroidal anti-inflammatory drugs and risk of endometrial cancer

    Brøns, Nanna; Baandrup, Louise; Dehlendorff, Christian


    PURPOSE: We examined the association between use of low-dose aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) and endometrial cancer risk in a nationwide case-control study. METHODS: Cases were all women in Denmark diagnosed with endometrial cancer during 2000-2009. Age...... for potential confounders. Analyses were stratified by endometrial cancer type, and potential effect modification by parity, obesity, and hormone replacement therapy (HRT) use was investigated. RESULTS: We identified 5,382 endometrial cancer cases and 72,127 controls. Endometrial cancer was not associated...... with use of low-dose aspirin (OR 0.97, 95 % CI 0.89-1.05) or non-aspirin NSAIDs (OR 0.96, 95 % CI 0.91-1.02) compared with nonuse. The ORs did not vary with increasing duration or intensity of NSAID use or with type of endometrial cancer. Interaction analyses showed reduced endometrial cancer risk...

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

    Skriver, Charlotte; Dehlendorff, Christian; Borre, Michael


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

  10. Non-steroidal anti-inflammatory drugs and renal response to exercise

    Olsen, Niels Vidiendal; Jensen, N G; Hansen, J M


    Nabumetone, a newer non-steroidal anti-inflammatory drug (NSAID) which preferentially blocks cyclo-oxygenase-2 activity, may be less nephrotoxic than indomethacin. This study tested whether nabumetone has effects different from those of indomethacin on exercise-induced changes in renal function...... at baseline, during graded 20-min exercise sessions at 25%, 50% and 75% of the maximal oxygen uptake rate, and subsequently during two 1-h recovery periods. Heart rate, arterial blood pressure, cardiac output and plasma catecholamines at rest and during exercise were not altered by indomethacin or nabumetone....... Indomethacin decreased urinary rates of excretion of 6-oxo-prostaglandin F(1alpha) (6-oxo-PGF(1alpha)) and thromboxane B(2) in all study periods. Nabumetone decreased 6-oxo-PGF(1alpha) excretion during and after exercise. Excretion rates for PGE(2) did not change. Neither indomethacin nor nabumetone changed...

  11. Herbal Remedy: An Alternate Therapy of Nonsteroidal Anti-Inflammatory Drug Induced Gastric Ulcer Healing

    Ananya Chatterjee


    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are one of the most commonly used therapeutic drug groups used worldwide for curing an array of health problems like pain, inflammation, cardiovascular complications, and many other diseases, but they may cause different side effects including gastroduodenal disorders. So, there is a growing interest and need to search for nontoxic, antiulcer formulations from medicinal plants to treat NSAIDs induced gastric ulcer. Extensive research has reported on many natural plants like Camellia sinensis, Phyllanthus emblica, Myristica malabarica, Piper betle, Picrorhiza kurroa, and so forth, and their active constituents reduced NSAIDs induced gastric ulcer via their antioxidative as well as immunomodulatory activity. Therefore, use of herbal formulations in daily life may prevent NSAIDs induced gastric ulceration and other side effects.

  12. The effect of nonsteroidal anti-inflammatory drugs on the equine intestine.

    Marshall, J F; Blikslager, A T


    Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in the management of pain and endotoxaemia associated with colic in the horse. While NSAIDs effectively treat the symptoms of colic, there is evidence to suggest that their administration is associated with adverse gastrointestinal effects including right dorsal colitis and inhibition of mucosal barrier healing. Several studies have examined the pathophysiology of NSAID associated effects on the large and small intestine in an effort to avoid these complications and identify effective alternative medications. Differences in the response of the large and small intestines to injury and NSAID treatment have been identified. Flunixin meglumine has been shown in the small intestine to inhibit barrier function recovery and increase permeability to lipopolysaccharide (LPS). A range of NSAIDs has been examined in the small intestine and experimental evidence suggests that those NSAIDs with cyclooxygenase independent anti-inflammatory effects or a COX-2 selective mode of action may offer significant advantages over traditional NSAIDs.

  13. The non-steroidal anti-inflammatory drug diclofenac is readily biodegradable in agricultural soils

    Al-Rajab, Abdul Jabbar; Sabourin, Lyne [Agriculture and Agri-Food Canada, London, ON, Canada N5V 4T3 (Canada); Lapen, David R. [Agriculture and Agri-Food Canada, Ottawa ON, Canada K1A 0C6 (Canada); Topp, Edward, E-mail: [Agriculture and Agri-Food Canada, London, ON, Canada N5V 4T3 (Canada)


    Diclofenac, 2-[2-[(2,6-dichlorophenyl)amino]phenyl]acetic acid, is an important non-steroidal anti-inflammatory drug widely used for human and animals to reduce inflammation and pain. Diclofenac could potentially reach agricultural lands through the application of municipal biosolids or wastewater, and in the absence of any environmental fate data, we evaluated its persistence in agricultural soils incubated in the laboratory. {sup 14}C-Diclofenac was rapidly mineralized without a lag when added to soils varying widely in texture (sandy loam, loam, clay loam). Over a range of temperature and moisture conditions extractable {sup 14}C-diclofenac residues decreased with half lives < 5 days. No extractable transformation products were detectable by HPLC. Diclofenac mineralization in the loam soil was abolished by heat sterilization. Addition of biosolids to sterile or non-sterile soil did not accelerate the dissipation of diclofenac. These findings indicate that diclofenac is readily biodegradable in agricultural soils.

  14. Use of nonsteroidal anti-inflammatory drugs prior to chronic renal replacement therapy initiation

    Fosbøl, Emil L; Kamper, Anne-Lise; Køber, Lars;


    PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with severe renal complications, including acute renal failure, reduced glomerular filtration rate and interstitial nephritis. Caution against NSAIDs is therefore recommended in advanced chronic kidney disease. In this study......, we examined NSAID use, aetiology and comorbidity among a national cohort of patients before the initiation of chronic renal replacement therapy (RRT). METHODS: Patients initiated on chronic RRT in the period 1997-2006 were identified in the Danish National Registry on Regular Dialysis...... and Transplantation, including etiological diagnosis. The use of NSAID before the start of RRT was studied by linkage to the National Prescription Register and comorbidity by linkage to the National Patient Registry. RESULTS: A total of 6663 patients were included in the study, and 2407 patients (36.1%) were...

  15. Sunscreening Agents

    Martis, Jacintha; Shobha, V; Sham Shinde, Rutuja; Bangera, Sudhakar; Krishnankutty, Binny; Bellary, Shantala; Varughese, Sunoj; Rao, Prabhakar; Naveen Kumar, B.R.


    The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines. The United States Food and Drug Administration and European Union have incorporated changes in their guidelines to help consumers select products based on their sun protection factor and protection against ultraviolet radiation, whereas the Indian regulatory agency has not yet issued any special guidance on sunscreening agents, as they are classified under cosmetics. In this article, the authors discuss the pharmacological actions of sunscreening agents as well as the available formulations, their benefits, possible health hazards, safety, challenges, and proper application technique. New technologies and scope for the development of sunscreening agents are also discussed as well as the role of the physician in patient education about the use of these agents. PMID:23320122

  16. Mobile Agents

    Satoh, Ichiro

    Mobile agents are autonomous programs that can travel from computer to computer in a network, at times and to places of their own choosing. The state of the running program is saved, by being transmitted to the destination. The program is resumed at the destination continuing its processing with the saved state. They can provide a convenient, efficient, and robust framework for implementing distributed applications and smart environments for several reasons, including improvements to the latency and bandwidth of client-server applications and reducing vulnerability to network disconnection. In fact, mobile agents have several advantages in the development of various services in smart environments in addition to distributed applications.

  17. Synthesis, crystal structure and spectroscopy of bioactive Cd(II) polymeric complex of the non-steroidal anti-inflammatory drug diclofenac sodium: Antiproliferative and biological activity

    Tabrizi, Leila; Chiniforoshan, Hossein; McArdle, Patrick


    The interaction of Cd(II) with the non-steroidal anti-inflammatory drug diclofenac sodium (Dic) leads to the formation of the complex [Cd2(L)41.5(MeOH)2(H2O)]n(L = Dic), 1, which has been isolated and structurally characterized by X-ray crystallography. Diclofenac sodium and its metal complex 1 have also been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines, MCF-7 (breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma), and a mouse fibroblast L-929 cell line. The results of cytotoxic activity in vitro expressed as IC50 values indicated the diclofenac sodium and cadmium chloride are non active or less active than the metal complex of diclofenac (1). Complex 1 was also found to be a more potent cytotoxic agent against T-24 and MCF-7 cancer cell lines than the prevalent benchmark metallodrug, cisplatin, under the same experimental conditions. The superoxide dismutase activity was measured by Fridovich test which showed that complex 1 shows a low value in comparison with Cu complexes. The binding properties of this complex to biomolecules, bovine or human serum albumin, are presented and evaluated. Antibacterial and growth inhibitory activity is also higher than that of the parent ligand compound.

  18. Multitarget fatty acid amide hydrolase/cyclooxygenase blockade suppresses intestinal inflammation and protects against nonsteroidal anti-inflammatory drug-dependent gastrointestinal damage.

    Sasso, Oscar; Migliore, Marco; Habrant, Damien; Armirotti, Andrea; Albani, Clara; Summa, Maria; Moreno-Sanz, Guillermo; Scarpelli, Rita; Piomelli, Daniele


    The ability of nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit cyclooxygenase (Cox)-1 and Cox-2 underlies the therapeutic efficacy of these drugs, as well as their propensity to damage the gastrointestinal (GI) epithelium. This toxic action greatly limits the use of NSAIDs in inflammatory bowel disease (IBD) and other chronic pathologies. Fatty acid amide hydrolase (FAAH) degrades the endocannabinoid anandamide, which attenuates inflammation and promotes GI healing. Here, we describe the first class of systemically active agents that simultaneously inhibit FAAH, Cox-1, and Cox-2 with high potency and selectivity. The class prototype 4: (ARN2508) is potent at inhibiting FAAH, Cox-1, and Cox-2 (median inhibitory concentration: FAAH, 0.031 ± 0.002 µM; Cox-1, 0.012 ± 0.002 µM; and Cox-2, 0.43 ± 0.025 µM) but does not significantly interact with a panel of >100 off targets. After oral administration in mice, ARN2508 engages its intended targets and exerts profound therapeutic effects in models of intestinal inflammation. Unlike NSAIDs, ARN2508 causes no gastric damage and indeed protects the GI from NSAID-induced damage through a mechanism that requires FAAH inhibition. Multitarget FAAH/Cox blockade may provide a transformative approach to IBD and other pathologies in which FAAH and Cox are overactive.

  19. Motion – Cyclo-oxygenase-2 Selective Nonsteroidal Anti-Inflammatory Drugs are as Safe as Placebo for the Stomach: Arguments Against the Motion

    Andreas Maetzel


    Full Text Available Cyclo-oxygenase (COX exists in two isoforms, COX-1 and COX-2, that direct the synthesis of prostaglandins, prostacyclin and thromboxane. Traditional nonsteroidal anti-inflammatory drugs (NSAIDs inhibit both isoenzymes, resulting in damage to the mucosa of the stomach and duodenum, but also in cardioprotection. Selective COX-2 inhibitors are less likely to damage the upper gastrointestinal tract, as has been shown by large, randomized, controlled trials. Specifically, the newer agents are superior to ibuprofen and naproxen in this regard, but celecoxib and diclofenac were not significantly different in patients who were not also taking low-dose acetylsalicylic acid. These studies did not include a placebo arm, however, and controlled comparisons of COX-2 inhibitors with placebo have not enlisted enough subjects to demonstrate conclusively that they are equally safe. Selectivity for the COX-2 isoform affords protection against upper gastrointestinal toxicity possibly at the expense of the cardioprotective effect of traditional NSAIDs. This might explain the higher rate of nonfatal myocardial infarction in patients who aregiven rofecoxib compared with naproxen. A traditional NSAID, combined with either misoprostol or a proton pump inhibitor, is still a suitable alternative to selective COX-2 inhibitors for the treatment of arthritis.

  20. Radioprotective Agents


    claimed to be effective are gallic acid derivatives, eg, sodium gallate 12053-21-61 (295-297) and propyl gallate 1121-79-91 (298). p...inhibition of a-adrenergic receptors can be achieved through the use of the antiradiation agents 2-(5-aminopentylamino)ethanephos- phorothioic acid ...tissue was ap- preciated immediately as a potential medical set, and they were put to use en- thusiastically. Early workers did notice an erythematous

  1. Endocrinological properties of two novel nonsteroidal progesterone receptor modulators, CP8816 and CP8863.

    Kurata, Yasushi; Tabata, Yuji; Shinei, Rie; Iizuka, Yumiko; Masuda, Naomi Takei; Kurihara, Ken-ichi; Okonogi, Tsuneo; Hoshiko, Shigeru


    We have isolated PF1092A, B, and C, novel nonsteroidal progesterone ligands with preferential affinity for the progesterone receptor, from fermentation broth of a fungus [Tabata Y, Miike N, Hatsu M, Kurata Y, Yaguchi T, Someya A, Miyadoh S, Hoshiko S, Tsuruoka T, and Omoto S (1997) J Antibiot 50:304-308; Tabata Y, Hatsu M, Kurata Y, Miyajima K, Tani M, Sasaki T, Kodama Y, Tsuruoka T, and Omoto S (1997) J Antibiot 50:309-313]. The original skeleton of PF1092, tetrahydronaphthofuranone, was modified synthetically to produce a new skeleton, tetrahydrobenzindrone, and in the present study, biological activities of two derivatives, CP8816 [(4aR,5R,6R,7R)-6-(N,N-dimethylaminocarbonyl)oxy-7-methoxy-4a,5,6,7-tetrahydro-1,3,4a,5-tetramethylbenz[f]indol-2(4H)-one] and CP8863 [(4aR,5R,6R,7R)-7-hydroxy-6-(N-methylcarbamoyl)oxy-4a,5,6,7-tetrahydro-1,3,4a,5-tetramethylbenz[f]indol-2(4H)-one], were investigated. Both CP8816 and CP8863 demonstrated selective binding to progesterone receptor and partial agonistic activity in a progesterone-dependent endogenous alkaline phosphatase expression assay. In the Clauberg-McPhail test, progestational activity of CP8816 (0.1 mg/kg s.c. or 10 mg/kg p.o.) was comparable to that of progesterone (0.15 mg/kg s.c.), and oral administration of CP8863 at more than 1.0 mg/kg also exerted similar effects. Anti-estrogenic (antiuterotropic) activity was confirmed on daily oral application of more than 0.1 mg/kg CP8863 for 3 days by inhibition of estrogen-dependent uterine wet weight gain in ovariectomized rats. CP8816 also exerted antiuterotropic activity at doses of 10 mg/kg (s.c.) and 100 mg/kg (p.o.). These results indicate that our nonsteroidal progesterone ligands have affinity for the progesterone receptor with partial progestational activity in vitro and clear progestational effects in vivo. Thus, these progesterone receptor modulator profiles suggest that CP8863 and CP8816 are good candidate compounds for treatment of hormone

  2. [Cardiovascular side effects of non-steroidal anti-inflammatory drugs in the light of recent recommendations. Diclofenac is not more dangerous].

    Horváth, Viktor József; Tabák, Gy Ádám; Szabó, Gergely; Putz, Zsuzsanna; Koós, Csaba Géza; Lakatos, Péter


    Among their beneficial effects, non-steroidal anti-inflammatory drugs may also exert several side effects which depend on the dosage and the type of these medications. The most frequent gastrointestinal side effects usually develop shortly after the beginning of their administration, but others such as cardiovascular interactions (which are present much less frequently than gastrointestinal side effects) can also occur after the beginning of drug administration without a latency period. For a long-term treatment, non-steroidal anti-inflammatory drugs are most frequently used in the elderly population where patients typically have high cardiovascular risk and take other medicines, e.g. low dose acetylsalicylic acid that can interact with non-steroidal anti-inflammatory drugs; in this aspect diclofenac may cause less side effects. In this review, the authors briefly review cardiovascular side effects of non-steroidal anti-inflammatory drugs, the processes which potentially influence them, therapeutic consequences and their interaction with acetylsalicylic acid.

  3. Editorial Commentary: The Efficacy of Nonsteroidal Anti-inflammatory Drugs for Prophylaxis of Heterotopic Ossification in Hip Arthroscopy--Do We Treat Patients or X-rays?

    Miller, G Klaud


    A systematic review of 5 series comparing the incidence of heterotopic ossification after hip arthroscopy with and without nonsteroidal anti-inflammatory drug prophylaxis showed a statistically significant improvement with the use of prophylaxis.

  4. Topical nonsteroidal anti-inflammatory drugs for the treatment of pain due to soft tissue injury: diclofenac epolamine topical patch

    Lionberger, David R; Brennan, Michael J.


    David R Lionberger1, Michael J Brennan21Southwest Orthopedic Group, Houston, TX, USA; 2Department of Medicine, Bridgeport Hospital, Bridgeport, CT, USAAbstract: The objective of this article is to review published clinical data on diclofenac epolamine topical patch 1.3% (DETP) in the treatment of acute soft tissue injuries, such as strains, sprains, and contusions. Review of published literature on topical nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac, and DETP in patients with ac...

  5. Non-steroidal Anti-inflammatory Drugs Ranking by Nondeterministic Assessments of Probabilistic Type

    Madalina luiza MOLDOVEANU


    Full Text Available With a number of common therapeutic prescriptions, common mechanisms, common pharmacological effects - analgesic, antipyretic and anti-inflammatory (acetaminophen excepted, common side effects (SE (platelet dysfunction, gastritis and peptic ulcers, renal insufficiency in susceptible patients, water and sodium retention, edemas, nephropathies, and only a few different characteristics – different chemical structures, pharmacokinetics and different therapeutic possibility, different selectivities according to cyclooxygenase pathway 1 and 2, non-steroidal anti-inflammatory drugs (NSAIDs similarities are more apparent than differences. Being known that in a correct treatment benefits would exceed risks, the question “Which anti-inflammatory drug presents the lowest risks for a patient?” is just natural. By the Global Risk Method (GRM and the Maximum Risk Method (MRM we have determined the ranking of fourteen NSAIDs considering the risks presented by each particular NSAID. Nimesulide, Etoricoxib and Celecoxib safety level came superior to the other NSAIDs, whereas Etodolac and Indomethacin present an increased side effects risk.

  6. Non-steroidal anti-inflammatory drug prescriptions in hospital inpatients: are we assessing the risks?

    Kitchen, J


    AIM: To determine non-steroidal anti-inflammatory drug (NSAID) prescribing practices in a tertiary referral hospital. METHODS: A single time-point audit of drug kardexes and clinical notes of n = 388 patients on 2 July 2008 was carried out assessing demographics, gastrointestinal and coronary heart disease risk factors, renal function and co-prescribed medications. RESULTS: Fifty-seven of 388 (14.7%) hospital patients were on NSAIDs. Forty-nine were prescribed NSAID after admission. Nineteen (32.2%) were on regular NSAID (11\\/19 on PPI) and 38 patients were on PRN NSAID (12\\/38 on PPI). Seventeen of 49 patients were on other medications associated with gastrointestinal bleeding (10\\/17 were on PPI). Nineteen patients (33.3%) were >60 years. Eight patients had three or four risk factors for gastrointestinal bleeding; six were on PPI. Thirteen patients had two risks; 7 were on PPI. Six of 19 patients with one risk factor were on PPI. 40.3% had stage 2\\/3 chronic kidney disease. 35.1% had ischaemic heart disease. CONCLUSIONS: NSAIDs and PPIs are often prescribed inappropriately.

  7. Transdermal enhancement effect and mechanism of iontophoresis for non-steroidal anti-inflammatory drugs.

    Zuo, Jing; Du, Lina; Li, Miao; Liu, Boming; Zhu, Weinan; Jin, Yiguang


    Iontophoresis is an important approach to improve transdermal drug delivery. However, The transdermal enhancement mechanism of iontophoresis was not well known. The relationship between the physicochemical properties of drugs and the transdermal enhancement effect of iontophoresis was revealed in this study. Non-steroidal anti-inflammatory drugs (NSAIDs) were used as the models, including aspirin, ibuprofen and indomethacin. Their oil-water partition coefficients were measured. The carbomer-based hydrogels of them were prepared. Iontophoresis significantly enhanced in vitro transdermal delivery across the rat skins. Strong lipophilicity could lead to high permeation of drugs. However, the dissociation extent (indicated as pKa) of drugs was the key factor to determine the transdermal enhancement effect of iontophoresis. The more dissociation the drugs were, the higher the transdermal enhancement effect of iontophoresis. The drug-loaded hydrogels combined with iontophoresis improved the treatment of rat raw's inflammatory syndrome. Iontophoresis significantly improved the drugs penetrating into the hypodermis, dermis and epidermis, more deeply than the application of drugs alone according to the experimental result of 5-carboxylfluorescein hydrogels. Iontophoresis led to the unordered arrangement of skin intercellular lipids, the significantly increased flowability and loose stratum corneum structure. Iontophoresis is a promising approach to improve transdermal drug delivery with safety and high efficiency.

  8. Nonsteroidal anti-inflammatory drug use and Alzheimer's disease risk: the MIRAGE Study

    Huyck Matthew


    Full Text Available Abstract Background Nonsteroidal anti-inflammatory drugs (NSAID use may protect against Alzheimer's disease (AD risk. We sought examine the association between NSAID use and risk of AD, and potential effect modification by APOE-ε4 carrier status and ethnicity. Methods The MIRAGE Study is a multi-center family study of genetic and environmental risk factors for AD. Subjects comprised 691 AD patients (probands and 973 family members enrolled at 15 research centers between 1996 and 2002. The primary independent and dependent variables were prior NSAID use and AD case status, respectively. We stratified the dataset in order to evaluate whether the association between NSAID use and AD was similar in APOE-ε4 carriers and non-carriers. Ethnicity was similarly examined as an effect modifier. Results NSAID use was less frequent in cases compared to controls in the overall sample (adjusted OR = 0.64; 95% CI = 0.38–1.05. The benefit of NSAID use appeared more pronounced among APOE-ε4 carriers (adjusted OR = 0.49; 95% CI = 0.24–0.98 compared to non-carriers, although this association was not statistically significant. The pattern of association was similar in Caucasian and African Americans. Conclusions NSAID use is inversely associated with AD and may be modified by APOE genotype. Prospective studies and clinical trials of sufficient power to detect effect modification by APOE-ε4 carrier status are needed.

  9. Promoting rational self-medication of nonsteroidal anti-inflammatory drugs in Nepal

    Santosh Thapa


    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are a commonly used class of drugs. They are used for self-medication worldwide including Nepal to treat self-limiting conditions, and mild to moderate symptoms associated with disease. Similar degree of care like prescription-only drugs is needed for these drugs as these are also linked with many adverse effects. However, nephrotoxicity remains a major concern with these drugs; other systems such as gastrointestinal, cardiovascular, hematologic, respiratory, and hepatic are also affected. The renal effects of analgesics are pronounced among patients with comorbid conditions, hypovolemic state of body and those with concomitant use of nephrotoxic or other drugs. A number of studies on self-medication all over the world have revealed that NSAIDs are the most commonly used drugs as self-medication. Easy access to these drugs either in pharmacy or in nonpharmacy outlets has become a reason for proper monitoring of over-the-counter use of these drugs. Responsibility remains with all healthcare professionals, either at individual or institutional level, to establish the balance between the benefits and risks associated with these drugs. The consumer who uses the drugs and the policy-framing bodies are others who could intervene in promoting the rational use of NSAIDs.

  10. Non-steroidal anti-inflammatory drugs and statins in relation to colorectal cancer risk

    Mazyar Shadman; Polly A Newcomb; John M Hampton; Karen J Wernli; Amy Trentham-Dietz


    AIM: To investigate the association between individual or combined use of non-steroidal anti-inflammatory drugs (NSAIDs) or statins and colorectal cancer risk. METHODS: In a population-based case-control study in women, we examined the association between NSAIDs and statin use and the risk of colorectal cancers. We further investigated whether the use of statins modifies the protective effect of NSAIDs. Female cases ( n = 669)of colorectal cancer aged 50-74 years were identified from a statewide registry in Wisconsin during 1999-2001. Community control women ( n = 1375) were randomly selected from lists of licensed drivers and Medicare beneficiaries. Medication use and risk factor information were gathered during a structured telephone interview. A multivariable logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval (CI). RESULTS: Overall, NSAIDs users had a 30% reduction in risk of colorectal cancer (95% CI: 0.56-0.88). Statin use was not associated with colorectal cancer risk (OR = 1.17, 95% CI: 0.74-1.85), regardless of structural type (lipophilic or hydrophilic), duration of use, or recency. There was no evidence of an interaction between NSAIDs and statins and colorectal cancer risk ( P-interaction = 0.28). CONCLUSION: Although our results confirm the inverse association between NSAIDs use and colorectal cancer risk, they do not support a risk reduction in statin users, or an interaction effect of combined NSAIDs and statin use.

  11. Influence of non-steroidal anti-inflammatory drugs on Drosophila melanogaster longevity.

    Danilov, Anton; Shaposhnikov, Mikhail; Shevchenko, Oksana; Zemskaya, Nadezhda; Zhavoronkov, Alex; Moskalev, Alexey


    Most age-related diseases and aging itself are associated with chronic inflammation. Thus pharmacological inhibition of inflammatory processes may be effective antiaging strategy. In this study we demonstrated that treatment of Drosophila melanogaster with 10 non-steroidal anti-inflammatory drugs (NSAIDs: CAY10404, aspirin, APHS, SC-560, NS-398, SC-58125, valeroyl salicylate, trans-resveratrol, valdecoxib, licofelone) leads to extension of lifespan, delays age-dependent decline of locomotor activity and increases stress resistance. The effect of the lifespan increase was associated with decrease of fecundity. Depending on the concentration, NSAIDs demonstrated both anti- and pro-oxidant properties in Drosophila tissues. However, we failed to identify clear correlation between antioxidant properties of NSAIDs and their pro-longevity effects. The lifespan extending effects of APHS, SC-58125, valeroyl salicylate, trans-resveratrol, valdecoxib, and licofelone were more pronounced in males, valdecoxib and aspirin - in females. We demonstrated that lifespan extension effect of NSAIDs was abolished in flies with defective genes involved in Pkh2-ypk1-lem3-tat2 pathway.

  12. Identification of New Nonsteroidal RORα Ligands; Related Structure-Activity Relationships and Docking Studies.

    Dubernet, Mathieu; Duguet, Nicolas; Colliandre, Lionel; Berini, Christophe; Helleboid, Stéphane; Bourotte, Marilyne; Daillet, Matthieu; Maingot, Lucie; Daix, Sébastien; Delhomel, Jean-François; Morin-Allory, Luc; Routier, Sylvain; Walczak, Robert


    A high throughput screen was developed to identify novel, nonsteroidal RORα agonists. Among the validated hit compounds, the 4-(4-(benzyloxy)phenyl)-5-carbonyl-2-oxo-1,2,3,4-tetrahydropyrimidine scaffold was the most prominent. Among the numerous analogues tested, compounds 8 and 9 showed the highest activity. Key structure-activity relationships (SAR) were established, where benzyl and urea moieties were both identified as very important elements to maintain the activity. Most notably, the SAR were consistent with the binding mode of the compound 8 (S-isomer) in the RORα docking model that was developed in this program. As predicted by the model, the urea moiety is engaged in the formation of key hydrogen bonds with the backbone of Tyr380 and Asp382. The benzyl group is located in a wide hydrophobic pocket. The structural relationships reported in this letter will help in further optimization of this compound series and will provide novel synthetic probes helpful for elucidation of complex RORα physiopathology.

  13. Pathogenesis of Nonsteroidal Anti-Inflammatory Drug Gastropathy: Clues to Preventative Therapy

    Salim MA Bastaki


    Full Text Available Gastric ulceration and bleeding are major impediments to the chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs. The development of effective therapies for prevention of these adverse effects requires better understanding of their pathogenesis. Several features of NSAIDs contribute to the development of damage in the stomach, including the topical irritant effects of these drugs on the epithelium, impairment of the barrier properties of the mucosa, suppression of gastric prostaglandin synthesis, reduction of gastric mucosal blood flow and interference with the repair of superficial injury. The presence of acid in the lumen of the stomach also contributes to the pathogenesis of NSAID-induced ulcers and bleeding in a number of ways. Acid impairs the restitution process, interferes with hemostasis and can inactivate several growth factors that are important in mucosal integrity and repair. Profound suppression of gastric acid secretion has been shown to be effective in preventing NSAID-induced ulceration. There is a strong possibility that new NSAIDs entering the market will have greatly reduced toxicity in the gastrointestinal tract.

  14. Chromatographic determination of aqueous dissociation constants of some water-insoluble nonsteroidal antiinflammatory drugs.

    Oumada, Fadoua Z; Ràfols, Clara; Rosés, Martí; Bosch, Elisabeth


    The purpose of this work is to propose a new, useful, and easy chromatographic method to determine accurately the aqueous dissociation constant of drugs sparingly soluble in water. The method uses the rigorous intersolvental pH scale, (w)(s)pH, i.e., the pH measurements are made in the mobile phase after mixing the aqueous buffer with methanol by a combined glass electrode previously standardised with common aqueous buffers. The measured pK allows the determination of the drug's pK(a) in the mobile phase, (w)(s)pK(a), which can be easily converted in the aqueous pK(a), (w)(w)pK(a), by means of previously established equations. A series of nonsteroidal carboxylic acids with antiinflammatory properties were selected to test the method because their aqueous pK(a) values, (w)(w)pK(a), had been previously evaluated from different approaches that gave consistent results. The comparison of the aqueous pK(a) values obtained by means of the proposed procedure with those of literature allows the accurate evaluation of this new methodology. The results obtained show very good precision and accuracy.

  15. The Time Delay Between Drug Intake and Bronchospasm for Nonsteroidal Antiinflammatory Drugs Sensitive Patients


    A study was performed to assess the time between drug intake and drug induced hypersensitivity reaction for patients sensitive to nonsteroidal antiinflammatory drugs (NSAID) in clinical patient history and after oral provocation tests. Drug hypersensitivity ENDA questionnaires were filled for the patients with suspected sensitivity to NSAID. Oral provocation tests were performed with suspected NSAID according to the ENDA/EAACI recommendations. There were 76 patients with history of hypersensitivity reactions after use of NSAID enrolled in the study. Recorded were 154 hypersensitivity reactions to NSAID in the clinical history. In the clinical history median time of immediate reactions (76 cases, 81%) between drug intake and bronchospasm was 20 minutes [15-30 minutes]. Median time of nonimmediate reactions (18 cases, 19%) was 120 minutes [120-390 minutes]. There were 50 oral provocation tests performed, 14 of them (28%) were positive. Median time between drug intake and immediate reactions (8; 57% of cases) was 22.5 minutes [20-30 minutes] and median time of nonimmediate reactions (6; 43% of cases) was 167.5 minutes [125-206.25 minutes]. Time delay between drug intake and bronchospasm in the clinical history and after oral provocation test was not statistically different. PMID:23282984

  16. Gastroprotective effect of zinc acexamate against damage induced by nonsteroidal antiinflammatory drugs. A morphological study.

    Bulbena, O; Escolar, G; Navarro, C; Bravo, L; Pfeiffer, C J


    The gastroprotective effect of zinc acexamate against gastric damage induced by different nonsteroidal antiinflammatory drugs (indomethacin, diclofenac, and piroxicam) was morphologically assessed in the rat glandular stomach by light and scanning electron microscopy. In addition, the capability of these antiinflammatory drugs to inhibit gastric prostaglandin E2 production was compared with their ability to induce gastric lesions. Microscopically, disappearance of mucus glycoprotein and exfoliation of the mucosal surface were the most common findings. Surface ultrastructural lesions varied from minimal lesions of the surface epithelial cells to deep erosions of the gastric mucosa with release of associated cellular elements and sloughing of the denuded lamina propria. Diclofenac elicited the most powerful inhibitory activity on mucosal prostaglandin E2 (98% inhibition vs control), closely followed by piroxicam (97.8%) and indomethacin (91.05%). Pretreatment of animals with zinc acexamate significantly increased the presence of mucus glycoprotein, maintained the continuity of the surface epithelial cells, and decreased the depth of the mucosal erosions. The degree of protection exerted by zinc acexamate varied with the antiinflammatory, but was always evident.

  17. Systematic review for evaluation of tolerability of nonsteroidal antiinflammatory drugs in osteoarthritis patients in Japan.

    Uemura, Shinichi; Ochi, Takahiro; Sugano, Kentaro; Makuch, Robert W


    To evaluate the gastrointestinal tolerability of nonsteroidal antiinflammatory drugs (NSAIDs) in osteoarthritis patients in Japan, a systematic review of Japanese randomized controlled trials was performed. This study consisted of double-blind, randomized, controlled clinical trials with 4-week NSAID treatment of osteoarthritis patients in Japan. The analysis included 4725 patients from 25 trials. On average the cumulative incidences of patients who had experienced any adverse reaction and any adverse digestive reaction were 14.3% [95% confidence interval (CI) 13.3%-15.3%] and 10.4% (95% CI 9.4%-11.4%), respectively. The cumulative incidence for the upper gastrointestinal (GI) symptoms such as abdominal pain, nausea/vomiting, and dyspepsia was estimated to be approximately 10.9%. When the risk of upper GI symptoms was compared between males and females, the summary odds ratio was 1.71 (95% CI 1.11-2.65). Comparing the risk of upper GI symptoms between patients 59 years of age and younger and those 60+ years old, the summary odds ratio was 1.07 (95% CI 0.75-1.52). Despite the incidence of adverse reactions varying across the drugs being used, there was an obvious increased risk of GI symptoms.

  18. Quality of Life in Arthritis Patients Using Nonsteroidal Anti-Inflammatory Drugs

    Ingela Wiklund


    Full Text Available Arthritis is a painful and disabling condition. To suppress the pain and the inflammatory process, patients are often chronic nonsteroidal anti-inflammatory drug (NSAID users. Chronic use of NSAIDs may induce peptic ulcer, dyspeptic problems and heartburn. Therefore, these patients are often provided with treatment to relieve and/or protect against gastrointestinal problems. Rheumatic disorders also affect a range of health-related quality of life domains. In one study, patients with NSAID-associated gastroduodenal lesions complained about lack of energy, sleep disturbances, emotional distress and social isolation in addition to pain and mobility limitations. The degree of distress and dysfunction differed markedly from scores in an unselected population. Clinical trial data suggest that acid-suppressing therapy with omeprazole is superior to therapy with misoprostol and ranitidine in healing gastroduodenal lesions and preventing abdominal pain, heartburn and indigestion symptoms during continued NSAID treatment. Because arthritic patients are severely incapacitated by their condition regarding most aspects of health-related quality of life, it is important to offer a treatment that is effective in healing and preventing NSAID-induced ulcers and gastrointestinal symptoms during continued NSAID treatment without further compromising the patients’ quality of life. Treatment with omeprazole once daily has been shown to be superior to that with ranitidine and misoprostol in this respect.

  19. Helicobacter pylori-negative, non-steroidal anti-inflammatory drug: negative idiopathic ulcers in Asia.

    Iijima, Katsunori; Kanno, Takeshi; Koike, Tomoyuki; Shimosegawa, Tooru


    Since the discovery of Helicobacter pylori (H. pylori) infection in the stomach, the bacteria infection and non-steroidal anti-inflammatory drugs (NSAIDs) use had been considered to be the 2 main causes of peptic ulcers. However, there have been recent reports of an increase in the proportion of peptic ulcers without these known risk factors; these are termed idiopathic peptic ulcers. Such trend was firstly indicated in 1990s from some reports in North America. In Asia, numerous studies reported that idiopathic ulcers accounted for a small percentage of all ulcers in the 1990s, but in the 2000s, multiple studies reported that the proportion of idiopathic ulcers had reached 10%-30%, indicating that the incidence of idiopathic ulcers in Asia has also been rising in recent years. While a decline in H. pylori infection rates of general population in Asia is seen as the main reason for the increased incidence of idiopathic ulcers, it is also possible that the absolute number of idiopathic ulcer cases has increased. Advanced age, serious systemic complication, and psychological stress are considered to be the potential risk factors for idiopathic ulcers. Management of idiopathic ulcers is challenging, at present, because there is no effective preventative measure against recurrence in contrast with cases of H. pylori-positive ulcers and NSAIDs-induced ulcers. As it is expected that H. pylori infection rates in Asia will decline further in the future, measures to treat idiopathic ulcers will also likely become more important.

  20. Lead evaluation of tetrahydroquinolines as nonsteroidal selective androgen receptor modulators for the treatment of osteoporosis.

    Nagata, Naoya; Furuya, Kazuyuki; Oguro, Nao; Nishiyama, Daisuke; Kawai, Kentaro; Yamamoto, Noriko; Ohyabu, Yuki; Satsukawa, Masahiro; Miyakawa, Motonori


    Tetrahydroquinoline (THQ) was deemed to be a suitable scaffold for our nonsteroidal selective androgen receptor modulator (SARM) concept. We adapted the strategy of switching the antagonist function of cyano-group-containing THQ (CN-THQ) to the agonist function and optimized CN-THQ as an orally available drug candidate with suitable pharmacological and ADME profiles. Based on binding mode analyses and synthetic accessibility, we designed and synthesized a compound that possesses a para-substituted aromatic ring attached through an amide linker. The long-tail THQ derivative 6-acetamido-N-(2-(8-cyano-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-4-yl)-2-methylpropyl)nicotinamide (1 d), which bears a para-acetamide-substituted aromatic group, showed an appropriate in vitro biological profile, as expected. We considered that the large conformational change at Trp741 of the androgen receptor (AR) and the hydrogen bond between 1 d and helix 12 of the AR could maintain the structure of the AR in its agonist form; indeed, 1 d displays strong AR agonistic activity. Furthermore, 1 d showed an appropriate in vivo profile for use as an orally available SARM, displaying clear tissue selectivity, with a separation between its desirable osteoanabolic effect on femoral bone mineral density and its undesirable virilizing effects on the uterus and clitoral gland in a female osteoporosis model.

  1. Design, Synthesis, and Biological Evaluation of Novel Nonsteroidal Farnesoid X Receptor (FXR) Antagonists: Molecular Basis of FXR Antagonism.

    Huang, Huang; Si, Pei; Wang, Lei; Xu, Yong; Xu, Xin; Zhu, Jin; Jiang, Hualiang; Li, Weihua; Chen, Lili; Li, Jian


    Farnesoid X receptor (FXR) plays an important role in the regulation of cholesterol, lipid, and glucose metabolism. Recently, several studies on the molecular basis of FXR antagonism have been reported. However, none of these studies employs an FXR antagonist with nonsteroidal scaffold. On the basis of our previously reported FXR antagonist with a trisubstituted isoxazole scaffold, a novel nonsteroidal FXR ligand was designed and used as a lead for structural modification. In total, 39 new trisubstituted isoxazole derivatives were designed and synthesized, which led to pharmacological profiles ranging from agonist to antagonist toward FXR. Notably, compound 5s (4'-[(3-{[3-(2-chlorophenyl)-5-(2-thienyl)isoxazol-4-yl]methoxy}-1H-pyrazol-1-yl)methyl]biphenyl-2-carboxylic acid), containing a thienyl-substituted isoxazole ring, displayed the best antagonistic activity against FXR with good cellular potency (IC50 =12.2 ± 0.2 μM). Eventually, this compound was used as a probe in a molecular dynamics simulation assay. Our results allowed us to propose an essential molecular basis for FXR antagonism, which is consistent with a previously reported antagonistic mechanism; furthermore, E467 on H12 was found to be a hot-spot residue and may be important for the future design of nonsteroidal antagonists of FXR.

  2. Graphene oxide-based microspheres for the dispersive solid-phase extraction of non-steroidal estrogens from water samples.

    Wen, Yingying; Niu, Zongliang; Ma, Yanling; Ma, Jiping; Chen, Lingxin


    A modified Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) method based on the dispersive solid-phase extraction (dSPE) combined with high performance liquid chromatography (HPLC) was developed for the determination of non-steroidal estrogens in water samples. In this study, graphene oxide-based silica microspheres (SiO2@GO) were used as dSPE material for the preconcentration of analytes. HPLC was used for the separation and detection. This was the first time that the synthesized SiO2@GO microspheres were used as stationary phases for the off-line preconcentration of the non-steroidal estrogens in dSPE. dSPE parameters, such as sample pH, volume and type of eluent were optimized. Application of the developed method to analyze spiked lake, reservoir and tap water samples resulted in good recoveries values ranging from 70 to 106% with relative standard deviation values lower than 7.0% in all cases. Limits of detection were in the range of 0.2-6.1 μg/L. The combined data obtained in this study recommended that the proposed method is very fast, simple, repeatable and accurate for the detection of non-steroidal estrogens. Furthermore, the SiO2@GO microspheres application could potentially be expanded to extract and pre-concentrate other compounds in various matrices.

  3. Trading Agents

    Wellman, Michael


    Automated trading in electronic markets is one of the most common and consequential applications of autonomous software agents. Design of effective trading strategies requires thorough understanding of how market mechanisms operate, and appreciation of strategic issues that commonly manifest in trading scenarios. Drawing on research in auction theory and artificial intelligence, this book presents core principles of strategic reasoning that apply to market situations. The author illustrates trading strategy choices through examples of concrete market environments, such as eBay, as well as abst

  4. Molecular dynamics in liquid and glassy states of non-steroidal anti-inflammatory drug: ketoprofen.

    Sailaja, U; Shahin Thayyil, M; Krishna Kumar, N S; Govindaraj, G


    Ketoprofen is a well known nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic effects. It acts by inhibiting the body's production of prostaglandin. The molecular mobility of amorphous ketoprofen has been investigated by broadband dielectric spectroscopy (BDS) covering wide temperature and frequency range. Multiple relaxation processes were observed. Besides the primary α-relaxation, one secondary relaxation, γ-have been identified. The γ-process visible in the dielectric spectra at very low temperature is non-JG relaxation, and has an activation energy E=37.91 kJ/mol typical for local mobility. Based on Ngai's coupling model smaller n or a larger Kohlrausch exponent (1-n) of the α-relaxation associated with larger τβ (Tg). In the case of ketoprofen we conclude that the secondary relaxation (β) emerging from intermolecular motions, is hidden under the dominant α-peak. The temperature dependence of the relaxation time of the α-process can be described over the entire measured range by a single Vogel-Fulcher-Tammann (VFT) equation. From VFT fits, the glass transition temperature (Tg) was estimated as 267.07 K, and a fragility or steepness index m=86.57 was calculated, showing that ketoprofen is a fragile glass former. Our differential scanning calorimetry (DSC) study shows that ketoprofen is a non-crystallizing compound. To confirm the hydrogen bond patterns of ketoprofen FTIR spectroscopy was applied in both crystalline and amorphous phases. Solubility test performed at 37 °C proved that amorphous phase is more soluble than the crystalline phase.

  5. Effects of non-steroidal anti-inflammatory drug (NSAID) diclofenac exposure in mussel Mytilus galloprovincialis.

    Gonzalez-Rey, Maria; Bebianno, Maria João


    In recent years, research studies have increasingly focused on assessing the occurrence of active pharmaceutical ingredients (APIs) in ecosystems. However, much remains unknown concerning the potential effects on APIs on non-target organisms due to the complexity of the mode of action, reactivity and bioconcentration potential for each specific drug. The non-steroidal anti-inflammatory drug (NSAID) diclofenac (DCF) is one of the most frequently detected APIs in surface waters worldwide and has recently been included in the list of priority substances under the European Commission. In this study, mussels (Mytilus galloprovincialis) were exposed to an environmentally relevant nominal concentration of DCF (250 ng L(-1)) over 15 days. The responses of several biomarkers were assessed in the mussel tissues: condition index (CI); superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and phase II glutathione-S-transferase (GST) activities, lipid peroxidation levels (LPO) associated with oxidative stress, acetylcholinesterase (AChE) activity related to neurotoxic effects and vitellogenin-like proteins linked to endocrine disruption. This study demonstrated significant induction of SOD and GR activities in the gills in addition to high CAT activity and LPO levels in the digestive gland. Phase II GST remained unaltered in both tissues, while the up-regulation of the AChE activity was directly related to the vitellogenin-like protein levels in exposed females, indicating an alteration in the estrogenic activity, rather than a breakdown in cholinergic neurotransmission function. This study confirmed that DCF at a concentration often observed in surface water induces tissue-specific biomarker responses. Finally, this study also revealed the importance of a multi-biomarker approach when assessing the potentially deleterious effects in a species that may be vulnerable to the continuously discharge of APIs into the ecosystems; this approach provides crucial new

  6. Insulinotropic effect of the non-steroidal compound STX in pancreatic β-cells.

    Ana B Ropero

    Full Text Available The non-steroidal compound STX modulates the hypothalamic control of core body temperature and energy homeostasis. The aim of this work was to study the potential effects of STX on pancreatic β-cell function. 1-10 nM STX produced an increase in glucose-induced insulin secretion in isolated islets from male mice, whereas it had no effect in islets from female mice. This insulinotropic effect of STX was abolished by the anti-estrogen ICI 182,780. STX increased intracellular calcium entry in both whole islets and isolated β-cells, and closed the K(ATP channel, suggesting a direct effect on β-cells. When intraperitoneal glucose tolerance test was performed, a single dose of 100 µg/kg body weight STX improved glucose sensitivity in males, yet it had a slight effect on females. In agreement with the effect on isolated islets, 100 µg/kg dose of STX enhanced the plasma insulin increase in response to a glucose load, while it did not in females. Long-term treatment (100 µg/kg, 6 days of male mice with STX did not alter body weight, fasting glucose, glucose sensitivity or islet insulin content. Ovariectomized females were insensitive to STX (100 µg/kg, after either an acute administration or a 6-day treatment. This long-term treatment was also ineffective in a mouse model of mild diabetes. Therefore, STX appears to have a gender-specific effect on blood glucose homeostasis, which is only manifested after an acute administration. The insulinotropic effect of STX in pancreatic β-cells is mediated by the closure of the K(ATP channel and the increase in intracellular calcium concentration. The in vivo improvement in glucose tolerance appears to be mostly due to the enhancement of insulin secretion from β-cells.

  7. Helicobacter pylori infection in bleeding peptic ulcer patients after non-steroidal antiinflammatory drug consumption

    Francesco Manguso; Elena Trimarco; Antonio Balzano; Elisabetta Riccio; Germana de Nucci; Maria Luisa Aiezza; Gerardino Amato; Linda Degl'Innocenti; Maria Maddalena Piccirillo; Gianfranco De Dominicis; Tara Santoro


    AIM: To establish the prevalence of Helicobacter pylori (H. pylori ) infection in patients with a bleeding peptic ulcer after consumption of non-steroidal antiinflammatory drugs (NSAIDs). METHODS: A very early upper endoscopy was performed to find the source of upper gastrointestinal bleeding and to take biopsy specimens for analysis of H. pylori infection by the rapid urease (CLO) test, histological examination, and bacterial culture. IgG anti- CagA were also sought. The gold standard for identifying H. pylori infection was positive culture of biopsy specimens or contemporary positivity of the CLO test and the presence of H. pylori on tissue sections. RESULTS: Eighty patients, 61 males (76.3%), mean age 61.2 ± 15.9 years, were consecutively enrolled. Forty-seven (58.8%) patients occasionally consumed NSAIDs, while 33 (41.3%) were on chronic treatment with low-dose aspirin (LD ASA). Forty-four (55.0%) patients were considered infected by H. pylori . The infection rate was not different between patients who occasionally or chronically consumed NSAIDs. The culture of biopsy specimens had a sensitivity of 86.4% and a specificity of 100%; corresponding figures for histological analysis were 65.9% and 77.8%, for the CLO test were 68.2% and 75%, for the combined use of histology and the CLO test were 56.8% and 100%, and for IgG anti-CagA were 90% and 98%. The highest accuracy (92.5%) was obtained with the culture of biopsy specimens. CONCLUSION: Patients with a bleeding peptic ulcer after NSAID/LD ASA consumption frequently have H. pylori infection. Biopsy specimen culture after an early upper gastrointestinal tract endoscopy seems the most efficient test to detect this infection.

  8. Role of Helicobacter pylori eradication in aspirin or non-steroidal anti-inflammatory drug users

    George V. Papatheodoridis; Athanasios J. Archimandritis


    Helicobacter pylori (H pylori) infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin at any dosage and formulation represent well-established risk factors for the development of uncomplicated and complicated peptic ulcer disease accounting for the majority of such cases. Although the interaction between H pylori and NSAID/aspirin use in the same individuals was questioned in some epidemiological studies, it has now become widely accepted that they are at least independent risk factors for peptic ulcer disease. According to data from randomized intervention trials, naive NSAID users certainly benefit from testing for H pylori infection and, if positive,H pylori eradication therapy prior to the initiation of NSAID. A similar strategy is also suggested for naive aspirin users, although the efficacy of such an approach has not been evaluated yet. Strong data also support that chronic aspirin users with a recent ulcer complication should be tested for H pyloriinfection and, if positive, receive H pylori eradication therapy after ulcer healing, while they appear to benefit from additional long-term therapy with a proton pump inhibitor (PPI).A similar approach is often recommended to chronic aspirin users at a high risk of ulcer complication. H pylori eradication alone does not efficiently protect chronic NSAID users with a recent ulcer complication or those at a high-risk, who certainly should be treated with long-term PPI therapy, but H pylori eradication may be additionally offered even in this setting. In contrast, testing for H pylorior PPI therapy is not recommended for chronic NSAID/aspirin users with no ulcer complications or those at a low risk of complications.

  9. The Toxicity of Nonsteroidal Anti-inflammatory Eye Drops against Human Corneal Epithelial Cells in Vitro.

    Lee, Jong Soo; Kim, Young Hi; Park, Young Min


    This study investigated the toxicity of commercial non-steroid anti-inflammatory drug (NSAID) eye solutions against corneal epithelial cells in vitro. The biologic effects of 1/100-, 1/50-, and 1/10-diluted bromfenac sodium, pranoprofen, diclofenac sodium, and the fluorometholone on corneal epithelial cells were evaluated after 1-, 4-, 12-, and 24-hr of exposure compared to corneal epithelial cell treated with balanced salt solution as control. Cellular metabolic activity, cellular damage, and morphology were assessed. Corneal epithelial cell migration was quantified by the scratch-wound assay. Compared to bromfenac and pranoprofen, the cellular metabolic activity of diclofenac and fluorometholone significantly decreased after 12-hr exposure, which was maintained for 24-hr compared to control. Especially, at 1/10-diluted eye solution for 24-hr exposure, the LDH titers of fluorometholone and diclofenac sodium markedly increased more than those of bromfenac and pranoprofen. In diclofenac sodium, the Na(+) concentration was lower and amount of preservatives was higher than other NSAIDs eye solutions tested. However, the K(+) and Cl(-) concentration, pH, and osmolarity were similar for all NSAIDs eye solutions. Bromfenac and pranoprofen significantly promoted cell migration, and restored wound gap after 48-hr exposure, compared with that of diclofenac or fluorometholone. At 1/50-diluted eye solution for 48-hr exposure, the corneal epithelial cellular morphology of diclofenac and fluorometholone induced more damage than that of bromfenac or pranoprofen. Overall, the corneal epithelial cells in bromfenac and pranoprofen NSAID eye solutions are less damaged compared to those in diclofenac, included fluorometholone as steroid eye solution.

  10. Mucosal acid causes gastric mucosal microcirculatory disturbance in nonsteroidal anti-inflammatory drug-treated rats.

    Funatsu, Toshiyuki; Chono, Koji; Hirata, Takuya; Keto, Yoshihiro; Kimoto, Aishi; Sasamata, Masao


    The mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) suppress gastric mucosal blood flow is not fully understood, although the depletion of mucosal prostaglandin E2 has been proposed as one possible explanation. We investigated the role of gastric acid on gastric mucosal blood flow in NSAID-treated rats. A rat stomach was mounted in an ex vivo chamber, and gastric mucosal blood flow was measured sequentially in a 5-mm2 area of the gastric corpus using a scanning laser Doppler perfusion image system. Results showed that diclofenac (5 mg/kg s.c.) and indomethacin (10 mg/kg s.c.) did not affect gastric mucosal blood flow, although both strongly decreased mucosal prostaglandin E2 when saline was instilled into the gastric chamber. On replacement of the saline in the chamber with 100 mM hydrochloric acid, these drugs caused a decrease in gastric mucosal blood flow levels within 30 min. The specific cyclooxygenase (COX)-2 inhibitors celecoxib (50 mg/kg s.c.) and rofecoxib (25 mg/kg s.c.) did not affect mucosal prostaglandin E2 level, nor did they decrease gastric mucosal blood flow, even when hydrochloric acid was added to the chamber. Furthermore, measurement of vasoconstrictive factors present in the mucosa showed that endothelin-1 levels increased after administration of diclofenac s.c. in the presence of intragastric hydrochloric acid. This indicates that the presence of mucosal hydrochloric acid plays an important role in the NSAID-induced decrease in gastric mucosal blood flow, while the COX-1-derived basal prostaglandin E2, which is unlikely to control gastric mucosal blood flow itself, protects microcirculatory systems from mucosal hydrochloric acid.

  11. Management of Nonsteroidal Anti-Inflammatory Drug-Induced Gastroduodenal Disease by Acid Suppression

    R Lad


    Full Text Available One major cause of peptic ulceration is the use of nonsteroidal anti-inflammatory drugs (NSAIDs. The precise mechanisms through which NSAIDs cause peptic ulceration are unknown, but the discovery that they reduce the production of ‘cytoprotective’ prostaglandins led to the hypothesis that coadministration of exogenous prostaglandins heals and prevents NSAID-induced gastroduodenal ulcers and other mucosal lesions. Studies using high doses of misoprostol have shown that it does have a protective effect; however, gastrointestinal intolerance of this prostaglandin E2 analogue is common. Early indications that acid suppression was effective in the management of NSAID-related peptic ulcers came from studies showing that gastric ulcers could be healed by omeprazole in patients who continued to take NSAIDs. Other studies suggested that acid suppression reduces the incidence of mucosal lesions but that standard dose ranitidine protects only against duodenal lesions. Subsequent studies reported that higher dose H2 receptor antagonist therapy can protect against both gastric and duodenal ulcers during continued NSAID therapy. An ideal therapeutic strategy would heal NSAID-related ulcers and prevent the development of new NSAID-related lesions and complications in patients who are unable to discontinue NSAID therapy. A number of recent studies indicate that effective acid-suppressive treatment with the proton pump inhibitor omeprazole can achieve these aims. Overall, data from recent studies show that acid suppression with the proton pump inhibitor omeprazole at a dose of 20 mg daily is the most effective means of healing NSAID-associated gastroduodenal lesions and that it is the most effective prophylactic therapy. In the long run, the role of omeprazole will have to be evaluated with respect to its cost effectiveness compared with other strategies and with respect to the development of less damaging NSAIDs.

  12. Selective non-steroidal inhibitors of 5 alpha-reductase type 1.

    Occhiato, Ernesto G; Guarna, Antonio; Danza, Giovanna; Serio, Mario


    The enzyme 5 alpha-reductase (5 alpha R) catalyses the reduction of testosterone (T) into the more potent androgen dihydrotestosterone (DHT). The abnormal production of DHT is associated to pathologies of the main target organs of this hormone: the prostate and the skin. Benign prostatic hyperplasia (BPH), prostate cancer, acne, androgenetic alopecia in men, and hirsutism in women appear related to the DHT production. Two isozymes of 5 alpha-reductase have been cloned, expressed and characterized (5 alpha R-1 and 5 alpha R-2). They share a poor homology, have different chromosomal localization, enzyme kinetic parameters, and tissue expression patterns. Since 5 alpha R-1 and 5 alpha R-2 are differently distributed in the androgen target organs, a different involvement of the two isozymes in the pathogenesis of prostate and skin disorders can be hypothesized. High interest has been paid to the synthesis of inhibitors of 5 alpha-reductase for the treatment of DHT related pathologies, and the selective inhibition of any single isozyme represents a great challenge for medical and pharmaceutical research in order to have more specific drugs. At present, no 5 alpha R-1 inhibitor is marketed for the treatment of 5 alpha R-1 related pathologies but pharmaceutical research is very active in this field. This paper will review the major classes of 5 alpha R inhibitors focusing in particular on non-steroidal inhibitors and on structural features that enhance the selectivity versus the type 1 isozyme. Biological tests to assess the inhibitory activity towards the two 5 alpha R isozymes will be also discussed.

  13. Association of individual non-steroidal anti-inflammatory drugs and chronic kidney disease: a population-based case control study.

    Ylenia Ingrasciotta

    Full Text Available Non-steroidal anti-inflammatory agents (NSAIDs are known to be associated with renal damage. No clear evidence exists regarding differential risk of chronic kidney disease (CKD, specifically, across various NSAIDs.The aim of this population-based case-control study was to evaluate the association between use of individual NSAIDs and risk of CKD in a general population of Southern Italy.A nested case-control study was carried out using the general practice Arianna database, identifying incident CKD patients as cases and matched controls from 2006 to 2011. The date of first CKD diagnosis was defined as the index date (ID. Conditional logistic regressions were performed to estimate the risk of CKD associated with NSAIDs by class and individual drugs as compared to non-use during different time windows (within one year, six or three months prior to ID, with the latter being defined as current users. Among current users, the effect of cumulative exposure to these drugs was evaluated.Overall, 1,989 CKD cases and 7,906 matched controls were identified. A statistically significant increase in the risk of CKD was found for current users of oxicams (adjusted OR: 1.68; 95% CI: 1.15-2.44 and concerning individual compounds, for ketorolac (adj. OR: 2.54; 95% CI: 1.45-4.44, meloxicam (adj. OR: 1.98; 95% CI: 1.01-3.87 and piroxicam (adj. OR: 1.95; 95% CI: 1.19-3.21.The risk of CKD varies across individual NSAIDs. Increased risk has been found for ketorolac, which may precipitate subclinical CKD through acute renal damage, and long-term exposure to oxicams, especially meloxicam and piroxicam.

  14. Systematic review and meta-analysis on the prophylacticrole of non-steroidal anti-inflammatory drugs to preventpost-endoscopic retrograde cholangiopancreatographypancreatitis


    AIM To critically appraise the published randomized,controlled trials on the prophylactic effectiveness ofthe non-steroidal anti-inflammatory drugs (NSAIDs),in reducing the risk of post-endoscopic retrogradecholangiopancreatography (ERCP) pancreatitis.METHODS: A systematic literature search (MEDLINE,Embase and the Cochrane Library, from inception of thedatabases until May 2015) was conducted to identifyrandomized, clinical trials investigating the role ofNSAIDs in reducing the risk of post-ERCP pancreatitis.Random effects model of the meta-analysis was carriedout, and results were presented as odds ratios (OR)with corresponding 95%CI.RESULTS: Thirteen randomized controlled trials on3378 patients were included in the final meta-analysis.There were 1718 patients in the NSAIDs group and 1660patients in non-NSAIDs group undergoing ERCP. Theuse of NSAIDs (through rectal route or intramuscularroute) was associated with the reduced risk of post-ERCPpancreatitis [OR, 0.52 (0.38-0.72), P = 0.0001]. Theuse of pre-procedure NSAIDs was effective in reducingapproximately 48% incidence of post-ERCP pancreatitis,number needed to treat were 16 with absolute riskreduction of 0.05. But the risk of post-ERCP pancreattiswas reduced by 55% if NSAIDs were administered afterprocedure. Similarly, diclofenac was more effective (55%)prophylactic agent compared to indomethacin (41%).CONCLUSION: NSAIDs seem to have clinically provenadvantage of reducing the risk of post-ERCP pancreatitis.

  15. Clinical Management of Adult Patients with a History of Nonsteroidal Anti-Inflammatory Drug-Induced Urticaria/Angioedema: Update

    Asero Riccardo


    Full Text Available In the large majority of previous studies, patients with a history of acute urticaria induced by nonsteroidal anti-inflammatory drugs (NSAIDs seeking safe alternative drugs have undergone tolerance tests uniquely with compounds exerting little or no inhibitory effect on the cyclooxygenase 1 enzyme. In light of recently published studies, however, this approach seems inadequate and should be changed. The present article critically reviews the clinical management of patients presenting with a history of urticaria induced by a single NSAID or multiple NSAIDs and suggests a simple, updated diagnostic algorithm that may assist clinicians in correctly classifying their patients.

  16. Mebendazole and a non-steroidal anti-inflammatory combine to reduce tumor initiation in a colon cancer preclinical model.

    Williamson, Tara; Bai, Ren-Yuan; Staedtke, Verena; Huso, David; Riggins, Gregory J


    Inheritance of a gene mutation leads to the initiation of 5 to 10% of most cancers, including colon cancer cases. We developed a chemoprevention strategy using a novel combination of the non-steroidal anti-inflammatory (NSAID) sulindac plus the anthelminthic benzimidazole, mebendazole. This oral drug combination was effective in the ApcMin/+ mouse model of Familial Adenomatous Polyposis (FAP). Treatment with 35 mg/kg daily mebendazole reduced the number of intestinal adenomas by 56% (P = 0.0002), 160 ppm sulindac by 74% (P cancer patients using mebendazole either alone or in combination. The findings have implications for populations with moderate and above risk for developing cancer.

  17. Randomized trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib

    Macdonald, Thomas M; Hawkey, Chris J; Ford, Ian;


    BACKGROUND: Selective cyclooxygenase-2 inhibitors and conventional non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) have been associated with adverse cardiovascular (CV) effects. We compared the CV safety of switching to celecoxib vs. continuing nsNSAID therapy in a European setting...... primary events per 1000 patient-years exposure. There were only 15 adjudicated secondary upper gastrointestinal complication endpoints (0.078/100 patient-years on celecoxib vs. 0.053 on nsNSAIDs OT, 0.078 vs. 0.053 ITT). More gastrointestinal serious adverse reactions and haematological adverse reactions...

  18. Tetrahydroquinolines as a novel series of nonsteroidal selective androgen receptor modulators: structural requirements for better physicochemical and biological properties.

    Nagata, Naoya; Miyakawa, Motonori; Amano, Seiji; Furuya, Kazuyuki; Yamamoto, Noriko; Nejishima, Hiroaki; Inoguchi, Kiyoshi


    A rationally designed tetrahydroquinoline (1) for nonsteroidal selective androgen receptor modulators was modified for the exploration of promising compounds by Grieco three-component condensation using various dienophiles. Based on the in vitro effects and physicochemical properties of the synthesized compounds, compound 4c was selected for further study. Compound 4c increased the femoral bone mineral density as much as DHT, but it reduced the uterus effect compared with DHT in ovariectomized rats. Thus, compound 4c has desirable osteoanabolic effects with weak undesirable effects on the uterus in a female osteoporosis model.

  19. New insights into the use of currently available non-steroidal anti-inflammatory drugs

    Brune K


    Full Text Available Kay Brune,1 Paola Patrignani2 1Department of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany; 2Department of Neuroscience, Imaging and Clinical Sciences, Center of Excellence on Aging, G d’Annunzio University, Chieti, Italy Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs, which act via inhibition of the cyclooxygenase (COX isozymes, were discovered more than 100 years ago. They remain a key component of the pharmacological management of acute and chronic pain. The COX-1 and COX-2 isozymes have different biological functions; analgesic activity is primarily (although not exclusively associated with inhibition of COX-2, while different side effects result from the inhibition of COX-1 and COX-2. All available NSAIDs, including acetaminophen and aspirin, are associated with potential side effects, particularly gastrointestinal and cardiovascular effects, related to their relative selectivity for COX-1 and COX-2. Since all NSAIDs exert their therapeutic activity through inhibition of the COX isozymes, strategies are needed to reduce the risks associated with NSAIDs while achieving sufficient pain relief. A better understanding of the inhibitory activity and COX-1/COX-2 selectivity of an NSAID at therapeutic doses, based on pharmacokinetic and pharmacodynamic properties (eg, inhibitory dose, absorption, plasma versus tissue distribution, and elimination, and the impact on drug tolerability and safety can guide the selection of appropriate NSAIDs for pain management. For example, many NSAIDs with moderate to high selectivity for COX-2 versus COX-1 can be administered at doses that maximize efficacy (~80% inhibition of COX-2 while minimizing COX-1 inhibition and associated side effects, such as gastrointestinal toxicity. Acidic NSAIDs with favorable tissue distribution and short plasma half-lives can additionally be dosed to provide near-constant analgesia while

  20. 2-hydroxy arachidonic acid: a new non-steroidal anti-inflammatory drug.

    Daniel H Lopez

    Full Text Available BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs are a family of COX1 and COX2 inhibitors used to reduce the synthesis of pro-inflammatory mediators. In addition, inflammation often leads to a harmful generation of nitric oxide. Efforts are being done in discovering safer NSAIDs molecules capable of inhibiting the synthesis of pro-inflammatory lipid mediators and nitric oxide to reduce the side effects associated with long term therapies. METHODOLOGY/PRINCIPAL FINDINGS: The analogue of arachidonic acid (AA, 2-hydroxy-arachidonic acid (2OAA, was designed to inhibit the activities of COX1 and COX2 and it was predicted to have similar binding energies as AA for the catalytic sites of COX1 and COX2. The interaction of AA and 2OAA with COX1 and COX2 was investigated calculating the free energy of binding and the Fukui function. Toxicity was determined in mouse microglial BV-2 cells. COX1 and COX2 (PGH2 production activities were measured in vitro. COX1 and COX2 expression in human macrophage-like U937 cells were carried out by Western blot, immunocytochemistry and RT-PCR analysis. NO production (Griess method and iNOS (Western blot were determined in mouse microglial BV-2 cells. The comparative efficacy of 2OAA, ibuprofen and cortisone in lowering TNF-α serum levels was determined in C57BL6/J mice challenged with LPS. We show that the presence of the -OH group reduces the likelihood of 2OAA being subjected to H* abstraction in COX, without altering significantly the free energy of binding. The 2OAA inhibited COX1 and COX2 activities and the expression of COX2 in human U937 derived macrophages challenged with LPS. In addition, 2OAA inhibited iNOS expression and the production of NO in BV-2 microglial cells. Finally, oral administration of 2OAA decreased the plasma TNF-α levels in vivo. CONCLUSION/SIGNIFICANCE: These findings demonstrate the potential of 2OAA as a NSAID.

  1. Non-steroidal anti-inflammatory drugs affect the methotrexate transport in IEC-6 cells.

    Sosogi, Aiko; Gao, Feng; Tomimatsu, Takashi; Hirata, Koji; Horie, Toshiharu


    Methotrexate (MTX) is used not only for the cancer chemotherapy but also for the treatment of rheumatic disease, often together with non-steroidal anti-inflammatory drugs (NSAIDs). MTX is actively cotransported with H(+) in the small intestine, mediated by a reduced folate carrier (RFC). The coadministration of some NSAIDs with MTX to rats caused a decrease of MTX absorption through the small intestine. This may be due to the uncoupling effect of oxidative phosphorylation of the NSAIDs. The present study investigated whether flufenamic acid, diclofenac and indomethacin, NSAIDs, decreased ATP content of rat-derived intestinal epithelial cell line IEC-6 cells and affected the MTX transport in IEC-6 cells. The MTX uptake in IEC-6 cells was dependent on medium pH and maximum around pH 4.5-5.5. The MTX uptake was composed of a transport inhibited by 4, 4'-diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS) and a non-saturable one. The DIDS-sensitive component in the MTX uptake showed a saturation kinetics (Michaelis-Menten constant (Km): 3.91 +/- 0.52 microM, Maximum velocity (Vmax): 94.66 +/- 6.56 pmol/mg protein/5 min). The cellular ATP content in IEC-6 cells decreased significantly at 30 min after the cells were started to incubate with the NSAIDs (250 microM flufenamic acid, 500 microM diclofenac and 500 microM indomethacin). The MTX uptake in IEC-6 cells in the presence of the NSAIDs decreased with the reduction of cellular ATP content and showed a good correlation with the ATP content (correlation coefficient: 0.982). Thus it seems likely that the ATP content in IEC-6 cells with the NSAIDs decreased due to the uncoupling effect of oxidative phosphorylation of the NSAIDs, resulting in the inhibition of the secondary active transport of MTX in IEC-6 cells. The present results also suggest that IEC-6 cells are useful to evaluate the drug interaction relating to this carrier system.




    Mobile agent technology has been promoted as an emerging technology that makes it much easier to design, implement, and maintain distributed systems, introduction to basic concepts of mobile agents like agent mobility, agent types and places and agent communication. Then benefits of the usage of mobile agents are summarized and illustrated by selected applications. The next section lists requirements and desirable properties for mobile agent languages and systems. We study the main features, ...

  3. Potentiated clinoptilolite: artificially enhanced aluminosilicate reduces symptoms associated with endoscopically negative gastroesophageal reflux disease and nonsteroidal anti-inflammatory drug induced gastritis

    Potgieter W


    Full Text Available Wilna Potgieter, Caroline Selma Samuels, Jacques Renè SnymanDepartment of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, Gauteng, South AfricaPurpose: The cation exchanger, a potentiated clinoptilolite (Absorbatox™ 2.4D, is a synthetically enhanced aluminosilicate. The aim of this study was to evaluate the possible benefits of a potentiated clinoptilolite as a gastroprotective agent in reducing the severity of clinical symptoms and signs associated with 1 endoscopically negative gastroesophageal reflux disease (ENGORD and 2 nonsteroidal anti-inflammatory drug (NSAID medication.Methods and patients: Two randomized, double-blind, placebo-controlled, pilot studies, the ENGORD and NSAID studies, were conducted. After initial negative gastroscopy, a total of 25 patients suffering from ENGORD were randomized to receive either placebo capsules or 750 mg Absorbatox twice daily for 14 days. The NSAID study recruited 23 healthy patients who received orally either 1,500 mg Absorbatox or placebo three times daily, plus 500 mg naproxen twice daily. Patients underwent gastroscopic evaluation of their stomach linings prior to and on day 14 of the study. Gastric biopsies were obtained and evaluated via the upgraded Sydney system, whereas visible gastric events and status of the gastric mucosa were evaluated via a 0–3 rating scale. During both studies, patients recorded gastric symptoms in a daily symptom diary.Results: In the ENGORD study, patients who received the potentiated clinoptilolite reported a significant reduction (P≤0.05 in severity of symptoms including reduction in heartburn (44%, discomfort (54%, and pain (56%. Symptom-free days improved by 41% compared to the group who received placebo (not significant. This was over and above the benefits seen with the proton pump inhibitor. In the NSAID study, the reduction in gastric symptom severity was echoed in the group who received the potentiated

  4. The novel non-steroidal selective androgen receptor modulator S-101479 has additive effects with bisphosphonate, selective estrogen receptor modulator, and parathyroid hormone on the bones of osteoporotic female rats.

    Furuya, Kazuyuki; Yamamoto, Noriko; Ohyabu, Yuki; Makino, Akito; Morikyu, Teruyuki; Ishige, Hirohide; Kuzutani, Kazuya; Endo, Yasuhisa


    We have studied non-steroidal selective androgen receptor modulators (SARMs) to develop anti-osteoporosis drugs for males and females. Many SARMs have been studied for their anabolic effects on bone or muscle with reduced virilizing effects in male animals. However, the tissue selectivities of these agents in female animals have not been fully evaluated. We evaluated the novel SARM S-101479 from tetrahydroquinoline libraries in ovariectomized (OVX) rats. S-101479 preferentially bound to the androgen receptor with nanomolar affinity among nuclear receptors. It increased the bone mineral density (BMD) of femurs and diminished the effects on the uterus and clitoral gland in OVX rats. We then compared the effect of S-101479 on bone with those of commercial anti-osteoporosis drugs such as alendronate, raloxifene, and teriparatide. Furthermore, we evaluated the effects of combination treatments with these agents in OVX rats. After 16-week treatment, all agents significantly increased BMD, but the magnitude of bone mineral content (BMC) and/or bone size (projected bone area) were different. Alendronate, raloxifene, and teriparatide maintained BMC and bone size in this experimental dose. Only S-101479 increased BMC with bone size on single treatments. In combination treatment, S-101479 significantly increased BMC and bone size compared with single treatments of other agents. S-101479, like natural androgen, may have showed periosteal bone formation of the cortical area and indicated additive effects with commercial anti-osteoporosis drugs. These results indicate that S-101479 may be a useful anti-osteoporosis drug, particularly for patients with established severe osteoporosis.

  5. Protective Effect of Wheat Peptides Against Small Intestinal Damage Induced by Non-Steroidal Anti-Inlfammatory Drugs in Rats

    YIN Hong; PAN Xing-chang; WANG Shao-kang; YANG Li-gang; SUN Gui-ju


    Non-steroidal anti-inlfammatory drugs (NSAIDs) were able to produce tissue damage and oxidative stress in animal models of small intestinal damage. In this study, the putative protective effect of wheat peptides was evaluated in a NSAID-induced small intestinal damage model in rats, different doses of wheat peptides or distilled water were administered daily by intragastric administration for 30 d until small intestinal damage was caused. Before sacriifcing, NSAIDs (aspirin and indomethacin) or physiological saline were infused into the digestive tract twice. Wheat peptides administration reduced edema and small intestinal damage, and signiifcantly decreased the level of tumor necrosis factor (TNF)-α in mucous membrane of small intestine. Oxidative stress was signiifcantly increased after NSAID infusion and was reduced by wheat peptides. Wheat peptides increased glutathione peroxidase(GSH-Px) activity in mucous membrane of small intestine. µ-Opioid receptor mRNA expression decreased more signiifcantly in wheat peptides treated rats than in the model control group. Overall, the results suggest that non-steroidal anti-inlfammatory drugs induced small intestinal damage in rats and wheat peptides administration may be an effective tool for protecting small intestinal tissue against NSAID-induced small intestinal damage and oxidative stress.

  6. Interacting agents in finance

    C. Hommes


    Interacting agents in finance represent a behavioural, agent-based approach in which financial markets are viewed as complex adaptive systems consisting of many boundedly rational agents interacting through simple heterogeneous investment strategies, constantly adapting their behaviour in response t

  7. Riot Control Agents

    ... Submit What's this? Submit Button Facts About Riot Control Agents Interim document Recommend on Facebook Tweet Share Compartir FACT SHEET What riot control agents are Riot control agents (sometimes referred to ...

  8. Cardiovascular risk and inhibition of cyclooxygenase: traditional nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors

    M. Campanini


    Full Text Available BACKGROUND The development of non-selective nonsteroidal anti-inflammatory drugs (tNSAIDs and, more recently, of selective inhibitors of the cycloooxygenase-2 isoform (COXIBs, has contributed greatly towards the effective management of patients with arthritis and pain complaints. Although COXIBs have demonstrated an improved gastrointestinal tolerability compared with tNSAIDs, the cardiovascular effects of the two drugs types are much controversial. By blocking prostacyclin formation but leaving platelet-derived thromboxane A2 generation unopposed, the potential gastrointestinal benefit of COXIBs may come at cost of increased thrombotic risk. AIM OF THE STUDY This review aims at analysing the cardiovascular effects of the tNSAIDs and COXIBs. METHOD This review addresses the controversy of effects of COXIBs and tNSAIDs in 4 segments. It begins with a discussion about pathophysiological effects of cyclooxygenase inhibition on cardiovascular system. This is followed by a systematic review and meta-analysis of a control, randomized, double blind study and population-based matched case-control study to compare the risk of serious cardiovascular events with tNSAIDs and COXIBs. Then it answers to key questions with the aim to assist the clinicians for a systematic approach to evaluate the risk-benefit-ratio of NSAIDs in the clinical practice. Finally we analyse the open questions associated with the use of NSAIDs and the cardiovascular events. RESULTS The use of rofecoxib demonstrated an increase in adverse cardiovascular events. This toxic effect is not dose-related. The relationship between celecoxib and cardiovascular risk is less clear. The results of different clinical trials are conflicting: some didn’t demonstrate increase in cardiovascular toxicity but the APC study and recently a metanalysis reported a significant incidence of adverse cardiovascular events. Also valdecoxib and parecoxib appear to have increased risk for cardiovascular

  9. Aspirin as a chemoprevention agent for colorectal cancer.

    Lee, Chun Seng


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

  10. Inhibition of tolbutamide 4-methylhydroxylation by a series of non-steroidal anti-inflammatory drugs in V79-NH cells expressing human cytochrome P4502C10

    Kappers, W.A.; Groene, E.M. de; Kleij, L.A.; Witkamp, R.F.; Zweers-Zeilmaker, W.M.; Feron, V.J.; Horbach, G.J.


    1. To study the role of cytochrome P4502C10 in the metabolism of the non-steroidal antiinflammatory drugs (NSAIDs) diclofenac, phenylbutazone, fenoprofen, ibuprofen, flurbiprofen, ketoprofen and naproxen, a cell line was developed stably expressing CYP2C10 cDNA. A retroviral vector construct, contai

  11. Interaction of nonsteroidal anti-inflammatory drugs with multidrug resistance protein (MRP) 2/ABCC2- and MRP4/ABCC4-mediated methotrexate transport

    El-Sheikh, A.A.K.; Heuvel, J.J.M.W. van den; Koenderink, J.B.; Russel, F.G.M.


    Methotrexate (MTX) has been used in combination with nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of inflammatory diseases as well as malignancies. Especially at high MTX dosages, severe adverse effects with this combination may occur, usually resulting from an impaired renal elimi

  12. Use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs in high doses increases mortality and risk of reinfarction in patients with prior myocardial infarction

    Sørensen, Rikke; Abildstrøm, Steen Zabell; Torp-Pedersen, C.


    The selective cyclooxygenase-2 (COX-2) inhibitors and other nonselective nonsteroidal antiinflammatory drugs (NSAIDs) have been associated with increased cardiovascular risk, but the risk in patients with established cardiovascular disease is unknown. In the present study, we analyzed the risk of...

  13. Efficacy of triple therapy and sequential therapy in the eradication of Helicobacter pylor in patients receiving long-term non-steroidal anti-inflammatory drugs treatnent



    Objective To explore the efficacy of triple therapy and sequential therapy in the eradication of Helicobacter pylori(Hp) in patients receiving long-term non-steroidal antiinflammatorv drugs(NSAID) treatment. Methods Patients receiving long-term NSAID treatment were enrolled

  14. An efficient route for annulation of pyrimidines to steroids and non-steroids via a base catalyzed one-pot three component reaction.

    Saikia, Pallabi; Gogoi, Shyamalee; Gogoi, Sanjib; Boruah, Romesh C


    A facile strategy for the synthesis of steroidal A- and D-ring fused pyrimidines has been accomplished in high yields via a one-pot reaction of steroidal ketones, aromatic aldehydes and amidine derivatives in presence of potassium tert-butoxide in refluxing ethanol. The generality of the reaction was also extended to non-steroidal ketones.

  15. Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy

    Lamberts, Morten; Lip, Gregory Y H; Hansen, Morten Lock;


    BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are assumed to increase bleeding risk, but their actual relation to serious bleeding in patients with atrial fibrillation (AF) who are receiving antithrombotic medication is unknown. OBJECTIVE: To investigate the risk for serious bleeding ...

  16. Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients

    Petersen, Susanne G; Beyer, Nina; Hansen, Mette Rud;


    To investigate the effect of 12 weeks of strength training in combination with a nonsteroidal anti-inflammatory drug (NSAID), glucosamine, or placebo on muscle cross-sectional area (CSA), strength (primary outcome parameters), and function, power, pain, and satellite cell number (secondary outcome...

  17. Non-steroidal anti-inflammatory high digestive bleeding hospital income / Ingresos hospitalarios por hemorragia digestiva alta por antiinflamatorios no esteroidicos

    Valls MD


    Full Text Available From year 1997 the Requena Hospital Pharmacy Service maintain a program of detection and prevention of drugs-related problems hospital income (DRPI. The program is coordinated with the Primary Care Pharmacy Service for the establishment of the preventive measures. The DRPI program establishes feedback, collective and/or individualized, on the agents of health of the Health Area and on the population in general, according to the cases, as it bases for the prevention of DRPIs. Methods: The detection of IDRP is made by means of revision of the diagnoses gathered in the admission book of the Emergency Department and the HIGIA database. Clinical records of the patients are retrospectively analyzed. Medical criteria, specifically gathered in clinical history, are accepted for the imputability establishment. Results: In period 1997-2003, 195 drug-related high digestive hemorrhage hospital income (HDH have been detected: 188 by non-steroidal anti-inflammatory drugs (NSAID, in two cases the NSAID could not settle down cause, 3 by ticlopidine, 3 by metamizole and 1 by clopidogrel. In 45 cases (23% the involved medicine was over the counter (OTC, 58 cases were related to low doses aspirin (AAS, 15 cases related to the association of NSAIDs or NSAIDs with low doses AAS and 70 cases were produced by non-aspirin-NSAIDs or non-OTC-AAS to doses of 500mg. 80% of the cases of HDH by AAS to low doses took place in patients of 69 years old or older. In 85% of the cases of HDH by non-aspirin- NSAID or non-OTC-AAS of 500mg with gastro-protection criteria this had not been used. In the three cases of HDH by metamizole patients were older than 80 years and with HDH antecedents. Conclusions: The low use of gastroprotection between the affected population of HDH by NSAIDs in spite of the existence of clear factors of risk concludes. Gastroprotection in patients dealt with low doses AAS and equal or greater age about 69 years although the age were the only factor of risk

  18. Prescribing patterns of non-steroidal anti-inflammatory drugs in chronic kidney disease patients in the South African private sector.

    Meuwesen, Willem P; du Plessis, Jesslee M; Burger, Johanita R; Lubbe, Martie S; Cockeran, Marike


    Background Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used pharmaceutical agents worldwide. NSAIDs are considered nephrotoxic and should therefore be used with caution or be avoided completely in high risk patients, such as chronic kidney disease (CKD) patients. Objective This study aimed to investigate the prescribing of NSAIDs in CKD patients in order to generate awareness and improve the outcome of these patients. Setting The study was conducted using medicine claims data in the private health sector of South Africa. Method A descriptive, quantitative study was performed, using retrospective data obtained from a Pharmaceutical Benefit Management company. Data from 1 January 2009 to 31 December 2013 were analysed. The study population consisted of all patients with an ICD-10 code for a CKD (N18), in association with a paid claim for an NSAID. Main outcome measure The stratification of NSAID prescribing volume among the CKD population in terms of gender, age, NSAID type, dosage and prescriber type. Results The prescribing of NSAIDs in CKD patients varied between 26 and 40 % over the 5 year study period. No association between gender and CKD patients who received NSAIDs versus those who did not was found, with p > 0.05 and Cramer's V < 0.1 for each year of the study. The association between age groups and CKD patients who received NSAIDs versus those who did not was statistically significant, but practically weak (p < 0.05; Cramer's V ≥ 0.1). Most NSAID prescriptions (52-63 %) were for patients aged 35-64 years. Diclofenac (34.25 %) was the single most frequently prescribed NSAID, but the COX-2-inhibitors (celecoxib, meloxicam and etoricoxib) were the preferred NSAID class to be prescribed. The majority (61.6 %) of the NSAIDs were prescribed by general medical practitioners in dosages meeting and even exceeding the recommended daily dosage of patients with normal kidney function. Conclusions Even though NSAIDs are

  19. Non-steroidal anti-inflammatory drugs and risk of cardiovascular disease in patients with rheumatoid arthritis

    Lindhardsen, Jesper; Gislason, Gunnar Hilmar; Jacobsen, Søren;


    -level registry data on inpatient and outpatient health care provision, pharmacotherapy and income during 1997-2009. 17 320 RA patients were identified and matched with 69 280 controls (4 : 1) by age and sex. NSAID-associated risk of major cardiovascular disease defined as the combined endpoint of myocardial......OBJECTIVE: To examine the risk of major cardiovascular disease associated with non-steroidal anti-inflammatory drugs (NSAIDs) in a large 'real-world' contemporary rheumatoid arthritis (RA) cohort. METHODS: A longitudinal cohort study was conducted with use of Danish nationwide individual...... infarction, stroke or cardiovascular mortality was assessed in multivariable survival models. RESULTS: During follow-up (median 4.9 years) 6283 events occurred. The cardiovascular risk associated with overall NSAID use was significantly lower in RA patients than in controls (HR 1.22 (95% CI 1.09 to 1.37) vs...

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

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


    BACKGROUND: Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and selective COX-2 inhibitors may improve outcomes in breast cancer patients. We investigated the association of aspirin, NSAIDs, and use of selective COX-2 inhibitors with breast cancer recurrence. METHODS: We identified incident...... stage I-III Danish breast cancer patients in the Danish Breast Cancer Cooperative Group registry, who were diagnosed during 1996-2008. Prescriptions for aspirin (>99% low-dose aspirin), NSAIDs, and selective COX-2 inhibitors were ascertained from the National Prescription Registry. Follow-up began...... on the date of breast cancer primary surgery and continued until the first of recurrence, death, emigration, or 1 January 2013. We used Cox regression models to compute hazard ratios (HR) and corresponding 95% confidence intervals (95% CI) associating prescriptions with recurrence, adjusting for confounders...

  1. Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer

    Trabert, Britton; Ness, Roberta B; Lo-Ciganic, Wei-Hsuan


    BACKGROUND: Regular aspirin use is associated with reduced risk of several malignancies. Epidemiologic studies analyzing aspirin, nonaspirin nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen use and ovarian cancer risk have been inconclusive. METHODS: We analyzed pooled data from 12...... population-based case-control studies of ovarian cancer, including 7776 case patients and 11843 control subjects accrued between 1992 and 2007. Odds ratios (ORs) for associations of medication use with invasive epithelial ovarian cancer were estimated in individual studies using logistic regression...... and combined using random effects meta-analysis. Associations between frequency, dose, and duration of analgesic use and risk of ovarian cancer were also assessed. All statistical tests were two-sided. RESULTS: Aspirin use was associated with a reduced risk of ovarian cancer (OR = 0.91; 95% confidence interval...

  2. Post-cataract prevention of inflammation and macular edema by steroid and nonsteroidal anti-inflammatory eye drops

    Kessel, Line; Tendal, Britta; Jørgensen, Karsten Juhl;


    PURPOSE: Favorable outcome after cataract surgery depends on proper control of the inflammatory response induced by cataract surgery. Pseudophakic cystoid macular edema is an important cause of visual decline after uncomplicated cataract surgery. DESIGN: We compared the efficacy of topical steroids...... with topical nonsteroidal anti-inflammatory drugs (NSAIDs) in controlling inflammation and preventing pseudophakic cystoid macular edema (PCME) after uncomplicated cataract surgery. PARTICIPANTS: Patients undergoing uncomplicated surgery for age-related cataract. METHODS: We performed a systematic literature...... are more effective in controlling postoperative inflammation after cataract surgery. We found high-quality evidence that topical NSAIDs are more effective than topical steroids in preventing PCME. The use of topical NSAIDs was not associated with an increased events. We recommend using topical NSAIDs...

  3. Femtosecond dynamics of a non-steroidal anti-inflammatory drug (piroxicam) in solution: The involvement of twisting motion

    Gil, Michał; Douhal, Abderrazzak


    In this contribution, we report on fast and ultrafast dynamics of a non-steroidal anti-inflammatory drug, piroxicam (PX), in methyl acetate (MAC) and triacetin (TAC), two solvents of different viscosities. The enol form of PX undergoes a femtosecond (shorter than 100 fs) electronically excited state intramolecular proton-transfer reaction to produce keto tautomers. These structures exhibit an internal twisting motion to generate keto rotamers in ˜2-5 ps, a time being longer in TAC. The transient absorption/emission spectrum is very broad indicating that the potential-energy surface at the electronically excited state is very flat, and reflecting the involvement of several coordinates along which the wavepacket of the fs-produced structures evolve.

  4. [Low-dose aspirin (LDA)/nonsteroidal anti-inflammatory drugs(NSAIDs)-induced gastrointestinal injury in Japan].

    Sugano, Kentaro


    Low-dose aspirin (LDA) and nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed in Japan mostly due to increasing elderly population. Since LDA/NSAIDs cause gastrointestinal injury, serious side effects such as bleeding accompanied with their usage have been frequently reported. Awareness of such problems prompted clinical trials to facilitate a more effective approach to prevent LDA/NSAIDs-induced gastrointestinal ulcer. Two drugs recently approved for health insurance reimbursement, celecoxib, a cyclooxygenase (COX)-2 specific inhibitor and low-dose lansoprazole for prevention of recurrent peptic ulcer due to LDA/NSAIDs will be instrumental in mitigating the gastrointestinal injuries. However, continuous, intensive educational programs will be required to the change in the prescription behaviors of the general physicians. Furthermore, we need to search for effective measures to detect and prevent mid and lower gastrointestinal injury caused by LDA/NSAIDs which account for about 30% of all GI bleedings.

  5. Design and synthesis of tricyclic tetrahydroquinolines as a new series of nonsteroidal selective androgen receptor modulators (SARMs).

    Nagata, Naoya; Miyakawa, Motonori; Amano, Seiji; Furuya, Kazuyuki; Yamamoto, Noriko; Inoguchi, Kiyoshi


    Some tricyclic tetrahydroquinolines (THQs) were found to have the potential of a new series of nonsteroidal selective androgen receptor modulators (SARMs). Compound 5b was first designed and synthesized under our hypothesis based on a four-point pharmacophoric requirement of the 3-carbonyl, 18-methyl, 17-hydroxyl, and 13-quaternary carbon groups of dihydrotestosterone (DHT). It was revealed that this compound exhibits not only a strong androgen receptor (AR) agonistic activity (EC(50)=9.2 nM) but also the highest selectivity in binding affinity to AR among the steroid hormone receptors. Furthermore, this compound showed a weak virilizing effect with retention of the desired anabolic effect as compared with DHT in vivo.

  6. Biological warfare agents.

    Pohanka, Miroslav; Kuca, Kamil


    Biological warfare agents are a group of pathogens and toxins of biological origin that can be potentially misused for military or criminal purposes. The present review attempts to summarize necessary knowledge about biological warfare agents. The historical aspects, examples of applications of these agents such as anthrax letters, biological weapons impact, a summary of biological warfare agents and epidemiology of infections are described. The last section tries to estimate future trends in research on biological warfare agents.

  7. [Comparative enantioselectivity of the disposition of two non-steroidal anti-inflammatory agents, ketoprofen and carprofen, in man and animals].

    Delatour, P; Benoit, E; Bourdin, M; Gobron, M; Moysan, F


    After the administration of racemic ketoprofen and carprofen to man, both enantiomers of each compound exhibit similar plasma profiles. This contrasts with the rat where the active S(+) enantiomer is predominant. For carprofen, regardless of the route of administration, the R(-) enantiomer is predominant in the plasma of all investigated animal species. The S(+)/R(-) ratio of the "areas under the curves" during the time course of the kinetics, is: 0.60 in dogs, 0.53 in Yucatan micro-pigs, 0.48 in mini-goats, 0.67 in calves and 0.19 in horses. For ketoprofen, the S(+) enantiomer is predominant in dogs, cats and horses, with ratios of 30.3, 5.3 and 1.5, respectively, while R(-) is the predominant enantiomer in sheep. The interpretation of these inter-species differences can be supported by experimental evidence, however some informations are lacking and additional investigation is required. In the case of ketoprofen where S(+) is predominant in rats, dogs and horses, the metabolic chiral inversion from R(-) to S(+), which has been demonstrated in rats, may also take place in the latter two species. In addition, the well documented stereoselective clearance of the glucuronides, possibly in favour of the enantiomer S(+), may explain the lower body clearance of the R(-) enantiomer in sheep. For carprofen, no metabolic chiral inversion was shown in rats and dogs after administration of each enantiomer individually, but for this compound, stereoselective clearance of glucuronides has been demonstrated which may support the idea of a plasma concentration shift of the enantiomeric proportions vs time in favour of the R(-) enantiomer. Regardless of the possible biological mechanisms which are responsible for these inter-species differences, the existence of these differences gives rise to at least two important issues: The choice of animal species which can be used in the research of drugs destined for human therapeutics: the most pertinent animal species will be the one which demonstrates an enantiomeric plasma profile closest to that observed in man. The present data show that the ideal animal species from this respect has still to be identified. For application in veterinary therapeutics, a careful balance must be established between the requirement of favourable bioavailability of the active S(+) enantiomer and the potential of any possible chiral inversion of R(-) to generate hybrid molecules in meat and milk which in turn may lead to residues, the toxicity of which to the human consumer is still unknown.

  8. Animal Capture Agents


    agents and delivery systems reviewed . Questionnaires were sent to 137 Air Force bases to obtain information about the chemical agents and delivery systems...used by animal control personnel. A literature review included chemical agents, delivery methods, toxicity information and emergency procedures from...34-like agent. Users should familiarize themselves with catatonia in general and particularly that its successful use as an immobilizer doesn’t necessarily

  9. Intelligent Agents: A Primer.

    Yu, Edmund; Feldman, Susan


    Provides an in-depth introduction to the various technologies that are bringing intelligent agents into the forefront of information technology, explaining how such agents work, the standards involved, and how agent-based applications can be developed. (Author/AEF)

  10. Reasoning about emotional agents

    Meyer, J.-J.


    In this paper we discuss the role of emotions in artificial agent design, and the use of logic in reasoning about the emotional or affective states an agent can reside in. We do so by extending the KARO framework for reasoning about rational agents appropriately. In particular we formalize in this f

  11. Users, Bystanders and Agents

    Krummheuer, Antonia Lina


    Human-agent interaction (HAI), especially in the field of embodied conversational agents (ECA), is mainly construed as dyadic communication between a human user and a virtual agent. This is despite the fact that many application scenarios for future ECAs involve the presence of others. This paper...


    Christina Popova


    evaluation of gene expression levels of IL-1beta and PGE2 in gingival tissue of periodontal patients was applied. Results: Statistically significant differences were found between additional Aulin® therapy group and conventional therapy group. Received correlative coefficient with Spearman analysis was respectively t = -0.72 (p< 0,05 for IL-1beta and t = 0.81(p<0,05 for PGE2. The negative values of ddCt in test group reveal lower level of inhibition of gene expression. The comparative analysis of the collected data demonstrates fewer differences between both groups. The deviations in gene expression levels of IL -1beta and PGE2 are higher in the patients treated with adjunctive medication with Aulin®. Conclusion: This study confirms the effectiveness of non-surgical therapy in moderate and severe periodontitis. Additional use of non-steroidal anti-inflammatory agent Aulin® results in higher inhibition of the pro-inflammatory cytokines IL-1beta and PGE2. This data may be the base for modifying the conventional non-surgical therapy by including anti-inflammatory agents in the treatment of chronic periodontitis.

  13. Powder microscopy of bark--poison used for abortion: moringa pterygosperma gaertn.

    Bhattacharya, J; Guha, G; Bhattacharya, B


    Moringa pterygosperma Gaertn. (Moringaceae) is a soft white wood tree with a gummy juice which grows all over India. The bark of the tree, powdered, produces an abortifacient which causes violent uterine contractions giving fatal results. This abortifacient agent is used in the Bengali area of India. Laboratory preparation and analysis of the powdered bark is described.

  14. Cutaneous reactions to analgesic-antipyretics and nonsteroidal anti-inflammatory drugs. Analysis of reports to the spontaneous reporting system of the Gruppo Italiano Studi Epidemiologici in Dermatologia.


    We analyzed the cutaneous reactions to systemic analgesic-antipyretics and non-steroidal anti-inflammatory drugs reported to the spontaneous reporting system of the Gruppo Italiano Studi Epidemiologici in Dermatologia (GISED). The system has been active since 1988, with periodic intensive surveillance exercises, and 202 dermatologists have collaborated. Up to December 1991, 2,137 reactions had been collected, of which 713 were reactions to systemic analgesic-antipyretics and nonsteroidal anti-inflammatory drugs. A general profile of the reactions was identifiable. It included, in order of frequency, urticaria/angioedema, fixed eruptions, exanthemas, erythema multiforme and Stevens Johnson syndrome. Fixed eruptions and Stevens Johnson syndrome were reported with exceedingly high frequency in association with feprazone. Our system also revealed previously unreported reactions, including fixed eruption to nimesulide, fixed eruption to piroxicam and fixed eruption to flurbiprofen.

  15. Diclofenac sodium topical solution with dimethyl sulfoxide, a viable alternative to oral nonsteroidal anti-inflammatories in osteoarthritis: review of current evidence

    Fuller P; Roth SH


    Philip Fuller¹, Sanford Roth²¹Covidien, Hazelwood, MO; ²Arizona Research and Education, Arthritis Research Laboratory, Arizona State University, Phoenix, AZ, USAAbstract: Topical nonsteroidal anti-inflammatory drugs (NSAIDs) may offer a safer alternative to their oral counterparts for the management of osteoarthritis. Diclofenac sodium topical solution with dimethyl sulfoxide (TDiclo) was evaluated in five randomized, controlled trials and is indicated for ...

  16. Nonsteroidal anti-inflammatory drugs modulate cellular glycosaminoglycan synthesis by affecting EGFR and PI3K signaling pathways

    Mozolewski, Paweł; Moskot, Marta; Jakóbkiewicz-Banecka, Joanna; Węgrzyn, Grzegorz; Bocheńska, Katarzyna; Banecki, Bogdan; Gabig-Cimińska, Magdalena


    In this report, selected non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin and nimesulide, and analgesics acetaminophen, alone, as well as in combination with isoflavone genistein as potential glycosaminoglycan (GAG) metabolism modulators were considered for the treatment of mucopolysaccharidoses (MPSs) with neurological symptoms due to the effective blood-brain barrier (BBB) penetration properties of these compounds. We found that indomethacin and nimesulide, but not acetaminophen, inhibited GAG synthesis in fibroblasts significantly, while the most pronounced impairment of glycosaminoglycan production was observed after exposure to the mixture of nimesulide and genistein. Phosphorylation of the EGF receptor (EGFR) was inhibited even more effective in the presence of indomethacin and nimesulide than in the presence of genistein. When examined the activity of phosphatidylinositol-3-kinase (PI3K) production, we observed its most significant decrease in the case of fibroblast exposition to nimesulide, and afterwards to indomethacin and genistein mix, rather than indomethacin used alone. Some effects on expression of individual GAG metabolism-related and lysosomal function genes, and significant activity modulation of a number of genes involved in intracellular signal transduction pathways and metabolism of DNA and proteins were detected. This study documents that NSAIDs, and their mixtures with genistein modulate cellular glycosaminoglycan synthesis by affecting EGFR and PI3K signaling pathways. PMID:28240227

  17. Is Alzheimer's Disease Autoimmune Inflammation of the Brain That Can be Treated With Nasal Nonsteroidal Anti-Inflammatory Drugs?

    Lehrer, Steven; Rheinstein, Peter H


    The Alzheimer's Association recently reported that a woman's estimated lifetime risk of developing Alzheimer's at age 65 is 1 in 6, compared to nearly 1 in 11 for a man (ie, female to male ratio 1.8). Based on female to male ratio, Alzheimer's disease could well be an autoimmune disorder. Like Alzheimer's, multiple sclerosis, an autoimmune inflammation of the central nervous system, has a female to male ratio of 2.3. Also based on female to male ratio, Alzheimer's resembles the autoimmune inflammatory disease rheumatoid arthritis, which has a female to male ratio of 2.7. The reasons for the female preponderance in autoimmune disease are unclear, but nonsteroidal anti-inflammatory drugs (NSAIDs) are widely and successfully employed to treat autoimmune anti-inflammatory disease and dramatically relieve symptoms. Moreover, oral NSAIDs consistently reduce the risk of Alzheimer's disease, although they have been totally ineffective as a treatment in multiple failed clinical trials. A basis for this failure might well be that the brain dose after oral administration is too small and not sufficiently early in the pathogenesis of the disorder. But NSAID brain dose could be significantly increased by delivering the NSAIDs intranasally.

  18. Analysis of chiral non-steroidal anti-inflammatory drugs flurbiprofen, ketoprofen and etodolac binding with HSA

    Chang-Chuan Guo; Yi-Hong Tang; Hai-Hong Hu; Lu-Shan Yu; Hui-Di Jiang; Su Zeng


    The protein binding of non-steroidal anti-inflammatory drugs flurbiprofen, ketoprofen and etodolac with human serum albumin (HSA) was investigated using indirect chiral high performance liquid chromatography (HPLC) and ultrafiltration techniques. S-(-)-1-(1-naphthyl)- ethylamine (S-NEA) was utilized as chiral derivatization reagent and pre-column derivatization RP-HPLC method was established for the separation and assay of the three pairs of enantiomer. The method had good linear relationship over the investigated concentration range without interference. The average extraction efficiency was higher than 85% in different systems, and the intra-day and inter-day precisions were less than 15%. In serum albumin, the protein binding of etodolac enantiomers showed significant stereoselectivity that the affinity of S-enantiomer was stronger than R-enantiomer, and the stereoselectivity ratio reached 6.06; Flurbiprofen had only weak stereoselectivity in HSA, and ketoprofen had no stereoselectivity at all. Scatchard curves showed that all the three chiral drugs had two types of binding sites in HSA.

  19. Comparison of pharmaceutical properties of topical non-steroidal anti-inflammatory drug preparations on quality of life.

    Shibata, Yuuka; Ikeda, Hiroaki; Kondou, Yoshihiro; Kihira, Kenji


    To compare the effects of different pharmaceutical properties of commercially available topical nonsteroidal antiinflammatory drugs (NSAIDs) on the quality of life, we administered a questionnaire to 65 healthy volunteers. We investigated five creams, five gels, and four solutions of topical NSAID preparations in this study. The survey was conducted to clarify the relationship of their answers and pharmaceutical properties of the topical NSAID preparations. Questions addressed spreadability, smell, viscosity, and comfort level of the topical NSAID preparations. Among the five creams, Napageln had lower spreadability, less smell, and greater viscosity than the other preparations. Because of its easy spreadability, weak smell, and low viscosity, the volunteers favored Sector cream among the cream preparations. Among the five gel preparations, Inteban had less spreadability, stronger smell, and higher viscosity than the other preparations. The volunteers favored Epatec over the other gel preparations. All four solutions had the odor of menthol and other artificial ingredients, except for Napageln. These findings indicate that information on the pharmaceutical properties of commercially available topical NSAID preparations will be helpful to physicians and pharmacists in conducting medical treatment and prescribing.

  20. Aspirin and non-aspirin non-steroidal anti-inflammatory drug use and risk of lung cancer.

    Lim, Wei-Yen; Chuah, Khoon Leong; Eng, Philip; Leong, Swan Swan; Lim, Elaine; Lim, Tow Keang; Ng, Alan; Poh, Wee Teng; Tee, Augustine; Teh, Ming; Salim, Agus; Seow, Adeline


    There is evidence that aspirin and non-aspirin non-steroidal anti-inflammatory drug (NSAID) have anti-carcinogenic properties, but their effect on lung cancer, in particular in never-smokers, is unclear. Information on past or current use of anti-inflammatory medication was obtained in 398 Chinese female primary lung cancer cases and 814 controls in a hospital-based study in Singapore. 65% of cases and 88% of controls were never-smokers. Controls were excluded if they had been admitted for conditions associated with aspirin or NSAID use (n=174). Regular aspirin use (twice a week or more, for a month or more) was associated with a reduced risk of lung cancer (adjusted odds ratio [OR] 0.50, 95% confidence intervals [95%CI] 0.31-0.81 in non-smokers; OR 0.38, 95%CI 0.16-0.93 in smokers). Regular use of non-aspirin NSAID, paracetamol, steroid creams and steroid pills was uncommon and no association with lung cancer was detected. Our results suggest that aspirin consumption may reduce lung cancer risk in Asian women and are consistent with current understanding of the role of cyclooxygenase in lung carcinogenesis.

  1. Non-steroidal anti-inflammatory drug, nabumetone, prevents indometacin-induced gastric damage via inhibition of neutrophil functions.

    Ishiwata, Yoshiro; Okamoto, Masayuki; Yokochi, Shoji; Hashimoto, Hiroyuki; Nakamura, Takashi; Miyachi, Atsushi; Naito, Yuji; Yoshikawa, Toshikazu


    Nabumetone is a non-steroidal anti-inflammatory drug (NSAID). It works as a prodrug and is extensively metabolized to an active metabolite, 6-methoxy-2-naphthylacetic acid (6MNA). It is well known that neutrophil infiltration and activation are critical in the pathogenesis of NSAID-induced gastric injury, and nabumetone shows less incidence of gastrointestinal irritancy. We examined the effects of nabumetone on neutrophil activation and on indometacin-induced gastric damage. In the indometacin-induced gastric mucosal injury, rats were treated with indometacin and then nabumetone or 6MNA was orally administered. Nabumetone prevented gastric damage accompanied by the reduction of neutrophil infiltration into gastric mucosa, but such an effect was not observed with 6MNA. Nabumetone reduced the formyl methionyl leucyl phenylalanine (fMLP)-induced respiratory burst of human neutrophils to 30% of the control level in-vitro, but 6MNA did not. In addition, nabumetone prevented the fMLP-induced migration of neutrophils. Nabumetone did not inhibit O2- generation in the xanthine-xanthine oxidase system. These results suggest that nabumetone prevents gastric damage induced by the active metabolite, 6MNA, via the suppression of neutrophil activation in gastric mucosa.

  2. Safety of celecoxib and nonselective nonsteroidal anti-inflammatory drugs in juvenile idiopathic arthritis: results of the phase 4 registry


    Background This study aimed to assess long-term safety and developmental data on juvenile idiopathic arthritis (JIA) patients treated in routine clinical practice with celecoxib or nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs). Methods Children aged ≥2 to nabumetone were the most frequently used nsNSAIDs. At baseline, the celecoxib group was older, had a numerically longer median time since diagnosis, and a numerically higher proportion of patients with a history of gastrointestinal-related NSAID intolerance. AEs reported were those frequently observed with NSAID treatment and were similar across groups (nsNSAIDs: 52.0%; celecoxib: 52.9%). Twelve unique patients experienced a total of 18 serious AEs; the most frequent were infections, and none was attributed to NSAID use. Conclusions The safety profile of celecoxib and nsNSAIDs appears similar overall. The results from this registry, ongoing pharmacovigilance, and the phase 3 trial that led to the approval of celecoxib for children with JIA provide evidence that the benefit-risk for celecoxib treatment in JIA remains positive. Trial registration identifier NCT00688545. PMID:25057265

  3. Concentration of Non-Steroidal Anti-Inflammatory Drugs in the Pelvic Floor Muscles: An Experimental Comparative Rat Model

    Chin, Hung-Yen; Changchien, Eileen; Lin, Mei-Fung; Chiang, Chi-Hsin


    Purpose The aim of this study is to explore non-steroid anti-inflammation drugs (NSAIDs) potency for pelvic floor muscle pain by measuring local concentration in a rat model. Materials and Methods We used nine NSAIDs, including nabumetone, naproxen, ibuprofen, meloxicam, piroxicam, diclofenac potassium, etodolac, indomethacin, and sulindac, and 9 groups of female Wister rats. Each group of rats was fed with one kind of NSAID (2 mg/mL) for three consecutive days. Thereafter, one mL of blood and one gram of pelvic floor muscle were taken to measure drug pharmacokinetics, including partition coefficient, lipophilicity, elimination of half-life (T1/2) and muscle/plasma converting ratio (Css, muscle/Css, plasma). Results Diclofenac potassium had the lowest T1/2 and the highest mean Css, muscle/Css, plasma (1.9 hours and 0.85±0.53, respectively). The mean Css, muscle/Css, plasma of sulindac, naproxen and ibuprofen were lower than other experimental NSAIDs. Conclusion Diclofenac potassium had the highest disposition in pelvic floor muscle in a rat model. The finding implies that diclofenac potassium might be the choice for pain relief in pelvic muscle. PMID:24954342

  4. Thermal nociception as a measure of non-steroidal anti-inflammatory drug effectiveness in broiler chickens with articular pain.

    Caplen, Gina; Baker, Laurence; Hothersall, Becky; McKeegan, Dorothy E F; Sandilands, Victoria; Sparks, Nick H C; Waterman-Pearson, Avril E; Murrell, Joanna C


    Pain associated with poultry lameness is poorly understood. The anti-nociceptive properties of two non-steroidal anti-inflammatory drugs (NSAIDs) were evaluated using threshold testing in combination with an acute inflammatory arthropathy model. Broilers were tested in six groups (n=8 per group). Each group underwent a treatment (saline, meloxicam (3 or 5mg/kg) or carprofen (15 or 25mg/kg)) and a procedure (Induced (arthropathy-induction) or sham (sham-handling)) prior to testing. Induced groups had Freund's complete adjuvant injected intra-articularly into the left intertarsal joint (hock). A ramped thermal stimulus (1°C/s) was applied to the skin of the left metatarsal. Data were analysed using random-intercept multi-level models. Saline-induced birds had a significantly higher skin temperature (± SD) than saline-sham birds (37.6 ± 0.8°C vs. 36.5 ± 0.5°C; Z=-3.47, Pnociception). Quantification of nociceptive responsiveness in a predictable broiler pain model identified thermal anti-hyperalgesic properties of two NSAIDs, which suggested that therapeutically effective treatment was provided at the doses administered. Such validation of analgesic strategies will increase the understanding of pain associated with specific natural broiler lameness types.

  5. Sunlight-driven photocatalytic degradation of non-steroidal anti-inflammatory drug based on TiO₂ quantum dots.

    Kaur, Amandeep; Umar, Ahmad; Kansal, Sushil Kumar


    This paper reports the facile synthesis, characterization and solar-light driven photocatalytic degradation of TiO2 quantum dots (QDs). The TiO2 QDs were synthesized by a facile ultrasonic-assisted hydrothermal process and characterized in terms of their structural, morphological, optical and photocatalytic properties. The detailed studies confirmed that the prepared QDs are well-crystalline, grown in high density and exhibiting good optical properties. Further, the prepared QDs were efficiently used as effective photocatalyst for the sun-light driven photocatalytic degradation of ketorolac tromethamine, a well-known non-steroidal anti-inflammatory drug (NSAID). To optimize the photocatalytic degradation conditions, various dose-dependent, pH-dependent, and initial drug-concentration dependent experiments were performed. The detailed solar-light driven photocatalytic experiments revealed that ∼99% photodegradation of ketorolac tromethamine drug solution (10 mg L(-1)) was observed with optimized amount of TiO2 QDs and pH (0.5 g L(-1) and 4.4, respectively) under solar-light irradiations. The observed results demonstrate that simply synthesized TiO2 QDs can efficiently be used for the solar-light driven photocatalytic degradation of harmful drugs and chemicals.

  6. Effects of non-steroidal anti-inflammatory drugs on proliferation, differentiation and migration in equine mesenchymal stem cells.

    Müller, Maike; Raabe, Oksana; Addicks, Klaus; Wenisch, Sabine; Arnhold, Stefan


    In equine medicine, stem cell therapies for orthopaedic diseases are routinely accompanied by application of NSAIDs (non-steroidal anti-inflammatory drugs). Thus, it has to be analysed how NSAIDs actually affect the growth and differentiation potential of MSCs (mesenchymal stem cells) in vitro in order to predict the influence of NSAIDs such as phenylbutazone, meloxicam, celecoxib and flunixin on MSCs after grafting in vivo. The effects of NSAIDs were evaluated regarding cell viability and proliferation. Additionally, the multilineage differentiation capacity and cell migration was analysed. NSAIDs at lower concentrations (0.1-1 μM for celecoxib and meloxicam and 10-50 μM for flunixin) exert a positive effect on cell proliferation and migration, while at higher concentrations (10-200 μM for celecoxib and meloxicam and 100-1000 μM for flunixin and phenylbutazone), there is rather a negative influence. While there is hardly any influence on the adipogenic as well as on the chondrogenic MSC differentiation, the osteogenic differentiation potential, as demonstrated with the von Kossa staining, is significantly disturbed. Thus, it can be concluded that the effects of NSAIDs on MSCs are largely dependent on the concentrations used. Additionally, for some differentiation lineages, also the choice of NSAID is critical.

  7. In vivo modulation of the inflammatory response by nonsteroidal antiinflammatory drug-related compounds that trigger L-selectin shedding.

    Herrera-García, Ada; Domínguez-Luis, María; Arce-Franco, Mayte; López-Fernández, Judith; Feria, Manuel; Barreiro, Olga; Sánchez-Madrid, Francisco; Díaz-González, Federico


    Diphenylamine-based nonsteroidal antiinflammatory drugs (NSAIDs) are able to cause in vitro the shedding of L-selectin. The aim of this work was to determine the physio-logic relevance of L-selectin shedding in the antiinflammatory effect exerted by NSAIDs in vivo. Chemical compounds structurally related to NSAIDs - including diphenyl-amine, N-phenylanthranilic acid (N-Ph), diphenylacetic acid - as well as the traditional NSAID indomethacin were studied using the zymosan air-pouch mouse model. Animals intramuscularly pretreated with indomethacin or N-Ph, but not with diphenyl-amine or diphenylacetic acid, showed a significant dose-dependent reduction in the number of neutrophils compared with untreated animals (N-Ph, IC50 = 6.7 mg/kg). Except for indomethacin, none of these compounds caused any significant reduction in cyclooxygenase-1 activity in vivo. In flow chamber experiments, N-Ph reduced the capability of human neutrophils to pass across the endothelial barrier by interfering with leukocyte rolling step on HUVEC. N-Ph, but not diphenylacetic acid, induced activation-independent L-selectin shedding in mouse neutrophils. Interestingly, N-Ph exerted an antiinflammatory effect similar to that of the anti-L-selectin blocking antibody Mel-14, although no additive action was observed when both compounds were combined. These data suggest that the L-selectin shedding induced by NSAIDs may be involved in the antiinflammatory action exerted by these compounds in clinical settings.

  8. Charge transfer complex studies between some non-steroidal anti-inflammatory drugs and π-electron acceptors

    Duymus, Hulya; Arslan, Mustafa; Kucukislamoglu, Mustafa; Zengin, Mustafa


    Charge transfer (CT) complexes of some non-steroidal anti-inflammatory drugs, naproxen and etodolac which are electron donors with some π-acceptors, such as tetracyanoethylene (TCNE), 2,3-dichloro-5,6-dicyano- p-benzoquinone (DDQ), p-chloranil ( p-CHL), have been investigated spectrophotometrically in chloroform at 21 °C. The coloured products are measured spectrophotometrically at different wavelength depending on the electronic transition between donors and acceptors. Beer's law is obeyed and colours were produced in non-aqueous media. All complexes were stable at least 2 h except for etodolac with DDQ stable for 5 min. The equilibrium constants of the CT complexes were determined by the Benesi-Hildebrand equation. The thermodynamic parameters Δ H, Δ S, Δ G° were calculated by Van't Hoff equation. Stochiometries of the complexes formed between donors and acceptors were defined by the Job's method of the continuous variation and found in 1:1 complexation with donor and acceptor at the maximum absorption bands in all cases.

  9. Apparent tolerance of turkey vultures (Cathartes aura) to the non-steroidal anti-inflammatory drug diclofenac

    Rattner, B.A.; Whitehead, M.A.; Gasper, G.; Meteyer, C.U.; Link, W.A.; Taggart, M.A.; Meharg, A.A.; Pattee, O.H.; Pain, D.J.


    The nonsteroidal anti-inflammatory drug diclofenac is extremely toxic to Old World Gyps vultures (median lethal dose 0.1?0.2 mg/kg), evoking visceral gout, renal necrosis, and mortality within a few days of exposure. Unintentional secondary poisoning of vultures that fed upon carcasses of diclofenac-treated livestock decimated populations in the Indian subcontinent. Because of the widespread use of diclofenac and other cyclooxygenase-2 inhibiting drugs, a toxicological study was undertaken in turkey vultures (Cathartes aura) as an initial step in examining sensitivity of New World scavenging birds. Two trials were conducted entailing oral gavage of diclofenac at doses ranging from 0.08 to 25 mg/kg body weight. Birds were observed for 7 d, blood samples were collected for plasma chemistry (predose and 12, 24, and 48 h and 7 d postdose), and select individuals were necropsied. Diclofenac failed to evoke overt signs of toxicity, visceral gout, renal necrosis, or elevate plasma uric acid at concentrations greater than 100 times the estimated median lethal dose reported for Gyps vultures. For turkey vultures receiving 8 or 25 mg/kg, the plasma half-life of diclofenac was estimated to be 6 h, and it was apparently cleared after several days as no residues were detectable in liver or kidney at necropsy. Differential sensitivity among avian species is a hallmark of cyclooxygenase-2 inhibitors, and despite the tolerance of turkey vultures to diclofenac, additional studies in related scavenging species seem warranted.

  10. Bacterial microbiota profiling in gastritis without Helicobacter pylori infection or non-steroidal anti-inflammatory drug use.

    Xiao-Xing Li

    Full Text Available Recent 16S ribosomal RNA gene (rRNA molecular profiling of the stomach mucosa revealed a surprising complexity of microbiota. Helicobacter pylori infection and non-steroidal anti-inflammatory drug (NSAID use are two main contributors to gastritis and peptic ulcer. However, little is known about the association between other members of the stomach microbiota and gastric diseases. In this study, cloning and sequencing of the 16S rRNA was used to profile the stomach microbiota from normal and gastritis patients. One hundred and thirty three phylotypes from eight bacterial phyla were identified. The stomach microbiota was found to be closely adhered to the mucosa. Eleven Streptococcus phylotypes were successfully cultivated from the biopsies. One to two genera represented a majority of clones within any of the identified phyla. We further developed two real-time quantitative PCR assays to quantify the relative abundance of the Firmicutes phylum and the Streptococcus genus. Significantly higher abundance of the Firmicutes phylum and the Streptococcus genus within the Firmicutes phylum was observed in patients with antral gastritis, compared with normal controls. This study suggests that the genus taxon level can largely represent much higher taxa such as the phylum. The clinical relevance and the mechanism underlying the altered microbiota composition in gastritis require further functional studies.

  11. Pregnant women and non-steroidal anti-inflammatory drugs: Knowledge, perception and drug consumption pattern during pregnancy in Ethiopia

    Chalelgn Kassaw


    Full Text Available Background: Non-steroidal anti-inflammatory drugs (NSAIDs are among the widely used drugs and are often used by pregnant women. However, they can have significant teratogenic effects. The aim of the study was to investigate pregnant women′s knowledge about NSAIDs use during pregnancy and their perception and consumption pattern. Materials and Methods: The study was a cross sectional study on women waiting for a consultation in the selected maternity hospitals in Addis Ababa, Ethiopia. The pregnant women were selected randomly and then interviewed by using standardized questionnaires. Result : A total of 224 pregnant women were involved in the study. Out of those, 203 (90.6% of them have taken NSAIDs since the beginning of their pregnancy. About 201 (89.7%, 198 (88.4% and 189 (84.4% of the pregnant women considered that ibuprofen, diclofenac and aspirin are not NSAIDs respectively. Regarding analgesic effect of NSAIDs, 97 (43.3% of the pregnant women believed that NSAIDs are effective for treating pain. Acetaminophen was considered as the most effective treatment for pain by 84 (37.50% of the patients. Conclusion: Acetaminophen is the most common analgesic that was taken by most pregnant women. The knowledge of pregnant women about NSAIDs is poor.

  12. Dynamic model of eicosanoid production with special reference to non-steroidal anti-inflammatory drug-triggered hypersensitivity.

    Fajmut, Aleš; Emeršič, Tadej; Dobovišek, Andrej; Antić, Nataša; Schäfer, Dirk; Brumen, Milan


    The authors developed a mathematical model of arachidonic acid (AA) degradation to prostaglandins (PGs) and leukotrienes (LTs), which are implicated in the processes of inflammation and hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs). The model focuses on two PGs (PGE2 and PGD2) and one LT (LTC4), their % increases and their ratios. Results are compared with experimental studies obtained from non-asthmatics (NAs), and asthmatics tolerant (ATA) or intolerant (AIA) to aspirin. Simulations are carried out for predefined model populations NA, ATA and three AIA, based on the differences of two enzymes, PG E synthase and/or LTC4-synthase in two states, that is, no-inflammation and inflammation. Their model reveals that the model population with concomitant malfunctions in both enzymes is the most sensitive to NSAIDs, since the duration and the capacity for bronchoconstriction risk are highest after simulated oral dosing of indomethacin. Furthermore, inflammation prolongs the duration of the bronchoconstriction risk in all AIA model populations, and the sensitivity analysis reveals multiple possible scenarios leading to hypersensitivity, especially if inflammatory processes affect the expression of multiple enzymes of the AA metabolic pathway. Their model estimates the expected fold-changes in enzyme activities and gives valuable information for further targeted transcriptomic/proteomic and metabolomic studies.

  13. Ibuprofen and other widely used non-steroidal anti-inflammatory drugs inhibit antibody production in human cells.

    Bancos, Simona; Bernard, Matthew P; Topham, David J; Phipps, Richard P


    The widely used non-steroidal anti-inflammatory drugs (NSAIDs) function mainly through inhibition of cyclooxygenases 1 and 2 (Cox-1 and Cox-2). Unlike Cox-1, Cox-2 is considered an inducible and pro-inflammatory enzyme. We previously reported that Cox-2 is upregulated in activated human B lymphocytes and using Cox-2 selective inhibitors that Cox-2 is required for optimal antibody synthesis. It is not known whether commonly used non-prescription and non-Cox-2 selective drugs also influence antibody synthesis. Herein, we tested a variety of Cox-1/Cox-2 non-selective NSAIDs, namely ibuprofen, tylenol, aspirin and naproxen and report that they blunt IgM and IgG synthesis in stimulated human peripheral blood mononuclear cells (PBMC). Ibuprofen had its most profound effects in inhibiting human PBMCs and purified B lymphocyte IgM and IgG synthesis when administered in the first few days after activation. As shown by viability assays, ibuprofen did not kill B cells. The implications of this research are that the use of widely available NSAIDs after infection or vaccination may lower host defense. This may be especially true for the elderly who respond poorly to vaccines and heavily use NSAIDs.

  14. Latest concepts on the association between nonsteroidal anti-inflammatory drug-induced small intestinal injury and intestinal bacterial flora.

    Fujimori, Shunji; Sakamoto, Choitsu


    Luminal bacteria, one of the main aggressive factors of nonsteroidal anti-inflammatory drugs (NSAIDs), induce small intestinal mucosal injury. Because most bacteria invading from the mouth are eliminated by the highly acidic gastric environment, the upper small intestine contains relatively low numbers of microorganisms. With decreased peristalsis, decreased acidity, and lower oxidation-reduction potential, the ileum maintains a more diverse microflora and a higher bacterial population. As NSAID-induced small intestinal ulcerations tend to localize in the small intestinal distal part, as viewed by capsule endoscopy, the ulcers are in contact with a large amount of luminal bacteria. Recently, it was reported that proton-pump inhibitors (PPIs) exacerbate NSAID-induced small intestinal injury in rats. The study showed that PPIs impair the ability to disinfect due to the PPI-induced low acidic gastric environment, and this resulted in transubstantiation of intestinal flora which exacerbated NSAID-induced small intestinal injury. If it is true that PPIs exacerbate small intestinal injury, the methods of preventing NSAID-induced gastroduodenal injury to defend PPI-induced small intestinal injury should be reconsidered. Following several studies, there may be a possibility that probiotics and prebiotics are useful treatments for the prevention of NSAID-induced small intestinal injury. A method of determining bacterial flora maintenance including alteration of the environment and the administration of various drugs is required.

  15. Non-steroidal anti-inflammatory drugs and amyotrophic lateral sclerosis: results from five prospective cohort studies.

    Fondell, Elinor; O'Reilly, Éilis J; Fitzgerald, Kathryn C; Falcone, Guido J; McCullough, Marjorie L; Thun, Michael J; Park, Yikyung; Kolonel, Laurence N; Ascherio, Alberto


    Animal and pathological studies suggest that inflammation may contribute to amyotrophic lateral sclerosis (ALS) pathology and that non-steroidal anti-inflammatory drugs (NSAIDs) might be protective. However, there are no prospective data on the relation between NSAID use and ALS risk in humans. The relation between NSAID use and ALS risk was explored in five large prospective cohort studies (the Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health - AARP Diet and Health Study). Detailed NSAID information was sought from 780,000 participants, 708 of whom developed ALS during follow-up. Cox proportional hazards models were used within each cohort and cohort-specific estimates were pooled with random effects models. Results showed that neither non-aspirin NSAID use, nor aspirin use was associated with ALS risk overall. The multivariable, pooled relative risk was 0.96 (95% CI 0.76-1.22) among non-aspirin NSAID users compared with non-users. Duration of NSAID use in years and frequency of NSAID use were not associated with ALS risk overall. In conclusion, the results do not support an overall effect of NSAIDs on ALS risk, but because NSAIDs have heterogeneous effects, a role of individual compounds cannot be excluded.

  16. Aspirin and other non-steroidal anti-inflammatory drugs and risk of colorectal cancer: A Danish cohort study

    Friis, Søren; Poulsen, Aslak H; Sørensen, Henrik Toft;


    The optimal duration and dose of aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) in the potential prevention of colorectal cancer (CRC) have not been established. We examined this issue in the Danish Diet, Cancer, and Health Study. Self-reported NSAID use at entry (January...... subjects, we identified 615 CRC cases during 1995-2006. Daily aspirin use at entry was associated with a decreased risk of CRC (RR, 0.73; 95% CI, 0.49-1.10). A similar risk reduction was seen among subjects with 10 or more prescriptions for aspirin or non-aspirin NSAIDs and five or more years of follow......-up. Most aspirin prescriptions were for 75-150 mg aspirin tablets. Among non-aspirin NSAID users, only those with body mass index (BMI) above 25 showed risk reductions [RR, 0.69 (0.47-1.03) for 10 or more prescriptions]. Long-term consistent use of aspirin or non-aspirin NSAIDs appears necessary to achieve...

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

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


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

  18. Effects of nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NONO-NSAIDs) on melanoma cell adhesion

    Cheng, Huiwen [Edison Biotechnology Institute, Ohio University, Athens, OH 45701 (United States); Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701 (United States); Mollica, Molly Y.; Lee, Shin Hee [Edison Biotechnology Institute, Ohio University, Athens, OH 45701 (United States); Wang, Lei [Edison Biotechnology Institute, Ohio University, Athens, OH 45701 (United States); Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701 (United States); Velázquez-Martínez, Carlos A., E-mail: [Chemistry Section, Laboratory of Comparative Carcinogenesis and Basic Research Program, SAIC-Frederick Inc., National Cancer Institute at Frederick, Frederick, MD 21702 (United States); Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton Alberta, Canada T6G 2N8 (Canada); Wu, Shiyong, E-mail: [Edison Biotechnology Institute, Ohio University, Athens, OH 45701 (United States); Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701 (United States)


    A new class of nitric oxide (NO•)-releasing nonsteroidal anti-inflammatory drugs (NONO-NSAIDs) were developed in recent years and have shown promising potential as NSAID substitutes due to their gentle nature on cardiovascular and gastrointestinal systems. Since nitric oxide plays a role in regulation of cell adhesion, we assessed the potential use of NONO-NSAIDs as anti-metastasis drugs. In this regard, we compared the effects of NONO-aspirin and a novel NONO-naproxen to those exerted by their respective parent NSAIDs on avidities of human melanoma M624 cells. Both NONO-NSAIDs, but not the corresponding parent NSAIDs, reduced M624 adhesion on vascular cellular adhesion molecule-1 (VCAM-1) by 20–30% and fibronectin by 25–44% under fluid flow conditions and static conditions, respectively. Only NONO-naproxen reduced (∼ 56%) the activity of β1 integrin, which binds to α4 integrin to form very late antigen-4 (VLA-4), the ligand of VCAM-1. These results indicate that the diazeniumdiolate (NO•)-donor moiety is critical for reducing the adhesion between VLA-4 and its ligands, while the NSAID moiety can impact the regulation mechanism of melanoma cell adhesion. -- Highlights: ► NONO-naproxen, a novel nitric oxide-releasing NSAID, was synthesized. ► NONO-NSAIDs, but not their parent NSAIDs, reduced melanoma adhesion. ► NONO-naproxen, but not NONO-aspirin and NSAIDs, reduced activity of β1 integrin.

  19. Subtle structural changes in tetrahydroquinolines, a new class of nonsteroidal selective androgen receptor modulators, induce different functions.

    Nagata, Naoya; Kawai, Kentaro; Nakanishi, Isao


    Tetrahydroquinolines (THQs), a new class of nonsteroidal selective androgen receptor (AR) modulators, have two indispensable functional groups, that is, a hydroxyl group for AR binding and a nitro group for agonistic activity. Interestingly, switching the nitro to a cyano group, the compound acts as an antagonist. To understand this phenomenon, molecular dynamics simulations were applied for dihydrotestosterone (DHT) and representative THQs complexes with AR. Upon ligand binding, the hydroxyl group formed a tight hydrogen-bond (H-bond) with Asn705 on Helix 3 (H3). The immobilization of Asn705 on H3 is helpful in the formation of tight H-bonds with Asp890 on loop 11-12, and this immobilization consequently leads to a stabilization of H12. The difference in the DHT carbonyl isosteres affected the presence or absence of the H-bonds between the hydroxyl group of THQ and Thr877 and the distortion of H12, which is caused by the methyl group of THQ. Thus, the binding, agonist, and antagonist functions were controlled by subtle structural changes in THQ.

  20. Moral actor, selfish agent.

    Frimer, Jeremy A; Schaefer, Nicola K; Oakes, Harrison


    People are motivated to behave selfishly while appearing moral. This tension gives rise to 2 divergently motivated selves. The actor-the watched self-tends to be moral; the agent-the self as executor-tends to be selfish. Three studies present direct evidence of the actor's and agent's distinct motives. To recruit the self-as-actor, we asked people to rate the importance of various goals. To recruit the self-as-agent, we asked people to describe their goals verbally. In Study 1, actors claimed their goals were equally about helping the self and others (viz., moral); agents claimed their goals were primarily about helping the self (viz., selfish). This disparity was evident in both individualist and collectivist cultures, attesting to the universality of the selfish agent. Study 2 compared actors' and agents' motives to those of people role-playing highly prosocial or selfish exemplars. In content (Study 2a) and in the impressions they made on an outside observer (Study 2b), actors' motives were similar to those of the prosocial role-players, whereas agents' motives were similar to those of the selfish role-players. Study 3 accounted for the difference between the actor and agent: Participants claimed that their agent's motives were the more realistic and that their actor's motives were the more idealistic. The selfish agent/moral actor duality may account for why implicit and explicit measures of the same construct diverge, and why feeling watched brings out the better angels of human nature.

  1. [Effect of protracted therapy with chondroprotectors and non-steroidal anti-inflammatory drugs on the quality of life in patients with osteoarthrosis].

    Maĭko, O Iu; Bagirova, G G


    Dynamics of clinical parameters and quality of life (QL) was evaluated in 281 patients with knee and hip osteoarthrosis (OA) during long-term treatment of different duration. The group was dominated by women (71%) aged 41-65 yr with grade I-III OA according to Kellgren. Patients of groups I and II received only non-steroidal anti-inflammatory drugs (diclofenac, nize), those of groups III-IV the same drugs in combination with structum, chondrolon, and zeel T respectively. Clinical parameters were assessed based on VAS at rest and in motion, Leken's indices, and WOMAC, QL from SF-36 questionnaire. Variable clinical course was recorded in patients treated with non-steroidal drugs alone that caused rapid improvement after the very first treatment sessions followed by deterioration of the patients' condition. Addition of structum resulted in marked optimization of clinical and QL parameters within 3 months after the onset of combined therapy. Similar effect was obtained using chondrolon and zeel T, but 2-3 clinical parameters and 3 QL parameters were not significantly different from the initial ones after 12 and 24 months of therapy. It is concluded that structum produced the best therapeutic effect followed by chondrolon and zeel T. Non-steroidal anti-inflammatory drugs had no beneficial action whatever in patients with OA.

  2. Mobile agent security using proxy-agents and trusted domains

    Mitrovic, Nikola; Arronategui Arribalzaga, Unai


    Commercial or wide-network deployment of Mobile Agent Systems is not possible without satisfying security architecture. In this paper we propose architecture for secure Mobile Agent Systems, using Trusted Domains and Proxy agents. Existing approaches are based on security services at the level of an agent system, library or specific objects. Our concept uses proxy agents to enable transparent security services both to security-aware mobile agents and legacy agents. Per-agent and domain-level...


    Maleković, Mirko; Čubrilo, Mirko


    [n this paper, we characterize the integrated agent in multi-agent systems. The following result is proved: if a multi-agent system is reflexive (symmetric, transitive, Euclidean) then the integrated agent of the multi-agent system is reflexive (symmetric, transitive, Euclidean), respectively. We also prove that the analogous result does not hold for multi-agent system's serial ness. A knowledge relationship between the integrated agent and agents in a multiagent system is presented.

  4. Agent Architectures for Compliance

    Burgemeestre, Brigitte; Hulstijn, Joris; Tan, Yao-Hua

    A Normative Multi-Agent System consists of autonomous agents who must comply with social norms. Different kinds of norms make different assumptions about the cognitive architecture of the agents. For example, a principle-based norm assumes that agents can reflect upon the consequences of their actions; a rule-based formulation only assumes that agents can avoid violations. In this paper we present several cognitive agent architectures for self-monitoring and compliance. We show how different assumptions about the cognitive architecture lead to different information needs when assessing compliance. The approach is validated with a case study of horizontal monitoring, an approach to corporate tax auditing recently introduced by the Dutch Customs and Tax Authority.

  5. Decontamination Data - Blister Agents

    U.S. Environmental Protection Agency — Decontamination efficacy data for blister agents on various building materials using various decontamination solutions. This dataset is associated with the following...

  6. Change Agent Survival Guide

    Dunbar, Folwell L.


    Consulting is a rough racket. Only a tarantula hair above IRS agents, meter maids and used car sales people, the profession is a prickly burr for slings and arrows. Throw in education, focus on dysfunctional schools and call oneself a "change agent," and this bad rap all but disappears. Unfortunately, though, consulting/coaching/mentoring in…

  7. Agents in domestic environments

    Moergestel, Leo van; Langerak, Wouter; Meerstra, Glenn; Nieuwenburg, Niels van; Pape, Franc; Telgen, Daniël; Puik, Erik; Meyer, John-Jules


    Athor supplied : "This paper describes an agent-based architecture for domotics. This architecture is based on requirements about expandability and hardware independence. The heart of the system is a multi-agent system. This system is distributed over several platforms to open the possibility to ti

  8. Avoidance of nonsteroidal anti-inflammatory drugs after negative provocation tests in urticaria/angioedema reactions: Real-world experience.

    Bommarito, Luisa; Zisa, Giuliana; Riccobono, Francesca; Villa, Elisa; D'Antonio, Cristian; Calamari, Ambra M; Poppa, Mariangela; Moschella, Adele; Di Pietrantonj, Carlo; Galimberti, Maurizio


    Drug provocation tests (DPTs) are the gold standard in diagnosing nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity; however, only few data about follow-up of patients with negative DPTs are actually available. The aim of this study was to assess patients' behavior in taking NSAIDs again and to evaluate NSAID tolerability after negative allergological workup. This is a follow-up study involving patients evaluated for history of cutaneous reactions (urticaria and or angioedema) after NSAID intake and with negative DPTs with the suspected NSAID. Patients were asked during a phone interview about the intake of NSAIDs, tolerance, or reasons of avoidance. The negative predictive value (NPV) of NSAIDs DPTs was calculated. One hundred eleven of 142 patients were successfully contacted; 46/111 (41.44%) took the same NSAID previously tested with two adverse reactions reported (4.34%). Fifty-three of 111 (47.74%) patients did not take the same NSAID, but 34 of them took at least another strong cyclooxygenase (COX) 1 inhibitor, with 1 adverse reaction (2.94%) and 19 of them took only weak COX-1 inhibitors. Twelve of 111 patients (10.8%) did not take any NSAID. Reasons for drug avoidance were mainly fear of reactions (70.8%) and no need (29.2%). NPV, overall, was 96.97% (95% confidence interval, 91-99%). Although NSAID hypersensitivity diagnosis was ruled out by oral provocation test, the majority of patients with a history of urticaria/angioedema avoided the intake of the tested NSAIDs for fear of new reactions, particularly when strong COX-1 inhibitor NSAIDs were involved. The high NPV value of DPT resulting from this study should reassure NSAID intake.

  9. Provocation tests with the offending nonsteroidal anti-inflammatory drugs in patients with urticaria/angioedema reactions.

    Zisa, Giuliana; Riccobono, Francesca; Bommarito, Luisa; D'Antonio, Cristian; Calamari, Ambra Marianna; Poppa, Mariangela; Moschella, Maria Adele; Di Pietrantonj, Carlo; Galimberti, Maurizio


    The provocation test (PT) with the suspected drug represents the gold standard in the diagnosis of non-IgE hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs). Nevertheless, there is no consensus regarding the clinical management of suspected NSAID-sensitive patients. This study assessed if a PT with the suspected drug is a reliable and safe proceeding to confirm NSAID hypersensitivity in patients with a clinical history of urticaria/angioedema (Urt/AE). It also analyzed different patient characteristics (such as gender, age, atopy, dermographism, time interval between the last drug reaction, and number of previous NSAID reactions) in relation to PT positivity. One hundred fifty-nine patients with Urt/AE apparently related to assumption of one or more NSAIDs underwent PT with the suspected drugs. Moreover, to distinguish single/multiple NSAID reactivity in patients who did not tolerate the offending NSAID, another strong cyclooxygenase-1 inhibitor PT was performed. PT was negative in 142/159 patients (89.31%), ruling out a diagnosis of NSAIDs hypersensitivity; 17/159 patients (10.69%) experienced a reaction of Urt/AE during the PT: 8 patients were diagnosed as single reactors to NSAIDs and 4 as multiple reactors to NSAIDs. Those with a history of multiple NSAID reactions and male patients were both more likely to have a positive PT. Our results suggest that in all patients with history of NSAID cutaneous reactions, the NSAID hypersensitivity should be confirmed by an oral PT and that the diagnostic proceeding can safely start with the offending NSAID.

  10. Interaction or relationship between Helicobacter pylori and non-steroidal anti-inflammatory drugs in upper gastrointestinal diseases

    Kai-Yu Ji; Fu-Lian Hu


    According to a meta-analysis, H pylori and non-steroidal anti-inflammatory drugs (NSAID) independently and significantly increase the risk of gastroduodenal ulcer and ulcer bleeding. Their coincidence is frequent,demonstration of a possible relationship and consequent attitude is of important implications. But unfortunately,no consensus has been approved in the past years and their interactions are still controversial. H pylori and NSAID are known to share a number of pathogenic mechanisms, but there is no evidence for the significant synergic action between these two risk factors. Their relationship is independent, additive, synergistic or antagonistic without considering the influence of other factors because studies on this subject are different in almost all aspects of their methodology, including the definition of a NSAID user as well as the types,doses, duration and their indications for NSAID use,as well as their end-points, definition of dyspepsia and regimes used for eradication of H pylori. These might contribute to the conflicting results and opinions. H pylori infection in humans does not act synergistically with NSAID on ulcer healing, and there is no need to eradicate it. This notion is supported by the finding that the eradication of H pylori does not affect NSAIDinduced gastropathy treated with omeprazole and that H pylori infection induces a strong cyclooxygenase-2(COX-2) expression resulting in excessive biosynthesis of gastroprotective prostaglandin which in turn counteracts NSAID-induced gastropathy and heals the existing ulcer.Other investigators claimed that H pylori infection acts synergistically with NSAID on ulcer development, and H pylori should be eradicated, particularly at the start of long-term NSAID therapy. Eradication of H pylori prior to NSAID treatment does not appear to accelerate ulcer healing or to prevent recurrent ulcers in NSAID users.However, some recommendations can be drawn from the results of clinical trails.

  11. Special diaphragm-like strictures of small bowel unrelated to non-steroidal anti-inflammatory drugs

    Ming-Liang Wang; Fei Miao; Yong-Hua Tang; Xue-Song Zhao; Jie Zhong; Fei Yuan


    AIM: To summarize clinical, endoscopic, radiologic and pathologic ffeatures off special diaphragm-like strictures ffound in small bowel, with no patient use off non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: From January 2000 to Ddecember 2009, 5 cases (2 men and 3 women, with a mean age of 41.6 years) were diagnosed as having diaphragm-like strictures off small bowel on imaging,operationand, operationandoperation and pathology. All the patients denied the use of NSAIDs. The clinical, endoscopic, radiologic and pathologic findings in these 5 patients were retrospectively reviewed from the hospital database. Images of capsule endoscopy (CE) and small bowel follow-through (SBFT) obtained in 3 and 3 patients, respectively, and images off double-balloon enteroscopy and computed tomography enterography (CTE) obtained in all 5 patients were available for review. RESULTS: All patients presented with long-term (2-16 years) symptoms of gastrointestinal bleeding and varying degrees of anemia. There was only one stricture in ffour cases and three lesions in one case, and all the lesions were located in the middle or distal segment off ileum. Circumferential stricture was shown in the small bowel in three cases in the CE image, but the capsule was retained in the small bowel of 2 patients. Routine abdomen computed tomography scan showed no other abnormal results except gallstones in one patient. The lesions were shown as circumfferential strictures accompanied by dilated small bowel loops in the small bowel on the images of CTE (in all 5 cases), SBFT (in 2 cases) and double-balloon enteroscopy (in all cases). On microscopy, a chronic infflammatory inffiltrate and circumferential diaphragm were found in all lesions. CONCLUSION: Ddiaphragm-like strictures off small bowel might be a special consequence off unclear damaging insults to the intestine, having similar clinical, endoscopic, radiologic and pathologic features.

  12. Non-steroidal anti-inflammatory drug for pulmonary administration: design and investigation of ketoprofen lysinate fine dry powders.

    Stigliani, Mariateresa; Aquino, Rita P; Del Gaudio, Pasquale; Mencherini, Teresa; Sansone, Francesca; Russo, Paola


    Pulmonary inflammation is an important therapeutic target in cystic fibrosis (CF) patients, aiming to limit and delay the lung damage. The purpose of the present research was to produce respirable engineered particles of ketoprofen lysinate, a non-steroidal anti-inflammatory drug able to fight lung inflammatory status by direct administration to the site of action. Micronized drug powders containing leucine as dispersibility enhancer were prepared by co-spray drying the active compound and the excipient from water or hydro-alcoholic feeds. Microparticles were fully characterized in terms of process yield, particle size distribution, morphology and drug content. The ability of the drug to reach the deepest airways after aerosolization of spray-dried formulations was evaluated by Andersen cascade impactor, using the monodose DPI as device. In order to investigate the behaviour of the drug once in contact with lung fluid, an artificial CF mucus was prepared. Drug permeation properties were evaluated interposing the mucus layer between the drug and a synthetic membrane mounted in Franz-type diffusion cells. Finally, the effect of the engineered particles on vitality of human airway epithelial cells of patients homozygous for ΔF 508 CF (CuFi1) was studied and compared to that of raw active compound. Results indicated that powders engineering changed the diameter and shape of the particles, making them suitable for inhalation. The mucus layer in the donor compartment of vertical diffusion cells slowed down drug dissolution and permeation, leucine having no influence. Cell proliferation studies evidenced that the spray drying process together with the addition of leucine reduced the cytotoxic effect of ketoprofen lysine salt as raw material, making the ketoprofen lysinate DPI a very promising product for the inflammation control in CF patients.

  13. Safe full-dose one-step nabumetone challenge in patients with nonsteroidal anti-inflammatory drug hypersensitivity.

    Confino-Cohen, Ronit; Goldberg, Arnon


    Aspirin and all nonsteroidal anti-inflammatory drugs (NSAIDs) are a chemically heterogeneous group of compounds that share the ability to inhibit the enzyme cyclooxygenase (COX). This inhibitory effect, especially of COX-1, is suggested as the mechanism underlying NSAID-induced hypersensitivity reactions. In this study, we evaluated the safety and convenience of a single full-dose challenge with nabumetone, a selective COX-2 inhibitor, in patients with hypersensitivity to nonselective NSAIDs (ns-NSAIDs). Twenty-four subjects with a history of hypersensitivity reactions to at least two different ns-NSAIDs on two different occasions were enrolled in the study. The patients were otherwise healthy and did not suffer from NSAID- or aspirin-induced asthma or urticaria. All subjects were orally challenged by a single full dose (1000 mg) of nabumetone, monitored closely in the hospital for the next 4 hours and contacted by telephone the next morning and 3-12 months afterward. Twenty-two patients tolerated nabumetone without any reaction during and after the challenge. One patient had a single urticarial lesion and one patient reported mild pruritus without objective signs, both of which resolved spontaneously. Thirteen patients, including the patient who responded with pruritus to the challenge, used nabumetone on several occasions during the follow-up period without any adverse reaction. Our study shows that in patients with a history of aspirin- and ns-NSAID-induced hypersensitivity reaction, a rapid one-step challenge with nabumetone was well tolerated. These initial data support the possibility that a single full dose of nabumetone can be tried as a safe alternative in most patients with a hypersensitivity reaction to ns-NSAIDs.

  14. Non-steroidal anti-inflammatory drugs and renal response to exercise: a comparison of indomethacin and nabumetone.

    Olsen, N V; Jensen, N G; Hansen, J M; Christensen, N J; Fogh-Andersen, N; Kanstrup, I L


    Nabumetone, a newer non-steroidal anti-inflammatory drug (NSAID) which preferentially blocks cyclo-oxygenase-2 activity, may be less nephrotoxic than indomethacin. This study tested whether nabumetone has effects different from those of indomethacin on exercise-induced changes in renal function and the renin-aldosterone system. In a randomized fashion, ten subjects were studied after indomethacin (100 mg), nabumetone (1 g) or no medication (control) administered orally at 22.00 hours on the day before each study day, and again at 8.00 hours upon arrival at the laboratory. Renal function was studied at baseline, during graded 20-min exercise sessions at 25%, 50% and 75% of the maximal oxygen uptake rate, and subsequently during two 1-h recovery periods. Heart rate, arterial blood pressure, cardiac output and plasma catecholamines at rest and during exercise were not altered by indomethacin or nabumetone. Indomethacin decreased urinary rates of excretion of 6-oxo-prostaglandin F(1alpha) (6-oxo-PGF(1alpha)) and thromboxane B(2) in all study periods. Nabumetone decreased 6-oxo-PGF(1alpha) excretion during and after exercise. Excretion rates for PGE(2) did not change. Neither indomethacin nor nabumetone changed baseline values or exercise-induced decreases in renal plasma flow or glomerular filtration rate. Indomethacin, but not nabumetone, decreased sodium excretion, urine flow rate and free water clearance. The renal response to exercise, however, remained unchanged. In contrast with nabumatone, indomethacin decreased the plasma renin concentration. Thus, during exercise, nabumetone may decrease the excretion of 6-oxo-PGF(1alpha) by inhibition of cyclo-oxygenase-1 or by inhibition of specific exercise-induced activation of cyclo-oxygenase-2, or both. None of the drugs changed the renal response to exercise. Inhibition by indomethacin of angiotensin II and thromboxane A(2) synthesis may, during exercise, counterbalance renal vasoconstriction caused by blockade of

  15. Risk factors of adverse drug reaction from non-steroidal anti-inflammatory drugs in Shanghai patients with arthropathy

    Wen SHI; Yong-ming WANG; Shao-li LI; Min YAN; Duan Li; Bin-yah CHEN; Neng-neng CHENG


    AIM: The study was to screen the possible risk factors of adverse drug reaction (ADR) induced by non-steroidal anti-inflammatory drugs (NSAIDs) in Shanghai patients with arthropathy. METHODS: The subjects were randomly selected from a database of outpatients with arthropathy from 9 main hospitals in Shanghai. A door to door retrospective epidemiological survey was used to collect demographic information about the patients, both individual and familial. This included data on their medical histories, lifestyle and dietary habits, history of smoking and alcohol consumption, history of drug therapy, quality of life (QOL) prior to NSAIDs intake, history of NSAIDs therapy and its ADR events, etc. Descriptive statistical methods and univariate analysis were also used to identify possible risk factors for ADRs induced by NSAIDs. RESULTS: Of the 1002 patients surveyed, the average length of NSAIDs intake was 2 years. ADR incidence from different NSAIDs was high, in a range from 46.7 %-66.2 %.In general, the candidate risk factors for ADRs were different for each NSAID. Each of the candidate risk factors were defined and studied in order to evaluate its role in the determination of ADRs from NSAIDs. "Family history of ADRs caused by NSAIDs" was found to be a significant risk factor for the four commonly used NSAIDs:meloxicam, diclofenac, nimesulide, and nabumetone. CONCLUSION: A retrospective epidemiological survey was useful in detecting the risk factors for ADRs caused by NSAIDs. The study found that different NSAIDs might have different risk factors and that there is no single risk factor universally applicable to all NSAIDs.

  16. Validation of a micellar liquid chromatographic method for determination of caffeine and non-steroidal anti-inflammatories.

    El Sherbiny, Dina; Wahba, Mary E K


    An accurate, simple, sensitive and selective micellar liquid chromatographic method has been developed for the simultaneous determination of caffeine (CAF) and two non-steroidal anti-inflammatory drugs, namely ibuprofen (IBU) and ketoprofen (KET). The chemometric approach was applied to the optimization of separation of the studied drugs. To optimize their separation, the effect of six experimental parameters on retention was investigated by means of multivariate analysis. Separation was conducted using an ODS C18 (150 × 4.6 mm i.d.) stainless steel column at ambient temperature with UV detection at 260 nm. A mobile phase composed of 40 mM sodium dodecyl sulphate (SDS), 10% 1-propanol and 0.3% tri-ethylamine in 0.02 M phosphoric acid adjusted to pH 3 has been used at a flow rate of 1 mL/min. Regression models were characterized by both descriptive and predictive ability (R(2) ≥ 97.9% and R(cv)(2) ≥ 96.2%) and allowed the chromatographic separation of the drugs with a good resolution and a total analysis time within 15 min. The calibration curves were rectilinear over the concentration ranges of 2.0-25.0, 1.5-15.0 and 1.0-10.0 µg/mL for IBU, KET and CAF, respectively, with detection limits of 1.2, 1.0 and 0.6 µg/mL, and quantification limits of 1.6, 1.2 and 0.8 µg/mL, respectively. The results obtained were in good agreement with those obtained by the comparison method.

  17. Inhibition of Human Transthyretin Aggregation by Non-Steroidal Anti-Inflammatory Compounds: A Structural and Thermodynamic Analysis

    Luis Mauricio T. R. Lima


    Full Text Available Transthyretin (TTR is a homotetrameric protein that circulates in plasma and cerebral spinal fluid (CSF whose aggregation into amyloid fibrils has been associated with at least two different amyloid diseases: senile systemic amyloidosis (SSA and familial amyloid polyneuropathy (FAP. In SSA aggregates are composed of WT-TTR, while in FAP more than 100 already-described variants have been found in deposits. Until now, TTR-related diseases have been untreatable, although a new drug called Tafamidis has been approved only in Europe to specifically treat V30M patients. Thus, new strategies are still necessary to treat FAP caused by other variants of TTR. TTR has two channels in the dimer interface that bind to the hormone thyroxin and that have been used to accommodate anti-amyloidogenic compounds. These compounds stabilize the tetramers, rendering TTR less amyloidogenic. Here, we investigated the effects of three non-steroidal anti-inflammatory compounds—sulindac (SUL, indomethacin (IND and lumiracoxib (LUM—as tetramer stabilizers and aggregation inhibitors. WT-TTR and the very aggressive TTR variant L55P were used as models. These compounds were able to stabilize TTR against high hydrostatic pressure (HHP, increasing the ΔGf by several kcal. They were also effective in inhibiting WT-TTR and L55P acid- or HHP-induced aggregation; in particular, LUM and IND were very effective, inhibiting almost 100% of the aggregation of both proteins under certain conditions. The species formed when aggregation was performed in the presence of these compounds were much less toxic to cells in culture. The crystal structures of WT-TTR bound to the three compounds were solved at high resolution, allowing the identification of the relevant protein:drug interactions. We discuss here the ligand-binding features of LUM, IND and SUL to TTR, emphasizing the critical interactions that render the protein more stable and less amyloidogenic.

  18. Gastric mucin expression in Helicobacter pylori-related,nonsteroidal anti-inflammatory drug-related and idiopathic ulcers

    Doron Boltin; Marisa Halpern; Zohar Levi; Alex Vilkin; Sara Morgenstern; Samuel B Ho; Yaron Niv


    AIM:To determine the pattern of secreted mucin expression in Helicobacter pylori (H.pylori)-related,nonsteroidal anti-inflammatory drug (NSAID)-related and idiopathic gastric ulcers.METHODS:We randomly selected 92 patients with H.pylori-associated (n =30),NSAID-associated (n =18),combined H.pylori and NSAID-associated gastric ulcers (n =24),and patients with idiopathic gastric ulcers (n =20).Immunohistochemistry for T-cell CD4/CD8,and for mucin 5AC (MUC5AC) and mucin 6 (MUC6),was performed on sections of the mucosa from the ulcer margin.Inflammation score was assessed according to the Sydney system.RESULTS:MUC5AC was expressed on the surface epithelium (98.9%) and neck glands (98.9%) with minimal expression in the deep glands (6.5%).MUC6 was strongly expressed in the deep glands (97.8%),variable in the neck glands (19.6%) and absent in the surface epithelium (0%).The pattern of mucin expression in idiopathic ulcer margins was not different from the expression in ulcers associated with H.pylori,NSAIDs,or combined H.pylori and NSAIDs.CD4/CD8 ratio was higher in H.pylori-positive patients (P =0.009).Idiopathic ulcers are associated with hospitalized patients and have higher bleeding and mortality rates.CONCLUSION:Idiopathic ulcers have a unique clinical profile.Gastric mucin expression in idiopathic gastric ulcers is unchanged compared with H.pylori and/or NSAID-associated ulcers.

  19. The Diamine Oxidase Gene Is Associated with Hypersensitivity Response to Non-Steroidal Anti-Inflammatory Drugs

    Agúndez, José A. G.; Ayuso, Pedro; Cornejo-García, José A.; Blanca, Miguel; Torres, María J.; Doña, Inmaculada; Salas, María; Blanca-López, Natalia; Canto, Gabriela; Rondon, Carmen; Campo, Paloma; Laguna, José J.; Fernández, Javier; Martínez, Carmen; García-Martín, Elena


    Non-steroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in hypersensitivity drug reactions. Histamine is released in the allergic response to NSAIDs and is responsible for some of the clinical symptoms. The aim of this study is to analyze clinical association of functional polymorphisms in the genes coding for enzymes involved in histamine homeostasis with hypersensitivity response to NSAIDs. We studied a cohort of 442 unrelated Caucasian patients with hypersensitivity to NSAIDs. Patients who experienced three or more episodes with two or more different NSAIDs were included. If this requirement was not met diagnosis was established by challenge. A total of 414 healthy unrelated controls ethnically matched with patients and from the same geographic area were recruited. Analyses of the SNPs rs17740607, rs2073440, rs1801105, rs2052129, rs10156191, rs1049742 and rs1049793 in the HDC, HNMT and DAO genes were carried out by means of TaqMan assays. The detrimental DAO 16 Met allele (rs10156191), which causes decreased metabolic capacity, is overrepresented among patients with crossed-hypersensitivity to NSAIDs with an OR  = 1.7 (95% CI  = 1.3–2.1; Pc  = 0.0003) with a gene-dose effect (P = 0.0001). The association was replicated in two populations from different geographic areas (Pc  = 0.008 and Pc  = 0.004, respectively). Conclusions and implications The DAO polymorphism rs10156191 which causes impaired metabolism of circulating histamine is associated with the clinical response in crossed-hypersensitivity to NSAIDs and could be used as a biomarker of response. PMID:23152756

  20. Deep Tissue Massage and Nonsteroidal Anti-Inflammatory Drugs for Low Back Pain: A Prospective Randomized Trial

    Marian Majchrzycki


    Full Text Available Objective. To investigate whether chronic low back pain therapy with deep tissue massage (DTM gives similar results to combined therapy consisting of DTM and non-steroid anti-inflammatory drugs (NSAID. Design. Prospective controlled randomized single blinded trial. Settings. Ambulatory care of rehabilitation. Participants. 59 patients, age 51.8 ± 9.0 years, with chronic low back pain. Interventions. 2 weeks of DTM in the treatment group (TG versus 2 weeks of DTM combined with NSAID in the control group (CG. Main Outcome Measures. Visual analogue scale, Oswestry disability index (ODI, and Roland-Morris questionnaire (RM. Results. In both the TG and the CG, a significant pain reduction and function improvement were observed. VAS decreased from 58.3 ± 18.2 to 42.2 ± 21.1 (TG and from 51.8 ± 18.8 to 30.6 ± 21.9 (CG. RM value decreased from 9.8 ± 5.1 to 6.4 ± 4.4 (TG, and from 9.3 ± 5.5 to 6.1 ± 4.6 (CG. ODI value decreased from 29.2 ± 17.3 to 21.4 ± 15.1 (TG and from 21.4 ± 9.4 to 16.6 ± 9.4 (CG. All pre-post-treatment differences were significant; however, there was no significant difference between the TG and the CG. Conclusion. DTM had a positive effect on reducing pain in patients with chronic low back pain. Concurrent use of DTM and NSAID contributed to low back pain reduction in a similar degree that the DTM did.

  1. Factors Affecting the Efficacy of Nonsteroidal Anti-inflammatory Drugs in Preventing Post–Endoscopic Retrograde Cholangiopancreatography Pancreatitis

    Rustagi, Tarun; Njei, Basile


    Objectives To identify the factors affecting the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in preventing post–endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Methods We systematically searched databases for relevant studies published from inception to November 2013. Results A meta-analysis of 11 randomized trials (n = 2497) revealed a significant reduction in PEP in patients who received NSAIDs compared with that in patients who received placebo (relative risk [RR], 0.59; 95% confidence interval [CI], 0.41–0.85; P = 0.005). In subgroup analysis by treatment type, indomethacin had no significant effect (RR, 0.66; 95% CI, 0.38–1.15; P = 0.14), whereas other NSAIDs showed significant benefit (RR, 0.51; 95% CI, 0.29–0.91; P = 0.02). Only rectal administration significantly reduced the incidence of PEP (RR, 0.43; 95% CI, 0.32–0.58; P < 0.00001). The risk for PEP was the lowest among patients who received NSAIDs before ERCP (RR, 0.48; 95% CI, 0.29–0.78; P = 0.003). NSAIDs did not significantly reduce the risk of PEP in men (RR, 0.61; 95% CI, 0.34–1.09), patients with sphincter of Oddi dysfunction (RR, 0.98; 95% CI, 0.38–2.54), or patients with pancreatic duct injection (RR, 0.64; 95% CI, 0.35–1.18). Conclusions Rectal administration of NSAIDs (especially diclofenac), before ERCP, seemed to be the most effective strategy for preventing PEP. PMID:26168316

  2. Use of nonsteroidal anti-inflammatory drugs and bladder cancer risk: a meta-analysis of epidemiologic studies.

    Haifeng Zhang

    Full Text Available PURPOSE: Several epidemiologic studies have evaluated the association between nonsteroidal anti-inflammatory drugs (NSAIDs and bladder cancer risk and the results were varied. Thus, we conducted a comprehensive meta-analysis of studies exclusively dedicated to the relationship between the 3 most commonly used analgesics and bladder cancer risk. METHODS: A systematic literature search up to November 2012 was performed in PubMed database for 3 categories of analgesics: acetaminophen, aspirin or non-aspirin NSAIDs. Study-specific risk estimates were pooled using a random-effects model. RESULTS: Seventeen studies (8 cohort and 9 case-control studies, involving a total of 10,618 bladder cancer cases, were contributed to the analysis. We found that acetaminophen (relative risk [RR] 1.01, 95% confidence interval [CI] 0.88-1.17 and aspirin (RR 1.02, 95% CI 0.91-1.14 were not associated with bladder cancer risk. Although non-aspirin NSAIDs was statistically significantly associated with reduced risk of bladder cancer among case-control studies (but not cohort studies, the overall risk was not statistically significant (RR 0.87, 95% CI 0.73-1.05. Furthermore, we also found that non-aspirin NSAIDs use was significantly associated with a 43% reduction in bladder cancer risk among nonsmokers (RR 0.57, 95% CI 0.43-0.76, but not among current smokers. CONCLUSION: The results of our meta-analysis suggest that there is no association between use of acetaminophen, aspirin or non-aspirin NSAIDs and bladder cancer risk. However, non-aspirin NSAIDs use might be associated with a reduction in risk of bladder cancer for nonsmokers.

  3. Asimovian Adaptive Agents

    Gordon, D F


    The goal of this research is to develop agents that are adaptive and predictable and timely. At first blush, these three requirements seem contradictory. For example, adaptation risks introducing undesirable side effects, thereby making agents' behavior less predictable. Furthermore, although formal verification can assist in ensuring behavioral predictability, it is known to be time-consuming. Our solution to the challenge of satisfying all three requirements is the following. Agents have finite-state automaton plans, which are adapted online via evolutionary learning (perturbation) operators. To ensure that critical behavioral constraints are always satisfied, agents' plans are first formally verified. They are then reverified after every adaptation. If reverification concludes that constraints are violated, the plans are repaired. The main objective of this paper is to improve the efficiency of reverification after learning, so that agents have a sufficiently rapid response time. We present two solutions: ...

  4. Evaluation of preventive and therapeutic activity of novel non-steroidal anti-inflammatory drug, CG100649, in colon cancer: Increased expression of TNF-related apoptosis-inducing ligand receptors enhance the apoptotic response to combination treatment with TRAIL.

    Woo, Jong Kyu; Kang, Ju-Hee; Jang, Yeong-Su; Ro, Seonggu; Cho, Joong Myung; Kim, Hwan-Mook; Lee, Sang-Jin; Oh, Seung Hyun


    Non-steroidal anti-inflammatory drugs (NSAIDs) have been suggested as the potential new class of preventive or therapeutic antitumor agents. The aim of the present study was to evaluate the antitumor activity of the novel NSAID, CG100649. CG100649 is a novel NSAID dual inhibitor for COX-2 and carbonic anhydrase (CA)-I/-II. In the present study, we investigated the alternative mechanism by which CG100649 mediated suppression of the colon cancer growth and development. The anchorage‑dependent and -independent clonogenic assay showed that CG100649 inhibited the clonogenicity of human colon cancer cells. The flow cytometric analysis showed that CG100649 induced the G2/M cell cycle arrest in colon cancer cells. Animal studies showed that CG100649 inhibited the tumor growth in colon cancer xenograft in nude mice. Furthermore, quantitative PCR and FACS analysis demonstrated that CG100649 upregulated the expression of TNF-related apoptosis-inducing ligand (TRAIL) receptors (DR4 and DR5) but decreased the expression of decoy receptors (DcR1 and DcR2) in colon cancer cells. The results showed that CG100649 treatment sensitized TRAIL‑mediated growth suppression and apoptotic cell death. The combination treatment resulted in significant repression of the intestinal polyp formation in APCmin/+ mice. Our data clearly demonstrated that CG100649 contains preventive and therapeutic activity for colon cancer. The present study may be useful for identification of the potential benefit of the NSAID CG100649, for the achievement of a better treatment response in colon cancer.

  5. Effects of β-d-mannuronic acid, as a novel non-steroidal anti-inflammatory medication within immunosuppressive properties, on IL17, RORγt, IL4 and GATA3 gene expressions in rheumatoid arthritis patients

    Barati, Anis; Jamshidi, Ahmad Reza; Ahmadi, Hossein; Aghazadeh, Zahra; Mirshafiey, Abbas


    Rheumatoid arthritis (RA) is the most common form of chronic inflammatory arthritis characterized by pain, swelling and destruction of joints, with a resultant disability. Disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs can interfere with the disease process. In this study, the effect of β-d-mannuronic acid (M2000) as a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive and anti-inflammatory effects together with antioxidant effects was evaluated on IL17, RORγt, IL4 and GATA3 gene expression in 12 RA patients. Previously, M2000 driven from sodium alginate (natural product; patented, DEU: 102016113018.4) has shown a notable efficacy in experimental models of multiple sclerosis, RA and nephrotic syndrome. This study was performed on 12 patients with RA who had an inadequate response to conventional treatments. During this trial, patients were permitted to continue the conventional therapy excluding NSAIDs. M2000 was administered orally at a dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells (PBMCs) were collected before and after treatment to evaluate the expression levels of IL4, GATA3, IL17 and RORγt. The gene expression results showed that M2000 has a potent efficacy, so that it could not only significantly decrease IL17 and RORγt levels but also increase IL4 and GATA3 levels after 12 weeks of treatment. Moreover, the gene expression results were in accordance with the clinical and preclinical assessments. In conclusion, M2000 as a natural novel agent has therapeutic and immunosuppressive properties on RA patients (identifier: IRCT2014011213739N2).

  6. Biological warfare agents

    Duraipandian Thavaselvam


    Full Text Available The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies.

  7. Culturally Aware Agent Communication

    Rehm, Matthias; Nakano, Yukiko; Koda, Tomoko


    available for expressing not only task-relevant but also socially and psychologically relevant information makes it necessary to take influences into account that are not readily implemented like emotions or cultural heuristics. These influences have a huge impact on the success of an interaction......Agent based interaction in the form of Embodied Conversational Agents (ECAs) has matured over the last decade and agents have become more and more sophisticated in terms of their verbal and nonverbal behavior like facial expressions or gestures. Having such “natural” communication channels...

  8. Agent-Based Optimization

    Jędrzejowicz, Piotr; Kacprzyk, Janusz


    This volume presents a collection of original research works by leading specialists focusing on novel and promising approaches in which the multi-agent system paradigm is used to support, enhance or replace traditional approaches to solving difficult optimization problems. The editors have invited several well-known specialists to present their solutions, tools, and models falling under the common denominator of the agent-based optimization. The book consists of eight chapters covering examples of application of the multi-agent paradigm and respective customized tools to solve  difficult optimization problems arising in different areas such as machine learning, scheduling, transportation and, more generally, distributed and cooperative problem solving.

  9. Steroidal neuromuscular blocking agents

    Wierda, JMKH; Mori, K; Ohmura, A; Toyooka, H; Hatano, Y; Shingu, K; Fukuda, K


    Since 1964 approximately 20 steroidal neuromuscular blocking agents have been evaluated clinically. Pancuronium, a bisquaternary compound designed on the drawingboard, was the first steroidal relaxant introduced into clinical practice worldwide in the 1970's. Although a major improvement, pancuroniu

  10. Agent Standards Project

    National Aeronautics and Space Administration — The innovation of the work herein proposed is the development of standards for software autonomous agents. These standards are essential to achieve software...

  11. The relationship between non-steroid anti-inflammatory drugs and cardiovascular risk - the myths, the misconceptions, the news, the realities -

    Mirela-Anca STOIA


    Full Text Available While the number of clinical experiments investigating the effects of non-steroid anti-inflammatory drugs (NSAIDs on the cardiovascular (CV events has significantly increased over the last two decades, basic research related to the mechanism by which NSAIDs cause CV dysfunction is limited. High variability in the clinical trials conducted (different populations, dosages, exposure and types of NSAIDs has led to results which are difficult to interpret and compare between studies. Are there some NSAIDs safer than other from the standpoint of CV risk? We have try to answer at some aspects of this question.

  12. Regular use of non-steroidal anti-inflammatory drugs increases the risk of adult-onset asthma: a population-based follow-up study

    Thomsen, Simon Francis; Kyvik, Kirsten Ohm; Skadhauge, Lars Rauff;


    BACKGROUND: Little is known about the relation between regular use of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of asthma at the population level. The aim of this study was to examine a possible association between intake of NSAIDs and risk of adult-onset asthma. METHODS: Using...... data from two multidisciplinary postal questionnaire surveys concerning health and lifestyle, we prospectively studied 19 349 adult twins enrolled in the nationwide Danish Twin Registry. RESULTS: We found a higher prevalence of new-onset asthma in subjects who used NSAIDs (other than aspirin) regularly...

  13. Variable Effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs on Selected Biochemical Processes Mediated by Soil Microorganisms

    Mariusz Sebastian Cycoń


    Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs are the most frequently used group of pharmaceuticals. The high consumption and the uncontrolled disposal of unused drugs into municipal waste or their deposit in landfills can result in an increased concentration of these compounds in soils. Moreover, these drugs can affect the microbial activity. However, there is a lack of knowledge about these effects or it is very limited. Therefore, the objective of this study was to compare the impact of selected commercially available NSAIDs, i.e. diclofenac (DCF, naproxen (NPX, ibuprofen (IBF and ketoprofen (KTP, applied at concentrations of 1 and 10 mg/kg soil, on the activity of soil microorganisms during the 90-day experiment. To ascertain this impact, substrate-induced respiration (SIR, soil enzyme activities, i.e. dehydrogenase (DHA, acid and alkaline phosphatases (PHOS-H and PHOS-OH and urease (URE as well as changes in the rates of nitrification and ammonification processes were determined. In addition, the number of culturable bacteria and fungi were enumerated. In general, the obtained data showed a significant stimulatory effect of NSAIDs on the microbial activity. Higher concentrations of NSAIDs caused a greater effect, which was observed for SIR, PHOS-H, PHOS-OH, URE, N-NO3- and N-NH4+, even during the whole incubation period. Moreover, the number of heterotrophic bacteria and fungi increased significantly during the experiment, which was probably a consequence of the evolution of specific microorganisms that were capable of degrading NSAIDs and used them as an additional source of carbon and energy. However, an inhibitory effect of NPX, IBF or KTP for SIR, DHA, on both phosphatases and culturable bacteria and fungi was observed at the beginning of the experiment. At lower concentrations of NSAIDs, in turn, the effects were negligible or transient. In conclusion, the application of NSAIDs altered the biochemical and microbial activity of soil

  14. Optimization of antiaggregant therapy in rheumatoid arthritis and coronary heart disease patients receiving nonsteroidal anti-inflammatory drugs

    Tatyana Vladimirovna Kropotina


    Full Text Available Objective: to study coagulative and vascular-thrombocytic hemostases in patients with rheumatoid arthritis (RA and coronary heart disease (CHD depending on therapy with different nonsteroidal anti-inflammatory drugs (NSAIDs alone and in combination with low-dose aspirin. Subjects and methods. The trial enrolled 58 patients (43 women and 15 men with a valid diagnosis of RA. The patients' mean age was 61.2 years; the disease duration averaged 10 years. All the patients received therapy with disease-modifying antirheumatic drugs (DMARDs and NSAIDs. All had CHD; 52 of the 58 patients presented with arterial hypertension; 30 had noncoronary atherosclerosis. Cardiovascular diseases were first identified in 18 patients. All took heart medications. Coagulative and vascular-thrombocytic hemostases were studied in all the patients and the results were compared depending on to the taken NSAID (diclofenac, tenoxicam, nimesulide, meloxicam. Thirty-seven patients who had not previously received antiaggregant therapy were given aspirin in a dose of 100 mg when they were found to have platelet hyperaggregation and aggregation was restudied on aspirin therapy days 7-8. A control group consisted of 26 healthy men (mean age 55 years who received no medications. Results. In patients with RA and CHD, activated coagulative hemostasis was identified in 65.5% of cases. The signs of hypercoagulation were observed in 35 of the 58 patients. When different NSAIDs were used, the coagulative hemostatic changes were unidirectional and no statistically significant differences were found between the groups. The patients taking diclofenac, nimesulide, or meloxicam were found to have activated vascular-thrombocytic hemostasis. Those receiving tenoxicam showed a tendency towards decreased adrenaline-induced platelet aggregation (the drug's aspirin-like effect; however, no statistical processing was made because of few cases. The use of aspirin in the patients taking diclofenac

  15. IL6, aspirin, nonsteroidal anti-inflammatory drugs, and breast cancer risk in women living in the southwestern United States.

    Slattery, Martha L; Curtin, Karen; Baumgartner, Richard; Sweeney, Carol; Byers, Tim; Giuliano, Anna R; Baumgartner, Kathy B; Wolff, Roger R


    Interleukin-6 is a cytokine thought to be involved in inflammation, insulin, and estrogen-related pathways. We evaluate genetic variation in the IL6 gene with risk of breast cancer. We also evaluate breast cancer associations with aspirin and nonsteroidal anti-inflammatory drugs. A breast cancer case-control study (n = 1,527 non-Hispanic white cases, 1,601 non-Hispanic white controls, 798 Hispanic/Native American cases, and 924 Hispanic/Native American controls) was conducted among women living in the southwestern United States (4-Corner's Breast Cancer Study). Five IL6 single nucleotide polymorphisms (SNP) and IL6 haplotypes based on these SNPs were evaluated. Allele frequencies were significantly different between non-Hispanic white and Hispanic/Native American women. Among postmenopausal women not recently exposed to hormones, the AG/GG genotypes of rs1800797 (-596A>G) and the GC/CC genotypes of rs1800795 (-174G>C) significantly reduced risk of breast cancer among non-Hispanic white women [odds ratio (OR), 0.69; 95% confidence interval (95% CI), 0.48-1.00 and OR, 0.68; 95% CI, 0.47-0.99, respectively] and Hispanic/Native American women (OR, 0.48; 95% CI, 0.28-0.83 and OR, 0.44; 95% CI, 0.26-0.99, respectively). Haplotypes of the five IL6 SNPs further defined these associations. Recent aspirin use significantly decreased risk of breast cancer among postmenopausal Hispanic/Native American women not recently exposed to hormones (OR, 0.56; 95% CI, 0.33-0.96). Among non-Hispanic white, the inverse association with aspirin was not statistically significant. IL6 genotype and haplotype significantly modified the association between aspirin and breast cancer, with the greatest effect modification being among women not recently exposed to hormones [P interaction = 0.06 (for non-Hispanic white) and 0.04 (for Hispanic/Native American) and SNP rs1800796 or -572G>C]. These data suggest that IL6 is associated with breast cancer risk and modifies the association between

  16. Non-Steroid Anti-Inflammatory Drugs Are Better than Acetaminophen on Fever Control at Acute Stage of Fracture.

    Kuang-Ting Yeh

    Full Text Available In addition to adequate surgical fixation and an aggressive rehabilitation program, pain relief is one of the most critical factors in the acute stage of fracture treatment. The most common analgesics are nonsteroid anti-inflammatory drugs and Acetaminophen, both of which relieve pain and reduce body temperature. In clinical experiences, they exhibit effective pain control; however, their influence on body temperature remains controversial. This study is aimed at determining the effects of analgesics at the acute stage of traumatic fracture by performing a clinical retrospective study of patients with fractures and a fracture animal model. The retrospective study revealed that, in the acetaminophen group, the mean value of postmedication body temperature (BT was significantly higher than that of the premedication BT. The change in BT was highly related with the medication rather than other risk factors. Forty eight 12-week-old male Wistar rats were divided into 6 groups: a control group, fracture group, fracture-Acetaminophen group, Acetaminophen group, fracture-Arcoxia group, and Arcoxia group. Fracture rats were prepared by breaking their unilateral tibia and fibula. Their inflammation conditions were evaluated by measuring their serum cytokine level and their physiological status was evaluated by estimating their central temperature, heart rate, and mean blood pressure. The hepatic adverse effects were assessed by measuring the serum levels of aspartate aminotransferase (sGOT and alanine aminotransferase (sGPT. The central temperature in the fracture-Acetaminophen group exceeded that in the groups fed normal saline water or Arcoxia. Accumulated hepatic injury was presented as steadily ascending curves of sGOT and sGPT. Inflammation-related cytokine levels were not higher in the Acetaminophen fracture group and were significantly lower in the fracture-Arcoxia group. Fever appeared to be aggravated by acetaminophen and more related to the

  17. Dexamethasone decreases migraine recurrence observed after treatment with a triptan combined with a nonsteroidal anti-inflammatory drug

    Krymchantowski Abouch V.


    Full Text Available BACKGROUND AND OBJECTIVES: Triptans are effective drugs for the acute treatment of migraine. However, 30-40% of the patients commonly present recurrence before 24 hours therefore requiring another dose. Nonsteroidal anti-inflammatory drugs (NSAID such as tolfenamic acid and naproxen sodium combined with sumatriptan have demonstrated efficacy in reducing recurrence observed with the single use of this drug. Steroids also have been suggested to treat refractory migraine and status migranosus. The aim of this study was to evaluate whether patients presenting frequent recurrence with the combination triptan plus NSAID, would decrease it with the association of dexamethasone. METHOD: Twenty three patients, 17 women and 6 men with migraine according to IHS criteria were prospectively studied. All patients presented frequent recurrence ( > or = 60%, mean recurrence rate 74,8% with the single use of sumatritpan 100mg or zolmitriptan 2,5mg or rizatriptan 10mg in at least 5 consecutive attacks, and didn't present a reduction of the recurrence rate superior than 20% with the combination of tolfenamic acid 200mg or rofecoxib 25mg in at least 5 other consecutive attacks (mean recurrence rate 60%. The patients had to treat 6 consecutive moderate or severe migraine attacks with their usual combination plus 4mg of dexamathasone with a maximum of twice a week, and fill out a diary reporting headache parameters. RESULTS: Twenty patients, 16 women and 4 men completed the study. Of those who completed the study, 11 took rizatriptan plus rofecoxib, 4 rizatriptan plus tolfenamic acid, 3 zolmitriptan plus rofecoxib, 1 zolmitriptan plus tolfenamic acid and 1 patient took sumatriptan plus tolfenamic acid, having the 20 patients taken as a third medication, a single tablet of 4mg of dexamethasone. All patients took oral formulations and none presented vomiting after that. Among all 20 patients, one female and one male patient presented recurrence in 3 out of the 6

  18. Non-Steroid Anti-Inflammatory Drugs Are Better than Acetaminophen on Fever Control at Acute Stage of Fracture.

    Yeh, Kuang-Ting; Wu, Wen-Tien; Subeq, Yi-Maun; Niu, Chi-Chien; Liao, Kuang-Wen; Chen, Ing-Ho; Wang, Jen-Hung; Lee, Ru-Ping


    In addition to adequate surgical fixation and an aggressive rehabilitation program, pain relief is one of the most critical factors in the acute stage of fracture treatment. The most common analgesics are nonsteroid anti-inflammatory drugs and Acetaminophen, both of which relieve pain and reduce body temperature. In clinical experiences, they exhibit effective pain control; however, their influence on body temperature remains controversial. This study is aimed at determining the effects of analgesics at the acute stage of traumatic fracture by performing a clinical retrospective study of patients with fractures and a fracture animal model. The retrospective study revealed that, in the acetaminophen group, the mean value of postmedication body temperature (BT) was significantly higher than that of the premedication BT. The change in BT was highly related with the medication rather than other risk factors. Forty eight 12-week-old male Wistar rats were divided into 6 groups: a control group, fracture group, fracture-Acetaminophen group, Acetaminophen group, fracture-Arcoxia group, and Arcoxia group. Fracture rats were prepared by breaking their unilateral tibia and fibula. Their inflammation conditions were evaluated by measuring their serum cytokine level and their physiological status was evaluated by estimating their central temperature, heart rate, and mean blood pressure. The hepatic adverse effects were assessed by measuring the serum levels of aspartate aminotransferase (sGOT) and alanine aminotransferase (sGPT). The central temperature in the fracture-Acetaminophen group exceeded that in the groups fed normal saline water or Arcoxia. Accumulated hepatic injury was presented as steadily ascending curves of sGOT and sGPT. Inflammation-related cytokine levels were not higher in the Acetaminophen fracture group and were significantly lower in the fracture-Arcoxia group. Fever appeared to be aggravated by acetaminophen and more related to the elevation of hepatic

  19. Bleeding gastroduodenal ulcers in patients without Helicobacter pylori infection and without exposure to non-steroidal anti-inflammatory drugs

    Smolović Brigita


    Full Text Available Background/Aim. A high risk of bleeding in Helicobacter pylori (H.pylori-negative, non-steroidal anti-inflammatory drugs (NSAID-negative ulcers highlights the clinical importance of analysis of the changing trends of peptic ulcer disease. The aim of the study was to investigate the risk factors for ulcer bleeding in patients with non-H. pylori infection, and with no NSAIDs use. Methods. A prospective study included patients with endoscopically diagnosed ulcer disease. The patients were without H. pylori infection (verified by pathohistology and serology and without exposure to NSAIDs and proton pump inhibitors (PPI within 4 weeks before endoscopy. After endoscopy the patients were divided into 2 groups: the study group of 48 patients with bleeding ulcer and the control group of 47 patients with ulcer, but with no bleeding. Prior to endoscopy they had completed a questionnaire about demographics, risk factors and habits. The platelet function, von Willebrand factor (vWF and blood groups were determined. Histopathological analysis of biopsy samples were performed with a modified Sydney system. The influence of bile reflux was analyzed by Bile reflux index (BRI. Results. Age, gender, tobacco and alcohol use did not affect the bleeding rate. The risk of bleeding did not depend on concomitant diseases (p = 0.509 and exposure to stress (p = 0.944. Aspirin was used by 16/48 (33.3% patients with bleeding ulcer, as opposed to 7/47 (14.9% patients who did not bleed (p = 0.036. Abnormal platelet function had 12/48 (25.0% patients who bled, as opposed to 2/47 (4.3% patients who did not bleed (p = 0.004. Patients with BRI < 14 bled in 79.2%, and did not bleed in 57.4% of the cases (p = 0.023. There was no statistical difference between groups in regards to blood groups and range of vWF. Antrum atrophy was found in 14/48 (29.2% patients with bleeding ulcer and in only 5/47 (10.6% patients who had ulcer without bleeding (p = 0.024. Conclusion. Abnormal

  20. Development of novel agents based on nitric oxide for the control of colon cancer

    Vassiliki KOZONI; Theophilos ROSENBERG; Basil RIGAS


    Nitric oxide-donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs) repre-sent a novel class of compounds that hold promise as agents for the control of colon cancer. They are derivatives of conventional NSAIDs that have been modi-fied by adding to them, via a spacer molecule, a nitric oxide releasing moiety. The expectation is that the combined effects of NO and the NSAID moiety will exceed those of each structural component alone. Extensive work has demonstrated their potency and efficacy in preclinical models of colon cancer. The mechanism of action of NO-NSAIDs involves the modulation of several critical cellular signaling pathways, whereas the induction of a state of oxidative stress, at least by NO-aspirin, appears to be a major proximal event. Clinical trials are needed to assess the role of NO-NSAIDs in the control of colon cancer.

  1. Biological Warfare Agents

    Dev Vrat Kamboj


    Full Text Available There is a long historic record of use of biological warfare (BW agents by warring countriesagainst their enemies. However, the frequency of their use has increased since the beginningof the twentieth century. World war I witnessed the use of anthrax agent against human beingsand animals by Germans, followed by large-scale field trials by Japanese against war prisonersand Chinese population during world war II. Ironically, research and development in biologicalwarfare agents increased tremendously after the Geneva Protocol, signed in 1925, because ofits drawbacks which were overcome by Biological and Toxin Weapons Convention (BTWC in1972. Biological warfare programme took back seat after the 1972 convention but biologicalagents regained their importance after the bioterrorist attacks of anthrax powder in 2001. In thelight of these attacks, many of which turned out to be hoax, general awareness is required aboutbiological warfare agents that can be used against them. This review has been written highlightingimportant biological warfare agents, diseases caused by them, possible therapies and otherprotection measures.

  2. Use of multiple immunosuppressive agents in recalcitrant ACANTHAMOEBA scleritis.

    Igras, Estera; Murphy, Conor


    A 48-year-old woman who is a contact lens wearer presented with unilateral ACANTHAMOEBA keratitis, confirmed by PCR, which responded initially to topical polyhexamethylene biguanide (PHMB) and brolene. Three months later, despite continued treatment, she developed diffuse anterior scleritis with severe pain and marked scleral injection but without evidence of recurrence keratitis. Oral non-steroidal anti-inflammatories and oral high-dose corticosteroids were added without success. Subsequent treatment with intravenous methylprednisolone and high-dose cyclosporine led to a temporary improvement. Re-presenting with signs of recurrent scleritis and severe pain, the antitumor necrosis factor monoclonal antibody adalimumab, and later oral cyclophosphamide, were added. This led to complete quiescence of the scleritis. Unfortunately, frequent recurrences of ACANTHAMOEBA keratitis and anterior uveitis occurred on immunosuppression requiring continued treatment with PHMB, brolene and topical corticosteroids. This is the first case of severe refractory ACANTHAMOEBA scleritis requiring the concomitant use of four immunosuppressive agents to achieve continued disease control. The challenges in managing this case are discussed.

  3. Approaches to the diagnosis and management of patients with a history of nonsteroidal anti-inflammatory drug-related urticaria and angioedema.

    Kowalski, Marek L; Woessner, Katharine; Sanak, Marek


    Nonsteroidal anti-inflammatory drug (NSAID)-induced urticarial and angioedema reactions are among the most commonly encountered drug hypersensitivity reactions in clinical practice. Three major clinical phenotypes of NSAID-induced acute skin reactions manifesting with angioedema, urticaria, or both have been distinguished: NSAID-exacerbated cutaneous disease, nonsteroidal anti-inflammatory drug-induced urticaria/angioedema (NIUA), and single NSAID-induced urticaria and angioedema. In some patients clinical history alone might be sufficient to establish the diagnosis of a specific type of NSAID hypersensitivity, whereas in other cases oral provocation challenges are necessary to confirm the diagnosis. Moreover, classification of the type of cutaneous reaction is critical for proper management. For example, in patients with single NSAID-induced reactions, chemically nonrelated COX-1 inhibitors can be safely used. However, there is cross-reactivity between the NSAIDs in patients with NSAID-exacerbated cutaneous disease and NIUA, and thus only use of selective COX-2 inhibitors can replace the culprit drug if the chronic treatment is necessary, although aspirin desensitization will allow for chronic treatment with NSAIDs in some patients with NIUA. In this review we present a practical clinical approach to the patient with NSAID-induced urticaria and angioedema.

  4. Diclofenac sodium topical solution with dimethyl sulfoxide, a viable alternative to oral nonsteroidal anti-inflammatories in osteoarthritis: review of current evidence

    Fuller P


    Full Text Available Philip Fuller¹, Sanford Roth²¹Covidien, Hazelwood, MO; ²Arizona Research and Education, Arthritis Research Laboratory, Arizona State University, Phoenix, AZ, USAAbstract: Topical nonsteroidal anti-inflammatory drugs (NSAIDs may offer a safer alternative to their oral counterparts for the management of osteoarthritis. Diclofenac sodium topical solution with dimethyl sulfoxide (TDiclo was evaluated in five randomized, controlled trials and is indicated for treatment of the signs and symptoms associated with osteoarthritis of the knee. Three studies showed that TDiclo is superior to placebo and vehicle control with respect to pain, physical function, and perception of osteoarthritis symptoms. Two studies showed that benefits are similar to those of oral diclofenac, with one study demonstrating statistical equivalence. The most common adverse event associated with TDiclo in these studies was dry skin. Incidences of gastrointestinal adverse events and abnormal levels of liver enzymes were lower with TDiclo compared with oral diclofenac in active-controlled studies. Based on these studies, TDiclo represents a practical, evidence-based option for the management of osteoarthritis of the knee.Keywords: osteoarthritis, nonsteroidal anti-inflammatory drugs, diclofenac, topical analgesic

  5. Agent Oriented Programming进展%Advances in Agent Oriented Programming

    王一川; 石纯一


    Agent-oriented programming (AOP) is a framework to develop agents, and it aims to link the gap betweentheory and practical in agent research. The core of an AOP framework is its language and semantics. In this paper,we propose the necessary properties which agents should have, and then give a summary and analysis about differentAOP languages based on these properties.

  6. Agents unleashed a public domain look at agent technology

    Wayner, Peter


    Agents Unleashed: A Public Domain Look at Agent Technology covers details of building a secure agent realm. The book discusses the technology for creating seamlessly integrated networks that allow programs to move from machine to machine without leaving a trail of havoc; as well as the technical details of how an agent will move through the network, prove its identity, and execute its code without endangering the host. The text also describes the organization of the host's work processing an agent; error messages, bad agent expulsion, and errors in XLISP-agents; and the simulators of errors, f

  7. Developing Enculturated Agents

    Rehm, Matthias


    Embodied Conversational Agents (ECAs) are complex multimodal systems with rich verbal and nonverbal repertoires. There human-like appearance raises severe expectations regarding natural communicative behaviors on the side of the user. But what is regarded as “natural” is to a large degree dependent...... on our cultural profiles that provide us with heuristics of behavior and interpretation. Thus, integrating cultural aspects of communicative behaviors in virtual agents and thus enculturating such systems seems to be inevitable. But culture is a multi-defined domain and thus a number of pitfalls arise...

  8. Agent Persuasion Mechanism of Acquaintance

    Jinghua, Wu; Wenguang, Lu; Hailiang, Meng

    Agent persuasion can improve negotiation efficiency in dynamic environment based on its initiative and autonomy, and etc., which is being affected much more by acquaintance. Classification of acquaintance on agent persuasion is illustrated, and the agent persuasion model of acquaintance is also illustrated. Then the concept of agent persuasion degree of acquaintance is given. Finally, relative interactive mechanism is elaborated.

  9. Software Agent Techniques in Design

    Hartvig, Susanne C


    This paper briefly presents studies of software agent techniques and outline aspects of these which can be applied in design agents in integrated civil engineering design environments.......This paper briefly presents studies of software agent techniques and outline aspects of these which can be applied in design agents in integrated civil engineering design environments....

  10. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies.

    Patricia McGettigan


    Full Text Available BACKGROUND: Randomised trials have highlighted the cardiovascular risks of non-steroidal anti-inflammatory drugs (NSAIDs in high doses and sometimes atypical settings. Here, we provide estimates of the comparative risks with individual NSAIDs at typical doses in community settings. METHODS AND FINDINGS: We performed a systematic review of community-based controlled observational studies. We conducted comprehensive literature searches, extracted adjusted relative risk (RR estimates, and pooled the estimates for major cardiovascular events associated with use of individual NSAIDs, in different doses, and in populations with low and high background risks of cardiovascular events. We also compared individual drugs in pair-wise (within study analyses, generating ratios of RRs (RRRs. Thirty case-control studies included 184,946 cardiovascular events, and 21 cohort studies described outcomes in >2.7 million exposed individuals. Of the extensively studied drugs (ten or more studies, the highest overall risks were seen with rofecoxib, 1.45 (95% CI 1.33, 1.59, and diclofenac, 1.40 (1.27, 1.55, and the lowest with ibuprofen, 1.18 (1.11, 1.25, and naproxen, 1.09 (1.02, 1.16. In a sub-set of studies, risk was elevated with low doses of rofecoxib, 1.37 (1.20, 1.57, celecoxib, 1.26 (1.09, 1.47, and diclofenac, 1.22 (1.12, 1.33, and rose in each case with higher doses. Ibuprofen risk was seen only with higher doses. Naproxen was risk-neutral at all doses. Of the less studied drugs etoricoxib, 2.05 (1.45, 2.88, etodolac, 1.55 (1.28, 1.87, and indomethacin, 1.30 (1.19, 1.41, had the highest risks. In pair-wise comparisons, etoricoxib had a higher RR than ibuprofen, RRR = 1.68 (99% CI 1.14, 2.49, and naproxen, RRR = 1.75 (1.16, 2.64; etodolac was not significantly different from naproxen and ibuprofen. Naproxen had a significantly lower risk than ibuprofen, RRR = 0.92 (0.87, 0.99. RR estimates were constant with different background risks for




    Last year the buying agent LOGITRADE started operations on the CERN site, processing purchasing requests for well-defined families of products up to a certain value. It was planned from the outset that a second buying agent would be brought in to handle the remaining product families. So, according to that plan, the company CHARLES KENDALL will be commencing operations at CERN on 8 May 2000 in Building 73, 1st floor, offices 31 and 35 (phone and fax numbers to be announced).Each buying agent will have its own specific list of product families and will handle purchasing requests up to 10'000 CHF.Whenever possible they will provide the requested supplies at a price (including the cost of their own services) which must be equivalent to or lower than the price mentioned on the purchasing request, changing the supplier if necessary. If a lower price cannot be obtained, agents will provide the necessary administrative support free of charge.To ensure that all orders are processed in the best possible conditions, us...

  12. The need for agents

    Abolfazlian, Ali Reza Kian


    I denne artikel arbejder vi med begrebet Intelligent Software Agents (ISAs), som autonomous, social, reactive, proactive og subservient computer systemer. Baseret på socialt psykologiske argumenter viser jeg endvidere, hvordan både den menneskelige natur og det teknologiske stadium, som mennesket...

  13. Programming Agents with Emotions

    Dastani, Mehdi; Floor, Chr.; Meyer, John-Jules Charles


    In this paper we show how a cognitive agent programming language can be endowed with ways to program emotions. In particular we show how the programming language 2APL can be augmented so that it can work together with the computational emotion model ALMA to deal with appraisal, emotion/mood generati

  14. Remote Agent Experiment

    Benard, Doug; Dorais, Gregory A.; Gamble, Ed; Kanefsky, Bob; Kurien, James; Millar, William; Muscettola, Nicola; Nayak, Pandu; Rouquette, Nicolas; Rajan, Kanna; Norvig, Peter (Technical Monitor)


    Remote Agent (RA) is a model-based, reusable artificial intelligence (At) software system that enables goal-based spacecraft commanding and robust fault recovery. RA was flight validated during an experiment on board of DS1 between May 17th and May 21th, 1999.

  15. Agent-Based Cloud Computing

    Sim, Kwang Mong


    Agent-based cloud computing is concerned with the design and development of software agents for bolstering cloud service\\ud discovery, service negotiation, and service composition. The significance of this work is introducing an agent-based paradigm for\\ud constructing software tools and testbeds for cloud resource management. The novel contributions of this work include: 1) developing\\ud Cloudle: an agent-based search engine for cloud service discovery, 2) showing that agent-based negotiatio...

  16. Announcements to Attentive Agents

    Bolander, Thomas; van Ditmarsch, Hans; Herzig, Andreas;


    In public announcement logic it is assumed that all agents pay attention to the announcement. Weaker observational conditions can be modelled in action model logic. In this work, we propose a version of public announcement logic wherein it is encoded in the states of the epistemic model which...... agents pay attention to the announcement. This logic is called attention-based announcement logic. We give an axiomatization of the logic and prove that complexity of satisfiability is the same as that of public announcement logic, and therefore lower than that of action model logic. An attention......-based announcement can also be described as an action model. We extend our logic by integrating attention change. Finally, we add the notion of common belief to the language, we exploit this to formalize the concept of joint attention, that has been widely discussed in the philosophical and cognitive science...

  17. Pharmacology of antiplatelet agents.

    Kalra, Kiran; Franzese, Christopher J; Gesheff, Martin G; Lev, Eli I; Pandya, Shachi; Bliden, Kevin P; Tantry, Udaya S; Gurbel, Paul A


    Pharmacotherapies with agents that inhibit platelet function have proven to be effective in the treatment of acute coronary syndromes, and in the prevention of complications during and after percutaneous coronary intervention. Because of multiple synergetic pathways of platelet activation and their close interplay with coagulation, current treatment strategies are based not only on platelet inhibition, but also on the attenuation of procoagulant activity, inhibition of thrombin generation, and enhancement of clot dissolution. Current strategies can be broadly categorized as anticoagulants, antiplatelet agents, and fibrinolytics. This review focuses on the pharmacology of current antiplatelet therapy primarily targeting the inhibition of the enzyme cyclooxygenase 1, the P2Y12 receptor, the glycoprotein IIb/IIIa receptor, and protease-activated receptor 1.

  18. [Pharmacology of inotropic agents].

    Pastelín Hernández, Gustavo


    High-risk patients, during anesthesia and after surgery present changes in pharmacokinetics (biotransformation reactions, renal clearance, drug interactions, etc.) modifying the usefulness of most drugs, cardiac inotropics included. This group of substances is formed by adrenergic agents, phospodiesterase inhibitors and digitalis compounds. Adrenergic agents are the catecholamines, adrenaline (A), noradrenaline (NA) and dopamine (D), plus dopaminergic agonists as dobutamine and pirbuterol. Phosphodiesterase inhibitors, as amrinone and milrinone, produce their inotropic action by preserving cyclic adenosine monophosphate (AMPc) from its intracellular catabolism. Recent studies on the utility of digitalis compounds demonstrated the valuable applicability of digoxin in chronic and acute heart failure. Another group of substances whose mechanism of action differs from that of the inotropics, offers future utility in high risk patients, they include: inhibitors of nitric oxide sintases, natriuretic atrial peptide inhibitors, Q-10 coenzyme, endothelin antagonists, and anti-tumoral necrosis factor.

  19. [The antiretroviral agent Fullevir].

    Nosik, D N; Lialina, I K; Kalnina, L B; Lobach, O A; Chataeva, M S; Rasnetsov, L D


    The antiretroviral properties of Fullevir (sodium salt of fullerenepolyhydropolyaminocaproic acid) manufactured by IntelFarm Co.) were studied in the human cell culture infected with human immunodeficiency virus (HIV). The agent was ascertained to be able to protect the cell from the cytopathic action of HIV. The 90% effective concentration (EF90) was 5 microg/ml. The 50% average toxic concentration was 400 microg/ml. Testing of different (preventive and therapeutic) Fullevir dosage regimens has shown that the drug is effective when used both an hour before and an hour after infection and when administered simultaneously with cell infection. The longer contact time for the agent with the cells increased the degree of antiviral defense. Co-administration of Fullevir and the HIV reverse transcriptase inhibitor Retrovir (azidothymidine) showed a synergistic antiretroviral effect. Thus, Fullevir may be regarded as a new promising antiretroviral drug for the treatment of HIV infection.

  20. Intelligent Agent Integration Technology


    The DARPA knowledge sharing effort: Progress report. In B. Nebel , C. Rich, and W. Swartout, editors, Principles of Knowledge Representation and...and Automation, pages 2,785-2,788. IEEE CS Press. [18] Carl Hewitt. Offices are open systems. Communications of the ACM, 4(3):271-287, July 1986...19] Carl Hewitt and Jeff Inman. DAI betwixt and be- tween: From "intelligent agents" to open systems sci- ence. IEEE Transactions on Systems, Man

  1. Sunscreening Agents: A Review

    Latha, M. S.; Martis, Jacintha; Shobha, V; Sham Shinde, Rutuja; Bangera, Sudhakar; Krishnankutty, Binny; Bellary, Shantala; Varughese, Sunoj; Rao, Prabhakar; B R Naveen Kumar


    The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines. The United States Food an...


    Vijay Vinay


    Full Text Available Antipsychotics are a group of drugs commonly but not exclusively used to treat psychosis. Antipsychotic agents are grouped in two categories: Typical and Atypical antipsychotics. The first antipsychotic was chlorpromazine, which was developed as a surgical anesthetic. The first atypical anti-psychotic medication, clozapine, was discovered in the 1950s, and introduced in clinical practice in the 1970s. Both typical and atypical antipsychotics are effective in reducing positive and negative symptoms of schizophrenia. Blockade of D2 receptor in mesolimbic pathway is responsible for antipsychotic action. Typical antipsychotics are not particularly selective and also block Dopamine receptors in the mesocortical pathway, tuberoinfundibular pathway, and the nigrostriatal pathway. Blocking D2 receptors in these other pathways is thought to produce some of the unwanted side effects. Atypical antipsychotics differ from typical psychotics in their "limbic-specific" dopamine type 2 (D2-receptor binding and high ratio of serotonin type 2 (5-HT2-receptor binding to D2. Atypical antipsychotics are associated with a decreased capacity to cause EPSs, TD, narcoleptic malignant syndrome, and hyperprolactinemia. Atypical antipsychotic agents were developed in response to problems with typical agents, including lack of efficacy in some patients, lack of improvement in negative symptoms, and troublesome adverse effects, especially extrapyramidal symptoms (EPSs and tardive dyskinesia (TD.

  3. Determination of the total concentration of highly protein-bound drugs in plasma by on-line dialysis and column liquid chromatography : application to non-steroidal anti-inflammatory drugs

    Herráez-Hernández, R; van de Merbel, N C; Brinkman, U A


    The potential of on-line dialysis as a sample preparation procedure for compounds highly bound to plasma proteins is evaluated, using non-steroidal anti-inflammatory drugs as model compounds and column liquid chromatography as the separation technique. Different strategies to reduce the degree of dr

  4. Incremental cost-effectiveness of cyclooxygenase 2-selective versus nonselective nonsteroidal, anti-inflammatory drugs in a cohort of coumarin users : A pharmacoeconomic analysis linked to a case-control study

    Knijff-Dutmer, EAJ; Postma, MJ; van der Palen, J; Brouwers, JRBJ; van de Laar, MAFJ


    Background: A previous case-control study involving concomitant users of coumarin and nonsteroidal anti-inflammatory drugs (NSAIDs) found that cyclooxygenase 2 (COX-2)-selective NSAIDs were associated with fewer bleeding complications than nonselective NSAIDs. Objective: The goal of this study was t

  5. Incremental cost-effectiveness of cyclooxygenase 2-selective versus nonselective nonsteroidal anti-inflammatory drugs in a cohort of coumarin users: A pharmacoeconomic analysis linked to a case-control study

    Knijff-Dutmer, Ellen A.J.; Postma, Maarten J.; Palen, van der Job; Brouwers, Jacobus R.B.J.; Laar, van de Martin A.F.J.


    Background: A previous case-control study involving concomitant users of coumarin and nonsteroidal anti-inflammatory drugs (NSAIDs) found that cyclooxygenase 2 (COX-2)-selective NSAIDs were associated with fewer bleeding complications than nonselective NSAIDs. Objective: The goal of this study was

  6. Proton-pump inhibitors are associated with a reduced risk for bleeding and perforated gastroduodenal ulcers attributable to non-steroidal anti-inflammatory drugs : a nested case-control study

    Vonkeman, Harald E; Fernandes, Robert W; van der Palen, Job; van Roon, Eric N; van de Laar, Mart A F J


    Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by gastrointestinal ulcer complications, such as ulcer bleeding and perforation. The efficacy of proton-pump inhibitors in the primary prevention of ulcer complications arising from the use of NSAIDs remains unproven. Selectiv

  7. Incremental cost effectiveness of proton pump inhibitors for the prevention of non-steroidal anti-inflammatory drug ulcers : a pharmacoeconomic analysis linked to a case-control study

    Vonkeman, Harald E.; Braakman-Jansen, Louise M. A.; Klok, Rogier M.; Postma, Maarten J.; Brouwers, Jacobus R. B. J.; van de laar, Mart A. F. J.


    Introduction We estimated the cost effectiveness of concomitant proton pump inhibitors (PPIs) in relation to the occurrence of non-steroidal anti-inflammatory drug (NSAID) ulcer complications. Methods This study was linked to a nested case-control study. Patients with NSAID ulcer complications were

  8. Incremental cost effectiveness of proton pump inhibitors for the prevention of non-steroidal anti-inflammatory drug ulcers : a pharmacoeconomic analysis linked to a case-control study

    Vonkeman, H.E.; Braakman-Jansen, L.M.A.; Klok, R.M.; Postma, M.J.; Brouwers, J.R.B.J.; van de Laar, M.A.F.J.


    Introduction We estimated the cost effectiveness of concomitant proton pump inhibitors (PPIs) in relation to the occurrence of non-steroidal anti-inflammatory drug (NSAID) ulcer complications. Methods This study was linked to a nested case-control study. Patients with NSAID ulcer complications were

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

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


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

  10. Two non-steroidal anti-inflammatory drugs, niflumic acid and diclofenac, inhibit the human glutamate transporter EAAT1 through different mechanisms.

    Takahashi, Kanako; Ishii-Nozawa, Reiko; Takeuchi, Kouichi; Nakazawa, Ken; Sato, Kaoru


    We investigated the effects of non-steroidal anti-inflammatory drugs on substrate-induced currents of L-glutamate (L-Glu) transporter EAAT1 expressed in Xenopus laevis oocytes. Niflumic acid (NFA) and diclofenac inhibited L-Glu-induced current through EAAT1 in a non-competitive manner. NFA produced a leftward shift in reversal potential (E(rev)) of L-Glu-induced current and increased current amplitude at the potentials more negative than -100 mV. Diclofenac had no effects on E(rev) and inhibited the current amplitude to the same extent at all negative potentials. These results indicate that NFA and diclofenac inhibit the L-Glu-induced EAAT1 current via different mechanisms.

  11. A sensitive enzyme-linked immunosorbent assay amplified by biotin-streptavidin system for detecting non-steroidal anti-inflammatory drug ketoprofen.

    Bu, Dan; Zhuang, Hui S; Yang, Guang X


    A sensitive biotin-streptavidin-amplified enzyme-linked immunosorbent assay (BA-ELISA) method was developed for detecting non-steroidal anti-inflammatory drug ketoprofen. Compared with traditional ELISA method, the sensitivity of proposed immunoassay was enhanced by the biotin-streptavidin system. Under the optimal condition, the median inhibitory concentration (IC50) was 0.25 ng mL(-1), with minor cross-reactivity to a number of structural analogs. This developed assay was successfully applied to detect the ketoprofen residues in different fish samples, and good recoveries (72.6-105.5%) were obtained. The results indicated that this immunoassay method could specifically detect trace ketoprofen residues and could be widely used for routine monitoring of food samples.

  12. Aspirin and some other nonsteroidal anti-inflammatory drugs inhibit cystic fibrosis transmembrane conductance regulator protein gene expression in T-84 cells.

    Tondelier, D; Brouillard, F; Lipecka, J; Labarthe, R; Bali, M; Costa de Beauregard, M A; Torossi, T; Cougnon, M; Edelman, A; Baudouin-Legros, M


    Cystic fibrosis (CF) is caused by mutations in the CF gene, which encodes CF transmembrane conductance regulator protein (CFTR), a transmembrane protein that acts as a cAMP-regulated chloride channel The disease is characterized by inflammation but the relationship between inflammation, abnormal transepithelial ion transport, and the clinical manifestations of CF are uncertain. The present study was undertaken to determine whether three nonsteroidal anti-inflammatory drugs (NSAIDs) (aspirin, ibuprofen, and indomethacin) modulate CFTR gene expression in T-84 cells. Treatment with NSAIDs reduced CFTR transcripts, and decreased cAMP-stimulated anion fluxes, an index of CFTR function. However, the two phenomena occurred at different concentrations of both drugs. The results indicate that NSAIDs can regulate both CFTR gene expression and the function of CFTR-related chloride transport, and suggest that NSAIDs act via multiple transduction pathways.

  13. Aspirin and Some Other Nonsteroidal Anti-Inflammatory Drugs Inhibit Cystic Fibrosis Transmembrane Conductance Regulator Protein Gene Expression in T-84 Cells

    Danielle Tondelier


    Full Text Available Cystic fibrosis (CF is caused by mutations in the CF gene, which encodes CF transmembrane conductance regulator protein (CFTR, a transmembrane protein that acts as a cAMP-regulated chloride channel. The disease is characterized by inflammation but the relationship between inflammation, abnormal transepithelial ion transport, and the clinical manifestations of CF are uncertain. The present study was undertaken to determine whether three nonsteroidal anti-inflammatory drugs (NSAIDs (aspirin, ibuprofen, and indomethacin modulate CFTR gene expression in T-84 cells. Treatment with NSAIDs reduced CFTR transcripts, and decreased cAMP-stimulated anion fluxes, an index of CFTR function. However, the two phenomena occurred at different concentrations of both drugs. The results indicate that NSAIDs can regulate both CFTR gene expression and the function of CFTR-related chloride transport, and suggest that NSAIDs act via multiple transduction pathways.

  14. The effect of non-steroidal anti-inflammatory drugs on the metabolism of /sup 14/C-arachidonic acid by human gingival tissue in vitro

    Elattar, T.M.; Lin, H.S.; Tira, D.E.


    We investigated the effect of non-steroidal anti-inflammatory drugs on prostaglandins (PGs) and 12-hydroxyeicosatetraenoic acid (12-HETE) formation by inflamed human gingival tissues. Gingival tissue homogenates were incubated with /sup 14/C-arachidonic acid in the presence of indomethacin, piroxicam, or ibuprofen, and the organic solvent extracts were chromatographed on silica gel plates with standards for radiometric assay. There was a significant negative trend between the doses (10(-7)-10(-3) M) of each of indomethacin, piroxicam, and ibuprofen, and the amounts of PGF2 alpha, PGE2, PGD2, and 15-keto-PGE2 produced. All three drugs have a significant inhibitory effect on PGs and 12-HETE production at 10(-3) M when compared with the control. The rank order effectiveness of the drugs, at 10(-3) M, on PG inhibition was indomethacin greater than piroxicam greater than ibuprofen, and on 12-HETE inhibition was indomethacin greater than ibuprofen greater than piroxicam.


    Mr. Adeolu O. Ajala


    Full Text Available The premise for this article is that a significant proportion of patients presenting in the clinic with osteoarthritis have hypertension as co-morbidity. A common drug of choice in managing symptoms of osteoarthritis including those affecting the knee joint is the Non-Steroidal Anti-Inflammatory Drugs (NSAIDS groups. It has been reported however that NSAIDs diminish the effects of anti-hypertensive drugs and may lead to an ineffective hypertension therapy. In order to avoid complications in the health of the patient with concomitant hypertension and osteoarthritis and who are on both antihypertensive and NSAIDs, it becomes imperative to consider using non-pharmacologic approaches such as physiotherapy in managing the symptoms of osteoarthritis in this group of patients and thereby maximizing the effects of their antihypertensive therapy. This is more so that information exists on efficacy of physiotherapy in form of therapeutic exercises and electrotherapeutic modalities in management of clinical features of osteoarthritis.

  16. Risk of myocardial infarction and death associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) among healthy individuals: a nationwide cohort study

    Fosbøl, E L; Gislason, G H; Jacobsen, S


    Use of some nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased cardiovascular risk in several patient groups, but whether this excess risk exists in apparently healthy individuals has not been clarified. Using a historical cohort design, we estimated the risk of death and ......, of whom 1,028,437 were included in the study after applying selection criteria. Compared to no NSAID use, hazard ratios (95% confidence limits) for death/myocardial infarction were 1.01 (0.96-1.07) for ibuprofen, 1.63 (1.52-1.76) for diclofenac, 0.97 (0.83-1.12) for naproxen, 2.13 (1.......89-2.41) for rofecoxib, and 2.01 (1.78-2.27) for celecoxib. A dose-dependent increase in cardiovascular risk was seen for selective COX-2 inhibitors and diclofenac. Caution should be exercised in NSAID use in all individuals, and particularly high doses should be avoided if possible....

  17. Pharmacological treatment of spondyloarthritis: exploring the effectiveness of nonsteroidal anti-inflammatory drugs, traditional disease-modifying antirheumatic drugs and biological therapies

    Caso, Francesco; Costa, Luisa; Del Puente, Antonio; Di Minno, Matteo Nicola Dario; Lupoli, Gelsy; Scarpa, Raffaele; Peluso, Rosario


    Spondyloarthritis represents a heterogeneous group of articular inflammatory diseases that share common genetic, clinical and radiological features. The therapy target of spondyloarthritis relies mainly in improving patients’ quality of life, controlling articular inflammation, preventing the structural joints damage and preserving the functional abilities, autonomy and social participation of patients. Among these, traditional disease-modifying antirheumatic drugs have been demonstrated to be effective in the management of peripheral arthritis; moreover, in the last decade, biological therapies have improved the approach to spondyloarthritis. In patients with axial spondyloarthritis, tumor necrosis factor α inhibitors are currently the only effective therapy in patients for whom conventional therapy with nonsteroidal anti-inflammatory drugs has failed. The aim of this review is to summarize the current experience and evidence about the pharmacological approach in spondyloarthritis patients. PMID:26568809

  18. Analysis of effect of non-steroidal anti-inflammatory drugs on teeth and oral tissues during orthodontic treatment. Report based on literature review.

    Krasny, Marta; Zadurska, Małgorzata; Cessak, Grzegorz; Fiedor, Piotr


    In view of high availability and diversity of non-steroidal anti-inflammatory drugs (NSAIDs) on Polish market it is important for orthodontists to be aware of NSAID effect on the range of orthodontic tooth movement as well as the risk of root resorption in the moved teeth and other adverse effects, which might occur within oral cavity. The disadvantages of NSAID non-selective inhibition of COX include common oral inflammatory conditions, gingival bleeding, and disturbances of salivary secretion. Both, the selective and non-selective COX inhibitors, meloxicam excluded, used to alleviate the pain of orthodontic tooth movement, impede the movement of teeth. Paracetamol, explicitly indicated by most authors as the safest NSAID, seems to be the drug of choice in view of no influence on the range of tooth movement, the risk of root resorption or other adverse effects within oral cavity.

  19. Psychological Stress Increases Risk for Peptic Ulcer, Regardless of Helicobacter pylori Infection or Use of Nonsteroidal Anti-inflammatory Drugs

    Levenstein, Susan; Rosenstock, Steffen; Jacobsen, Rikke Kart;


    antibodies against Helicobacter pylori in stored sera, alcohol consumption, or sleep duration but lower after adjusting for socioeconomic status (1.17; 95% CI, 1.07-1.29; P ....11; 95% CI, 1.01-1.23; P = .04). The risk for ulcer related to stress was similar among subjects who were H pylori seropositive, those who were H pylori seronegative, and those exposed to neither H pylori nor nonsteroidal anti-inflammatory drugs. On multivariable analysis, stress, socioeconomic status......-12 years. METHODS: We collected blood samples and psychological, social, behavioral, and medical data in 1982-1983 from a population-based sample of 3379 Danish adults without a history of ulcer participating in the World Health Organization's MONICA study. A 0- to 10-point stress index scale was used...

  20. Effects of non-steroidal anti-inflammatory drugs on cyanobacteria and algae in laboratory strains and in natural algal assemblages.

    Bácsi, István; B-Béres, Viktória; Kókai, Zsuzsanna; Gonda, Sándor; Novák, Zoltán; Nagy, Sándor Alex; Vasas, Gábor


    In recent years measurable concentrations of non-steroidal anti-inflammatory drugs (NSAIDs) have been shown in the aquatic environment as a result of increasing human consumption. Effects of five frequently used non-steroidal anti-inflammatory drugs (diclofenac, diflunisal, ibuprofen, mefenamic acid and piroxicam in 0.1 mg ml(-1) concentration) in batch cultures of cyanobacteria (Synechococcus elongatus, Microcystis aeruginosa, Cylindrospermopsis raciborskii), and eukaryotic algae (Desmodesmus communis, Haematococcus pluvialis, Cryptomonas ovata) were studied. Furthermore, the effects of the same concentrations of NSAIDs were investigated in natural algal assemblages in microcosms. According to the changes of chlorophyll-a content, unicellular cyanobacteria seemed to be more tolerant to NSAIDs than eukaryotic algae in laboratory experiments. Growth of eukaryotic algae was reduced by all drugs, the cryptomonad C. ovata was the most sensitive to NSAIDs, while the flagellated green alga H. pluvialis was more sensitive than the non-motile green alga D. communis. NSAID treatments had weaker impact in the natural assemblages dominated by cyanobacteria than in the ones dominated by eukaryotic algae, confirming the results of laboratory experiments. Diversity and number of functional groups did not change notably in cyanobacteria dominated assemblages, while they decreased significantly in eukaryotic algae dominated ones compared to controls. The results highlight that cyanobacteria (especially unicellular ones) are less sensitive to the studied, mostly hardly degradable NSAIDs, which suggest that their accumulation in water bodies may contribute to the expansion of cyanobacterial mass productions in appropriate environmental circumstances by pushing back eukaryotic algae. Thus, these contaminants require special attention during wastewater treatment and monitoring of surface waters.

  1. Agents Play Mix-game

    Gou, C


    In mix-game which is an extension of minority game, there are two groups of agents; group1 plays the majority game, but the group2 plays the minority game. This paper studies the change of the average winnings of agents and volatilities vs. the change of mixture of agents in mix-game model. It finds that the correlations between the average winnings of agents and the mean of local volatilities are different with different combinations of agent memory length when the proportion of agents in group 1 increases. This study result suggests that memory length of agents in group1 be smaller than that of agent in group2 when mix-game model is used to simulate the financial markets.

  2. Cultural Differentiation of Negotiating Agents

    Hofstede, G.J.; Jonker, C.M.; Verwaart, D.


    Negotiations proceed differently across cultures. For realistic modeling of agents in multicultural negotiations, the agents must display culturally differentiated behavior. This paper presents an agent-based simulation model that tackles these challenges, based on Hofstede’s model of national cultu

  3. Cultural differentiation of negotiating agents

    Hofstede, G.J.; Jonker, C.M.; Verwaart, T.


    Negotiations proceed differently across cultures. For realistic modeling of agents in multicultural negotiations, the agents must display culturally differentiated behavior. This paper presents an agent-based simulation model that tackles these challenges, based on Hofstede’s model of national cultu

  4. Product and Agent

    Montecino, Alex; Valero, Paola


    In this paper we will explore how the “mathematics teacher” becomes a subject and, at the same time, is subjected as part of diverse dispositive of power. We argue that the mathematics teacher becomes both a product and a social agent, which has been set, within current societies, from the ideas...... of globalization, social progress, and competitive logic. For our approximation, we use the concepts societies of control, dispositive, and discourses from a Foucault–Deleuze toolbox. Our purpose is to cast light on the social and cultural constitution of the ways of thinking about the mathematics teacher. Hence...

  5. Secure Mobile Trade Agent

    Musbah M. Aqe


    Full Text Available E-commerce on the internet has the ability to produce millions of transactions and a great number of merchants whose supply merchandise over the internet. As a result, it is difficult for entities to roam over every site on the internet and choose the best merchandise to trade. So, in this paper we introduced a mobile trade agent that visit the sites to gather and evaluate the information from merchant servers and decide to trade goods on behalf of the user. We observed that the combination of public key cryptosystem with distributed object technology make this proposed scheme more secure and efficient than the already existed schemes.

  6. Agentes selladores en endodoncia


    Recibido: Noviembre 2002 Aceptado: Enero 2003 La gutapercha sigue siendo uno de los materiales predilectos, pero debido a su falta de adhesión a las paredes dentinarias, debe estar siempre combinada con un sellador que actúe como interfase entre la masa de gutapercha y la estructura dentaria. El uso de un agente sellador para obturar los conductos radiculares es esencial para el éxito del proceso de obturación. Un buen sellador debe ser biocompatible y bien tolerado por los tejid...

  7. Agentes de información Information Agents

    Alfonso López Yepes


    Full Text Available Este artículo realiza un repaso sobre las tipologías de agentes de información y describe aspectos como movilidad, racionalidad y adaptatividad, y el ajuste final de estos conceptos a entornos distribuidos como Internet, donde este tipo de agentes tienen un amplio grado de aplicación. Asimismo, se propone una arquitectura de agentes para un sistema multiagente de recuperación de información donde se aplica un paradigma documental basado en el concepto de ciclo documental.This article summarizes the main information agent types reflecting on issues such as mobility, rationality, adaptability and the final adjustment of this concepts to distributed environments such as the Internet, where this kind of agents has wide range application. Likewise, an information agent architecture is proposed to create a multi-agent information retrieval system in which a documentary paradigm based on the documentary cycle is developed.

  8. Holograms as Teaching Agents

    Walker, Robin A.


    Hungarian physicist Dennis Gabor won the Pulitzer Prize for his 1947 introduction of basic holographic principles, but it was not until the invention of the laser in 1960 that research scientists, physicians, technologists and the general public began to seriously consider the interdisciplinary potentiality of holography. Questions around whether and when Three-Dimensional (3-D) images and systems would impact American entertainment and the arts would be answered before educators, instructional designers and students would discover how much Three-Dimensional Hologram Technology (3DHT) would affect teaching practices and learning environments. In the following International Symposium on Display Holograms (ISDH) poster presentation, the author features a traditional board game as well as a reflection hologram to illustrate conventional and evolving Three-Dimensional representations and technology for education. Using elements from the American children's toy Operation® (Hasbro, 2005) as well as a reflection hologram of a human brain (Ko, 1998), this poster design highlights the pedagogical effects of 3-D images, games and systems on learning science. As teaching agents, holograms can be considered substitutes for real objects, (human beings, organs, and animated characters) as well as agents (pedagogical, avatars, reflective) in various learning environments using many systems (direct, emergent, augmented reality) and electronic tools (cellphones, computers, tablets, television). In order to understand the particular importance of utilizing holography in school, clinical and public settings, the author identifies advantages and benefits of using 3-D images and technology as instructional tools.

  9. Amphoteric surface active agents

    Eissa, A.M. F.


    Full Text Available 2-[trimethyl ammonium, triethyl ammonium, pyridinium and 2-amino pyridinium] alkanoates, four series of surface active agents containing carbon chain C12, C14, C16 and C18carbon atoms, were prepared. Their structures were characterized by microanalysis, infrared (IR and nuclear magnetic resonance (NMR. Surface and interfacial tension, Krafft point, wetting time, emulsification power, foaming height and critical micelle concentration (cmc were determined and a comparative study was made between their chemical structure and surface active properties. Antimicrobial activity of these surfactants was also determined.

    Se prepararon cuatro series de agentes tensioactivos del tipo 2-[trimetil amonio, trietil amonio, piridinio y 2-amino piridinio] alcanoatos, que contienen cadenas carbonadas con C12, C14, C16 y C18 átomos de carbono.
    Se determinaron la tensión superficial e interfacial, el punto de Krafft, el tiempo humectante, el poder de emulsionamiento, la altura espumante y la concentración critica de miscela (cmc y se hizo un estudio comparativo entre la estructura química y sus propiedades tensioactivas. Se determinó también la actividad antimicrobiana de estos tensioactivos. Estas estructuras se caracterizaron por microanálisis, infrarrojo (IR y resonancia magnética nuclear (RMN.

  10. Agent-oriented Software Engineering

    GUAN Xu; CHENG Ming; LIU Bao


    An increasing number of computer systems are being viewed in terms of autonomous agents.Most people believe that agent-oriented approach is well suited to design and build complex systems. Yet. todate, little effort had been devoted to discuss the advantages of agent-oriented approach as a mainstreamsoftware engineering paradigm. Here both of this issues and the relation between object-oriented and agent-oriented will be argued. we describe an agent-oriented methodology and provide a quote for designing anauction system.


    Shrivastava Neelesh


    Full Text Available This paper discuss on clinical representation of morbid jealousy which often termed delusional jealousy or ‘Othello Syndrome’ is a psychiatric condition where a lover believes against all reason and their beloved is being sexually unfaithful. Patients will be preoccupied with their partner’s perceived lack of sexual fidelity and will often behave in an unacceptable or extreme way as they endeavor to prove their ideas. Misuse of any psychomotor is an important association cause morbidity jealousy agents, like CNS stimulants that release the catecholamine, particularly dopamine, from pre synaptic terminals substance should be treated as a priority. Where higher levels of violence are reported Sildenafil may be useful as a diagnostic as well as therapeutic test in such cases .Many studies have shown an association between high alcohol consumption and developing morbid jealousy. Amphetamine-induced psychosis has been extensively studied because of its close resemblance to schizophrenia.

  12. UTBot: A Virtual Agent Platform for Teaching Agent System Design

    In-Cheol Kim


    Full Text Available We introduce UTBot, a virtual agent platform for teaching agent system design. UTBot implements a client for the Unreal Tournament game server and Gamebots system. It provides students with the basic functionality required to start developing their own intelligent virtual agents to play autonomously UT games. UTBot includes a generic agent architecture, CAA (Context-sensitive Agent Architecture, a domain-specific world model, a visualization tool, several basic strategies (represented by internal modes and internal behaviors, and skills (represented by external behaviors. The CAA architecture can support complex long-term behaviors as well as reactive short-term behaviors. It also realizes high context-sensitivity of behaviors. We also discuss our experience using UTBot as a pedagogical tool for teaching agent system design in undergraduate Artificial Intelligence course.

  13. Chemopreventive response of diclofenac, a non-steroidal anti-inflammatory drug in experimental carcinogenesis Respuesta quimiopreventiva del diclofenaco, un fármaco antiinflamatorio no esteroideo en la carcinogénesis de colon experimental

    M. Kaur Saini


    Full Text Available The chemopreventive response was evaluated of nonsteroidal anti-inflammatory drug, Diclofenac, a preferential cyclooxygenase-2 (COX-2 inhibitor in 1,2-dimethyhydrazine (DMH-induced colon cancer in rat model. The signs of neoplasm were evident in the animals receiving 30mg of DMH per kg body weight in a weekly s.c injection for six weeks. The putative biomarker of carcinogenesis was visible in the form of multiple plaque lesions in DMH treatment and then regression seen in those animals which also received an oral dose of Diclofenac, 8 mg/kg body weight whereas no such macroscopic neoplastic lesions were seen in the animals receiving Diclofenac only or the control animals receiving the vehicle of the drug. Histopathological results showed the presence of early aberrant changes in the form of severe dysplasia and also numerous crypt fissions in the apical surface of the colonic mucosa. A very high expression of COX-2 was seen in the colonic epithelium of DMH-treated rats, as analyzed by immunohistochemistry. Also, the apoptotic events were assessed by terminal deoxynucleotidyl dUTP nick end labeling (TUNEL assay, where the DMH group shows few number of TUNEL positive cells which dramatically increased in the Diclofenac treatment. The results suggest that Diclofenac could be an effective chemopreventive agent in colon cancer, where perhaps apoptosis plays a very dominant end effect in cancer cell killings.Se evaluó la respuesta quimiopreventiva del fármaco antiinflamatorio no esteroideo, diclofenaco, un inhibidor preferente de la ciclooxigenasa-2 (Cox-2, en el cáncer de colon inducido por 1,2-dimetilhidracina (DMH en un modelo de rata. Los signos de neoplasia fueron evidentes en los animales que recibieron 30 mg de DMH por kg de peso corporal mediante inyecciones s.c. semanales durante 6 semanas. El biomarcador putativo de la carcinogénesis fue visible en la forma de múltiples lesiones en placas con el tratamiento de DMH y la posterior regresi

  14. Cause for concern in the use of non-steroidal anti-inflammatory medications in the community -a population-based study

    Adams Robert J


    Full Text Available Abstract Background Non-steroidal anti-inflammatory (NSAID medications are a common cause of reported adverse drug side-effects. This study describes the prevalence of non-steroidal anti-inflammatory (NSAID use (other than low-dose aspirin and the presence of co-existing relative contraindications to NSAID use and chronic conditions in a representative population sample. Methods Data were analysed from 3,206 adults attending first follow-up of the North West Adelaide Health Study (NWAHS in 2004 - 2006, a longitudinal representative population study. Medications were brought into study clinic visits by participants. Clinical assessment included measured blood pressure, kidney function, serum cholesterol, blood glucose. Questionnaires assessed demographics, lifestyle risk factors, physician-diagnosed chronic conditions. Data were weighted to census measures by region, age group, gender, and probability of selection in the household, to provide population representative estimates. Pearson's Chi-square tests determined significant differences in proportions. Multiple logistic regression was used to examine associations of socio-demographic characteristics with use of NSAIDs. Results Of 3,175 participants, 357 (11.2%, and 16% of those aged > 55 years, reported using either non-specific NSAIDs or COX-2 inhibitors, other than low-dose aspirin. Among people using NSAIDs, 60.8% had hypertension, 30.8% had Stage 3 or higher chronic kidney disease, 17.2% had a history of cardiovascular disease (CVD and 20.7% had a > 15% 10-year CVD risk. The prevalence of NSAID use among people with hypertension was 16%, with kidney disease 15.9%, and a history of CVD 20.0%. Among people taking diuretics, 24.1% were also taking NSAIDs, and of those taking medications for gastro-esophageal reflux, 24.7% were on NSAIDs. Prescription-only COX-2 inhibitors, but not other NSAIDs, were used more by people > 75 years than by 35-54 year olds (OR 3.7, 95% CI 2.0, 6.7, and also were

  15. Non-Steroidal Constituents from the Leaves of Dregea volubilis%南山藤叶非甾体类化学成分研究

    李佳; 赵岑; 张朝凤; 张勉


    To study the non-steroidal constituents of the leaves from Dregea Volubilis and to clarify the material basis. Methods: The ethyl acetate extracts of the 80% ethanol extracts of Dregea volubilis were separated by means of silica gel, Sephadex LH-20 and MCI chromatography. The compounds isolated from the plant were identified by spectrum methods such as MS and NMR. Results: Nine non-steroidal compounds were isolated from the leaves of Dregea volubilis (Asclepiadaceae) and identified as:taraxerol (1), β-sitosterol (2), syringaresinol (3), medioresinol (4), queretaroic acid (5), β-daucosterol (6), auranti-amide benzoate (7), indole-3-carboxaldehyde (8) and aurantiamide acetate (9). Conclusion: Among them, amide (or dipeptide) -type compounds 7 and 9 were firstly obtained from this family.%目的:研究南山藤叶中的非甾体类化学成分,阐明其物质基础。方法:利用硅胶、凝胶、MCI等色谱技术手段,对南山藤叶80%乙醇提取物的乙酸乙酯萃取部位进行分离,运用MS、NMR等波谱方法确定所得化合物结构。结果:从萝藦科南山藤属植物南山藤的干燥叶中分离鉴定了9个化合物:蒲公英赛醇(1),谷甾醇(2),丁香树脂醇(3),梣皮树脂醇(4),栎焦油酸(5),β-胡萝卜苷(6),橙黄胡椒酰胺苯甲酸酯(7),吲哚-3-甲醛(8),橙黄胡椒酰胺乙酸酯(9)。结论:酰胺类化合物7和9为首次从萝藦科中分得。

  16. Agent-based enterprise integration

    N. M. Berry; C. M. Pancerella


    The authors are developing and deploying software agents in an enterprise information architecture such that the agents manage enterprise resources and facilitate user interaction with these resources. The enterprise agents are built on top of a robust software architecture for data exchange and tool integration across heterogeneous hardware and software. The resulting distributed multi-agent system serves as a method of enhancing enterprises in the following ways: providing users with knowledge about enterprise resources and applications; accessing the dynamically changing enterprise; locating enterprise applications and services; and improving search capabilities for applications and data. Furthermore, agents can access non-agents (i.e., databases and tools) through the enterprise framework. The ultimate target of the effort is the user; they are attempting to increase user productivity in the enterprise. This paper describes their design and early implementation and discusses the planned future work.

  17. Odor Classification using Agent Technology

    Sigeru OMATU


    Full Text Available In order to measure and classify odors, Quartz Crystal Microbalance (QCM can be used. In the present study, seven QCM sensors and three different odors are used. The system has been developed as a virtual organization of agents using an agent platform called PANGEA (Platform for Automatic coNstruction of orGanizations of intElligent Agents. This is a platform for developing open multi-agent systems, specifically those including organizational aspects. The main reason for the use of agents is the scalability of the platform, i.e. the way in which it models the services. The system models functionalities as services inside the agents, or as Service Oriented Approach (SOA architecture compliant services using Web Services. This way the adaptation of the odor classification systems with new algorithms, tools and classification techniques is allowed.

  18. Radiation proctitis in the rat. Sequential changes and effects of anti-inflammatory agents

    Northway, M.G.; Scobey, M.W.; Geisinger, K.R.


    Female Wistar rats were treated with single exposure irradiation to 2 cm of distal colon to cause radiation proctitis. All animals were evaluated by examination, colonoscopy and histologic evaluation for changes post-irradiation. Exposures of 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5 and 30 Gy caused dose-related clinical and histologic changes peaking at 7 to 15 days post-exposure. Rats treated with 20 Gy were colonoscoped and biopsied daily and showed sequential post-irradiation endoscopic changes ranging from mucosal edema and mild inflammatory changes to erosion and ulcers. Histologically, crypt abscess and mural wall necrosis similar to changes found in the human rectum after radiotherapy were noted. Treatment with nonsteroidal anti-inflammatory agents, (aspirin, indomethacin, piroxicam), misoprostol (a prostaglandin E1 analogue), or sucralfate (an anti-ulcer agent) did not ameliorate nor exacerbate radiation proctitis in rats exposed to 22.5 Gy. We conclude from these data that the female Wistar rat is a good model for studying radiation proctitis because endoscopic, histologic, and clinical changes seen post-exposure closely resemble those found in man.

  19. Available therapies and current management of fibromyalgia: focusing on pharmacological agents.

    Han, C; Lee, S-J; Lee, S-Y; Seo, H-J; Wang, S-M; Park, M-H; Patkar, A A; Koh, J; Masand, P S; Pae, C-U


    Fibromyalgia (FM) is a chronic medical condition characterized by physical, psychiatric and psychological symptoms. Widespread pain, fatigue, sleep disturbances, heightened sensitivity, morning stiffness, decreased volition, depressed mood and a history of early abuse are frequently reported by patients with FM. Treatment of fibromyalgia is multidisciplinary, with an emphasis on active patient participation, medications, cognitive-behavioral therapy and physical modalities. No single medication has yet been found to sufficiently control all the symptoms of FM; currently available medication classes include antidepressants, nonsteroidal anti-inflammatory drugs, opioids, sedatives, muscle relaxants, analgesics, hypnotic agents and anticonvulsants. Hence, treatment for patients with FM, including pharmacological and non-pharmacological approaches, should be individualized based on each patient's clinical history, target symptoms and functional impairments. Although nonpharmacological modalities are also frequently used, recent research has focused on identifying more effective pharmacological treatments, particularly antidepressants and anticonvulsants. Furthermore, several new pharmacological agents have been now officially approved for the treatment of patients with FM. Thus, the purpose of this review is to help healthcare professionals make informed decisions about the appropriate use of a number of pharmacological treatments for patients with FM.

  20. Agent 与Multi-Agent System 技术研究%The Research on Agent and Multi-Agent System

    党建武; 韩泉叶; 崔文华


    分析了Multi-Agent System 涉及的相关问题,在普通的Multi-Agent System的组织结构的基础上提出了管理服务机构,中介服务机构和主控流动服务机构的Multi-Agent System,并对不同组织结构的Agent之间的协同进行了讨论.

  1. Research on Negotiating Agent Development

    WEI Ding-guo; PENG Hong


    The paper presents a flexible and effective method of development of negotiating agents.A strategy specification, which is specified by a state chart and defeasible rules, can be dynamically inserted into an agent shell incorporating a state chart interpreter and a defeasible logic inference engine, in order to yield a desirable agent.The set of desirable criteria and rules is required to be justified with different context of the application.

  2. Business Intelligence using Software Agents

    Ana-Ramona BOLOGA


    Full Text Available This paper presents some ideas about business intelligence today and the importance of developing real time business solutions. The authors make an exploration of links between business intelligence and artificial intelligence and focuses specifically on the implementation of software agents-based systems in business intelligence. There are briefly presented some of the few solutions proposed so far that use software agents properties for the benefit of business intelligence. The authors then propose some basic ideas for developing real-time agent-based software system for business intelligence in supply chain management, using Case Base Reasoning Agents.

  3. Broad-spectrum antiviral agents

    Jun-Da eZhu


    Full Text Available Development of highly effective, broad-spectrum antiviral agents is the major objective shared by the fields of virology and pharmaceutics. Antiviral drug development has focused on targeting viral entry and replication, as well as modulating cellular defense system. High throughput screening of molecules, genetic engineering of peptides, and functional screening of agents have identified promising candidates for development of optimal broad-spectrum antiviral agents to intervene in viral infection and control viral epidemics. This review discusses current knowledge, prospective applications, opportunities, and challenges in the development of broad-spectrum antiviral agents.

  4. Incorporating BDI Agents into Human-Agent Decision Making Research

    Kamphorst, Bart; van Wissen, Arlette; Dignum, Virginia

    Artificial agents, people, institutes and societies all have the ability to make decisions. Decision making as a research area therefore involves a broad spectrum of sciences, ranging from Artificial Intelligence to economics to psychology. The Colored Trails (CT) framework is designed to aid researchers in all fields in examining decision making processes. It is developed both to study interaction between multiple actors (humans or software agents) in a dynamic environment, and to study and model the decision making of these actors. However, agents in the current implementation of CT lack the explanatory power to help understand the reasoning processes involved in decision making. The BDI paradigm that has been proposed in the agent research area to describe rational agents, enables the specification of agents that reason in abstract concepts such as beliefs, goals, plans and events. In this paper, we present CTAPL: an extension to CT that allows BDI software agents that are written in the practical agent programming language 2APL to reason about and interact with a CT environment.

  5. Deliberate evolution in multi-agent systems

    Brazier, F.M.T.; Jonker, C.M.; Treur, J.; Wijngaards, N.J.E.


    This paper presents an architecture for an agent capable of deliberation about the creation of new agents, and of actually creating a new agent in the multi-agent system, on the basis of this deliberation. After its creation the new agent participates fully in the running multi-agent system. The age

  6. TACtic- A Multi Behavioral Agent for Trading Agent Competition

    Khosravi, Hassan; Shiri, Mohammad E.; Khosravi, Hamid; Iranmanesh, Ehsan; Davoodi, Alireza

    Software agents are increasingly being used to represent humans in online auctions. Such agents have the advantages of being able to systematically monitor a wide variety of auctions and then make rapid decisions about what bids to place in what auctions. They can do this continuously and repetitively without losing concentration. To provide a means of evaluating and comparing (benchmarking) research methods in this area the trading agent competition (TAC) was established. This paper describes the design, of TACtic. Our agent uses multi behavioral techniques at the heart of its decision making to make bidding decisions in the face of uncertainty, to make predictions about the likely outcomes of auctions, and to alter the agent's bidding strategy in response to the prevailing market conditions.

  7. Intestinal toxicity of non-steroideal anti-inflammatory drugs with differential cyclooxigenase inhibition selectivity Toxicidad intestinal de los fármacos antiinflamatorios no esteroideos con una selectividad diferenciada en la inhibición de la ciclooxigenasa

    Chopra, S; R. Kishore Saini; S. Nath Sanyal


    The present study was designed to investigate the gastrointestinal side effects of cycloxygenase (COX) inhibitor with varying selectivity, called the non-steroidal antiinflammatory drugs (NSAIDs) viz., non-selective COX-1 & 2 inhibitor -aspirin, prefentially selective COX-2 inhibitor- nimesulide and highly selective COX-2 inhibitor- celecoxib. Treatment with NSAIDs exhibited a decrease in the activity of rat intestinal brush border membrane associated enzymes such as sucrase, lactase, maltase...

  8. Acupuncture with non-steroidal anti-inflammatory drugs (NSAIDs) versus acupuncture or NSAIDs alone for the treatment of chronic neck pain: an assessor-blinded randomised controlled pilot study


    Objective To investigate the feasibility and sample size required for a full-scale randomised controlled trial of the effectiveness of acupuncture with non-steroidal anti-inflammatory drugs (NSAIDs) for chronic neck pain compared with acupuncture or NSAID treatment alone. Methods A total of 45 patients with chronic neck pain participated in the study. For 3 weeks the acupuncture with NSAIDs treatment group took NSAIDs (zaltoprofen, 80 mg) daily while receiving acupuncture treatment three time...

  9. LC - MS/MS determination of 23 nonsteroidal anti - inflammatory drugs in traditional Chinese medicine preparation%LC-MS/MS法测定中成药制剂中23个非甾体抗炎药

    潘炜; 顾鑫荣; 刘志璋; 胡侠


    spectrometer equipped with electrospray ionization source ( ESI) was used in positive - negative ion mode,multiple reaction monitoring(MRM) was performed to quantify these compounds. Results:23 linear calibration curves were obtained with r2≥0. 9901. The precision of the method were showed as RSD(n =6) ranged from 2. 1% to 7. 7% . The recoveries were tested at two concentrations (0. 05,1. 0 mg· g-1) and ranged from 94. 2% to 110% for the higher concentration. The lowest limit of quantification (LLOQ) is defined as the lowest concentration giving the signal - to - noise ≥ 10= 1,the data were 0. 0013 -0. 05 μg·g-1. Conclusion:The results indicate that the method can be used in quantificational measure of nonsteroidal anti - inflammatory agents on traditional Chinese medicine preparations.

  10. Does the Preemptive Use of Oral Nonsteroidal Anti-inflammatory Drugs Reduce Postoperative Pain in Surgical Removal of Third Molars? A Meta-analysis of Randomized Clinical Trials.

    Costa, Fábio Wildson Gurgel; Esses, Diego Felipe Silveira; de Barros Silva, Paulo Goberlânio; Carvalho, Francisco Samuel Rodrigues; Sá, Carlos Diego Lopes; Albuquerque, Assis Filipe Medeiros; Bezerra, Tácio Pinheiro; Ribeiro, Thyciana Rodrigues; Sá Roriz Fonteles, Cristiane; Soares, Eduardo Costa Studart


    The purpose of this study was to investigate the effectiveness of preemptive analgesia with nonsteroidal anti-inflammatory drugs (NSAIDs) in third-molar surgery. A PubMed literature search was conducted for articles restricted to the English language using the following terms (DeCS/MeSH) or combinations: analgesia, third molar, and preemptive. From a total of 704 articles, 6 (n=420 subjects) were selected. All studies presented a low risk of bias (Cochrane criteria) but exhibited high heterogeneity of methods. Two studies were excluded from the meta-analysis because they did not have adequate numeric values (dichotomous data) for the calculations. Preemptive analgesia showed no significant benefit (n=298, P=.2227, odds ratio: 2.30, 0.60-8.73) in reducing postoperative pain after removal of lower impacted third molars. However, there was a probable direct relationship between the effectiveness of NSAIDs in preemptive analgesia for removal of third molars and its selectivity for the cyclooxygenase-2 (COX-2). Preemptive analgesia did not have a significant effect in reducing postoperative pain after removal of lower impacted third molars. More homogeneous and well-delineated clinical studies are necessary to determine a possible association between NSAIDs' selectivity for COX-2 and treatment effectiveness.

  11. Interaction between Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs and/or low-dose aspirin use: old question new insights.

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


    Previous reports clearly demonstrated that Helicobacter pylori (H. pylori) infection, nonsteroidal anti-inflammatory drugs (NSAID) or low dose aspirin (ASA) use significantly and independently increased the risk for the development of peptic ulcer disease. Today, the presence of H. pylori infection associated with low dose ASA and/or NSAID use in the same patient is becoming more frequent and therefore the potential interaction between these factors and the consequences of it has important implications. Whether NSAID intake in the presence of H. pylori infection may further increase the risk of peptic ulcer carried by the presence of only one risk factor is still a matter of debate. Studies on the interaction between the two risk factors yielded conflicting data and no consensus has been reached in the last years. In addition, the interaction between H. pylori infection and low-dose ASA remains even more controversial. In real clinical practice, we can find different clinical scenarios involving these three factors associated with the presence of different gastrointestinal and cardiovascular risk factors. These huge variety of possible combinations greatly hinder the decision making process of physicians.

  12. Role of carbonyl reducing enzymes in the phase I biotransformation of the non-steroidal anti-inflammatory drug nabumetone in vitro.

    Skarydova, Lucie; Nobilis, Milan; Wsól, Vladimir


    1. Nabumetone is a clinically used non-steroidal anti-inflammatory drug, its biotransformation includes major active metabolite 6-methoxy-2-naphtylacetic acid and another three phase I as well as corresponding phase II metabolites which are regarded as inactive. One important biotransformation pathway is carbonyl reduction, which leads to the phase I metabolite, reduced nabumetone. 2. The aim of this study is the determination of the role of a particular human liver subcellular fraction in the nabumetone reduction and the identification of participating carbonyl reducing enzymes along with their stereospecificities. 3. Both subcellular fractions take part in the carbonyl reduction of nabumetone and the reduction is at least in vitro the main biotransformation pathway. The activities of eight cytosolic carbonyl reducing enzymes--CBR1, CBR3, AKR1B1, AKR1B10, AKR1C1-4--toward nabumetone were tested. Except for CBR3, all tested reductases transform nabumetone to its reduced metabolite. AKR1C4 and AKR1C3 have the highest intrinsic clearances. 4. The stereospecificity of the majority of the tested enzymes is shifted to the production of an (+)-enantiomer of reduced nabumetone; only AKR1C1 and AKR1C4 produce predominantly an (-)-enantiomer. This project provides for the first time evidence that seven specific carbonyl reducing enzymes participate in nabumetone metabolism.

  13. Mechanisms of Nonsteroidal Anti-Inflammatory Drug-Induced Gastrointestinal Injury and Repair: A Window of Opportunity for Cyclooxygenase-Inhibiting Nitric Oxide Donors

    Rafael Perini


    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs cause damage in the upper gastrointestinal (GI tract by impairing the ability of the mucosa to resist and respond to injury. Many of these effects of NSAIDs can be attributed to their ability to suppress mucosal prostaglandin synthesis. Selective inhibitors of cyclooxygenase (COX-2 are less likely to disrupt mucosal defence and do not interfere with platelet aggregation. Thus, their use is associated with a reduced incidence of serious GI adverse events; however, a significant risk of such events still persists. At least in animal models, selective COX-2 inhibitors interfere with ulcer healing to the same extent as conventional NSAIDs. In contrast, COX-inhibiting nitric oxide donors (CINODs produce anti-inflammatory and analgesic effects comparable or superior to those of NSAIDs, but with greatly reduced GI toxicity. Unlike NSAIDs and selective COX-2 inhibitors, CINODs do not interfere with ulcer healing. Moreover, because CINODs suppress the activity of both COX-1 and COX-2, they do not share with selective COX-2 inhibitors the lack of cardioprotection afforded by significant suppression of platelet aggregation. Because of their safety profile, CINODs may be particularly useful for long term prevention applications, such as for colon cancer, cardiovascular disease and Alzheimer's disease.

  14. Side-Effects of Non-Steroidal Anti-Inflammatory Drugs on the Liver in Dogs and Hepatoprotective Effect of Plant Remedies

    Szweda Magdalena


    Full Text Available Hepatoprotective effect of plant drugs against hepatic tissue injury induced by non-steroidal anti-inflammatory drugs (NSAIDs was assessed on Beagle dogs. The adverse effects of carprofen and robenacoxib on the hepatic tissue were evaluated on the basis of histopathological examination of liver sections. It was demonstrated that the use of NSAIDs with liquorice and composed plant remedy Pectosol¯ caused a reduction of hepatic adverse effects induced by the administration of NSAIDs. This fact indicates a hepatoprotective effect of the tested plant remedies during the treatment with NSAIDs. However, the results require further studies on a larger group of animals. Liquorice and Pectosol¯ reduce the hepatic side effects, which develop after the treatment with carprofen and, to a lesser extent, robenacoxib in young Beagles. Such studies allow to investigate the negative and positive effects of using robenacoxib and carprofen in dogs and, therefore, help to limit the NSAID-induced side effects on the liver in these animals.

  15. Structural Mechanism of the Interaction of Alzheimer Disease Aβ Fibrils with the Non-steroidal Anti-inflammatory Drug (NSAID) Sulindac Sulfide.

    Prade, Elke; Bittner, Heiko J; Sarkar, Riddhiman; Lopez Del Amo, Juan Miguel; Althoff-Ospelt, Gerhard; Multhaup, Gerd; Hildebrand, Peter W; Reif, Bernd


    Alzheimer disease is the most severe neurodegenerative disease worldwide. In the past years, a plethora of small molecules interfering with amyloid-β (Aβ) aggregation has been reported. However, their mode of interaction with amyloid fibers is not understood. Non-steroidal anti-inflammatory drugs (NSAIDs) are known γ-secretase modulators; they influence Aβ populations. It has been suggested that NSAIDs are pleiotrophic and can interact with more than one pathomechanism. Here we present a magic angle spinning solid-state NMR study demonstrating that the NSAID sulindac sulfide interacts specifically with Alzheimer disease Aβ fibrils. We find that sulindac sulfide does not induce drastic architectural changes in the fibrillar structure but intercalates between the two β-strands of the amyloid fibril and binds to hydrophobic cavities, which are found consistently in all analyzed structures. The characteristic Asp(23)-Lys(28) salt bridge is not affected upon interacting with sulindac sulfide. The primary binding site is located in the vicinity of residue Gly(33), a residue involved in Met(35) oxidation. The results presented here will assist the search for pharmacologically active molecules that can potentially be employed as lead structures to guide the design of small molecules for the treatment of Alzheimer disease.

  16. Use of non-steroidal anti-inflammatory drugs and prostate cancer risk: a population-based nested case-control study.

    Salaheddin M Mahmud

    Full Text Available BACKGROUND: Despite strong laboratory evidence that non-steroidal anti-inflammatory drugs (NSAIDs could prevent prostate cancer, epidemiological studies have so far reported conflicting results. Most studies were limited by lack of information on dosage and duration of use of the different classes of NSAIDs. METHODS: We conducted a nested case-control study using data from Saskatchewan Prescription Drug Plan (SPDP and Cancer Registry to examine the effects of dose and duration of use of five classes of NSAIDs on prostate cancer risk. Cases (N = 9,007 were men aged ≥40 years diagnosed with prostatic carcinoma between 1985 and 2000, and were matched to four controls on age and duration of SPDP membership. Detailed histories of exposure to prescription NSAIDs and other drugs were obtained from the SPDP. RESULTS: Any use of propionates (e.g., ibuprofen, naproxen was associated with a modest reduction in prostate cancer risk (Odds ratio = 0.90; 95%CI 0.84-0.95, whereas use of other NSAIDs was not. In particular, we did not observe the hypothesized inverse association with aspirin use (1.01; 0.95-1.07. There was no clear evidence of dose-response or duration-response relationships for any of the examined NSAID classes. CONCLUSIONS: Our findings suggest modest benefits of at least some NSAIDs in reducing prostate cancer risk.

  17. Effect of non-steroidal anti-inflammatory drugs on biological properties of Acanthamoeba castellanii belonging to the T4 genotype.

    Siddiqui, Ruqaiyyah; Lakhundi, Sahreena; Iqbal, Junaid; Khan, Naveed Ahmed


    Non-steroidal anti-inflammatory drug, Diclofenac, targeting COX have shown promise in the treatment of Acanthamoeba keratitis, but the underlying mechanisms remain unknown. Using various NSAIDs, Diclofenac sodium, Indomethacin, and Acetaminophen, here we determined the effects of NSAIDs on the biological properties of Acanthamoeba castellanii belonging to the T4 genotype. Using amoebicidal assays, the results revealed that Diclofenac sodium, and Indomethacin affected growth of A. castellanii. In contrast, none of the compounds tested had any effect on the viability of A. castellanii. Importantly, all NSAIDs tested abolished A. castellanii encystation. This is a significant finding as the ability of amoebae to transform into the dormant cyst form presents a significant challenge in the successful treatment of infection. The NSAIDs inhibit production of cyclo-oxegenase, which regulates the synthesis of prostaglandins suggesting that cyclooxygenases (COX-1 and COX-2) and prostaglandins play significant role(s) in Acanthamoeba biology. As NSAIDs are routinely used in the clinical practice, these findings may help design improved preventative strategies and/or of therapeutic value to improve prognosis, when used in combination with other anti-amoebic drugs.

  18. Practical experience with the treatment of recipient mares with a non-steroidal anti-inflammatory drug in an equine embryo transfer programme.

    Koblischke, P; Budik, S; Müller, J; Aurich, C


    As part of a commercial embryo transfer programme, 20 embryos were transferred to spontaneously synchronous or synchronized recipient mares. In 14 cases, embryo recipients were treated with non-steroidal anti-inflammatory drugs (NSAID), receiving flunixin meglumine i.v. at the time of transfer and vedaprofen orally twice a day on the 3 days after embryo transfer, while six embryos were transferred to untreated mares that served as controls. Out of the 14 recipient mares treated with NSAID, 11 (79%) were pregnant at 6-8 days after transfer and in 10 mares, the pregnancy was continued. From the six untreated recipients, only one became pregnant but underwent early embryonic death between day 14 and 35 after ovulation. In conclusion, pregnancy rate in NSAID-treated recipients is higher than that in untreated recipients and above reported average values, indicating that treatment of recipient mares with NSAID helps to increase pregnancy rates after transcervical transfer and can be recommended for equine embryo transfer.

  19. Metal-organic frameworks@graphene hybrid aerogels for solid-phase extraction of non-steroidal anti-inflammatory drugs and selective enrichment of proteins.

    Zhang, Xiaoqiong; Liang, Qionglin; Han, Qiang; Wan, Wei; Ding, Mingyu


    Graphene aerogel (GA)-supported metal-organic framework (MOF) particles with a three-dimensional (3D) architecture were fabricated for the first time via a facile template-free "sol-cryo" method. The prepared MOFs@graphene hybrid aerogels exhibit a 3D interconnected macroporous framework of graphene sheets with uniform dispersion of MOF particles. We also report the first attempt at using the hybrid aerogels as adsorbents for the solid-phase extraction (SPE) of non-steroidal anti-inflammatory drugs (NSAIDs) and the selective enrichment of proteins. The macroporous skeletons of GA provide both low backpressure and rapid mass transfer in SPE application, thus overcoming the obstacle of high backpressure caused by directly packing submicron or micron sized MOF particles into SPE cartridges. Excellent performances including satisfactory recoveries, high sensitivity and good reproducibility were achieved in the extraction of five NSAIDs. The hybrid aerogels also showed an interesting ability for selective enrichment of ribonuclease A (RNase A) and simultaneous exclusion of cytochrome C (Cyt C) and lysozyme (Lyz), which could be attributed to the electrostatic interactions between proteins and the positively charged coordinatively unsaturated metal sites (CUS) in MIL-101. We believe that this work will promote the application of MOFs in adsorption and separation, and our synthetic strategy could be further extended to develop other graphene-based hybrid aerogels.

  20. The nonsteroidal antiinflammatory drug piroxicam reverses the onset of depressive-like behavior in 6-OHDA animal model of Parkinson's disease.

    Santiago, R M; Tonin, F S; Barbiero, J; Zaminelli, T; Boschen, S L; Andreatini, R; Da Cunha, C; Lima, M M S; Vital, M A B F


    Depression is one of the most common psychiatric symptoms in patients with Parkinson's disease (PD). Some authors have reported that depression is characterized by activation of the inflammatory response. Animal models of PD also present with depressive-like behavior, such as increased immobility time in the modified forced swim test and anhedonia-like behavior in the sucrose preference test. Considering the potential neuroprotective effect of nonsteroidal antiinflammatory drugs in neurodegenerative diseases, the objective of the present study was to investigate the effects of piroxicam on depressive-like behavior in male Wistar rats lesioned with 6-hydroxydopamine (6-OHDA) in the substantia nigra (SN). Antidepressant-like effects were observed after prolonged administration of piroxicam for 21days. In the forced swim test, the 6-OHDA+saline group exhibited significant reductions in swimming time and increased immobility time compared with the sham+saline. In the sucrose preference test, the 6-OHDA+piroxicam group exhibited no reduction of sucrose preference compared with the sham+saline, with significant effects of treatment and time and a significant treatment×time interaction. 5-Hydroxytryptamine (5-HT) levels significantly decreased in the hippocampus in the 6-OHDA+saline group and not changed in the 6-OHDA+piroxicam group when compared with the sham+saline on day 21. In conclusion, 21-day treatment with piroxicam reversed the onset of depressive-like behavior and prevented the reduction of hippocampal 5-HT levels.

  1. Development of high-throughput multi-residue method for non-steroidal anti-inflammatory drugs monitoring in swine muscle by LC-MS/MS.

    Castilhos, Tamara S; Barreto, Fabiano; Meneghini, Leonardo; Bergold, Ana Maria


    A reliable and simple method for the detection and quantification of residues of 14 non-steroidal anti-inflammatory drugs and a metamizole metabolite in swine muscle was developed using liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS). The samples were extracted with acetonitrile (ACN) in solid-liquid extraction followed by a low-temperature partitioning (LLE-LTP) process at -20 ± 2°C. After evaporation to dryness, the residue was reconstituted with hexane and a mixture of water:acetonitrile (1:1). LC separation was achieved on a reversed-phase (RP18) column with gradient elution using water (phase A) and ACN (phase B) both containing 1 mmol l(-)(1) ammonium acetate (NH4COO) with 0.025% acetic acid. Analysis was carried out on a triple-quadrupole tandem mass spectrometer (LC-MS/MS) in multiple reaction monitoring mode using an electrospray interface in negative and positive mode in a single run. Method validation was performed according to the criteria of Commission Decision No. 2002/657/EC. The matrix effect and linearity were evaluated. Decision limit (CCα), detection capability (CCβ), accuracy and repeatability of the method are also reported. The proposed method proved to be simple, easy and adequate for high-throughput analysis and was applied to routine analysis by the Brazilian Ministry of Agriculture, Livestock and Food Supply.

  2. Non-steroidal anti-inflammatory drugs decrease E2F1 expression and inhibit cell growth in ovarian cancer cells.

    Blanca L Valle

    Full Text Available Epidemiological studies have shown that the regular use of non-steroidal anti-inflammatory (NSAIDs drugs is associated with a reduced risk of various cancers. In addition, in vitro and experiments in mouse models have demonstrated that NSAIDs decrease tumor initiation and/or progression of several cancers. However, there are limited preclinical studies investigating the effects of NSAIDs in ovarian cancer. Here, we have studied the effects of two NSAIDs, diclofenac and indomethacin, in ovarian cancer cell lines and in a xenograft mouse model. Diclofenac and indomethacin treatment decreased cell growth by inducing cell cycle arrest and apoptosis. In addition, diclofenac and indomethacin reduced tumor volume in a xenograft model of ovarian cancer. To identify possible molecular pathways mediating the effects of NSAID treatment in ovarian cancer, we performed microarray analysis of ovarian cancer cells treated with indomethacin or diclofenac. Interestingly, several of the genes found downregulated following diclofenac or indomethacin treatment are transcriptional target genes of E2F1. E2F1 was downregulated at the mRNA and protein level upon treatment with diclofenac and indomethacin, and overexpression of E2F1 rescued cells from the growth inhibitory effects of diclofenac and indomethacin. In conclusion, NSAIDs diclofenac and indomethacin exert an anti-proliferative effect in ovarian cancer in vitro and in vivo and the effects of NSAIDs may be mediated, in part, by downregulation of E2F1.

  3. Isolated and combined effects of photobiomodulation therapy, topical nonsteroidal anti-inflammatory drugs, and physical activity in the treatment of osteoarthritis induced by papain

    Tomazoni, Shaiane Silva; Leal-Junior, Ernesto Cesar Pinto; Frigo, Lúcio; Pallotta, Rodney Capp; Teixeira, Simone; de Almeida, Patricia; Bjordal, Jan Magnus; Lopes-Martins, Rodrigo Álvaro Brandão


    Osteoarthritis (OA) is a chronic inflammatory disease and is characterized as a degenerative process. This study aimed to evaluate and compare the effects of a topical nonsteroidal anti-inflammatory drug (NSAID), physical activity, and photobiomodulation therapy (PBMT) applied alone and/or in combination between them in an experimental model of knee OA. OA was induced by injection of papain in the knees of rats. After 21 days, the animals started to be treated with the above treatment. Histological analysis shows that the experimental model of OA induction causes morphological changes consistent with the disease, and among treatments, the PBMT is the most effective for reducing these changes. Moreover, the results demonstrate that PBMT and NSAID reduce the total number of cells in the inflammatory infiltrate (p<0.05) and PBMT was the most effective for reducing the activity of myeloperoxidase (p<0.05). Finally, we observed that both NSAID and PBMT were effective for reducing the gene expression of MMP-3 (p<0.05), but in relation to the gene expression of MMP-13, PBMT was the most effective treatment (p<0.05). The results of this study indicate that PBMT is the most effective therapy in stopping disease progression, and improving inflammatory conditions observed in OA.

  4. Gastrotoxic activity and inhibitory effects on gastric mucosal PGE2 production with different non-steroidal anti-inflammatory drugs: modifications induced by pretreatment with zinc acexamate.

    Navarro, C; Bravo, M L; Carulla, C; Bulbena, O


    Gastrotoxic activities of different non-steroidal anti-inflammatory drugs (NSAIDs) (diclofenac, indomethacin, ketoprofen, naproxen and piroxicam) administered per os were compared with their ability to inhibit gastric prostaglandin E2 (PGE2) synthesis in the rat. In a parallel study, effects of pretreatment with zinc acexamate (ZAC) were also assessed. NSAIDs invariably caused gastric mucosal damage and a decrease of PGE2 levels. A good correlation between the decrease of PGE2 levels and the index of gastric lesion (r = 0.41; p < 0.021) was observed when results obtained with the different NSAIDs were pooled. ZAC pretreatment significantly decreased the overall severity of lesions induced by NSAIDs. However, no correlation between gastric lesion index and depletion of PGE2 gastric levels was observed after treatment with ZAC (r = 0.012; p < 0.948). These data corroborate the hypothesis that preservation of the capability to synthesize endogenous PGs is of critical importance in the maintenance of gastric mucosal integrity. The gastroprotective action observed with ZAC involves alternative mechanisms other than modification of PGE2 levels.

  5. Tolerance effects of non-steroidal anti-inflammatory drugs microinjected into central amygdala, periaqueductal grey, and nucleus raphe Possible cellular mechanism

    Merab G. Tsagareli; Nana Tsiklauri; Ivliane Nozadze; Gulnaz Gurtskaia


    Pain is a sensation related to potential or actual damage in some tissue of the body. The mainstay of medical pain therapy remains drugs that have been around for decades, like non-steroidal anti-inflammatory drugs (NSAIDs), or opiates. However, adverse effects of opiates, particularly tolerance, limit their clinical use. Several lines of investigations have shown that systemic (intraperitoneal) administration of NSAIDs induces antinociception with some effects of tolerance. In this review, we report that repeated microinjection of NSAIDs analgin, clodifen, ketorolac and xefocam into the central nucleus of amygdala, the midbrain periaqueductal grey matter and nucleus raphe magnus in the following 4 days result in progressively less antinociception compared to the saline control testing in the tail-flick reflex and hot plate latency tests. Hence, tolerance develops to these drugs and cross-tolerance to morphine in male rats. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, the periaqueductal grey-rostral ventro-medial part of medulla circuit should be viewed as a pain-modulation system. These data are important for human medicine. In particular, cross-tolerance between non-opioid and opioid analgesics should be important in the clinical setting.

  6. Effects of chronic therapy with non-steroideal antinflammatory drugs on gastric permeability of sucrose: A study on 71 patients with rheumatoid arthritis

    Marta Maino; Angelo Franzè; Francesco Di Mario; Nicola Mantovani; Roberta Merli; Giulia Martina Cavestro; Gioacchino Leandro; Lucas Giovanni Cavallaro; Vincenzo Corrente; Veronica Iori; Alberto Pilotto


    AIM: To evaluate the gastric permeability after both acute and chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) and to assess the clinical usefulness of sucrose test in detecting and following NSAIDs- induced gastric damage mainly in asymptomatic patients and the efficacy of a single pantoprazole dose in chronic users.METHODS: Seventy-one consecutive patients on chronic therapy with NSAIDs were enrolled in the study and divided into groups A and B (group A receiving 40 mg pantoprazole daily, group B only receiving NSAIDs). Sucrose test was performed at baseline and after 2, 4 and 12 wk,respectively. The symptoms in the upper gastrointestinal tract were recorded.RESULTS: The patients treated with pantoprazole had sucrose excretion under the limit during the entire follow-up period. The patients without gastroprotection had sucrose excretion above the limit after 2 wk, with an increasing trend in the following weeks (P = 0.000). A number of patients in this group revealed a significantly altered gastric permeability although they were asymptomatic during the follow-up period.CONCLUSION: Sucrose test can be proposed as a valid tool for the clinical evaluation of NSAIDs- induced gastric damage in both acute and chronic therapy. This tecnique helps to identify patients with clinically silent gastric damages. Pantoprazole (40 mg daily) is effective and well tolerated in chronic NSAID users.

  7. Therapeutic Doses of Nonsteroidal Anti-Inflammatory Drugs Inhibit Osteosarcoma MG-63 Osteoblast-Like Cells Maturation, Viability, and Biomineralization Potential

    E. De Luna-Bertos


    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are frequently used to reduce pain and inflammation. However, their effect on bone metabolisms is not well known, and results in the literature are contradictory. The present study focusses on the effect of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid, at therapeutic doses, on different biochemical and phenotypic pathways in human osteoblast-like cells. Osteoblasts (MG-63 cell line were incubated in culture medium with 1–10 μM of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid. Flow cytometry was used to study antigenic profile and phagocytic activity. The osteoblastic differentiation was evaluated by mineralization and synthesis of collagen fibers by microscopy and alkaline phosphatase activity (ALP by spectrophotometric assay. Short-term treatment with therapeutic doses of NSAIDs modulated differentiation, antigenic profile, and phagocyte activity of osteoblast-like cells. The treatment reduced ALP synthesis and matrix mineralization. However, nonsignificant differences were observed on collagen syntheses after treatments. The percentage of CD54 expression was increased with all treatments. CD80, CD86, and HLA-DR showed a decreased expression, which depended on NSAID and the dose applied. The treatments also decreased phagocyte activity in this cellular population. The results of this paper provide evidences that NSAIDs inhibit the osteoblast differentiation process thus reducing their ability to produce new bone mineralized extracellular matrix.

  8. The effect of sulindac, a non-steroidal anti-inflammatory drug, attenuates inflammation and fibrosis in a mouse model of chronic pancreatitis

    Bai Han


    Full Text Available Abstract Background Chronic pancreatitis is characterized by progressive fibrosis, pain and loss of exocrine and endocrine functions. The long-standing chronic pancreatitis and its associated pancreatic fibrosis are the most common pathogenic events involved in human pancreatic carcinogenesis, but the therapeutic strategies to chronic pancreatitis and the chemoprevention of pancreatic carcinogenesis are very limited. Methods We investigated the effect of sulindac, a non-steroidal anti-inflammatory drug (NSAID, on inhibition of chronic pancreatitis in a caerulein induced chronic pancreatitis mouse model. Results Sulindac significantly reduced the severity of chronic pancreatitis including the extent of acini loss, inflammatory cell infiltration and stromal fibrosis. The protein expression of phosphorylation of MEK/ERK was inhibited in the chronic pancreatic tissues by sulindac treatment as measured by Western blot assay. The levels of inflammatory cytokines including TNF-α and MCP-1 were also significantly decreased with sulindac treatment, as well as the expression of TGF-β, PDGF-β, SHH and Gli in the chronic pancreatic tissue detected by qPCR assay and confirmed by western blot assay. The activation of pancreatic satellet cells was also inhibited by sulindac as measured by the activity of α-smooth muscle actin (α-SMA in the pancreatic tissue of chronic pancreatitis. Conclusions Sulindac is a promising reagent for the treatment of chronic pancreatitis via inhibition of inflammatory cell infiltration and stromal fibrosis, the inhibitory effect of sulindac on chronic pancreatitis may through targeting the activation ERK/MAPK signaling pathway.

  9. Prevalence of Helicobacter Pylori-Negative, Non-Steroidal Anti-Inflammatory Drug Related Peptic Ulcer Disease in Patients Referred to Afzalipour Hospital.

    Seyed Mirzaei, Seyed Mahdi; Zahedi, Mohammad Javad; Shafiei Pour, Sara


    BACKGROUND Although Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs) are the main causes of peptic ulcers disease (PUD), recently the prevalence of idiopathic peptic ulcer (IPU) is increasing in most parts of the world. The aim of this study was to assess the prevalence of IPU in Kerman, the center of largest province in south-east Iran. METHODS We included 215 patients with peptic ulcer in our study. Combined methods rapid urease test (RUT), histology, and real time polymerase chain reaction (PCR) was performed on endoscopic samples of peptic ulcers. NSAID use was determined by medical history. SPSS software version 16 was used for data analysis. p valueulcer, four (1.8%) had H.pylorinegative and NSAID-negative PUD. There were not significant differences between patients with IPU and patients with peptic ulcer associated with H.pylori or NSAIDs regarding the sex, age, cigarette smoking, and opioid abuse. CONCLUSION Our study showed that in contrast to other reports from western and some Asian countries, the prevalence of IPU is low in Kerman and H.pylori infection is still the major cause of PUD. We recommend a large and multi-central study to determine the prevalence of IPU in Iran.

  10. Prevalence and diversity of Arcobacter spp. isolated from the internal organs of spontaneous porcine abortions in Denmark

    On, Stephen L.W.; Jensen, Tim Kåre; Bille-Hansen, Vivi


    aborted fetuses from a single sow. The high prevalence of arcobacters in Danish pig abortions may account for at least some of the >90% of cases in which no established abortifacient agent is detected, but further studies are needed to define the role of each species, especially where co...... to examine pooled tissue samples for Campylobacter, Arcobacter and Helicobacter spp. Routine microbiological, immunological, and histopathological examinations were also performed to identify concurrent infections or histopathological change. The abortions tested negative for established abortifacient...

  11. Implementing Lego Agents Using Jason

    Jensen, Andreas Schmidt


    Since many of the currently available multi-agent frameworks are generally mostly intended for research, it can be difficult to built multi-agent systems using physical robots. In this report I describe a way to combine the multi-agent framework Jason, an extended version of the agent-oriented programming language AgentSpeak, with Lego robots to address this problem. By extending parts of the Jason reasoning cycle I show how Lego robots are able to complete tasks such as following lines on a floor and communicating to be able to avoid obstacles with minimal amount of coding. The final implementation is a functional extension that is able to built multi-agent systems using Lego agents, however there are some issues that have not been addressed. If the agents are highly dependent on percepts from their sensors, they are required to move quite slowly, because there currently is a high delay in the reasoning cycle, when it is combined with a robot. Overall the system is quite robust and can be used to make simple...

  12. Topical agents in burn care

    Momčilović Dragan


    Full Text Available Introduction Understanding of fluid shifts and recognition of the importance of early and appropriate fluid replacement therapy have significantly reduced mortality in the early post burn period. After the bum patient successfully passes the resuscitation period, the burn wound represents the greatest threat to survival. History Since the dawn of civilization, man has been trying to find an agent which would help burn wounds heal, and at the same time, not harm general condition of the injured. It was not until the XX century, after the discovery of antibiotics, when this condition was fulfilled. In 1968, combining silver and sulfadiazine, fox made silver-sulfadiazine, which is a 1% hydro-soluble cream and a superior agent in topical treatment of burns today. Current topical agents None of the topical antimicrobial agents available today, alone or combined, have the characteristics of ideal prophylactic agents, but they eliminate colonization of burn wound, and invasive infections are infrequent. With an excellent spectrum of activity, low toxicity, and ease of application with minimal pain, silver-sulfadiazine is still the most frequently used topical agent. Conclusion The incidence of invasive infections and overall mortality have been significantly reduced after introduction of topical burn wound antimicrobial agents into practice. In most burn patients the drug of choice for prophylaxis is silver sulfadiazine. Other agents may be useful in certain clinical situations.

  13. Pharmacologic Agents for Chronic Diarrhea

    Lee, Kwang Jae


    Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reductio...

  14. Activity Recognition for Agent Teams


    seek to use in the upcoming confrontation. There is not a simple mapping between a character capabilities and this policy; an effective team role must...additional research challenges, specific to the team role assumed by the agent. Agents that support individual human team members face the following chal

  15. Mobile agent driven by aspect

    Youssef Hannad


    Full Text Available Domain application of mobile agents is quite large. They are used for network management and the monitoring of complex architecture. Mobile agent is also essential into specific software architecture such that adaptable grid architecture. Even if the concept of mobile agent seems to be obvious, the development is always complex because it needs to understand network features but also security features and negotiation algorithms. We present a work about an application of aspects dedicated to mobile agent development over a local network. At this level, the underlying protocol is called jini and allows managing several essential concepts such that short transaction and permission management. Three subsets of aspects are defined in this work. A part is for the description of agent host and its security level, accessible resource, etc. A second part is about mobile agent and their collaboration. This means how they can operate on an agent host with the respect of the execution context. All the results are illustrated through a distributed monitoring application called DMA. Its main objective is the observation of component servers.

  16. Agent Based Individual Traffic Guidance

    Wanscher, Jørgen

    This thesis investigates the possibilities in applying Operations Research (OR) to autonomous vehicular traffic. The explicit difference to most other research today is that we presume that an agent is present in every vehicle - hence Agent Based Individual Traffic guidance (ABIT). The next...... evolutionary step for the in-vehicle route planners is the introduction of two-way communication. We presume that the agent is capable of exactly this. Based on this presumption we discuss the possibilities and define a taxonomy and use this to discuss the ABIT system. Based on a set of scenarios we conclude...

  17. Agent Based Multiviews Requirements Model


    Based on the current researches of viewpoints oriented requirements engineering and intelligent agent, we present the concept of viewpoint agent and its abstract model based on a meta-language for multiviews requirements engineering. It provided a basis for consistency checking and integration of different viewpoint requirements, at the same time, these checking and integration works can automatically realized in virtue of intelligent agent's autonomy, proactiveness and social ability. Finally, we introduce the practical application of the model by the case study of data flow diagram.

  18. Antibacterial agents in the cinema.

    García Sánchez, J E; García Sánchez, E; Merino Marcos, M L


    Numerous procedures used as antibacterial therapy are present in many films and include strategies ranging from different antimicrobial drugs to surgery and supporting measures. Films also explore the correct use and misuse of antimicrobial agents. Side effects and other aspects related to antibacterial therapy have also been reflected in some films. This article refers to the presence of antibacterial agents in different popular movies. There are movies in which antibacterial agents form part of the central plot, while in others it is merely an important part of the plot. In still others, its presence is isolated, and in these it plays an ambient or anecdotal role.

  19. Deliberate Evolution in Multi-Agent Systems

    Brazier, F.M.T.; Jonker, C.M.; Treur, J.; Wijngaards, N.J.E.


    This paper presents an architecture for an agent capable of deliberation about the creation of new agents, and of actually creating a new agent in the multi-agent system, on the basis of this deliberation. The agent architecture is based on an existing

  20. Implication of Agathic Acid from Utah Juniper Bark as an Abortifacient Compound in Cattle.

    Freshly ground Utah juniper (Juniperus osteosperma (Torr.) Little) bark was given via gavage at a dosage of 2.3 kg/cow twice daily to three pregnant cows starting on day 255 of gestation. All three cows aborted the calves after four, five and six days of treatment. A fourth cow was dosed Utah juni...

  1. Variants of CEP68 gene are associated with acute urticaria/angioedema induced by multiple non-steroidal anti-inflammatory drugs.

    José Antonio Cornejo-García

    Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs are the most consumed drugs worldwide because of their efficacy and utility in the treatment of pain and inflammatory diseases. However, they are also responsible for an important number of adverse effects including hypersensitivity reactions. The most important group of these reactions is triggered by non-immunological, pharmacological mechanisms catalogued under the denomination of cross-intolerance (CRI, with acute urticaria/angioedema induced by multiple NSAIDs (MNSAID-UA the most frequently associated clinical entity. A recent genome-wide association study identified the gene encoding the centrosomal protein of 68 KDa (CEP68 as the major locus associated with aspirin intolerance susceptibility in asthmatics. In this study, we aimed to assess the role of this locus in susceptibility to CRI to NSAIDs by examining 53 common gene variants in a total of 635 patients that were classified as MNSAID-UA (n = 399, airway exacerbations (n = 110 or blended pattern (n = 126, and 425 controls. We found in the MNSAID-UA group a number of variants (17 associated (lowest p-value = 1.13 × 10(-6, including the non-synonymous Gly74Ser variant (rs7572857 previously associated with aspirin intolerance susceptibility in asthmatics. Although not being significant in the context of multiple testing, eight of these variants were also associated with exacerbated respiratory disease or blended reactions. Our results suggest that CEP68 gene variants may play an important role in MNSAID-UA susceptibility and, despite the different regulatory mechanisms involved depending on the specific affected organ, in the development of hypersensitivity reactions to NSAIDs.

  2. Variants of CEP68 gene are associated with acute urticaria/angioedema induced by multiple non-steroidal anti-inflammatory drugs.

    Cornejo-García, José Antonio; Flores, Carlos; Plaza-Serón, María C; Acosta-Herrera, Marialbert; Blanca-López, Natalia; Doña, Inmaculada; Torres, María J; Mayorga, Cristobalina; Guéant-Rodríguez, Rosa M; Ayuso, Pedro; Fernández, Javier; Laguna, José J; Agúndez, José A G; García-Martín, Elena; Guéant, Jean-Louis; Canto, Gabriela; Blanca, Miguel


    Non-steroidal anti-inflammatory drugs (NSAIDs) are the most consumed drugs worldwide because of their efficacy and utility in the treatment of pain and inflammatory diseases. However, they are also responsible for an important number of adverse effects including hypersensitivity reactions. The most important group of these reactions is triggered by non-immunological, pharmacological mechanisms catalogued under the denomination of cross-intolerance (CRI), with acute urticaria/angioedema induced by multiple NSAIDs (MNSAID-UA) the most frequently associated clinical entity. A recent genome-wide association study identified the gene encoding the centrosomal protein of 68 KDa (CEP68) as the major locus associated with aspirin intolerance susceptibility in asthmatics. In this study, we aimed to assess the role of this locus in susceptibility to CRI to NSAIDs by examining 53 common gene variants in a total of 635 patients that were classified as MNSAID-UA (n = 399), airway exacerbations (n = 110) or blended pattern (n = 126), and 425 controls. We found in the MNSAID-UA group a number of variants (17) associated (lowest p-value = 1.13 × 10(-6)), including the non-synonymous Gly74Ser variant (rs7572857) previously associated with aspirin intolerance susceptibility in asthmatics. Although not being significant in the context of multiple testing, eight of these variants were also associated with exacerbated respiratory disease or blended reactions. Our results suggest that CEP68 gene variants may play an important role in MNSAID-UA susceptibility and, despite the different regulatory mechanisms involved depending on the specific affected organ, in the development of hypersensitivity reactions to NSAIDs.


    Diana Pérez-Alzate


    Full Text Available In subjects with non-steroidal anti-inflammatory drugs (NSAIDs- exacerbated respiratory disease (NERD symptoms are triggered by acetyl salicylic acid (ASA and other strong COX-1 inhibitors, and in some cases by weak COX-1 or by selective COX-2 inhibitors. The mechanism involved is related to prostaglandin pathway inhibition and leukotriene release. Subjects who react to a single NSAID and tolerate others are considered selective responders, and often present urticaria and/or angioedema and anaphylaxis (SNIUAA. An immunological mechanism is implicated in these reactions. However, anecdotal evidence suggests that selective responders who present respiratory airway symptoms may also exist.Our objective was to determine if subjects might develop selective responses to NSAIDs/paracetamol that manifest as upper/lower airways respiratory symptoms. For this purpose we studied patients reporting asthma and/or rhinitis induced by paracetamol or a single NSAID that tolerated ASA. An allergological evaluation plus controlled challenge with ASA was carried out. If ASA tolerance was found, we proceeded with an oral challenge with the culprit drug. The appearance of symptoms was monitored by a clinical questionnaire and by measuring FEV1 and/or nasal airways volume changes pre and post challenge. From a total of 21 initial cases, we confirmed the appearance of nasal and/or bronchial manifestations in ten, characterised by a significant decrease in FEV1% and/or a decrease in nasal volume cavity after drug administration. All cases tolerated ASA.This shows that ASA tolerant subjects with asthma and/or rhinitis induced by paracetamol or a single NSAID without skin/systemic manifestations exist. Whether these patients represent a new clinical phenotype to be included within the current classification of hypersensitivity reactions to NSAIDs requires further investigation.

  4. Changes of nitric oxide system and lipid peroxidation parameters in the digestive system of rats under conditions of acute stress, and use of nonsteroidal anti-inflammatory drugs

    Fomenko Iryna


    Full Text Available The use of nonsteroidal anti-inflammatory drugs (NSAIDs in combination with being physiologically stressed often occurs in in the course of different pathologies. This situation may result in the alteration of digestive system functioning. The effect of stress brings about changes in the activity of nitric oxide synthase (NOS, arginase, cyclooxygenase (COX and lipid peroxidation, whereas the use of NSAIDs interrupts the multiple functions of the cell via the inhibition of prostaglandins (PGs synthesis. Taking into account that NOS and COX-systems are connected in their regulation, the aim of the study was to determine the role played by NOS and lipid peroxidation under conditions of the combined action of NSAIDs and stress. In our study, male rats were used. The NSAIDs (naproxen - a non-selective COX inhibitor, celecoxib - a selective COX-2 blocker, and the compound 2A5DHT (which is the active substance of dual COX, and the lipoxygenase (LOX inhibitor, darbufelone were all administered at a dose 10 mg/kg, prior to water restraint stress (WRS. WRS brought about an increase of inducible NOS (iNOS activity in the intestinal mucosal and muscular membranes, as well as in the pancreas. Because of this, constitutive NOS izoform (cNOS and arginase activities decreased. Moreover, the MDA concentration increased, indicating the development of oxidative stress. In our work, pretreatment with naproxen, as in the WRS model, engendered a decrease in iNOS activity. What is more, administration of Celecoxib did not change iNOS activity, as compared to WRS alone, and it showed a tendency to reduce lipid peroxidation. In addition, 2A5DHT prior WRS brought about a decrease of iNOS activity, with the subsequent rise of cNOS activity. Of note, MDA concentration decreased in all studied organs, indicating the reduction of lipid peroxidation under the action of the darbufelone active substance.

  5. Non-steroidal anti-inflammatory drugs, Cyclooxygenase-2 inhibitors and paracetamol use in Queensland and in the whole of Australia

    Tett Susan E


    Full Text Available Abstract Background Cross national drug utilization studies can provide information about different influences on physician prescribing. This is important for medicines with issues around safety and quality of use, like non selective non-steroidal anti-inflammatory drugs (ns-NSAIDs and cyclo-oxygenase-2 (COX-2 inhibitors. To enable comparison of prescription medicine use across different jurisdictions with a range of population sizes, data first need to be compared within Australia to understand whether use in a smaller sub-population may be considered as representative of the total use within Australia. The aim of this study was to compare the utilization of non selective NSAID, COX-2 inhibitors and paracetamol between Queensland and Australia. Method Dispensing data were obtained for concession beneficiaries for Australia for ns-NSAIDs, COX-2 inhibitors and paracetamol subsidized by the PBS over the period 1997–2003. The same data were purchased for Queensland. Data were converted to Defined Daily Dose (DDD/1000 beneficiaries/day (World Health Organization anatomical therapeutic chemical classification, 2005. Results Total NSAID and paracetamol consumption were similar in Australia and Queensland. Ns-NSAID use decreased sharply with the introduction of COX-2 inhibitors (from approximately 80 to 40 DDD/1000 beneficiaries/day. Paracetamol was constant (approximately 45 DDD/1000 beneficiaries/day. COX-2 inhibitors consumption was initially higher in Queensland than in the whole of Australia. Conclusion Despite initial divergence in celecoxib use between Queensland and Australia, the use of ns-NSAIDs, COX-2 inhibitors and paracetamol overall, in concession beneficiaries, was comparable in Australia and Queensland.

  6. Receptor subtype-dependent positive and negative modulation of GABA(A) receptor function by niflumic acid, a nonsteroidal anti-inflammatory drug.

    Sinkkonen, Saku T; Mansikkamäki, Salla; Möykkynen, Tommi; Lüddens, Hartmut; Uusi-Oukari, Mikko; Korpi, Esa R


    In addition to blocking cyclooxygenases, members of the fenamate group of nonsteroidal anti-inflammatory drugs have been proposed to affect brain GABAA receptors. Using quantitative autoradiography with GABAA receptor-associated ionophore ligand [35S]t-butylbicyclophosphorothionate (TBPS) on rat brain sections, one of the fenamates, niflumate, at micromolar concentration was found to potentiate GABA actions in most brain areas, whereas being in the cerebellar granule cell layer an efficient antagonist similar to furosemide. With recombinant GABAA receptors expressed in Xenopus laevis oocytes, we found that niflumate potentiated 3 microM GABA responses up to 160% and shifted the GABA concentration-response curve to the left in alpha1beta2gamma2 receptors, the predominant GABAA receptor subtype in the brain. This effect needed the gamma2 subunit, because on alpha1beta2 receptors, niflumate exhibited solely an antagonistic effect at high concentrations. The potentiation was not abolished by the specific benzodiazepine site antagonist flumazenil. Niflumate acted as a potent antagonist of alpha6beta2 receptors (with or without gamma2 subunit) and of alphaXbeta2gamma2 receptors containing a chimeric alpha1 to alpha6 subunit, which suggests that niflumate antagonism is dependent on the same transmembrane domain 1- and 2-including fragment of the alpha6 subunit as furosemide antagonism. This antagonism was noncompetitive because the maximal GABA response, but not the potency, was reduced by niflumate. These data show receptor subtype-dependent positive and negative modulatory actions of niflumate on GABAA receptors at clinically relevant concentrations, and they suggest the existence of a novel positive modulatory site on alpha1beta2gamma2 receptors that is dependent on the gamma2 subunit but not associated with the benzodiazepine binding site.

  7. Molecular modeling and simulation studies of recombinant laccase from Yersinia enterocolitica suggests significant role in the biotransformation of non-steroidal anti-inflammatory drugs.

    Singh, Deepti; Rawat, Surender; Waseem, Mohd; Gupta, Sunita; Lynn, Andrew; Nitin, Mukesh; Ramchiary, Nirala; Sharma, Krishna Kant


    The YacK gene from Yersinia enterocolitica strain 7, cloned in pET28a vector and expressed in Escherichia coli BL21 (DE3), showed laccase activity when oxidized with 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and guaiacol. The recombinant laccase protein was purified and characterized biochemically with a molecular mass of ≈58 KDa on SDS-PAGE and showed positive zymogram with ABTS. The protein was highly robust with optimum pH 9.0 and stable at 70 °C upto 12 h with residual activity of 70%. Kinetic constants, Km values, for ABTS and guaiacol were 675 μM and 2070 μM, respectively, with corresponding Vmax values of 0.125 μmol/ml/min and 6500 μmol/ml/min. It also possess antioxidative property against BSA and Cu(2+)/H2O2 model system. Constant pH MD simulation studies at different protonation states of the system showed ABTS to be most stable at acidic pH, whereas, diclofenac at neutral pH. Interestingly, aspirin drifted out of the binding pocket at acidic and neutral pH, but showed stable binding at alkaline pH. The biotransformation of diclofenac and aspirin by laccase also corroborated the in silico results. This is the first report on biotransformation of non-steroidal anti-inflammatory drugs (NSAIDs) using recombinant laccase from gut bacteria, supported by in silico simulation studies.

  8. Comparison of cardiovascular thrombotic events in patients with osteoarthritis treated with rofecoxib versus nonselective nonsteroidal anti-inflammatory drugs (ibuprofen, diclofenac, and nabumetone).

    Reicin, Alise S; Shapiro, Deborah; Sperling, Rhoda S; Barr, Eliav; Yu, Qinfen


    Aspirin, nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), and specific cyclooxygenase-2 (COX-2) inhibitors each have distinctive effects on COX-1-mediated thromboxane biosynthesis, the major determinant of platelet aggregation. It is unclear whether these effects are associated with differences in thrombogenic risks. To compare the risk for thrombotic cardiovascular events among patients receiving rofecoxib, nonselective NSAIDs, and placebo, cardiovascular safety was assessed in 5,435 participants in 8 phase IIB/III osteoarthritis trials. The median treatment exposure was 31/2 months. The primary end point assessed was the risk of any arterial or venous thrombotic cardiovascular adverse event (AE). A second analysis assessed differences in the Anti-Platelet Trialists' Collaboration (APTC) events, a cluster end point that consists of the combined incidence of (1) cardiovascular, hemorrhagic, and unknown death; (2) myocardial infarction; and (3) cerebrovascular accident. Similar rates of thrombotic cardiovascular AEs were reported with rofecoxib, placebo, and comparator nonselective NSAIDs (ibuprofen, diclofenac, or nabumetone). In trials that compared rofecoxib with NSAIDs, the incidence of thrombotic cardiovascular AEs was 1.93/100 patient-years in the rofecoxib treatment group compared with 2.27/100 patient-years in the combined nonselective NSAID group. In trials that compared rofecoxib with placebo, the incidence of thrombotic cardiovascular AEs was 2.71/100 patient-years in the rofecoxib group compared with 2.57/100 patient-years in the placebo group. Consistent with the risks of cardiovascular AEs, similar rates of APTC events were reported with rofecoxib, placebo, and comparator nonselective NSAIDs. Thus, in the rofecoxib osteoarthritis development program, there was no difference between rofecoxib, comparator nonselective NSAIDs, and placebo in the risks of cardiovascular thrombotic events.

  9. Occurrence and behavior of non-steroidal anti-inflammatory drugs and lipid regulators in wastewater and urban river water of the Pearl River Delta, South China.

    Huang, Qiuxin; Yu, Yiyi; Tang, Caiming; Zhang, Kun; Cui, Jianlan; Peng, Xianzhi


    Occurrence of five non-steroidal anti-inflammatory drugs (salicylic acid, ibuprofen, naproxen, indomethacin and diclofenac) and three lipid regulators (bezafibrate, clofibric acid and gemfibrozil) was investigated in wastewater, sewage sludge, and river water of the urban section of the Pearl River at Guangzhou in South China. Behavior and fate of the pharmaceuticals during treatment in two sewage treatment plants (STPs) were also studied in depth by determining concentrations in the influents and effluents at major treatment units and the sewage sludge. Concentrations of the pharmaceuticals in the raw wastewater were mostly at ng L(-1) levels except salicylic acid whose concentrations ranged from 9.6 to 23.3 μg L(-1). No significant amount of the pharmaceuticals was detected in the suspended particulate matter of wastewater and sewage sludge. Salicylic acid, indomethacin, and naproxen were almost completely removed (≥ 99%); gemfibrozil, ibuprofen and bezafibrate were significantly removed (>75%), whereas diclofenac and clofibric acid were removed by 60-70% during treatment in the STPs. Generally, biodegradation was the governing process for elimination of the investigated pharmaceuticals. Anaerobic biodegradation was responsible for most of the removal of diclofenac whereas aerobic biodegradation also played an important role in elimination of the other pharmaceuticals except SA, which was nearly completely removed after the anoxic process. In the Pearl River, the pharmaceuticals were widely detected. Both the concentrations and detection frequency were higher in March 2008 than those in the other seasons, which may be ascribed mainly to less dilution caused by lower precipitation. Besides the STPs, urban canals directly connected with the Pearl River may also be important contributors to the pharmaceutical contamination in the river.

  10. Exacerbation of nonsteroidal anti-inflammatory drug-induced small intestinal lesions by antisecretory drugs in rats: the role of intestinal motility.

    Satoh, Hiroshi; Amagase, Kikuko; Takeuchi, Koji


    Antisecretory drugs such as histamine H2-receptor antagonists (H2-RAs) and proton pump inhibitors (PPIs) are commonly used for the treatment of gastric and duodenal ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs). However, the effects of these drugs on NSAID-induced small intestinal ulcers are not fully understood. The effects of H2-RAs and PPIs on NSAID-induced gastrointestinal lesions and small intestinal motility were examined in rats. Male Wistar rats (180-220 g) were used. Indomethacin (10 mg/kg) was administered orally in fasted or fed rats, and gastrointestinal lesions were examined 24 h after indomethacin administration. Intestinal motility was measured by using a balloon method under urethane anesthesia. Indomethacin produced multiple lesions in the gastric corpus in fasted rats and in the small intestine in fed rats: 1) H2-RAs (cimetidine, ranitidine, and famotidine) and PPIs (omeprazole, lansoprazole, and rabeprazole) markedly inhibited the formation of gastric lesions. 2) The drugs, except for lansoprazole, increased intestinal lesions. 3) H2-RAs augmented the increase in intestinal motility caused by indomethacin, and the effects of H2-RAs on motility and intestinal lesions were markedly inhibited by atropine. 4) Lansoprazole inhibited the formation of intestinal lesions, and the effect was prevented by both pharmacological ablation of capsaicin-sensitive sensory neurons and pretreatment with N-nitro-l-arginine methyl ester, a selective inhibitor of nitric-oxide synthesis. The results suggest that: 1) inhibition of acid secretion by antisecretory drugs may exacerbate NSAID-induced intestinal lesions, 2) H2-RAs further aggravate lesions by increasing intestinal motility via the activation of cholinergic pathways, and 3) lansoprazole protects the intestinal mucosa against NSAID-related ulcerative stimuli.

  11. The Structural Basis for the Prevention of Nonsteroidal Antiinflammatory Drug-Induced Gastrointestinal Tract Damage by the C-Lobe of Bovine Colostrum Lactoferrin

    Mir, Rafia; Singh, Nagendra; Vikram, Gopalakrishnapillai; Kumar, Ramasamy Prem; Sinha, Mau; Bhushan, Asha; Kaur, Punit; Srinivasan, Alagiri; Sharma, Sujata; Singh, Tej P.


    Abstract Nonsteroidal antiinflammatory drugs (NSAIDs), due to their good efficacy in the treatment of pain, inflammation, and fever, are among the most prescribed class of medicines in the world. The main drawback of NSAIDs is that they induce gastric complications such as peptic ulceration and injury to the intestine. Four NSAIDs, indomethacin, diclofenac, aspirin, and ibuprofen were selected to induce gastropathy in mouse models. It was found that the addition of C-terminal half of bovine lactoferrin (C-lobe) reversed the NSAID-induced injuries to the extent of 47–70% whereas the coadministration of C-lobe prevented it significantly. The C-lobe was prepared proteolytically using serine proteases. The binding studies of C-lobe with NSAIDs showed that these compounds bind to C-lobe with affinities ranging from 2.6 to 4.8 × 10−4 M. The complexes of C-lobe were prepared with the above four NSAIDs. All four complexes were crystallized and their detailed three-dimensional structures were determined using x-ray crystallographic method. The structures showed that all the four NSAID molecules bound to C-lobe at the newly identified ligand binding site in C-lobe that is formed involving two α-helices, α10 and α11. The ligand binding site is separated from the well known iron binding site by the longest and the most stable β-strand, βj, in the structure. Similar results were also obtained with the full length lactoferrin molecule. This novel, to our knowledge, binding site in C-lobe of lactoferrin shows a good complementarity for the acidic and lipophilic compounds such as NSAIDs. We believe this indicates that C-lobe of lactoferrin can be exploited for the prevention of NSAID-induced gastropathy. PMID:20006955

  12. Nonsteroidal anti-inflammatory drugs suppress cancer stem cells via inhibiting PTGS2 (cyclooxygenase 2) and NOTCH/HES1 and activating PPARG in colorectal cancer.

    Moon, Chang Mo; Kwon, Ji-Hee; Kim, Ji Suk; Oh, Sun-Hee; Jin Lee, Kyoung; Park, Jae Jun; Pil Hong, Sung; Cheon, Jae Hee; Kim, Tae Il; Kim, Won Ho


    Cancer stem cells (CSCs) play a pivotal role in cancer relapse or metastasis. We investigated the CSC-suppressing effect of nonsteroidal anti-inflammatory drugs (NSAIDs) and the relevant mechanisms in colorectal cancer. We measured the effect of NSAIDs on CSC populations in Caco-2 or SW620 cells using colosphere formation and flow cytometric analysis of PROM1 (CD133)(+) CD44(+) cells after indomethacin treatment with/without prostaglandin E2 (PGE2) or peroxisome proliferator-activated receptor γ (PPARG) antagonist, and examined the effect of indomethacin on transcriptional activity and protein expression of NOTCH/HES1 and PPARG. These effects of indomethacin were also evaluated in a xenograft mouse model. NSAIDs (indomethacin, sulindac and aspirin), celecoxib, γ-secretase inhibitor and PPARG agonist significantly decreased the number of colospheres formation compared to controls. In Caco-2 and SW620 cells, compared to controls, PROM1 (CD133)(+) CD44(+) cells were significantly decreased by indomethacin treatment, and increased by 5-fluorouracil (5-FU) treatment. This 5-FU-induced increase of PROM1 (CD133)(+) CD44(+) cells was significantly attenuated by combination with indomethacin. This CSC-inhibitory effect of indomethacin was reversed by addition of PGE2 and PPARG antagonist. Indomethacin significantly decreased CBFRE and increased PPRE transcriptional activity and their relative protein expressions. In xenograft mouse experiments using 5-FU-resistant SW620 cells, the 5-FU treatment combined with indomethacin significantly reduced tumor growth, compared to 5-FU alone. In addition, treatment of indomethacin alone or combination of 5-FU and indomethacin decreased the expressions of PROM1 (CD133), CD44, PTGS2 (cyclooxygenase 2) and HES1, and increased PPARG expression. NSAIDs could selectively reduce the colon CSCs and suppress 5-FU-induced increase of CSCs via inhibiting PTGS2 (cyclooxygenase 2) and NOTCH/HES1, and activating PPARG.

  13. The role of activated carbon and disinfection on the removal of endocrine disrupting chemicals and non-steroidal anti-inflammatory drugs from wastewater.

    Noutsopoulos, Constantinos; Mamais, Daniel; Mpouras, Thanasis; Kokkinidou, Despina; Samaras, Vasilios; Antoniou, Korina; Gioldasi, Marianna


    Endocrine disrupting chemicals and non-steroidal anti-inflammatory drugs are two important groups of emerging pollutants due to their toxicological and chemical characteristics and their persistent detection in the aquatic environment. Wastewater treatment plants are a significant pathway for their transfer to the water courses. It is well evidenced that these chemicals are only partially removed through biological treatment of wastewater and therefore being detected in secondary effluents. This work focuses on the evaluation of the efficiency of two well-established disinfection technologies (chlorination and UV irradiation) along with UV/H2O2 and powdered activated carbon (PAC) to remove these chemicals from biologically treated wastewater. Based on the results it is shown that appreciable removal efficiencies due to chlorination should be expected for most of the target compounds, whereas this was not the case for ibuprofen and ketoprofen. With the exemption of diclofenac and ketoprofen direct UV irradiation did not efficiently removed target compounds for UV doses usually applied for disinfection purposes. The application of advanced UV treatment through the addition of H2O2 although resulted in increased removal of the target compounds is not sufficient at moderate UV and H2O2 doses to achieve satisfactory removal efficiencies. PAC use resulted in sufficient removal of target compounds although high PAC doses were required for some chemicals. Comparison of Freundlich isotherms of this study with those of other studies, derived employing water samples, suggested that the water matrix along with the target compounds concentration range can significantly affect the outcome of the experiments.

  14. Non-steroidal anti-inflammatory drugs and paracetamol in self-therapy of various disorders in students of different fields of study.

    Wiliński, Jerzy; Lechowicz, Marta; Kameczura, Tomasz; Głowacki, Mikołaj; Kameczura, Anna; Chrapusta, Anna; Wiliński, Bogdan


    Over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol are most commonly the first-line pharmacotherapy in combating different pain and inflammatory disorders and fever. Unfortunately, those drugs might have serious side effects, especially when they are used in an inappropriate way. The aim of the study was to explore various aspects of NSAIDs and paracetamol use in the self-therapy of miscellaneous disorders in young adults. The questionnaire-based survey comprised 250 consecutive students aged 22.1 ± 1.9 years (189 women) of diverse fields of study. The drugs were applied in clinical conditions in which they should be avoided including asthma attack (1.2%), vomiting (2.4%), malaise and depression (3.6%), in autumn and winter as a preventive measure against infections (14.0%), heart-burn (2.0%) and during food poisoning (16.0%). As many as 6.0% of the students claimed that studied medications are ultimately free of adverse reactions. Men more frequently than women used NSAIDs and paracetamol during alcohol consumption (49.2% vs 30.7%, p = 0.009, respectively) but less often were aware that there are maximum doses of medications which should not be exceeded (57.4% vs 76.7%, p = 0.003, respectively). The students of medical-related degree courses (n = 82) compared with individuals of other subjects (n = 168) declared they more often have the custom of always reading medications' leaflets (46.3% vs 31.0%, p = 0.017, respectively). Side effects of medicines were reported by 65 participants - 26.0%. In conclusion, students' knowledge about NSAIDs and paracetamol is low. Participants do not search for information on drug related endangerments, the medication group choice for the given disorder is often inappropriate and the drugs are applied in conditions in which they are contraindicated.


    Hans Raj


    Full Text Available Pain is not only an unpleasant sensation but also increases morbidity of any operation like atelectasis, ileus, requirement of intensive care and increase in hospital stay. By neuro-modulation based on the gate control theory, we can achieve the similar results as with pharmaceutics without their side effects. Aim of this study was to compare the Non-Steroidal Anti-Inflammatory Drug (NSAID with Transcutaneous Nerve Stimulation (TENS in terms of postoperative pain and duration of pain relief by using a visual analogue scale. MATERIAL AND METHODS Our study included open cholecystectomy patients, 25 patients in each group (Groups I with NSAID, group II with TENS use. The lower limit of age was 20 years. All patients who underwent open cholecystectomy and above 20 years of age without any comorbidities were included in the study. Data was analysed by using SPSS software version 16. RESULTS In TENS therapy group, patient’s acceptance was 84%. Patients in group I had a higher VAS score and less duration of pain relief than group II at 24 and 48 hours (VAS = 4 v/s 2, duration of pain relief = 8.0 and 8.8 hours v/s 10.8 and 11.2 hours. Average numbers of application for the group I was higher than group II (3 v/s 2.1. Both showed no complications of pain equal physiologic parameters like pulse and blood pressure, so both modalities were effective in controlling pain. CONCLUSION TENS can be used without analgesic for the postoperative pain of cholecystectomy with good patient acceptance and effectiveness.

  16. Fabrication of aluminum terephthalate metal-organic framework incorporated polymer monolith for the microextraction of non-steroidal anti-inflammatory drugs in water and urine samples.

    Lyu, Dan-Ya; Yang, Cheng-Xiong; Yan, Xiu-Ping


    Polymer monolith microextraction (PMME) based on capillary monolithic column is an effective and useful technique to preconcentrate trace analytes from environmental and biological samples. Here, we report the fabrication of a novel aluminum terephthalate metal-organic framework (MIL-53(Al)) incorporated capillary monolithic column via in situ polymerization for the PMME of non-steroidal anti-inflammatory drugs (NSAIDs) (ketoprofen, fenbufen and ibuprofen) in water and urine samples. The fabricated MIL-53(Al) incorporated monolith was characterized by X-ray powder diffractometry, scanning electron microscopy, Fourier transform infrared spectrometry, and nitrogen adsorption experiment. The MIL-53(Al) incorporated monolith gave larger surface area than the neat polymer monolith. A 2-cm long MIL-53(Al) incorporated capillary monolith was applied for PMME coupled with high-performance liquid chromatography for the determination of the NSAIDs. Potential factors affecting the PMME were studied in detail. Under the optimized conditions, the developed method gave the enhancement factors of 46-51, the linear range of 0.40-200μgL(-1), the detection limits (S/N=3) of 0.12-0.24μgL(-1), and the quantification limits (S/N=10) of 0.40-0.85μgL(-1). The recoveries for spiked NSAIDs (20μgL(-1)) in water and urine samples were in the range of 77.3-104%. Besides, the MIL-53(Al) incorporated monolith was stable enough for 120 extraction cycles without significant loss of extraction efficiency. The developed method was successfully applied to the determination of NSAIDs in water and urine samples.

  17. Monitoring the concentrations of nonsteroidal anti-inflammatory drugs and cyclooxygenase-inhibiting activities in the surface waters of the Tone Canal and Edo River Basin.

    Nishi, Iwaki; Kawakami, Tsuyoshi; Onodera, Sukeo


    Environmental pollution by pharmaceuticals has become a major problem in many countries worldwide. However, little is known about the concentrations of pharmaceuticals in water sources in Japan. The objective of this study was to clarify variations in the concentrations of seven nonsteroidal anti-inflammatory drugs (NSAIDs) and in cyclooxygenase(COX)-inhibiting activities in river water and domestic wastewater collected from the Tone Canal and the Edo River Basin in Japan. Total NSAID concentrations were higher in the Tone Canal than in the Edo River, and the highest concentration was observed at the domestic wastewater inflow point located in the Tone Canal (concentration averages of salicylic acid, ibuprofen, felbinac, naproxen, mefenamic acid, diclofenac, and ketoprofen in wastewater samples were 55.3, 162.9, 39.7, 11.8, 30.8, 259.7, and 48.3 ng L(-1), respectively). Gas chromatography-tandem mass spectrometry showed that wastewater samples collected during cooler seasons contained higher levels of COX-inhibiting activity. COX-inhibiting activities were highly correlated with NSAID concentrations (particularly for ketoprofen and diclofenac); however, other COX inhibitors, such as NSAIDs that were not examined in this study and/or other chemicals with COX-inhibiting activity, could exist in the water samples because the concentrations of NSAIDs obtained from the water samples did not account for the total COX-inhibiting activities observed. Therefore, COX inhibition assays may be helpful for evaluating the aquatic toxicity of COX inhibitors. In this study, we demonstrated that COX inhibitors in surface water may influence aquatic organisms more than was expected based on NSAID concentrations. Thus, further studies examining other COX inhibitors in the aquatic environment are necessary.

  18. (1)H-Nuclear magnetic resonance-based metabolic profiling of nonsteroidal anti-inflammatory drug-induced adverse effects in rats.

    Um, So Young; Park, Jung Hyun; Chung, Myeon Woo; Choi, Ki Hwan; Lee, Hwa Jeong


    Nonsteroidal anti-inflammatory drugs (NSAIDs), which are globally prescribed, exhibit mainly anti-inflammatory and analgesic effects but also can cause adverse effects including gastrointestinal erosions, ulceration, bleeding, and perforation. The purpose of this study was to investigate surrogate biomarkers associated with the gastrointestinal (GI) damage caused by NSAID treatment using pattern recognition analysis of (1)H-nuclear magnetic resonance ((1)H NMR) spectra of rat urine. Urine was collected for 5h after oral administration of the following NSAIDs at low or high doses: acetylsalicylic acid (10 or 200mgkg(-1)), diclofenac (0.5 or 15mgkg(-1)), piroxicam (1 or 10mgkg(-1)), indomethacin (1 or 25mgkg(-1)), or ibuprofen (10, or 150mgkg(-1)) as nonselective COX inhibitors and celecoxib (10 or 100mgkg(-1)) as a COX-2 selective inhibitor. The urine was analyzed using 500MHz (1)H NMR for spectral binning and targeted profiling and the level of gastric damage was examined. The nonselective COX inhibitors caused severe gastric damage while no lesions were observed in the celecoxib-treated rats. The (1)H NMR urine spectra were divided into spectral bins (0.04ppm) for global profiling, and a total of 44 endogenous metabolites were assigned for targeted profiling. Multivariate data analyses were performed to recognize the spectral pattern of endogenous metabolites related to NSAIDs using partial least square-discrimination analysis (PLS-DA). The (1)H NMR spectra clustered differently according to gastric damage score in global profiling. In targeted profiling, the endogenous metabolites of citrate, allantoin, 2-oxoglutarate, acetate, benzoate, glycine, and trimethylamine N-oxide were selected as putative biomarkers for gastric damage caused by NSAIDs. These putative biomarkers might be useful for predicting the risk of adverse effects caused by NSAIDs in the early stage of drug development process.

  19. Variants of CEP68 Gene Are Associated with Acute Urticaria/Angioedema Induced by Multiple Non-Steroidal Anti-Inflammatory Drugs

    Cornejo-García, José Antonio; Flores, Carlos; Plaza-Serón, María C.; Acosta-Herrera, Marialbert; Blanca-López, Natalia; Doña, Inmaculada; Torres, María J.; Mayorga, Cristobalina; Guéant-Rodríguez, Rosa M.; Ayuso, Pedro; Fernández, Javier; Laguna, José J.; Agúndez, José A. G.; García-Martín, Elena; Guéant, Jean-Louis; Canto, Gabriela; Blanca, Miguel


    Non-steroidal anti-inflammatory drugs (NSAIDs) are the most consumed drugs worldwide because of their efficacy and utility in the treatment of pain and inflammatory diseases. However, they are also responsible for an important number of adverse effects including hypersensitivity reactions. The most important group of these reactions is triggered by non-immunological, pharmacological mechanisms catalogued under the denomination of cross-intolerance (CRI), with acute urticaria/angioedema induced by multiple NSAIDs (MNSAID-UA) the most frequently associated clinical entity. A recent genome-wide association study identified the gene encoding the centrosomal protein of 68 KDa (CEP68) as the major locus associated with aspirin intolerance susceptibility in asthmatics. In this study, we aimed to assess the role of this locus in susceptibility to CRI to NSAIDs by examining 53 common gene variants in a total of 635 patients that were classified as MNSAID-UA (n = 399), airway exacerbations (n = 110) or blended pattern (n = 126), and 425 controls. We found in the MNSAID-UA group a number of variants (17) associated (lowest p-value = 1.13×10−6), including the non-synonymous Gly74Ser variant (rs7572857) previously associated with aspirin intolerance susceptibility in asthmatics. Although not being significant in the context of multiple testing, eight of these variants were also associated with exacerbated respiratory disease or blended reactions. Our results suggest that CEP68 gene variants may play an important role in MNSAID-UA susceptibility and, despite the different regulatory mechanisms involved depending on the specific affected organ, in the development of hypersensitivity reactions to NSAIDs. PMID:24618698

  20. Non-steroidal anti-inflammatory drugs use is associated with reduced risk of inflammation-associated cancers: NIH-AARP study.

    Fatma M Shebl

    Full Text Available BACKGROUND: Chronic inflammation has been linked to cancers, and use of non-steroidal anti-inflammatory drugs (NSAIDs has been associated with reduced risk of several cancers. To further refine the magnitude of NSAID-related associations, in particular for cancers related to inflammation, such as alcohol-, infection-, obesity-, and smoking-related cancers, as well as for less common cancers, we evaluated the use of NSAIDs and cancer risk in a very large cohort. We used propensity scores to account for potential selection bias and hypothesized that NSAID use is associated with decreased cancer incidence. METHODS: We conducted a prospective study among 314,522 participants in the NIH-AARP Diet and Health Study. Individuals who completed the lifestyle questionnaire, which included NSAID use, in 1996-1997 were followed through 2006. Information on cancer incidence was ascertained by linking to cancer registries and vital status databases. FINDINGS: During 2,715,994 person-years of follow-up (median 10.1 person-years, there were 51,894 incident cancers. Compared with non-users of NSAIDs, individuals who reported use in the 12 months prior to interview had a significantly lower risk of all inflammation-related cancer, alcohol-related, infection-related, obesity-related, and smoking-related cancers [hazard ratio (HR (95% CI 0.90 (0.87-0.93, 0.80 (0.74-0.85, 0.82 (0.78-0.87, 0.88 (0.84-0.92, and 0.88 (0.85-0.92 respectively]. CONCLUSIONS: After accounting for potential selection bias, our data showed an inverse association between NSAID use and alcohol-related, infection-related, obesity-related, and smoking-related cancers and support the hypothesis that inflammation is related to an increased risk of certain cancers.

  1. Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes.

    Nadanaciva, Sashi; Aleo, Michael D; Strock, Christopher J; Stedman, Donald B; Wang, Huijun; Will, Yvonne


    To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs) as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify "toxic" and "non-toxic" drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition.

  2. Long-term use of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population

    González-Pérez Antonio


    Full Text Available Abstract Background Recent data indicate that chronic use of coxibs leads to an increased occurrence of thrombotic cardiovascular events. This raises the question as to whether traditional non-steroidal anti-inflammatory drugs (tNSAIDs might also produce similar hazards. Our aim has been to evaluate the association between the chronic use of tNSAIDs and the risk of myocardial infarction (MI in patients. Methods We performed a nested case-control analysis with 4,975 cases of acute MI and 20,000 controls, frequency matched to cases by age, sex, and calendar year. Results Overall, current use of tNSAID was not associated with an increased risk of MI (RR:1.07;95%CI: 0.95–1.21. However, we found that the relative risk (RR of MI for durations of tNSAID treatment of >1 year was 1.21 (95% CI, 1.00–1.48. The corresponding RR was 1.34 (95% CI, 1.06–1.70 for non-fatal MI. The effect was independent from dose. The small risk associated with long-term use of tNSAIDs was observed among patients not taking low-dose aspirin (RR: 1.29; 95% CI, 1.01–1.65. The effect of long-term use for individual tNSAIDs ranged from a RR of 0.87 (95% CI, 0.47–1.62 with naproxen to 1.38 (95% CI, 1.00–1.90 with diclofenac. Conclusion This study adds support to the hypothesis that chronic treatment with some tNSAIDs is associated with a small increased risk of non-fatal MI. Our data are consistent with a substantial variability in cardiovascular risks between individual tNSAIDs.

  3. Effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs on the production of reactive oxygen species by activated rat neutrophils

    Paino I.M.M.


    Full Text Available The release of reactive oxygen specie (ROS by activated neutrophil is involved in both the antimicrobial and deleterious effects in chronic inflammation. The objective of the present investigation was to determine the effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs (NSAIDs on the production of ROS by stimulated rat neutrophils. Diclofenac (3.6 µM, indomethacin (12 µM, naproxen (160 µM, piroxicam (13 µM, and tenoxicam (30 µM were incubated at 37ºC in PBS (10 mM, pH 7.4, for 30 min with rat neutrophils (1 x 10(6 cells/ml stimulated by phorbol-12-myristate-13-acetate (100 nM. The ROS production was measured by luminol and lucigenin-dependent chemiluminescence. Except for naproxen, NSAIDs reduced ROS production: 58 ± 2% diclofenac, 90 ± 2% indomethacin, 33 ± 3% piroxicam, and 45 ± 6% tenoxicam (N = 6. For the lucigenin assay, naproxen, piroxicam and tenoxicam were ineffective. For indomethacin the inhibition was 52 ± 5% and diclofenac showed amplification in the light emission of 181 ± 60% (N = 6. Using the myeloperoxidase (MPO/H2O2/luminol system, the effects of NSAIDs on MPO activity were also screened. We found that NSAIDs inhibited both the peroxidation and chlorinating activity of MPO as follows: diclofenac (36 ± 10, 45 ± 3%, indomethacin (97 ± 2, 100 ± 1%, naproxen (56 ± 8, 76 ± 3%, piroxicam (77 ± 5, 99 ± 1%, and tenoxicam (90 ± 2, 100 ± 1%, respectively (N = 3. These results show that therapeutic levels of NSAIDs are able to suppress the oxygen-dependent antimicrobial or oxidative functions of neutrophils by inhibiting the generation of hypochlorous acid.

  4. Effects of Preoperative Non-Steroidal Anti-Inflammatory Drugs on Pain Mitigation and Patients’ Shoulder Performance Following Rotator Cuff Repair

    Alireza Rouhani


    Full Text Available Purpose: Pain is one of the most important factors adversely affecting clinical outcomes of operated patients. The present study aims at evaluating effects of preoperative COX2 non-steroidal anti-inflammatory inhibitors on pain mitigation and performance of patients with shoulder rotator cuff tear. Methods: This case-control study was conducted on 60 patients suffering from rotator cuff injury candidate for arthroscopic repair. The patients were classified in two parallel and matched groups. One group (case group was treated using Celecoxib (200mg/12h started 48 hours before surgery and continued for 10 days after operation. In the control group, the placebo was prescribed in the same way. Postoperative pain, side effects, sleep disturbance, and short-term outcomes were compared between two groups using DASH questionnaire. Results: Postoperative pain in the Celecoxib group significantly decreased in comparison with the control one. The difference was statistically meaningful (P<0.001. Well motion ability was seen in 80% of patients of the Celecoxib group. It was 26.6% in the placebo group since pain inhibited them from exercising more motions. In this regard, there was a statistically meaningful difference between these two groups (P=0.02. Sleep disturbance was meaningfully at higher levels in the placebo group (P=0.001. Following up the patients for three months, it was made clear that performance of the Celecoxib group was better than that of the placebo one. Conclusion: COX2 inhibitors are well efficient in patients’ pain management after arthroscopic rotator cuff repair surgery. It results in less life complications, less sleep disturbances, improvement of patients’ short-term clinical outcome, and more quick recovery.

  5. Crystal structure of a mixed-ligand silver(I) complex of the non-steroidal anti-inflammatory drug diclofenac and pyrimidine

    Hamamci Alisir, Sevim; Dege, Necmi


    In the title mixed-ligand silver(I) coordination polymeric complex with the non-steroidal anti-inflammatory drug diclofenac (C14H11Cl2NO2) (diclH) and pyrimidine (pym), namely poly[{μ2-2-[2-(2,6-di­chloro­anilino)phen­yl]acetato-κ2 O:O′}(μ2-pyrimidine-κ2 N 1:N 3)silver(I)], [Ag(C14H10Cl2NO2)(C4H4N2)]n or [Ag(μ-dicl)(μ-pym)]n, the very distorted tetra­hedral AgN2O2 coordination centres comprise two N-atom donors from bridging pym ligands [Ag—N = 2.381 (3) and 2.412 (3) Å] and two carboxyl­ate O-atom donors from dicl ligands [Ag—O = 2.279 (2) and 2.280 (2) Å], which bridge Ag atoms, giving a centrosymmetric dinuclear units with a short Ag⋯Ag separation [2.8931 (5) Å]. Within the units are short intra­ligand C—Cl⋯π(pym) inter­actions [3.6409 (15) Å]. The units are linked through the bridging N atoms of the pym ligand into a two-dimensional sheet–polymer structure lying parallel to (100) and stabilized by inter-ring π–π inter­actions between the pym ligands [Cg⋯Cg = 3.4199 (17) Å]. Additional inter-unit C—H⋯O and C—H⋯Cg hydrogen-bonding inter­actions between the sheets give an overall three-dimensional structure. PMID:27746945

  6. Poly(2-aminobenzothiazole)-coated graphene oxide/magnetite nanoparticles composite as an efficient sorbent for determination of non-steroidal anti-inflammatory drugs in urine sample.

    Asgharinezhad, Ali Akbar; Ebrahimzadeh, Homeira


    In this study, for the first time, 2-aminobenzothiazole monomer was polymerized on Fe3O4 NPs, graphene oxide/Fe3O4 (GO/Fe3O4) and graphene/Fe3O4 (G/Fe3O4) nanocomposites. The synthesized magnetic nanosorbents were characterized by various techniques. The extraction ability of these nanosorbents including Fe3O4, GO/Fe3O4, G/Fe3O4, Fe3O4@poly(2-aminobenzothiazole) (Fe3O4@PABT), GO/Fe3O4@PABT and G/Fe3O4@PABT were compared for dispersive-micro-solid phase extraction of three non-steroidal anti-inflammatory drugs. The results revealed that GO/Fe3O4@PABT nanocomposite demonstrates higher extraction efficiency for naproxen, diclofenac and ibuprofen as selected model analytes. Following the sorption and elution steps, the model analytes were quantified by high performance liquid chromatography-photo diode array detection. Afterwards, a central composite design methodology combined with desirability function approach was applied to find out the optimal experimental conditions. Under the optimized conditions, the limits of detection and linear dynamic ranges were achieved in the range of 0.07-0.3 μg L(-1) and 0.25-2000 μg L(-1), respectively. The percent of extraction recovery was 87.4, 85.5 and 90.5% for naproxen, diclofenac and ibuprofen, respectively. The obtained relative standard deviation (n=5) was 7.2, 5.4 and 6.4% for naproxen, diclofenac and ibuprofen, respectively. Ultimately, this method was employed for urinary monitoring of the target analytes and satisfactory results were obtained.

  7. Combined use of nonsteroidal anti-inflammatory drugs with diuretics and/or renin-angiotensin system inhibitors in the community increases the risk of acute kidney injury.

    Dreischulte, Tobias; Morales, Daniel R; Bell, Samira; Guthrie, Bruce


    Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI) when used in triple combination with renin-angiotensin system inhibitors and diuretics, but previous research reported that NSAIDs in dual combinations with either renin-angiotensin system inhibitors or diuretics alone were not. However, earlier studies relied on hospital coding to define AKI, which may underestimate true risk. This nested case-control study characterized the risk of community-acquired AKI associated with NSAID use among 78,379 users of renin-angiotensin system inhibitors and/or diuretics, where AKI was defined as a 50% or greater increase in creatinine from baseline. The AKI incidence was 68/10,000 person-years. The relative increase in AKI risk was similar for NSAID use in both triple (adjusted rate ratio 1.64 (95% CI 1.25-2.14)) and dual combinations with either renin-angiotensin system inhibitors (1.60 (1.18-2.17)) or diuretics (1.64 (1.17-2.29)). However, the absolute increase in AKI risk was higher for NSAIDs used in triple versus dual combinations with renin-angiotensin system inhibitors or diuretics alone (numbers needed to harm for 1 year treatment with NSAID of 158 vs. over 300). AKI risk was highest among users of loop diuretic/aldosterone antagonist combinations, in those over 75 years of age, and in those with renal impairment. Thus, the nephrotoxic potential of both dual and triple combinations of NSAIDs with renin-angiotensin system inhibitors and/or diuretics yields a higher incidence of AKI than previously thought.

  8. Proton pump inhibitors are not the key for therapying non-steroidal anti-inflammatory drugs-induced small intestinal injury.

    Zhang, Shuo; Chao, Guan-qun; Lu, Bin


    The ability of non-steroidal anti-inflammatory drugs (NSAIDs) to injure the small intestine has been well established in humans and animals. Proton pump inhibitors (PPIs) are frequently prescribed to reduce gastric and duodenal injury caused in high-risk patients taking NSAIDs. However, scarce information is available concerning the effects of PPIs on intestinal damage induced by NSAIDs, and the suppression of gastric acid secretion by PPIs is hard to provide any protection against the damage caused by NSAIDs in the small intestine. The present study was designed to examine the effects of intragastric treatment of two PPIs widely used in clinical practice, namely omeprazole and pantoprazole, on the intestinal damage induced by administration of diclofenac in rat. Male SD rats were treated with omeprazole or pantoprazole for 9 days, with concomitant treatment with anti-inflammatory doses of diclofenac on the final 5 days. The anatomical lesion, villous height, the thickness, and the section area of small intestine were quantitatively analyzed. The change of ultrastructural organization was observed. Endotoxin level in blood was measured by photometry. Epidermal growth factor was observed by immunohistochemistry. Omeprazole and pantoprazole didn't decrease the macroscopic and histologic damage induced by diclofenac in the rat's small intestine. In the two PPI groups, villous height was (89.6 ± 11.8 and 92.6 ± 19.3 μm) lower than which of the control group (P thickness became thinning, and the section area became small. LPS levels in the portal blood of omeprazole and pantoprazole were (4.36 ± 1.26 and 4.25 ± 1.17 EU/ml), significantly higher than in controls (P small intestine from the damage induced by diclofenac in the conscious rat. PPIs cannot repair NSAID-induced intestinal damage at least in part because of significant lesion in mechanical barrier function and reduction in epidermal growth factor.

  9. Asthma and Rhinitis Induced by Selective Immediate Reactions to Paracetamol and Non-steroidal Anti-inflammatory Drugs in Aspirin Tolerant Subjects

    Pérez-Alzate, Diana; Blanca-López, Natalia; Doña, Inmaculada; Agúndez, José A.; García-Martín, Elena; Cornejo-García, José A.; Perkins, James R.; Blanca, Miguel; Canto, Gabriela


    In subjects with non-steroidal anti-inflammatory drugs (NSAIDs)- exacerbated respiratory disease (NERD) symptoms are triggered by acetyl salicylic acid (ASA) and other strong COX-1 inhibitors, and in some cases by weak COX-1 or by selective COX-2 inhibitors. The mechanism involved is related to prostaglandin pathway inhibition and leukotriene release. Subjects who react to a single NSAID and tolerate others are considered selective responders, and often present urticaria and/or angioedema and anaphylaxis (SNIUAA). An immunological mechanism is implicated in these reactions. However, anecdotal evidence suggests that selective responders who present respiratory airway symptoms may also exist. Our objective was to determine if subjects might develop selective responses to NSAIDs/paracetamol that manifest as upper/lower airways respiratory symptoms. For this purpose, we studied patients reporting asthma and/or rhinitis induced by paracetamol or a single NSAID that tolerated ASA. An allergological evaluation plus controlled challenge with ASA was carried out. If ASA tolerance was found, we proceeded with an oral challenge with the culprit drug. The appearance of symptoms was monitored by a clinical questionnaire and by measuring FEV1 and/or nasal airways volume changes pre and post challenge. From a total of 21 initial cases, we confirmed the appearance of nasal and/or bronchial manifestations in ten, characterized by a significant decrease in FEV1% and/or a decrease in nasal volume cavity after drug administration. All cases tolerated ASA. This shows that ASA tolerant subjects with asthma and/or rhinitis induced by paracetamol or a single NSAID without skin/systemic manifestations exist. Whether these patients represent a new clinical phenotype to be included within the current classification of hypersensitivity reactions to NSAIDs requires further investigation. PMID:27489545

  10. Long-term frequent use of non-steroidal anti-inflammatory drugs might protect patients with ankylosing spondylitis from cardiovascular diseases: a nationwide case-control study.

    Wen-Chan Tsai

    Full Text Available The objective of this case-control study was to investigate the risk of cardiovascular disease (CVD following non-steroidal anti-inflammatory drug (NSAID use in patients with ankylosing spondylitis (AS. A total of 10,763 new AS patients were identified from the National Taiwan Health Insurance claims database during the period from 1997 to 2008. In all, 421 AS patients with CVD were recruited as cases, and up to 2-fold as many sex- and age-matched controls were selected. Logistic regression models were used to estimate the odds ratio (OR between NSAID use and CVD incidence. The medication possession rate (MPR was used to evaluate NSAID exposure during the study period. AS patients had increased risk of CVD (OR, 1.68; 95% confidence interval (CI, 1.57 to 1.80. Among frequent (MPR≥80% COX II users, the risks for all types of CVD were ten times lower than those among non-users at 24 months (OR, 0.08; 95% CI, 0.01 to 0.92. Among frequent NSAID users, the risks of major adverse cardiac event (MACE were significantly lower at 12 months (OR, 0.23; 95% CI, 0.07 to 0.76--a trend showing that longer exposure correlated with lower risk. Regarding non-frequent NSAID users (MPR<80%, short-term exposure did carry higher risk (for 6 months: OR, 1.41; 95% CI, 1.07 to 1.86, but after 12 months, the risk no longer existed. We conclude that long-term frequent use of NSAIDs might protect AS patients from CVD; however, NSAIDs still carried higher short-term risk in the non-frequent users.

  11. Significance of Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs in patients with bleeding from upper part of the gastrointestinal tract

    Golubović Gradimir


    Full Text Available Background/Aim. Helicobacter pylori (H. pylori infection and nonsteroidal anti-inflammatory drugs (NSAIDs use are considered to be the most important risk factors having influence on the onset of bleeding gastroduodenal lesions. Whether there is an interaction between H. pylori infection and the use of NSAIDs in the development of peptic ulcer disease is still controversial. The aim of the present study was to evaluate the prevalence of NSAIDs use and H. pylori infection in patients presented with bleeding gastroduodenal lesions. Methods. During the period from January 2003 - December 2003 we prospectively obtained data of all the patients (n=106 presented with signs of upper gastrointestinal bleeding. All the patients were admitted to the intensive care unit, with the endoscopy performed within 12 hours after admission. Histologic analysis was used for the detection of H. pylori infection. The NSAIDs and aspirin use data were obtained by anamnesis. Results. The results of our study revealed that the most common sources of upper gastrointestinal bleeding were duodenal (57 patients, 53.77% and ventricular (36 patients, 33.96% ulcers. The majority of the examined cases were associated with both H. pylori infection and NSAIDs use. A statistically significant difference among the studied groups of patients was proven. Conclusion. The majority of bleeding gastroduodenal lesions were associated with the coexistence of H. pylori infection and NSAIDs use, while their independent influences were statistically less important. Eradication of H. pylori infection in patients using NSAIDs might prevent upper gastrointestinal hemorrhage and reduce peptic ulcer bleeding risk. .

  12. A multiresidue liquid chromatographic/tandem mass spectrometric method for the detection and quantitation of 15 nonsteroidal anti-inflammatory drugs (NSAIDs) in bovine meat and milk.

    van Pamel, Els; Daeseleire, Els


    This study concerns a validated liquid chromatographic/tandem mass spectrometric (LC-MS/MS) multiresidue method for the simultaneous detection, identification, and quantitation of 15 nonsteroidal anti-inflammatory drugs (NSAIDs) in bovine meat and milk. The NSAIDs considered are carprofen, diclofenac, flufenamic acid, flunixin (5-hydroxyflunixin as marker metabolite in milk), ketoprofen, mefenamic acid, meloxicam, 4-methylaminoantipyrine (marker metabolite of metamizole in meat and milk), naproxen, niflumic acid, phenylbutazone (and metabolite oxyphenbutazone), ramifenazone, salicylic acid, and tolfenamic acid. These compounds were chosen as representatives of different chemical subclasses of NSAIDs. Flunixin-d3, diclofenac-d4, 4-aminoantipyrine-d3, and phenylbutazone-d10 were used as internal standards. Performance characteristics were validated according to the Commission Decision 2002/657/EC (Off J Eur Communities, L221: 8-36). Recovery percentages varied between 81 and 114% for bovine meat and between 79 and 118% for milk. Repeatability percentages were within the range of 1-12% for meat and between 1 and 17% for milk, whereas the intralaboratory reproducibility varied between 3 and 19% for meat and between 3 and 23% for milk. The decision limit and the detection capability for bovine meat were within the range of 0.5-579 μg kg(-1)and 0.6-642 μg kg(-1), respectively. Those for milk were within the range of 0.12-55 μg kg(-1) and 0.14-61 μg kg(-1), respectively. The methods developed were successfully applied for proficiency test samples and routine samples analyzed in the laboratory. The methodology concerns fast, user-friendly, and sensitive methods, which can be easily extended for other compounds and matrices. In general, such multiresidue methods contribute to the reduction of human exposure to these veterinary drug residues by consumption of contaminated bovine-derived products such as meat and milk.

  13. Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes

    Nadanaciva, Sashi [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States); Aleo, Michael D. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Strock, Christopher J. [Cyprotex US, Watertown, MA 02472 (United States); Stedman, Donald B. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Wang, Huijun [Computational Sciences, Pfizer Inc., Groton, CT 06340 (United States); Will, Yvonne, E-mail: [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States)


    To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs) as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify “toxic” and “non-toxic” drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition. - Highlights: • NSAIDS cause liver and GI toxicity. • Mitochondrial uncoupling contributes to NSAID liver toxicity. • ER stress is a mechanism that contributes to liver toxicity. • Zebrafish and cell based assays are complimentary.

  14. Studies on the protective effect of ebrotidine on experimental ulcers induced by non-steroidal anti-inflammatory drugs in healthy volunteers.

    Puscas, I; Puscas, C; Coltau, M; Torres, J; Márquez, M; Herrero, E; Fillat, O; Ortiz, J A


    Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]- 4-thiazolyl]methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamid e, CAS 100981-43-9, FI-3542) is a new H2-receptor antagonist providing a new therapy for the prevention and healing of non-steroidal anti-inflammatory drugs-induced gastroduodenal lesions. Carbonic anhydrase is a zinc enzyme, and its isozyme (carbonic anhydrase II) in parietal cells plays a central role in HCl secretion. The effects of ebrotidine on carbonic anhydrase in human subjects are reported. Eighteen healthy volunteers were distributed in 3 equal subgroups and treated for 10 days as follows: ebrotidine 800 mg/d p.o. (Group A); indometacin 4 mg/kg/d p.o. in 3 divided doses (Group B); ebrotidine 800 mg/d p.o. plus indometacin 4 mg/kg/d p.o. (Group C). Assessment of the enzymatic activity of carbonic anhydrase was based on the colorimetric method of changing pH with the stopped-flow technique. In group A, ebrotidine reduced total gastric mucosal carbonic anhydrase activity by 62%; in group B, indometacin increased carbonic anhydrase activity in gastric mucosa by 138%; in group C, the combined treatment with ebrotidine plus indometacin decreased gastric mucosal carbonic anhydrase activity by 38%. The present study shows that, unlike ranitidine, ebrotidine, a competitive H2-receptor antagonist, is also a non-competitive inhibitor of carbonic anhydrase I and II. By antagonizing the activating effects of indometacin on gastric mucosal carbonic anhydrase, ebrotidine prevents mucosal lesions caused by anti-inflammatory drugs.

  15. Determination of Residual Nonsteroidal Anti-Inflammatory Drugs in Aqueous Sample Using Magnetic Nanoparticles Modified with Cetyltrimethylammonium Bromide by High Performance Liquid Chromatography

    Malihe Khoeini Sharifabadi


    Full Text Available A simple and sensitive solid-phase extraction method for separation and preconcentration of trace amount of four nonsteroidal anti-inflammatory drugs (naproxen, indomethacin, diclofenac, and ibuprofen using Fe3O4 magnetic nanoparticles modified with cetyltrimethylammonium bromide has been developed. For this purpose, the surface of MNPs was modified with cetyltrimethylammonium bromide (CTAB as a cationic surfactant. Effects of different parameters influencing the extraction efficiency of drugs including the pH, amount of salt, shaking time, eluent type, the volume of solvent, amount of adsorbent, sample volume, and the time of desorption were investigated and optimized. Methanol has been used as desorption solvent and the extracts were analysed on a reversed-phase octadecyl silica column using 0.02 M phosphate-buffer (pH = 6.02 acetonitrile (65 : 35 v/v as the mobile phase and the effluents were measured at 202 nm with ultraviolet detector. The relative standard deviation (RSD% of the method was investigated at three concentrations (25, 50, and 200 ng/mL and was in the range of 3.98–9.83% (n=6 for 50 ng/mL. The calibration curves obtained for studied drugs show reasonable linearity (R2>0.99 and the limit of detection (LODs ranged between 2 and 7 ng/mL. Finally, the proposed method has been effectively employed in extraction and determination of the drugs in biological and environmental samples.

  16. Use of Nonsteroidal Anti-Inflammatory Drugs and Risk of Chronic Kidney Disease in Subjects With Hypertension: Nationwide Longitudinal Cohort Study.

    Hsu, Chih-Cheng; Wang, Hongjian; Hsu, Yueh-Han; Chuang, Shao-Yuan; Huang, Ya-Wen; Chang, Yu-Kang; Liu, Jia-Sin; Hsiung, Chao A; Tsai, Hui-Ju


    Limited studies have examined the effects of nonsteroidal anti-inflammatory drug (NSAID) use on the risk of chronic kidney disease (CKD), especially in subjects with hypertension. Using National Health Insurance claims data in Taiwan, we conducted a propensity score-matched cohort study to investigate the relationship between NSAID use and CKD in subjects with hypertension. A total of 31976 subjects were included in this study: subjects not taking any NSAIDs in 2007 (n=10782); subjects taking NSAIDs for 1 to 89 days in 2007 (n=10605); and subjects taking NSAIDs for ≥90 days in 2007 (n=10589). We performed multivariable proportional hazard models to determine the relationship between NSAID use and CKD. The results showed that NSAID use was associated with a 1.18-fold increased risk of CKD in subjects taking NSAIDs for 1 to 89 days; and a 1.32-fold increased risk of CKD in hypertension subjects taking NSAIDs for ≥90 days, compared with subjects not taking any NSAIDs, after controlling for the confounding factors. In subgroup analyses, subjects taking NSAIDs for ≥90 days, >1 defined daily dose per day or taking NSAIDs >15 cumulative defined daily doses had a greater risk of CKD than subjects not taking any NSAID, but not for congestive heart failure, stroke, cancer, osteoarthritis, or rheumatoid arthritis. These results provide supportive evidence that NSAID use is associated with increased risk of CKD in subjects with hypertension. It is important to closely monitor the effects of NSAID use, particularly in patients with hypertension, a susceptible population for CKD.

  17. Anti-Clotting Agents Explained

    ... or may require special dosage adjustments. Anticoagulants While antiplatelets keep clots from forming by inhibiting the production of thromboxane, anticoagulants target clotting factors, which are other agents that are crucial to the blood-clotting process. ...

  18. Computational Environment of Software Agents

    Martin Tomášek


    Full Text Available Presented process calculus for software agent communication and mobility canbe used to express distributed computational environment and mobile code applications ingeneral. Agents are abstraction of the functional part of the system architecture and theyare modeled as process terms. Agent actions model interactions within the distributedenvironment: local/remote communication and mobility. Places are abstraction of thesingle computational environment where the agents are evaluated and where interactionstake place. Distributed environment is modeled as a parallel composition of places whereeach place is evolving asynchronously. Operational semantics defines rules to describebehavior within the distributed environment and provides a guideline for implementations.Via a series of examples we show that mobile code applications can be naturally modeled.

  19. Humor and embodied conversational agents

    Nijholt, A.


    This report surveys the role of humor in human-to-human interaction and the possible role of humor in human-computer interaction. The aim is to see whether it is useful for embodied conversational agents to integrate humor capabilities in their internal model of intelligence, emotions and interaction (verbal and nonverbal) capabilities. A current state of the art of research in embodied conversational agents, affective computing and verbal and nonverbal interaction is presented. The report ad...

  20. Antimicrobials for bacterial bioterrorism agents.

    Sarkar-Tyson, Mitali; Atkins, Helen S


    The limitations of current antimicrobials for highly virulent pathogens considered as potential bioterrorism agents drives the requirement for new antimicrobials that are suitable for use in populations in the event of a deliberate release. Strategies targeting bacterial virulence offer the potential for new countermeasures to combat bacterial bioterrorism agents, including those active against a broad spectrum of pathogens. Although early in the development of antivirulence approaches, inhibitors of bacterial type III secretion systems and cell division mechanisms show promise for the future.

  1. Business Intelligence using Software Agents

    Ana-Ramona BOLOGA; Razvan BOLOGA


    This paper presents some ideas about business intelligence today and the importance of developing real time business solutions. The authors make an exploration of links between business intelligence and artificial intelligence and focuses specifically on the implementation of software agents-based systems in business intelligence. There are briefly presented some of the few solutions proposed so far that use software agents properties for the benefit of business intelligence. The authors then...

  2. Natural products as antimitotic agents.

    Dall'Acqua, Stefano


    Natural products still play an important role in the medicinal chemistry, especially in some therapeutic areas. As example more than 60% of currently-used anticancer agents are derives from natural sources including plants, marine organisms or micro-organism. Thus natural products (NP) are an high-impact source of new "lead compounds" or new potential therapeutic agents despite the large development of biotechnology and combinatorial chemistry in the drug discovery and development. Many examples of anticancer drugs as paclitaxel, combretastatin, bryostatin and discodermolide have shown the importance of NP in the anticancer chemotherapy through many years. Many organisms have been studied as sources of drugs namely plants, micro-organisms and marine organisms and the obtained NP can be considered a group of "privileged chemical structures" evolved in nature to interact with other organisms. For this reason NP are a good starting points for pharmaceutical research and also for library design. Tubulin and microtubules are one of the most studied targets for the search of anticancer compounds. Microtubule targeting agents (MTA) also named antimitotic agents are compounds that are able to perturb mitosis but are also able to arrest cell growing during interphase. The anticancer drugs, taxanes and vinca alkaloids have established tubulin as important target in cancer therapy. More recently the vascular disrupting agents (VDA) combretastatin analogues were studied for their antimitotics properties. This review will consider the anti mitotic NP and their potential impact in the development of new therapeutic agents.

  3. What makes virtual agents believable?

    Bogdanovych, Anton; Trescak, Tomas; Simoff, Simeon


    In this paper we investigate the concept of believability and make an attempt to isolate individual characteristics (features) that contribute to making virtual characters believable. As the result of this investigation we have produced a formalisation of believability and based on this formalisation built a computational framework focused on simulation of believable virtual agents that possess the identified features. In order to test whether the identified features are, in fact, responsible for agents being perceived as more believable, we have conducted a user study. In this study we tested user reactions towards the virtual characters that were created for a simulation of aboriginal inhabitants of a particular area of Sydney, Australia in 1770 A.D. The participants of our user study were exposed to short simulated scenes, in which virtual agents performed some behaviour in two different ways (while possessing a certain aspect of believability vs. not possessing it). The results of the study indicate that virtual agents that appear resource bounded, are aware of their environment, own interaction capabilities and their state in the world, agents that can adapt to changes in the environment and exist in correct social context are those that are being perceived as more believable. Further in the paper we discuss these and other believability features and provide a quantitative analysis of the level of contribution for each such feature to the overall perceived believability of a virtual agent.

  4. Geo-Agents: Design and Implement


    Geo-Agents, a multi-agent system that processes distr ib utedgeospatial information and geospatial service was presented. Firstly, the requirement for distributed geographical information process was discussed, and the architecture of Geo-Agents was introduced. Then in-depth discussions were r aised on agent system implementation, such as the basic agent, agent advertising , message passing, and collaborating. An example was also given to explain the p roblem solving process.

  5. Colitis associated with biological agents

    Hugh James Freeman


    In the past,there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity.Now,a variety of new biological monoclonal antibody agents,usually administered by infusion,have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents,adverse effects have been documented,including apparently new forms of immune-mediated inflammatory bowel disease.In some,only limited symptoms have been recorded,but in others,severe colitis with serious complications,such as bowel perforation has been recorded.In others,adverse effects may have a direct vascular or ischemic basis,while other intestinal effects may be related to a superimposed infection.Some new onset cases of ulcerative colitis or Crohn's disease may also be attributed to the same agents used to treat these diseases,or be responsible for disease exacerbation.Dramatic and well documented side effects have been observed with ipilimumab,a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4,a key negative feedback regulator of the T-cell anti-tumor response.This agent has frequently been used in the treatment of different malignancies,notably,malignant melanoma.Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated.One of these is a form of enterocolitis that may be severe,and occasionally,fatal.Other agents include rituximab (an antiCD20 monoclonal antibody),bevacizumab (a monoclonal antibody against the vascular endothelial growth factor) and anti-tumor necrosis factor agents,including infliximab,adalimumab and etanercept.

  6. Recommendations for the Appropriate Use of Anti-Inflammatory Drugs in the Era of the Coxibs: Defining the Role of Gastroprotective Agents

    Richard H Hunt


    Full Text Available Treatment with anti-inflammatory drugs and the analgesic efficacy of conventional nonsteroidal anti-inflammatory drugs (NSAIDs are compromised by a two- to fourfold increased risk of gastrointestinal complications. This increased risk has resulted in an increasing use of the new selective cyclooxygenase-2 inhibitors or coxibs, which, in clinical trials and outcomes studies, reduced gastrointestinal adverse events by 50% to 65% compared with conventional NSAIDs. However, the coxibs are not available to all patients who need them, and NSAIDs are still widely used. Moreover, treatment with a coxib cannot heal pre-existing gastrointestinal lesions, and cotherapy with an anti-secretory drug or mucosal protective agent may be required.

  7. A multi-agent architecture for geosimulation of moving agents

    Vahidnia, Mohammad H.; Alesheikh, Ali A.; Alavipanah, Seyed Kazem


    In this paper, a novel architecture is proposed in which an axiomatic derivation system in the form of first-order logic facilitates declarative explanation and spatial reasoning. Simulation of environmental perception and interaction between autonomous agents is designed with a geographic belief-desire-intention and a request-inform-query model. The architecture has a complementary quantitative component that supports collaborative planning based on the concept of equilibrium and game theory. This new architecture presents a departure from current best practices geographic agent-based modelling. Implementation tasks are discussed in some detail, as well as scenarios for fleet management and disaster management.

  8. [Place of anti-inflammatory agents in the prevention of deep phlebitis].

    Guilmet, C


    The inflammatory reaction includes, after an initial tissue lesion, a catabolic phase with proteolysis, an exudative reaction phase, and finally an anabolic phase with the formation of an inflammatory granuloma. The reaction should be considered, however, as an initial inflammation, rapid and limited to the affected tissues, and a secondary inflammation induced at a distance by a humoral mechanism with the appearance of pathological globulins. Only certain anti-inflammatory agents act at these two levels : steroids and non-steroids. Corticosteroids can be used effectively in small doses. Courses of salicylates are difficult to manage and are not standardized. Fenamates and indometacine lead to psychiatric disorders. The only useful drugs are phenylbutazone and hydroxyphenylbutazone. These two drugs can be used alone, or in combination, or eventually being superseded by anti-coagulants. As they are derived from pyrazolidine, they are above all preventive. Their absorption in the digestive tract is rapid and almost complete ; the maximum plasma concentration occurs 2-4 h. after injection. Delayed accidents occur 7-15 days after the last dose. Suppotanderil and suppophenylbutazone are used at the dose of 250ml, 2 or 3 times a day. They may be combined with AVK depending on the clinical signs and the prothrombin and Howell's time. These drugs are contraindicated in patients with ulcers, with haematological diseases, and with severe cirrhosis. They should always be replaced straight away by anti-coagulants in patients with valve prostheses or with severe rhythm disorders.

  9. Dopamine agents for hepatic encephalopathy

    Junker, Anders Ellekær; Als-Nielsen, Bodil; Gluud, Christian


    BACKGROUND: Patients with hepatic encephalopathy may present with extrapyramidal symptoms and changes in basal ganglia. These changes are similar to those seen in patients with Parkinson's disease. Dopamine agents (such as bromocriptine and levodopa, used for patients with Parkinson's disease) have...... therefore been assessed as a potential treatment for patients with hepatic encephalopathy. OBJECTIVES: To evaluate the beneficial and harmful effects of dopamine agents versus placebo or no intervention for patients with hepatic encephalopathy. SEARCH METHODS: Trials were identified through the Cochrane...... of the trials followed participants after the end of treatment. Only one trial reported adequate bias control; the remaining four trials were considered to have high risk of bias. Random-effects model meta-analyses showed that dopamine agents had no beneficial or detrimental effect on hepatic encephalopathy...

  10. Dual Rationality and Deliberative Agents

    Debenham, John; Sierra, Carles

    Human agents deliberate using models based on reason for only a minute proportion of the decisions that they make. In stark contrast, the deliberation of artificial agents is heavily dominated by formal models based on reason such as game theory, decision theory and logic—despite that fact that formal reasoning will not necessarily lead to superior real-world decisions. Further the Nobel Laureate Friedrich Hayek warns us of the ‘fatal conceit’ in controlling deliberative systems using models based on reason as the particular model chosen will then shape the system’s future and either impede, or eventually destroy, the subtle evolutionary processes that are an integral part of human systems and institutions, and are crucial to their evolution and long-term survival. We describe an architecture for artificial agents that is founded on Hayek’s two rationalities and supports the two forms of deliberation used by mankind.

  11. Relational agents in clinical psychiatry.

    Bickmore, Timothy; Gruber, Amanda


    Relational agents are computational artifacts, such as animated, screen-based characters or social robots, that are designed to establish a sense of rapport, trust, and even therapeutic alliance with patients, using ideal therapeutic relationships between human counselors and patients as role models. We describe the development and evaluation of several such agents designed for health counseling and behavioral-change interventions, in which a therapeutic alliance is established with patients in order to enhance the efficacy of the intervention. We also discuss the promise of using such agents as adjuncts to clinical psychiatry, a range of possible applications, and some of the challenges and ethical issues in developing and fielding them in psychiatric interventions.

  12. [Anti-influenza virus agent].

    Nakamura, Shigeki; Kohno, Shigeru


    The necessity of newly anti-influenza agents is increasing rapidly after the prevalence of pandemic influenza A (H1N1) 2009. In addition to the existing anti-influenza drugs, novel neuraminidase inhibitors such as peramivir (a first intravenous anti-influenza agent) and laninamivir (long acting inhaled anti-influenza agent) can be available. Moreover favipiravir, which shows a novel anti-influenza mechanism acting as RNA polymerase inhibitor, has been developing. These drugs are expected to improve the prognosis of severe cases caused by not only seasonal influenza but pandemic influenza A (H1N1) 2009 virus and H5N1 avian influenza, and also treat oseltamivir-resistant influenza effectively.

  13. Agent review phase one report.

    Zubelewicz, Alex Tadeusz; Davis, Christopher Edward; Bauer, Travis LaDell


    This report summarizes the findings for phase one of the agent review and discusses the review methods and results. The phase one review identified a short list of agent systems that would prove most useful in the service architecture of an information management, analysis, and retrieval system. Reviewers evaluated open-source and commercial multi-agent systems and scored them based upon viability, uniqueness, ease of development, ease of deployment, and ease of integration with other products. Based on these criteria, reviewers identified the ten most appropriate systems. The report also mentions several systems that reviewers deemed noteworthy for the ideas they implement, even if those systems are not the best choices for information management purposes.

  14. Non-steroidal Anti-inflammatory Drugs induced Urticaria and Angioedema%非甾体类抗炎药所致荨麻疹和血管性水肿

    徐迎阳; 支玉香


    非甾体抗炎药(nonsteroidal anti-inflammatory drugs,NSAIDs)较易引起药物不良反应,其中大部分是由于个体对NSIADs高敏感所致,最常见表现为荨麻疹和(或)血管性水肿.本文将针对NSAIDs所致的荨麻疹和血管性水肿分类、表现、诊断及处理原则进行阐述.

  15. Quinolones and non-steroidal anti-inflammatory drugs interacting with copper(II), nickel(II), cobalt(II) and zinc(II): structural features, biological evaluation and perspectives.

    Psomas, George; Kessissoglou, Dimitris P


    The structural features of copper(II), nickel(II), cobalt(II) and zinc(II) complexes with the antimicrobial drugs quinolones and non-steroidal anti-inflammatory drugs (NSAIDs) as ligands are discussed. The binding properties of these complexes to biomolecules (calf-thymus DNA, bovine or human serum albumin) are presented and evaluated. The biological activity (antimicrobial, antioxidant and antiproliferative) of selected complexes is investigated. Further perspectives concerning the synthesis and the biological activity of novel complexes with quinolones or NSAIDs attractive to synthetic chemists, biochemists and/or biologists are presented.


    I. Z. Gaidukova


    Full Text Available The paper gives the draft guidelines elaborated  by the Expert Spondyloarthritis  Diagnosis and Treatment Group  by order of the Association of Rheumatologists  of Russia. The guidelines include the essentials of how to use nonsteroidal  anti-inflammatory drugs in axial spondyloarthrititides, including ankylosing spondylitis, contain  instructions  for how long they should be administered, and describe possible patient  management tactics in the most common  clinical situations and a preferential  algorithm for evaluating the efficiency and safety of treatment.

  17. Thyroid dysfunction from antineoplastic agents.

    Hamnvik, Ole-Petter Riksfjord; Larsen, P Reed; Marqusee, Ellen


    Unlike cytotoxic agents that indiscriminately affect rapidly dividing cells, newer antineoplastic agents such as targeted therapies and immunotherapies are associated with thyroid dysfunction. These include tyrosine kinase inhibitors, bexarotene, radioiodine-based cancer therapies, denileukin diftitox, alemtuzumab, interferon-α, interleukin-2, ipilimumab, tremelimumab, thalidomide, and lenalidomide. Primary hypothyroidism is the most common side effect, although thyrotoxicosis and effects on thyroid-stimulating hormone secretion and thyroid hormone metabolism have also been described. Most agents cause thyroid dysfunction in 20%-50% of patients, although some have even higher rates. Despite this, physicians may overlook drug-induced thyroid dysfunction because of the complexity of the clinical picture in the cancer patient. Symptoms of hypothyroidism, such as fatigue, weakness, depression, memory loss, cold intolerance, and cardiovascular effects, may be incorrectly attributed to the primary disease or to the antineoplastic agent. Underdiagnosis of thyroid dysfunction can have important consequences for cancer patient management. At a minimum, the symptoms will adversely affect the patient's quality of life. Alternatively, such symptoms can lead to dose reductions of potentially life-saving therapies. Hypothyroidism can also alter the kinetics and clearance of medications, which may lead to undesirable side effects. Thyrotoxicosis can be mistaken for sepsis or a nonendocrinologic drug side effect. In some patients, thyroid disease may indicate a higher likelihood of tumor response to the agent. Both hypothyroidism and thyrotoxicosis are easily diagnosed with inexpensive and specific tests. In many patients, particularly those with hypothyroidism, the treatment is straightforward. We therefore recommend routine testing for thyroid abnormalities in patients receiving these antineoplastic agents.

  18. Tenoxicam, a non-steroid anti-inflammatory drug, is unable to increase the response rate in patients with chronic hepatitis C treated by alpha interferon.

    Zarski, J P; Maynard-Muet, M; Chousterman, S; Baud, M; Barnoud, R; Abergel, A; Bacq, Y; Combis, J M; Causse, X; Tran, A; Oberti, F; Minello, A; Bresson-Hadni, S; Bailly, F; Raabe, J J; Leroy, V; Hamici, L; Hicham, T; Girardin, M F


    The purpose of this study is to compare a combination of interferon (IFN)-alpha2a (Roferon) + Tenoxicam with IFN-alpha2a alone in the treatment of chronic hepatitis C. This prospective, randomized double-blind study included 149 patients, all of whom were diagnosed with active chronic hepatitis C but non-cirrhotic (ALT > or = 1.5 upper limit of normal, anti-hepatitis C virus (HCV) positive by enzyme-linked immunosorbant assay2 and RIBA3). The patients were randomized in two groups, as follows: G1 (n = 76): IFNalpha2a 3 million units times per week during 6 months + placebo; and G2 (n = 73): IFNalpha2a 3 million units three times per week + Tenoxicam (20 mg/day) during 6 months. Alanine aminotransferase (ALT) and HCV RNA were determined before and at months 6 and 12 of treatment. 2'5' oligoadenylate synthetase activity (2'5' AS) was dosed in mononuclear cells before and at 3-month treatment intervals in 28 patients. Liver biopsy was performed before and 6 months after the end of therapy. Parameters were similar before therapy for both groups. Biochemical and virological responses were similar for both groups at month 6 (49.3% vs. 42.9% and 43.3% vs. 38.3%, respectively) and month 12 (28.3% vs. 23.8% and 17.2% vs. 17.5%, respectively). HCV RNA level significantly decreased in both groups at month 6, with no difference whatever the therapy; however, the HCV RNA level returned to initial values at month 12 and was the only significant prognostic factor of a sustained response. No peak of 2'5' AS activity was observed during treatment in patients with dual therapy. A histological improvement was also noted in both groups without difference, regardless of therapy. The percentage of adverse events was identical for both groups. Paracetamol intake, assessed in 80 patients, was 49.1 g per 6 months in the G1 group and 22.5 g per 6 months in the G2 group (not significant). In conclusion, the non-steroid anti-inflammatory drug, Tenoxicam, does not increase IFNalpha efficacy in

  19. Detection of the non-steroidal anti-inflammatory drug niflumic acid in humans: a combined 19F-MRS in vivo and in vitro study.

    Bilecen, Deniz; Schulte, Anja-Carina; Kaspar, Armin; Küstermann, Eckerhardt; Seelig, Joachim; Elverfeldt, Dominik; Scheffler, Klaus


    This study describes for the first time results of a (19)F-MRS study on humans exposed to the fluorinated non-steroidal anti-inflammatory drug niflumic acid. The accumulation and elimination of this commercially available selective prostaglandin synthase inhibitor is studied after an oral bolus in the human liver, in blood plasma and in urine samples. The in vivo spectra of the liver display two resonances with a similar increase in signal intensity during the investigation period of 240 min. One resonance refers to the parent compound niflumic acid (P), whereas the second resonance corresponds to a metabolite (M1) formed by the biotransformation by liver enzymes. The spectroscopic comparison with model compounds suggests 4'-hydroxyniflumic acid as the metabolite. During the entire experiment the concentration ratios of these resonances (P/M1) ranged between 0.7 and 0.9, indicating a high metabolite concentration most probably due to an efficient first pass metabolism. Both resonances (P, M1) were observed in the in vitro study of the blood plasma samples after plasma protein denaturation. However, in comparison to the liver spectra, the amount of the metabolite M1 is very small with a P/M1-ratio of 36.6 after 90 min and 16.1 after the end of measurement. This finding suggests an efficient biliary excretion of the metabolite M1, which bypasses the blood circulation system. Both resonances are also identified in the native urine samples. The signal intensity of the parent compound dominates the spectra of all urine samples, whereas the signal intensity of M1 increases slowly reaching a similar value to the parent compound P at the end of the measurement. This observation demonstrates an effective renal elimination of niflumic acid and suggests the existence of an enterohepatic circuit with a re-entry mechanism for the biliary excreted metabolite M1. In the urine spectra, an additional metabolite M2 is found. This resonance exhibits a low but constant signal

  20. Lansoprazole prevents experimental gastric injury induced by non-steroidal anti-inflammatory drugs through a reduction of mucosal oxidative damage

    Corrado Blandizzi; Matteo Fornai; Rocchina Colucci; Gianfranco Natale; Valter Lubrano; Cristina Vassalle; Luca Antonioli; Gloria Lazzeri; Mario Del Tacca


    AIM: This study investigated the mechanisms of protection afforded by the proton pump inhibitor lansoprazole against gastric injury induced by different non-steroidal antiinflammatory drugs (NSAIDs) in rats.METHODS: Male Sprague-Dawley rats were orally treated with indomethacin (100 μmol/kg), diclofenac (60 μmol/kg),piroxicam (150 μmol/kg) or ketoprofen (150 μmol/kg).Thirty minutes before NSAIDs, animals were orally treated with lansoprazole 18 or 90 μmol/kg. Four hours after the end of treatments, the following parameters were assessed: gastric mucosal PGE2, malondialdehyde (MDA), myeloperoxidase (MPO) or non-proteic sulfhydryl compounds (GSH) levels; reverse transcription-polymerase chain reaction (RT-PCR) of mucosal COX-2 mRNA; gastric acid secretion in pylorus-ligated animals; in vitro effects of lansoprazole (1-300 μmol/L) on the oxidation of low density lipoproteins (LDLs) induced by copper sulphate.RESULTS: All NSAIDs elicited mucosal necrotic lesions which were associated with neutrophil infiltration and reduction of PGE2 levels. Increments of MPO and MDA contents, as well as a decrease in GSH levels were detected in the gastric mucosa of indomethacin- or piroxicam-treated animals. Indomethacin enhanced mucosal cyclooxygenase-2 expression, while not affecting cyclooxygenase-1. At the oral dose of 18 μmol/kg lansoprazole partly counteracted diclofenac-induced mucosal damage, whereas at 90 μmol/kg it markedly prevented injuries evoked by all test NSAIDs. Lansoprazole at 90 μmol/kg reversed also the effects of NSAIDs on MPO, MDA and GSH mucosal contents, without interfering with the decrease in PGE2 levels or indomethacin-induced cyclooxygenase-2 expression. However, both lansoprazole doses markedly inhibited acid secretion in pylorus-ligated rats. Lansoprazole concentration-dependently reduced the oxidation of LDLs in vitro.CONCLUSION: These results suggest that, besides the inhibition of acid secretion, lansoprazole protection against NSAID

  1. Crystal structures of three classes of non-steroidal anti-inflammatory drugs in complex with aldo-keto reductase 1C3.

    Jack U Flanagan

    Full Text Available Aldo-keto reductase 1C3 (AKR1C3 catalyses the NADPH dependent reduction of carbonyl groups in a number of important steroid and prostanoid molecules. The enzyme is also over-expressed in prostate and breast cancer and its expression is correlated with the aggressiveness of the disease. The steroid products of AKR1C3 catalysis are important in proliferative signalling of hormone-responsive cells, while the prostanoid products promote prostaglandin-dependent proliferative pathways. In these ways, AKR1C3 contributes to tumour development and maintenance, and suggest that inhibition of AKR1C3 activity is an attractive target for the development of new anti-cancer therapies. Non-steroidal anti-inflammatory drugs (NSAIDs are one well-known class of compounds that inhibits AKR1C3, yet crystal structures have only been determined for this enzyme with flufenamic acid, indomethacin, and closely related analogues bound. While the flufenamic acid and indomethacin structures have been used to design novel inhibitors, they provide only limited coverage of the NSAIDs that inhibit AKR1C3 and that may be used for the development of new AKR1C3 targeted drugs. To understand how other NSAIDs bind to AKR1C3, we have determined ten crystal structures of AKR1C3 complexes that cover three different classes of NSAID, N-phenylanthranilic acids (meclofenamic acid, mefenamic acid, arylpropionic acids (flurbiprofen, ibuprofen, naproxen, and indomethacin analogues (indomethacin, sulindac, zomepirac. The N-phenylanthranilic and arylpropionic acids bind to common sites including the enzyme catalytic centre and a constitutive active site pocket, with the arylpropionic acids probing the constitutive pocket more effectively. By contrast, indomethacin and the indomethacin analogues sulindac and zomepirac, display three distinctly different binding modes that explain their relative inhibition of the AKR1C family members. This new data from ten crystal structures greatly broadens

  2. Potential of prescription registries to capture individual-level use of aspirin and other nonsteroidal anti-inflammatory drugs in Denmark: trends in utilization 1999–2012

    Schmidt M


    Full Text Available Morten Schmidt,1 Jesper Hallas,2 Søren Friis1,31Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Clinical Pharmacology, University of Southern Denmark, Odense, Denmark; 3Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, DenmarkBackground: Due to over-the-counter availability, no consensus exists on whether adequate information on nonsteroidal anti-inflammatory drug (NSAID use can be obtained from prescription registries.Objectives: To examine utilization of aspirin and nonaspirin NSAIDs in Denmark between 1999 and 2012 and to quantify the proportion of total sales that was sold on prescription.Method: Based on nationwide data from the Danish Serum Institute and the Danish National Prescription Registry, we retrieved sales statistics for the Danish primary health care sector to calculate 1-year prevalences of prescription users of aspirin or nonaspirin NSAIDs, and to estimate the corresponding proportions of total sales dispensed on prescription.Results: Both low-dose aspirin and nonaspirin NSAIDs were commonly used in the Danish population between 1999 and 2012, particularly among elderly individuals. The 1-year prevalence of prescribed low-dose aspirin increased throughout the study period, notably among men. Nonaspirin NSAID use was frequent in all age groups above 15 years and showed a female preponderance. Overall, the prevalence of prescribed nonaspirin NSAIDs decreased moderately after 2004, but substantial variation according to NSAID subtype was observed; ibuprofen use increased, use of all newer selective cyclooxygenase-2 inhibitors nearly ceased after 2004, diclofenac use decreased by nearly 50% after 2008, and naproxen use remained stable. As of 2012, the prescribed proportion of individual-level NSAID sales was 92% for low-dose aspirin, 66% for ibuprofen, and 100% for all other NSAIDs.Conclusion: The potential for identifying NSAID use from prescription

  3. Nonsteroidal anti-inflammatory drugs: add an anti-ulcer drug for patients at high risk only. Always limit the dose and duration of treatment with NSAIDs.


    In addition to their cardiac, renal, hepatic, cutaneous and neuropsychological adverse effects, nonsteroidal anti-inflammatory drugs (NSAIDs) can have severe effects on the entire gastrointestinal tract, including bleeding, perforation and occlusion. Which anti-ulcer drugs reduce the risk of the severe gastrointestinal adverse effects of NSAIDs, and which patients should receive them? To answer these questions, we conducted a review of the literature, using the standard Prescrire methodology. The main risk factors for severe gastrointestinal adverse effects during NSAID therapy are: a high dose regimen; age over 65 years; a history of gastric or duodenal ulcer or gastrointestinal bleeding; heavy use of both alcohol and tobacco; and concomitant treatment with a corticosteroid, antiplatelet drug, anticoagulant, or selective serotonin reuptake inhibitor (SSRI) antidepressant. Gastrointestinal symptoms and ulceration (on endoscopy) are poor predictors of severe gastrointestinal reactions. A meta-analysis examined randomised placebo-controlled trials of misoprostol in more than 11 000 patients. The results were mainly based on a large trial including about 9000 rheumatoid arthritis patients with an average age of 68 years. Misoprostol (400 microg to 800 microg/day, in 4 doses) prevented about 4 severe gastroduodenal events when 1000 patients over 60 years of age were treated for 6 months. Diarrhoea and other mild gastrointestinal disorders were frequent. There are no randomised trials comparing proton pump inhibitors (PPIs) and histamine H2 receptor antagonists versus misoprostol or versus placebo therapy for the prevention of severe adverse effects associated with NSAIDs. PPIs and H2 antagonists both reduce the incidence of gastric or duodenal ulceration detected by routine endoscopy. A randomised trial compared an H2 antagonist (famotidine) versus a PPI (pantoprazole) in 128 patients with an average age of 69 years who had a very high risk of serious gastrointestinal

  4. Agent communication and artificial institutions

    Fornara, Nicoletta; Viganò, Francesco; Colombetti, Marco


    In this paper we propose an application-independent model for the definition of artificial institutions that can be used to define open multi-agent systems. Such a model of institutional reality makes us able also to define an objective and external semantics of a commitment-based Agent Communication Language (ACL). In particular we propose to regard an ACL as a set of conventions to act on a fragment of institutional reality, defined in the context of an artificial institution. Another c...

  5. Agentes infecciosos y enfermedades autoinmunes

    Carlos Riebeling; Vicente Madrid; Beatriz Elena Camarena; Oscar Peralta; Raúl Barrera


    En este trabajo se describen los aspectos molecidares de la relación entre agentes infecciosos y enfermedades autoinrnitnes; los mecanismos de respuesta inmune a los agentes infecciosos, y las Iiiyótesis más recientes de la causa de las enfermedades autoinmunes. Los antígenos son procesados y seleccionados por su inmitnogenicidad, ypresentadospor lasmolécitlasde HLA a los receptores de antígeno de los linfocitos T. Aunque existen rnuclias hipótesk sobre el origen de las enfermedades arrtoinmu...

  6. Autonomous sensor manager agents (ASMA)

    Osadciw, Lisa A.


    Autonomous sensor manager agents are presented as an algorithm to perform sensor management within a multisensor fusion network. The design of the hybrid ant system/particle swarm agents is described in detail with some insight into their performance. Although the algorithm is designed for the general sensor management problem, a simulation example involving 2 radar systems is presented. Algorithmic parameters are determined by the size of the region covered by the sensor network, the number of sensors, and the number of parameters to be selected. With straight forward modifications, this algorithm can be adapted for most sensor management problems.

  7. Biologic agents for rheumatoid arthritis treatment%类风湿关节炎的生物制剂治疗

    陈龙; 袁国华


    Rheumatoid arthritis is a common disabling diease, seriously affecting the patients' quality of life. Traditional drugs treatment for rheumatoid arthritis include nonsteroid anti-inflammatory drugs, corticosteroids, and disease modifying antirheumatic drugs,however,these drugs are often not satisfied to control the condition of refractory rheumatoid arthritis,and resulting in severe joint damage. Recently , the emergence of multiple biological agents brought hope to the treatment of refractory rheumatoid arthritis patients These agents play an important role in the control of rheumatic conditions and the improvement of quality of life in PtA patients.%类风湿关节炎(rheumatoid arthritis,RA)是一种常见的致残性疾病,严重影响患者的生活质量.传统的RA药物治疗主要包括非甾体抗炎药、糖皮质激素以及慢作用药物,然而这些药物常常不能满意控制那些难治性RA患者的病情,最终导致关节进行性破坏.近年,由于多种生物制剂的出现,为治疗难治性RA带来了希望,这些生物制剂在控制风湿病情和改善生活质量方面发挥了重要作用.

  8. 13 CFR 120.952 - Fiscal agent.


    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Fiscal agent. 120.952 Section 120... Loan Program (504) Debenture Sales and Service Agents § 120.952 Fiscal agent. SBA shall appoint a Fiscal Agent to assess the financial markets, minimize the cost of sales, arrange for the production...

  9. Anti-inflamatórios não esteroides: Efeitos cardiovasculares, cérebro-vasculares e renais Antiinflamatorios no esteroides: efectos cardiovasculares, cerebrovasculares y renales Nonsteroidal anti-inflammatory drugs: cardiovascular, cerebrovascular and renal effects

    Michel Batlouni


    Full Text Available Os anti-inflamatórios não esteroides (AINEs encontram-se entre os medicamentos mais prescritos em todo o mundo. Essa classe heterogênea de fármacos inclui a aspirina e vários outros agentes inibidores da ciclo-oxigenase (COX, seletivos ou não. Os AINEs não seletivos são os mais antigos, e designados como tradicionais ou convencionais. Os AINEs seletivos para a COX-2 são designados COXIBEs. Nos últimos anos, tem sido questionada a segurança do uso dos AINEs na prática clínica, particularmente dos inibidores seletivos da COX-2. As evidências sobre o aumento do risco cardiovascular com o uso de AINEs são ainda incompletos, pela ausência de ensaios randomizados e controlados com poder para avaliar desfechos cardiovasculares relevantes. Entretanto, os resultados de estudos clínicos prospectivos e de meta-análises indicam que os inibidores seletivos da COX-2 exercem importantes efeitos cardiovasculares adversos, que incluem aumento do risco de infarto do miocárdio, acidente vascular cerebral, insuficiência cardíaca, insuficiência renal e hipertensão arterial. O risco desses efeitos adversos é maior em pacientes com história prévia de doença cardiovascular ou com alto risco para desenvolvê-la. Nesses pacientes, o uso de inibidores da COX-2 deve ser limitado àqueles para os quais não há alternativa apropriada e, mesmo assim, somente em doses baixas e pelo menor tempo necessário. Embora os efeitos adversos mais frequentes tenham sido relacionados à inibição seletiva da COX-2, a ausência de seletividade para essa isoenzima não elimina completamente o risco de eventos cardiovasculares, de modo que todos os fármacos do largo espectro dos AINEs somente devem ser prescritos após consideração do balanço risco/benefício.Los antiinflamatorios no esteroides (AINEs se encuentran entre los medicamentos más prescriptos en todo el mundo. Esta clase heterogénea de fármacos incluye la aspirina y varios otros agentes

  10. Biotech drugs : biological therapeutic agents

    Grech, Godfrey; Fenech, Anthony


    The recent years has seen significant growth in a new therapeutic approach to the management of disease. Biological therapeutic agents, constitute a broad category of drugs, usually generated by recombinant techniques from living organisms. These therapies revolutionise the traditional approaches to drug design and development, and regulatory agencies have been swift in developing the necessary structures to ensure their optimal use.

  11. Identity Management in Agent Systems

    Brazier, F.M.T.; Groot, de D.R.A.


    If agent-based applications are to be used in large scale, open environments, security is a main issue; digital identity management (DIDM) an essential element. DIDM is needed to be able to determine the rights and obligations of the four main

  12. The Power Trading Agent Competition

    W. Ketter (Wolfgang); J. Collins (John); P. Reddy (Prashant); C. Flath (Christoph); M.M. de Weerdt (Mathijs)


    textabstractThis is the specification for the Power Trading Agent Competition for 2012 (Power TAC 2012). Power TAC is a competitive simulation that models a “liberalized” retail electrical energy market, where competing business entities or “brokers” offer energy services to customers through tariff

  13. The Power Trading Agent Competition

    Ketter, W.; Collins, J.; Reddy, P.; Flath, C.; De Weerdt, M.M.


    This is the specification for the Power Trading Agent Competition for 2012 (Power TAC 2012). Power TAC is a competitive simulation that models a “liberalized” retail electrical energy market, where competing business entities or “brokers” offer energy services to customers through tariff contracts,

  14. Raspberry Pi for secret agents

    Sjogelid, Stefan


    This book is an easy-to-follow guide with practical examples in each chapter. Suitable for the novice and expert alike, each topic provides a fast and easy way to get started with exciting applications and also guides you through setting up the Raspberry Pi as a secret agent toolbox.

  15. Humor and embodied conversational agents

    Nijholt, A.


    This report surveys the role of humor in human-to-human interaction and the possible role of humor in human-computer interaction. The aim is to see whether it is useful for embodied conversational agents to integrate humor capabilities in their internal model of intelligence, emotions and interactio

  16. SEM: A Cultural Change Agent

    Barnes, Bradley; Bourke, Brian


    The authors advance the concept that institutional culture is a purposeful framework by which to view SEM's utility, particularly as a cultural change agent. Through the connection of seemingly independent functions of performance and behavior, implications emerge that deepen the understanding of the influence of culture on performance outcomes…

  17. An Introduction to Software Agents


    applicable to modelling red force entities for VMSA. This paper provides an overview of software agents and represents the first step in the...ordinateur, et que la simulation en cours modélise leurs capteurs , leurs armes et leurs caractéristiques matérielles. vi DRDC Atlantic TM...34 9 Sample Applications

  18. Relational agents: A critical review

    Campbell, Robert H.; Grimshaw, Mark Nicholas; Green, Gill


    Relationships between people who meet in virtual worlds are common and these relationships can be long term, in some cases lasting a life-time. Although relationships formed in virtual worlds have invited a lot of recent interest, surprisingly little work has been done on developing computer agents...

  19. Kriitikute lemmikfilm on "Agent Sinikael"


    Eesti Filmiajakirjanike Ühing andis kümnendat korda välja auhinda Aasta film 2002. Parimaks filmiks tunnistati mängufilm "Agent Sinikael" : režissöör Marko Raat. Viimane sai preemiaks Neitsi Maali kuju ja 12 000 krooni

  20. Multi-Agent Transport Planning

    Zutt, J.; Witteveen, C.


    We discuss a distributed transport planning problem with competitive autonomous actors that carry out time-constrained pick-up delivery orders from customers. The agents have to find conflict-free routes to execute a series of orders they have accepted. Hatzack and Nebel [2] were the first to sugges

  1. Drug: D01049 [KEGG MEDICUS

    Full Text Available PRODUCTS, NON-STEROIDS M01AX Other antiinflammatory and antirheumatic agents, non-steroids M01AX17 Nimesuli...INT AND MUSCULAR PAIN M02AA Antiinflammatory preparations, non-steroids for topic

  2. 5-aminosalicylic acid is an attractive candidate agent for chemoprevention of colon cancer in patients with inflammatory bowel disease

    Yang Cheng; Pierre Desreumaux


    Inflammatory bowel disease (IBD) is classically subdivided into ulcerative colitis (UC) and Crohn's disease (CD). Patients with IBD have increased risk for colorectal cancer. Because the pathogenesis of colorectal carcinoma has not been entirely defined yet and there is no ideal treatment for colon cancer, cancer prevention has become increasingly important in patients with IBD. The two adopted methods to prevent the development of colon cancer in clinical practice include the prophylactic colectomy and colonoscopic surveillance.But patients and physicians seldom accept colectomy as a routine preventive method and most patients do not undergo appropriate colonoscopic surveillance. Chemoprevention refers to the use of natural or synthetic chemical agents to reverse, suppress, or to delay the process of carcinogenesis.Chemoprevention is a particularly useful method in the management of patients at high risk for the development of specific cancers based on inborn genetic susceptibility, the presence of cancer-associated disease, or other known risk factors. Prevention of colorectal cancer by administration of chemopreventive agents is one of the most promising options for IBD patients who are at increased risks of the disease. The chemopreventive efficacy of nonsteroidal antiinflammatory drugs (NSAIDs) against intestinal tumors has been well established. But with reports that NSAIDs aggravated the symptoms of colitis, their sustained use for the purpose of cancer chemoprevention has been relatively contraindicated in IBD patients. Another hopeful candidate chemoprevention drug for IBD patients is 5-aminosalicylic acid (5-ASA), which is well tolerated by most patients and has limited systemic adverse effects, and no gastrointestinal toxicity. 5-ASA lacks the well-known side effects of longterm NSAIDs use. Retrospective correlative studies have suggested that the long-term use of 5-ASA in IBD patients may significantly reduce the risk of development of colorectal cancer

  3. Persuasive Teachable Agent for Intergenerational Learning

    Lim, Su Fang


    Teachable agents are computer agents based on the pedagogical concept of learning-by-teaching. During the tutoring process, where students take on the role of the tutor to teach a computer agent tutee, learners have been observed to gain deeper understanding of the subject matter. Teachable agents are commonly used in the areas of science and mathematics learning where learners are able to learn complex concepts and deep reasoning by teaching the teachable agent through graphic representation...

  4. Halide test agent replacement study

    Banks, E.M.; Freeman, W.P.; Kovach, B.J. [and others


    The intended phaseout of the chlorofluorocarbons (CFCs) from commercial use required the evaluation of substitute materials for the testing for leak paths through both individual adsorbers and installed adsorbent banks. The American Society of Mechanical Engineers (ASME) Committee on Nuclear Air and Gas Treatment (CONAGT) is in charge of maintaining the standards and codes specifying adsorbent leak test methods for the nuclear safety related air cleaning systems. The currently published standards and codes cite the use of R-11, R-12 and R-112 for leak path test agents. All of these compounds are CFCs. There are other agencies and organizations (USDOE, USDOD and USNRC) also specifying testing for leak paths or in some cases for special life tests using the above compounds. The CONAGT has recently developed criteria for the suitability evaluation of substitute test agents. On the basis of these criteria, several compounds were evaluated for their acceptability as adsorbent bed leak and life test agents. The ASME CONAGT Test Agent Qualification Criteria. The test agent qualification is based on the following parameters: (1) Similar retention times on activated carbons at the same concentration levels as one of the following: R-11, R-12, R-112 or R-112a. (2) Similar lower detection limit sensitivity and precision in the concentration range of use as R-11, R-12, R-112 and R-112a. (3) Gives the same in-place leak test results as R-11, R-12, R-112, or R-112a. (4) Chemical and radiological stability under the use conditions. (5) Causes no degradation of the carbon and its impregnant or of the other NATS components under the use conditions. (6) Is listed in the USEPA Toxic Substances Control Act (TSCA) inventory for commercial use.

  5. Novel Penicillin Analogues as Potential Antimicrobial Agents; Design, Synthesis and Docking Studies.

    Zaman Ashraf

    Full Text Available A number of penicillin derivatives (4a-h were synthesized by the condensation of 6-amino penicillinic acid (6-APA with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents.

  6. Migration Dynamics in Artificial Agent Societies

    Harjot Kaur


    Full Text Available An Artificial Agent Society can be defined as a collection of agents interacting with each other for some purpose and/or inhabiting a specific locality, possibly in accordance to some common norms/rules. These societies are analogous to human and ecological societies, and are an expanding and emerging field in research about social systems. Social networks, electronic markets and disaster management organizations can be viewed as such artificial (open agent societies and can be best understood as computational societies. Members of such artificial agent societies are heterogeneous intelligent software agents which are operating locally and cooperating and coordinating with each other in order to achieve goals of an agent society. These artificial agent societies have some kind of dynamics existing in them in terms of dynamics of Agent Migration, Role-Assignment, Norm- Emergence, Security and Agent-Interaction. In this paper, we have described the dynamics of agent migration process, starting from the various types of agent migration, causes or reasons for agent migration, consequences of agent migration, and an agent migration framework to model the its behavior for migration of agents between societies.

  7. Adverse drug reactions and cost effectiveness of non-steroidal anti-inflammatory drugs, muscle relaxants, and neurotropic drugs in patients with low back pain

    I. B. Patel


    Conclusion: Patient on combination of three drugs (NSAIDs, muscle relaxants, and neurotropic agents had maximum ADRs and their prescription cost per day was highest among the three groups. [Int J Basic Clin Pharmacol 2015; 4(2.000: 273-277

  8. CATS-based Agents That Err

    Callantine, Todd J.


    This report describes preliminary research on intelligent agents that make errors. Such agents are crucial to the development of novel agent-based techniques for assessing system safety. The agents extend an agent architecture derived from the Crew Activity Tracking System that has been used as the basis for air traffic controller agents. The report first reviews several error taxonomies. Next, it presents an overview of the air traffic controller agents, then details several mechanisms for causing the agents to err in realistic ways. The report presents a performance assessment of the error-generating agents, and identifies directions for further research. The research was supported by the System-Wide Accident Prevention element of the FAA/NASA Aviation Safety Program.

  9. Needs, Pains, and Motivations in Autonomous Agents.

    Starzyk, Janusz A; Graham, James; Puzio, Leszek


    This paper presents the development of a motivated learning (ML) agent with symbolic I/O. Our earlier work on the ML agent was enhanced, giving it autonomy for interaction with other agents. Specifically, we equipped the agent with drives and pains that establish its motivations to learn how to respond to desired and undesired events and create related abstract goals. The purpose of this paper is to explore the autonomous development of motivations and memory in agents within a simulated environment. The ML agent has been implemented in a virtual environment created within the NeoAxis game engine. Additionally, to illustrate the benefits of an ML-based agent, we compared the performance of our algorithm against various reinforcement learning (RL) algorithms in a dynamic test scenario, and demonstrated that our ML agent learns better than any of the tested RL agents.

  10. Chaotic neurodynamics for autonomous agents.

    Harter, Derek; Kozma, Robert


    Mesoscopic level neurodynamics study the collective dynamical behavior of neural populations. Such models are becoming increasingly important in understanding large-scale brain processes. Brains exhibit aperiodic oscillations with a much more rich dynamical behavior than fixed-point and limit-cycle approximation allow. Here we present a discretized model inspired by Freeman's K-set mesoscopic level population model. We show that this version is capable of replicating the important principles of aperiodic/chaotic neurodynamics while being fast enough for use in real-time autonomous agent applications. This simplification of the K model provides many advantages not only in terms of efficiency but in simplicity and its ability to be analyzed in terms of its dynamical properties. We study the discrete version using a multilayer, highly recurrent model of the neural architecture of perceptual brain areas. We use this architecture to develop example action selection mechanisms in an autonomous agent.

  11. Subharmonic imaging of contrast agents.

    Forsberg, F; Shi, W T; Goldberg, B B


    Ultrasound contrast agents promise to improve the sensitivity and specificity of diagnostic ultrasound imaging. It is of great importance to adapt ultrasound equipment for optimal use with contrast agents e.g., by exploiting the nonlinear properties of the contrast microbubbles. Harmonic imaging is one technique that has been extensively studied and is commercially available. However, harmonic imaging is associated with problems, due to second harmonic generation and accumulation within the tissue itself. Given the lack of subharmonic generation in tissue, one alternative is the creation of subharmonic images by transmitting at the fundamental frequency (fo) and receiving at the subharmonic (fo/2). Subharmonic imaging should have a much better lateral resolution and may be suitable for scanning deep-lying structures owing to the higher transmit frequency and the much smaller attenuation of scattered subharmonic signals. In this paper, we will review different aspects of subharmonic imaging including implementation, in-vitro gray-scale imaging and subharmonic aided pressure estimation.

  12. Extension agents and conflict narratives

    Bond, Jennifer Lauren


    conflict. Originality: This work contributes to a growing body of literature interested in the role of extension agents in conflict management. By applying Q methodology, this work has shown that while extension agents are involved in conflict management, their perceptions of these conflicts are subjective......Purpose: This work investigated the narratives of development extensionists in relation to natural resource conflict, in order to understand the competing discourses surrounding the wicked problems of natural resource management in Laikipia County, Kenya. Methodology: Q methodology was used...... to elicit the conflict narratives present among extension professionals. A concourse of 221 statements were devised from interviews and group discussions with key informants and a final sample of 49 statements was used for the sorting. Thirteen Q-sorts were undertaken with among rural extension...

  13. Logical Theories for Agent Introspection

    Bolander, Thomas


    Artificial intelligence systems (agents) generally have models of the environments they inhabit which they use for representing facts, for reasoning about these facts and for planning actions. Much intelligent behaviour seems to involve an ability to model not only one's external environment...... introspective reasoning, the presence of self-reference causes the theory to be prone to inconsistency. The challenge therefore becomes to construct logical theories supporting introspective reasoning while at the same time ensuring that consistency is retained. In the thesis, we meet this challenge by devising...... by developments within semantics for logic programming within computational logic and formal theories of truth within philosophical logic. The thesis provides a number of examples showing how the developed theories can be used as reasoning frameworks for agents with introspective abilities. In Danish...

  14. Bacteriocins as potential anticancer agents

    Sukhraj eKaur


    Full Text Available Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have nonspecific toxicity towards normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeutic potential of bacteriocins against various types of cancer cell lines. Bacteriocins are ribosomally-synthesized cationic peptides secreted by almost all groups of bacteria. Some bacteriocins have shown selective cytotoxicity towards cancer cells as compared to normal cells. This makes them promising candidates for further investigation and clinical trials. In this review article, we present the overview of the various cancer cell-specific cytotoxic bacteriocins, their mode of action and efficacies.

  15. Heterogeneous Agents, Distribution and Growth

    Paquin, Lloyd


    We modify the Uzawa-Lucas representative agent model of endogenous economic growth to allow for a variety of differences among households: differences in their tastes, in their human capital production technologies, and in their initial endowments. Some differences are incompatible with the existence of a steady- state equilibrium, while others have no effect upon the steady-state growth rate. However, a variety of differences give rise to inequalities in the distribution of income and to var...

  16. 非甾体抗炎药物临床应用分析%Analysis of clinical application of nonsteroidal anti-inflammatory drugs



    目的 通过评估非甾体抗炎药物在我院的使用情况,监测此类药物用药的合理性及药物利用情况.方法 分析2010年1-12月我院门诊处方.结果 共调查2010年度门诊处方304 089张,其中含NSMDs的处方30 503张,占总处方的10.03%.使用频率前10位的药物包括尼美舒利胶囊(12 278张)、25 mg阿司匹林(5098张)、美洛昔康分散片(3193张)、尼美舒利颗粒(2143张)、丙氧氨酚片(2139张)、萘丁美酮胶囊(2129张)、布洛芬片(968张)、尼美舒利分散片(906张)、洛索洛芬颗粒(676张)、布洛芬混悬液(506张).应用此类药物最多的是骨科(7354张,21.77%),其后依次为急诊科(6968张,20.62%)、神经内科(3879张,11.48%)、康复科(3536张,10.46%)、风湿科(2298张,6.80%)等.用药总量前10种NSAIDs的药物利用指数均<1.结论 我院门诊非甾体抗炎药物的利用基本合理.%Objective To monitor the rational use of nonsteroidal anti-inflammatory drugs (NSAIDs).Methods Analysis on outpatient prescription in our hospital from January to December in 2010 was performed.Results Totally 304089 outpatient prescriptions were evaluated,including 30503 prescriptions of NSAIDs.Top 10prescribed medicines were:Nimesulide capsule (12278 prescriptions),25mg aspirin (5098 prescriptions),Meloxicam dispersible tablet (3193 prescriptions),Nimesulide granules (2134 prescriptions),Propoxyphene Napsylate and Paracetamol Tablets (2139 prescriptions)Nabumetone capsule (2129 prescriptions),ibuprofen tablet(968 prescriptions),Nimesulide dispersible tablet (906 prescriptions),loxoprofen granules (676 prescriptions)and Ibuprofen Suspension (506 prescriptions).NSAIDs were used most frequently in orthopedics (7354 prescriptions,21.77% ),followed by emergency department (6968 prescriptions,20.62% ),neurology (3879 prescriptions,11.48% ),rehabilitation department ( 3536prescriptions,10.64% ) and Rheumatology ( 2298 prescriptions,6.80% ).The drug utilization

  17. Antiinflamatórios não-hormonais: inibidores da ciclooxigenase 2 Nonsteroidal anti-inflammatory drugs: cyclooxygenase 2 inhibitors

    Maria Odete Esteves Hilário


    Full Text Available OBJETIVO: Analisar os antiinflamatórios não-hormonais (AINH inibidores seletivos da Cox 2 quanto ao mecanismo de ação, principais indicações, posologia e efeitos adversos mais comuns. FONTES DOS DADOS: MEDLINE e LILACS, sites da Food and Drug Administration (FDA e da Agência Nacional de Vigilância Sanitária (ANVISA. Foram selecionados os artigos mais importantes, com destaque para as publicações dos últimos 5 anos. SÍNTESE DOS DADOS: As principais indicações dos AINH são o controle da dor e da inflamação aguda e crônica. Não existem evidências que demonstrem maior efetividade de um AINH sobre outro. Até a presente data, nenhum inibidor da Cox2 foi liberado para uso na faixa etária pediátrica. Apenas o meloxicam e o etoricoxibe podem ser prescritos para adolescentes (13 e 16 anos, respectivamente. Os inibidores seletivos da Cox 2 são indicados em pacientes com efeitos adversos comprovadamente relacionados aos AINH não seletivos. Em alguns casos de alergia à aspirina, os Cox 2 seletivos podem ser prescritos, mas seu uso deve ser cuidadoso. Os principais efeitos adversos incluem os cardiovasculares e os fenômenos trombóticos. CONCLUSÕES: Os inibidores seletivos da Cox 2 são medicamentos que vêm sendo utilizados em algumas situações clínicas bem determinadas e podem oferecer algumas vantagens com relação aos AINH não seletivos. No entanto, devido ao custo mais elevado e aos potenciais efeitos adversos cardiovasculares, seu emprego deve ser criterioso.OBJECTIVE: To analyze selective COX 2 inhibitor nonsteroidal anti-inflammatory drugs (NSAID in terms of their mechanism of action, principal indications, posology and most common adverse effects. SOURCES: MEDLINE and LILACS databases and Food and Drug Administration (FDA and National Agency for Sanitary Vigilance (ANVISA - Agência Nacional de Vigilância Sanitária websites. The most important articles were selected and preference was given to articles published

  18. Chemotherapy and Dietary Phytochemical Agents

    Katrin Sak


    Full Text Available Chemotherapy has been used for cancer treatment already for almost 70 years by targeting the proliferation potential and metastasising ability of tumour cells. Despite the progress made in the development of potent chemotherapy drugs, their toxicity to normal tissues and adverse side effects in multiple organ systems as well as drug resistance have remained the major obstacles for the successful clinical use. Cytotoxic agents decrease considerably the quality of life of cancer patients manifesting as acute complaints and impacting the life of survivors also for years after the treatment. Toxicity often limits the usefulness of anticancer agents being also the reason why many patients discontinue the treatment. The nutritional approach may be the means of helping to raise cancer therapy to a new level of success as supplementing or supporting the body with natural phytochemicals cannot only reduce adverse side effects but improve also the effectiveness of chemotherapeutics. Various plant-derived compounds improve the efficiency of cytotoxic agents, decrease their resistance, lower and alleviate toxic side effects, reduce the risk of tumour lysis syndrome, and detoxify the body of chemotherapeutics. The personalised approach using various phytochemicals provides thus a new dimension to the standard cancer therapy for improving its outcome in a complex and complementary way.

  19. Multi-agent autonomous system

    Fink, Wolfgang (Inventor); Dohm, James (Inventor); Tarbell, Mark A. (Inventor)


    A multi-agent autonomous system for exploration of hazardous or inaccessible locations. The multi-agent autonomous system includes simple surface-based agents or craft controlled by an airborne tracking and command system. The airborne tracking and command system includes an instrument suite used to image an operational area and any craft deployed within the operational area. The image data is used to identify the craft, targets for exploration, and obstacles in the operational area. The tracking and command system determines paths for the surface-based craft using the identified targets and obstacles and commands the craft using simple movement commands to move through the operational area to the targets while avoiding the obstacles. Each craft includes its own instrument suite to collect information about the operational area that is transmitted back to the tracking and command system. The tracking and command system may be further coupled to a satellite system to provide additional image information about the operational area and provide operational and location commands to the tracking and command system.

  20. Preponderant agent, what is that?

    Clara Luz Álvarez


    Full Text Available Purpose – Preponderant agent is a new instrument for preventing and reverting adverse impact in competition due to highly concentrated markets. Therefore, this paper's objective is to present and analyze the preponderant agent concept in Mexico with emphasis on the broadcast sector, the telecommunication regulator decisions and the courts' interpretation. Methodology/approach/design – The objectives were achieved by researching and analyzing the main legal documents, the Congress reports and debates, the regulator's decisions and other relevant regulator's documents, as well as final decisions by the courts in connection with broadcast sector. Findings – Among the findings are that certain topics were not duly addressed by the Mexican regulator, or by the Congress, whereas the courts were more willing to hold decisions in favor of public interest based on constitutional intent and deference to the regulator's decision. Originality/value – This paper will be valuable for persons interested in telecommunications, broadcast and antitrust. Although the preponderant agent concept created in Mexico is not necessarily a “best practice”, it does provide an alternative instrument in antitrust. Moreover, the courts decisions also provide criteria regarding regulatory deference for the regulator.

  1. New agents in HSC mobilization.

    Domingues, Mélanie J; Nilsson, Susan K; Cao, Benjamin


    Mobilized peripheral blood (PB) is the most common source of hematopoietic stem cells (HSC) for autologous transplantation. Granulocyte colony stimulating factor (G-CSF) is the most commonly used mobilization agent, yet despite its widespread use, a considerable number of patients still fail to mobilize. Recently, a greater understanding of the interactions that regulate HSC homeostasis in the bone marrow (BM) microenvironment has enabled the development of new molecules that mobilize HSC through specific inhibition, modulation or perturbation of these interactions. AMD3100 (plerixafor), a small molecule that selectively inhibits the chemokine receptor CXCR4 is approved for mobilization in combination with G-CSF in patients with Non-Hodgkin's lymphoma and multiple myeloma. Nevertheless, identifying mobilization strategies that not only enhance HSC number, but are rapid and generate an optimal "mobilized product" for improved transplant outcomes remains an area of clinical importance. In recent times, new agents based on recombinant proteins, peptides and small molecules have been identified as potential candidates for therapeutic HSC mobilization. In this review, we describe the most recent developments in HSC mobilization agents and their potential impact in HSC transplantation.

  2. An Agent Based Classification Model

    Gu, Feng; Greensmith, Julie


    The major function of this model is to access the UCI Wisconsin Breast Can- cer data-set[1] and classify the data items into two categories, which are normal and anomalous. This kind of classifi cation can be referred as anomaly detection, which discriminates anomalous behaviour from normal behaviour in computer systems. One popular solution for anomaly detection is Artifi cial Immune Sys- tems (AIS). AIS are adaptive systems inspired by theoretical immunology and observed immune functions, principles and models which are applied to prob- lem solving. The Dendritic Cell Algorithm (DCA)[2] is an AIS algorithm that is developed specifi cally for anomaly detection. It has been successfully applied to intrusion detection in computer security. It is believed that agent-based mod- elling is an ideal approach for implementing AIS, as intelligent agents could be the perfect representations of immune entities in AIS. This model evaluates the feasibility of re-implementing the DCA in an agent-based simulation environ- ...

  3. A Framework for Organization-Aware Agents

    Jensen, Andreas Schmidt; Dignum, Virginia; Villadsen, Jørgen


    This short paper introduces and summarizes the AORTA reasoning framework that can be integrated into BDI-agents to enable organizational decision-making. This work has recently been published in the Journal of Autonomous Agents and Multi-Agent Systems (JAAMAS), as [3].......This short paper introduces and summarizes the AORTA reasoning framework that can be integrated into BDI-agents to enable organizational decision-making. This work has recently been published in the Journal of Autonomous Agents and Multi-Agent Systems (JAAMAS), as [3]....


    Atef GHARBI; Ben Ahmed, Samir


    The paper deals with distributed planning in a Multi-Agent System (MAS) constituted by several intelligent agents each one has to interact with the other autonomous agents. The problem faced is how to ensure a distributed planning through the cooperation in our multi-agent system. To do so, we propose the use of fuzzy logic to represent the response of the agent in case of interaction with the other. Finally, we use JADE platform to create agents and ensure the communication be...

  5. On Programming Organization-Aware Agents

    Jensen, Andreas Schmidt


    Since it is difficult (or even impossible) to assume anything about the agents’ behavior and goals in an open multi-agent system, it is often suggested that an organization is imposed upon the agents, whichhich, by abstracting away from the agents, specifies boundaries and objectives that the age......Since it is difficult (or even impossible) to assume anything about the agents’ behavior and goals in an open multi-agent system, it is often suggested that an organization is imposed upon the agents, whichhich, by abstracting away from the agents, specifies boundaries and objectives...

  6. Antagonistic formation motion of cooperative agents

    卢婉婷; 代明香; 薛方正


    This paper investigates a new formation motion problem of a class of first-order multi-agent systems with antagonis-tic interactions. A distributed formation control algorithm is proposed for each agent to realize the antagonistic formation motion. A sufficient condition is derived to ensure that all agents make an antagonistic formation motion in a distributed manner. It is shown that all agents can be spontaneously divided into several groups, and agents in the same group collab-orate while agents in different groups compete. Finally, a numerical simulation is included to demonstrate our theoretical results.

  7. 14th International Conference on Practical Applications of Agents and Multi-Agent Systems : Special Sessions

    Escalona, María; Corchuelo, Rafael; Mathieu, Philippe; Vale, Zita; Campbell, Andrew; Rossi, Silvia; Adam, Emmanuel; Jiménez-López, María; Navarro, Elena; Moreno, María


    PAAMS, the International Conference on Practical Applications of Agents and Multi-Agent Systems is an evolution of the International Workshop on Practical Applications of Agents and Multi-Agent Systems. PAAMS is an international yearly tribune to present, to discuss, and to disseminate the latest developments and the most important outcomes related to real-world applications. It provides a unique opportunity to bring multi-disciplinary experts, academics and practitioners together to exchange their experience in the development of Agents and Multi-Agent Systems. This volume presents the papers that have been accepted for the 2016 in the special sessions: Agents Behaviours and Artificial Markets (ABAM); Advances on Demand Response and Renewable Energy Sources in Agent Based Smart Grids (ADRESS); Agents and Mobile Devices (AM); Agent Methodologies for Intelligent Robotics Applications (AMIRA); Learning, Agents and Formal Languages (LAFLang); Multi-Agent Systems and Ambient Intelligence (MASMAI); Web Mining and ...

  8. Borrelioses, agentes e vetores Borrelioses, agents and vectors: a review

    Cleber O. Soares


    Full Text Available As borrelioses são enfermidades infecciosas determinadas por espiroquetas do gênero Borrelia, agentes transmissíveis, principalmente, por carrapatos aos animais e/ou ao homem. Nesta revisão são apresentadas e discutidas as enfermidades determinadas por borrélias, bem como as características gerais das espiroquetas, os aspectos relacionados a transmissão por artrópodes, as enfermidades nos animais domésticos e silvestres, quanto aos aspectos biológicos e patológicos, a doença de Lyme como principal zoonose do grupo, a associação de borrélia com outros agentes hematozoários e os métodos diagnósticos e a epidemiologia comparativa entre dados obtidos no Brasil com os de outros países. Estas borrelioses possuem características patológicas, clínicas e epidemiológicas variadas de acordo à região fisiográfica, devido à existência de distintas espécies, genoespécies e cepas; estes aspectos variam ainda em função dos artrópodes vetores, da interação vetor-patógeno e dos ecossistemas distintos.Borrelioses are infectous diseases caused by spirochaetes of the genus Borrelia. They are born mainly through ticks at animals and/or human beings. In this review are shown and discussed five groups of diseases determined by borrelia, general characteristics of the spirochaetes, aspects related to transmission by arthropods, biological and pathological aspects of the diseases in domestic and wild animals, Lyme disease as an important zoonosis, the association of borrelia with other hematozoa agents, the diagnostic methods and the comparative epidemiology with data obtained from Brazil and other countries. The borrelioses have pathological, clinical and epidemiological characteristics which vary according to physiographic regions due to the existence of different species, genospecies and strains of borrelia, of arthropod vectors, vector-agent relationship and of different ecocystems.

  9. Novel series of potent, nonsteroidal, selective androgen receptor modulators based on 7H-[1,4]oxazino[3,2-g]quinolin-7-ones.

    Higuchi, Robert I; Arienti, Kristen L; López, Francisco J; Mani, Neelakhanda S; Mais, Dale E; Caferro, Thomas R; Long, Yun Oliver; Jones, Todd K; Edwards, James P; Zhi, Lin; Schrader, William T; Negro-Vilar, Andrés; Marschke, Keith B


    Recent interest in orally available androgens has fueled the search for new androgens for use in hormone replacement therapy and as anabolic agents. In pursuit of this, we have discovered a series of novel androgen receptor modulators derived from 7H-[1,4]oxazino[3,2-g]quinolin-7-ones. These compounds were synthesized and evaluated in competitive binding assays and an androgen receptor transcriptional activation assay. A number of compounds from the series demonstrated single-digit nanomolar agonist activity in vitro. In addition, lead compound (R)-16e was orally active in established rodent models that measure androgenic and anabolic properties of these agents. In this assay, (R)-16e demonstrated full efficacy in muscle and only partially stimulated the prostate at 100 mg/kg. These data suggest that these compounds may be utilized as selective androgen receptor modulators or SARMs. This series represents a novel class of compounds for use in androgen replacement therapy.

  10. A Framework for Multi-Agent Planning

    Bos, A.; Tonino, J.F.M.; De Weerdt, M.M.; Witteveen, C.


    We introduce a computational framework, consisting of resources, skills, goals and services to represent the plans of individual agents and to develop models and algorithms for cooperation processes between a collection of agents.

  11. Preoperative management of anticoagulation and antiplatelet agents.

    Gleason, Lauren Jan; Friedman, Susan M


    This article describes current literature and treatment plans for managing anticoagulation and antiplatelet agents in patients presenting with hip fractures. Indications for anticoagulation and antiplatelet agents are discussed, and management techniques for when patients present with hip fractures are reviewed.

  12. What Are Anticoagulants and Antiplatelet Agents?

    ... by heart Treatments + Tests What Are Anticoagulants and Antiplatelet Agents? Anticoagulants and antiplatelet agents are medicines that reduce blood clotting in an artery, a vein or the heart. Blood clots can block the ...

  13. Security Measures to Protect Mobile Agents

    Dadhich, Piyanka; Govil, M. C.; Dutta, Kamlesh


    The security issues of mobile agent systems have embarrassed its widespread implementation. Mobile agents that move around the network are not safe because the remote hosts that accommodate the agents initiates all kinds of attacks. These hosts try to analyze the agent's decision logic and their accumulated data. So, mobile agent security is the most challenging unsolved problems. The paper analyzes various security measures deeply. Security especially the attacks performed by hosts to the visiting mobile agent (the malicious hosts problem) is a major obstacle that prevents mobile agent technology from being widely adopted. Being the running environment for mobile agent, the host has full control over them and could easily perform many kinds of attacks against them.

  14. Analysis and Optimization for Mobile Agent Communication

    YANGBo; LIUDayou


    Communication performance is one of the most important factors affecting the efficiency of mobile agent system. Only traditional optimization techniques for communication performance are not enough, especially in large-scale intelligent mobile agent system, so more intelligent optimization techniques are needed. In the background, the paper studies communication of mobile agent system from the viewpoint of performance. The paper makes qualitative and quantitative analysis of four important factors that will affect the communication performance of mobile agent system and presents the communication performance optimization model. The model hasthree primary functions. First, the model provides a formalism method to describe the communication task and process of mobile agent. Second, the model provides a means to make quantitative analysis of the performance of mobile agent system. Third, the model can plan out an optimal communication scheme for mobile agent to minimize the cost of whole communication. The model could thus be a building block for the optimization of the communication behavior of mobile agent.

  15. Agent Communication Channel Based on BACnet

    Jiang Wen-bin; Zhou Man-li


    We analyze the common shortcoming in the existing agent MTPs (message transport protocols). With employing the File object and related service AtomicWriteFile of BACnet (a data communication protocol building automation and control networks), a new method of agent message transport is proposed and implemented. Every agent platform (AP) has one specified File object and agents in another AP can communicate with agents in the AP by using AtomicWriteFile service. Agent messages can be in a variety of formats. In implementation, BACnet/IP and Ethernet are applied as the BACnet data link layers respectively. The experiment results show that the BACnet can provide perfect support for agent communication like other conventional protocols such as hypertext transfer protocol(HTTP), remote method invocation (RMI) etc. and has broken through the restriction of TCP/IP. By this approach, the agent technology is introduced into the building automation control network system.

  16. Integration of Agent System with Legacy Software

    SHEN Qi; ZHAO Yan-hong; YIN Zhao-lin


    Agent technique is a new method that can analyze, design and realize a distributed open system. It has been used in almost every field. But if act for the real practical words in technique, it must integrate with legacy software, such as database system etc, and control them. This paper introduces the specification of agent software integration, ontology, instances database as implementing agent software integration with CORBA technique and takes XML, ACL as language communicating among agents.

  17. Kansei Evaluation in Agent Rearing Game

    野路, 浩一朗; 西野, 順二; 小高, 知宏; 小倉, 久和; NOJI, Koichiro; NISHINO, Junji; ODAKA, Tomohiro; OGURA, Hisakazu


    In this paper, We have studied the Kansei evaluation of the agent rearing game. The agent rearing game is a game by which the characters who are the agents are brouht up. The Kansei evaluation is an evaluation by Kansei engineering like the sensibility and feelings, etc. to treat technological1y. In this research, We produced the agent rearing game. We propose the method of the interesting the game using the technique of Kansei engineering for the evaluation.

  18. Sports Agent Industry Emerges in China

    HeiZiand; YiYou


    The agent profession is not new to Chinese. First appearing in the Western Zhou Dynasty, agents were called "Zhi Ren" then and "Ya Ren" from the Tang Dynasty onwards. In the Ming Dynasty, a certain amount of property and a license were required if one wanted to become an agent. In the late Qing Dynasty, Mai Ban (Chinese executives working in foreign firms), also a sort of agents, began to emerge in major cities of China.

  19. Honey - A Novel Antidiabetic Agent

    Omotayo O. Erejuwa, Siti A. Sulaiman, Mohd S. Ab Wahab


    Full Text Available Diabetes mellitus remains a burden worldwide in spite of the availability of numerous antidiabetic drugs. Honey is a natural substance produced by bees from nectar. Several evidence-based health benefits have been ascribed to honey in the recent years. In this review article, we highlight findings which demonstrate the beneficial or potential effects of honey in the gastrointestinal tract (GIT, on the gut microbiota, in the liver, in the pancreas and how these effects could improve glycemic control and metabolic derangements. In healthy subjects or patients with impaired glucose tolerance or diabetes mellitus, various studies revealed that honey reduced blood glucose or was more tolerable than most common sugars or sweeteners. Pre-clinical studies provided more convincing evidence in support of honey as a potential antidiabetic agent than clinical studies did. The not-too-impressive clinical data could mainly be attributed to poor study designs or due to the fact that the clinical studies were preliminary. Based on the key constituents of honey, the possible mechanisms of action of antidiabetic effect of honey are proposed. The paper also highlights the potential impacts and future perspectives on the use of honey as an antidiabetic agent. It makes recommendations for further clinical studies on the potential antidiabetic effect of honey. This review provides insight on the potential use of honey, especially as a complementary agent, in the management of diabetes mellitus. Hence, it is very important to have well-designed, randomized controlled clinical trials that investigate the reproducibility (or otherwise of these experimental data in diabetic human subjects.

  20. Pathogenic agents in freshwater resources

    Geldreich, Edwin E.


    Numerous pathogenic agents have been found in freshwaters used as sources for water supplies, recreational bathing and irrigation. These agents include bacterial pathogens, enteric viruses, several protozoans and parasitic worms more common to tropical waters. Although infected humans are a major source of pathogens, farm animals (cattle, sheep, pigs), animal pets (dogs, cats) and wildlife serve as significant reservoirs and should not be ignored. The range of infected individuals within a given warm-blooded animal group (humans included) may range from 1 to 25%. Survival times for pathogens in the water environment may range from a few days to as much as a year (Ascaris, Taenia eggs), with infective dose levels varying from one viable cell for several primary pathogenic agents to many thousands of cells for a given opportunistic pathogen.As pathogen detection in water is complex and not readily incorporated into routine monitoring, a surrogate is necessary. In general, indicators of faecal contamination provide a positive correlation with intestinal pathogen occurrences only when appropriate sample volumes are examined by sensitive methodology.Pathways by which pathogens reach susceptible water users include ingestion of contaminated water, body contact with polluted recreational waters and consumption of salad crops irrigated by polluted freshwaters. Major contributors to the spread of various water-borne pathogens are sewage, polluted surface waters and stormwater runoff. All of these contributions are intensified during periods of major floods. Several water-borne case histories are cited as examples of breakdowns in public health protection related to water supply, recreational waters and the consumption of contaminated salad crops. In the long term, water resource management must focus on pollution prevention from point sources of waste discharges and the spread of pathogens in watershed stormwater runoff.

  1. Preferences of Agents in Defeasible Logic

    Dastani, M.; Governatori, G.; Rotolo, A.; Torre, L.W.N. van der


    Defeasible Logic is extended to programming languages for cognitive agents with preferences and actions for planning. We define rule-based agent theories that contain preferences and actions, together with inference procedures. We discuss patterns of agent types in this setting. Finally, we illustra

  2. Stability of Evolving Multi-Agent Systems

    De Wilde, Philippe; 10.1109/TSMCB.2011.2110642


    A Multi-Agent System is a distributed system where the agents or nodes perform complex functions that cannot be written down in analytic form. Multi-Agent Systems are highly connected, and the information they contain is mostly stored in the connections. When agents update their state, they take into account the state of the other agents, and they have access to those states via the connections. There is also external, user-generated input into the Multi-Agent System. As so much information is stored in the connections, agents are often memory-less. This memory-less property, together with the randomness of the external input, has allowed us to model Multi-Agent Systems using Markov chains. In this paper, we look at Multi-Agent Systems that evolve, i.e. the number of agents varies according to the fitness of the individual agents. We extend our Markov chain model, and define stability. This is the start of a methodology to control Multi-Agent Systems. We then build upon this to construct an entropy-based defi...

  3. Do pedagogical agents enhance software training?

    Meij, van der Hans


    This study investigates whether a tutorial for software training can be enhanced by adding a pedagogical agent, and whether the type of agent matters (i.e., cognitive, motivational, or mixed). The cognitive agent was designed to stimulate students to process their experiences actively. The motivatio

  4. Properties of Ettringite Type Expansive Agent


    By employing different forms and amounts of materials,many kinds of ettringite type expansive agents had been prepared.The relationship between the compositions and properties of expansive agents was analyzed.The design methods of expansive agent have been put forward according to the property requirement of expansive concrete.

  5. A principal-agent model of corruption

    Groenendijk, Nico


    One of the new avenues in the study of political corruption is that of neo-institutional economics, of which the principal-agent theory is a part. In this article a principal-agent model of corruption is presented, in which there are two principals (one of which is corrupting), and one agent (who is

  6. 31 CFR 332.12 - Fiscal agents.


    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Fiscal agents. 332.12 Section 332.12 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE....12 Fiscal agents. (a) Federal Reserve Banks and Branches referred to below, as fiscal agents of...

  7. 31 CFR 339.6 - Fiscal agents.


    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Fiscal agents. 339.6 Section 339.6 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE... H § 339.6 Fiscal agents. Federal Reserve Banks and Branches, as fiscal agents of the United...

  8. 31 CFR 352.13 - Fiscal agents.


    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Fiscal agents. 352.13 Section 352.13 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE....13 Fiscal agents. (a) Federal Reserve Banks and Branches, referred to below, as fiscal agents of...

  9. 31 CFR 316.12 - Fiscal agents.


    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Fiscal agents. 316.12 Section 316.12 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE....12 Fiscal agents. (a) Federal Reserve Banks and Branches referred to below, as fiscal agents of...

  10. Touching virtual agents: embodiment and mind

    Huisman, Gijs; Bruijnes, Merijn; Kolkmeier, Jan; Jung, Merel; Darriba Frederiks, Aduén; Rybarczyk, Yves


    In this paper we outline the design and development of an embodied conversational agent setup that incorporates an augmented reality screen and tactile sleeve. With this setup the agent can visually and physically touch the user. We provide a literature overview of embodied conversational agents, as

  11. Agents and Lattice-valued Logic

    Germanno Resconi


    In fuzzy set theory, instead of the underlying membership set being a two -valued set it is a multi-valued set that generally has the structure of a lattice L with a minimal element O and the maximal element I. Furthermore if ∧, ∨, → and (「) are defined in the set L, then we can use these operations to define, as in the ordinary set theory, operations on fuzzy subsets. In this paper we give a model of the Lattice-Valued Logic with set of agents.Any agents know the logic value of a sentence p. The logic value is compatible with all of the accessible conceptual models or worlds of p inside the agent. Agent can be rational or irrational in the use of the logic operation.Every agent of n agents can have the same set of conceptual models for p and know the same logic for p in this case the agents form a consistent group of agents.When agents have different conceptual models for p,different subgroup of agents know different logic value for p. In this case the n agents are inconsistent in the expression of the logic value for p. The valuation structure of set of agents can be used as a semantic model for the Lattice-valued Logic and fuzzy logic.

  12. Multi-Agent Planning with Planning Graph

    Bui, The Duy; Jamroga, Wojciech


    In this paper, we consider planning for multi-agents situations in STRIPS-like domains with planning graph. Three possible relationships between agents' goals are considered in order to evaluate plans: the agents may be collaborative, adversarial or indifferent entities. We propose algorithms to dea

  13. Embedded Automation in Human-Agent Environment

    Tweedale, Jeffrey W


    This research book proposes a general conceptual framework for the development of automation in human-agents environments that will allow human- agent teams to work effectively and efficiently. We examine various schemes to implement artificial intelligence techniques in agents.  The text is directed to the scientists, application engineers, professors and students of all disciplines, interested in the agency methodology and applications.

  14. Deliberative evolution in multi-agent systems

    Brazier, F.M.T.; Jonker, C.M.; Treur, J.; Wijngaards, N.J.E.


    Evolution of automated systems, in particular evolution of automated agents based on agent deliberation, is the topic of this paper. Evolution is not a merely material process, it requires interaction within and between individuals, their environments and societies of agents. An architecture for an

  15. Compositional Design of a Generic Design Agent

    Brazier, F.M.T.; Jonker, C.M.; Treur, J.; Wijngaards, N.J.E.


    This paper presents a generic architecture for a design agent, to be used in an Internet environment. The design agent is based on an existing generic agent model, and includes a refinement of a generic model for design, in which strategic reasoning

  16. A theoretical framework for explaining agent behavior

    Harbers, M.; Bosch, K. van den; Meyer, J.J.C.


    To understand emergent processes in multi-agent-based simulations it is important to study the global processes in a simulation as well as the processes on the agent level. The behavior of individual agents is easier to understand when they are able to explain their own behavior. In this paper, a th

  17. Mobile Agents in Networking and Distributed Computing

    Cao, Jiannong


    The book focuses on mobile agents, which are computer programs that can autonomously migrate between network sites. This text introduces the concepts and principles of mobile agents, provides an overview of mobile agent technology, and focuses on applications in networking and distributed computing.

  18. Animated BDP agents in virtual environments

    Nijholt, A.; Egges, A.; Akker, op den H.J.A.; Zwiers, J.; Krose, B.; de Rijke, M.; Schreiber, G.; van Someren, M.


    We introduce a Believes, Desires and Plans (BDP) agent that acts in a virtual environment using multi-modal interaction with the user. The environment is our virtual theatre environment. In this environment different agents have been introduced. In order to obtain a more uniform framework for agent

  19. Multi agent gathering waste system



    Full Text Available Along this paper, we present a new multi agent-based system to gather waste on cities and villages. We have developed a low cost wireless sensor prototype to measure the volume level of the containers. Furthermore a route system is developed to optimize the routes of the trucks and a mobile application has been developed to help drivers in their working days. In order to evaluate and validate the proposed system a practical case study in a real city environment is modeled using open data available and with the purpose of identifying limitations of the system.

  20. Social communication with virtual agents

    Marschner, Linda; Pannasch, Sebastian; Schulz, Johannes


    In social communication, the gaze direction of other persons provides important information to perceive and interpret their emotional response. Previous research investigated the influence of gaze by manipulating mutual eye contact. Therefore, gaze and body direction has been changed as a whole...... response, and emotional experience to agents of different gender and facial expressions were investigated. Eye movement data revealed longer fixation durations, i.e. a stronger allocation of attention, when gaze and body direction were not congruent with each other or when both were directed towards...