Hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs (HS-NSAIDs) are an emerging novel class of compounds with significant anti-inflammatory properties. They consist of a traditional NSAID to which an H(2)S-releasing moiety is covalently attached. We examined the effects of four different HS-NSAIDs on the growth properties of eleven different human cancer cell lines of six different tissue origins. Human colon, breast, pancreatic, prostate, lung, and leukemia cancer cell lines were treated with HS-aspirin, -sulindac, -iburofen, -naproxen, and their traditional counterparts. HS-NSAIDs inhibited the growth of all cancer cell lines studied, with potencies of 28- to >3000-fold greater than that of their traditional counterparts. HS-aspirin (HS-ASA) was consistently the most potent. HS-NSAIDs inhibited cell proliferation, induced apoptosis, and caused G(0)/G(1) cell cycle block. Metabolism of HS-ASA by colon cells showed that the acetyl group of ASA was hydrolyzed rapidly, followed by hydrolysis of the ester bond linking the salicylate anion to the H(2)S releasing moiety, producing salicylic acid and ADT-OH from which H(2)S is released. In reconstitution studies, ASA and ADT-OH were individually less active than the intact HS-ASA towards cell growth inhibition. Additionally, the combination of these two components representing a fairly close approximation to the intact HS-ASA, was 95-fold less active than the intact HS-ASA for growth inhibition. Taken together, these results demonstrate that HS-NSAIDs have potential anti-growth activity against a wide variety of human cancer cells.
To compare the efficacy of the COX-2 specific inhibitor valdecoxib with the conventional NSAID naproxen and placebo in treating rheumatoid arthritis (RA).
We compared the incidence of PUBs in a combined analysis of 20 randomized, double-blind, clinical trials of rofecoxib versus NSAIDs. Men and women (N = 17,072) from multinational trial sites with osteoarthritis or rheumatoid arthritis were studied. There was no upper age limit in any of the trials. Investigator-reported PUBs were reviewed by a blinded, external adjudication committee using pre-specified criteria. The incidence of confirmed PUBs, the main outcome measure, among patients treated with rofecoxib 12.5 mg, 25 mg, or 50 mg (combined, N = 10 026) was compared to that among patients treated with ibuprofen, diclofenac, nabumetone, or naproxen (combined, N = 7046).
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Consciously perceived clinical and subjective symptoms do not necessarily run in parallel with their behavioral equivalents. It, thus, may be important to assess the effects of treatment on behavioral functioning in the evaluation of the general efficacy of antimigraine drugs in the acute treatment of a migraine attack.
(S)-Naproxen was used to synthesize a chiral reagent, (S)-2-(6-methoxynaphthalen-2-yl)propanehydrazide, by itsreaction with hydrazine hydrate in the presence of dicyclohexylcarbodiimide as coupling agent. The reagent was characterized and its chiral purity was established. It was used as a chiral derivatizing reagent for the synthesis of hydrazone diastereomers, under microwave irradiation, of certain chiral aldehydes and ketones. The respective diastereomers were separated by reversed-phase high-performance liquid chromatography using a binary solvent combination containing trifluoroacetic acid. The diastereomers were detected at 231 nm. The method was validated for accuracy, precision, and limit of detection (LOD). For a series of hydrazones the LOD was found to be in the range 1.62-1.65 pmol/mL.
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The aim of this pilot study was to assess the prescription knowledge and common mistakes in fourth-year students at the School of Dentistry at the Universidad Nacional Autónoma de México.
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Standardized skin examination, skin biopsy with mast cell count, urinary levels of leukotriene E4 (LTE4), and serum levels of mast cell tryptase.
The CORS response categories in both the static and comparative modules demonstrated limited floor or ceiling effects and few missing values (<3%). Inter-item correlations, principal components analysis (component loading range: 0.62 to 0.95), and high estimates of internal consistency (alpha range: 0.88 to 0.94) for each composite score supported the structure and proposed scoring algorithm for the static module. The pattern of correlations between the CORS static and comparative items and composites with the revised Patient Perception of Migraine Questionnaire items and subscales, as well as the relationships between responses to selected static CORS items and the migraine diary, supported the construct validity of the CORS.
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The voluntary withdrawal of Vioxx (rofecoxib) from the market in 2004, as well as the 2005 and 2014 US FDA Advisory Committee meetings about non-steroidal anti-inflammatory drugs (NSAIDs) and cardiovascular risk, have raised questions surrounding the use of NSAIDs in at-risk populations. This paper discusses the cardiovascular safety profile of naproxen in the context of the NSAID class. The balance of evidence suggests that cardiovascular risk correlates with cyclooxygenase (COX)-2 selectivity, and the low COX-2 selectivity of naproxen results in a lower cardiovascular risk than that of other NSAIDs. The over-the-counter (OTC) use of naproxen is expected to pose minimal cardiovascular risk; however, the benefit-risk ratio and appropriate use should be considered at an individual patient level, particularly to assess underlying conditions that may increase the risk of events. Likewise, regulatory authorities should revisit label information periodically to ensure labeling reflects the current understanding of benefits and risks.
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We explored effects of nonselective cyclooxygenase and selective cyclooxygenase 2 inhibition on collateral development in a model of chronic myocardial ischemia. We hypothesized that cyclooxygenase 2 inhibitors would negatively effect angiogenic and inflammatory pathways.
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The effects of indomethacin and naproxen on zidovudine (ZDV) pharmacokinetics were studied in six patients with the acquired immunodeficiency syndrome (AIDS), AIDS related complex (ARC) or asymptomatic HIV disease using a placebo-controlled crossover design. Indomethacin 25 mg twice daily or naproxen 250 mg twice daily did not alter ZDV pharmacokinetics compared with placebo. The mean AUC value for the glucuronidated metabolite, GZDV, was reduced from 26.6 +/- 11.7 mumol l-1 h in the presence of placebo to 20.9 +/- 8.3 mumol l-1 h (95% C.I. of the difference 1.39-9.98; P < 0.05) following treatment with naproxen 250 mg twice daily for 3 days. The small decrease in plasma GZDV in the naproxen phase reflects an increase in clearance of ZDV to other metabolites and/or a decrease in the formation clearance to GZDV and/or an increase in the clearance of GZDV. A decrease in formation clearance to GZDV would be consistent with the results of in vitro studies reported previously. No significant increase in ZDV concentration in the presence of naproxen may reflect a lower sensitivity of parent drug measurements to selective inhibition of parallel pathways of metabolism. The clinical significance of these findings is unknown but toxicity may be increased if a decreased formation of GZDV is accompanied by shunting of metabolism to 3'-amino-3'-deoxythymidine which is alleged to be cytotoxic.
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Non-steroidal anti-inflammatory drugs may precipitate a relapse in some patients with inflammatory bowel disease. This may be an idiosyncratic reaction. The published evidence does not support the view that non-steroidal anti-inflammatory drugs are important in inducing relapse of inflammatory bowel disease. There is weak evidence that paracetamol may be more important.
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To quantify and compare the time-course and potency of the analgesic and antipyretic effects of naproxen in conjunction with the inhibition of PGE(2) and TXB(2).