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Sample records for anti-inflammatory drug inhibits

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

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

    2002-01-01

    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.

  2. Nonsteroid Anti-inflammatory Drugs and Kidney

    OpenAIRE

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

    2016-01-01

    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...

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

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    M. Campanini

    2013-05-01

    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

  4. Nonsteroid Anti-inflammatory Drugs and Kidney

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    Yaşar Yıldırım1

    2016-03-01

    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.

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

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

    2009-01-01

    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.

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

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

    2003-02-01

    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.

  7. Anti-inflammatory drug therapy in asthma

    NARCIS (Netherlands)

    Rottier, Bart L.; Duiverman, Eric J.

    2009-01-01

    Asthma is a disease with chronic inflammation of the airways and and-inflammatory treatment is a logical treatment. Inhaled corticosteroids [ICS] remain the cornerstone of anti-inflammatory therapy in recent international guidelines. Asthma cannot be cured by any medication: if the drug is discontin

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

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

    2016-01-18

    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.

  9. Purification and properties of a 3 alpha-hydroxysteroid dehydrogenase of rat liver cytosol and its inhibition by anti-inflammatory drugs.

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    Penning, T M; Mukharji, I; Barrows, S; Talalay, P

    1984-01-01

    An NAD(P)-dependent 3 alpha-hydroxysteroid dehydrogenase (EC 1.1.1.50) was purified to homogeneity from rat liver cytosol, where it is responsible for most if not all of the capacity for the oxidation of androsterone, 1-acenaphthenol and benzenedihydrodiol (trans-1,2-dihydroxycyclohexa-3,5-diene). The dehydrogenase has many properties (substrate specificity, pI, Mr, amino acid composition) in common with the dihydrodiol dehydrogenase (EC 1.3.1.20) purified from the same source [Vogel, Bentley, Platt & Oesch (1980) J. Biol. Chem. 255, 9621-9625]. Since 3 alpha-hydroxysteroids are by far the most efficient substrates, the enzyme is more appropriately designated a 3 alpha-hydroxysteroid dehydrogenase. It also promotes the NAD(P)H-dependent reductions of quinones (e.g. 9,10-phenanthrenequinone, 1,4-benzoquinone), aromatic aldehydes (4-nitrobenzaldehyde) and aromatic ketones (4-nitroacetophenone). The dehydrogenase is not inhibited by dicoumarol, disulfiram, hexobarbital or pyrazole. The mechanism of the powerful inhibition of this enzyme by both non-steroidal and steroidal anti-inflammatory drugs [Penning & Talalay (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 4504-4508] was examined with several substrates. Most non-steroidal anti-inflammatory drugs are competitive inhibitors (e.g. Ki for indomethacin, 0.20 microM for 9,10-phenanthrenequinone reduction at pH 6.0, and 0.835 microM for androsterone oxidation at pH 7.0), except for salicylates, which act non-competitively (e.g. Ki for aspirin, 650 microM for androsterone oxidation). The inhibitory potency of these agents falls sharply as the pH is increased from 6 to 9. Most anti-inflammatory steroids are likewise competitive inhibitors, except for the most potent (betamethasone and dexamethasone), which act non-competitively. The enzyme is inhibited competitively by arachidonic acid and various prostaglandins. PMID:6435601

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

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

    2010-01-01

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

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    Rafael Perini

    2004-01-01

    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.

  12. [Non steroidal anti-inflammatory drugs and rheumatic diseases].

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    Cossermelli, W; Pastor, E H

    1995-01-01

    Nonsteroidal anti-inflammatory drugs (NSAID) comprise an important class of medicaments that reduced the symptoms of inflamation in rheumatic disease. This article emphasizes similarities and class characteristics of the NSAID, mechanisms of action, and drug-interactions.

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

    NARCIS (Netherlands)

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

    2010-01-01

    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

  14. Inhibition of tumour necrosis factor-alpha (TNF-alpha) release from mast cells by the anti-inflammatory drugs, sodium cromoglycate and nedocromil sodium.

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    Bissonnette, E Y; Enciso, J A; Befus, A D

    1995-01-01

    TNF-alpha is a cytokine thought to be involved in the pathogenesis of asthma and in several other inflammatory conditions. Given recent evidence that mast cells (MC) are an important source of TNF-alpha, we investigated the effects of two anti-inflammatory drugs, nedocromil sodium (NED) and sodium cromoglycate (SCG), on rat MC-derived TNF-alpha. We established that at least 2 h pretreatment with NED or SCG followed by washing was required to inhibit TNF-alpha-dependent cytotoxicity by rat peritoneal MC (PMC). A maximum inhibition of TNF-alpha occurred after 6 h treatment. The inhibitory effect of NED and SCG (10(-5)-10(-3)M) was concentration-dependent (20-37% for NED and 16-37% for SCG). The time-course analysis and the use of cycloheximide, an inhibitor of protein synthesis, provided strong evidence that new protein synthesis by the MC is required for this inhibitory effect. Furthermore, 24 h treatment with 1 mM NED inhibited the levels of mRNA for TNF-alpha by 59-83%. In addition to the effect on TNF-alpha-dependent cytotoxicity by MC, 20 min pretreatment with 10(-4) M NED and SCG inhibited antigen-stimulated TNF-alpha release (6h) by 42% and 48%, respectively. Interestingly, the functionally distinct intestinal mucosal MC (IMMC) is unresponsive to these drugs with regard to histamine secretion. However, as with PMC, 2h pretreatment with NED or SCG inhibited TNF-alpha-dependent cytotoxicity by IMMC. These effects may be important in the action of these drugs in vivo in the late phase reaction in asthma or other inflammatory conditions. Images Fig. 6 PMID:7554404

  15. Nonsteroidal Anti-Inflammatory Drugs and the Kidney

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    Walter H. Hörl

    2010-07-01

    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.

  16. Monitoring the concentrations of nonsteroidal anti-inflammatory drugs and cyclooxygenase-inhibiting activities in the surface waters of the Tone Canal and Edo River Basin.

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    Nishi, Iwaki; Kawakami, Tsuyoshi; Onodera, Sukeo

    2015-01-01

    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.

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

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    E. De Luna-Bertos

    2013-01-01

    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.

  18. Anti-inflammatory drugs and experimental bronchitis.

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    Jeffery, P K

    1986-01-01

    Chronic bronchitis (chronic hypersecretion) and chronic bronchiolitis (small airways disease) are two conditions associated with cigarette smoking: both contribute to airflow obstruction in man, the latter associated with progressive deterioration in lung function. Mucous metaplasia and hyperplasia are characteristic histological changes. Experimentally, cigarette smoke given daily for two weeks, induces similar histological changes in the airways of specific pathogen-free rats, providing a suitable animal model for study: an early proliferation of basal cells, accompanied by mucous metaplasia of surface epithelial serous cells is followed by proliferation of newly formed mucous cells. There is also a significant increase in epithelial thickness due to cell hypertrophy without stratification or prior ulceration. Experimentally, secretory cell hyperplasia is inhibited completely or to varying degrees by prophylactic administration (intraperitoneal injection) of either indomethacin, flurbiprofen, dexamethasone, prednisolone, hydrocortisone (each at 2 or 4 mg/kg body weight) or a mucolytic drug, N-acetylcysteine(Nac), given orally as a 1% solution of the drinking water. Nac also inhibits the associated mucus-hypersecretion. It takes between 21 and 84 days, depending on airway level, for the increase in secretory cell number to return to control values (ie recover). Indomethacin and flurbiprofen (4 mg/kg, by ip injection) shorten recovery to between 4 and 9 days in intrapulmonary airways but have no effect on recovery time in the rat trachea. Nac is effective in 6 of 7 airway levels which showed cigarette smoke-induced mucous cell hyperplasia. In conclusion, in the rat, the response to cigarette smoke is one of mucous cell metaplasia and both basal and mucous cell proliferation. Cigarette smoke-induced mucous cell hyperplasia can be inhibited when selected drugs are given concurrently with the cigarette smoke: indomethacin, fluriprofen and Nac are also therapeutic.

  19. Cannabinoids as novel anti-inflammatory drugs.

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    Nagarkatti, Prakash; Pandey, Rupal; Rieder, Sadiye Amcaoglu; Hegde, Venkatesh L; Nagarkatti, Mitzi

    2009-10-01

    Cannabinoids are a group of compounds that mediate their effects through cannabinoid receptors. The discovery of Δ9-tetrahydrocannabinol (THC) as the major psychoactive principle in marijuana, as well as the identification of cannabinoid receptors and their endogenous ligands, has led to a significant growth in research aimed at understanding the physiological functions of cannabinoids. Cannabinoid receptors include CB1, which is predominantly expressed in the brain, and CB2, which is primarily found on the cells of the immune system. The fact that both CB1 and CB2 receptors have been found on immune cells suggests that cannabinoids play an important role in the regulation of the immune system. Recent studies demonstrated that administration of THC into mice triggered marked apoptosis in T cells and dendritic cells, resulting in immunosuppression. In addition, several studies showed that cannabinoids downregulate cytokine and chemokine production and, in some models, upregulate T-regulatory cells (Tregs) as a mechanism to suppress inflammatory responses. The endocannabinoid system is also involved in immunoregulation. For example, administration of endocannabinoids or use of inhibitors of enzymes that break down the endocannabinoids, led to immunosuppression and recovery from immune-mediated injury to organs such as the liver. Manipulation of endocannabinoids and/or use of exogenous cannabinoids in vivo can constitute a potent treatment modality against inflammatory disorders. This review will focus on the potential use of cannabinoids as a new class of anti-inflammatory agents against a number of inflammatory and autoimmune diseases that are primarily triggered by activated T cells or other cellular immune components.

  20. Nonsteroidal anti-inflammatory drugs suppress cancer stem cells via inhibiting PTGS2 (cyclooxygenase 2) and NOTCH/HES1 and activating PPARG in colorectal cancer.

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    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

    2014-02-01

    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.

  1. Rose geranium essential oil as a source of new and safe anti-inflammatory drugs

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    Boukhatem, Mohamed Nadjib; Kameli, Abdelkrim; Ferhat, Mohamed Amine; Saidi, Fairouz; Mekarnia, Maamar

    2013-01-01

    Background Since the available anti-inflammatory drugs exert an extensive variety of side effects, the search for new anti-inflammatory agents has been a priority of pharmaceutical industries. Aims The aim of the present study was to assess the anti-inflammatory activities of the essential oil of rose geranium (RGEO). Methods The chemical composition of the RGEO was investigated by gas chromatography. The major components were citronellol (29.13%), geraniol (12.62%), and citronellyl formate (8.06%). In the carrageenan-induced paw edema, five different groups were established and RGEO was administered orally in three different doses. Results RGEO (100 mg/kg) was able to significantly reduce the paw edema with a comparable effect to that observed with diclofenac, the positive control. In addition, RGEO showed a potent anti-inflammatory activity by topical treatment in the method of croton oil-induced ear edema. When the dose was 5 or 10 µl of RGEO per ear, the inflammation was reduced by 73 and 88%, respectively. This is the first report to demonstrate a significant anti-inflammatory activity of Algerian RGEO. In addition, histological analysis confirmed that RGEO inhibited the inflammatory responses in the skin. Conclusion Our results indicate that RGEO may have significant potential for the development of novel anti-inflammatory drugs with improved safety profile. PMID:24103319

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

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

    1999-01-01

    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.

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

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    Danielle Tondelier

    1999-01-01

    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.

  4. Anti-inflammatory drugs and psychosis

    NARCIS (Netherlands)

    Laan, W.

    2008-01-01

    This thesis focuses on the disorder we know as schizophrenia. Although there is treatment for schizophrenia in the form of anti-psychotic drugs, not all patients respond well to this treatment. A large part of patients will have remaining symptoms for the rest of their lives. A number of hypotheses

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    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)....

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

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

    2005-01-20

    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.

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

    NARCIS (Netherlands)

    Huls, G; Koornstra, JJ; Kleibeuker, JH

    2003-01-01

    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

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

    Science.gov (United States)

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

    1997-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

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

    1985-01-01

    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...

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

    Science.gov (United States)

    Zheng, Liuying; Du, Xinping

    2014-06-01

    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.

  12. Anti-inflammatory glucocorticoid drugs: reflections after 60 years.

    Science.gov (United States)

    Whitehouse, Michael W

    2011-02-01

    This review considers the problem of the serious concomitant side effects of powerful anti-inflammatory drugs modelled upon the principal human glucocorticoid hormone, cortisol. The very nature of the original bio-assays to validate their cortisol-like hormonal and anti-inflammatory activities ensured that pleiotropic toxins were selected for clinical studies. Other complicating factors have been (1) considerable reliance on bio-assays conducted in laboratory animals that primarily secrete corticosterone, not cortisol, as their principal anti-inflammatory adrenal hormone; (2) some differences in the binding of xenobiotic cortisol analogues (vis á vis cortisol) to transport proteins, detoxifying enzymes and even some intra-cellular receptors; (3) the "rogue" properties of these hormonal xenobiotics, acting independently of--but still able to suppress--hormonal mechanisms regulating endogenous cortisol; and (4) problems of intrinsic/acquired "steroid resistance", diminishing their clinical efficacy, but not necessarily all their toxicities. The rather gloomy conclusion is that devising new drugs to reproduce the effect of multi-potent hormones may be a recipe for disaster, in contexts other than simply remedying an endocrine deficiency. Promising new developments include "designed" combination therapies that allow some reduction in total steroid doses (and hopefully their side effects); sharpening strategies to limit the actual duration of steroid administration; and resurgent interest in searching for more selective analogues (both steroidal and non-steroid) with less harmful side effects. Some oversights and neglected areas of research are also considered. Overall, it now seems timely to engage in some drastic rethinking about (retaining?) these "licensed toxins" as fundamental therapies for chronic inflammation.

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

    OpenAIRE

    Brune K; Patrignani P

    2015-01-01

    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...

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

    Science.gov (United States)

    Marshall, J F; Blikslager, A T

    2011-08-01

    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.

  15. Anti-inflammatory drugs for Duchenne muscular dystrophy: focus on skeletal muscle-releasing factors.

    Science.gov (United States)

    Miyatake, Shouta; Shimizu-Motohashi, Yuko; Takeda, Shin'ichi; Aoki, Yoshitsugu

    2016-01-01

    Duchenne muscular dystrophy (DMD), an incurable and a progressive muscle wasting disease, is caused by the absence of dystrophin protein, leading to recurrent muscle fiber damage during contraction. The inflammatory response to fiber damage is a compelling candidate mechanism for disease exacerbation. The only established pharmacological treatment for DMD is corticosteroids to suppress muscle inflammation, however this treatment is limited by its insufficient therapeutic efficacy and considerable side effects. Recent reports show the therapeutic potential of inhibiting or enhancing pro- or anti-inflammatory factors released from DMD skeletal muscles, resulting in significant recovery from muscle atrophy and dysfunction. We discuss and review the recent findings of DMD inflammation and opportunities for drug development targeting specific releasing factors from skeletal muscles. It has been speculated that nonsteroidal anti-inflammatory drugs targeting specific inflammatory factors are more effective and have less side effects for DMD compared with steroidal drugs. For example, calcium channels, reactive oxygen species, and nuclear factor-κB signaling factors are the most promising targets as master regulators of inflammatory response in DMD skeletal muscles. If they are combined with an oligonucleotide-based exon skipping therapy to restore dystrophin expression, the anti-inflammatory drug therapies may address the present therapeutic limitation of low efficiency for DMD.

  16. A short history of anti-rheumatic therapy. III. Non steroidal anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    P. Marson

    2011-06-01

    Full Text Available The chemical advances of the 20th century led to the synthesis of non steroidal anti-inflammatory drugs (NSAIDs, beginning from phenylbutazone and indomethacin and continuing with other new drugs, including ibuprofen, diclofenac, naproxen, piroxicam and, more recently, the highly selective COX-2 inhibitors (coxibs. This progress derived from the discovery of the mechanism of action of these drugs: the inhibition of synthesis of prostaglandins due to the cycloxigenase enzyme system, according to the experimental contributions of John R. Vane.

  17. Non-steroidal Anti-inflammatory Drugs in Raptors

    Science.gov (United States)

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

    2012-01-01

    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.

  18. Topical nonsteroidal anti-inflammatory drugs for osteoarthritis.

    Science.gov (United States)

    Barthel, H Richard; Axford-Gatley, Robert A

    2010-11-01

    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.

  19. Endoscopical appearances of nonsteroidal anti inflammatory drug (NSAID- enteropathy

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    Marcellus Simadibrata

    2005-12-01

    Full Text Available Non Steroidal Anti Inflammatory Drugs (NSAID have been associated with a sudden and sustained rise in the incidence of gastrointestinal ulcer complications. The aim of the study was to reveal the endoscopical abnormalities found in the duodenum & proximal jejunum due to NSAID. Thirty eight patients taking NSAID for their arthritis or rheumatism were included in this study. Gastro-duodeno-jejunoscopy was done with Olympus PCF-10. The endoscopical appearances of NSAID entero gastropathy were evaluated with a scoring system. The NSAID-entero-gastropathy appearances were endoscopically seen as hyperemia, erosion and ulcer. From all patient recruited, 7.9% complaint of diarrhea and 71.1% complaint of dyspepsia. Endoscopically, in the duodenal bulb we found 79% cases of hyperemia, 39.5% cases of erosion and 7.9% cases of ulcer. In the second part (descending part of the duodenum we found 28.9% cases of hyperemia, 15.8% cases of erosion and 2.6% case of ulcer. In the jejunum, we found 7.9% cases of hyperemia, 2.6% case of erosion and no ulcer. It is concluded that the most frequent abnormal endoscopical appearances in NSAID- enteropathy was hyperemia. The most frequent site of NSAID-enteropathy abnormal findings was in the duodenal bulb. (Med J Indones 2005; 14: 225-9Keywords: NSAID-enteropathy, endoscopical appearances.

  20. On radiation damage to normal tissues and its treatment. Pt. 2; Anti-inflammatory drugs

    Energy Technology Data Exchange (ETDEWEB)

    Michalowski, A.S. (MRC Cyclotron Unit, Hammersmith Hospital, London (United Kingdom))

    1994-01-01

    In addition to transiently inhibiting cell cycle progression and sterilizing those cells capable of proliferation, irradiation disturbs the homeostasis effected by endogenous mediators of intercellular communication (humoral component of tissue response to radiation). Changes in the mediator levels may modulate radiation effects either by a assisting a return to normality (e.g., through a rise in H-type cell lineage-specific growth factors) or by aggravating the damage. The latter mode is illustrated with reports on changes in eicosanoid levels after irradiation and on results of empirical treatment of radiation injuries with anti-inflammatory drugs. Prodromal, acute and chronic effects of radiation are accompanied by excessive production of eicosanoids (prostaglandins, prostacyclin, thromboxanes and leukotrienes). These endogenous mediators of inflammatory reactions may be responsible for the vasodilatation, vasoconstriction, increased microvascular permeability, thrombosis and chemotaxis observed after radiation exposure. Glucocorticoids inhibit eicosanoid synthesis primarily by interfering with phospholipase A[sub 2] whilst non-steroidal anti-inflammatory drugs prevent prostaglandin/thromboxane synthesis by inhibiting cycloxygenase. When administered after irradiation on empirical grounds, drugs belonging to both groups tend to attenuate a range of prodomal, acute and chronic effects of radiation in man and animals. Taken together, these two sets of observations are highly suggestive of a contribution of humoral factors to the adverse responses of normal tissues and organs to radiation. A full account of radiation damage should therefore consist of complementary descriptions of cellular and humoral events. Further studies on anti-inflammatory drug treatment of radiation damage to normal organs are justified and desirable. (orig.).

  1. The Epidemiology of Nonsteroidal Anti-Inflammatory Drugs

    Directory of Open Access Journals (Sweden)

    Jerry Tenenbaum

    1999-01-01

    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

  2. In vitro inhibitory effects of non-steroidal anti-inflammatory drugs on 4-methylumbelliferone glucuronidation in recombinant human UDP-glucuronosyltransferase 1A9--potent inhibition by niflumic acid.

    Science.gov (United States)

    Mano, Yuji; Usui, Takashi; Kamimura, Hidetaka

    2006-01-01

    The inhibitory potencies of non-steroidal anti-inflammatory drugs (NSAIDs) on UDP-glucuronosyltransferase (UGT) 1A9 activity were investigated in recombinant human UGT1A9 using 4-methylumbelliferone (4-MU) as a substrate for glucuronidation. 4-MU glucuronidation (4-MUG) showed Michaelis-Menten kinetics with a Km value of 6.7 microM. The inhibitory effects of the following seven NSAIDs were investigated: acetaminophen, diclofenac, diflunisal, indomethacin, ketoprofen, naproxen and niflumic acid. Niflumic acid had the most potent inhibitory effect on 4-MUG with an IC50 value of 0.0341 microM. The IC50 values of diflunisal, diclofenac and indomethacin were 1.31, 24.2, and 34.1 microM, respectively, while acetaminophen, ketoprofen and naproxen showed less potent inhibition. Niflumic acid, diflunisal, diclofenac and indomethacin inhibited 4-MUG competitively with Ki values of 0.0275, 0.710, 53.3 and 69.9 microM, respectively, being similar to each IC50 value. In conclusion, of the seven NSAIDs investigated, niflumic acid was the most potent inhibitor of recombinant UGT1A9 via 4-MUG in a competitive manner.

  3. Anti-inflammatory drugs for Duchenne muscular dystrophy: focus on skeletal muscle-releasing factors

    Directory of Open Access Journals (Sweden)

    Miyatake S

    2016-08-01

    Full Text Available Shouta Miyatake,1 Yuko Shimizu-Motohashi,2 Shin’ichi Takeda,1 Yoshitsugu Aoki1 1Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan; 2Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan Abstract: Duchenne muscular dystrophy (DMD, an incurable and a progressive muscle wasting disease, is caused by the absence of dystrophin protein, leading to recurrent muscle fiber damage during contraction. The inflammatory response to fiber damage is a compelling candidate mechanism for disease exacerbation. The only established pharmacological treatment for DMD is corticosteroids to suppress muscle inflammation, however this treatment is limited by its insufficient therapeutic efficacy and considerable side effects. Recent reports show the therapeutic potential of inhibiting or enhancing pro- or anti-inflammatory factors released from DMD skeletal muscles, resulting in significant recovery from muscle atrophy and dysfunction. We discuss and review the recent findings of DMD inflammation and opportunities for drug development targeting specific releasing factors from skeletal muscles. It has been speculated that nonsteroidal anti-inflammatory drugs targeting specific inflammatory factors are more effective and have less side effects for DMD compared with steroidal drugs. For example, calcium channels, reactive oxygen species, and nuclear factor-κB signaling factors are the most promising targets as master regulators of inflammatory response in DMD skeletal muscles. If they are combined with an oligonucleotide-based exon skipping therapy to restore dystrophin expression, the anti-inflammatory drug therapies may address the present therapeutic limitation of low efficiency for DMD. Keywords: calcium channels, ryanodine receptor 1, exon skipping, NF-κB, myokine, ROS

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

    Science.gov (United States)

    Miranda, H F; Pinardi, G

    2004-09-01

    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.

  5. N-Acetylcysteine enhances the action of anti-inflammatory drugs as suppressors of prostaglandin production in monocytes

    Directory of Open Access Journals (Sweden)

    Erica Hoffer

    2002-01-01

    Full Text Available The anti-inflammatory effect of non-steroidal anti-inflammatory drugs (NSAIDs is associated with inhibition of cyclooxygenase (COX, the rate-limiting enzyme responsible for the synthesis of prostaglandins. Since oxygen free radicals can act as second cellular messengers, especially to modulate the metabolism of arachidonic acid and the prostaglandin tract, it seems plausible that antioxidants might affect the production of prostaglandin by activated cells. This research is focused on the effect of the antioxidant N-acetylcysteine (NAC on the inhibition of prostaglandin E2 formation in activated monocytes by specific and non-specific COX inhibitors. We found that lipopolysaccharide-induced prostaglandin E2 formation was significantly reduced by rofecoxib and by diclofenac, two NSAIDs. Addition of NAC to each of these drugs enhanced the effect of the NSAIDs. These results suggest that one might expect either a potentiation of the anti-inflammatory effect of COX inhibitors by their simultaneous administration with NAC, or obtaining the same anti-inflammatory at lower drug levels.

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

    NARCIS (Netherlands)

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

    1996-01-01

    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

  7. Lemon grass (Cymbopogon citratus essential oil as a potent anti-inflammatory and antifungal drugs

    Directory of Open Access Journals (Sweden)

    Mohamed Nadjib Boukhatem

    2014-09-01

    Full Text Available Background: Volatile oils obtained from lemon grass [Cymbopogon citratus (DC. Stapf, Poaceae family] are used in traditional medicine as remedies for the treatment of various diseases. Aims: In the present study, lemon grass essential oil (LGEO was evaluated for its in vivo topical and oral anti-inflammatory effects, and for its in vitro antifungal activity using both liquid and vapor phases. Methods: The chemical profile of LGEO as determined by gas chromatography–mass spectrometry analysis revealed two major components: geranial (42.2%, and neral (31.5%. The antifungal activity of LGEO was evaluated against several pathogenic yeasts and filamentous fungi using disc diffusion and vapor diffusion methods. Results: LGEO exhibited promising antifungal effect against Candida albicans, C. tropicalis, and Aspergillus niger, with different inhibition zone diameters (IZDs (35–90 mm. IZD increased with increasing oil volume. Significantly, higher anti-Candida activity was observed in the vapor phase. For the evaluation of the anti-inflammatory effect, LGEO (10 mg/kg, administered orally significantly reduced carrageenan-induced paw edema with a similar effect to that observed for oral diclofenac (50 mg/kg, which was used as the positive control. Oral administration of LGEO showed dose-dependent anti-inflammatory activity. In addition, topical application of LGEO in vivo resulted in a potent anti-inflammatory effect, as demonstrated by using the mouse model of croton oil-induced ear edema. To our knowledge, this is the first such report to be published. The topical application of LGEO at doses of 5 and 10 µL/ear significantly reduced acute ear edema induced by croton oil in 62.5 and 75% of the mice, respectively. In addition, histological analysis clearly confirmed that LGEO inhibits the skin inflammatory response in animal models. Conclusion: Results of the present study indicate that LGEO has a noteworthy potential for the development of drugs for

  8. Breast Cancer Stem Cell Potent Copper(II)-Non-Steroidal Anti-Inflammatory Drug Complexes.

    Science.gov (United States)

    Boodram, Janine N; Mcgregor, Iain J; Bruno, Peter M; Cressey, Paul B; Hemann, Michael T; Suntharalingam, Kogularamanan

    2016-02-18

    The breast cancer stem cell (CSC) potency of a series of copper(II)-phenanthroline complexes containing the nonsteroidal anti-inflammatory drug (NSAID), indomethacin, is reported. The most effective copper(II) complex in this series, 4, selectivity kills breast CSC-enriched HMLER-shEcad cells over breast CSC-depleted HMLER cells. Furthermore, 4 reduces the formation, size, and viability of mammospheres, to a greater extent than salinomycin, a potassium ionophore known to selectively inhibit CSCs. Mechanistic studies revealed that the CSC-specificity observed for 4 arises from its ability to generate intracellular reactive oxygen species (ROS) and inhibit cyclooxygenase-2 (COX-2), an enzyme that is overexpressed in breast CSCs. The former induces DNA damage, activates JNK and p38 pathways, and leads to apoptosis.

  9. Evaluation of Anti-Inflammatory Drug-Conjugated Silicon Quantum Dots: Their Cytotoxicity and Biological Effect

    Directory of Open Access Journals (Sweden)

    Kenji Yamamoto

    2013-01-01

    Full Text Available Silicon quantum dots (Si-QDs have great potential for biomedical applications, including their use as biological fluorescent markers and carriers for drug delivery systems. Biologically inert Si-QDs are less toxic than conventional cadmium-based QDs, and can modify the surface of the Si-QD with covalent bond. We synthesized water-soluble alminoprofen-conjugated Si-QDs (Ap-Si. Alminoprofen is a non-steroid anti-inflammatory drug (NSAID used as an analgesic for rheumatism. Our results showed that the “silicon drug” is less toxic than the control Si-QD and the original drug. These phenomena indicate that the condensed surface integration of ligand/receptor-type drugs might reduce the adverse interaction between the cells and drug molecules. In addition, the medicinal effect of the Si-QDs (i.e., the inhibition of COX-2 enzyme was maintained compared to that of the original drug. The same drug effect is related to the integration ratio of original drugs, which might control the binding interaction between COX-2 and the silicon drug. We conclude that drug conjugation with biocompatible Si-QDs is a potential method for functional pharmaceutical drug development.

  10. Inhibition viral RNP and anti-inflammatory activity of coumarins against influenza virus.

    Science.gov (United States)

    Wang, YuTao; Yan, Wen; Chen, QiaoLian; Huang, WanYi; Yang, Zifeng; Li, Xiong; Wang, XinHua

    2017-03-01

    Influenza viruses pose a severe threat to human health and a significant increase in antiviral drug-resistant among influenza viruses worldwide has been observed. Therefore, there is an urgent need to develop the new antiviral drugs, specifically from the natural products. In this study, the anti-viral and anti-inflammatory activities of coumarins against influenza A virus in vitro were investigated. One of the derivatives eleutheroside B1 showed a wide spectrum of anti- human influenza virus effect with the IC50 value of 64-125μg/ml in vitro, but it showed no effects against avian influenza virus. The time of addition was done and the results indicated that it had a potent antiviral effect when added at 0-6h, and also the virus yield was reduced by 60%. The influenza virus ribonucleoprotein was inhibited at 200μg/ml, and also the NP mRNA expression was inhibited at 50 and 200μg/ml. The expression level of cytokines and chemokines influenced by eleutheroside B1 was further demonstrated, the IL-6, CXCL-8, CCL-2 expression were all inhibited by the eleuthe roside B1 at concentration 200μg/ml. The findings of study suggest that eleutheroside B1 can be as potential agent to develop for the prevention and treatment of influenza A virus.

  11. Anti-inflammatory properties of drugs from saffron crocus.

    Science.gov (United States)

    Poma, Anna; Fontecchio, Gabriella; Carlucci, Giuseppe; Chichiriccò, Giuseppe

    2012-01-01

    The medicinal uses of saffron (Crocus sativus Linnaeus) have a long history beginning in Asian countries since the Late Bronze Age. Recent studies have validated its potential to lower the risk of several diseases. Some metabolites derived from saffron stigmas exert numerous therapeutic effects due to hypolipidemic, antitussive, antioxidant, antidiabetic activities and many others. Water and ethanol extracts of Crocus sativus L. are cardioprotective and counteract neurodegenerative disorders. Many of these medicinal properties of saffron can be attributed to a number of its compounds such as crocetin, crocins and other substances having strong antioxidant and radical scavenger properties against a variety of radical oxygen species and pro-inflammatory cytokines. Botany, worldwide spreading of cultivars, biochemical pathways, active constituents and chemical detection methods are reviewed. Therapeutic uses of saffron principles with particular regard to those exhibiting antioxidant and thus anti-inflammatory features are discussed. To date, very few adverse health effects of saffron have been demonstrated. At high doses (more than 5 g/die day), it should be avoided in pregnancy owing to its uterine stimulation activity.

  12. Development of anti-inflammatory drugs - the research and development process.

    Science.gov (United States)

    Knowles, Richard Graham

    2014-01-01

    The research and development process for novel drugs to treat inflammatory diseases is described, and several current issues and debates relevant to this are raised: the decline in productivity, attrition, challenges and trends in developing anti-inflammatory drugs, the poor clinical predictivity of experimental models of inflammatory diseases, heterogeneity within inflammatory diseases, 'improving on the Beatles' in treating inflammation, and the relationships between big pharma and biotechs. The pharmaceutical research and development community is responding to these challenges in multiple ways which it is hoped will lead to the discovery and development of a new generation of anti-inflammatory medicines.

  13. COX-independent mechanisms of cancer chemoprevention by anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Evrim eGurpinar

    2013-07-01

    Full Text Available Epidemiological and clinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs, including cyclooxygenase (COX-2 selective inhibitors, reduce the risk of developing cancer. Experimental studies in human cancer cell lines and rodent models of carcinogenesis support these observations by providing strong evidence for the antineoplastic properties of NSAIDs. The involvement of COX-2 in tumorigenesis and its overexpression in various cancer tissues suggest that inhibition of COX-2 is responsible for the chemopreventive efficacy of these agents. However, the precise mechanisms by which NSAIDs exert their antiproliferative effects are still a matter of debate. Numerous other studies have shown that NSAIDs can act through COX-independent mechanisms. This review provides a detailed description of the major COX-independent molecular targets of NSAIDs and discusses how these targets may be involved in their anticancer effects. Toxicities resulting from COX inhibition and the suppression of prostaglandin synthesis preclude the long-term use of NSAIDs for cancer chemoprevention. Furthermore, chemopreventive efficacy is incomplete and treatment often leads to the development of resistance. Identification of alternative NSAID targets and elucidation of the biochemical processes by which they inhibit tumor growth could lead to the development of safer and more efficacious drugs for cancer chemoprevention.

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

    DEFF Research Database (Denmark)

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

    1995-01-01

    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...

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

    NARCIS (Netherlands)

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

    2008-01-01

    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

  16. PBOSPECTS FOR CLINICAL APPLICATION OF THE CURRENT ANTI-INFLAMMATORY DRUG MELOXICAM (AMELOTEX

    Directory of Open Access Journals (Sweden)

    M S Eliseev

    2008-01-01

    Full Text Available The paper presents data on the effectiveness, safety, tolerance, major mechanisms of action, and prospects for clinically using meloxicam, a current selective nonsteroidal anti-inflammatory drug, against cyclooxygenase-2. It describes the advantages of meloxicam for injections, which begins acting promptly and shows an adequate long analgesic effect.

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

    NARCIS (Netherlands)

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

    2016-01-01

    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

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

    NARCIS (Netherlands)

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

    2004-01-01

    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

  19. Neutrophilia and an Anti-Inflammatory Drug as Markers of Inflammation in Delayed Muscle Soreness.

    Science.gov (United States)

    Smith, Lucille L.; And Others

    This study reexamined the concept that delayed muscle soreness (DMS) is a form of inflammatory pain. This was accomplished by having 32 male volunteers perform exercise known to induce DMS and then assess the total and differential white blood cell changes. In addition, an anti-inflammatory drug, idomethacin, was administered to determine whether…

  20. Effects of Non-Steroidal Anti-Inflammatory Drugs on the Gastrointestinal and Cardiovascular System

    NARCIS (Netherlands)

    G.M.C. Masclee (Gwen)

    2016-01-01

    markdownabstractNon-steroidal anti-inflammatory drugs (NSAIDs) are frequently used for pain relief and antiinflammatory purposes. They are often combined with proton pump inhibitors (PPIs), the most potent blockers of gastric acid secretion to reduce gastroduodenal complications of NSAID use. This t

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

    Directory of Open Access Journals (Sweden)

    P. van der Bijl

    2002-02-01

    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.

  2. Endotoxin Molecule Lipopolysaccharide-Induced Zebrafish Inflammation Model: A Novel Screening Method for Anti-Inflammatory Drugs

    Directory of Open Access Journals (Sweden)

    Li-Ling Yang

    2014-02-01

    Full Text Available Lipopolysaccharide (LPS, an endotoxin molecule, has been used to induce inflammatory responses. In this study, LPS was used to establish an in vivo inflammation model in zebrafish for drug screening. We present an experimental method that conveniently and rapidly assesses the anti-inflammatory properties of drugs. The yolks of 3-day post-fertilization (dpf larvae were injected with 0.5 mg/mL LPS to induce fatal inflammation. After LPS stimulation, macrophages were tracked by NR and SB staining and neutrophil migration was observed using the MPO:GFP line. Larval mortality was used as the primary end-point. Expression levels of key cytokines involved in the inflammatory response including IL-1β, IL-6, and TNF-α, were measured using quantitative reverse transcription polymerase chain reaction (RT-PCR. Macrophages and neutrophils were both recruited to the LPS-injected site during the inflammatory response. Mortality was increased by LPS in a dose-dependent manner within 48 h. Analyses of IL-1β, IL-6, and TNF-α expression levels revealed the upregulation of the inflammatory response in the LPS-injected larvae. Further, the anti-inflammatory activity of chlorogenic acid (CA was evaluated in this zebrafish model to screen for anti-inflammatory drugs. A preliminary result showed that CA revealed a similar effect as the corticosteroid dexamethasone (DEX, which was used as a positive control, by inhibiting macrophage and neutrophil recruitment to the LPS site and improving survival. Our results suggest that this zebrafish screening model could be applied to study inflammation-mediated diseases. Moreover, the Traditional Chinese Medicine CA displays potential anti-inflammatory activity.

  3. NONSTEROIDAL ANTI-INFLAMMATORY DRUGS: CURRENT ASPECTS OF THEIR USE

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2013-01-01

    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.

  4. Novel 2,5-disubstituted-1,3,4-oxadiazoles as anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Ega Durgashivaprasad

    2014-01-01

    Full Text Available Objective: 1,3,4-oxadiazole ring is a versatile moiety with a wide range of pharmacological properties. The present work deals with the synthesis and evaluation of the anti-inflammatory activity of two novel 2,5-disubstituted-1,3,4-oxadiazoles (OSD and OPD. Materials and Methods: Carrageenan-induced rat hind paw edema was employed as an acute model of inflammation. For evaluating sub-acute anti-inflammatory activity, carrageenan-induced inflammation in rat air pouch was employed. Complete Freund′s adjuvant-induced arthritis in rats was used as a model of chronic inflammation. To evaluate in vitro anti-inflammatory activity, lipopolysaccharide (LPS-stimulated RAW264.7 cells were used. Results: OSD (100 mg/kg reduced carrageen-induced paw edema by 60%, and OPD (100 mg/kg produced a modest 32.5% reduction. OSD also reduced leukocyte influx and myeloperoxidase in carrageenan-induced rat air pouch model. In complete Freund′s adjuvant-induced arthritis model, both OSD and OPD (200 mg/kg for 14 days reduced paw edema and NO levels. In LPS-stimulated RAW264.7 cells, OSD and OPD inhibited formation of nitric oxide and reactive oxygen species, with OPD showing a better activity in comparison to OSD. Conclusions: OSD was the better of the two compounds in in vivo models of inflammation. The o-phenol substitution at position 2 of oxadiazole ring in OSD may be responsible for its better in vivo anti-inflammatory activity. The ability of the compounds to inhibit LPS-induced pro-inflammatory mediator release suggests an anti-inflammatory mechanism targeting LPS-TLR4-NF-κB signalling pathway, which needs to be explored in detail. The disparate efficacy in vitro and in vivo also requires in-depth evaluation of the pharmacokinetics of these novel oxadiazoles.

  5. Study of Osteoarthritis Treatment with Anti-Inflammatory Drugs: Cyclooxygenase-2 Inhibitor and Steroids

    Directory of Open Access Journals (Sweden)

    Hongsik Cho

    2015-01-01

    Full Text Available Patients with osteoarthritis (OA, a condition characterized by cartilage degradation, are often treated with steroids, nonsteroidal anti-inflammatory drugs (NSAIDs, and cyclooxygenase-2 (COX-2 selective NSAIDs. Due to their inhibition of the inflammatory cascade, the drugs affect the balance of matrix metalloproteinases (MMPs and inflammatory cytokines, resulting in preservation of extracellular matrix (ECM. To compare the effects of these treatments on chondrocyte metabolism, TNF-α was incubated with cultured chondrocytes to mimic a proinflammatory environment with increasing production of MMP-1 and prostaglandin E2 (PGE2. The chondrocytes were then treated with either a steroid (prednisone, a nonspecific COX inhibitor NSAID (piroxicam, or a COX-2 selective NSAID (celecoxib. Both prednisone and celecoxib decreased MMP-1 and PGE-2 production while the nonspecific piroxicam decreased only the latter. Both prednisone and celecoxib decreased gene expression of MMP-1 and increased expression of aggrecan. Increased gene expression of type II collagen was also noted with celecoxib. The nonspecific piroxicam did not show these effects. The efficacy of celecoxib in vivo was investigated using a posttraumatic OA (PTOA mouse model. In vivo, celecoxib increases aggrecan synthesis and suppresses MMP-1. In conclusion, this study demonstrates that celecoxib and steroids exert similar effects on MMP-1 and PGE2 production in vitro and that celecoxib may demonstrate beneficial effects on anabolic metabolism in vivo.

  6. Treatment with some anti-inflammatory drugs reduces germ tube formation in Candida albicans strains

    Directory of Open Access Journals (Sweden)

    Elena Rusu

    2014-12-01

    Full Text Available Candida albicans is an opportunistic dimorphic fungus that inhabits various host mucosal sites. It can cause both superficial and serious systemic disease. Conversion from the yeast to the hyphal form has been associated with increased virulence and mucosal invasiveness. The aim of this study was to investigate the effect of sodium diclofenac and aspirin on germs tube formation of different Candida albicans strains. Prostaglandins may play an important role in fungal colonization. Nonsteroidal anti-inflammatory drugs are inhibitors of the cyclooxygenase isoenzymes. These drugs specifically block the biosynthesis of mammalian prostaglandins by inhibiting one or both of cyclooxygenase isoenzymes. In tests for germ tube formation sodium diclofenac reduced the filamentation to the 12.5%- 5.1%. In the presence of aspirin the filamentation was reduced up to 85-45% depending on the tested strain. Our results suggest that cyclooxygenase-depending synthesis of fungal prostaglandins is important for morphogenesis and fungal virulence. Inhibitors of cyclooxygenase isoensymes (aspirin and diclofenac are effective in decreasing germ tube formation of Candida albicans.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    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....

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

    DEFF Research Database (Denmark)

    Aalykke, C; Lauritsen, Jens; Hallas, J

    1999-01-01

    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...

  9. The anti-inflammatory drug leflunomide is an agonist of the aryl hydrocarbon receptor.

    Directory of Open Access Journals (Sweden)

    Edmond F O'Donnell

    Full Text Available BACKGROUND: The aryl hydrocarbon receptor (AhR is a ligand-activated transcription factor that mediates the toxicity and biological activity of dioxins and related chemicals. The AhR influences a variety of processes involved in cellular growth and differentiation, and recent studies have suggested that the AhR is a potential target for immune-mediated diseases. METHODOLOGY/PRINCIPAL FINDINGS: During a screen for molecules that activate the AhR, leflunomide, an immunomodulatory drug presently used in the clinic for the treatment of rheumatoid arthritis, was identified as an AhR agonist. We aimed to determine whether any biological activity of leflunomide could be attributed to a previously unappreciated interaction with the AhR. The currently established mechanism of action of leflunomide involves its metabolism to A771726, possibly by cytochrome P450 enzymes, followed by inhibition of de novo pyrimidine biosynthesis by A771726. Our results demonstrate that leflunomide, but not its metabolite A771726, caused nuclear translocation of AhR into the nucleus and increased expression of AhR-responsive reporter genes and endogenous AhR target genes in an AhR-dependent manner. In silico Molecular Docking studies employing AhR ligand binding domain revealed favorable binding energy for leflunomide, but not for A771726. Further, leflunomide, but not A771726, inhibited in vivo epimorphic regeneration in a zebrafish model of tissue regeneration in an AhR-dependent manner. However, suppression of lymphocyte proliferation by leflunomide or A771726 was not dependent on AhR. CONCLUSIONS: These data reveal that leflunomide, an anti-inflammatory drug, is an agonist of the AhR. Our findings link AhR activation by leflunomide to inhibition of fin regeneration in zebrafish. Identification of alternative AhR agonists is a critical step in evaluating the AhR as a therapeutic target for the treatment of immune disorders.

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

    Institute of Scientific and Technical Information of China (English)

    Hugh; James; Freeman

    2012-01-01

    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.

  11. Baicalein exhibits anti-inflammatory effects via inhibition of NF-κB transactivation.

    Science.gov (United States)

    Patwardhan, Raghavendra S; Sharma, Deepak; Thoh, Maikho; Checker, Rahul; Sandur, Santosh K

    2016-05-15

    NF-κB is a crucial mediator of inflammatory and immune responses and a number of phytochemicals that can suppress this immune-regulatory transcription factor are known to have promising anti-inflammatory potential. However, we report that inducer of pro-inflammatory transcription factor NF-κB functions as an anti-inflammatory agent. Our findings reveal that a plant derived flavonoid baicalein could suppress mitogen induced T cell activation, proliferation and cytokine secretion. Treatment of CD4+ T cells with baicalein prior to transfer in to lymphopenic allogenic host significantly suppressed graft versus host disease. Interestingly, addition of baicalein to murine splenic lymphocytes induced DNA binding of NF-κB but did not suppress Concanavalin A induced NF-κB. Since baicalein did not inhibit NF-κB binding to DNA, we hypothesized that baicalein may be suppressing NF-κB trans-activation. Thioredoxin system is implicated in the regulation of NF-κB trans-activation potential and therefore inhibition of thioredoxin system may be responsible for suppression of NF-κB dependent genes. Baicalein not only inhibited TrxR activity in cell free system but also suppressed mitogen induced thioredoxin activity in the nuclear compartment of lymphocytes. Similar to baicalein, pharmacological inhibitors of thioredoxin system also could suppress mitogen induced T cell proliferation without inhibiting DNA binding of NF-κB. Further, activation of cellular thioredoxin system by the use of pharmacological activator or over-expression of thioredoxin could abrogate the anti-inflammatory action of baicalein. We propose a novel strategy using baicalein to limit NF-κB dependent inflammatory responses via inhibition of thioredoxin system.

  12. MULTIFACTORINESS OF THE MECHANISMS OF ACTION OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS IN OSTEOARTHROSIS

    Directory of Open Access Journals (Sweden)

    Vladimir Vasilyevich Badokin

    2009-01-01

    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

  13. MULTIFACTORINESS OF THE MECHANISMS OF ACTION OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS IN OSTEOARTHROSIS

    Directory of Open Access Journals (Sweden)

    Vladimir Vasilyevich Badokin

    2009-12-01

    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

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

    DEFF Research Database (Denmark)

    Kehlet, H; Dahl, J B

    1992-01-01

    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...

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

    Directory of Open Access Journals (Sweden)

    Viktoriya Georgievna Barskova

    2011-01-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

    Mario Guslandi

    2012-01-01

    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.

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

    OpenAIRE

    2010-01-01

    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...

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

    NARCIS (Netherlands)

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

    2005-01-01

    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

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

    Science.gov (United States)

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

    2015-08-14

    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.

  20. Psoriatic arthritis: treatment strategies using anti-inflammatory drugs and classical DMARDs

    Directory of Open Access Journals (Sweden)

    E. Lubrano

    2012-06-01

    Full Text Available Psoriatic Arthritis (PsA is a chronic inflammatory disease typically characterized by arthritis and psoriasis variably associated with other extra-articular manifestations. PsA has been considered a milder and less disabling disease compared with rheumatoid arthritis (RA, even if some studies showed that PsA had joint erosions and damage. In addition, about 20-40% of PsA patients have axial skeleton involvement that may lead to functional limitation and deformity. The treatment of PsA ranged from initial treatment with non-steroidal anti-inflammatory drugs (NSAIDs to one or more disease-modifying anti-rheumatic agents (DMARDs for the suppression of inflammation in patients with recalcitrant peripheral joint disease. In clinical practice, the most widely used DMARDs are methotrexate (level of evidence B, sulfasalazine (level of evidence A, leflunomide (level of evidence A, and ciclosporin (level of evidence B. However, the efficacy of these agents in inhibiting joint erosions has not been assessed in controlled studies. Finally, the effectiveness of DMARDs in treating enthesitis and dactylitis is controversial. The present paper revised the evidence-based results on treatment with “conventional” therapy for PsA. The revision was based on all the subsets of the diseases, namely the various manifestations of the articular involvement (peripheral, axial, enthesitis, dactylitis as well as the skin and nail involvement.

  1. Increased temperature and entropy production in cancer: the role of anti-inflammatory drugs.

    Science.gov (United States)

    Pitt, Michael A

    2015-02-01

    Some cancers have been shown to have a higher temperature than surrounding normal tissue. This higher temperature is due to heat generated internally in the cancer. The higher temperature of cancer (compared to surrounding tissue) enables a thermodynamic analysis to be carried out. Here I show that there is increased entropy production in cancer compared with surrounding tissue. This is termed excess entropy production. The excess entropy production is expressed in terms of heat flow from the cancer to surrounding tissue and enzymic reactions in the cancer and surrounding tissue. The excess entropy production in cancer drives it away from the stationary state that is characterised by minimum entropy production. Treatments that reduce inflammation (and therefore temperature) should drive a cancer towards the stationary state. Anti-inflammatory agents, such as aspirin, other non-steroidal anti-inflammatory drugs, corticosteroids and also thyroxine analogues have been shown (using various criteria) to reduce the progress of cancer.

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

    Directory of Open Access Journals (Sweden)

    Madalina luiza MOLDOVEANU

    2012-09-01

    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.

  3. Hepatotoxicity of anti-inflammatory and analgesic drugs:ultrastructural aspects

    Institute of Scientific and Technical Information of China (English)

    Irena MANOV; Helen MOTANIS; Idan FRUMIN; Theodore C IANCU

    2006-01-01

    With the increasing incidence of drug-induced liver disease,attempts are being made to better understand the mechanisms behind these frequently life-endangering reactions.Analgesics and anti-inflammatory drugs are a major group exhibiting hepatotoxicity.We review research relating to these reactions,focusing on ultrastructural findings,which may contribute to the comprehension and possible avoidance of drug-induced liver disease.We also present some original observations on clinical material and cultured cells exposed to acetaminophen alone or in combination with the antioxidant N-acetylcysteine or the P-glycoprotein inhibitor verapamil.

  4. ANTIOXIDANT, ANTI-INFLAMMATORY AND DIABETES RELATED ENZYME INHIBITION PROPERTIES OF LEAVES EXTRACT FROM SELECTED VARIETIES OF PHOENYX DACTYLIFERA L.

    OpenAIRE

    Laouini Salah Eddine

    2013-01-01

    Objective: to investigate the antioxidant, anti-inflammatory, and antidiabetic activities of ethanolic leaves extracts of three selected varieties of Phoenyx dactylifera L. namely: “Ghars”, “Deglet Nour” and “Hamraya”. Methods: The assessment of the antioxidant potential of crude leaves extracts, using superoxide anions inhibition, DPPH and total antioxidant activity essays, was carried out. Furthermore, the anti-inflammatory properties of the extracts were determined by measuring the inhibi...

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

    Directory of Open Access Journals (Sweden)

    Brune K

    2015-02-01

    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

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

    Directory of Open Access Journals (Sweden)

    Amjad M. Qandil

    2012-12-01

    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.

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

    DEFF Research Database (Denmark)

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

    1996-01-01

    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. Evaluation of Anti-Inflammatory Drug-Conjugated Silicon Quantum Dots: Their Cytotoxicity and Biological Effect

    OpenAIRE

    Kenji Yamamoto; Akiyoshi Hoshino; Yasuhiro Futamura; Noriyoshi Manabe; Kouki Fujioka; Sanshiro Hanada

    2013-01-01

    Silicon quantum dots (Si-QDs) have great potential for biomedical applications, including their use as biological fluorescent markers and carriers for drug delivery systems. Biologically inert Si-QDs are less toxic than conventional cadmium-based QDs, and can modify the surface of the Si-QD with covalent bond. We synthesized water-soluble alminoprofen-conjugated Si-QDs (Ap-Si). Alminoprofen is a non-steroid anti-inflammatory drug (NSAID) used as an analgesic for rheumatism. Our results showed...

  9. Inhibition of chronic skin inflammation by topical anti-inflammatory flavonoid preparation, Ato Formula.

    Science.gov (United States)

    Lim, Hyun; Son, Kun Ho; Chang, Hyeun Wook; Kang, Sam Sik; Kim, Hyun Pyo

    2006-06-01

    Flavonoids are known as natural anti-inflammatory agents. In this investigation, an anti-inflammatory potential of new topical preparation (SK Ato Formula) containing flavonoid mixtures from Scutellaria baicalensis Georgi roots and Ginkgo biloba L. leaves with an extract of Gentiana scabra Bunge roots was evaluated in an animal model of chronic skin inflammation. Multiple 12-O-tetradecanoylphorbol-13-acetate treatments for 7 consecutive days on ICR mouse ear provoked a chronic type of skin inflammation: dermal edema, epidermal hyperplasia and infiltration of inflammatory cells. When topically applied in this model, this new formulation (5-20 microL/ear/treatment) reduced these responses. Furthermore, it inhibited prostaglandin E2 generation (17.1-33.3%) and suppressed the expression of proinflammatory genes, cyclooxygenase-2 and interleulin-1beta in the skin lesion. Although the potency of inhibition was lower than that of prednisolone, all these results suggest that Ato Formula may be beneficial for treating chronic skin inflammatory disorders such as atopic dermatitis.

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

    Science.gov (United States)

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

    2013-05-13

    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.

  11. Design, syntheses, characterization, and evaluation of 2-substituted-1,3-bis(1-naphthylmethyl-imidazolidine derivatives in search of safer nonsteroidal anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Umesh Kumar

    2015-01-01

    Full Text Available Background: 1,2,3-trisubstituted imidazolidines are reported to have better anti-inflammatory activity than the reference drug indomethacin. Similarly, naphthalene nucleus plays a significant role in the drug design. Nabumetone and naproxen are naphthalene nucleus containing anti-inflammatory drugs available in the market. There are also reports that compounds having two naphthalene rings incorporated with a heterocyclic nucleus have good medicinal value. Based on these reports it was planned to synthesize hybrid compounds containing two naphthalene rings with imidazolidine nucleus. Aim: To obtain potent compounds having anti-inflammatory and analgesic activities with reduced gastrointestinal side effects. Materials and Methods: The reaction scheme includes the reaction between 1-naphthaldehyde with ethylenediamine to obtain diSchiff′s base (1 Reduction of this diSchiff′s base with NaBH 4 gave tetrahydrodiSchiff′s base (2 Further cyclization of 2 with appropriate aldehyde in the presence of ethanol formed 2-substituted-1,3-bis(1-naphthylmethyl-imidazolidine derivatives (3a-n. The structures of these compounds were established on the basis of spectral data. All these compounds were tested for their anti-inflammatory, analgesic, ulcerogenic, and lipid peroxidation activities. Results and Discussion: The tested compounds (3a-n showed anti-inflammatory activity ranging between 27.61% and 53.43%. The compound 3h showed the highest activity of 53.43% and 3n showed 53.02% inhibition at 20 mg/kg dose in rats compared with the standard drug indomethacin which showed 61.45% inhibition at the same dose. It was encouraging to note that both the compounds showed reduced ulcerogenic activity (less than half compared to the standard drug indomethacin.

  12. Early responses to deep brain stimulation in depression are modulated by anti-inflammatory drugs.

    Science.gov (United States)

    Perez-Caballero, L; Pérez-Egea, R; Romero-Grimaldi, C; Puigdemont, D; Molet, J; Caso, J-R; Mico, J-A; Pérez, V; Leza, J-C; Berrocoso, E

    2014-05-01

    Deep brain stimulation (DBS) in the subgenual cingulated gyrus (SCG) is a promising new technique that may provide sustained remission in resistant major depressive disorder (MDD). Initial studies reported a significant early improvement in patients, followed by a decline within the first month of treatment, an unexpected phenomenon attributed to potential placebo effects or a physiological response to probe insertion that remains poorly understood. Here we characterized the behavioural antidepressant-like effect of DBS in the rat medial prefrontal cortex, focusing on modifications to rodent SCG correlate (prelimbic and infralimbic (IL) cortex). In addition, we evaluated the early outcome of DBS in the SCG of eight patients with resistant MDD involved in a clinical trial. We found similar antidepressant-like effects in rats implanted with electrodes, irrespective of whether they received electrical brain stimulation or not. This effect was due to regional inflammation, as it was temporally correlated with an increase of glial-fibrillary-acidic-protein immunoreactivity, and it was blocked by anti-inflammatory drugs. Indeed, inflammatory mediators and neuronal p11 expression also changed. Furthermore, a retrospective study indicated that the early response of MDD patients subjected to DBS was poorer when they received anti-inflammatory drugs. Our study demonstrates that electrode implantation up to the IL cortex is sufficient to produce an antidepressant-like effect of a similar magnitude to that observed in rats receiving brain stimulation. Moreover, both preclinical and clinical findings suggest that the use of anti-inflammatory drugs after electrode implantation may attenuate the early anti-depressive response in patients who are subjected to DBS.

  13. Anti-inflammatory drugs as moderators of antidepressant effects, especially those of the selective serotonin-reuptake inhibitor class.

    Science.gov (United States)

    Kronenberg, Sefi

    2011-09-01

    Large studies examining remission rates obtained by antidepressants have yielded somewhat dismal results. In the well-reported Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, only 36.8% of patients exhibited remission with the selective serotonin-reuptake inhibitor (SSRI) citalopram and the cumulative remission rate was 67% after multiple treatments were attempted. Warner-Schmidt et al. recently published an interesting paper that suggests specific mechanisms by which anti-inflammatory drugs inhibit the antidepressant effects of SSRIs. They employed well-established mouse models of depression: the tail suspension test and the forced swim test. In their experiment, ibuprofen significantly attenuated the antidepressant-like effects of SSRIs in both tests. The authors also presented data from the STAR*D study itself. These data - demonstrating higher remission rates for depressed patients receiving citalopram without concomitant NSAIDs (55.2%) than those receiving citalopram with NSAIDs (44.5%) - serve to illustrate the potential hindering effects of anti-inflammatory drugs.

  14. Inhibition of SIK2 and SIK3 during differentiation enhances the anti-inflammatory phenotype of macrophages

    Science.gov (United States)

    Darling, Nicola J.; Toth, Rachel; Arthur, J. Simon C.

    2017-01-01

    The salt-inducible kinases (SIKs) control a novel molecular switch regulating macrophage polarization. Pharmacological inhibition of the SIKs induces a macrophage phenotype characterized by the secretion of high levels of anti-inflammatory cytokines, including interleukin (IL)-10, and the secretion of very low levels of pro-inflammatory cytokines, such as tumour necrosis factor α. The SIKs, therefore, represent attractive new drug targets for the treatment of macrophage-driven diseases, but which of the three isoforms, SIK1, SIK2 or SIK3, would be appropriate to target remains unknown. To address this question, we developed knock-in (KI) mice for SIK1, SIK2 and SIK3, in which we introduced a mutation that renders the enzymes catalytically inactive. Characterization of primary macrophages from the single and double KI mice established that all three SIK isoforms, and in particular SIK2 and SIK3, contribute to macrophage polarization. Moreover, we discovered that inhibition of SIK2 and SIK3 during macrophage differentiation greatly enhanced the production of IL-10 compared with their inhibition in mature macrophages. Interestingly, macrophages differentiated in the presence of SIK inhibitors, MRT199665 and HG-9-91-01, still produced very large amounts of IL-10, but very low levels of pro-inflammatory cytokines, even after the SIKs had been reactivated by removal of the drugs. Our data highlight an integral role for SIK2 and SIK3 in innate immunity by preventing the differentiation of macrophages into a potent and stable anti-inflammatory phenotype. PMID:27920213

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

    Directory of Open Access Journals (Sweden)

    John S. Witte

    2010-10-01

    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.

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

    Science.gov (United States)

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

    2005-06-01

    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.

  17. Safety study, anti-inflammatory and antioxidant action of drug caramel with polyhexamethylene guanidine phosphate

    Directory of Open Access Journals (Sweden)

    Anton V. Kurinnyi

    2016-08-01

    Conclusions: The developed dosage form caramel and ldquo;Guamel and rdquo; for external use of the safety performance meets the requirements for such drugs. The developed dosage form caramel and ldquo;Guamel and rdquo; exhibits high anti-inflammatory and antioxidant activity, which is the force exceeds the reference value. All of this is experimental rationale for the industrial production of this dosage form caramel and ldquo;Guamel and rdquo;. [Int J Basic Clin Pharmacol 2016; 5(4.000: 1456-1461

  18. 2-hydroxy arachidonic acid: a new non-steroidal anti-inflammatory drug.

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Barkin, Robert L

    2015-01-01

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

    Directory of Open Access Journals (Sweden)

    Wawryk-Gawda Ewelina

    2014-09-01

    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.

  1. Anti-inflammatory drug incorporation into polymeric nano-hybrids for local controlled release.

    Science.gov (United States)

    Sammartino, G; Marenzi, G; Tammaro, L; Bolognese, A; Calignano, A; Costantino, U; Califano, L; Mastrangelo, F; Tetè, S; Vittoria, V

    2005-01-01

    In this paper we present the formulation, preparation and characterization of new polymeric composite materials containing a nano-hybrid to be used for the controlled molecular delivery of an anti-inflammatory molecule, Diclofenac. The nano-hybrid consists of a layer of double hydroxide of an Mg-Al hydrotalcite type, in which we replaced the chloride anions present in the host galleries with Diclofenac anions by a simple ion-exchange reaction. Different amounts of the hybrid material were incorporated in polycaprolactone and processed as films of 0.15 mm thickness. The composite materials were analyzed by X-ray diffractometry, thermogravimetry and for their mechanical properties, and showed properties even better than those for the pristine polymer. The release process of the anti-inflammatory molecules was very interesting and promising for tuneable drug delivery. It consists of two stages: a first stage, very rapid as a burst in which a small fraction of the drug is released, and of a second stage that is much slower, extending for longer and longer periods. The parameters influencing the drug release were individuated and discussed.

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

    Science.gov (United States)

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

    2003-06-13

    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.

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

    Science.gov (United States)

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

    2016-03-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Santosh Thapa

    2016-01-01

    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.

  5. Inhibitory effect of herbal remedy PERVIVO and anti-inflammatory drug sulindac on L-1 sarcoma tumor growth and tumor angiogenesis in Balb/c mice.

    Science.gov (United States)

    Skopiński, P; Bałan, B J; Kocik, J; Zdanowski, R; Lewicki, S; Niemcewicz, M; Gawrychowski, K; Skopińska-Różewska, E; Stankiewicz, W

    2013-01-01

    Anticancer activity of many herbs was observed for hundreds of years. They act as modifiers of biologic response, and their effectiveness may be increased by combining multiple herbal extracts . PERVIVO, traditional digestive herbal remedy, contains some of them, and we previously described its antiangiogenic activity. Numerous studies documented anticancer effects of nonsteroidal anti-inflammatory drugs. We were the first to show that sulindac and its metabolites inhibit angiogenesis. In the present paper the combined in vivo effect of multicomponent herbal remedy PERVIVO and nonsteroidal anti-inflammatory drug sulindac on tumor growth, tumor angiogenesis, and tumor volume in Balb/c mice was studied. These effects were checked after grafting cells collected from syngeneic sarcoma L-1 tumors into mice skin. The strongest inhibitory effect was observed in experimental groups treated with PERVIVO and sulindac together. The results of our investigation showed that combined effect of examined drugs may be the best way to get the strongest antiangiogenic and antitumor effect.

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

    Institute of Scientific and Technical Information of China (English)

    Yun Dai; Wei-Hong Wang

    2006-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Ananya Chatterjee

    2014-01-01

    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.

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

    Science.gov (United States)

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

    2014-05-15

    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.

  9. Birth outcome in women with ulcerative colitis and Crohn's disease, and pharmacoepidemiological aspects of anti-inflammatory drug therapy

    DEFF Research Database (Denmark)

    Nørgård, Bente Mertz

    2011-01-01

    of anti-inflammatory drug treatment during pregnancy, and the degree of disease activity during pregnancy. At the same time one also has to realize that the existing evidence is still limited, especially in the field of reproductive safety after therapeutic drug treatment during pregnancy and possible...

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

    Science.gov (United States)

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

    2009-11-01

    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.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    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...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    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...

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

    DEFF Research Database (Denmark)

    Brøns, Nanna; Baandrup, Louise; Dehlendorff, Christian

    2015-01-01

    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...

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

    DEFF Research Database (Denmark)

    Skriver, Charlotte; Dehlendorff, Christian; Borre, Michael

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    1999-01-01

    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...

  16. Cardiovascular disease event rates in patients with severe psoriasis treated with systemic anti-inflammatory drugs

    DEFF Research Database (Denmark)

    Ahlehoff, Ole; Skov, L; Gislason, Gunnar Hilmar

    2012-01-01

    with use of biological agents, methotrexate or other therapies, including retinoids, cyclosporine and phototherapy, in Denmark from 2007 to 2009. MAIN OUTCOME MEASURE: Death, myocardial infarction and stroke. RESULTS: A total of 2400 patients with severe psoriasis, including 693 patients treated......OBJECTIVES: Psoriasis is a chronic inflammatory disorder associated with cardiovascular morbidity and mortality. Systemic anti-inflammatory drugs, including biological agents, are widely used in the treatment of patients with moderate to severe psoriasis and may attenuate the risk of cardiovascular...... and other therapies, respectively. Age- and sex-adjusted hazard ratios (HRs) were 0.28 (95% CI 0.12-0.64) and 0.65 (95% CI 0.42-1.00) for patients treated with biological agents and methotrexate, respectively, using other therapies as the reference cohort. Corresponding HRs for a secondary composite...

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

    Energy Technology Data Exchange (ETDEWEB)

    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: ed.topp@agr.gc.ca [Agriculture and Agri-Food Canada, London, ON, Canada N5V 4T3 (Canada)

    2010-12-01

    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.

  18. Rehabilitation of muscle after injury - the role of anti-inflammatory drugs

    DEFF Research Database (Denmark)

    Mackey, Abigail; Mikkelsen, U R; Magnusson, S P

    2012-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely consumed among athletes worldwide in relation to muscle injury and soreness. This review aims to provide an overview of studies investigating their effects on skeletal muscle, in particular the repair processes in injured muscle. Muscle...... injury occurs in diverse situations and the nature of muscle injuries varies significantly, complicating extrapolations between experimental models and "real life." Classical muscle strain injuries occur at the interphase between the muscle fibers and connective tissue, most often in the myotendinuous...... junction, whereas contusion or overload injury can damage both myofibers and intramuscular connective tissue. The role of NSAIDs in muscle repair is complicated by differences in injury models used, variables evaluated, and time point(s) selected for evaluations. While the temporal pattern of the influence...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...

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

    Directory of Open Access Journals (Sweden)

    Thomas Wex

    2010-07-01

    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.

  1. Viscum album exerts anti-inflammatory effect by selectively inhibiting cytokine-induced expression of cyclooxygenase-2.

    Directory of Open Access Journals (Sweden)

    Pushpa Hegde

    Full Text Available Viscum album (VA preparations are extensively used as complementary therapy in cancer and are shown to exert anti-tumor activities which involve the cytotoxic properties, induction of apoptosis, inhibition of angiogenesis and several other immunomodulatory mechanisms. In addition to their application in cancer therapy, VA preparations have also been successfully utilized in the treatment of several inflammatory pathologies. Owing to the intricate association of inflammation and cancer and in view of the fact that several anti-tumor phytotherapeutics also exert a potent anti-inflammatory effect, we hypothesized that VA exerts an anti-inflammatory effect that is responsible for its therapeutic benefit. Since, inflammatory cytokine-induced cyclo-oxygenase-2 (COX-2 and prostaglandin E2 (PGE2 play a critical role in the pathogenesis of inflammatory diseases, we investigated the anti-inflammatory effect of VA on regulation of cyclo-oxygenase expression and PGE2 biosynthesis by using human lung adenocarcinoma cells (A549 cells as a model. A549 cells were stimulated with IL-1β and treated with VA preparation (VA Qu Spez for 18 hours. PGE2 was analysed in the culture supernatants by enzyme immunoassay. Expression of COX-2 and COX-1 proteins was analyzed by immunoblotting and the expression of COX-2 mRNA was assessed by semi-quantitative RT-PCR. We found that VA Qu Spez inhibit the secretion of IL-1β-induced PGE2 in a dose-dependent manner. Further, we also show that this inhibitory action was associated with a reduced expression of COX-2 without modulating the COX-1 expression. Together these results demonstrate a novel anti-inflammatory mechanism of action of VA preparations wherein VA exerts an anti-inflammatory effect by inhibiting cytokine-induced PGE2 via selective inhibition of COX-2.

  2. Electrocatalytic oxidation of some anti-inflammatory drugs on a nickel hydroxide-modified nickel electrode

    Energy Technology Data Exchange (ETDEWEB)

    Hajjizadeh, M. [Department of Chemistry, Faculty of Science, K. N. Toosi University of Technology, P.O. Box 16315-1618, Tehran (Iran, Islamic Republic of); Jabbari, A. [Department of Chemistry, Faculty of Science, K. N. Toosi University of Technology, P.O. Box 16315-1618, Tehran (Iran, Islamic Republic of)], E-mail: jabbari@kntu.ac.ir; Heli, H.; Moosavi-Movahedi, A.A. [Institute of Biochemistry and Biophysics, University of Tehran, Tehran (Iran, Islamic Republic of); Haghgoo, S. [Center of Quality Control of Drug, Tehran (Iran, Islamic Republic of)

    2007-12-31

    The electrocatalytic oxidation of several anti-inflammatory drugs (mefenamic acid, diclofenac and indomethacin) was investigated on a nickel hydroxide-modified nickel (NHMN) electrode in alkaline solution. This oxidation process and its kinetics were studied using cyclic voltammetry, chronoamperometry, and electrochemical impedance spectroscopy techniques. Voltammetric studies indicated that in the presence of drugs, the anodic peak current of low-valence nickel species increases, followed by a decrease in the corresponding cathodic current. This pattern indicates that drugs were oxidized on the redox mediator immobilized on the electrode surface via an electrocatalytic mechanism. A mechanism based on the electrochemical generation of Ni(III) active sites and their subsequent consumption by drugs was also investigated. The corresponding rate law under the control of charge transfer was developed and kinetic parameters were derived. In this context, the charge-transfer resistance accessible both theoretically and through impedancemetry was used as a criterion. The rate constants of the catalytic oxidation of drugs and the electron-transfer coefficients are reported. A sensitive, simple and time-saving amperometric procedure was developed for the analysis of these drugs in bulk form and for the direct assay of tablets, using the NHMN electrode.

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

    NARCIS (Netherlands)

    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.

    2010-01-01

    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

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

    Institute of Scientific and Technical Information of China (English)

    Mario Guslandi

    2006-01-01

    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. Evaluation of the analgesic and anti-inflammatory activity of fixed dose combination: Non-steroidal anti-inflammatory drugs in experimental animals

    Directory of Open Access Journals (Sweden)

    Amit Lahoti

    2014-01-01

    Conclusion: Combining paracetamol with ibuprofen enhances analgesic/anti-inflammatory activity over their individual component but potentiation of analgesic activity of diclofenac was not seen when paracetamol was added to it.

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

    Science.gov (United States)

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

    2014-01-01

    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.

  7. FORMULATION AND EVALUATION OF PROBIOTIC TABLETS CONTAINING ANTI-INFLAMMATORY DRUG

    Directory of Open Access Journals (Sweden)

    K. D. Lone* and J. A. Dhole

    2013-01-01

    Full Text Available The aim of present study was to formulate and evaluate probiotic tablets containing anti-inflammatory drug Mesalazine. Matrix tablets were prepared using Sodium alginate and Hydroxypropylmethylcellulose acetate succinate (HPMCAS as matrix forming components, with three different combinations by wet granulation method. The granules were evaluated for angle of repose, bulk density, tapped density, compressibility index and Hausners ratio. The tablets were subjected to weight variation, hardness, friability and drug content test and invitro release studies. Additionally the tablets were tested for contents of viable cell counts of probiotic lactobacilli using standard plate count (SPC method. Invitro release studies revealed that all formulations qualified both stages for release of the drug i.e. acid stage and buffer stage 1. The release profiles were affected by variable concentrations of sodium alginate when combined with HPMC-AS. The combination at 1:2 (SA2 prevented the escape of both actives more effectively than the other two formulations at all the three stages of dissolution test. A few numbers of bacterial cells were lost in acid stage as well as in the subsequent buffer stage1. However, at the end of buffer stage 2 the viable cell count for L .acidophilus, were found to be 9 × 109 CFU. The combinations of HPMCAS (HF and sodium alginate together increased acid tolerance of probiotic lactobacilli strain added in matrix tablets.

  8. Interactions Between Sirolimus and Anti-Inflammatory Drugs: Competitive Binding for Human Serum Albumin

    Science.gov (United States)

    Khodaei, Arash; Bolandnazar, Soheila; Valizadeh, Hadi; Hasani, Leila; Zakeri-Milani, Parvin

    2016-01-01

    Purpose: The aim of the present study was investigating the effects of three anti-inflammatory drugs, on Sirolimus protein biding. The binding site of Sirolimus on human serum albumin (HSA) was also determined. Methods: Six different concentrations of Sirolimus were separately exposed to HSA at pH 7.4 and 37°C. Ultrafiltration method was used for separating free drug; then free drug concentrations were measured by HPLC. Finally, Sirolimus protein binding parameters was calculated using Scatchard plots. The same processes were conducted in the presence of NSAIDs at lower concentration of albumin and different pH conditions. To characterize the binding site of Sirolimus on albumin, the free concentration of warfarin sodium and Diazepam, site I and II specific probes, bound to albumin were measured upon the addition of increasing Sirolimus concentrations. Results: Based on the obtained results presence of Diclofenac, Piroxicam and Naproxen, could significantly decrease the percentage of Sirolimus protein binding. The Binding reduction was the most in the presence of Piroxicam. Sirolimus-NSAIDs interactions were increased in higher pH values and also in lower albumin concentrations. Probe displacement study showed that Sirolimus may mainly bind to site I on albumin molecule. Conclusion: More considerations in co-administration of NSAIDs and Sirolimus is recommended. PMID:27478785

  9. Labdanolic acid methyl ester (LAME) exerts anti-inflammatory effects through inhibition of TAK-1 activation

    Energy Technology Data Exchange (ETDEWEB)

    Cuadrado, Irene [Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense, Plaza Ramón y Cajal s/n, 28040 Madrid (Spain); Cidre, Florencia; Herranz, Sandra [Unidad de Inflamación y Cáncer. Área de Biología Celular y Desarrollo. Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid (Spain); Estevez-Braun, Ana [Instituto Universitario de Bio-Orgánica “Antonio González”. Universidad de La Laguna. Avda. Astrofísico Fco. Sánchez 2. 38206. La Laguna, Tenerife (Spain); Instituto Canario de Investigaciones del Cáncer (ICIC) (Spain); Heras, Beatriz de las, E-mail: lasheras@farm.ucm.es [Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense, Plaza Ramón y Cajal s/n, 28040 Madrid (Spain); Hortelano, Sonsoles, E-mail: shortelano@isciii.es [Unidad de Inflamación y Cáncer. Área de Biología Celular y Desarrollo. Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid (Spain)

    2012-01-01

    Labdane derivatives obtained from the diterpenoid labdanediol suppressed NO and PGE{sub 2} production in LPS-stimulated RAW 264.7 macrophages. However, mechanisms involved in these inhibitory effects are not elucidated. In this study, we investigated the signaling pathways involved in the anti-inflammatory effects of labdanolic acid methyl ester (LAME) in peritoneal macrophages and examined its therapeutic effect in a mouse endotoxic shock model. LAME reduced the production of NO and PGE{sub 2} in LPS-activated macrophages. This effect involved the inhibition of NOS-2 and COX-2 gene expression, acting at the transcription level. Examination of the effects of the diterpene on NF-κB signaling showed that LAME inhibits the phosphorylation of IκBα and IκBβ, preventing their degradation and the nuclear translocation of the NF-κB p65 subunit. Moreover, inhibition of MAPK signaling was also observed. A further experiment revealed that LAME inhibited the phosphorylation of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1), an upstream signaling molecule required for IKK and mitogen-activated protein kinases (MAPKs) activation. Inflammatory cytokines such as IL-6, TNF-α and IP-10 were downregulated in the presence of this compound after stimulation with LPS. Additionally, LAME also improved survival in a mouse model of endotoxemia and reduced the circulatory levels of cytokines (IL-6, TNF-α). In conclusion, these results indicate that labdane diterpene LAME significantly attenuates the pro-inflammatory response induced by LPS both in vivo and in vitro. Highlights: ► LAME reduced the production of NO and PGE{sub 2} in LPS-activated macrophages. ► IL-6, TNF-α and IP-10 were also inhibited by LAME. ► Inhibition of TAK-1 activation is the mechanism involved in this process. ► LAME improved survival in a mouse model of endotoxemia. ► LAME reduced the circulatory levels of cytokines (IL-6, TNF-α).

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

    LENUS (Irish Health Repository)

    Kitchen, J

    2012-02-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Salim MA Bastaki

    1999-01-01

    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.

  12. Evaluation of Topical Preparations Containing Curcuma, Acacia and Lupinus Extracts as an Anti-inflammatory Drugs

    Directory of Open Access Journals (Sweden)

    M M Hamzah

    2011-06-01

    Full Text Available Summary: This work was suggested on the basis of presence of curcuminoids in curcuma and the presence of flavonoidal constituent in acacia and lupinus. The aim of this study was to study their possible anti-inflammatory effect by separately formulation of the three extracts in a suitable gel formula for topical administration and comparison of the prepared gels with a standard gel in the market (diclosal Emulgel by using the carrageenan induced paw edema model in albino rats. The extracts were subjected to phytochemical screening tests using reported methods to determine the presence of various phytoconstituents. Gel formulation was prepared containing 8% of each extract separately in gel base, namely sodium carboxy methyl cellulose (NaCMC. The pharmacological screening revealed that percent reduction of edema produced by curcuma extract was 30.0%, by acacia extract was 4%, by ethanol fraction lupinus was 18% and by chloroform fraction lupinus was 11.3%, while diclofenac sodium topical gel produced 48% reduction of edema. Industrial relevance: Medicinal plants provide a host of chemical compounds, which have been optimized on the basis of their biological activities. Chemical compounds present in medicinal plants have shown great promise in the management of various inflammatory disorders and have continued to serve as alternative and complementary therapies. The present study will help the industry to produce herbal drug effective in the treatment of inflammation with less side effect and less costly when compared to the synthetic drugs.

  13. Topical Anti-inflammatory Activity of New Hybrid Molecules of Terpenes and Synthetic Drugs.

    Science.gov (United States)

    Theoduloz, Cristina; Delporte, Carla; Valenzuela-Barra, Gabriela; Silva, Ximena; Cádiz, Solange; Bustamante, Fernanda; Pertino, Mariano Walter; Schmeda-Hirschmann, Guillermo

    2015-06-18

    The aim of the study was to assess changes in the activity of anti-inflammatory terpenes from Chilean medicinal plants after the formation of derivatives incorporating synthetic anti-inflammatory agents. Ten new hybrid molecules were synthesized combining terpenes (ferruginol (1), imbricatolic acid (2) and oleanolic acid (3)) with ibuprofen (4) or naproxen (5). The topical anti-inflammatory activity of the compounds was assessed in mice by the arachidonic acid (AA) and 12-O-tetradecanoyl phorbol 13-acetate (TPA) induced ear edema assays. Basal cytotoxicity was determined towards human lung fibroblasts, gastric epithelial cells and hepatocytes. At 1.4 µmol/mouse, a strong anti-inflammatory effect in the TPA assay was observed for oleanoyl ibuprofenate 12 (79.9%) and oleanoyl ibuprofenate methyl ester 15 (80.0%). In the AA assay, the best activity was observed for 12 at 3.2 µmol/mouse, with 56.8% reduction of inflammation, in the same range as nimesulide (48.9%). All the terpenyl-synthetic anti-inflammatory hybrids showed better effects in the TPA assay, with best activity for 6, 12 and 15. The cytotoxicity of the compounds 8 and 10 with a free COOH, was higher than that of 2. The derivatives from 3 were less toxic than the triterpene. Several of the new compounds presented better anti-inflammatory effect and lower cytotoxicity than the parent terpenes.

  14. Anti-inflammatory activities of Physalis alkekengi var. franchetii extract through the inhibition of MMP-9 and AP-1 activation.

    Science.gov (United States)

    Hong, Ju-Mi; Kwon, Ok-Kyoung; Shin, In-Sik; Song, Hyuck-Hwan; Shin, Na-Rae; Jeon, Chan-Mi; Oh, Sei-Ryang; Han, Sang-Bae; Ahn, Kyung-Seop

    2015-01-01

    Physalis alkekengi has been traditionally used for the treatment of coughs, middle ear infections, and sore throats in Korea, Europe, and China. It exhibits a variety of pharmacological activities such as anti-inflammatory, anti-oxidant, and anti-cancer effects. The anti-inflammatory effects of the P. alkekengi methanol extract (PA) and its molecular mechanisms have not yet been fully investigated. In the present study, the chromatogram of PA was established by UPLC analysis. The anti-inflammatory effects of PA were also investigated using murine microphage cell lines, RAW 264.7 cells, and a murine model of OVA induced asthma. In LPS-stimulated RAW264.7 cells, PA reduced the MMP-9 expression with decreases in the production of nitric oxide, inteleukin-6, and tumor necrosis factor-α. Furthermore, PA suppressed the phosphorylation of MAPKs, which resulted in the inhibition of AP-1 activation. These effects of PA were consistent with the results of the in vivo experiment. PA-treated mice significantly inhibited inflammatory cell counts and cytokine production in bronchoalveolar lavage fluids and airway-hyperresponsiveness in OVA-induced asthmatic mice. PA treated mice also showed a marked inhibition of inducible nitric oxide synthase and MMP-9 expression. In conclusion, our results suggest that PA may be a valuable therapeutic material in treating various inflammatory diseases, including allergic asthma.

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

    Science.gov (United States)

    Mather, L E

    1992-01-01

    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. Anti-inflammatory Diets.

    Science.gov (United States)

    Sears, Barry

    2015-01-01

    Chronic disease is driven by inflammation. This article will provide an overview on how the balance of macronutrients and omega-6 and omega-3 fatty acids in the diet can alter the expression of inflammatory genes. In particular, how the balance of the protein to glycemic load of a meal can alter the generation of insulin and glucagon and the how the balance of omega-6 and omega-3 fatty acids can effect eicosanoid formation. Clinical results on the reduction of inflammation following anti-inflammatory diets are discussed as well as the molecular targets of anti-inflammatory nutrition. To overcome silent inflammation requires an anti-inflammatory diet (with omega-3s and polyphenols, in particular those of Maqui). The most important aspect of such an anti-inflammatory diet is the stabilization of insulin and reduced intake of omega-6 fatty acids. The ultimate treatment lies in reestablishing hormonal and genetic balance to generate satiety instead of constant hunger. Anti-inflammatory nutrition, balanced 40:30:30 with caloric restriction, should be considered as a form of gene silencing technology, in particular the silencing of the genes involved in the generation of silent inflammation. To this anti-inflammatory diet foundation supplemental omega-3 fatty acids at the level of 2-3 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day should be added. Finally, a diet rich in colorful, nonstarchy vegetables would contribute adequate amounts of polyphenols to help not only to inhibit nuclear factor (NF)-κB (primary molecular target of inflammation) but also activate AMP kinase. Understanding the impact of an anti-inflammatory diet on silent inflammation can elevate the diet from simply a source of calories to being on the cutting edge of gene-silencing technology.

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

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    Huyck Matthew

    2005-01-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

    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.

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

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    T A Raskina

    2011-12-01

    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

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

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    T A Raskina

    2011-01-01

    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

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

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    Ingela Wiklund

    1999-01-01

    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.

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

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

    2014-01-21

    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.

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

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

    2017-01-01

    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

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

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

    2001-05-15

    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.

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

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    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.

    2008-01-01

    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.

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

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    Luis Mauricio T. R. Lima

    2013-03-01

    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.

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

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    N. V. Chichasova

    2016-01-01

    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.

  8. Selected mucolytic, anti-inflammatory and cardiovascular drugs change the ability of neutrophils to form extracellular traps (NETs).

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    Zawrotniak, Marcin; Kozik, Andrzej; Rapala-Kozik, Maria

    2015-01-01

    Neutrophils form the first line of host defense against infections that combat pathogens using two major mechanisms, the phagocytosis or the release of neutrophil extracellular traps (NETs). The netosis (NET formation) exerts additional, unfavorable effects on the fitness of host cells and is also involved at the sites of lung infection, increasing the mucus viscosity and in the circulatory system where it can influence the intravascular clot formation. Although molecular mechanisms underlying the netosis are still incompletely understood, a role of NADPH oxidase that activates the production of reactive oxygen species (ROS) during the initiation of NETs has been well documented. Since several commonly used drugs can affects the netosis, our current study was aimed to determine the effects of selected mucolytic, anti-inflammatory and cardiovascular drugs on NET formation, with a special emphasis on ROS production and NADPH oxidase activity. The treatment of neutrophils with N-acetylcysteine, ketoprofen and ethamsylate reduced the production of ROS by these cells in a dose-dependent manner. NET formation was also modulated by selected drugs. N-acetylcysteine inhibited the netosis but in the presence of H2O2 this neutrophil ability was restored, indicating that N-acetylcysteine may influence the NET formation by modulating ROS productivity. The administration of ethamsylate led to a significant reduction in NET formation and this effect was not restored by H2O2 or S. aureus, suggesting the unexpected additional side effects of this drug. Ketoprofen seemed to promote ROS-independent NET release, simultaneously inhibiting ROS production. The results, obtained in this study strongly suggest that the therapeutic strategies applied in many neutrophil-mediated diseases should take into account the NET-associated effects.

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

    Science.gov (United States)

    Gonzalez-Rey, Maria; Bebianno, Maria João

    2014-03-01

    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

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

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

    2007-01-01

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

    Science.gov (United States)

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

    1999-10-01

    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

  12. Neuroinflammation in the pathophysiology of Parkinson’s disease and therapeutic evidence of anti-inflammatory drugs

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    Taysa Bervian Bassani

    2015-07-01

    Full Text Available Parkinson’s disease (PD is the second most common neurodegenerative disease affecting approximately 1.6% of the population over 60 years old. The cardinal motor symptoms are the result of progressive degeneration of substantia nigra pars compacta dopaminergic neurons which are involved in the fine motor control. Currently, there is no cure for this pathology and the cause of the neurodegeneration remains unknown. Several studies suggest the involvement of neuroinflammation in the pathophysiology of PD as well as a protective effect of anti-inflammatory drugs both in animal models and epidemiological studies, although there are controversial reports. In this review, we address evidences of involvement of inflammatory process and possible therapeutic usefulness of anti-inflammatory drugs in PD.

  13. Novel anti-inflammatory chalcone derivatives inhibit the induction of nitric oxide synthase and cyclooxygenase-2 in mouse peritoneal macrophages.

    Science.gov (United States)

    Herencia, F; Ferrándiz, M L; Ubeda, A; Guillén, I; Dominguez, J N; Charris, J E; Lobo, G M; Alcaraz, M J

    1999-06-18

    In a previous work, we tested a series of chalcone derivatives as possible anti-inflammatory compounds. We now investigate the effects of three of those compounds, CHI, CH8 and CH12, on nitric oxide and prostanoid generation in mouse peritoneal macrophages stimulated with lipopolysaccharide and in the mouse air pouch injected with zymosan, where they showed a dose-dependent inhibition with inhibitory concentration 50% values in the microM range. This effect was not the consequence of a direct inhibitory action on enzyme activities. Our results demonstrated that chalcone derivatives inhibited de novo inducible nitric oxide synthase and cyclooxygenase-2 synthesis, being a novel therapeutic approach for inflammatory diseases.

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

    OpenAIRE

    Lionberger, David R; Brennan, Michael J.

    2010-01-01

    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...

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

    Institute of Scientific and Technical Information of China (English)

    George V. Papatheodoridis; Athanasios J. Archimandritis

    2005-01-01

    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.

  16. Effect of selected anti-inflammatory drugs on the lethal actions of Leiurus quinquestriatus venom

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    N. A. Abdoon

    2006-01-01

    Full Text Available The cumulative actions of scorpion neurotoxins are complex and may be traced to activation of different ion channels with subsequent release of various transmitters and modulators including inflammatory mediators. This could lead to various pathological manifestations such as acute respiratory distress syndrome (ARDS, systemic inflammatory response syndrome (SIRS, and multiple organ failure (MOF. Several approaches have been advocated to treat the multitude of scorpion-venom-elicited pathological changes. However, few have tried to combat the venom-induced effects on the inflammatory process, which manifest as ARDS, SIDS and MOF. Thus, the aim of this study was to determine the capability of inhibitors of different steps of the inflammatory sequence of events in scorpion envenomation to ameliorate the detrimental action of the venom and prolong survival of mice injected with Leiurus quinquestriatus quinquestriatus (LQQ venom. Animals were divided into groups (n = 10 and given montelukast (10 or 20 mg.kg-1, orally, hydrocortisone (5 or 10 mg.kg-1, intravenously or indomethacin (10 or 20 mg kg-1, intravenously. Then, all animals were subcutaneously injected with either 0.25 or 0.3 mg.kg-1 LQQ venom. Signs and symptoms of envenomation were recorded and survival percentages after 24 hours as well as survival time were determined in each group. To analyze data, we utilized Covariance Wilcoxon survival statistics and survival distribution curves. In general, when compared to venom alone, administration of montelukast (p<0.001, hydrocortisone (p<0.05 and indomethacin (p<0.05 prolonged survival time and increased the percentage of surviving animals per group, with montelukast exhibiting the greatest protecting power. Thus, anti-inflammatory drugs may play an important role in protection against the lethal effects of scorpion venoms.

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

    Directory of Open Access Journals (Sweden)

    R Lad

    1999-01-01

    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.

  18. 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

    OpenAIRE

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

    2007-01-01

    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...

  19. Non-corticosteroid anti-inflammatory drugs in asthma - Clinical pharmacology and recommendations for use

    NARCIS (Netherlands)

    deJong, JW; Postma, DS

    1997-01-01

    Asthma is a chronic inflammatory disease of the airways, As airways inflammation plays a principal role in the pathogenesis of asthma, even in patients with mild disease, current recommendations give anti-inflammatory therapy a central position in the treatment of asthma, Although inhaled corticoste

  20. Flurbiprofen-antioxidant mutual prodrugs as safer nonsteroidal anti-inflammatory drugs: synthesis, pharmacological investigation, and computational molecular modeling.

    Science.gov (United States)

    Ashraf, Zaman; Alamgeer; Kanwal, Munazza; Hassan, Mubashir; Abdullah, Sahar; Waheed, Mamuna; Ahsan, Haseeb; Kim, Song Ja

    2016-01-01

    Flurbiprofen-antioxidant mutual prodrugs were synthesized to reduce the gastrointestinal (GI) effects associated with flurbiprofen. For reducing the GI toxicity, the free carboxylic group (-COOH) was temporarily masked by esterification with phenolic -OH of natural antioxidants vanillin, thymol, umbelliferone, and sesamol. The in vitro hydrolysis of synthesized prodrugs showed that they were stable in buffer solution at pH 1.2, indicating their stability in the stomach. The synthesized prodrugs undergo significant hydrolysis in 80% human plasma and thus release free flurbiprofen. The minimum reversion was observed at pH 1.2, suggesting that prodrugs are less irritating to the stomach than flurbiprofen. The anti-inflammatory, analgesic, antipyretic, and ulcerogenic activities of prodrugs were evaluated. All the synthesized prodrugs significantly (P<0.001) reduced the inflammation against carrageenan and egg albumin-induced paw edema at 4 hours of study. The reduction in the size of the inflamed paw showed that most of the compounds inhibited the later phase of inflammation. The prodrug 2-oxo-2H-chromen-7-yl-2-(2-fluorobiphenyl-4-yl)propanoate (4b) showed significant reduction in paw licking with percentage inhibition of 58%. It also exhibited higher analgesic activity, reducing the number of writhes with a percentage of 75%, whereas flurbiprofen showed 69% inhibition. Antipyretic activity was investigated using brewer's yeast-induced pyrexia model, and significant (P<0.001) reduction in rectal temperature was shown by all prodrugs at all times of assessment. The results of ulcerogenic activity showed that all prodrugs produced less GI irritation than flurbiprofen. Molecular docking and simulation studies were carried out with cyclooxygenase (COX-1 and COX-2) proteins, and it was observed that our prodrugs have more potential to selectively bind to COX-2 than to COX-1. It is concluded that the synthesized prodrugs have promising pharmacological activities with

  1. Flurbiprofen–antioxidant mutual prodrugs as safer nonsteroidal anti-inflammatory drugs: synthesis, pharmacological investigation, and computational molecular modeling

    Science.gov (United States)

    Ashraf, Zaman; Alamgeer; Kanwal, Munazza; Hassan, Mubashir; Abdullah, Sahar; Waheed, Mamuna; Ahsan, Haseeb; Kim, Song Ja

    2016-01-01

    Flurbiprofen–antioxidant mutual prodrugs were synthesized to reduce the gastrointestinal (GI) effects associated with flurbiprofen. For reducing the GI toxicity, the free carboxylic group (–COOH) was temporarily masked by esterification with phenolic –OH of natural antioxidants vanillin, thymol, umbelliferone, and sesamol. The in vitro hydrolysis of synthesized prodrugs showed that they were stable in buffer solution at pH 1.2, indicating their stability in the stomach. The synthesized prodrugs undergo significant hydrolysis in 80% human plasma and thus release free flurbiprofen. The minimum reversion was observed at pH 1.2, suggesting that prodrugs are less irritating to the stomach than flurbiprofen. The anti-inflammatory, analgesic, antipyretic, and ulcerogenic activities of prodrugs were evaluated. All the synthesized prodrugs significantly (P<0.001) reduced the inflammation against carrageenan and egg albumin-induced paw edema at 4 hours of study. The reduction in the size of the inflamed paw showed that most of the compounds inhibited the later phase of inflammation. The prodrug 2-oxo-2H-chromen-7-yl-2-(2-fluorobiphenyl-4-yl)propanoate (4b) showed significant reduction in paw licking with percentage inhibition of 58%. It also exhibited higher analgesic activity, reducing the number of writhes with a percentage of 75%, whereas flurbiprofen showed 69% inhibition. Antipyretic activity was investigated using brewer’s yeast-induced pyrexia model, and significant (P<0.001) reduction in rectal temperature was shown by all prodrugs at all times of assessment. The results of ulcerogenic activity showed that all prodrugs produced less GI irritation than flurbiprofen. Molecular docking and simulation studies were carried out with cyclooxygenase (COX-1 and COX-2) proteins, and it was observed that our prodrugs have more potential to selectively bind to COX-2 than to COX-1. It is concluded that the synthesized prodrugs have promising pharmacological activities

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

    Science.gov (United States)

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

    2015-03-29

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

    Science.gov (United States)

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

    2012-05-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1983-09-01

    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.

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

    Science.gov (United States)

    Miller, G Klaud

    2016-03-01

    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.

  6. 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

    Directory of Open Access Journals (Sweden)

    S. Chopra

    2007-10-01

    Full Text Available 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 and alkaline phosphatase as compared to the control in the duodenum, jejunum and ileum. The uptake of D-glucose and L-histidine in the everted intestinal sac was found to be decreased. Also the decease of glucose and histidine uptake was found to be dependent on the substrate concentration, temperature and the time interval of incubation. The physical state and composition of brush border membrane was found to be altered as evident in the FTIR spectrum, by appearance of new peaks while disappearance of certain peaks occurred which were characteristics of the control membrane. The changes in wave number as well as peaks height were also noticed. Alterations in protein profile of the membrane were demonstrated using SDS-PAGE analysis where disappearance of few bands and change in the relative intensities of the bands were noticed and correlated with the alterations that have taken place at the molecular level. Histological studies have depicted a marked decrease in the absorption surface area such as the villi height of the intestinal segment. In addition, crypt number also deceased in the treated animals, an indication that such changes also correlate well with the changes in the transport of the end product nutrients.Se diseñó este estudio para investigar los efectos adversos gastrointestinales de los inhibidores de la ciclooxigenasa (COX con selectividad variable, denominados fármacos antiinflamatorios no esteroideos (AINE, inhibidores no selectivos de la

  7. Interactions between inflammation and lipid metabolism: relevance for efficacy of anti-inflammatory drugs in the treatment of atherosclerosis.

    Science.gov (United States)

    van Diepen, Janna A; Berbée, Jimmy F P; Havekes, Louis M; Rensen, Patrick C N

    2013-06-01

    Dyslipidemia and inflammation are well known causal risk factors the development of atherosclerosis. The interplay between lipid metabolism and inflammation at multiple levels in metabolic active tissues may exacerbate the development of atherosclerosis, and will be discussed in this review. Cholesterol, fatty acids and modified lipids can directly activate inflammatory pathways. In addition, circulating (modified) lipoproteins modulate the activity of leukocytes. Vice versa, proinflammatory signaling (i.e. cytokines) in pre-clinical models directly affects lipid metabolism. Whereas the main lipid-lowering drugs all have potent anti-inflammatory actions, the lipid-modulating actions of anti-inflammatory agents appear to be less straightforward. The latter have mainly been evaluated in pre-clinical models and in patients with chronic inflammatory diseases, which will be discussed. The clinical trials that are currently conducted to evaluate the efficacy of anti-inflammatory agents in the treatment of cardiovascular diseases may additionally reveal potential (beneficial) effects of these therapeutics on lipid metabolism in the general population at risk for CVD.

  8. SCAVENGING ACTIVITY, ANTI-INFLAMMATORY AND DIABETES RELATED ENZYME INHIBITION PROPERTIES OF ETHANOL LEAVES EXTRACT OF PHOENYX DACTYLIFERA

    Directory of Open Access Journals (Sweden)

    S. E. Laouini

    2015-07-01

    Full Text Available In this study we investigate the antioxidant, anti-inflammatory, and antidiabetic activities of ethanolic leaf extracts of three selected varieties of Phoenyx dactylifera L. namely: “Ghars”, “Deglet Nour” and “Hamraya”. The assessment of the antioxidant potential of crude leaf extracts, using superoxide anions inhibition, radical scavenging activity "DPPH" and total antioxidant activity essays, was carried out. Furthermore, the anti-inflammatory properties of the extracts were determined by measuring the inhibition of nitric oxide (NO production. Moreover, the antidiabetic effect was evaluated by inhibition of α-amylase and α-glucosidase enzymes. The total phenolic content measured by Folin-ciocalteu method. The raw leaf extracts of the selected varieties were found to contain a high content of total phenolic content (342.45 mg GAE/ gDW for GE and therefore exhibited a higher antioxidant activity and inhibitory effect of radicals scavenging activity against DPPH and superoxide anion (IC50=7.44 μg/mL and 39.11 μg/mL respectively.

  9. SCAVENGING ACTIVITY, ANTI-INFLAMMATORY AND DIABETES RELATED ENZYME INHIBITION PROPERTIES OF ETHANOL LEAVES EXTRACT OF PHOENYX DACTYLIFERA

    Directory of Open Access Journals (Sweden)

    S. E. Laouini

    2013-12-01

    Full Text Available In this study we investigate the antioxidant, anti-inflammatory, and antidiabetic activities of ethanolic leaf extracts of three selected varieties of Phoenyx dactylifera L. namely: “Ghars”, “Deglet Nour” and “Hamraya”. The assessment of the antioxidant potential of crude leaf extracts, using superoxide anions inhibition, radical scavenging activity "DPPH" and total antioxidant activity essays, was carried out. Furthermore, the anti-inflammatory properties of the extracts were determined by measuring the inhibition of nitric oxide (NO production. Moreover, the antidiabetic effect was evaluated by inhibition of α-amylase and α-glucosidase enzymes. The total phenolic content measured by Folin-ciocalteu method. The raw leaf extracts of the selected varieties were found to contain a high content of total phenolic content (342.45 mg GAE/ gDW for GE and therefore exhibited a higher antioxidant activity and inhibitory effect of radicals scavenging activity against DPPH and superoxide anion (IC50=7.44 μg/mL and 39.11 μg/mL respectively.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Effects of Catechol O-Methyl Transferase Inhibition on Anti-Inflammatory Activity of Luteolin Metabolites.

    Science.gov (United States)

    Ha, Sang Keun; Lee, Jin-Ah; Cho, Eun Jung; Choi, Inwook

    2017-02-01

    Although luteolin is known to have potent anti-inflammatory activities, much less information has been provided on such activities of its hepatic metabolites. Luteolin was subjected to hepatic metabolism in HepG2 cells either without or with catechol O-methyl transferase (COMT) inhibitor. To identify hepatic metabolites of luteolin without (luteolin metabolites, LMs) or with COMT inhibitor (LMs+CI), metabolites were treated by β-glucuronidase and sulfatase, and found that they were composed of glucuronide and sulfate conjugates of diosmetin in LMs or these conjugates of luteolin in LMs+CI. LMs and LMs+CI were examined for their anti-inflammatory activities on LPS stimulated Raw 264.7 cells. Expression of iNOS and production of nitric oxide and pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 were suppressed more effectively by the treatment with LMs+CI than LMs. Our data provide a new insight on possible improvement in functional properties of luteolin on target cells by modifying their metabolic pathway in hepatocytes.

  12. Licorice: a possible anti-inflammatory and anti-ulcer drug.

    Science.gov (United States)

    Aly, Adel M; Al-Alousi, Laith; Salem, Hatem A

    2005-09-20

    The purpose of this investigation was to study the anti-inflammatory activities of both glycerrhitinic acid (GA) and the aqueous licorice extract (ALE) in comparison with diclofenac sodium (DS) (10 mg/kg), using the carrageenan-induced paw edema model in male albino rats. In addition, the anti-ulcer activities of ALE, famotidine (FT), and a combination of ALE and FT using indomethacin-induced ulceration technique in rat stomach were investigated. Conventional DS tablets containing GA, as well as DS chewable tablets containing either GA or ALE with different tastes were prepared. Also, rapidly disintegrating FT tablets were prepared using direct compression and camphor sublimation methods. ALE or GA produced significant anti-inflammatory activity similar to DS, and when taken concomitantly, there is no possible antagonism. The anti-ulcer activity of licorice was found to be similar to that of FT in indomethacin-induced ulceration technique in rat stomach. Combination therapy of both FT and licorice showed higher anti-ulcer activity than either of them alone. Generally, tablets containing the crosslinked sodium carboxymethyl cellulose (AcDisol) showed more rapidly disintegrating effect than those including Sodium starch glycolate (Primojel). The oral disintegration was very rapid for all the tested formulations. Also, the amount of FT absorbed from the oral cavity was nearly 9 from 10 mg theoretically present in each formula. It could be concluded that both GA and ALE have anti-inflammatory activity comparable with DS. It may be recommended to add ALE to either FT or diclofinac for more effective anti-inflammatory or anti-ulcer formulations, respectively.

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

    Directory of Open Access Journals (Sweden)

    Asero Riccardo

    2007-03-01

    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.

  14. Inhibitory Effect of Herbal Remedy PERVIVO and Anti-Inflammatory Drug Sulindac on L-1 Sarcoma Tumor Growth and Tumor Angiogenesis in Balb/c Mice

    Directory of Open Access Journals (Sweden)

    P. Skopiński

    2013-01-01

    Full Text Available Anticancer activity of many herbs was observed for hundreds of years. They act as modifiers of biologic response, and their effectiveness may be increased by combining multiple herbal extracts . PERVIVO, traditional digestive herbal remedy, contains some of them, and we previously described its antiangiogenic activity. Numerous studies documented anticancer effects of nonsteroidal anti-inflammatory drugs. We were the first to show that sulindac and its metabolites inhibit angiogenesis. In the present paper the combined in vivo effect of multicomponent herbal remedy PERVIVO and nonsteroidal anti-inflammatory drug sulindac on tumor growth, tumor angiogenesis, and tumor volume in Balb/c mice was studied. These effects were checked after grafting cells collected from syngeneic sarcoma L-1 tumors into mice skin. The strongest inhibitory effect was observed in experimental groups treated with PERVIVO and sulindac together. The results of our investigation showed that combined effect of examined drugs may be the best way to get the strongest antiangiogenic and antitumor effect.

  15. Influence of He-Ne laser therapy on the dynamics of wound healing in mice treated with anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    W.L.S. Gonçalves

    2007-06-01

    Full Text Available We determined the effects of helium-neon (He-Ne laser irradiation on wound healing dynamics in mice treated with steroidal and non-steroidal anti-inflammatory agents. Male albino mice, 28-32 g, were randomized into 6 groups of 6 animals each: control (C, He-Ne laser (L, dexamethasone (D, D + L, celecoxib (X, and X + L. D and X were injected im at doses of 5 and 22 mg/kg, respectively, 24 h before the experiment. A 1-cm long surgical wound was made with a scalpel on the abdomens of the mice. Animals from groups L, D + L and X + L were exposed to 4 J (cm²-1 day-1 of He-Ne laser for 12 s and were sacrificed on days 1, 2, or 3 after the procedure, when skin samples were taken for histological examination. A significant increase of collagen synthesis was observed in group L compared with C (168 ± 20 vs 63 ± 8 mm². The basal cellularity values on day 1 were: C = 763 ± 47, L = 1116 ± 85, D = 376 ± 24, D + L = 698 ± 31, X = 453 ± 29, X + L = 639 ± 32 U/mm². These data show that application of L increases while D and X decrease the inflammatory cellularity compared with C. They also show that L restores the diminished cellularity induced by the anti-inflammatory drugs. We suggest that He-Ne laser promotes collagen formation and restores the baseline cellularity after pharmacological inhibition, indicating new perspectives for laser therapy aiming to increase the healing process when anti-inflammatory drugs are used.

  16. A Novel Anti-Inflammatory Role for Ginkgolide B in Asthma via Inhibition of the ERK/MAPK Signaling Pathway

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    Xiao Chu

    2011-09-01

    Full Text Available Ginkgolide B is an anti-inflammatory extract of Ginkgo biloba and has been used therapeutically. It is a known inhibitor of platelet activating factor (PAF, which is important in the pathogenesis of asthma. Here, a non-infectious mouse model of asthma is used to evaluate the anti-inflammatory capacity of ginkgolide B (GKB and characterize the interaction of GKB with the mitogen activated protein kinase (MAPK pathway. BALB/c mice that were sensitized and challenged to ovalbumin (OVA were treated with GKB (40 mg/kg one hour before they were challenged with OVA. Our study demonstrated that GKB may effectively inhibit the increase of T-helper 2 cytokines, such as interleukin (IL-5 and IL-13 in bronchoalveolar lavage fluid (BALF. Furthermore, the eosinophil count in BALF significantly decreased after treatment of GKB when compared with the OVA-challenged group. Histological studies demonstrated that GKB substantially inhibited OVA-induced eosinophilia in lung tissue and mucus hyper-secretion by goblet cells in the airway. These results suggest that ginkgolide B may be useful for the treatment of asthma and its efficacy is related to suppression of extracellular regulating kinase/MAPK pathway.

  17. IFN-τ Displays Anti-Inflammatory Effects on Staphylococcus aureus Endometritis via Inhibiting the Activation of the NF-κB and MAPK Pathways in Mice

    Science.gov (United States)

    Zhang, Zhenbiao; Guo, Yingfang; Liu, Yuzhu; Li, Chengye

    2017-01-01

    The aim of the present study was to determine the anti-inflammatory effect of IFN-τ on endometritis using a mouse model of S. aureus-induced endometritis and to elucidate the mechanism of action underlying these effects. In the present study, the effect of IFN-τ on S. aureus growth was monitored by turbidimeter at 600 nm. IFN-τ did not affect S. aureus growth. The histopathological changes indicated that IFN-τ had a protective effect on uterus tissues with S. aureus infection. The ELISA and qPCR results showed the production of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 was decreased with IFN-τ treatment. In contrast, the level of the anti-inflammatory cytokine IL-10 was increased. We further studied the signaling pathway associated with these observations, and the qPCR results showed that the expression of TLR2 was repressed by IFN-τ. Furthermore, the western blotting results showed the phosphorylation of IκB, NF-κB p65, and MAPKs (p38, JNK, and ERK) was inhibited by IFN-τ treatment. The results suggested that IFN-τ may be a potential drug for the treatment of uterine infection due to S. aureus or other infectious inflammatory diseases.

  18. Piperine Plays an Anti-Inflammatory Role in Staphylococcus aureus Endometritis by Inhibiting Activation of NF-κB and MAPK Pathways in Mice

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    Wen-jun Zhai

    2016-01-01

    Full Text Available Endometritis is commonly caused by pathogenic microorganisms, including Staphylococcus aureus (S. aureus. Piperine, which is a natural medicine, has shown a variety of biological activities. To explore the effect and mechanism of piperine on S. aureus endometritis, a mouse model of S. aureus endometritis was successfully established in the present study. Histopathological changes were observed with H&E staining, cytokines were analyzed by ELISA, mRNA was analyzed by qPCR, and proteins were detected by western blot. The results showed that piperine could significantly alleviate inflammatory injury in S. aureus endometritis. The qPCR and ELISA results showed that piperine effectively reduced the S. aureus-induced overexpression of TNF-α, IL-1β, and IL-6 but increased the expression of IL-10. The S. aureus-induced inflammation was related to TLR-2 and TLR-4 because the results showed that their expression was increased in S. aureus infection but then decreased with piperine treatment. To further confirm that piperine caused an anti-inflammatory response by targeting NF-κB and MAPKs, the expression of I-κB, p65, p38, ERK, and JNK was measured. The phosphorylation of I-κB, p65, p38, ERK, and JNK was inhibited by piperine in a dose-dependent manner. All of the results indicated that piperine may be a potential anti-inflammatory drug both in endometritis and in other S. aureus-induced diseases.

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

    Science.gov (United States)

    Confino-Cohen, Ronit; Goldberg, Arnon

    2003-01-01

    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.

  20. Effects of Intermediates between Vitamins K2 and K3 on Mammalian DNA Polymerase Inhibition and Anti-Inflammatory Activity

    Directory of Open Access Journals (Sweden)

    Takeshi Azuma

    2011-02-01

    Full Text Available Previously, we reported that vitamin K3 (VK3, but not VK1 or VK2 (=MK-4, inhibits the activity of human DNA polymerase γ (pol γ. In this study, we chemically synthesized three intermediate compounds between VK2 and VK3, namely MK-3, MK-2 and MK-1, and investigated the inhibitory effects of all five compounds on the activity of mammalian pols. Among these compounds, MK-2 was the strongest inhibitor of mammalian pols α, κ and λ, which belong to the B, Y and X families of pols, respectively; whereas VK3 was the strongest inhibitor of human pol γ, an A-family pol. MK-2 potently inhibited the activity of all animal species of pol tested, and its inhibitory effect on pol λ activity was the strongest with an IC50 value of 24.6 μM. However, MK-2 did not affect the activity of plant or prokaryotic pols, or that of other DNA metabolic enzymes such as primase of pol α, RNA polymerase, polynucleotide kinase or deoxyribonuclease I. Because we previously found a positive relationship between pol λ inhibition and anti-inflammatory action, we examined whether these compounds could inhibit inflammatory responses. Among the five compounds tested, MK-2 caused the greatest reduction in 12-O-tetradecanoylphorbol-13-acetate (TPA-induced acute inflammation in mouse ear. In addition, in a cell culture system using mouse macrophages, MK-2 displayed the strongest suppression of the production of tumor necrosis factor (TNF-α induced by lipopolysaccharide (LPS. Moreover, MK-2 was found to inhibit the action of nuclear factor (NF-κB. In an in vivo mouse model of LPS-evoked acute inflammation, intraperitoneal injection of MK-2 in mice led to suppression of TNF-α production in serum. In conclusion, this study has identified VK2 and VK3 intermediates, such as MK-2, that are promising anti-inflammatory candidates.

  1. Anti-inflammatory activity of Chios mastic gum is associated with inhibition of TNF-alpha induced oxidative stress

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    Lerakis Stamatios

    2011-06-01

    Full Text Available Abstract Background Gum of Chios mastic (Pistacia lentiscus var. chia is a natural antimicrobial agent that has found extensive use in pharmaceutical products and as a nutritional supplement. The molecular mechanisms of its anti-inflammatory activity, however, are not clear. In this work, the potential role of antioxidant activity of Chios mastic gum has been evaluated. Methods Scavenging of superoxide radical was investigated by electron spin resonance and spin trapping technique using EMPO spin trap in xanthine oxidase system. Superoxide production in endothelial and smooth muscle cells stimulated with TNF-α or angiotensin II and treated with vehicle (DMSO or mastic gum (0.1-10 μg/ml was measured by DHE and HPLC. Cellular H2O2 was measured by Amplex Red. Inhibition of protein kinase C (PKC with mastic gum was determined by the decrease of purified PKC activity, by inhibition of PKC activity in cellular homogenate and by attenuation of superoxide production in cells treated with PKC activator phorbol 12-myristate 13-acetate (PMA. Results Spin trapping study did not show significant scavenging of superoxide by mastic gum itself. However, mastic gum inhibited cellular production of superoxide and H2O2 in dose dependent manner in TNF-α treated rat aortic smooth muscle cells but did not affect unstimulated cells. TNF-α significantly increased the cellular superoxide production by NADPH oxidase, while mastic gum completely abolished this stimulation. Mastic gum inhibited the activity of purified PKC, decreased PKC activity in cell homogenate, and attenuated superoxide production in cells stimulated with PKC activator PMA and PKC-dependent angiotensin II in endothelial cells. Conclusion We suggest that mastic gum inhibits PKC which attenuates production of superoxide and H2O2 by NADPH oxidases. This antioxidant property may have direct implication to the anti-inflammatory activity of the Chios mastic gum.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...

  3. Copper(II) complexes of a nonsteroidal anti-inflammatory drug niflumic acid. Synthesis, crystal structure of tetrakis-mu-(2-[3-(trifluoromethyl) phenyl]aminonicotinato)bis(dimethylsulfoxide)-dicopper(II) complex at 190 K. Anti-inflammatory properties.

    Science.gov (United States)

    Greenaway, F T; Riviere, E; Girerd, J J; Labouze, X; Morgant, G; Viossat, B; Daran, J C; Roch Arveiller, M; Dung, N H

    1999-07-30

    The synthesis and characterization of three complexes with a potent nonsteroidal anti-inflammatory drug niflumic acid {2-[3-(trifluoromethyl)phenyl]aminonicotinic acid} with formula [Cu(niflumato)2L] (L = H2O, DMSO = dimethylsulfoxide, DMF = N,N-dimethylformamide) were investigated. The crystal and molecular structure of the {Cu(niflumato)2(DMSO)}2 was reported. Crystallographic data are as follows: monoclinic system, space group P2(1)/n, Z = 2, a = 11.1318(8), b = 17.513(2), c = 15.336(1) A, beta = 103.316(8) degrees, V = 2909.4(4) A3. The structure was refined to R = 0.030 and wR = 0.037 for 3702 reflections with I > sigma (I). It consists of centrosymmetric binuclear units with the Cu-Cui (symmetry code i: 1-x, -y, 1-z) distance between two centrosymmetrically related ions of 2.6272(5) A. Each Cu(II) ion in [Cu2(DMSO)2(mu-niflumato)4] is coordinated to an apical dimethylsulfoxide O atom on the one hand and to the equatorial carbonyl and carboxylic O atoms of two crystallographically independent niflumate moieties and their centrosymmetric counterparts on the other hand. In spite of the low-temperature (190 K) crystal measurements, one L-CF3 grouping exhibits some disorder. The biological activities of these complexes were compared to that of niflumic acid. Niflumic acid and its various copper complexes significantly inhibited polymorphonuclear leukocyte (PMNL) oxidative metabolism, as assessed by chemiluminescence and O2- generation measurement. This effect was dose-dependent. All copper complexes exerted a similar inhibiting effect which was always significantly higher than that exerted by the parent drug.

  4. Exacerbation of nonsteroidal anti-inflammatory drug-induced small intestinal lesions by antisecretory drugs in rats: the role of intestinal motility.

    Science.gov (United States)

    Satoh, Hiroshi; Amagase, Kikuko; Takeuchi, Koji

    2012-11-01

    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.

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

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    Chalelgn Kassaw

    2012-01-01

    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.

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

    Science.gov (United States)

    Paul, Mithun; Dastidar, Parthasarathi

    2016-01-18

    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. Flurbiprofen–antioxidant mutual prodrugs as safer nonsteroidal anti-inflammatory drugs: synthesis, pharmacological investigation, and computational molecular modeling

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    Ashraf Z

    2016-07-01

    Full Text Available Zaman Ashraf,1,2 Alamgeer,3 Munazza Kanwal,1 Mubashir Hassan,2 Sahar Abdullah,3 Mamuna Waheed,3 Haseeb Ahsan,3 Song Ja Kim2 1Department of Chemistry, Allama Iqbal Open University, Islamabad, Pakistan; 2Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongju, Republic of Korea; 3Department of Pharmacology, Faculty of Pharmacy, University of Sargodha, Sargodha, Pakistan Abstract: Flurbiprofen–antioxidant mutual prodrugs were synthesized to reduce the gastrointestinal (GI effects associated with flurbiprofen. For reducing the GI toxicity, the free carboxylic group (–COOH was temporarily masked by esterification with phenolic –OH of natural antioxidants vanillin, thymol, umbelliferone, and sesamol. The in vitro hydrolysis of synthesized prodrugs showed that they were stable in buffer solution at pH 1.2, indicating their stability in the stomach. The synthesized prodrugs undergo significant hydrolysis in 80% human plasma and thus release free flurbiprofen. The minimum reversion was observed at pH 1.2, ­suggesting that prodrugs are less irritating to the stomach than flurbiprofen. The anti-inflammatory, analgesic, antipyretic, and ulcerogenic activities of prodrugs were evaluated. All the synthesized prodrugs significantly (P<0.001 reduced the inflammation against carrageenan and egg albumin-induced paw edema at 4 hours of study. The reduction in the size of the inflamed paw showed that most of the compounds inhibited the later phase of inflammation. The prodrug 2-oxo-2H-chromen-7-yl-2-(2-fluorobiphenyl-4-ylpropanoate (4b showed significant reduction in paw licking with percentage inhibition of 58%. It also exhibited higher analgesic activity, reducing the number of writhes with a percentage of 75%, whereas flurbiprofen showed 69% inhibition. Antipyretic activity was investigated using brewer’s yeast-induced pyrexia model, and significant (P<0.001 reduction in rectal temperature was shown by all

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

    Science.gov (United States)

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

    2013-01-01

    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.

  9. Oleanonic acid, a 3-oxotriterpene from Pistacia, inhibits leukotriene synthesis and has anti-inflammatory activity.

    Science.gov (United States)

    Giner-Larza, E M; Máñez, S; Recio, M C; Giner, R M; Prieto, J M; Cerdá-Nicolás, M; Ríos, J L

    2001-09-28

    One of the best known bioactive triterpenoids is oleanolic acid, a widespread 3-hydroxy-17-carboxy oleanane-type compound. In order to determine whether further oxidation of carbon 3 affects anti-inflammatory activity in mice, different tests were carried out on oleanolic acid and its 3-oxo-analogue oleanonic acid, which was obtained from Pistacia terebinthus galls. The last one showed activity on the ear oedema induced by 12-deoxyphorbol-13-phenylacetate (DPP), the dermatitis induced by multiple applications of 12-O-tetradecanoyl-13-acetate (TPA) and the paw oedemas induced by bradykinin and phospholipase A2. The production of leukotriene B4 from rat peritoneal leukocytes was reduced by oleanonic acid with an IC50 of 17 microM. Negligible differences were observed in the response of both triterpenes to DPP, bradykinin, and phospholipase A2, while oleanonic acid was more active on the dermatitis by TPA and on the in vitro leukotriene formation. In conclusion, the presence of a ketone at C-3 implies an increase in the inhibitory effects on models related to 5-lipoxygenase activity and on associated in vivo inflammatory processes.

  10. LPS-induced lung inflammation in marmoset monkeys - an acute model for anti-inflammatory drug testing.

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    Sophie Seehase

    Full Text Available Increasing incidence and substantial morbidity and mortality of respiratory diseases requires the development of new human-specific anti-inflammatory and disease-modifying therapeutics. Therefore, new predictive animal models that closely reflect human lung pathology are needed. In the current study, a tiered acute lipopolysaccharide (LPS-induced inflammation model was established in marmoset monkeys (Callithrix jacchus to reflect crucial features of inflammatory lung diseases. Firstly, in an ex vivo approach marmoset and, for the purposes of comparison, human precision-cut lung slices (PCLS were stimulated with LPS in the presence or absence of the phosphodiesterase-4 (PDE4 inhibitor roflumilast. Pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α and macrophage inflammatory protein-1 beta (MIP-1β were measured. The corticosteroid dexamethasone was used as treatment control. Secondly, in an in vivo approach marmosets were pre-treated with roflumilast or dexamethasone and unilaterally challenged with LPS. Ipsilateral bronchoalveolar lavage (BAL was conducted 18 hours after LPS challenge. BAL fluid was processed and analyzed for neutrophils, TNF-α, and MIP-1β. TNF-α release in marmoset PCLS correlated significantly with human PCLS. Roflumilast treatment significantly reduced TNF-α secretion ex vivo in both species, with comparable half maximal inhibitory concentration (IC(50. LPS instillation into marmoset lungs caused a profound inflammation as shown by neutrophilic influx and increased TNF-α and MIP-1β levels in BAL fluid. This inflammatory response was significantly suppressed by roflumilast and dexamethasone. The close similarity of marmoset and human lungs regarding LPS-induced inflammation and the significant anti-inflammatory effect of approved pharmaceuticals assess the suitability of marmoset monkeys to serve as a promising model for studying anti-inflammatory drugs.

  11. COMPARATIVE STUDY OF ANTI-INFLAMMATORY ACTIVITY OF NEWER MACROLIDES WITH ETORICOXIB

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    Gajendra Naidu

    2014-03-01

    Full Text Available The present study was designed to investigate the anti-inflammatory activity of macrolides and to compare with standard non- steroidal anti-inflammatory drug (NSAID etoricoxib. This study was conducted in male wistar albino rats by inducing edema with 1% carrageenan. Animals were divided into 5 groups with 6 in each and paw edema volume was measured by digital plethysmograph before and 3hrs after 1% carrageenan administration. Percentage of inhibition of paw edema was calculated. Results showed macrolides having significant anti-inflammatory activity & the anti-inflammatory activity of roxithromycin was almost equally comparable with etoricoxib

  12. Synthesis and anti-inflammatory effects of new piperazine and ethanolamine derivatives of H(1)-antihistaminic drugs.

    Science.gov (United States)

    Ahmadi, Abbas; Khalili, Mohsen; Nafarie, Ali; Yazdani, Arash; Nahri-Niknafs, Babak

    2012-10-01

    In addition to their antihistamine effects, H1-receptor antagonists possess pharmacological properties that are not uniformly distributed among this class of drugs, such as anti-inflammatory, anti-allergic and antiplatelet activities. In this paper, Cyclizine (1-benzhydryl-4-methyl-piperazine, I), bromodiphenhydramine (2-[(4-bromophenyl)-phenylmethoxy]-N, N-dimethylethanamine, II) and some of their new piperazine and ethanolamine derivatives (III-VIII) inducing changes in substitution of phenyl and amine moieties were synthesized and their acute and chronic antiinflammatory effects were evaluated by standard pharmacological tests. The results showed that substitution of phenyl by tolyl, anisol and cumene groups in piperazine family could remarkably decrease acute inflammation in these new drugs. Also, substitution of dimethylamine by morpholine group could not decrease this inflammation in new synthesized ethanolamine family. But the results from the cotton pellet-induced granuloma formation in rats showed that none of drugs (I-VIII) were effective to reduce the chronic inflammation.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

    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.

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

    Science.gov (United States)

    Lehrer, Steven; Rheinstein, Peter H

    2015-05-01

    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.

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

    Science.gov (United States)

    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

    2012-08-01

    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.

  16. Anti-inflammatory activities of inotilone from Phellinus linteus through the inhibition of MMP-9, NF-κB, and MAPK activation in vitro and in vivo.

    Science.gov (United States)

    Huang, Guan-Jhong; Huang, Shyh-Shyun; Deng, Jeng-Shyan

    2012-01-01

    Inotilone was isolated from Phellinus linteus. The anti-inflammatory effects of inotilone were studied by using lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells and λ-carrageenan (Carr)-induced hind mouse paw edema model. Inotilone was tested for its ability to reduce nitric oxide (NO) production, and the inducible nitric oxide synthase (iNOS) expression. Inotilone was tested in the inhibitor of mitogen-activated protein kinase (MAPK) [extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), p38], and nuclear factor-κB (NF-κB), matrix-metalloproteinase (MMP)-9 protein expressions in LPS-stimulated RAW264.7 cells. When RAW264.7 macrophages were treated with inotilone together with LPS, a significant concentration-dependent inhibition of NO production was detected. Western blotting revealed that inotilone blocked the protein expression of iNOS, NF-κB, and MMP-9 in LPS-stimulated RAW264.7 macrophages, significantly. Inotilone also inhibited LPS-induced ERK, JNK, and p38 phosphorylation. In in vivo tests, inotilone decreased the paw edema at the 4(th) and the 5(th) h after Carr administration, and it increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx). We also demonstrated that inotilone significantly attenuated the malondialdehyde (MDA) level in the edema paw at the 5(th) h after Carr injection. Inotilone decreased the NO and tumor necrosis factor (TNF-α) levels on serum at the 5(th) h after Carr injection. Western blotting revealed that inotilone decreased Carr-induced iNOS, cyclooxygenase-2 (COX-2), NF-κB, and MMP-9 expressions at the 5(th) h in the edema paw. An intraperitoneal (i.p.) injection treatment with inotilone diminished neutrophil infiltration into sites of inflammation, as did indomethacin (Indo). The anti-inflammatory activities of inotilone might be related to decrease the levels of MDA, iNOS, COX-2, NF-κB, and MMP-9 and increase the

  17. Anti-inflammatory activities of inotilone from Phellinus linteus through the inhibition of MMP-9, NF-κB, and MAPK activation in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Guan-Jhong Huang

    Full Text Available Inotilone was isolated from Phellinus linteus. The anti-inflammatory effects of inotilone were studied by using lipopolysaccharide (LPS-stimulated mouse macrophage RAW264.7 cells and λ-carrageenan (Carr-induced hind mouse paw edema model. Inotilone was tested for its ability to reduce nitric oxide (NO production, and the inducible nitric oxide synthase (iNOS expression. Inotilone was tested in the inhibitor of mitogen-activated protein kinase (MAPK [extracellular signal-regulated protein kinase (ERK, c-Jun NH(2-terminal kinase (JNK, p38], and nuclear factor-κB (NF-κB, matrix-metalloproteinase (MMP-9 protein expressions in LPS-stimulated RAW264.7 cells. When RAW264.7 macrophages were treated with inotilone together with LPS, a significant concentration-dependent inhibition of NO production was detected. Western blotting revealed that inotilone blocked the protein expression of iNOS, NF-κB, and MMP-9 in LPS-stimulated RAW264.7 macrophages, significantly. Inotilone also inhibited LPS-induced ERK, JNK, and p38 phosphorylation. In in vivo tests, inotilone decreased the paw edema at the 4(th and the 5(th h after Carr administration, and it increased the activities of catalase (CAT, superoxide dismutase (SOD, and glutathione peroxidase (GPx. We also demonstrated that inotilone significantly attenuated the malondialdehyde (MDA level in the edema paw at the 5(th h after Carr injection. Inotilone decreased the NO and tumor necrosis factor (TNF-α levels on serum at the 5(th h after Carr injection. Western blotting revealed that inotilone decreased Carr-induced iNOS, cyclooxygenase-2 (COX-2, NF-κB, and MMP-9 expressions at the 5(th h in the edema paw. An intraperitoneal (i.p. injection treatment with inotilone diminished neutrophil infiltration into sites of inflammation, as did indomethacin (Indo. The anti-inflammatory activities of inotilone might be related to decrease the levels of MDA, iNOS, COX-2, NF-κB, and MMP-9 and increase the activities

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

    Science.gov (United States)

    Sugano, Kentaro

    2011-06-01

    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.

  19. A STUDY OF PRESCRIBING PATTERN OF NON STEROIDAL ANTI INFLAMMATORY DRUGS IN ORTHOPEDIC OUT PATIENT DEPARTMENT AT A TERTIARY CARE HOSPITAL

    OpenAIRE

    Asha Latha; Srinivasu; Ananda Babu Naik; Jaya Chandra

    2015-01-01

    AIM: To determine the pattern of NON STEROIDAL ANTI INFLAMMATORY DRUGS prescribing for arthritic and non - arthritic conditions in orthopedic outpatient department . METHODOLOGY: 100 prescription duplicate collected and analyzed prospectively for the pattern of NSAID prescription for arthritic and non - arthritic conditions; the drug formulation , route , frequency, duration of adm issio n and concomitant medications results. NSAID were...

  20. 非甾体抗炎药与麻醉药的相互作用%Interaction of non-steroidal anti-inflammatory drugs and anesthetics

    Institute of Scientific and Technical Information of China (English)

    刘陆陆; 吕黄伟

    2012-01-01

    非甾体抗炎镇痛药(Non-steroidal anti-inflammatory drugs,NSAIDs)主要用于围手术期超前镇痛.本文对NSAIDs与常用的麻醉药如阿片类药、吸入麻醉药、静脉麻醉药和苯二氮艹卓类药物的相互作用加以综述.%Non-steroidal anti-inflammatory drugs( NSAIDs )is mainly used for perioperative preemptive analgesia. This article summarizes the interaction between NSAIDs and anesthetics such as opioids, inhalation anesthetics, intravenous anesthetics and benzodiazepines.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    -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...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and selective COX-2 inhibitors may improve outcomes in breast cancer patients. We investigated the association of aspirin, NSAIDs, and use of selective COX-2 inhibitors with breast cancer recurrence. METHODS: We identified incident...... stage I-III Danish breast cancer patients in the Danish Breast Cancer Cooperative Group registry, who were diagnosed during 1996-2008. Prescriptions for aspirin (>99% low-dose aspirin), NSAIDs, and selective COX-2 inhibitors were ascertained from the National Prescription Registry. Follow-up began...... 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...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...

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

    Science.gov (United States)

    Gil, Michał; Douhal, Abderrazzak

    2008-06-01

    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.

  5. Combination use of anti-inflammatory drugs and myorelaxants in the treatment of patients with ankylosing spondylitis in outpatient settings

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    Inna Zurabievna Gaidukova

    2015-01-01

    Full Text Available Objective: to assess different treatment regimens for ankylosing spondylitis (AS. The specific features of using topical and oral nonsteroidal anti-inflammatory drugs (NSAIDs and myorelaxants in outpatient settings were retrospectively analyzed.Subjects and methods. The investigation enrolled 96 AS patients admitted to the Department of Rheumatology, Saratov Regional Clinical Hospital, in 2010 to 2012, who took nimesulide during the last year (at least three 14-day cycles. The patients' mean age was 42.6±10.9 years; disease duration was 11.9±8.2 years; 83.33% were male. The diagnosis of AS was based on the 1984 modified New York criteria. Physical examination (clinical blood analysis, clinical urinalysis, C-reactive protein, total protein, albumins, urea, creatinine, glucose, bilirubin, serum aspartate aminotransferase and alanine aminotransferase was made. AS activity was determined using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI. Axial skeleton mobility and cervical spine rotation were evaluated. Therapy received by the patients at the moment of hospitalization and the attending physicians' recommendations for discharging patients from the hospital were analyzed. Saratov outpatient physicians were interviewed using a questionnaire to specify the aims and procedures of using anti-inflammatory drugs.Results. The outpatient physicians (n=100 were shown to use three-, two-, and one-component therapy in 53.12, 45, and 2% of the AS patients, respectively. Higher lumbar spine mobility and comparably reduced pain were established in the patients receiving threecomponent therapy (a combination of nimesulide 200 mg/day, tizanidine 4–8 mg/day, and topical NSAIDs than those who had NSAIDs only.

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

    Science.gov (United States)

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

    2015-06-01

    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.

  7. Formulation,Optimization and Evaluation of Orally Disintegrating Tablet of Non-Steroidal Anti-inflammatory Drug

    Directory of Open Access Journals (Sweden)

    Patel Minal Arvindbhai

    2012-05-01

    Full Text Available Piroxicam is a non steroidal anti-inflammatory drug with analgesic properties. The purpose of this studywas to develop a taste masked orally disintegrating tablet of poorly soluble Piroxicam by directcompression technique with β-cyclodextrin (ß-CD complexes using various superdisintegrants likesodium starch glycolate, crospovidone XL and croscarmellose sodium. Complex was characterizedusing infrared spectroscopy, differential scanning calorimetry, % drug release study, gustatoryevaluation for taste masking. A 32 full factorial design was applied to systematically optimize the drugdisintegration time. The concentration of Crospovidone (X1 and concentration of Croscarmellose (X2were selected as independent variables. The Disintegration time (Y1 and Wetting time (Y2 wereselected as dependent variables. The prepared tablets were evaluated for hardness, friability,disintegration time, wetting time and In-vitro drug release. FT-IR studies and physical compatibilitystudy were conducted for drug, and drug excipient mixture for interactions if any. The differentformulations showed disintegration time between 12 to 58 sec. The results indicated that concentrationof Crospovidone (X1 and concentration of Croscarmellose (X2 significantly affected theDisintegration time (Y1 and Wetting time (Y2. Regression analysis and numerical optimization wereperformed to identify the best formulation. Formulation F10 prepared with croscarmellose (4.23% &crospovidone (6.74% was found to be the best formulation with disintegration time 16 sec, wetting time21 sec and % drug release in 10 min 94.23%.

  8. Curcumin inhibits glyoxalase 1: a possible link to its anti-inflammatory and anti-tumor activity.

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    Thore Santel

    Full Text Available BACKGROUND: Glyoxalases (Glo1 and Glo2 are involved in the glycolytic pathway by detoxifying the reactive methylglyoxal (MGO into D-lactate in a two-step reaction using glutathione (GSH as cofactor. Inhibitors of glyoxalases are considered as anti-inflammatory and anti-carcinogenic agents. The recent finding that various polyphenols modulate Glo1 activity has prompted us to assess curcumin's potency as an Glo1 inhibitor. METHODOLOGY/PRINCIPAL FINDINGS: Cultures of whole blood cells and tumor cell lines (PC-3, JIM-1, MDA-MD 231 and 1321N1 were set up to investigate the effect of selected polyphenols, including curcumin, on the LPS-induced cytokine production (cytometric bead-based array, cell proliferation (WST-1 assay, cytosolic Glo1 and Glo2 enzymatic activity, apoptosis/necrosis (annexin V-FITC/propidium iodide staining; flow cytometric analysis as well as GSH and ATP content. Results of enzyme kinetics revealed that curcumin, compared to the polyphenols quercetin, myricetin, kaempferol, luteolin and rutin, elicited a stronger competitive inhibitory effect on Glo1 (K(i = 5.1+/-1.4 microM. Applying a whole blood assay, IC(50 values of pro-inflammatory cytokine release (TNF-alpha, IL-6, IL-8, IL-1beta were found to be positively correlated with the K(i-values of the aforementioned polyphenols. Moreover, whereas curcumin was found to hamper the growth of breast cancer (JIMT-1, MDA-MB-231, prostate cancer PC-3 and brain astrocytoma 1321N1 cells, no effect on growth or vitality of human primary hepatocytes was elucidated. Curcumin decreased D-lactate release by tumor cells, another clue for inhibition of intracellular Glo1. CONCLUSIONS/SIGNIFICANCE: The results described herein provide new insights into curcumin's biological activities as they indicate that inhibition of Glo1 by curcumin may result in non-tolerable levels of MGO and GSH, which, in turn, modulate various metabolic cellular pathways including depletion of cellular ATP and GSH content

  9. Influence of some anti-inflammatory drugs on the activity of aryl hydrocarbon hydroxylase and the cytochrome P450 content

    Energy Technology Data Exchange (ETDEWEB)

    Mostafa, M.H.; Sheweita, S.A.; Abdel-Moneam, N.M. (Alexandria Univ. (Egypt))

    1990-06-01

    The metabolism of benzo({alpha})pyrene is mediated by the mixed function oxidase system including the cytochrome P450-dependent aryl hydrocarbon hydroxylase. The data of the present study revealed the ability of various commonly used anti-inflammatory drugs to alter the activity of this enzyme system, where all the tested drugs, namely phenyl butazone, ketoprofen, piroxicam, and acetaminophen, caused an increase in both the activity of aryl hydrocarbon hydroxylase and the cytochrome P450 content whether administered as a single dose or as a repeated dose for 6 consecutive days. The percentage of change for all drugs except phenyl butazone was proportional to the duration of drug administration. On the other hand, pyrazole which is chemically related to phenyl butazone, had no significant effect when administered as a single dose but caused a decrease in both studied parameters when administered as a repeated dose for 6 consecutive days. The mechanisms by which these commonly used drugs modify the aryl hydrocarbon hydroxylase activity and the cytochrome p450 content are discussed in the text.

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

    Science.gov (United States)

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

    1981-01-01

    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

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

    Science.gov (United States)

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

    2015-12-01

    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.

  12. Polyphenolics isolated from virgin coconut oil inhibits adjuvant induced arthritis in rats through antioxidant and anti-inflammatory action.

    Science.gov (United States)

    Vysakh, A; Ratheesh, M; Rajmohanan, T P; Pramod, C; Premlal, S; Girish kumar, B; Sibi, P I

    2014-05-01

    We evaluated the protective efficacy of the polyphenolic fraction from virgin coconut oil (PV) against adjuvant induced arthritic rats. Arthritis was induced by intradermal injection of complete Freund's adjuvant. The activities of inflammatory, antioxidant enzymes and lipid peroxidation were estimated. PV showed high percentage of edema inhibition at a dose of 80mg/kg on 21st day of adjuvant arthritis and is non toxic. The expression of inflammatory genes such as COX-2, iNOS, TNF-α and IL-6 and the concentration of thiobarbituric acid reactive substance were decreased by treatment with PV. Antioxidant enzymes were increased and on treatment with PV. The increased level of total WBC count and C-reactive protein in the arthritic animals was reduced in PV treated rats. Synovial cytology showed that inflammatory cells and reactive mesothelial cells were suppressed by PV. Histopathology of paw tissue showed less edema formation and cellular infiltration on supplementation with PV. Thus the results demonstrated the potential beneficiary effect of PV on adjuvant induced arthritis in rats and the mechanism behind this action is due to its antioxidant and anti-inflammatory effects.

  13. Synthetic Zeolites as Controlled-Release Delivery Systems for Anti-Inflammatory Drugs.

    Science.gov (United States)

    Khodaverdi, Elham; Soleimani, Hossein Ali; Mohammadpour, Fatemeh; Hadizadeh, Farzin

    2016-06-01

    Scientists have always been trying to use artificial zeolites to make modified-release drug delivery systems in the gastrointestinal tract. An ideal carrier should have the capability to release the drug in the intestine, which is the main area of absorption. Zeolites are mineral aluminosilicate compounds with regular structure and huge porosity, which are available in natural and artificial forms. In this study, soaking, filtration and solvent evaporation methods were used to load the drugs after activation of the zeolites. Weight measurement, spectroscopy FTIR, thermogravimetry and scanning electronic microscope were used to determine drug loading on the systems. Finally, consideration of drug release was made in a simulated gastric fluid and a simulated intestinal fluid for all matrixes (zeolites containing drugs) and drugs without zeolites. Diclofenac sodium (D) and piroxicam (P) were used as the drug models, and zeolites X and Y as the carriers. Drug loading percentage showed that over 90% of drugs were loaded on zeolites. Dissolution tests in stomach pH environment showed that the control samples (drug without zeolite) released considerable amount of drugs (about 90%) within first 15 min when it was about 10-20% for the matrixes. These results are favorable as NSAIDs irritate the stomach wall and it is ideal not to release much drugs in the stomach. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples in intestine pH environment.

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

    NARCIS (Netherlands)

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

    2007-01-01

    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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

    Directory of Open Access Journals (Sweden)

    Bai Han

    2012-08-01

    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.

  18. The anti-inflammatory activity of standard aqueous stem bark extract of Mangifera indica L. as evident in inhibition of Group IA sPLA2.

    Science.gov (United States)

    Dhananjaya, Bhadrapura Lakkappa; Shivalingaiah, Sudharshan

    2016-03-01

    The standard aqueous stem bark extract is consumed as herbal drink and used in the pharmaceutical formulations to treat patients suffering from various disease conditions in Cuba. This study was carried out to evaluate the modulatory effect of standard aqueous bark extract of M. indica on Group IA sPLA2. M. indica extract, dose dependently inhibited the GIA sPLA2 (NN-XIa-PLA2) activity with an IC50 value 8.1 µg/ml. M. indica extract effectively inhibited the indirect hemolytic activity up to 98% at ~40 µg/ml concentration and at various concentrations (0-50 µg/ml), it dose dependently inhibited the edema formation. When examined as a function of increased substrate and calcium concentration, there was no relieve of inhibitory effect on the GIA sPLA2. Furthermore, the inhibition was irreversible as evidenced from binding studies. It is observed that the aqueous extract ofM. indica effectively inhibits sPLA2 and it is associated inflammatory activities, which substantiate their anti-inflammatory properties. The mode of inhibition could be due to direct interaction of components present in the extract, with sPLA2 enzyme. Further studies on understanding the principal constituents, responsible for the anti-inflammatory activity would be interesting to develop this into potent anti-inflammatory agent.

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

    Science.gov (United States)

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

    2013-05-01

    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.

  20. Modulating the innate immune response to influenza A virus: potential therapeutic use of anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Irene eRamos

    2015-07-01

    Full Text Available Infection by influenza A viruses (IAV is frequently characterized by robust inflammation that is usually more pronounced in the case of avian influenza. It is becoming clearer that the morbidity and pathogenesis caused by IAV is a consequence of this inflammatory response, with several components of the innate immune system acting as the main players. It has been postulated that using a therapeutic approach to limit the innate immune response in combination with antiviral drugs has the potential to diminish symptoms and tissue damage caused by IAV infection. Indeed, some anti-inflammatory agents have been shown to be effective in animal models at reducing IAV pathology as a proof of principle. The main challenge in developing such therapies is to selectively modulate signaling pathways that contribute to lung injury while maintaining the ability of the host cells to mount an antiviral response to control virus replication. However, the dissection of those pathways is very complex given the numerous components regulated by the same factors (i.e. NF kappa B transcription factors and the large number of players involved in this regulation, some of which may be undescribed or unknown. This article provides a comprehensive review of the current knowledge regarding the innate immune responses associated with tissue damage by IAV infection, the understanding of which is essential for the development of effective immunomodulatory drugs. Furthermore, we summarize the recent advances on the development and evaluation of such drugs as well as the lessons learned from those studies.

  1. A Review of Anti-Inflammatory Drug-Induced Gastrointestinal Injury: Focus on Prevention of Small Intestinal Injury

    Directory of Open Access Journals (Sweden)

    Shunji Fujimori

    2010-04-01

    Full Text Available Capsule endoscopy and balloon endoscopy, advanced modalities that allow full investigation of the entire small intestine, have revealed that nonsteroidal anti-inflammatory drugs (NSAIDs can cause a variety of abnormalities in the small intestine. Recently, several reports show that traditional NSAIDs (tNSAIDs and acetylsalicylic acid (ASA can induce small intestinal injuries. These reports have shown that the preventive effect of proton pump inhibitors (PPIs does not extend to the small intestine, suggesting that concomitant therapy may be required to prevent small intestinal side effects associated with tNSAID/ASA use. Recently, several randomized controlled trials used capsule endoscopy to evaluate the preventive effect of mucoprotective drugs against tNSAID/ASA-induced small intestinal injury. These studies show that misoprostol and rebamipide reduce the number and types of tNSAID-induced small intestinal mucosal injuries. However, those studies were limited to a small number of subjects and tested short-term tNSAID/ ASA treatment. Therefore, further extensive studies are clearly required to ascertain the beneficial effect of these drugs.

  2. Development of poly(glycerol adipate) nanoparticles loaded with non-steroidal anti-inflammatory drugs.

    NARCIS (Netherlands)

    Wahab, A.; Favretto, M.E.; Onyeagor, N.D.; Khan, G.M.; Douroumis, D.; Casely-Hayford, M.A.; Kallinteri, P.

    2012-01-01

    The aim of this study was to assess acylated and non-acylated poly(glycerol adipate) polymers (PGA) as suitable nanoparticulate systems for encapsulation and release of ibuprofen, ibuprofen sodium salt (IBU-Na) and ketoprofen as model drugs. Drug encapsulated nanoparticles were prepared using the in

  3. Rheology-sensitive response of zeolite-supported anti-inflammatory drug systems.

    Science.gov (United States)

    Pasquino, R; Di Domenico, M; Izzo, F; Gaudino, D; Vanzanella, V; Grizzuti, N; de Gennaro, B

    2016-10-01

    Drug release from inorganic supports is a challenge for the scientific community for various reasons, related to the low costs of the systems and the possibility of easily regulating the drug release. In the present work, surface-modified zeolite particles are used as carriers for non steroidal antiflammatory drugs (NSAIDs). The release of the drug has been studied in a solution that simulates the intestinal fluid as well as in a gel-like system, based on a surfactant and a binding salt. In the solution case, the quantity of drug released has been tracked via spectrophotometric assay. Release in the gel has been monitored by rheological methods. The molecular conformation of the NSAIDs is fundamental for the interaction with the zeolite surface, whose modified surface has a strong binding energy. It has been proven that the main mechanism for the drug release is anion exchange. It has been found that the NSAIDs, used in their sodic form, can act as binding salts by themselves in the gel-like system, thus changing the viscoelastic response of the overall solution. Drug release kinetics in the solution compare quantitatively well with the released drug in the gel-like fluid, as measured by rheometry.

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

    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.

  5. Mechanistic and conformational studies on the interaction of anti-inflammatory drugs, isoxicam and tenoxicam with bovine serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Punith, Reeta; Katrahalli, Umesha; Kalanur, Shankara S. [Department of Chemistry, Karnatak University, Dharwad 580 003 (India); Jaldappagari, Seetharamappa, E-mail: jseetharam@yahoo.co [Department of Chemistry, Karnatak University, Dharwad 580 003 (India)

    2010-11-15

    The mechanism of interaction of the non-steroidal anti-inflammatory drugs, isoxicam (IXM) and tenoxicam (TXM) with bovine serum albumin (BSA) has been studied using spectroscopic techniques, viz., spectrofluorescence, circular dichroism (CD), UV-visible absorption and FT-IR under simulative physiological conditions. Stern-Volmer analysis of fluorescence quenching data shows the presence of the static quenching mechanism. Thermodynamic parameters (negative {Delta}H{sup 0} and positive {Delta}S{sup 0} values obtained in the present study) revealed that the hydrophobic interactions played a major role in the interaction of these drugs with BSA. The distance, r between the donor (BSA) and acceptor (IXM/TXM) was calculated based on the Forster's theory of non-radiation energy transfer and the values were observed to be 3.85 nm and 2.60 nm in IXM-BSA and TXM-BSA system, respectively. CD and FT-IR studies indicated that the binding of IXM/TXM to BSA induced conformational changes in BSA. The effect of common ions on the binding of IXM/TXM to BSA has been investigated.

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

    Science.gov (United States)

    Fujimori, Shunji; Sakamoto, Choitsu

    2013-10-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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: velazque@ualberta.ca [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: wus1@ohio.edu [Edison Biotechnology Institute, Ohio University, Athens, OH 45701 (United States); Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701 (United States)

    2012-10-15

    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.

  8. Albumin binding of anti-inflammatory drugs. Utility of a site-oriented versus a stoichiometric analysis

    DEFF Research Database (Denmark)

    Honoré, B; Brodersen, R

    1984-01-01

    Binding equilibria of 12 nonsteroidal, anti-inflammatory substances, salicylic acid, diflunisal, phenylbutazone, azapropazone, fenbufen, biphenylacetic acid, naproxen, flurbiprofen, ibuprofin, diclofenac, indomethacin, and benoxaprofen, to defatted human serum albumin has been investigated at 37...

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

    Science.gov (United States)

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

    2012-01-01

    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. Anti-inflammatory activity of root of Alpinia galanga willd

    Directory of Open Access Journals (Sweden)

    Asim Kumar Ghosh

    2011-01-01

    Full Text Available Objective: The objective of the study is to evaluate the acute and chronic anti-inflammatory activities of root extract of Alpinia galanga in rodents. Materials and Methods: The study was carried out using albino rats of either sex (150-200 g. An extract of the root of A. galanga was prepared using absolute alcohol and distillation in a Soxhlet apparatus. The acute anti-inflammatory effects of this extract were evaluated using carrageenan-, bradykinin-, and 5-HT-induced rat paw edema. The chronic anti-inflammatory effects were evaluated using formaldehyde-induced rat paw edema. Results and Analysis: Inhibition of inflammation was seen to be 32.22% in carrageenan-induced, 37.70% in 5-HT-induced, and 35.21% in bradykinin-induced anti-inflammatory models. In chronic inflammatory model, a progressive inhibition of 34.73% (3 rd day, 37.50% (5 th day, 38.83% (7 th day, 44.66% (9 th day, 49.59% (11 th day, and 55.75% (13 th day was observed with study compound. The efficacy was comparable with the standard drugs. Conclusion: It can be thus concluded that A. galanga has anti-inflammatory properties and probably acts by blocking histaminic and serotonin pathways. It may be an effective alternative to NASAIDs and corticosteroid in inflammatory disorders.

  11. Design, Development and Characterization of Extended Release Multiunit Particulate System of Anti-Inflammatory Drug

    Directory of Open Access Journals (Sweden)

    Dhiren Daslaniya

    2009-07-01

    Full Text Available Multi unit particulate system has long been employed to improve the bioavailability of drugs. Mesalamine pellets were prepared by Coating drug solution on sugar sphere followed by various functional coating. The influence of rate controlling membrane made up of Eudragit RSPO and Eudragit RLPO in combination with delay release polymer coating with Eudragit L100 in different proportions on drug release kinetics was studied. Pellets were for the various parameter like Physical characteristics, assay and in-vitro dissolution profile. The study confirmed that mesalamine can be delivered by multi unit particulate system into lower part of intestine. Optimized formulations were evaluated for In-vitro release profile. The optimized formula was stable at accelerated storage condition 40°C / 75 % RH. Prepared Pellets can be used in the treatment of the ulcerative colitis.

  12. Inhibition of inflammatory mediators contributes to the anti-inflammatory activity of KYKZL-1 via MAPK and NF-κB pathway

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Guang-Lin [Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing (China); Department of Pharmacology, University of Michigan, Ann Arbor (United States); Du, Yi-Fang; Cheng, Jing; Huan, Lin [Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing (China); Chen, Shi-Cui [Jinhu Food and Drug Administration, Jiangsu (China); Wei, Shao-Hua [College of Chemistry and Materials Science, Nanjing Normal University, Nanjing (China); Gong, Zhu-Nan, E-mail: biopharmacology@126.com [Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing (China); Cai, Jie; Qiu, Ting; Wu, Hao; Sun, Ting [Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing (China); Ao, Gui-Zhen [Department of Medicinal Chemistry, School of Pharmacy, Soochow University, Jiangsu (China)

    2013-10-01

    KYKZL-1, a newly synthesized compound with COX/5-LOX dual inhibition, was subjected to the anti-inflammatory activity test focusing on its modulation of inflammatory mediators as well as intracellular MAPK and NF-κB signaling pathways. In acute ear edema model, pretreatment with KYKZL-1 (p.o.) dose-dependently inhibited the xylene-induced ear edema in mice with a higher inhibition than diclofenac. In a three-day TPA-induced inflammation, KYKZL-1 also showed significant anti-inflammatory activity with inhibition ranging between 20% and 64%. In gastric lesion test, KYKZL-1 elicited markedly fewer stomach lesions with a low index of ulcer as compared to diclofenac in rats. In further studies, KYKZL-1 was found to significantly inhibit the production of NO, PGE{sub 2}, LTB{sub 4} in LPS challenged RAW264.7, which is parallel to its attenuation of the expression of iNOS, COX-2, 5-LOX mRNAs or proteins and inhibition of phosphorylation of p38 and ERK MAPKs and activation of NF-κB. Taken together, our data indicate that KYKZL-1 comprises dual inhibition of COX and 5-LOX and exerts an obvious anti-inflammatory activity with an enhanced gastric safety profile via simultaneous inhibition of phosphorylation of p38 and ERK MAPKs and activation of NF-κB. - Highlights: • KYKZL-1 is designed to exhibit COX/5-LOX dual inhibition. • KYKZL-1 inhibits NO, PGE{sub 2} and LTB{sub 4} and iNOS, COX-2 and 5-LOX mRNAs and MAPKs. • KYKZL-1 inhibits phosphorylation of MAPKs. • KYKZL-1 inactivates NF-κB pathway.

  13. Chlorophyll revisited: anti-inflammatory activities of chlorophyll a and inhibition of expression of TNF-α gene by the same.

    Science.gov (United States)

    Subramoniam, Appian; Asha, Velikkakathu V; Nair, Sadasivan Ajikumaran; Sasidharan, Sreejith P; Sureshkumar, Parameswaran K; Rajendran, Krishnan Nair; Karunagaran, Devarajan; Ramalingam, Krishnan

    2012-06-01

    In view of the folklore use of green leaves to treat inflammation, the anti-inflammatory property of chlorophylls and their degradation products were studied. Chlorophyll a and pheophytin a (magnesium-free chlorophyll a) from fresh leaves showed potent anti-inflammatory activity against carrageenan-induced paw edema in mice and formalin-induced paw edema in rats. Chlorophyll a inhibited bacterial lipopolysaccharide-induced TNF-α (a pro-inflammatory cytokine) gene expression in HEK293 cells, but it did not influence the expression of inducible nitric acid synthase and cyclooxygenase-2 genes. Chlorophyll b only marginally inhibited both inflammation and TNF-α gene expression. But both chlorophyll a and chlorophyll b showed the same level of marginal inhibition on 12-O-tetradecanoyl-phorbol-13-acetate-induced NF-κB activation. Chlorophylls and pheophytins showed in vitro anti-oxidant activity. The study shows that chlorophyll a and its degradation products are valuable and abundantly available anti-inflammatory agents and promising for the development of phytomedicine or conventional medicine to treat inflammation and related diseases.

  14. New potential nonsteroidal anti-inflammatory drugs with antileukotrienic effects: influence on model proteins with catalytic activity.

    Science.gov (United States)

    Netopilová, Miloslava; Drsata, Jaroslav; Beránek, Martin; Palicka, Vladimír

    2002-01-01

    Unspecific and side effects caused by interaction with proteins belong to common problems of many structures synthesized as potential medicaments. Possible in vitro interactions with proteins of a group of phenylsulfonyl benzoic acid derivatives (VUFB 19363, 19369, 19370, 19371, and 19760) as new potential anti-inflammatory compounds with anti-leukotrienic activities were studied in the present work. Three purified enzymes were used as model proteins with catalytic activities: Pig heart aspartate aminotransferase (AST, EC 2.6.1.1), alanine aminotransferase (ALT, EC 2.6.1.2), and glutamate decarboxylase (GAD, EC 4.1.1.15) from E. coli. Catalytic activities during incubation of individual compounds (6 x 10(-5) M solution to 5 x 10(-2) M suspension) at 37 degrees C with enzymes served as criteria of stability and function of the proteins. No immediate influence of any compound studied on enzyme activities was found. Aminotransferase activities were not affected even during incubation up to 20 d. In the case of GAD, the compounds VUFB 19369, 19370, 19371, and 19760 had stabilizing influence on GAD activity during incubation at enzyme concentrations of 11.25 and 5.62 mg prot/l. The lack of an immediate effect of compounds and the stability of enzymes during incubation them are favorable and support the prospective of the compounds as potential drugs.

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

    Science.gov (United States)

    2014-01-01

    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 ClinicalTrials.gov identifier NCT00688545. PMID:25057265

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

    Science.gov (United States)

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

    2013-12-01

    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.

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

    Science.gov (United States)

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

    2011-03-01

    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.

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

    Science.gov (United States)

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

    2006-12-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2015-10-01

    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.

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

    Science.gov (United States)

    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

    2012-10-01

    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.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    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...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  4. Cardiovascular outcomes and systemic anti-inflammatory drugs in patients with severe psoriasis

    DEFF Research Database (Denmark)

    Ahlehoff, O; Skov, L; Gislason, G

    2014-01-01

    intervals (CIs) of cardiovascular events associated with use of biological drugs, methotrexate, cyclosporine, retinoids and other antipsoriatic therapies, including topical treatments, phototherapy and climate therapy. RESULTS: A total of 6902 patients (9662 treatment exposures) with a maximum follow......-up of 5 years were included. Incidence rates per 1000 patients-years for cardiovascular events were 4.16, 6.28, 6.08, 18.95 and 14.63 for biological drugs, methotrexate, cyclosporine, retinoid and other therapies respectively. Relative to other therapies, methotrexate (HR 0.53; CI 0...... during long-term follow-up compared to patients treated with other antipsoriatic therapies. The treatment strategy in patients with severe psoriasis may have an impact on cardiovascular outcomes and randomized trials to evaluate the cardiovascular safety and efficacy of systemic antipsoriatic therapies...

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

    Science.gov (United States)

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

    2016-09-01

    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.

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

    Science.gov (United States)

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

    2014-01-01

    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.

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

    Science.gov (United States)

    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

    2012-01-01

    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

  8. Recommendations for the Appropriate Use of Anti-Inflammatory Drugs in the Era of the Coxibs: Defining the Role of Gastroprotective Agents

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    Richard H Hunt

    2002-01-01

    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.

  9. [Non-Helicobacter pylori, Non-nonsteroidal Anti-inflammatory Drug Peptic Ulcer Disease].

    Science.gov (United States)

    Chang, Young Woon

    2016-06-25

    Non-Helicobacter pylori, non-NSAID peptic ulcer disease (PUD), termed idiopathic PUD, is increasing in Korea. Diagnosis is based on exclusion of common causes such as H. pylori infection, infection with other pathogens, surreptitious ulcerogenic drugs, malignancy, and uncommon systemic diseases with upper gastrointestinal manifestations. The clinical course of idiopathic PUD is delayed ulcer healing, higher recurrence, higher re-bleeding after initial ulcer healing, and higher mortality than the other types of PUD. Genetic predisposition, older age, chronic mesenteric ischemia, cigarette smoking, concomitant systemic diseases, and psychological stress are considered risk factors for idiopathic PUD. Diagnosis of idiopathic PUD should systematically explore all possible causes. Management of this disease is to treat underlying disease followed by regular endoscopic surveillance to confirm ulcer healing. Continuous proton pump inhibitor therapy is an option for patients who respond poorly to the standard ulcer regimen.

  10. Selective PDE4 inhibitors as potent anti-inflammatory drugs for the treatment of airway diseases

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    Vincent Lagente

    2005-03-01

    Full Text Available Phosphodiesterases (PDEs are responsible for the breakdown of intracellular cyclic nucleotides, from which PDE4 are the major cyclic AMP metabolizing isoenzymes found in inflammatory and immune cells. This generated greatest interest on PDE4 as a potential target to treat lung inflammatory diseases. For example, cigarette smoke-induced neutrophilia in BAL was dose and time dependently reduced by cilomilast. Beside the undesired side effects associated with the first generation of PDE4 inhibitors, the second generation of selective inhibitors such as cilomilast and roflumilast showed clinical efficacy in asthma and chronic obstrutive pulmonary diseases trials, thus re-enhancing the interest on these classes of compounds. However, the ability of PDE4 inhibitors to prevent or modulate the airway remodelling remains relatively unexplored. We demonstrated that selective PDE4 inhibitor RP 73-401 reduced matrix metalloproteinase (MMP-9 activity and TGF-beta1 release during LPS-induced lung injury in mice and that CI-1044 inhibited the production of MMP-1 and MMP-2 from human lung fibroblasts stimulated by pro-inflammatory cytokines. Since inflammatory diseases of the bronchial airways are associated with destruction of normal tissue structure, our data suggest a therapeutic benefit for PDE4 inhibitors in tissue remodelling associated with chronic lung diseases.

  11. [Nonsteroidal Anti-inflammatory Drug and Aspirin-induced Peptic Ulcer Disease].

    Science.gov (United States)

    Shim, Young Kwang; Kim, Nayoung

    2016-06-25

    Despite decreasing Helicobacter pylori prevalence, the prevalence of peptic ulcer disease is increasing in the aged population, mainly due to increasing use of NSAIDs to manage pain and inflammation. In addition, low dose aspirin is employed as an anti-coagulant for those who have suffered or are at high risk of ischemic stroke and cardiovascular disease. However, NSAIDs and aspirin are injurious to mucosa of stomach and duodenum. NSAID-induced inhibition of mucosal prostaglandin synthesis is thought to be a major mechanism of gastrointestinal mucosal injury. The proportion of elderly has increased rapidly in Korea, with the proportion over 65 years old expected to be 24.3% in 2030. In this higher-risk population, the strategy to reduce the incidence of NSAID-related peptic ulcers and complications such as bleeding, obstruction and perforation is very important. Proton pump inhibitors (PPIs) with cyclooxygenase-2 inhibitor can be used for reducing the risk of NSAID-related ulcers and upper gastrointestinal (GI) complications. However, continuous use of PPI has several problems. In addition, NSAID-related problems in the lower GI tract have increased, in contrast to the decrease of NSAID-related upper GI disease. The aim of this review is to provide an evidence-based knowledge regarding the mechanism, complications of treatment, and prevention strategies for NSAID- or aspirin-related peptic ulcer disease in Korea.

  12. Effects of anti-inflammatory drugs on fever and neutrophilia induced by Clostridium difficile toxin B

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    R. A. Cardoso

    1996-01-01

    Full Text Available This study investigated the ability of Clostridium difficile toxin B, isolated from the VPI 10463 strain, to induce fever and neutrophilia in rats. Intravenous injection of toxin B (0.005–0.5 μg/kg evoked a dose-dependent increase in body temperature. The febrile response to 0.5 μg/kg of the toxin started in 2.5 h, peaked at 5 h, and subsided fully within 24 h. Toxin B also induced a dosedependent neutrophilia. Pretreatment with indomethacin (2 mg/kg, i.p. did not affect the neutrophilia induced by toxin B, but significantly reduced the febrile response measured 4 to 8 h after toxin B injection. Dexamethasone (0.5 mg/ kg also markedly diminished the febrile response induced by toxin B. These results show that Clostridium difficile toxin B induced a febrile response susceptible to inhibition by dexamethasone and indomethacin. Furthermore, they suggest that prostaglandins are not involved in the neutrophilia caused by this toxin.

  13. Cause-specific cardiovascular risk associated with nonsteroidal anti-inflammatory drugs among myocardial infarction patients--a nationwide study.

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    Anne-Marie Schjerning Olsen

    Full Text Available BACKGROUND: Non steroidal anti-inflammatory drugs (NSAIDs increase mortality and morbidity after myocardial infarction (MI. We examined cause-specific mortality and morbidity associated with NSAIDs in a nationwide cohort of MI patients. METHODS AND RESULTS: By individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark, patients aged >30 years admitted with first-time MI during 1997-2009 and their subsequent NSAID use were identified. The risk of three cardiovascular specific endpoints: cardiovascular death, the composite of coronary death and nonfatal MI, and the composite of fatal and nonfatal stroke, associated with NSAID use was analyzed by Cox proportional hazard analyses. Of 97,698 patients included 44.0% received NSAIDs during follow-up. Overall use of NSAIDs was associated with an increased risk of cardiovascular death (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.36-1.49. In particular use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with increased risk of cardiovascular death (HR 1.96 [1.79-2.15] and HR1.66 [1.44-1.91], respectively with a dose dependent increase in risk. Use of ibuprofen was associated with increased risk of cardiovascular death (HR 1.34[1.26-1.44], whereas naproxen was associated with the lowest risk of (e.g., HR 1.27[1.01-1.59]. CONCLUSION: Use of individual NSAIDs is associated with different cause-specific cardiovascular risk and in particular rofecoxib and diclofenac were associated with increased cardiovascular morbidity and mortality. These results support caution with use of all NSAIDs in patients with prior MI.

  14. In vitro xanthine oxidase and albumin denaturation inhibition assay of Barringtonia racemosa L. and total phenolic content analysis for potential anti-inflammatory use in gouty arthritis

    Science.gov (United States)

    Osman, Nurul Izzati; Sidik, Norrizah Jaafar; Awal, Asmah; Adam, Nurul Athirah Mohamad; Rezali, Nur Inani

    2016-01-01

    Aim: This study was conducted to evaluate the in vitro anti-inflammatory activities and total phenolic content (TPC) of methanolic extracts of infloresence axes, endosperms, leaves, and pericarps of Barringtonia racemosa L. Methods: The anti-inflammatory study was conducted by assessing the potential through xanthine oxidase (XO) and albumin denaturation inhibition assays. Meanwhile, the TPC in the extracts were assessed by Folin-Ciocalteu assay. Results: In the XO inhibition assay, the infloresence axes extract was found to exert the highest inhibition capacity at 0.1% (w/v) with 59.54 ± 0.001% inhibition followed by leaves (58.82 ± 0.001%), pericarps (57.99 ± 0.003%), and endosperms (57.20 ± 0.003%) extracts. Similarly in the albumin denaturation inhibition assay, the infloresence axes extract had shown the greatest inhibition capacity with 70.58 ± 0.004% inhibition followed by endosperms (66.80 ± 0.024%), leaves (65.29 ± 0.006%), and pericarps extracts (43.33 ± 0.002%). Meanwhile, for TPC analysis, leaves extract was found to have the highest phenolic content (53.94 ± 0.000 mg gallic acid equivalent [GAE]/g DW) followed by infloresence axes (31.54 ± 0.001 mg GAE/g DW), endosperms (22.63 ± 0.001 mg GAE/g DW), and the least was found in pericarps (15.54 ± 0.001 mg GAE/g DW). Conclusion: The results indeed verified the in vitro anti-inflammatory activities of B. racemosa and supported its potential to be used in alleviating gouty arthritis and XO-related diseases. PMID:27757263

  15. [Antiphiogistic drugs. Sudies on the pharmocokinetics of anti-inflammatory agents].

    Science.gov (United States)

    Havemann, D

    1977-01-20

    The kinetic behaviour of radioactively labeled acetylsalicylic acid (ASA), phenylbutazone (PBZ), indometacin and dexamethasone in rabbits with knee joints experimentally inflamed can be summarized as follows: 1. Under control (non-inflammation) conditions as well as during inflammation, subthreshold doses of 14C-ASA intravenously (i.v.) administered were eliminated from the blood in a fast and slow biphasis process. The changes of the concentration in the perfusion fluid were very similar compared to the changes in the blood. However, they were enhanced during experimentally induced synovitis. 2. Subthreshold does of 3H-phenylbutazone i.v. administered were eliminated from the blood like 14C-ASA in a biphasic process. During an experimentally produced inflammation of the joints, the blood level decreased rapidly. The concentration of radioactivity in the perfusion fluid was very low. 3. In constrast, 3H-indometacin injected like ASA and PBZ in subtherapeutic dosage diappeared from the blood in a threephasic process. The uptake into both the normal and the inflamed synovial space was biphasic. Under both conditions the perfusion fluid contained low concentrations of the drug. 4. 3H-dexamethasone (subtherapeutic dosage) displayed a biphasis fall of concentration in the blood: a fast first phase and a slower second phase. With inflammation of the kneejoint, the elimination was characterized by a three-phase slope and was significantly faster compared with control animals. While the alterations of ASA and indometacin level in the perfusion fluid were corresponding to the decrease of the blood concentration, the uptake of dexamethasone into the synovial space did not show any change. 5. Under control conditions. 3H-dexamethasone (subthreshold doses) injected intraariculary was rapidly detectalbe in the blood. However, systemic absorption was considerably faster under inflammation conditions; the blood level was lower than following administration of 3H

  16. 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.

    Science.gov (United States)

    1993-01-01

    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.

  17. Ex vivo corneal epithelial wound healing following exposure to ophthalmic nonsteroidal anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Keping Xu

    2011-02-01

    Full Text Available Keping Xu1, Mark McDermott1, Linda Villanueva2, Rhett M Schiffman2, David A Hollander21The Kresge Eye Institute, Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI, USA; 2Allergan, Inc., Irvine, CA, USAPurpose: Ketorolac 0.45% is a new formulation of topical ketorolac in which preservative (benzalkonium chloride, BAK was removed and carboxymethylcellulose (CMC was added to improve tolerability and reduce dosing frequency. This study compared the effects of ketorolac 0.45% on corneal wound healing to prior ketorolac formulations (0.4% and 0.5%, bromfenac 0.09%, and nepafenac 0.1%.Methods: Two parallel-group comparisons were performed in series. A 5-mm central epithelial wound was made in fresh porcine corneas. After 24 hours in minimum essential medium (MEM, corneas were incubated for 10 minutes with study drugs, Triton X-100 1% (positive control, or MEM (negative control, followed by 24 hours in MEM. The remaining wound area was stained, photographed, and quantified (pixels. Study 1 compared ketorolac 0.45% to ketorolac 0.4% and ketorolac 0.5%. Study 2 compared ketorolac 0.45% to bromfenac 0.09% and nepafenac 0.1%.Results: The mean (±SD original wound area was 200,506 ± 4,363 pixels, which was reduced to 59,509 ± 4850 at 48 hours after exposure to Triton X-100 1%. In study 1, the mean remaining wound areas at 48 hours in pixels were 2969 ± 1633 with MEM, 586 ± 299 with ketorolac 0.45% (significantly reduced, P < 0.05 vs all other treatments, 10,228 ± 7541 with ketorolac 0.4%, and 50,674 ± 33,409 with ketorolac 0.5% (significantly enlarged, P < 0.05 vs MEM. In study 2, the mean remaining wound areas at 48 hours were 565 ± 1263 with MEM, 322 ± 229 with ketorolac 0.45% (significantly reduced, P < 0.01 vs bromfenac 0.09% and nepafenac 0.1%, 29,093 ± 14,295 with bromfenac 0.09% (significantly enlarged, P < 0.01 vs MEM and 47,322 ± 13,736 with nepafenac 0.1% (significantly enlarged, P < 0.01 vs MEM and vs

  18. Effect of a non-steroidal, anti-inflammatory drug (Indocin) on selected parameters of muscular function following concentric and eccentric work

    OpenAIRE

    Vejarano, Maria Eugenia

    1985-01-01

    Evidence from various studies indicates that eccentric contractions produce more post-exercise changes in muscular function than do concentric contractions. Delayed muscular soreness, the pain and tenderness present 1 or 2 days after exercise, is negatively correlated with muscular performance and occurs particularly after eccentric work. The action of an analgesic, anti-inflammatory drug (Indocin) on muscular soreness indicates it may be effective in accelerating recover...

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

    Directory of Open Access Journals (Sweden)

    Andreas Maetzel

    2003-01-01

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

    Science.gov (United States)

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

    1994-06-01

    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.

  1. Influence of Hydrothermal Treatment on Physicochemical Properties and Drug Release of Anti-Inflammatory Drugs of Intercalated Layered Double Hydroxide Nanoparticles

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    Zi Gu

    2014-05-01

    Full Text Available The synthesis method of layered double hydroxides (LDHs determines nanoparticles’ performance in biomedical applications. In this study, hydrothermal treatment as an important synthesis technique has been examined for its influence on the physicochemical properties and the drug release rate from drug-containing LDHs. We synthesised MgAl–LDHs intercalated with non-steroidal anti-inflammatory drugs (i.e., naproxen, diclofenac and ibuprofen using a co-precipitation method with or without hydrothermal treatment (150 °C, 4 h. After being hydrothermally treated, LDH–drug crystallites increased in particle size and crystallinity, but did not change in the interlayer anion orientation, gallery height and chemical composition. The drug release patterns of all studied LDH–drug hybrids were biphasic and sustained. LDHs loaded with diclofenac had a quicker drug release rate compared with those with naproxen and ibuprofen, and the drug release from the hydrothermally-treated LDH–drug was slower than the freshly precipitated LDH–drug. These results suggest that the drug release of LDH–drugs is influenced by the crystallite size of LDHs, which can be controlled by hydrothermal treatment, as well as by the drug molecular physicochemical properties.

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

    Institute of Scientific and Technical Information of China (English)

    Kai-Yu Ji; Fu-Lian Hu

    2006-01-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

    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.

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

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    Marian Majchrzycki

    2014-01-01

    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.

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

    Science.gov (United States)

    Rustagi, Tarun; Njei, Basile

    2016-01-01

    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

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

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    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.

  8. Combined anti-inflammatory and anti-AGE drug treatments have a protective effect on intervertebral discs in mice with diabetes.

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    Svenja Illien-Junger

    Full Text Available OBJECTIVE: Diabetes and low back pain are debilitating diseases and modern epidemics. Diabetes and obesity are also highly correlated with intervertebral disc (IVD degeneration and back pain. Advanced-glycation-end-products (AGEs increase reactive-oxygen-species (ROS and inflammation, and are one cause for early development of diabetes mellitus. We hypothesize that diabetes results in accumulation of AGEs in spines and associated spinal pathology via increased catabolism. We present a mouse model showing that: 1 diabetes induces pathological changes to structure and composition of IVDs and vertebrae; 2 diabetes is associated with accumulation of AGEs, TNFα, and increased catabolism spinal structures; and 3 oral-treatments with a combination of anti-inflammatory and anti-AGE drugs mitigate these diabetes-induced degenerative changes to the spine. METHODS: Three age-matched groups of ROP-Os mice were compared: non-diabetic, diabetic (streptozotocin (STZ-induced, or diabetic mice treated with pentosan-polysulfate (anti-inflammatory and pyridoxamine (AGE-inhibitor. Mice were euthanized and vertebra-IVD segments were analyzed by μCT, histology and Immunohistochemistry. RESULTS: Diabetic mice exhibited several pathological changes including loss in IVD height, decreased vertebral bone mass, decreased glycosaminoglycan content and morphologically altered IVDs with focal deposition of tissues highly expressing TNFα, MMP-13 and ADAMTS-5. Accumulation of larger amounts of methylglyoxal suggested that AGE accumulation was associated with these diabetic degenerative changes. However, treatment prevented or reduced these pathological effects on vertebrae and IVD. CONCLUSION: This is the first study to demonstrate specific degenerative changes to nucleus pulposus (NP morphology and their association with AGE accumulation in a diabetic mouse model. Furthermore, this is the first study to demonstrate that oral-treatments can inhibit AGE-induced ROS and

  9. Anti-Inflammatory Effect of 1,3,5,7-Tetrahydroxy-8-isoprenylxanthone Isolated from Twigs of Garcinia esculenta on Stimulated Macrophage

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    Dan-Dan Zhang; Hong Zhang; Yuan-zhi Lao; Rong Wu; Jin-wen Xu; Ferid Murad; Ka Bian; Hong-Xi Xu

    2015-01-01

    Garcinia Linn. plants having rich natural xanthones and benzophenones with anti-inflammatory activity attracted a great deal of attention to discover and develop them as potential drug candidates. Through screening targeting nitric oxide accumulation in stimulated macrophage, we found that 1,3,5,7-tetrahydroxy-8-isoprenylxanthone (TIE) had potential anti-inflammatory effect. To understand how TIE elicits its anti-inflammatory activity, we uncovered that it significantly inhibits the productio...

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

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    Mariusz Sebastian Cycoń

    2016-12-01

    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

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

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    Tatyana Vladimirovna Kropotina

    2012-01-01

    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

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

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    Krymchantowski Abouch V.

    2001-01-01

    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

  13. Effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs on the production of reactive oxygen species by activated rat neutrophils

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    Paino I.M.M.

    2005-01-01

    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.

  14. Erucin Exerts Anti-Inflammatory Properties in Murine Macrophages and Mouse Skin: Possible Mediation through the Inhibition of NFκB Signaling

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    Ki Won Lee

    2013-10-01

    Full Text Available Erucin, an isothiocyanate, is a hydrolysis product of glucoerucin found in arugula and has recently been reported to have anti-cancer properties in various cancer cells. In this study, we assessed the anti-inflammatory effects of erucin and the underlying mechanisms, using lipopolysaccharide (LPS-stimulated RAW 264.7 murine macrophages and 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin. In RAW 264.7 cells, erucin (2.5, 5 μmol/L inhibited LPS-induced production of nitric oxide and prostaglandin E2. Erucin inhibited LPS-induced degradation of the inhibitor of κBα and translocation of p65 to the nucleus and, subsequently, reduced LPS-induced nuclear factor κB (NFκB DNA binding activities, as well as the transcriptional activity of NFκB, leading to the decreased expression of NFκB-target genes, including tumor necrosis factor-α, interleukin (IL-6, IL-1β, inducible nitric oxide synthase (iNOS and cyclooxygenase (COX-2, as well as transcriptional activity of iNOS and COX-2. In mice, erucin (100, 300 nmoles treatment significantly inhibited phorbol ester-induced formation of ear edema and expression of iNOS and COX-2 proteins. These results indicate that erucin exerts a potent anti-inflammatory activity by inhibiting the pro-inflammatory enzymes and cytokines, which may be mediated, at least in part, via the inhibition of NFκB signaling.

  15. Erucin exerts anti-inflammatory properties in murine macrophages and mouse skin: possible mediation through the inhibition of NFκB signaling.

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    Cho, Han Jin; Lee, Ki Won; Park, Jung Han Yoon

    2013-10-15

    Erucin, an isothiocyanate, is a hydrolysis product of glucoerucin found in arugula and has recently been reported to have anti-cancer properties in various cancer cells. In this study, we assessed the anti-inflammatory effects of erucin and the underlying mechanisms, using lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages and 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin. In RAW 264.7 cells, erucin (2.5, 5 μmol/L) inhibited LPS-induced production of nitric oxide and prostaglandin E2. Erucin inhibited LPS-induced degradation of the inhibitor of κBα and translocation of p65 to the nucleus and, subsequently, reduced LPS-induced nuclear factor κB (NFκB) DNA binding activities, as well as the transcriptional activity of NFκB, leading to the decreased expression of NFκB-target genes, including tumor necrosis factor-α, interleukin (IL)-6, IL-1β, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, as well as transcriptional activity of iNOS and COX-2. In mice, erucin (100, 300 nmoles) treatment significantly inhibited phorbol ester-induced formation of ear edema and expression of iNOS and COX-2 proteins. These results indicate that erucin exerts a potent anti-inflammatory activity by inhibiting the pro-inflammatory enzymes and cytokines, which may be mediated, at least in part, via the inhibition of NFκB signaling.

  16. ASTHMA AND RHINITIS INDUCED BY SELECTIVE IMMEDIATE REACTIONS TO PARACETAMOL AND NON-STEROIDAL ANTI-INFLAMMATORY DRUGS IN ASPIRIN TOLERANT SUBJECTS

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    Diana Pérez-Alzate

    2016-07-01

    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.

  17. Asthma and Rhinitis Induced by Selective Immediate Reactions to Paracetamol and Non-steroidal Anti-inflammatory Drugs in Aspirin Tolerant Subjects

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    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

    2016-01-01

    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

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

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

    2015-01-01

    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

  19. Anti-inflammatory activity of edible oyster mushroom is mediated through the inhibition of NF-κB and AP-1 signaling

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    Simon James

    2011-05-01

    Full Text Available Abstract Background Mushrooms are well recognized for their culinary properties as well as for their potency to enhance immune response. In the present study, we evaluated anti-inflammatory properties of an edible oyster mushroom (Pleurotus ostreatus in vitro and in vivo. Methods RAW264.7 murine macrophage cell line and murine splenocytes were incubated with the oyster mushroom concentrate (OMC, 0-100 μg/ml in the absence or presence of lipopolysacharide (LPS or concanavalin A (ConA, respectively. Cell proliferation was determined by MTT assay. Expression of cytokines and proteins was measured by ELISA assay and Western blot analysis, respectively. DNA-binding activity was assayed by the gel-shift analysis. Inflammation in mice was induced by intraperitoneal injection of LPS. Results OMC suppressed LPS-induced secretion of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, and IL-12p40 from RAW264.7 macrophages. OMC inhibited LPS-induced production of prostaglandin E2 (PGE2 and nitric oxide (NO through the down-regulation of expression of COX-2 and iNOS, respectively. OMC also inhibited LPS-dependent DNA-binding activity of AP-1 and NF-κB in RAW264.7 cells. Oral administration of OMC markedly suppressed secretion of TNF-α and IL-6 in mice challenged with LPS in vivo. Anti-inflammatory activity of OMC was confirmed by the inhibition of proliferation and secretion of interferon-γ (IFN-γ, IL-2, and IL-6 from concanavalin A (ConA-stimulated mouse splenocytes. Conclusions Our study suggests that oyster mushroom possesses anti-inflammatory activities and could be considered a dietary agent against inflammation. The health benefits of the oyster mushroom warrant further clinical studies.

  20. Crystal structures of three classes of non-steroidal anti-inflammatory drugs in complex with aldo-keto reductase 1C3.

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    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

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

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    Patricia McGettigan

    2011-09-01

    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

  2. Pharmacoutilization of anti-inflammatory and gastroprotective drugs in patients with osteoarthritis: comparison between COXIBs and conventional NSAIDs by using administrative records

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    Luca Degli Esposti

    2006-12-01

    Full Text Available The aim of the study was to analyze anti-inflammatory and gastroprotective drug utilization in patients with osteoarthritis comparing conventional non-steroidal anti-inflammatory drugs (NSAIDs versus cyclo-oxygenase 2 (COX 2 inhibitors. A retrospective observational cohort study was conducted and health-assisted subjects from the Local Health Units of Turin and Caserta were enrolled. Data linkage techniques were used to cross demographical, pharmaceutical and nosological databases. All subjects aged ≥18 years who were hospitalized for osteoarthritis from July 1st 2002 to June 30th 2004 were enrolled in the study. Concurrent prescriptions of non-steroidal anti-inflammatory and gastroprotective drugs were considered. Other demographic and clinical characteristics were recorded. A total of 1,002 subjects with a diagnosis of osteoarthritis treated with NSAIDs were enrolled. Of these subjects, 438 patients were treated with non selective NSAIDs (80.8%, 104 with COXIBs (19.2% and 460 with multiple therapy. There were no significant differences between the demographic and clinical characteristics of the three groups. Gastroprotective drugs were prescribed in 37.0% and 35.6% of subjects treated with NSAIDs and COXIBs, respectively. Gastroprotective drug prescriptions increased from the index date to the follow-up period (from 20.4% to 41.1% of subjects treated with NSAIDs. In high-risk subjects with gastrointestinal events, gastroprotective drug utilization was undersized and increased from the index date to the follow up period (from 19.4% to 40.8% of high-risk subjects. Evidence from this study indicated that non selective NSAIDs and COXIBs are used indiscriminately with respect to patient characteristics and gastroprotection.

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

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

    2007-04-01

    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

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

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    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

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

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

    2015-01-01

    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

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

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    Smolović Brigita

    2014-01-01

    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

  7. Activation of the anti-inflammatory reflex blocks lipopolysaccharide-induced decrease in synaptic inhibition in the temporal cortex of the rat.

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    Garcia-Oscos, Francisco; Peña, David; Housini, Mohammad; Cheng, Derek; Lopez, Diego; Cuevas-Olguin, Roberto; Saderi, Nadia; Salgado Delgado, Roberto; Galindo Charles, Luis; Salgado Burgos, Humberto; Rose-John, Stefan; Flores, Gonzalo; Kilgard, Michael P; Atzori, Marco

    2015-06-01

    Stress is a potential trigger for a number of neuropsychiatric conditions, including anxiety syndromes and schizophrenic psychoses. The temporal neocortex is a stress-sensitive area involved in the development of such conditions. We have recently shown that aseptic inflammation and mild electric shock shift the balance between synaptic excitation and synaptic inhibition in favor of the former in this brain area (Garcia-Oscos et al., 2012), as well as in the prefrontal cortex (Garcia-Oscos et al., 2014). Given the potential clinical importance of this phenomenon in the etiology of hyperexcitable neuropsychiatric illness, this study investigates whether inactivation of the peripheral immune system by the "anti-inflammatory reflex" would reduce the central response to aseptic inflammation. For a model of aseptic inflammation, this study used i.p. injections of the bacterial toxin lipopolysaccharide (LPS; 5 µM) and activated the anti-inflammatory reflex either pharmacologically by i.p. injections of the nicotinic α7 receptor agonist PHA543613 or physiologically through electrical stimulation of the left vagal nerve (VNS). Patch-clamp recording was used to monitor synaptic function. Recordings from LPS-injected Sprague Dawley rats show that activation of the anti-inflammatory reflex either pharmacologically or by VNS blocks or greatly reduces the LPS-induced decrease of the synaptic inhibitory-to-excitatory ratio and the saturation level of inhibitory current input-output curves. Given the ample variety of pharmacologically available α7 nicotinic receptor agonists as well as the relative safety of clinical VNS already approved by the FDA for the treatment of epilepsy and depression, our findings suggest a new therapeutic avenue in the treatment of stress-induced hyperexcitable conditions mediated by a decrease in synaptic inhibition in the temporal cortex.

  8. 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.

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

    2004-12-09

    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

  9. Anti-inflammatory effects of physalin E from Physalis angulata on lipopolysaccharide-stimulated RAW 264.7 cells through inhibition of NF-κB pathway.

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    Yang, Yan-Jun; Yi, Lang; Wang, Qing; Xie, Bing-Bing; Dong, Yan; Sha, Cong-Wei

    2017-04-01

    Physalin E is a naturally occurring seco-steroid isolated from the stems and aerial parts of Physalis angulata L. (Solanaceae). This study was aimed to explore the anti-inflammatory effects of physalin E on RAW 264.7 mouse macrophages stimulated by lipopolysaccharide (LPS) and the potential underlying mechanisms. The results showed that physalin E significantly inhibited LPS-induced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression and secretion in a dose-dependent manner. Unlike dexamethasone, these effects could not be blocked by miferstone (RU486). Meanwhile, physalin E reduced the degradation of I-kappa B protein in the cytoplasm and downregulated the nuclear factor-κB (NF-κB) p65 protein in the nuclear, which resulted in the inhibition of the NF-κB nuclear translocation. In conclusion, physalin E exerts its anti-inflammatory activities in LPS-induced macrophages. Physalin E can inhibit the production of inflammatory cytokines by targeting the NF-κB signaling pathway.

  10. Physicochemical profile and in vitro permeation behavior of a new class of non-steroidal anti-inflammatory drug candidates.

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    Rolando, Barbara; Lazzarato, Loretta; Di Stilo, Antonella; Fruttero, Roberta; Carrupt, Pierre-Alain; Martel, Sophie; Gasco, Alberto

    2010-06-14

    Recently a new series of nitrooxy-acyl derivatives of salicylic acid (SA) was described presenting similar anti-inflammatory activities but reduced or no gastrotoxicity compared to aspirin. In this work, lipophilicity and permeability profiles of SA derivatives were performed to evaluate their ADME properties related to oral or transdermic delivery. All tested compounds showed potential good passive permeation through gastrointestinal track and also through percutaneous barrier which could be a way to avoid the first hepatic pass.

  11. Erdosteine: antitussive and anti-inflammatory effects.

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    Dal Negro, Roberto W

    2008-01-01

    Erdosteine is a multifactorial drug currently used in COPD for its rheologic activity on bronchial secretions and its positive effects on bacterial adhesiveness. Erdosteine produces an active metabolite (Met 1) which was shown to produce antioxidant effects during the respiratory burst of human PMNs, due to the presence of an SH group. The substantial antitussive effects of erdosteine were first documented in clinical trials even though mucolytic agents are regarded as not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Actually, a mucolytic drug could exert antitussive effects if it also affects mucus consistency and enhances ciliary function. In the last decade, data from several studies on animal models pointed to the possible antitussive and anti-inflammatory properties of erdosteine and an indirect anti-inflammatory mechanism of action was suggested. Recently, data from some controlled versus placebo studies documented the antioxidant properties of erdosteine in humans and in current smokers with COPD. The mechanism of action was described as related to erdosteine's ability to inhibit some inflammatory mediators and some pro-inflammatory cytokines that are specifically involved in oxidative stress. As oxidative stress is also presumed to impair beta-adrenoceptor function and contribute to airway obstruction, specific controlled studies recently investigated the effect of antioxidant intervention on short-term airway response to salbutamol in nonreversible COPD, according to a double-blind design versus placebo and NAC. Only erdosteine consistently restored a significant short-term reversibility in COPD subjects, previously unresponsive to beta(2) adrenergics. This peculiar activity of erdosteine (to our knowledge never previously assessed) proved related to the ROS scavenging activity (which actually proved equal to that of N), and its significant inhibiting effect on

  12. Evaluation of anti-inflammatory activity of Strobilanthus callosus Nees and Strobilanthus ixiocephala Benth

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    Rupali Vitthal Sarpate

    2012-01-01

    Full Text Available Context: Strobilanthus callosus Nees and Strobilanthus ixiocephala Benth belongs to family Acanthaceae. The plants have been the subject of scientific research which confirms its use in folk medicine as anti-inflammatory drugs showing potent anti-rheumatic effects. Previous research claims the anti-inflammatory and anti-arthritic activities of Lupeol and 19α-H Lupeol isolated from Strobilanthus callosus and Strobilanthus ixiocephala roots. Based on the literature cited, the unexplored parts stems and leaves of the two species were selected for the present study. Aim: The present study is designed to isolate steroidal and alkaloidal components from the two species Strobilanthus callosus and Strobilanthus ixiocephala using the unexplored parts viz. stems and leaves and to investigate its anti-inflammatory effect. Settings and Design: The anti-inflammatory effect was investigated employing subacute anti-inflammatory models namely cotton pellet granuloma and carrageenan-induced rat paw edema. Materials and Methods: Anti-inflammatory activity was carried out using isolated test components RVS-A (Lupeol, RVS-C (Doctriacantone and standard drug Diclofenac sodium (10 mg/kg. Results: The present study has dealt up with isolation of two phytoconstituents Lupeol and Dotriacontane which gave marked anti-inflammatory activity at the dose 20 mg/kg in both the models Carrageenan induced rat paw edema and Cotton pellet granuloma. Conclusion: The results confirm that the mechanism of the anti-inflammatory effect of RVS-A (Lupeol and RVS-C (Doctriacantone involves reduction of prostaglandins through inhibition of cyclooxygenase and suppression of proliferative phase of sub acute inflammation. Thus the steroidal and alkaloidal components Lupeol and Doctriacantone isolated from Strobilanthus callosus Nees and Strobilanthus ixiocephala Benth shows marked anti-inflammatory activity.

  13. Computational modeling-based discovery of novel classes of anti-inflammatory drugs that target lanthionine synthetase C-like protein 2.

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    Pinyi Lu

    Full Text Available BACKGROUND: Lanthionine synthetase component C-like protein 2 (LANCL2 is a member of the eukaryotic lanthionine synthetase component C-Like protein family involved in signal transduction and insulin sensitization. Recently, LANCL2 is a target for the binding and signaling of abscisic acid (ABA, a plant hormone with anti-diabetic and anti-inflammatory effects. METHODOLOGY/PRINCIPAL FINDINGS: The goal of this study was to determine the role of LANCL2 as a potential therapeutic target for developing novel drugs and nutraceuticals against inflammatory diseases. Previously, we performed homology modeling to construct a three-dimensional structure of LANCL2 using the crystal structure of lanthionine synthetase component C-like protein 1 (LANCL1 as a template. Using this model, structure-based virtual screening was performed using compounds from NCI (National Cancer Institute Diversity Set II, ChemBridge, ZINC natural products, and FDA-approved drugs databases. Several potential ligands were identified using molecular docking. In order to validate the anti-inflammatory efficacy of the top ranked compound (NSC61610 in the NCI Diversity Set II, a series of in vitro and pre-clinical efficacy studies were performed using a mouse model of dextran sodium sulfate (DSS-induced colitis. Our findings showed that the lead compound, NSC61610, activated peroxisome proliferator-activated receptor gamma in a LANCL2- and adenylate cyclase/cAMP dependent manner in vitro and ameliorated experimental colitis by down-modulating colonic inflammatory gene expression and favoring regulatory T cell responses. CONCLUSIONS/SIGNIFICANCE: LANCL2 is a novel therapeutic target for inflammatory diseases. High-throughput, structure-based virtual screening is an effective computational-based drug design method for discovering anti-inflammatory LANCL2-based drug candidates.

  14. Mechanisms Underlying the Anti-Inflammatory Effects of Clinacanthus nutans Lindau Extracts: Inhibition of Cytokine Production and Toll-Like Receptor-4 Activation.

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    Mai, Chun W; Yap, Kok S I; Kho, Mee T; Ismail, Nor H; Yusoff, Khatijah; Shaari, Khozirah; Chin, Swee Y; Lim, Erin S H

    2016-01-01

    Clinacanthus nutans has had a long history of use in folk medicine in Malaysia and Southeast Asia; mostly in the relief of inflammatory conditions. In this study, we investigated the effects of different extracts of C. nutans upon lipopolysaccharide (LPS) induced inflammation in order to identify its mechanism of action. Extracts of leaves and stem bark of C. nutans were prepared using polar and non-polar solvents to produce four extracts, namely polar leaf extract (LP), non-polar leaf extract (LN), polar stem extract (SP), and non-polar stem extracts (SN). The extracts were standardized by determining its total phenolic and total flavonoid contents. Its anti-inflammatory effects were assessed on LPS induced nitrite release in RAW264.7 macrophages and Toll-like receptor (TLR-4) activation in TLR-4 transfected human embryonic kidney cells (HEK-Blue(TM)-hTLR4 cells). The levels of inflammatory cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-12p40, and IL-17) in treated RAW264.7 macrophages were quantified to verify its anti-inflammatory effects. Western blotting was used to investigate the effect of the most potent extract (LP) on TLR-4 related inflammatory proteins (p65, p38, ERK, JNK, IRF3) in RAW264.7 macrophages. All four extracts produced a significant, concentration-dependent reduction in LPS-stimulated nitric oxide, LPS-induced TLR-4 activation in HEK-Blue(TM)-hTLR4 cells and LPS-stimulated cytokines production in RAW264.7 macrophages. The most potent extract, LP, also inhibited all LPS-induced TLR-4 inflammatory proteins. These results provide a basis for understanding the mechanisms underlying the previously demonstrated anti-inflammatory activity of C. nutans extracts.

  15. Mechanisms underlying the anti-inflammatory effects of Clinacanthus nutans Lindau extracts: inhibition of cytokine production and Toll-like receptor-4 activation

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    Chun Wai eMai

    2016-02-01

    Full Text Available Clinacanthus nutans has had a long history of use in folk medicine in Malaysia and Southeast Asia; mostly in the relief of inflammatory conditions. In this study, we investigated the effects of different extracts of C. nutans upon lipopolysaccharide (LPS induced inflammation in order to identify its mechanism of action. Extracts of leaves and stem bark of C. nutans were prepared using polar and non-polar solvents to produce four extracts, namely polar leaf extract (LP, non-polar leaf extract (LN, polar stem extract (SP and non-polar stem extracts (SN. The extracts were standardized by determining its total phenolic and total flavonoid contents. Its anti-inflammatory effects were assessed on LPS induced nitrite release in RAW264.7 macrophages and Toll-like receptor (TLR-4 activation in TLR-4 transfected human embryonic kidney cells (HEK-BlueTM-hTLR4 cells. The levels of inflammatory cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-12p40 and IL-17 in treated RAW264.7 macrophages were quantified to verify its anti-inflammatory effects. Western blotting was used to investigate the effect of the most potent extract (LP on TLR-4 related inflammatory proteins (p65, p38, ERK, JNK, IRF3 in RAW264.7 macrophages. All four extracts produced a significant, concentration-dependent reduction in LPS-stimulated nitric oxide, LPS-induced TLR-4 activation in HEK-BlueTM-hTLR4 cells and LPS-stimulated cytokines production in RAW264.7 macrophages. The most potent extract, LP, also inhibited all LPS-induced TLR-4 inflammatory proteins. These results provide a basis for understanding the mechanisms underlying the previously demonstrated anti-inflammatory activity of C. nutans extracts.

  16. 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

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    Fomenko Iryna

    2015-03-01

    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.

  17. Inhibition of S6K1 accounts partially for the anti-inflammatory effects of the arginase inhibitor L-norvaline

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    Ruffieux Jean

    2009-03-01

    Full Text Available Abstract Background Pharmacological inhibition of endothelial arginase-II has been shown to improve endothelial nitric oxide synthase (eNOS function and reduce atherogenesis in animal models. We investigated whether the endothelial arginase II is involved in inflammatory responses in endothelial cells. Methods Human endothelial cells were isolated from umbilical veins and stimulated with TNFα (10 ng/ml for 4 hours. Endothelial expression of the inflammatory molecules i.e. vascular cell adhesion molecule-1 (VCAM-1, intercellular adhesion molecule-1 (ICAM-1, and E-selectin were assessed by immunoblotting. Results The induction of the expression of endothelial VCAM-1, ICAM-1 and E-selectin by TNFα was concentration-dependently reduced by incubation of the endothelial cells with the arginase inhibitor L-norvaline. However, inhibition of arginase by another arginase inhibitor S-(2-boronoethyl-L-cysteine (BEC had no effects. To confirm the role of arginase-II (the prominent isoform expressed in HUVECs in the inflammatory responses, adenoviral mediated siRNA silencing of arginase-II knocked down the arginase II protein level, but did not inhibit the up-regulation of the adhesion molecules. Moreover, the inhibitory effect of L-norvaline was not reversed by the NOS inhibitor L-NAME and L-norvaline did not interfere with TNFα-induced activation of NF-κB, JNK, p38mapk, while it inhibited p70s6k (S6K1 activity. Silencing S6K1 prevented up-regulation of E-selectin, but not that of VCAM-1 or ICAM-1 induced by TNFα. Conclusion The arginase inhibitor L-norvaline exhibits anti-inflammatory effects independently of inhibition of arginase in human endothelial cells. The anti-inflammatory properties of L-norvaline are partially attributable to its ability to inhibit S6K1.

  18. Potent anti-inflammatory activity of novel microtubule-modulating brominated noscapine analogs.

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    Zughaier, Susu; Karna, Prasanthi; Stephens, David; Aneja, Ritu

    2010-02-11

    Noscapine, a plant-derived, non-toxic, over-the-counter antitussive alkaloid has tubulin-binding properties. Based upon the structural resemblance of noscapine to colchicine, a tubulin-binding anti-inflammatory drug, noscapine and its semi-synthetic brominated analogs were examined for in vitro anti-inflammatory activity. Brominated noscapine analogs were found to inhibit cytokine and chemokine release from macrophage cell lines but did not affect cell viability. Brominated noscapine analogs demonstrated anti-inflammatory properties in both TLR- and non-TLR induced in vitro innate immune pathway inflammation models, mimicking septic and sterile infection respectively. In addition, electron microscopy and immunoblotting data indicated that these analogs induced robust autophagy in human macrophages. This study is the first report to identify brominated noscapines as innate immune pathway anti-inflammatory molecules.

  19. Potent anti-inflammatory activity of novel microtubule-modulating brominated noscapine analogs.

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    Susu Zughaier

    Full Text Available Noscapine, a plant-derived, non-toxic, over-the-counter antitussive alkaloid has tubulin-binding properties. Based upon the structural resemblance of noscapine to colchicine, a tubulin-binding anti-inflammatory drug, noscapine and its semi-synthetic brominated analogs were examined for in vitro anti-inflammatory activity. Brominated noscapine analogs were found to inhibit cytokine and chemokine release from macrophage cell lines but did not affect cell viability. Brominated noscapine analogs demonstrated anti-inflammatory properties in both TLR- and non-TLR induced in vitro innate immune pathway inflammation models, mimicking septic and sterile infection respectively. In addition, electron microscopy and immunoblotting data indicated that these analogs induced robust autophagy in human macrophages. This study is the first report to identify brominated noscapines as innate immune pathway anti-inflammatory molecules.

  20. Exploration of possible mechanisms for anti-inflammatory activity of Ipomoea aquatica Forsk. (Convolvulaceae

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    Mital N. Manvar

    2015-11-01

    Full Text Available Currently used steroidal and non steroidal anti-inflammatory drugs have severe side effects. These side effects are very difficult to manage than the disease itself. Hence, there is to search new safe resources to cure such diseases that the use of plant based drugs. This study deals with anti-inflammatory evaluation of the hydroalcoholic extract of Ipomoea aquatica leaves as well as their possible mechanism of action. A carrageenan‐induced rat paw oedema model was used for anti-inflammatory study. The mechanism/s by which Ipomoea aquatica is mediated the ant-inflammatory activity was determined by its effects in antihistamine activity, prostaglandin synthesis inhibition activity, membrane stabilizing activity and protein denaturation inhibition activity. Dose dependent anti-inflammatory activity was found with HAEIA in rat paw oedema model using carrageenan. HAEIA effective to suppressed the wheal area formed by histamine. HAEIA revealed dose dependent prostaglandin synthesis inhibition activity. HAEIA was effectively inhibited the heat induced hemolysis of HRBCs as well as heat induced albumin denaturation. Therefore, it was concluded that the HAEIA has anti-inflammatory activity possibly mediated through inhibition of release of mediator histamine and prostaglandin and has also HRBCs membrane stabilization and protein denaturation inhibition properties.

  1. Mechanisms of action underlying the anti-inflammatory and immunomodulatory effects of propolis: a brief review

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    Marcio A. R. Araujo

    2012-02-01

    Full Text Available Many biological properties have been attributed to various types of propolis, including anti-inflammatory, antimicrobial, antioxidant, antitumor, wound healing, and immunomodulatory activities. This article reviewed studies published that investigated the anti-inflammatory activity of propolis of different origins and/or its isolated components, focusing on the mechanisms of action underlying this activity and also addressing some aspects of immunomodulatory effects. The search was performed of the following databases: PubMed, Science Direct, HighWire Press, Scielo, Google Academics, Research Gate and ISI Web of Knowledgement. The anti-inflammatory activity was associated with propolis or compounds such as polyphenols (flavonoids, phenolic acids and their esters, terpenoids, steroids and amino acids. CAPE is the most studied compounds. The main mechanisms underlying the anti-inflammatory activity of propolis included the inhibition of cyclooxygenase and consequent inhibition of prostaglandin biosynthesis, free radical scavenging, inhibition of nitric oxide synthesis, reduction in the concentration of inflammatory cytokines and immunosuppressive activity. Propolis was found to exert an anti-inflammatory activity in vivo and in vitro models of acute and chronic inflammation and others studies, indicating its promising potential as anti-inflammatory agent of natural origin and as a source of chemical compounds for the development of new drugs.

  2. Modulatory effects of non-steroidal anti-inflammatory drugs on the luminol and lucigenin amplified chemiluminescence of equine neutrophils.

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    Benbarek, H; Ayad, A; Deby-Dupont, G; Boukraa, L; Serteyn, D

    2012-03-01

    The purpose of this study was to explore the potential modulation of equine neutrophil oxidative burst by a series of classical NSAIDs which was subsequently monitored by the luminol or lucigenin-enhanced chemiluminescence (CL) technique. A significant dose-dependent inhibition of the luminol CL was observed with the majority of investigated drugs. This inhibition was very significant for phenylbutazone and Indomethacin; while for aspirin, a higher concentration is required. The action of Ketoprofen was significant during the first 5 min and only when the concentration was above 1 mM. Indomethacin and acetylsalicylic acid result in an inhibition dose-dependent of luminol CL. On the other hand, the phenylbutazone showed an inhibiting effect when used either luminol or lucigenin though luminol is slightly better. When the ketoprofen is considered, an inhibiting effect of luminal CL was observed but less significant than the other NSAIDs investigated. The flunixin meglumine enhances strongly the CL.

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

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

    2015-08-01

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

    Science.gov (United States)

    Maĭko, O Iu; Bagirova, G G

    2009-01-01

    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.

  5. Objective assessment of topical anti-inflammatory drug activity on experimentally induced nickel contact dermatitis: comparison between visual scoring, colorimetry, laser Doppler velocimetry and transepidermal water loss.

    Science.gov (United States)

    Queille-Roussel, C; Duteil, L; Padilla, J M; Poncet, M; Czernielewski, J

    1990-01-01

    Four topical anti-inflammatory drugs were investigated for their effect on allergic contact dermatitis. Nickel dermatitis was chosen for its high incidence in European healthy volunteers. Experimental lesions were treated twice daily with two steroids, two non-steroidal anti-inflammatory drugs and a blank base for 4.5 days without occlusion. The influence of treatments was assessed by daily visual grading and one site was left untreated for comparison over the same period. To quantify drug activities objectively, skin colour (colorimetry), skin blood flow (laser Doppler velocimetry) and transepidermal water loss (evaporimetry) were measured before drugs were first applied, then 6 hr after the last application. As expected, only Dermoval cream significantly improved the spontaneous clinical evolution in comparison with the other creams (Hydrocortisone Aster à 1%. Parfenac, indomethacin 2.5% and Skinbase) and the untreated site. Colorimetric parameter a* (redness) and L* (luminance) showed more differences between treatments than the other criteria and a close relationship was obtained between these two parameters and skin blood flow, all three being highly correlated to visual grading. Transepidermal water loss appeared less related to clinical improvement but this parameter could prove helpful for detecting compounds which could be irritant to diseased skin.

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

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    Mirela-Anca STOIA

    2015-12-01

    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.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    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...

  8. Preliminary evaluation of the analgesic and anti-inflammatory effects of Tacca integrifolia in rodents

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    Thatree Autsavakitipong

    2015-01-01

    Full Text Available Summary. This is a preliminary investigation of the ethyl acetate extract of the leaf of Tacca integrifolia (TIE for the analgesic activity using writhing response in mice, tail flick test in rats and for anti-inflammatory activity using ethyl phenyl propiolate (EPP-induced ear edema, carrageenan- and arachidonic acid-induced hind paw edema, as well as cotton pellet-induced granuloma formation in rats. The results showed that TIE (200 mg/kg, PO significantly inhibited pain caused by acetic acid injection (65.9% but did not exhibit effect in tail flick test in rats. These findings suggest that analgesic mechanism of TIE may act via peripherally pathway. The study of anti-inflammatory effect showed that TIE significantly inhibited ear edema induced by EPP. TIE (200 mg/kg, PO inhibited paw edema induced by carrageenan (55.5% and arachidonic acid (48.6% but had no effect on cotton-induced granuloma formation in rats. In conclusion, the ethyl acetate extract of leaf of T. integrifolia possessed anti-inflammatory activity in acute inflammation and analgesic activity.Industrial relevant. Plants of the genus Tacca have been reported to possess many activities such as analgesic, anti-inflammatory and, antipyretic activities. Many species have been used to treat high blood pressure, burn, gastric ulcer, and hepatitis. The scientific studies supporting the traditional uses of Tacca integrifolia for some of the alleged activities are still lacking. The screening test for analgesic and anti-inflammatory effect of the ethyl acetate extract of the leaf of Tacca integrifolia provides scientific data to confirm the potentials of T. integrifolia as an analgesic and anti-inflammatory medicinal plant. In addition, the outcomes may be useful to develop a new analgesic and anti-inflammatory drug in the future. Key words. Tacca integrifolia; Taccaceae; ethyl acetate extract; analgesic activity; anti-inflammatory activity

  9. WIN-34B May Have Analgesic and Anti-Inflammatory Effects by Reducing the Production of Pro-Inflammatory Mediators in Cells via Inhibition of IκB Signaling Pathways

    Science.gov (United States)

    Kim, Kyoung Soo; Choi, Hyun Mi; Yang, Hyung-In; Yoo, Myung Chul

    2012-01-01

    WIN-34B showed analgesic and anti-inflammatory effects in various animal models of pain and osteoarthritis. However, the molecular mechanism by which WIN-34B inhibits pain and inflammation in vivo remains to be elucidated. We investigated the molecular mechanisms of the actions of WIN-34B using various in vitro models using fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA FLSs), RAW264.7 cells and peritoneal macrophages. WIN-34B inhibited the level of IL-6, PGE2, and MMP-13 in IL-1β-stimulated RA FLSs in a dose-dependent manner. The mRNA levels were also inhibited by WIN-34B. The level of PGE2, NO, IL-1β, and TNF-α were inhibited by WIN-34B at different concentrations in LPS-stimulated RAW264.7 cells. The production of NO and PGE2 was inhibited by WIN-34B in a dose-dependent manner in LPS-stimulated peritoneal macrophages. All of these effects were comparable to the positive control, celecoxib or indomethacin. IκB signaling pathways were inhibited by WIN-34B, and the migration of NF-κB into the nucleus was inhibited, which is consistent with the degradation of IκB-α. Taken together, the results suggest that WIN-34B has potential as a therapeutic drug to reduce pain and inflammation by inhibiting the production of pro-inflammatory mediators. PMID:24116274

  10. 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

    NARCIS (Netherlands)

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

    1995-01-01

    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

  11. Effect of farrowing duration, parity number and the type of anti-inflammatory drug on postparturient disorders in sows: a clinical study.

    Science.gov (United States)

    Tummaruk, Padet; Sang-Gassanee, Kridtasak

    2013-04-01

    The aim of the present study was to investigate the effects of farrowing duration, parity number, and type of anti-inflammatory drug used postpartum on the incidence of postparturient disorders in sows. The duration of farrowing and postparturient disorders were examined in 64 sows at Days 0, 1, 2, and 3 after farrowing. The sows were classified according to parity number (1, 2-4, and 5-7), duration of farrowing (primiparous sows had fever, while 52.6 and 47.6 % of sows parity 2-4 and 5-7 had a fever (P<0.05). The presence of vaginal discharge on Day 1 of the postpartum was higher in sows of parity 5-7 than sows of parity 2-4 (85.7 and 52.6 %, P=0.029). The use of flunixin méglumine after parturition in sows reduced the percentage of sows with a fever from 61.3 to 22.6 % within 2 days (P=0.002), while, the percentage of sows with a fever was not decreased in sows treated with dipyrone. It can be concluded that the incidence of postparturient disorders in sows was affected by sow parity, farrowing duration and the type of anti-inflammatory drug used. Sows with a farrowing duration of ≥ 4 h were at a high risk of having fever at Day 1 after parturition.

  12. Laboratory monitoring of patients treated with antihypertensive drugs and newly exposed to non steroidal anti-inflammatory drugs: a cohort study.

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    Jean-Pascal Fournier

    Full Text Available BACKGROUND: Drug-Drug Interactions between Non Steroidal Anti-Inflammatory Drugs (NSAIDs and Angiotensin Converting Enzyme Inhibitors (ACEIs, Angiotensin Receptor Blocker (ARBs or diuretics can lead to renal failure and hyperkalemia. Thus, monitoring of serum creatinine and potassium is recommended when a first dispensing of NSAID occur in patients treated with these drugs. METHODS: We conducted a pharmacoepidemiological retrospective cohort study using data from the French Health Insurance Reimbursement Database to evaluate the proportion of serum creatinine and potassium laboratory monitoring in patients treated with ACEI, ARB or diuretic and receiving a first dispensing of NSAID. We described the first dispensing of NSAID among 3,500 patients of a 4-year cohort (6,633 patients treated with antihypertensive drugs and analyzed serum creatinine and potassium laboratory monitoring within the 3 weeks after the first NSAID dispensing. RESULTS: General Practitioners were the most frequent prescribers of NSAIDs (85.5%, 95% CI: 84.3-86.6. The more commonly prescribed NSAIDs were ibuprofen (20%, ketoprofen (15%, diclofenac (15% and piroxicam (12%. Serum creatinine and potassium monitoring was 10.7% (95% CI: 9.5-11.8 in patients treated by ACEIs, ARBs or diuretics. Overall, monitoring was more frequently performed to women aged over 60, treated with digoxin or glucose lowering drugs, but not to patients treated with ACEIs, ARBs or diuretics. Monitoring was more frequent when NSAIDs' prescribers were cardiologists or anesthesiologists. CONCLUSION: Monitoring of serum creatinine and potassium of patients treated with ACEIs, ARBs or diuretics and receiving a first NSAID dispensing is insufficiently performed and needs to be reinforced through specific interventions.

  13. A Review on Anti-Inflammatory Activity of Monoterpenes

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    Damião Pergentino de Sousa

    2013-01-01

    Full Text Available Faced with the need to find new anti-inflammatory agents, great effort has been expended on the development of drugs for the treatment of inflammation. This disorder reduces the quality of life and overall average productivity, causing huge financial losses. In this review the anti-inflammatory activity of 32 bioactive monoterpenes found in essential oils is discussed. The data demonstrate the pharmacological potential of this group of natural chemicals to act as anti-inflammatory drugs.

  14. INTERACTION BETWEEN ANTI-HYPERTENSIVE AND NON-STEROIDAL ANTI INFLAMMATORY DRUGS: IMPLICATIONS IN MANAGEMENT OF OSTEOARTHRITIS AND OPINION ON A COMPROMISE THERAPY

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    Mr. Adeolu O. Ajala

    2010-01-01

    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.

  15. Safety of selective cyclooxygenase-2 inhibitors and a basic non-steroidal anti-inflammatory drug (NSAID) in Japanese patients with NSAID-induced urticaria and/or angioedema: Comparison of meloxicam, etodolac and tiaramide.

    Science.gov (United States)

    Inomata, Naoko; Osuna, Hiroyuki; Yamaguchi, Junko; Onoda, Masahito; Takeshita, Yoshihiro; Chiba, Yoshiyuki; Kambara, Takeshi; Ikezawa, Zenro

    2007-03-01

    The identification of a safe and reliable alternative for patients with non-steroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema is a frequent problem for dermatologists and other practitioners. Cyclooxygenase-2 (COX-2) inhibitors have been reported to be safe for NSAID-intolerant patients from the US and Europe but not all of them have yet been approved for use in Japan. It was our objective to investigate the clinical manifestations of oral NSAID challenges in Japanese patients with histories of urticaria and/or angioedema after the intake of NSAIDs and to find safe alternative drugs, including COX-2 inhibitors and a basic anti-inflammatory drug. Twenty subjects suspected NSAID-induced urticaria/angioedema from histories were included in a double-blind or single-blind, placebo-controlled oral challenge protocol using NSAIDs. Skin prick tests using NSAIDs, which were dissolved in saline, were conducted. The mean age of the patients was 37.3 years; 14 patients were female. The results of other challenge tests showed that the most frequently intolerated drugs was loxoprofen (100%), followed by acetyl salicylic (94.4%), etodolac (53.3%), dicrofenac (50%), acetaminophen (38.5%), meloxicam (33%), and tiaramide (21.4%). Urticaria and angioedema were induced after aspirin intake in 83.3% and 22.2% of patients, respectively, whereas an asthmatic response was seen in 5.6%. Skin prick tests with NSAIDs were 100% negative. This study showed that among the NSAIDs that are available in Japan and that were investigated in this study, tiaramide, which does not inhibit COX, is the relatively safe alternative drug for Japanese patients with NSAID-induced urtiacaria and/or angioedema. Furthermore, meloxicam seems to be better tolerated than etodolac between two selective COX-2 inhibitors.

  16. In vitro evaluation of the effects of anti-fungals, benzodiazepines and non-steroidal anti-inflammatory drugs on the glucuronidation of 19-norandrosterone: implications on doping control analysis.

    Science.gov (United States)

    Palermo, Amelia; Alessi, Beatrice; Botrè, Francesco; de la Torre, Xavier; Fiacco, Ilaria; Mazzarino, Monica

    2016-09-01

    We have studied whether the phase II metabolism of 19-norandrosterone, the most representative metabolite of 19-nortestosterone (nandrolone), can be altered in the presence of other drugs that are not presently included on the Prohibited List of the World Anti-Doping Agency. In detail, we have evaluated the effect of non-prohibited drugs belonging to the classes of anti-fungals, benzodiazepines, and non-steroidal anti-inflammatory drugs on the glucuronidation of 19-norandrosterone. In vitro assays based on the use of either pooled human liver microsomes or specific recombinant isoforms of uridine diphosphoglucuronosyl-transferase were designed and performed to monitor the formation of 19-norandrosterone glucuronide from 19-norandrosterone. Determination of 19-norandrosterone (free and conjugated fraction) was performed by gas chromatography - mass spectrometry after sample pretreatment consisting of an enzymatic hydrolysis (performed only for the conjugated fraction), liquid/liquid extraction with tert-butylmethyl ether, and derivatization to form the trimethylsilyl derivative. In parallel, a method based on reversed-phase liquid chromatography coupled to tandem mass spectrometry in positive electrospray ionization with acquisition in selected reaction monitoring mode was also developed to identify the non-prohibited drugs considered in this study. Incubation experiments have preliminarily shown that the glucuronidation of 19-norandrosterone is principally carried out by UGT2B7 (39%) and UGT2B17 (31%). Inhibition studies have shown that the yield of the glucuronidation reaction is reduced in the presence of the anti-fungals itraconazole, ketoconazole, and miconazole, of the benzodiazepine triazolam and of the non-steroidal anti-inflammatory drugs diclofenac and ibuprofen, while no alteration was recorded in the presence of all other compounds considered in this study. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Hyperforin, an anti-inflammatory constituent from St. John’s wort, inhibits microsomal prostaglandin E2 synthase-1 and suppresses prostaglandin E2 formation in vivo

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    Andreas eKoeberle

    2011-02-01

    Full Text Available The acylphloroglucinol hyperforin (Hyp from St. John’s wort possesses anti-inflammatory and anti-carcinogenic properties which were ascribed among others to the inhibition of 5-lipoxygenase. Here, we investigated whether Hyp also interferes with prostanoid generation in biological systems, particularly with key enzymes participating in prostaglandin (PGE2 biosynthesis, i.e., cyclooxygenases (COX-1/2 and microsomal PGE2 synthase (mPGES-1 which play key roles in inflammation and tumorigenesis. Similar to the mPGES-1 inhibitors MK-886 and MD-52, Hyp significantly suppressed PGE2 formation in whole blood assays starting at 0.03 to 1 µM, whereas the concomitant generation of COX-derived 12(S-hydroxy-5-cis-8,10-trans-hepta¬deca¬trienoic acid, thromboxane B2, and 6-keto PGF1α was not significantly suppressed up to 30 µM. In cell-free assays, Hyp efficiently blocked the conversion of PGH2 to PGE2 mediated by mPGES-1 (IC50 = 1 µM, and isolated COX enzymes were not (COX-2 or hardly (COX-1 suppressed. Intraperitoneal (i.p. administration of Hyp (4 mg kg-1 to rats impaired exudate volume and leukocyte numbers in carrageenan-induced pleurisy associated with reduced PGE2 levels, and Hyp (given i.p. inhibited carrageenan-induced mouse paw edema formation (ED50 = 1 mg kg-1 being superior over indomethacin (ED50 = 5 mg kg-1. We conclude that the suppression of PGE2 biosynthesis in vitro and in vivo by acting on mPGES-1 critically contributes to the anti-inflammatory efficiency of Hyp.

  18. A novel chromone derivative with anti-inflammatory property via inhibition of ROS-dependent activation of TRAF6-ASK1-p38 pathway.

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    Hailiang Liu

    Full Text Available The p38 MAPK signaling pathway plays a pivotal role in inflammation. Targeting p38 MAPK may be a potential strategy for the treatment of inflammatory diseases. In the present study, we show that a novel chromone derivative, DCO-6, significantly reduced lipopolysaccharide (LPS-induced production of nitric oxide, IL-1β and IL-6, decreased the levels of iNOS, IL-1β and IL-6 mRNA expression in both RAW264.7 cells and mouse primary peritoneal macrophages, and inhibited LPS-induced activation of p38 MAPK but not of JNK, ERK. Moreover, DCO-6 specifically inhibited TLR4-dependent p38 activation without directly inhibiting its kinase activity. LPS-induced production of intracellular reactive oxygen species (ROS was remarkably impaired by DCO-6, which disrupted the formation of the TRAF6-ASK1 complex. Administering DCO-6 significantly protected mice from LPS-induced septic shock in parallel with the inhibition of p38 activation and ROS production. Our results indicate that DCO-6 showed anti-inflammatory properties through inhibition of ROS-dependent activation of TRAF6-ASK1-p38 pathway. Blockade of the upstream events required for p38 MAPK action by DCO-6 may provide a new therapeutic option in the treatment of inflammatory diseases.

  19. IBU-octyl-cytisine, a novel bifunctional compound eliciting anti-inflammatory and cholinergic activity, ameliorates CNS inflammation by inhibition of T-cell activity.

    Science.gov (United States)

    Nizri, Eran; Irony-Tur-Sinai, Michal; Lavon, Iris; Meshulam, Haim; Amitai, Gabi; Brenner, Talma

    2007-09-01

    Experimental autoimmune encephalomyelitis (EAE) is a central nervous system (CNS) inflammatory model in which MOG-specific T-cells initiate an autoimmune attack leading to demyelinization and consequently, neurological damage and morbidity. As EAE pathogenesis results from the involvement of immune cells, CNS resident-cells and inflammatory mediators, our treatment strategy was to use a bifunctional compound with dual anti-inflammatory properties: a non-steroidal anti-inflammatory moiety and a nicotinic agonist moiety, intended to interact with the alpha7 nicotinic receptor present on immune cells. We used IBU-Octyl-Cytisine, with an ibuprofen (IBU) moiety and Cytisine, as the nicotinic agonist. The two moieties are attached by an eight carbon (octyl) spacer. Treatment of EAE with IBU-Octyl-Cytisine (2.5 mg/kg/day, i.p.) reduced significantly (by 70%) disease severity and inflammatory infiltrates in the spinal cord. An equivalent dose of IBU was ineffective, whereas Cytisine was significantly toxic. Treatment with IBU-Octyl-Cytisine inhibited the T-cell response toward the encephalitogenic epitope of myelin oligodendrocyte glycoprotein (MOG). In addition, expression of CCR5 by CD4(+)T-cells was lower, indicating a reduced migratory capacity following treatment. IBU-Octyl-Cytisine reduced Th(1) but not Th(2) cytokine production. This reduction was accompanied by a drop in the level of T-bet mRNA, a transcription factor pivotal to Th(1) lineage differentiation. Thus, IBU-Octyl-Cytisine is an effective treatment for EAE, influencing T-cell responses in several stages of disease pathogenesis. This bifunctional compound was more efficient than IBU or Cytisine separately, as well as than both moieties unconjugated. Thus, it seems that this strategy may be applicable in wider context.

  20. Anti-inflammatory potential of an ethyl acetate fraction isolated from Justicia gendarussa roots through inhibition of iNOS and COX-2 expression via NF-κB pathway.

    Science.gov (United States)

    Kumar, Kavitha S; Vijayan, Viji; Bhaskar, Shobha; Krishnan, Kripa; Shalini, V; Helen, A

    2012-01-01

    Justicia gendarussa Burm.f. (J. gendarussa) is a plant used as traditional medicine in different parts of India and China to treat inflammatory disorders like rheumatoid arthritis. But its mechanism of anti-inflammatory action is still unclear. Hence in this context, the objective of our study is to reveal the mechanism of anti-inflammatory activity of J. gendarussa which would form an additional proof to the traditional knowledge of this plant. The anti-inflammatory function and mechanism(s) of action was studied in an ethyl acetate fraction isolated from methanolic extract of J. gendarussa roots (EJG). Anti-inflammatory studies were conducted on rats using partitioned fractions isolated from methanolic extract of J. gendarussa roots. In carrageenan-induced rat paw edema, ethyl acetate fraction brought about 80% and 93% edema inhibition at 3rd and 5th hour at a dose of 50 mg/kg, when compared to other extracts and Voveran. We investigated whether EJG inhibits the release of cycloxygenase (COX), 5-lipoxygenase (5-LOX), interleukin-6 (IL-6) and nuclear factor kappa B (NF-κB) in LPS stimulated human peripheral blood mononuclear cells (hPBMCs). Results shows that EJG dose dependently inhibited LPS-activated COX, 5-LOX, IL-6, and NF-κB in hPBMCs. EJG also reduced LPS induced levels of iNOS and COX-2 mRNA expression in hPBMCs. This study provides an insight into the probable mechanism(s) underlying the anti-inflammatory activity of EJG and therefore, we report the first confirmation of the anti-inflammatory potential of this traditionally employed herbal medicine in vitro.

  1. Anti-Inflammatory and Gastroprotective Evaluation of Prodrugs of Piroxicam

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    Vivekkumar K. Redasani

    2014-01-01

    Full Text Available Therapeutically potential prodrugs of piroxicam were synthesized by effective masking of enolic hydroxyl group through generation of ester congeners. The reaction facilitated using N,N′-dicyclohexylcarbodiimide coupled with acetic acid, benzoic acid, p-toluic acid, m-toluic acid, and cinnamic acid. Synthesized prodrugs were characterized for confirmation of the said structures. The modification of piroxicam showed better anti-inflammatory activity as evoked by all prodrugs. Interestingly, compound 3e, cinnamic acid ester prodrug, depicted 75 percent inhibition of rat paw edema as compared to 56 percent for parent piroxicam at 6 h of study. The present work proves the applicability not only with increased anti-inflammatory activity, but also with marked attenuation in ulcerogenicity. Novel prodrug 3e, cinnamic acid derivative, was found to be the least ulcerogenic having ulcer index of 0.67 as compared to parent drug piroxicam with 2.67.

  2. Anti-inflammatory and cytotoxic activities of Bursera copallifera

    Science.gov (United States)

    Columba-Palomares, M. F. María C.; Villareal, Dra. María L.; Acevedo Quiroz, M. C. Macdiel E.; Marquina Bahena, M. C. Silvia; Álvarez Berber, Dra. Laura P.; Rodríguez-López, Dra. Verónica

    2015-01-01

    Background: The plant species Bursera copallifera (DC) bullock is used in traditional medicine to treat inflammation. The leaves of this plant can be prepared as an infusion to treat migraines, bronchitis, and dental pain Objective: The purpose of this study was to determine the anti-inflammatory and cytotoxic activities of organic extracts from the stems, stem bark, and leaves of B. copallifera, which was selected based on the knowledge of its traditional use. Materials and Methods: We evaluated the ability of extracts to inhibit mouse ear inflammation in response to topical application of 12-O tetradecanoylphorbol-13-acetate. The extracts with anti-inflammatory activity were evaluated for their inhibition of pro-inflammatory enzymes. In addition, the in vitro cytotoxic activities of the organic extracts were evaluated using the sulforhodamine B assay. Results: The hydroalcoholic extract of the stems (HAS) exhibited an anti-inflammatory activity of 54.3% (0.5 mg/ear), whereas the anti-inflammatory activity of the dichloromethane-methanol extract from the leaves (DMeL) was 55.4% at a dose of 0.1 mg/ear. Methanol extract from the leaves (MeL) showed the highest anti-inflammatory activity (IC50 = 4.4 μg/mL), hydroalcoholic extract of leaves, and DMeL also reduce the enzyme activity, (IC50 = 6.5 μg/mL, IC50 = 5.7 μg/mL), respectively, from stems HAS exhibit activity at the evaluated concentrations (IC50 =6.4 μg/mL). The hydroalcoholic extract of the stems exhibited the highest cytotoxic activity against a breast adenocarcinoma cell line (MCF7, IC50 = 0.90 μg/mL), whereas DMeL exhibited an IC50 value of 19.9 μg/mL. Conclusion: In conclusion, extracts from leaves and stems inhibited cyclooxygenase-1, which is the target enzyme for nonsteroidal anti inflammatory drugs, and some of these extracts demonstrated substantial antiproliferative effects against the MCF7 cell line. These results validate the traditional use of B. copallifera. PMID:26664022

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

    Science.gov (United States)

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

    2016-05-01

    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.

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

    Science.gov (United States)

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

    2014-01-01

    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.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    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....

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...

  7. Rational design, synthesis and evaluation of chromone-indole and chromone-pyrazole based conjugates: identification of a lead for anti-inflammatory drug.

    Science.gov (United States)

    Shaveta; Singh, Amrinder; Kaur, Matinder; Sharma, Surbhi; Bhatti, Rajbir; Singh, Palwinder

    2014-04-22

    Conjugates of chromone-indole and chromone-pyrazole were screened for cyclooxygenase-2 (COX-2), cyclooxygenase-1 (COX-1) and 5-lipoxygenase (5-LOX) inhibitory activities. Compounds 8 and 9 were identified as preferred inhibitors of COX-2 over the other two enzymes. Their IC50 for COX-2 was 29 nM and 20 nM, respectively and selectivity indices (SI) for COX-2 over COX-1 was 46 and 337. NMR, mass spectral studies and molecular modelling also indicated preferential interactions of compounds 8 and 9 with COX-2. Tested on albino mice against capsaicin induced algesia, compound 8 exhibited analgesic potential comparable to diclofenac. In addition to the biological profile, the desirable physico-chemical properties of these compounds make them promising leads for anti-inflammatory drugs.

  8. (1)H-Nuclear magnetic resonance-based metabolic profiling of nonsteroidal anti-inflammatory drug-induced adverse effects in rats.

    Science.gov (United States)

    Um, So Young; Park, Jung Hyun; Chung, Myeon Woo; Choi, Ki Hwan; Lee, Hwa Jeong

    2016-09-10

    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.

  9. Studies on the protective effect of ebrotidine on experimental ulcers induced by non-steroidal anti-inflammatory drugs in healthy volunteers.

    Science.gov (United States)

    Puscas, I; Puscas, C; Coltau, M; Torres, J; Márquez, M; Herrero, E; Fillat, O; Ortiz, J A

    1997-04-01

    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.

  10. Anti-inflammatory effect of cannabinoid agonist WIN55, 212 on mouse experimental colitis is related to inhibition of p38MAPK

    Science.gov (United States)

    Feng, Ya-Jing; Li, Yong-Yu; Lin, Xu-Hong; Li, Kun; Cao, Ming-Hua

    2016-01-01

    AIM To investigate the anti-inflammatory effect and the possible mechanisms of an agonist of cannabinoid (CB) receptors, WIN55-212-2 (WIN55), in mice with experimental colitis, so as to supply experimental evidence for its clinical use in future. METHODS We established the colitis model in C57BL/6 mice by replacing the animals’ water supply with 4% dextran sulfate sodium (DSS) for 7 consecutive days. A colitis scoring system was used to evaluate the severity of colon local lesion. The plasma levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and the myeloperoxidase (MPO) activity in colon tissue were measured. The expressions of cannabinoid receptors, claudin-1 protein, p38 mitogen-activated protein kinase (p38MAPK) and its phosphorylated form (p-p38) in colon tissue were determined by immunohistochemistry and Western blot. In addition, the effect of SB203580 (SB), an inhibitor of p38, was investigated in parallel experiments, and the data were compared with those from intervention groups of WIN55 and SB alone or used together. RESULTS The results demonstrated that WIN55 or SB treatment alone or together improved the pathological changes in mice with DSS colitis, decreased the plasma levels of TNF-α, and IL-6, and MPO activity in colon. The enhanced expression of claudin-1 and the inhibited expression of p-p38 in colon tissues were found in the WIN55-treated group. Besides, the expression of CB1 and CB2 receptors was enhanced in the colon after the induction of DSS colitis, but reduced when p38MAPK was inhibited. CONCLUSION These results confirmed the anti-inflammatory effect and protective role of WIN55 on the mice with experimental colitis, and revealed that this agent exercises its action at least partially by inhibiting p38MAPK. Furthermore, the results showed that SB203580, affected the expression of CB1 and CB2 receptors in the mouse colon, suggesting a close linkage and cross-talk between the p38

  11. Anti-inflammatory activity of D-002: an active product isolated from beeswax.

    Science.gov (United States)

    Carbajal, D; Molina, V; Valdés, S; Arruzazabala, M L; Más, R; Magraner, J

    1998-10-01

    D-002 is a natural mixture of high molecular weight alcohols isolated and purified from beeswax, which contains triacontanol among its main components. This study was undertaken to investigate the anti-inflammatory effects of D-002 administered by the oral route in two animal models commonly used in the pharmacological screening of anti-inflammatory drugs. D-002 administered orally to rats (100 and 200 mg/kg) produced a mild but significant reduction of exudate volume in carrageenan-induced pleuritic inflammation that was accompanied by a marked and significant decrease of leukotriene B4 (LTB4) levels in the exudate. D-002 (25, 50 and 200 mg/kg) also significantly diminished the granuloma weight in the cotton pellet granuloma in rats. In both cases, D-002 was less effective than indomethacin, which was used as an established anti-inflammatory reference drug. On the other hand, D-002 administered from 25-1000 mg/kg did not induce erosions or gastromucosal lesions in rats, which differs from results usually obtained with non steroidal anti-inflammatory drugs. These results indicate that D-002 is a mild anti-inflammatory agent without any ulcerogenic effect associated. The results suggest that these effects are probably not mediated through an inhibition of cyclooxygenase, but a reduction in LTB4 levels induced by D-002 could explain these results.

  12. Antinociceptive and anti-inflammatory activities of a pomegranate (Punica granatum L.) extract rich in ellagitannins.

    Science.gov (United States)

    González-Trujano, María Eva; Pellicer, Francisco; Mena, Pedro; Moreno, Diego A; García-Viguera, Cristina

    2015-01-01

    Pomegranate (Punica granatum L.) has been used for centuries for the treatment of inflammatory diseases. However, there is a lack of comprehensive information focused on the properties of a certain pomegranate (poly)phenolic profile to cure pain and gastric injury induced by anti-inflammatory drugs. This study investigated the systemic effects of different doses of a HPLC-characterized pomegranate extract on the formalin-induced nociceptive behavior in mice. The effect of the extract against gastric injury caused by non-steroidal anti-inflammatory drugs and ethanol was also assessed. Pomegranate reduced nociception in both phases of the formalin test, suggesting central and peripheral activities to inhibit nociception. Indomethacin-induced gastric injury was not produced in the presence of pomegranate, which also protected against ethanol-induced gastric lesions. The present results reinforce the benefits of pomegranate (poly)phenolics in the treatment of pain as well as their anti-inflammatory properties.

  13. 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.

    Science.gov (United States)

    2011-09-01

    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

  14. Anti-wrinkle and anti-inflammatory effects of active garlic components and the inhibition of MMPs via NF-κB signaling.

    Directory of Open Access Journals (Sweden)

    So Ra Kim

    Full Text Available Skin aging is a multisystem degenerative process caused by several factors, such as, UV irradiation, stress, and smoke. Furthermore, wrinkle formation is a striking feature of photoaging and is associated with oxidative stress and inflammatory response. In the present study, we investigated whether caffeic acid, S-allyl cysteine, and uracil, which were isolated from garlic, modulate UVB-induced wrinkle formation and effect the expression of matrix-metalloproteinase (MMP and NF-κB signaling. The results obtained showed that all three compounds significantly inhibited the degradation of type І procollagen and the expressions of MMPs in vivo and attenuated the histological collagen fiber disorder and oxidative stress in vivo. Furthermore, caffeic acid and S-allyl cysteine were found to decrease oxidative stress and inflammation by modulating the activities of NF-κB and AP-1, and uracil exhibited an indirect anti-oxidant effect by suppressing cyclooxygenase-2 (COX-2 and inducible nitric oxide synthase (iNOS expressions levels and downregulating transcriptional factors. These results suggest that the anti-wrinkle effects of caffeic acid, S-allyl cysteine, and uracil are due to anti-oxidant and/or anti-inflammatory effects. Summarizing, caffeic acid, S-allyl cysteine, and uracil inhibited UVB-induced wrinkle formation by modulating MMP via NF-κB signaling.

  15. Proton pump inhibitors are not the key for therapying non-steroidal anti-inflammatory drugs-induced small intestinal injury.

    Science.gov (United States)

    Zhang, Shuo; Chao, Guan-qun; Lu, Bin

    2013-10-01

    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.

  16. Anti-inflammatory and antioxidant effect of Kerabala: a value-added ayurvedic formulation from virgin coconut oil inhibits pathogenesis in adjuvant-induced arthritis.

    Science.gov (United States)

    Ratheesh, M; Sandya, S; Pramod, C; Asha, S; Svenia, Jose P; Premlal, S; GrishKumar, B

    2017-02-01

    Kerabala (CB) is a novel ayurvedic formulation used for treating various inflammatory diseases. This formulation was made from virgin coconut oil and it comprises extracts of Sida cordifolia, coconut milk and sesame oil. The current study was performed to evaluate the anti-inflammatory action of CB on carrageenan-induced acute and adjuvant-induced chronic experimental models. 5 mg/kg bwt was found to be potent dose from carrageenan model and evaluated its effect in adjuvant-induced chronic arthritic model. The antioxidant assays like SOD, catalase, glutathione peroxidase, lipid peroxidation product, nitrate level and GSH were measured in paw tissue. Hematological parameters like hemoglobin (HB) count, ESR, WBC count, plasma CRP levels were analyzed. By RT-PCR, the inflammatory markers like cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) expressions were evaluated. The extracellular matrix proteins like MMP-2 and MMP-9 were determined by zymography and its expression by western blotting. Histopathology and cytology of paw tissue and synovium were analyzed. The result indicated that there was a significant increment in the levels of antioxidant enzymes on CB administration. The hematological markers such as ESR, WBC and plasma CRP levels were reduced by CB treatment and it also increases the HB level. The upregulated gene level expressions of inflammatory markers like COX-2, iNOS, TNF-α and IL-6 were down regulated by administration of CB. MMP-2 and MMP-9 expression significantly reduced by CB administration. Massive influx of inflammatory cell infiltration, proliferative collagen in histological analysis of paw tissue of arthritic rat was decreased by CB administration. Synovial cytology of CB administrated group shows reduced number of reactive mesothelial cells and synovial inflammatory cells. This current study shows that ayurvedic drug CB has an antioxidant, anti-inflammatory and

  17. Evaluation of anti-inflammatory activity of some Libyan medicinal plants in experimental animals

    Directory of Open Access Journals (Sweden)

    Nahar Lutfun

    2012-01-01

    Full Text Available Ballota pseudodictamnus (L. Benth. (Lamiaceae, Salvia fruticosa Mill. (Lamiaceae and Thapsia garganica L. (Apiaceae are three well-known medicinal plants from the Libyan flora, which have long been used for the treatment of inflammations. The aim of the present study was to investigate, for the first time, the anti-inflammatory property of the methanol (MeOH extracts of the aerial parts of these plants. Shade-dried and ground aerial parts of B. pseudodictamnus, S. fruticosa and T. garganica were Soxhlet-extracted with MeOH. The extracts were concentrated by evaporation under reduced pressure at 40°C. The anti-inflammatory activity of the extracts was evaluated using the carrageenan-induced mice paw edema model. The administration of the extracts at a dose of 500 mg/kg body weight produced statistically significant inhibition (p < 0.05 of edema within 3 h of carrageenan administration. The results demonstrated significant anti-inflammatory properties of the test extracts. Among the extracts, the S. fruticosa extract exhibited the most significant inhibition of inflammation after 3 h (62.1%. Thus, S. fruticosa could be a potential source for the discovery and development of newer anti-inflammatory ‘leads’ for drug development. The anti-inflammatory activity of B. pseudodictamnus and S. fruticosa could be assumed to be related to high levels of phenolic compounds, e.g., flavonoids, present in these plants.

  18. Detecting drug-drug interactions using a database for spontaneous adverse drug reactions : an example with diuretics and non-steroidal anti-inflammatory drugs

    NARCIS (Netherlands)

    van Puijenbroek, E P; Egberts, A C; Heerdink, E R; Leufkens, H G

    2000-01-01

    OBJECTIVE: Drug-drug interactions are relatively rarely reported to spontaneous reporting systems (SRSs) for adverse drug reactions. For this reason, the traditional approach for analysing SRS has major limitations for the detection of drug-drug interactions. We developed a method that may enable si

  19. A novel glucosamine derivative exerts anti-inflammatory actions via inhibition of nuclear factor-kappaB.

    Science.gov (United States)

    Shin, Jin-A; Hwang, Ji-Sun; Kim, Song-Yi; Oh, Sei-Kwan; Nam, Ghilsoo; Han, Inn-Oc

    2013-08-29

    Glucosamine suppresses lipopolysaccharide (LPS)-induced upregulation of pro-inflammatory mediators both in vivo and in culture systems of mouse microglia or macrophage. In the present study, we show that the novel glucosamine derivative, 2-deoxy-2-[(o-methylbenzylidene)]-β-glucopyranoside (NK-4), significantly reduced LPS-induced production of nitric oxide (NO) in BV2 microglia, RAW264.7 macrophage, and primary cultured peritoneal macrophages cells. NK-4 inhibited LPS-induced upregulation of inducible NO synthase (iNOS), cyclooxygenase-2, interleukin-6, tumor necrosis factor-α, and interleukin-1β in RAW264.7 cells in a time- and concentration-dependent manner. Furthermore, administering NK-4 significantly inhibited the induction of inflammatory cytokine mRNAs in the brains of LPS-injected mice. Although NK-4 inhibited LPS-induced nuclear factor-kappaB (NF-κB) activation, IκB-α degradation was not changed. Instead, NK-4 inhibited LPS-induced DNA-binding activity of NF-κB by suppressing p50 and c-Rel binding to NF-κB binding site of the iNOS promoter.

  20. 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

    NARCIS (Netherlands)

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

    2004-01-01

    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

  1. 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

    NARCIS (Netherlands)

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

    2004-01-01

    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

  2. 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

    NARCIS (Netherlands)

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

    2007-01-01

    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

  3. 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

    NARCIS (Netherlands)

    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.

    2008-01-01

    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

  4. 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

    NARCIS (Netherlands)

    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.

    2009-01-01

    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

  5. 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)

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...

  6. Anti-inflammatory activity of atractylenolide III through inhibition of nuclear factor-κB and mitogen-activated protein kinase pathways in mouse macrophages.

    Science.gov (United States)

    Ji, Guang-Quan; Chen, Ren-Qiong; Wang, Ling

    2016-01-01

    To elucidate the anti-inflammatory mechanisms involved, we investigated the effects of atractylenolide III (ATL-III) on cytokine expression, extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38 mitogen-activated protein kinase (p38), C-Jun-N-terminal protein kinase1/2 (JNK1/2) and nuclear factor-κB (NF-κB) pathways in lipopolysaccharide (LPS)-induced RAW264.7 mouse macrophages. Macrophages were incubated with various concentrations (0, 25, 50, 100 μM) of ATL-III and/or LPS (1 μg/mL) for 24 h. The production of nitric oxide (NO) was determined by the Greiss reagent. The production of tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE2) and interleukin 6 (IL-6) was determined by enzyme-linked immunosorbent assay (ELISA). Furthermore, macrophages were treated with ATL-III (0, 25, 100 μM) for 1 h and then stimulated by LPS. NF-κB, p38, JNK1/2 and ERK1/2 were determined by western blotting. We found ATL-III showed no inhibitory effect on cell proliferation at concentrations ranging from 1 μM to 100 μM. In addition, ATL-III decreased the release of NO, TNF-α, PGE2 and IL-6 in a dose-dependent manner and showed statistically significant at concentrations of 50 μM and 100 μM as well as cyclooxygenase-2 (COX-2) expression. Furthermore, ATL-III suppressed the transcriptional activity of NF-κB. ATL-III also inhibited the activation of ERK1/2, p38 and JNK1/2 in LPS-treated macrophages and showed statistically significant at concentrations of 25 μM and 100 μM. These data suggest that ATL-III shows an anti-inflammatory effect by suppressing the release of NO, PGE2, TNF-α and IL-6 related to the NF-κB- and MAPK-signaling pathways.

  7. Defining Therapeutic Targets by Using Adenovirus: Blocking NF-kappa B Inhibits Both Inflammatory and Destructive Mechanisms in Rheumatoid Synovium but Spares Anti-Inflammatory Mediators

    Science.gov (United States)

    Bondeson, Jan; Foxwell, Brian; Brennan, Fionula; Feldmann, Marc

    1999-05-01

    The role of the transcription factor NF-kappa B in the pathogenesis of rheumatoid arthritis has long been a subject of controversy. We used an adenoviral technique of blocking NF-kappa B through overexpression of the inhibitory subunit Ikappa Bα , which has the advantage that it can be used in the diseased tissue itself, with >90% of the synovial macrophages, fibroblasts, and T cells infected. We found that the spontaneous production of tumor necrosis factor α and other pro-inflammatory cytokines is NF-kappa B-dependent in rheumatoid synovial tissue, in contrast to the main anti-inflammatory mediators, like IL-10 and -11, and the IL-1 receptor antagonist. Of even more interest, Ikappa Bα overexpression inhibited the production of matrix metalloproteinases 1 and 3 while not affecting their tissue inhibitor. Blocking NF-kappa B in the rheumatoid joint thus has a very beneficial profile, reducing both the inflammatory response and the tissue destruction. The adenoviral technique described here has widespread applicability, allowing rapid testing of the effects of blocking a potential therapeutic target in either cultures of normal cells or in the diseased tissue itself.

  8. Anti-inflammatory effects of bifidobacteria by inhibition of LPS-induced NF-κB activation

    Institute of Scientific and Technical Information of China (English)

    Christian U Riedel; Francis Foata; David Philippe; Oskar Adolfsson; Bernhard J Eikmanns; Stephanie Blum

    2006-01-01

    AIM: Different strains of bifidobacteria were analysed for their effects on HT-29 intestinal epithelial cells (IECs)in in vitro models both of the non-inflamed and inflamed intestinal epithelium.METHODS: A reporter gene system in HT-29 cells was used to measure levels of NF-κB activation after challenge with bifidobacteria or after bacterial pre-treatment following LPS challenge. IL-8 protein and pro-inflammatory gene expression was investigated using normal HT-29 cells.RESULTS: None of the bifidobacteria tested induced activation of nuclear factor KB (NF-κB) indicating that bifidobacteria themselves do not induce inflammatory events in IECs. However, six out of eight bifidobacteria tested inhibited lipopolysaccharide- (LPS-) induced NFκB activation in a dose- and strain-dependent manner. In contrast, NF-κB activation in response to challenge with tumor necrosis factor-α (TNF-α) was affected by none of the tested bifidobacteria, indicating that the inhibitory effect of bifidobacteria is specific for LPS-induced infiammation in IECs. As shown with two of the six inhibitionpositive bifidobacteria, LPS-induced inhibition of NFκB activation was accompanied by a dose-dependent decrease of interleukin 8 (IL-8) secretion and by lower mRNA levels for IL-8, TNF-α, cyclooxygenase 2 (Cox-2),and intercellular adhesion molecule 1 (ICAM-1).CONCLUSION: Some strains of bifidobacteria are effective in inhibiting LPS-induced inflammation and thus might be appropriate candidates for probiotic intervention in chronic intestinal inflammation.

  9. A STUDY OF PRESCRIBING PATTERN OF NON STEROIDAL ANTI INFLAMMATORY DRUGS IN ORTHOPEDIC OUT PATIENT DEPARTMENT AT A TERTIARY CARE HOSPITAL

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    Asha Latha

    2015-01-01

    Full Text Available AIM: To determine the pattern of NON STEROIDAL ANTI INFLAMMATORY DRUGS prescribing for arthritic and non - arthritic conditions in orthopedic outpatient department . METHODOLOGY: 100 prescription duplicate collected and analyzed prospectively for the pattern of NSAID prescription for arthritic and non - arthritic conditions; the drug formulation , route , frequency, duration of adm issio n and concomitant medications results. NSAID were prescribed for non - traumatic musculo skeletal 35% pain, 25% post traumatic pain, 20% osteoarthritis, 10% post - operative pain, 3% ankylosing spondylitis, 6% degenerativ e disease of spine, 1% neuralgia. The NSAIDs commonly prescribed were Aceclofenac 45%, Etodolac 20%, Diclofenac 24%, and Ibuprofen 11%. Fixed dose combination of NSAIDs with adjuvante was prescribed in. The adjuvants, included are paracetamol 55.6%, serrat opeptidase 32.8%, chlorzoxazone 9.1%, Thiocolchichoside 2.5%. oral formulations of NSAIDs were prescribed in all patients, supplemented by Topical formulations as gel/cream in 15% of subjects. The dosing frequency was BID (65%, OD (25%, TID (2%, SOS (8% . Duration of administration ranged from 5 - 15 days . other classes of drugs used concomitantly were proton pump inhibitors , calcium supplements, Multivitamins, Anti microbials, Immuno suppressants, and Glucosamine. CONCLUSION: NSAIDs were prescribed empiric all y for various arthritic and Non - arthritic conditions, frequently as fixed dose combinations [FDC]s with various adjuvants as per the standard guide lines. However patient information was inadequate in most of the prescriptions. Proper patient Assessment deemed necessary for individualizing NSAIDs.

  10. Microextraction by packed sorbent and HPLC-PDA quantification of multiple anti-inflammatory drugs and fluoroquinolones in human plasma and urine.

    Science.gov (United States)

    D'Angelo, Veronica; Tessari, Francesco; Bellagamba, Giuseppe; De Luca, Elisa; Cifelli, Roberta; Celia, Christian; Primavera, Rosita; Di Francesco, Martina; Paolino, Donatella; Di Marzio, Luisa; Locatelli, Marcello

    2016-01-01

    We developed and validated an analytical method based on microextraction packed sorbent (MEPS) and high-performance liquid chromatography (HPLC) coupled to photodiode array (PDA) detector to simultaneously quantify multiple nonsteroidal anti-inflammatory drugs (NSAIDs) and fluoroquinolones (FLQs), which may provide as combination several adverse reactions in nephrology and neurology. The linearity range from LOQs (0.1 μg/mL) to 10 μg/mL, and LODs values were 0.03 μg/mL for both NSAIDs and FLQs. The validation was performed according to international guidelines and the accuracy was tested measuring the precision, intermediate precision and trueness. The drugs stability was tested under different storage conditions (+4 °C and -20 °C) and after three different cycles of freezing and thawing. The method can be a suitable tool to simultaneously detect a possible association of drugs in human biological samples and provide several potentialities for clinical applications, bioequivalence studies, pharmacodynamics and toxicodynamics of different pharmaceutical dosage forms showing NSAIDs and FLQs.

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

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    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

    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.

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

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    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.

  14. The anti-inflammatory effects of venlafaxine in the rat model of carrageenan-induced paw edema

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    Valiollah Hajhashemi

    2015-07-01

    Full Text Available Objective(s:Recently anti-inflammatory effects of antidepressants have been demonstrated. Venlafaxine belongs to newer antidepressants with serotonin norepinephrine reuptake inhibition property. The pain alleviating properties of venlafaxine in different pain models such as neurogenic pain, diabetic neuropathy, and fibromyalgia have been demonstrated. Anti-inflammatory effects of venlafaxine and also its underlying mechanisms remain unclear. The present study was designed to evaluate the anti-inflammatory effects of venlafaxine and determine possible underlying mechanisms. Materials and Methods: We examined the anti-inflammatory effects of intraperitoneal (IP and intracerebroventricular (ICV administration of venlafaxine in the rat model of carrageenan-induced paw edema. Results: Our results showed that both IP (50 and 100 mg/kg and ICV (50 and 100 μg/rat injection of venlafaxine inhibited carrageenan-induced paw edema. Also IP and ICV administration of venlafaxine significantly decreased myeloperoxidase (MPO activity and interleukin (IL-1β and tumor necrosis factor (TNF-α production. Finally, we tried to reverse the anti-inflammatory effect of venlafaxine by yohimbine (5 mg/kg, IP, an alpha2-adrenergic antagonist. Our results showed that applied antagonist failed to change the anti-inflammatory effect of venlafaxine. Conclusion: These results demonstrated that venlafaxine has potent anti-inflammatory effect which is related to the peripheral and central effects of this drug. Also we have shown that anti-inflammatory effect of venlafaxine is mediated mostly through the inhibition of IL-1β and TNF-α production and decreases MPO activity in the site of inflammation.

  15. Benzophenone-N-ethyl piperidine ether analogues--synthesis and efficacy as anti-inflammatory agent.

    Science.gov (United States)

    Khanum, Shaukath A; Girish, V; Suparshwa, S S; Khanum, Noor Fatima

    2009-04-01

    A sequence of substituted benzophenone-N-ethyl piperidine ether analogues has been synthesized and evaluated as orally active anti-inflammatory agents with reduced side effects. The anti-inflammatory and ulcerogenic activities of the compounds were compared with naproxen, indomethacin, and phenylbutazone. These analogues showed an interesting anti-inflammatory activity in carrageenan-induced foot pad edema assay. In the air-pouch test, some of the analogues reduced the total number of leukocytes of the exudate, which indicates inhibition of prostaglandin production. Side effects of the compounds were examined on gastric mucosa, in the liver and stomach. None of the compounds illustrated significant side effects compared with standard drugs like indomethacin and naproxen.

  16. Inhibition of Age-Related Cytokines Production by ATGL: A Mechanism Linked to the Anti-Inflammatory Effect of Resveratrol

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    Daniele Lettieri Barbato

    2014-01-01

    Full Text Available Ageing is characterized by the expansion and the decreased vascularization of visceral adipose tissue (vAT, disruption of metabolic activities, and decline of the function of the immune system, leading to chronic inflammatory states. We previously demonstrated that, in vAT of mice at early state of ageing, adipocytes mount a stress resistance response consisting in the upregulation of ATGL, which is functional in restraining the production of inflammatory cytokines. Here, we found that, in the late phase of ageing, such an adaptive response is impaired. In particular, 24-months-old mice and aged 3T3-L1 adipocytes display affected expression of ATGL and its downstream PPARα-mediated lipid signalling pathway, leading to upregulation of TNFα and IL-6 production. We show that the natural polyphenol compound resveratrol (RSV efficiently suppresses the expression of TNFα and IL-6 in an ATGL/PPARα dependent manner. Actually, adipocytes downregulating ATGL do not show a restored PPARα expression and display elevated cytokines production. Overall the results obtained highlight a crucial function of ATGL in inhibiting age-related inflammation and reinforce the idea that RSV could represent a valid natural compound to limit the onset and/or the exacerbation of the age-related inflammatory states.

  17. Partitioning of anti-inflammatory steroid drugs into phosphatidylcholine and phosphatidylcholine-cholesterol small unilamellar vesicles as studied by second-derivative spectrophotometry.

    Science.gov (United States)

    Takegami, Shigehiko; Kitamura, Keisuke; Funakoshi, Takako; Kitade, Tatsuya

    2008-05-01

    The partition coefficients (Kps) of six anti-inflammatory steroid drugs, dexamethasone (DMS), betamethasone (BMS), triamcinolone acetonide (TCLA), fluocinolone acetonide (FCLA), betamethasone 17,21-dipropionate (BMSDP), and clobetasole propionate (CBSP), for phosphatidylcholine (PC), and PC-cholesterol small unilamellar vesicles (SUVs) were determined by a second-derivative spectrophotometric method. The Kp values were obtained with a relative standard deviation of below 10% and the following order was observed: BMS< or =DMSdrugs examined, i.e., the Kp value of CBSP was 1.2 times that of BMSDP. The presence of 30 mol% cholesterol in the SUV bilayers reduced these Kp values to approximately 35-50% of those values for the PC SUVs, although the order of the Kp values remained unchanged. The order of the Kp values agreed with that of the reported dermatological therapeutic potency of these drugs, although the order of their log P values for n-octanol/water systems showed a discrepancy. Our results indicate that the potency of steroid drugs in dermatological treatments depends to some extent on the Kp values of the drug, that is, the affinity of steroid drugs for PC bilayers influences their clinical potency, since potency is related to transdermal absorption.

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

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    Szweda Magdalena

    2014-10-01

    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.

  19. Enhancement of Anti-Inflammatory Activity of Curcumin Using Phosphatidylserine-Containing Nanoparticles in Cultured Macrophages

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    Ji Wang

    2016-06-01

    Full Text Available Macrophages are one kind of innate immune cells, and produce a variety of inflammatory cytokines in response to various stimuli, such as oxidized low density lipoprotein found in the pathogenesis of atherosclerosis. In this study, the effect of phosphatidylserine on anti-inflammatory activity of curcumin-loaded nanostructured lipid carriers was investigated using macrophage cultures. Different amounts of phosphatidylserine were used in the preparation of curcumin nanoparticles, their physicochemical properties and biocompatibilities were then compared. Cellular uptake of the nanoparticles was investigated using a confocal laser scanning microscope and flow cytometry analysis in order to determine the optimal phosphatidylserine concentration. In vitro anti-inflammatory activities were evaluated in macrophages to test whether curcumin and phosphatidylserine have interactive effects on macrophage lipid uptake behavior and anti-inflammatory responses. Here, we showed that macrophage uptake of phosphatidylserine-containing nanostructured lipid carriers increased with increasing amount of phosphatidylserine in the range of 0%–8%, and decreased when the phosphatidylserine molar ratio reached over 12%. curcumin-loaded nanostructured lipid carriers significantly inhibited lipid accumulation and pro-inflammatory factor production in cultured macrophages, and evidently promoted release of anti-inflammatory cytokines, when compared with curcumin or phosphatidylserine alone. These results suggest that the delivery system using PS-based nanoparticles has great potential for efficient delivery of drugs such as curcumin, specifically targeting macrophages and modulation of their anti-inflammatory functions.

  20. Non-steroidal anti-inflammatory drugs and paracetamol in self-therapy of various disorders in students of different fields of study.

    Science.gov (United States)

    Wiliński, Jerzy; Lechowicz, Marta; Kameczura, Tomasz; Głowacki, Mikołaj; Kameczura, Anna; Chrapusta, Anna; Wiliński, Bogdan

    2015-01-01

    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.

  1. Efficacy of anti-inflammatory therapy in a model of acute seizures and in a population of pediatric drug resistant epileptics.

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    Nicola Marchi

    Full Text Available Targeting pro-inflammatory events to reduce seizures is gaining momentum. Experimentally, antagonism of inflammatory processes and of blood-brain barrier (BBB damage has been demonstrated to be beneficial in reducing status epilepticus (SE. Clinically, a role of inflammation in the pathophysiology of drug resistant epilepsies is suspected. However, the use anti-inflammatory drug such as glucocorticosteroids (GCs is limited to selected pediatric epileptic syndromes and spasms. Lack of animal data may be one of the reasons for the limited use of GCs in epilepsy. We evaluated the effect of the CG dexamethasone in reducing the onset and the severity of pilocarpine SE in rats. We assessed BBB integrity by measuring serum S100β and Evans Blue brain extravasation. Electrophysiological monitoring and hematologic measurements (WBCs and IL-1β were performed. We reviewed the effect of add on dexamethasone treatment on a population of pediatric patients affected by drug resistant epilepsy. We excluded subjects affected by West, Landau-Kleffner or Lennox-Gastaut syndromes and Rasmussen encephalitis, known to respond to GCs or adrenocorticotropic hormone (ACTH. The effect of two additional GCs, methylprednisolone and hydrocortisone, was also reviewed in this population. When dexamethasone treatment preceded exposure to the convulsive agent pilocarpine, the number of rats developing status epilepticus (SE was reduced. When SE developed, the time-to-onset was significantly delayed compared to pilocarpine alone and mortality associated with pilocarpine-SE was abolished. Dexamethasone significantly protected the BBB from damage. The clinical study included pediatric drug resistant epileptic subjects receiving add on GC treatments. Decreased seizure frequency (≥ 50% or interruption of status epilepticus was observed in the majority of the subjects, regardless of the underlying pathology. Our experimental results point to a seizure-reducing effect of

  2. Optimization and pharmacological validation of a leukocyte migration assay in zebrafish larvae for the rapid in vivo bioactivity analysis of anti-inflammatory secondary metabolites.

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    María Lorena Cordero-Maldonado

    Full Text Available Over the past decade, zebrafish (Danio rerio have emerged as an attractive model for in vivo drug discovery. In this study, we explore the suitability of zebrafish larvae to rapidly evaluate the anti-inflammatory activity of natural products (NPs and medicinal plants used in traditional medicine for the treatment of inflammatory disorders. First, we optimized a zebrafish assay for leukocyte migration. Inflammation was induced in four days post-fertilization (dpf zebrafish larvae by tail transection and co-incubation with bacterial lipopolysaccharides (LPS, resulting in a robust recruitment of leukocytes to the zone of injury. Migrating zebrafish leukocytes were detected in situ by myeloperoxidase (MPO staining, and anti-inflammatory activity was semi-quantitatively scored using a standardized scale of relative leukocyte migration (RLM. Pharmacological validation of this optimized assay was performed with a panel of anti-inflammatory drugs, demonstrating a concentration-responsive inhibition of leukocyte migration for both steroidal and non-steroidal anti-inflammatory drugs (SAIDs and NSAIDs. Subsequently, we evaluated the bioactivity of structurally diverse NPs with well-documented anti-inflammatory properties. Finally, we further used this zebrafish-based assay to quantify the anti-inflammatory activity in the aqueous and methanolic extracts of several medicinal plants. Our results indicate the suitability of this LPS-enhanced leukocyte migration assay in zebrafish larvae as a front-line screening platform in NP discovery, including for the bioassay-guided isolation of anti-inflammatory secondary metabolites from complex NP extracts.

  3. [Effect of anti-inflammatory drugs, alone and combined with ofloxacin, on the respiratory burst of human polymorphonuclear leukocytes].

    Science.gov (United States)

    Cabrera, E; Velert, M M; Orero, A; Martínez, P; Cantón, E

    2001-06-01

    The antibacterial activity of polymorphonuclear leukocytes (PMNs) is based on the production of superoxide anion and H(2)O(2) in the respiratory burst and can be impaired in different ways. The combination of an antibacterial agent and an antiinflammatory drug is quite common in immunodepressed patients whose respiratory burst of PMN could be impaired. In this study we examine in vitro the effect of pretreating (35 degrees C for 30 min) PMNs with the antiinflammatory drugs dexamethasone (0.4, 4 and 40 microgram/ml), methylprednisolone (0.37, 3.7 and 37 microgram/ ml), hydrocortisone (0.048, 0.48 and 4.8 microgram/ml), betamethasone (0.1, 1, 5 and 10 mg/ml), phenylbutazone (1000 microgram/ml) and acetylsalicylic acid (25, 250, 2500 microgram/ml) alone, and combined with 10 mg/ml of ofloxacin on the respiratory burst. Superoxide anion was measured by the cytochrome c reduction microtechnique and H(2)O(2) by phenol red. The antiinflammatory drugs alone decreased the production of H(2)O(2) (except dexamethasone and methylprednisolone) and superoxide anion (except betamethasone) from 15-45%, depending on the antiinflammatory drug and concentration, while ofloxacin increased the production of superoxide anion (20.2 +/- 6.7%). The combination of antiinflammatory drugs with ofloxacin neutralizes the inhibitory effect of the former on the respiratory burst of PMNs. It is therefore important to know the effect of drugs on the respiratory burst in order to choose those that have the same therapeutic effect without interfering with PMN functions.

  4. Anti-inflammatory and immunomodulatory properties of Carica papaya.

    Science.gov (United States)

    Pandey, Saurabh; Cabot, Peter J; Shaw, P Nicholas; Hewavitharana, Amitha K

    2016-07-01

    Chronic inflammation is linked with the generation and progression of various diseases such as cancer, diabetes and atherosclerosis, and anti-inflammatory drugs therefore have the potential to assist in the treatment of these conditions. Carica papaya is a tropical plant that is traditionally used in the treatment of various ailments including inflammatory conditions. A literature search was conducted by using the keywords "papaya", "anti-inflammatory and inflammation" and "immunomodulation and immune" along with cross-referencing. Both in vitro and in vivo investigation studies were included. This is a review of all studies published since 2000 on the anti-inflammatory activity of papaya extracts and their effects on various immune-inflammatory mediators. Studies on the anti-inflammatory activities of recognized phytochemicals present in papaya are also included. Although in vitro and in vivo studies have shown that papaya extracts and papaya-associated phytochemicals possess anti-inflammatory and immunomodulatory properties, clinical studies are lacking.

  5. Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes.

    Science.gov (United States)

    Nadanaciva, Sashi; Aleo, Michael D; Strock, Christopher J; Stedman, Donald B; Wang, Huijun; Will, Yvonne

    2013-10-15

    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.

  6. Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes

    Energy Technology Data Exchange (ETDEWEB)

    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: yvonne.will@pfizer.com [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States)

    2013-10-15

    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.

  7. Determination of Residual Nonsteroidal Anti-Inflammatory Drugs in Aqueous Sample Using Magnetic Nanoparticles Modified with Cetyltrimethylammonium Bromide by High Performance Liquid Chromatography

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    Malihe Khoeini Sharifabadi

    2014-01-01

    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.

  8. Anti-inflammatory effect of Mentha longifolia in lipopolysaccharide-stimulated macrophages: reduction of nitric oxide production through inhibition of inducible nitric oxide synthase.

    Science.gov (United States)

    Karimian, Parastoo; Kavoosi, Gholamreza; Amirghofran, Zahra

    2013-01-01

    Mentha longifolia is an aromatic plant used in flavoring and preserving foods and as an anti-inflammatory folk medicine remedy. The present study assessed the effects of M. longifolia extracts, including essential oil and crude methanol extract and its fractions (ethyl acetate, butanol and hexane), on nitric oxide (NO) production and inducible NO synthase (iNOS) mRNA expression in lipopolysaccharide (LPS)-stimulated J774A.1 cells using real-time polymerase chain reaction (PCR). The cytotoxic effects of the extracts on the cells were examined and non-cytotoxic concentrations (<0.2 mg/ml) were used to examine their effects on NO production and iNOS mRNA expression. Only the hexane fraction that contained high levels of phenolic and flavonoid compounds at concentrations from 0.05-0.20 mg/ml significantly reduced NO production in LPS-stimulated cells (p < 0.001). Real-time PCR analysis indicated the ability of this fraction at the same concentrations to significantly decrease iNOS as well as TNFα mRNA expression in the cells (p < 0.001). All extracts were able to scavenge NO radicals in a concentration-dependent manner. At concentrations greater than 0.2 mg/ml, total radicals were 100% scavenged. In conclusion, M. longifolia possibly reduces NO secretion in macrophages by scavenging NO and inhibiting iNOS mRNA expression, and also decreases TNFα pro-inflammatory cytokine expression, thus showing its usefulness in the inflammatory disease process.

  9. Sympathetic Nerve Activity Maintains an Anti-Inflammatory State in Adipose Tissue in Male Mice by Inhibiting TNF-α Gene Expression in Macrophages.

    Science.gov (United States)

    Tang, Lijun; Okamoto, Shiki; Shiuchi, Tetsuya; Toda, Chitoku; Takagi, Kazuyo; Sato, Tatsuya; Saito, Kumiko; Yokota, Shigefumi; Minokoshi, Yasuhiko

    2015-10-01

    Adipose tissue macrophages (ATMs) play an important role in the inflammatory response in obese animals. How ATMs are regulated in lean animals has remained elusive, however. We now show that the sympathetic nervous system (SNS) is necessary to maintain the abundance of the mRNA for the proinflammatory cytokine TNF-α at a low level in ATMs of lean mice. Intracerebroventricular injection of agouti-related neuropeptide increased the amount of TNF-α mRNA in epididymal (epi) white adipose tissue (WAT), but not in interscapular brown adipose tissue (BAT), through inhibition of sympathetic nerve activity in epiWAT. The surgical denervation and β-adrenergic antagonist propranolol up-regulated TNF-α mRNA in both epiWAT and BAT in vivo. Signaling by the β2-adrenergic receptor (AR) and protein kinase A down-regulated TNF-α mRNA in epiWAT explants and suppressed lipopolysaccharide-induced up-regulation of TNF-α mRNA in the stromal vascular fraction of this tissue. β-AR-deficient (β-less) mice manifested an increased plasma TNF-α concentration and increased TNF-α mRNA abundance in epiWAT and BAT. TNF-α mRNA abundance was greater in ATMs (CD11b(+) cells of the stromal vascular fraction) from epiWAT or BAT of wild-type mice than in corresponding CD11b(-) cells, and β2-AR mRNA abundance was greater in ATMs than in CD11b(-) cells of epiWAT. Our results show that the SNS and β2-AR-protein kinase A pathway maintain an anti-inflammatory state in ATMs of lean mice in vivo, and that the brain melanocortin pathway plays a role in maintaining this state in WAT of lean mice via the SNS.

  10. Multi-spectroscopic method study the interaction of anti-inflammatory drug ketoprofen and calf thymus DNA and its analytical application

    Science.gov (United States)

    Guo, Hongqin; Cai, Changqun; Gong, Hang; Chen, Xiaoming

    2011-06-01

    Interactions of the anti-inflammatory drug ketoprofen with calf thymus DNA (ctDNA) in aqueous solution have been studied by multi-spectroscopic method including resonance light scattering (RLS) technique, ultraviolet spectra (UV), 1H NMR, etc. The characteristics of RLS spectra, the effective factors and optimum conditions of the reaction have been unequivocally investigated. Mechanism investigations have shown that ketoprofen can bind to ctDNA by groove binding and form large particles, which resulted in the enhancement of RLS intensity. In Critic acid-Na 2HPO 4 buffer (pH = 6.5), ketoprofen has a maximum peak 451.5 nm and the RLS intensity is remarkably enhanced by trace amount of ctDNA due to the interaction between ketoprofen and ctDNA. The enhancement of RLS signal is directly proportional to the concentration of ctDNA in the range of 1.20 × 10 -6-1.0 × 10 -5 mol/L, and its detection limit (3 σ) is 1.33 × 10 -9 mol/L. The method is simple, rapid, practical and relatively free from interference generated by coexisting substance, and was applied to the determination of trace amounts of nucleic acid in synthetic samples with satisfactory results.

  11. 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.

    Science.gov (United States)

    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

    2015-01-01

    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.

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

    Science.gov (United States)

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

    2014-07-28

    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.

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

    Science.gov (United States)

    Skarydova, Lucie; Nobilis, Milan; Wsól, Vladimir

    2013-04-01

    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.

  14. Ecotoxicological potential of non-steroidal anti-inflammatory drugs (NSAIDs) in marine organisms: Bioavailability, biomarkers and natural occurrence in Mytilus galloprovincialis.

    Science.gov (United States)

    Mezzelani, M; Gorbi, S; Da Ros, Z; Fattorini, D; d'Errico, G; Milan, M; Bargelloni, L; Regoli, F

    2016-10-01

    Pharmaceuticals represent a major environmental concern since the knowledge on their occurrence, distribution and ecotoxicological potential is still limited particularly in coastal areas. In this study, bioaccumulation and cellular effects of various non steroidal anti-inflammatory drugs (NSAIDs) were investigated in mussels Mytilus galloprovincialis to reveal whether common molecules belonging to the same therapeutic class might cause different effects on non target organisms. Organisms exposed to environmental concentrations of acetaminophen (AMP), diclofenac (DIC), ibuprofen (IBU), ketoprofen (KET) and nimesulide (NIM) revealed a significant accumulation of DIC, IBU and NIM, while AMP and KET were always below detection limit. Nonetheless, for all tested NSAIDs, measurement of a large panel of ecotoxicological biomarkers highlighted impairment of immunological parameters, onset of genotoxicity and modulation of lipid metabolism, oxidative and neurotoxic effects. Laboratory results were integrated with a field study which provided the first evidence on the occurrence of DIC, IBU and NIM in tissues of wild mussels sampled during summer months from an unpolluted, touristic area of Central Adriatic Sea. Overall results demonstrated M. galloprovincialis as a good sentinel species for monitoring presence and ecotoxicological hazard of pharmaceuticals in the Mediterranean.

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

    Science.gov (United States)

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

    2015-11-27

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

    Science.gov (United States)

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

    2010-12-01

    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.

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

    Science.gov (United States)

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

    2016-06-20

    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.

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

    Science.gov (United States)

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

    2016-07-01

    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.

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

    Science.gov (United States)

    Tabrizi, Leila; Chiniforoshan, Hossein; McArdle, Patrick

    2015-02-01

    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.

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

    Science.gov (United States)

    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

    2016-10-01

    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.

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

    Science.gov (United States)

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

    2015-10-01

    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.

  2. A pharmacokinetic/pharmacodynamic approach vs. a dose titration for the determination of a dosage regimen: the case of nimesulide, a Cox-2 selective nonsteroidal anti-inflammatory drug in the dog.

    Science.gov (United States)

    Toutain, P L; Cester, C C; Haak, T; Laroute, V

    2001-02-01

    The present experiment was designed to determine a dosage regimen (dose, interval of administration) in the dog for nimesulide, a nonsteroidal anti-inflammatory drug with in vitro selectivity for the inhibition of cyclo-oxygenase 2 (Cox-2), using a pharmacokinetic/pharmacodynamic (PK/PD) approach. The PK/PD results were compared with those obtained using a classical dose titration study. In the PK/PD experiment, 11 dogs were subjected to Freund's adjuvant arthritis characterized by permanent hyperthermia. Nimesulide (5 mg/kg, oral route) was tested during the secondary phase of the inflammatory response. In the dose titration study, nimesulide (0, 3, 6 and 9 mg/kg, oral route) was tested in eight other dogs using a reversible urate crystal arthritis in a 4-period crossover design. Different PD endpoints (including lameness assessed by force plate and hyperthermia) were regularly measured during the PK/PD experiment, and plasma samples were obtained to determine the plasma nimesulide concentration. The data were modeled using an indirect effect model. The IC50 of nimesulide for lameness was 6.26 +/- 3.01 microg/mL, which was significantly higher than the EC50 value obtained for antipyretic effect (2.72 +/- 1.29 microg/mL). The ED50 estimated from the classical dose titration study were 1.34 mg/kg (lameness) and 3.0 mg/kg (skin temperature). The PK/PD parameters were used to simulate different dosage regimens (dose, interval of administration). The antipyretic and anti-inflammatory effects were calculated from the model for the recommended dosage regimen (5 mg/kg/24 h). It was apparent from this approach, that this dosage regimen enabled 76% of the theoretical maximal drug efficacy to be obtained for pyresis and 43% for lameness. It was concluded from the comparison of in vivo and in vitro IC50, that nimesulide is a potent NSAID for which some Cox-1 inhibition is required to obtain clinically relevant efficacy.

  3. Microbial Anti-Inflammatory Molecule (MAM) from Faecalibacterium prausnitzii Shows a Protective Effect on DNBS and DSS-Induced Colitis Model in Mice through Inhibition of NF-κB Pathway

    Science.gov (United States)

    Breyner, Natalia M.; Michon, Cristophe; de Sousa, Cassiana S.; Vilas Boas, Priscilla B.; Chain, Florian; Azevedo, Vasco A.; Langella, Philippe; Chatel, Jean M.

    2017-01-01

    Faecalibacterium prausnitzii and its supernatant showed protective effects in different chemically-induced colitis models in mice. Recently, we described 7 peptides found in the F. prausnitzii supernatant, all belonging to a protein called Microbial Anti-inflammatory Molecule (MAM). These peptides were able to inhibit NF-κB pathway in vitro and showed anti-inflammatory properties in vivo in a DiNitroBenzene Sulfate (DNBS)-induced colitis model. In this current proof we tested MAM effect on NF-κB pathway in vivo, using a transgenic model of mice producing luciferase under the control of NF-κB promoter. Moreover, we tested this protein on Dextran Sodium Sulfate (DSS)-induced colitis in mice. To study the effect of MAM we orally administered to the mice a Lactococcus lactis strain carrying a plasmid containing the cDNA of MAM under the control of a eukaryotic promoter. L. lactis delivered plasmids in epithelial cells of the intestinal membrane allowing thus the production of MAM directly by host. We showed that MAM administration inhibits NF-κB pathway in vivo. We confirmed the anti-inflammatory properties of MAM in DNBS-induced colitis but also in DSS model. In DSS model MAM was able to inhibit Th1 and Th17 immune response while in DNBS model MAM reduced Th1, Th2, and Th17 immune response and increased TGFβ production. PMID:28203226

  4. Anti-Inflammatory Effect of Methylpenicinoline from a Marine Isolate of Penicillium sp. (SF-5995: Inhibition of NF-κB and MAPK Pathways in Lipopolysaccharide-Induced RAW264.7 Macrophages and BV2 Microglia

    Directory of Open Access Journals (Sweden)

    Dong-Cheol Kim

    2014-11-01

    Full Text Available In the course of a search for anti-inflammatory metabolites from marine-derived fungi, methylpenicinoline (1 was isolated from a marine isolate of Penicillin sp. Compound 1 inhibited lipopolysaccharide (LPS-stimulated nitric oxide (NO production by suppressing the expression of inducible NO synthase (iNOS in RAW264.7 macrophages and BV2 microglia. It also attenuated prostaglandin E2 (PGE2 production by suppressing cyclooxygenase-2 (COX-2 expression in a concentration-dependent manner (from 10 μM to 80 μM without affecting cell viability. In addition, compound 1 reduced the production of the pro-inflammatory cytokine interleukin-1β (IL-1β. In a further study designed to elucidate the mechanism of its anti-inflammatory effects, compound 1 was shown to block nuclear factor-kappa B (NF-κB activation in LPS-induced RAW264.7 macrophages and BV2 microglia by inhibiting the phosphorylation of inhibitor kappa B-α (IκB-α, thereby suppressing the nuclear translocation of NF-κB dimers, namely p50 and p65, that are known to be crucial molecules associated with iNOS and COX-2 expression. In addition, compound 1 inhibited the activation of mitogen-activated protein kinase (MAPK pathways. Taken together, the results suggest that compound 1 might be a valuable therapeutic agent for the treatment of anti-inflammatory and anti-neuroinflammatory diseases.

  5. Evaluation of anti-inflammatory potential of leaf extracts of Skimmia anquetilia

    Institute of Scientific and Technical Information of China (English)

    Vijender Kumar; Zulfiqar Ali Bhat; Dinesh Kumar; NA Khan; IA Chashoo

    2012-01-01

    Objective: To evaluate anti-inflammatory potential of leaf extract of Skimmia anquetilia by in-vitro and in-vivo anti-inflammatory models. Methods: Acute toxicity study was carried out to determine the toxicity level of different extract using acute toxic class method as described in Organization of Economic Co-operation and Development Guidelines No.423. Carrageenan (1%w/w) was administered and inflammation was induced in rat paw. The leaf extracts of Skimmiaanquetilia were evaluated for anti-inflammatory activity by in-vitro human red blood cell (HRBC) membrane stabilization method and in-vivo carrangeenan-induced rat paw edema method.Results:The in-vitro membrane stabilizing test showed petroleum ether (PE), chloroform (CE), ethyl acetate (EE), methanol (ME) and aqueous extracts (AE) showed 49.44%, 59.39%, 60.15%, 68.40%and 52.18 % protection, respectively as compared to control groups. The in-vivo results of CE, EE and ME showed 58.20%, 60.17% and 67.53% inhibition of inflammation after 6h administration of test drugs in albino rats. The potency of the leaf extracts of Skimmia anquetilia were compared with standard diclofenac (10 mg/kg) which showed 74.18% protection in in-vitro HRBC membrane stabilization test and 71.64% inhibition in in-vivo carrangeenan-induced rat paw edema model. The ME showed a dose dependent significant (P< 0.01) anti-inflammatory activity in human red blood cell membrane stabilization test and reduction of edema in carrageenan induced rat paw edema. Conclusions: The present investigation has confirmed the anti-inflammatory activity ofSkimmia anquetilia due to presence of bioactive phytoconstitutes for the first time and provide the pharmacological evidence in favor of traditional claim of Skimmia anquetilia as an anti-inflammatory agent.

  6. Synthesis and anti-inflammatory activity of chalcone derivatives.

    Science.gov (United States)

    Herencia, F; Ferrándiz, M L; Ubeda, A; Domínguez, J N; Charris, J E; Lobo, G M; Alcaraz, M J

    1998-05-19

    Chalcones and their derivatives were synthesized and evaluated for their anti-inflammatory activity. In vitro, chalcones 2, 4, 8, 10 and 13 inhibited degranulation and 5-lipoxygenase in human neutrophils, whereas 11 behaved as scavenger of superoxide. Only four compounds (4-7) inhibited cyclo-oxygenase-2 activity. The majority of these samples showed anti-inflammatory effects in the mouse air pouch model.

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

    Science.gov (United States)

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

    2014-01-01

    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

  8. Preclinical analysis of nonsteroidal anti-inflammatory drug usefulness for the simultaneous prevention of steatohepatitis, atherosclerosis and hyperlipidemia

    Science.gov (United States)

    Madrigal-Perez, Violeta M; García-Rivera, Alejandro; Rodriguez-Hernandez, Alejandrina; Ceja-Espiritu, Gabriel; Briseño-Gomez, Xochitl G; Galvan-Salazar, Hector R; Soriano-Hernandez, Alejandro D; Guzman-Esquivel, Jose; Martinez-Fierro, Margarita L; Newton-Sanchez, Oscar A; Buenrostro, Bertha A Olmedo; Rodriguez-Sanchez, Iram P; López-Lemus, Uriel A; Lara-Esqueda, Agustin; Delgado-Enciso, Ivan

    2015-01-01

    Nonalcoholic steatohepatitis (NASH) is currently one of the primary liver diseases. Recent studies have shown a clinical relation between NASH and atherosclerosis. There is much interest in these two diseases because they are both associated with great morbidity and mortality. Inflammation and the overexpression of COX-2 participate in the pathophysiology of the two diseases, and therefore simultaneous treatment is feasible. The role of the four NSAIDs, meclofenamate, mefenamate, flufenamate, and aspirin, was analyzed in a mouse model of NASH, as well as preclinical atherosclerosis induced by a high-fat diet (HFD). Six mouse groups were formed. Five of the groups were fed a high-fat diet for 6 months and one group was fed a standard diet, acting as the normality reference. Of the five groups fed a high-fat diet, four received a NSAID, each of them identified by the specific drug administered. One group received no treatment. Serum markers (cholesterol, triglycerides, ALT, and AST) and histologic changes in the aorta and liver were analyzed for the study. Aspirin significantly reduced the hepaticsteatosis. All the drugs significantly reduced the hepatic inflammatory infiltrate. In relation to atherosclerosis, there were significant reductions in all the study variables with the use of aspirin and flufenamate. The four medications were able to stop steatosis from progressing into steatohepatitis by reducing inflammation. However, aspirin was the most beneficial, simultaneously reducing steatosis, atherosclerosis, and serum cholesterol levels. PMID:26885230

  9. Chemoprevention in gastrointestinal physiology and disease. Anti-inflammatory approaches for colorectal cancer chemoprevention

    Science.gov (United States)

    Piazza, Gary A.

    2015-01-01

    Colorectal cancer (CRC) is one of the most common human malignancies and a leading cause of cancer-related deaths in developed countries. Identifying effective preventive strategies aimed at inhibiting the development and progression of CRC is critical for reducing the incidence and mortality of this malignancy. The prevention of carcinogenesis by anti-inflammatory agents including nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, and natural products is an area of considerable interest and research. Numerous anti-inflammatory agents have been identified as potential CRC chemopreventive agents but vary in their mechanism of action. This review will discuss the molecular mechanisms being studied for the CRC chemopreventive activity of NSAIDs (i.e., aspirin, sulindac, and ibuprofen), COX-2 inhibitors (i.e., celecoxib), natural products (i.e., curcumin, resveratrol, EGCG, genistein, and baicalein), and metformin. A deeper understanding of how these anti-inflammatory agents inhibit CRC will provide insight into the development of potentially safer and more effective chemopreventive drugs. PMID:26021807

  10. Influence of the hydrophilicity of suppository bases on rectal absorption of carprofen, a lipophilic nonsteroidal anti-inflammatory drug.

    Science.gov (United States)

    Schmitt, M; Guentert, T W

    1990-04-01

    The influence of the hydrophilicity of fatty suppository bases on the rectal absorption of the lipophilic drug carprofen (octanol-buffer, pH 7.4; partition coefficient, 40) was investigated in dogs. Five animals received each of six carprofen formulations in a random sequence: intravenous, oral, and rectal solutions, and three suppository formulations. The suppository vehicles tested were semisynthetic glycerides containing saturated fatty acids mainly in the range of C10 to C18 [Massa Estarinum A (MEA), Massa Estarinum B (MEB), and Massa Estarinum 299 (ME299)]; their hydroxyl values increased from 1 for ME299, through 24 for MEB, to 45 for MEA. Following every drug administration, blood samples were collected over a period of 104 h and carprofen plasma concentrations were measured by a specific HPLC method with UV detection. The rate and extent of carprofen absorption were characterized by evaluation of the maximum plasma concentrations (Cmax), the time of their occurrence (tmax), absolute bioavailabilities, statistical moments, and by deconvolution. Carprofen was rapidly and completely absorbed from the oral solution. The maximum concentrations obtained with oral solutions were significantly higher than those observed with rectal solutions and with the three suppository formulations. Results obtained with the rectal solution exhibited a high degree of intersubject variability. After rectal administration of suppositories, the rate and extent of carprofen absorption increased with the hydroxyl value of the suppository base; the mean absorption times (MAT) and tmax were shorter with MEA (2.15 and 1.7 h, respectively) than with the less hydrophilic vehicles (MEB: 4.09 and 2.1 h, respectively; ME299: 4.22 and 2.4 h, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

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

    Science.gov (United States)

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

    2005-05-01

    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.

  12. Non-steroidal anti-inflammatory drug use is associated with increased risk of out-of-hospital cardiac arrest

    DEFF Research Database (Denmark)

    Sondergaard, Kathrine B; Weeke, Peter; Wissenberg, Mads

    2017-01-01

    Arrest Registry, all persons with OHCA during 2001-2010 were identified. NSAID use 30 days before OHCA was categorized as follows: diclofenac, naproxen, ibuprofen, rofecoxib, celecoxib, and other. Risk of OHCA associated with use of NSAIDs was analyzed by conditional logistic regression in case......-time-control models matching four controls on sex and age per case to account for variation in drug utilization over time.We identified 28 947 persons with OHCA of whom 3376 were treated with an NSAID up to 30 days before OHCA. Ibuprofen and diclofenac were the most commonly used NSAIDs and represented 51.0% and 21.......8% of total NSAID use, respectively. Use of diclofenac (odds ratio (OR), 1.50 [95% confidence interval (CI) 1.23-1.82]) and ibuprofen (OR, 1.31 [95% CI 1.14-1.51]) was associated with a significantly increased risk of OHCA. Use of naproxen (OR, 1.29 [95% CI 0.77-2.16]), celecoxib (OR, 1.13 [95% CI 0...

  13. Variants of CEP68 gene are associated with acute urticaria/angioedema induced by multiple non-steroidal anti-inflammatory drugs.

    Directory of Open Access Journals (Sweden)

    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.

  14. Variants of CEP68 gene are associated with acute urticaria/angioedema induced by multiple non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    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

    2014-01-01

    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.

  15. Non-steroidal anti-inflammatory drugs, Cyclooxygenase-2 inhibitors and paracetamol use in Queensland and in the whole of Australia

    Directory of Open Access Journals (Sweden)

    Tett Susan E

    2008-09-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Variants of CEP68 Gene Are Associated with Acute Urticaria/Angioedema Induced by Multiple Non-Steroidal Anti-Inflammatory Drugs

    Science.gov (United States)

    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

    2014-01-01

    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

  18. 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.

    Science.gov (United States)

    van Pamel, Els; Daeseleire, Els

    2015-06-01

    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.

  19. GINGIVAL TISSUE IL-1beta AND PGE2 LEVELS IN PATIENTS WITH CHRONIC PERIODONTITIS AFTER ADDITIONAL THERAPY WITH NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

    Directory of Open Access Journals (Sweden)

    Christina Popova

    2010-10-01

    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.

  20. Cyclo-oxygenase-2 selective inhibitors and nonsteroidal anti-inflammatory drugs: balancing gastrointestinal and cardiovascular risk

    Directory of Open Access Journals (Sweden)

    McQuay Henry J

    2007-08-01

    Full Text Available Abstract Background Differences between gastrointestinal and cardiovascular effects of traditional NSAID or cyclooxygenase-2 selective inhibitor (coxib are affected by drug, dose, duration, outcome definition, and patient gastrointestinal and cardiovascular risk factors. We calculated the absolute risk for each effect. Methods We sought studies with large amounts of information to calculate annualised rates for clearly defined gastrointestinal (complicated upper gastrointestinal perforations, ulcers, or bleeds, but not symptomatic or endoscopic ulcers and serious cardiovascular outcomes (antiplatelet trial collaborators – APTC – outcome of fatal or nonfatal myocardial infarction or stroke, or vascular death. Results Meta-analyses and large randomised trials specifically analysing serious gastrointestinal bleeding or cardiovascular events occurring with five different coxibs had appropriate data. In total there were 439 complicated upper gastrointestinal events in 49,006 patient years of exposure and 948 serious cardiovascular events in 99,400 patient years of exposure. Complicated gastrointestinal events occurred less frequently with coxibs than NSAIDs; serious cardiovascular events occurred at approximately equal rates. For each coxib, the reduction in complicated upper gastrointestinal events was numerically greater than any increase in APTC events. In the overall comparison, for every 1000 patients treated for a year with coxib rather than NSAID, there would be eight fewer complicated upper gastrointestinal events, but one more fatal or nonfatal heart attack or stroke. Three coxib-NSAID comparisons had sufficient numbers of events for individual comparisons. For every 1000 patients treated for a year with celecoxib rather than an NSAID there would be 12 fewer upper gastrointestinal complications, and two fewer fatal or nonfatal heart attacks or strokes. For rofecoxib there would be six fewer upper gastrointestinal complications, but three

  1. 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

    OpenAIRE

    2013-01-01

    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...

  2. Effects of Preoperative Non-Steroidal Anti-Inflammatory Drugs on Pain Mitigation and Patients’ Shoulder Performance Following Rotator Cuff Repair

    Directory of Open Access Journals (Sweden)

    Alireza Rouhani

    2014-12-01

    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.

  3. Receptor subtype-dependent positive and negative modulation of GABA(A) receptor function by niflumic acid, a nonsteroidal anti-inflammatory drug.

    Science.gov (United States)

    Sinkkonen, Saku T; Mansikkamäki, Salla; Möykkynen, Tommi; Lüddens, Hartmut; Uusi-Oukari, Mikko; Korpi, Esa R

    2003-09-01

    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.

  4. Molecular modeling and simulation studies of recombinant laccase from Yersinia enterocolitica suggests significant role in the biotransformation of non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    Singh, Deepti; Rawat, Surender; Waseem, Mohd; Gupta, Sunita; Lynn, Andrew; Nitin, Mukesh; Ramchiary, Nirala; Sharma, Krishna Kant

    2016-01-08

    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.

  5. Comparison of cardiovascular thrombotic events in patients with osteoarthritis treated with rofecoxib versus nonselective nonsteroidal anti-inflammatory drugs (ibuprofen, diclofenac, and nabumetone).

    Science.gov (United States)

    Reicin, Alise S; Shapiro, Deborah; Sperling, Rhoda S; Barr, Eliav; Yu, Qinfen

    2002-01-15

    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.

  6. 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.

    Science.gov (United States)

    Huang, Qiuxin; Yu, Yiyi; Tang, Caiming; Zhang, Kun; Cui, Jianlan; Peng, Xianzhi

    2011-04-01

    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.

  7. The role of activated carbon and disinfection on the removal of endocrine disrupting chemicals and non-steroidal anti-inflammatory drugs from wastewater.

    Science.gov (United States)

    Noutsopoulos, Constantinos; Mamais, Daniel; Mpouras, Thanasis; Kokkinidou, Despina; Samaras, Vasilios; Antoniou, Korina; Gioldasi, Marianna

    2014-01-01

    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.

  8. COMPARATIVE EVALUATION OF TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION (TENS V/S NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS FOR POSTOPERATIVE PAIN MANAGEMENT IN OPEN CHOLECYSTECTOMY

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    Hans Raj

    2016-06-01

    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.

  9. Fabrication of aluminum terephthalate metal-organic framework incorporated polymer monolith for the microextraction of non-steroidal anti-inflammatory drugs in water and urine samples.

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    Lyu, Dan-Ya; Yang, Cheng-Xiong; Yan, Xiu-Ping

    2015-05-08

    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.

  10. Non-steroidal anti-inflammatory drugs use is associated with reduced risk of inflammation-associated cancers: NIH-AARP study.

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    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.

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

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    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.

  12. Long-term use of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population

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    González-Pérez Antonio

    2005-11-01

    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.

  13. Crystal structure of a mixed-ligand silver(I) complex of the non-steroidal anti-inflammatory drug diclofenac and pyrimidine

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    Hamamci Alisir, Sevim; Dege, Necmi

    2016-01-01

    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

  14. Poly(2-aminobenzothiazole)-coated graphene oxide/magnetite nanoparticles composite as an efficient sorbent for determination of non-steroidal anti-inflammatory drugs in urine sample.

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    Asgharinezhad, Ali Akbar; Ebrahimzadeh, Homeira

    2016-02-26

    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.

  15. 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.

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    Dreischulte, Tobias; Morales, Daniel R; Bell, Samira; Guthrie, Bruce

    2015-08-01

    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.

  16. Long-term frequent use of non-steroidal anti-inflammatory drugs might protect patients with ankylosing spondylitis from cardiovascular diseases: a nationwide case-control study.

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    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.

  17. Significance of Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs in patients with bleeding from upper part of the gastrointestinal tract

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    Golubović Gradimir

    2007-01-01

    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. .

  18. Use of Nonsteroidal Anti-Inflammatory Drugs and Risk of Chronic Kidney Disease in Subjects With Hypertension: Nationwide Longitudinal Cohort Study.

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    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

    2015-09-01

    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.

  19. Effect of new hybrids based on 5,16-pregnadiene scaffold linked to an anti-inflammatory drug on the growth of a human astrocytoma cell line (U373).

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    Garrido, Mariana; González-Arenas, Aliesha; Camacho-Arroyo, Ignacio; Cabeza, Marisa; Alcaraz, Belén; Bratoeff, Eugene

    2015-03-26

    In spite of the fact that anaplastic astrocytoma is an uncommon disease, very often the pathology of this disease is associated with lethal effects due to the late diagnosis and unspecific treatments. This paper reports the synthesis and the biological effect on the growth of U373 cell line (human anaplastic astrocytoma) of new hybrid compounds based on 5,16-pregnadiene scaffold linked to an anti-inflammatory drug (6a-e). Moreover, we also determined the cell growth effect of five non-steroidal anti-inflammatory drugs (naproxen, ibuprofen, ketoprofen, indomethacin and sulindac) as well as the free steroidal alcohol 5. The results from this study indicated that sulindac as well as compound 5 decreased the number of U373 cells at different concentrations. However, when an anti-inflammatory drug was bound to the steroidal structure (5), the resulting compounds (6a-e) showed an enhanced biological effect with exception of hybrid 6c. Furthermore, derivative 6e (sulindac hybrid) did not allow cell growth during six days of experiment at a concentration of 10 μM. The overall data indicated that these molecules showed an anti-proliferative activity on anaplastic astrocytoma cell line.

  20. Medicinal plants with anti-inflammatory activities.

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    Maione, Francesco; Russo, Rosa; Khan, Haroon; Mascolo, Nicola

    2016-06-01

    Medicinal plants have been the main remedy to treat various ailments for a long time and nowadays, many drugs have been developed from traditional medicine. This paper reviews some medicinal plants and their main constituents which possess anti-inflammatory activities useful for curing joint inflammation, inflammatory skin disorders, cardiovascular inflammation and other inflammatory diseases. Here, we provide a brief overview of quick and easy reading on the role of medicinal plants and their main constituents in these inflammatory diseases. We hope that this overview will shed some light on the function of these natural anti-inflammatory compounds and attract the interest of investigators aiming at the design of novel therapeutic approaches for the treatment of various inflammatory conditions.

  1. In vitro anti-inflammatory, mutagenic and antimutagenic activities of ethanolic extract of Clerodendrum paniculatum root.

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    Phuneerub, Pravaree; Limpanasithikul, Wacharee; Palanuvej, Chanida; Ruangrungsi, Nijsiri

    2015-01-01

    Clerodendrum paniculatum L. (Family Verbenaceae) has been used as an antipyretic and anti-inflammatory drug in traditional Thai medicine. This present study investigated the in vitro anti-inflammatory, mutagenic and antimutagenic activities of the ethanolic extract of C. paniculatum (CPE) dried root collected from Sa Kaeo Province of Thailand. Murine macrophage J774A.1 cells were stimulated by lipopolysaccharide (LPS) to evaluate nitric oxide (NO), tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2) production in the anti-inflammatory test while the mutagenic and antimutagenic potential was performed by the Ames test. The outcome of this study displayed that the CPE root significantly inhibited LPS-induced NO, TNF-α, and PGE2 production in macrophage cell line. In addition, the CPE root was not mutagenic toward Salmonella typhimurium strain TA98 and TA100 with and without nitrite treatment. Moreover, it inhibited the mutagenicity of nitrite treated 1-aminopyrene on both strains. The findings suggested the anti-inflammatory and antimutagenic potentials of CPE root.

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

    Science.gov (United States)

    Navarro, C; Bravo, L; Bulbena, O

    1993-03-01

    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.

  3. Anti-Inflammatory Effect of Allium ursinum

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    Alina Elena PÂRVU

    2014-03-01

    Full Text Available The aim of the present study was to evaluate Allium ursinum leaves and flowers extract anti-inflammatory effect. Plant extract 1:1 (w:v was prepared from A. ursinum leaves by a modified Squibb repercolation method. The in vivo anti-inflammatory effects were evaluated on a rat turpentine oil-induced inflammation (i.m. 6 mL/kg BW. The animals were randomly assigned to nine groups (n=8: negative control, inflammation, A. ursinum flower extract (AUF, A. ursinum leaves extract (AUL, indomethacin (INDO (20 mg/kg BW, aminoguanidine (AG (50 mg/kg b.w./d i.p. as a selective NOS2 inhibitor, NG-nitro L-arginine methyl ester (NAME (5 mg/kg b.w./d i.p. as a nonselective NOS inhibitor, L-arginine (ARG (100 mg/kg b.w./d i.p., NO synthesis substrate, and Trolox (20 mg/kg b.w./d i.p as an antioxidant. At 24h from inflammation induction total oxidative status (TOS, oxidative stress index (OSI, nitric oxide (NOx and in vitro phagocytosis test were reduced and the total antioxidative reactivity (TAR was increased by the testes plant extracts. AUF had a better inhibitory effect than AUL. In conclusion, we provided evidence for the hypothesis that A. ursinum leaves and flowers extract exerts anti-inflammatory activity by inhibiting the phagocytosis through the reduction of the nitro-oxidative stress.

  4. Synthesis, toxicity study and anti-inflammatory effect of MHTP, a new tetrahydroisoquinoline alkaloid.

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    Pacheco de Oliveira, Maria Talita; de Oliveira Ramalho, Theresa Raquel; Paiva Ferreira, Laércia Karla Liege; Araújo Lima, Ana Luísa; Barbosa Cordeiro, Manuela; Ferreira Costa, Hermann; Rodrigues, Luís Cézar; Piuvezam, Marcia Regina

    2015-01-01

    The alkaloid 2-methoxy-4-(7-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)phenol (MHTP) was synthesized to prospect new compounds with therapeutic properties. Thus, the goal of this study was to evaluate the MHTP anti-inflammatory effect by in vivo and in vitro assays. The MHTP toxicity was analyzed. We found that MHTP pre-treatment (2.5-10 mg/kg) showed antiedematogenic effect (p alkaloid also reduced (p alkaloid, MHTP has anti-inflammatory effect by inhibiting PGE2 function as well as inhibiting inflammatory cell migration to the inflamed site and attenuated the acute lung injury disease by inhibiting the migration of neutrophil to the lung. However, further studies will be carried out to demonstrate the mechanisms of action of the molecule and explore its potential as a future drug to treat inflammatory processes.

  5. ANTI-INFLAMMATORY AND ANTIOXIDANT EFFECT OF ARECA CATECHU

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    Reena Rosy Nelson Anthikat* and A. Michael

    2012-01-01

    Full Text Available Context: The present investigation provides proof for the effectiveness of Arecanut extract as an anti-inflammatory agent. Arecanut extract is a natural plant product mimic of peroxidase.Objective: To explore the Anti-inflammatory activity of aqueous extract of Areca catechu L in carrageenan, dextran and formalin induced inflammation models in Swiss albino mice, by injection into the interdigital area, through the subplantar region of the paw. To explore the antioxidant effects of Arecanut extract on the in-vitro system.Method: Treatment with aqueous extract at 250 mg/kg.bwt and 500 mg/kg.body weight and untreated group was started orally 1 hour prior to the subplantar injection of carrageenan. The paw volume was measured using vernier calipers, before and one hour after carrageenan injection. Similarly in the case of dextran, initial readings were taken on the first day, prior to Formalin administration. Day one readings were taken one hour post formalin administration. This was taken during seven consecutive days challenge period. The drug aqueous arecanut extract at 200mg/kg.bwt, 500 mg/kg.bwt produced reduction in inflammation of the paw produced due to carrageenan, formalin and dextran. In-vitro antioxidant studies showed that aqueous arecanut extract could inhibit superoxide radical production, could inhibit hydroxyl radicals, and could prevent lipid peroxidation. Arecanut extract could scavenge DPPH radicals and also ABTS. In FRAP assay, the reduction of ferric to ferrous is also seen in a concentration dependant manner.Results: The present investigation provides proof for the effectiveness of treatment as an anti-inflammatory and antioxidant agent. Compared with the control group, the arecanut treated group showed free radical scavenging ability. Compared with the control group, the treatment of mice with Arecanut extract showed reduction in paw oedema in a dose dependent manner at 200 mg/kg.bwt and 500 mg/kg.bwt.Discussion and

  6. Potential of prescription registries to capture individual-level use of aspirin and other nonsteroidal anti-inflammatory drugs in Denmark: trends in utilization 1999–2012

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    Schmidt M

    2014-05-01

    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

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

    Science.gov (United States)

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

    2016-08-01

    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

  8. Topical anti-inflammatory properties of flutrimazole, a new imidazole antifungal agent.

    Science.gov (United States)

    Merlos, M; Vericat, M L; García-Rafanell, J; Forn, J

    1996-01-01

    The topical anti-inflammatory properties of flutrimazole, a new imidazole antifungal, have been evaluated. Flutrimazole inhibited mouse ear oedema induced by arachidonic acid, tetradecanoylphorbol-acetate and dithranol, with IC50 values of 3.32, 0.55 and 2.42 mumols/ear, respectively. Ketoconazole showed similar potency in arachidonic acid and dithranol models (IC50 = 3.76 and 2.41 mumols/ear) whereas it was less active against tetradecanoylphorbol acetate (IC50 = 1.96 mumols/ear). The standard anti-inflammatory sodium diclofenac was overall slightly more potent than antifungals (IC50 = 2.23, 0.57 and 0.57 mumols/ear against arachidonic acid, tetradecanoylphorbol acetate and dithranol, respectively). Both 2% flutrimazole and 2% ketoconazole creams, applied topically, inhibited carrageenan-induced rat paw oedema by about 40%. Under the same conditions, 1% flutrimazole and diclofenac creams inhibited by 26 and 54%, respectively. Flutrimazole may work through the inhibition of 5-lipoxygenase, as it inhibited LTB4 production by human granulocytes with an IC50 value of 11 microM (IC50 value for ketoconazole was 17 microM), whereas ram seminal vesicle cyclooxygenase was only inhibited by 16% at a concentration of 25 microM. Drugs such as flutrimazole, with dual anti-inflammatory/antifungal activity, may be advantageous in the treatment of topical fungal infections with an inflammatory component.

  9. 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.

    Science.gov (United States)

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

    2015-04-01

    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.

  10. Antioxidant, analgesic and anti-inflammatory effects of lavender essential oil

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    GABRIELA L. DA SILVA

    2015-08-01

    Full Text Available Several studies have investigated the antinociceptive, immunomodulatory and anti-inflammatory properties of compounds found in the lavender essential oil (LEO, however to date, there is still lack of substantial data. The objective of this study was to assess the antioxidant, anti-inflammatory and antinociceptive effects of lavender essential oil. The 1,1-diphenyl-2-picrylhydrazyl radical decolorization assay was used for antioxidant activity evaluation. The anti-inflammatory activity was tested using two models of acute inflammation: carrageenan-induced pleurisy and croton oil-induced ear edema. The antinociceptive activity was tested using the pain model induced by formalin. LEO has antioxidant activity, which is dose-dependent response. The inflammatory response evoked by carrageenan and by croton oil was reduced through the pre-treatment of animals with LEO. In the pleurisy model, the drug used as positive control, dexamethasone, was more efficacious. However, in the ear swelling, the antiedematogenic effect of the oil was similar to that observed for dexamethasone. In the formalin test, LEO consistently inhibited spontaneous nociception and presented a similar effect to that of tramadol. The results of this study reveal (in vivo the analgesic and anti-inflammatory activities of LEO and demonstrates its important therapeutic potential.

  11. The Anti-inflammatory Prostaglandin 15-Deoxy-Δ12,14-PGJ2 Inhibits CRM1-dependent Nuclear Protein Export*

    OpenAIRE

    Hilliard, Mark; Frohnert, Cornelia; Spillner, Christiane; Marcone, Simone; Nath, Annegret; Lampe, Tina; Fitzgerald, Desmond J; Kehlenbach, Ralph H.

    2010-01-01

    The signaling molecule 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) has been described as the “anti-inflammatory prostaglandin.” Here we show that substrates of the nuclear export receptor CRM1 accumulate in the nucleus in the presence of 15d-PGJ2, identifying this prostaglandin as a regulator of CRM1-dependent nuclear protein export that can be produced endogenously. Like leptomycin B (LMB), an established fungal CRM1-inhibitor, 15d-PGJ2 reacts with a conserved cysteine residue in the CRM1 se...

  12. Adverse drug reactions and cost effectiveness of non-steroidal anti-inflammatory drugs, muscle relaxants, and neurotropic drugs in patients with low back pain

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    I. B. Patel

    2015-04-01

    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

  13. Tenoxicam, a non-steroid anti-inflammatory drug, is unable to increase the response rate in patients with chronic hepatitis C treated by alpha interferon.

    Science.gov (United States)

    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

    1998-03-01

    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

  14. Detection of the non-steroidal anti-inflammatory drug niflumic acid in humans: a combined 19F-MRS in vivo and in vitro study.

    Science.gov (United States)

    Bilecen, Deniz; Schulte, Anja-Carina; Kaspar, Armin; Küstermann, Eckerhardt; Seelig, Joachim; Elverfeldt, Dominik; Scheffler, Klaus

    2003-05-01

    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

  15. LIVER FUNCTION CHANGES IN PATIENTS WITH SPONDYLOARTHRITIS TAKING NONSTEROIDAL ANTI-INFLAMMATORY DRUGS OVER A LONG PERIOD: RESULTS OF A 10-YEAR PROGRESS PROSPECTIVE STUDY

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    A. P. Rebrov

    2016-01-01

    worse liver function. Hepatoprotectors are less frequently prescribed to patients taking nimesulide than to those receiving diclofenac sodium or ibuprofen and more frequently to patients using meloxicam. In most cases, prescribing hepatoprotective agents to patients receiving NSAIDs does not require discontinuation of anti-inflammatory therapy. 

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

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    Potgieter W

    2014-07-01

    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

  17. Quinolones and non-steroidal anti-inflammatory drugs interacting with copper(II), nickel(II), cobalt(II) and zinc(II): structural features, biological evaluation and perspectives.

    Science.gov (United States)

    Psomas, George; Kessissoglou, Dimitris P

    2013-05-14

    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.

  18. Analgesic and Anti-inflammatory Effects of Ginger Oil

    Institute of Scientific and Technical Information of China (English)

    JIA Yong-liang; XIE Qiang-min; ZHAO Jun-ming; ZHANG Lin-hui; SUN Bao-shan; BAO Meng-jing; LI Fen-fen; SHEN Jian; SHEN Hui-jun; ZHAO Yu-qing

    2011-01-01

    Objective Ginger (Zingiber officinale) is widely used as a spice in cooking and as a medicinal herb in traditional herbal medicine. The present study was to investigate the analgesic and anti-inflammatory activities of ginger oil in experimental animal models. Methods The analgesic effect of the oils was evaluated by the "acetic acid" and "hot-plate" test models of pain in mice. The anti-inflammatory effect of the oil was investigated in rats, using rat paw edema induced by carrageenan, adjuvant arthritis, and vascular permeability induced by bradykinin, arachidonic acid, and histamine. Indomethacin (1 mg/kg), Aspirin (0.5 g/kg) and Dexamethasone (2.5 mg/kg) were used respectively as reference drugs for comparison. Results The ginger oil (0.25-1.0 g/kg) produced significant analgesic effect against chemically- and thermally-induced nociceptive pain stimuli in mice (P < 0.05, 0.01). And the ginger oil (0.25-1.0 g/kg) also significantly inhibited carrageenan-induced paw edema, adjuvant arthritis, and inflammatory mediators-induced vascular permeability in rats (P < 0.05, 0.001). Conclusion These findings confirm that the ginger oil can be used to treat pain and chronic inflammation such as rheumatic arthritis.

  19. HU-444, a Novel, Potent Anti-Inflammatory, Nonpsychotropic Cannabinoid.

    Science.gov (United States)

    Haj, Christeene G; Sumariwalla, Percy F; Hanuš, Lumír; Kogan, Natalya M; Yektin, Zhana; Mechoulam, Raphael; Feldmann, Mark; Gallily, Ruth

    2015-10-01

    Cannabidiol (CBD) is a component of cannabis, which does not cause the typical marijuana-type effects, but has a high potential for use in several therapeutic areas. In contrast to Δ(9)-tetrahydrocannabinol (Δ(9)-THC), it binds very weakly to the CB1 and CB2 cannabinoid receptors. It has potent activity in both in vitro and in vivo anti-inflammatory assays. Thus, it lowers the formation of tumor necrosis factor (TNF)-α, a proinflammatory cytokine, and was found to be an oral antiarthritic therapeutic in murine collagen-induced arthritis in vivo. However, in acidic media, it can cyclize to the psychoactive Δ(9)-THC. We report the synthesis of a novel CBD derivative, HU-444, which cannot be converted by acid cyclization into a Δ(9)-THC-like compound. In vitro HU-444 had anti-inflammatory activity (decrease of reactive oxygen intermediates and inhibition of TNF-α production by macrophages); in vivo it led to suppression of production of TNF-α and amelioration of liver damage as well as lowering of mouse collagen-induced arthritis. HU-444 did not cause Δ(9)-THC-like effects in mice. We believe that HU-444 represents a potential novel drug for rheumatoid arthritis and other inflammatory diseases.

  20. Anti-Inflammatory Oleanolic Triterpenes from Chinese Acorns

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    Jie Huang

    2016-05-01

    Full Text Available Acorns play an important role in human history and are a source of food and recipes for many cultures around the world. In this study, eleven oleanolic triterpenes, one of which was novel, were isolated from Chinese acorns (Quercus serrata var. brevipetiolata. The chemical structure of the novel triterpene, which was identified as 2α,3β,19α-trihydroxy-24-oxo-olean-12-en-28-oic acid (1, was established based on the interpretation of chemical and spectroscopic analyses, including IR, HR-ESI-MS, and NMR experiments (1H, 13C NMR, DEPT, 1H-1H COSY, HSQC, HMBC, and NOESY. All isolated compounds were tested for their inhibitory effects on LPS-induced nitric oxide (NO production in RAW 264.7 macrophages. Compared with the positive control drug indomethacin (IC50 = 47.4 μM, compounds 1, 3, 6 and 8 exhibited remarkable anti-inflammatory activities with IC50 values of 5.4, 7.8, 4.0 and 8.9 μM, respectively. Besides, compounds 2, 4, 7 and 9 also showed moderate anti-inflammatory activities with IC50 values of 10.1, 13.0, 20.1 and 17.2 μM, respectively. Furthermore, Compound 1 could inhibit TNF-α-induced IL-6 and IL-8 production in MH7A cells.

  1. Cecropia pachystachya: A Species with Expressive In Vivo Topical Anti-Inflammatory and In Vitro Antioxidant Effects

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    Natália Ramos Pacheco

    2014-01-01

    Full Text Available Cecropia pachystachya is a species traditionally used in Brazil to treat inflammation. This work aims to evaluate the topical anti-inflammatory and antioxidant activities of the methanolic extract of C. pachystachya (CPM and to perform its chemical fingerprint by HPLC-DAD. The topical anti-inflammatory activity was evaluated using the mouse models of acute ear inflammation induced by croton oil, arachidonic acid, capsaicin, EPP, phenol, and chronic inflammation induced by multiple application of croton oil. The in vitro antioxidant effect of CPM was investigated using DPPH, reducing power, β-carotene bleaching, and TBARS assays. HPLC analysis was performed to quantify the antioxidant phenolics orientin, isoorientin, and chlorogenic acid previously identified in CPM. CPM exhibited significant anti-inflammatory effect in the acute models, in some cases comparable to the reference drugs. Histopathological analysis showed a moderate chronic skin anti-inflammatory effect with decrease in vasodilation, edema, cell infiltration, and epidermal hyperproliferation. It also showed strong in vitro antioxidant activity. The contents of orientin, isoorientin, and chlorogenic acid were 66.5 ± 1.8, 118.8 ± 0.7, and 5.4 ± 0.2 µg/mg extract, respectively. The topical anti-inflammatory activity of CPM could be based on its antioxidant properties, although other effects are probably involved, including COX inhibition and other mechanisms.

  2. Cecropia pachystachya: a species with expressive in vivo topical anti-inflammatory and in vitro antioxidant effects.

    Science.gov (United States)

    Pacheco, Natália Ramos; Pinto, Nícolas de Castro Campos; da Silva, Josiane Mello; Mendes, Renata de Freitas; da Costa, Juliana de Carvalho; Aragão, Danielle Maria de Oliveira; Castañon, Maria Christina Marques Nogueira; Scio, Elita

    2014-01-01

    Cecropia pachystachya is a species traditionally used in Brazil to treat inflammation. This work aims to evaluate the topical anti-inflammatory and antioxidant activities of the methanolic extract of C. pachystachya (CPM) and to perform its chemical fingerprint by HPLC-DAD. The topical anti-inflammatory activity was evaluated using the mouse models of acute ear inflammation induced by croton oil, arachidonic acid, capsaicin, EPP, phenol, and chronic inflammation induced by multiple application of croton oil. The in vitro antioxidant effect of CPM was investigated using DPPH, reducing power, β -carotene bleaching, and TBARS assays. HPLC analysis was performed to quantify the antioxidant phenolics orientin, isoorientin, and chlorogenic acid previously identified in CPM. CPM exhibited significant anti-inflammatory effect in the acute models, in some cases comparable to the reference drugs. Histopathological analysis showed a moderate chronic skin anti-inflammatory effect with decrease in vasodilation, edema, cell infiltration, and epidermal hyperproliferation. It also showed strong in vitro antioxidant activity. The contents of orientin, isoorientin, and chlorogenic acid were 66.5 ± 1.8, 118.8 ± 0.7, and 5.4 ± 0.2 µg/mg extract, respectively. The topical anti-inflammatory activity of CPM could be based on its antioxidant properties, although other effects are probably involved, including COX inhibition and other mechanisms.

  3. 非甾体抗炎药物临床应用分析%Analysis of clinical application of nonsteroidal anti-inflammatory drugs

    Institute of Scientific and Technical Information of China (English)

    公为亮

    2011-01-01

    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

  4. Antiinflamatórios não-hormonais: inibidores da ciclooxigenase 2 Nonsteroidal anti-inflammatory drugs: cyclooxygenase 2 inhibitors

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    Maria Odete Esteves Hilário

    2006-11-01

    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

  5. Evaluation of anti-inflammatory and antioxidant activity of Ichnocarpus frutescens root

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    A Pandurangan

    2009-03-01

    Full Text Available ABSTRACT Background and the purpose of the study: Ichnocarpus frutescens has been widely used in the traditional medicine for the treatment of a variety of diseases.  In the present study anti-inflammatory and antioxidant property of roots of this plant was investigated. Methods: The anti-inflammatory activity of methanolic extract of Ichnocarpus frutescens (MEIF was evaluated by carrageenan, and cotton pellet induced granuloma tests to determine its effects on acute and chronic phase of inflammation models in rats. Results and major conclusion: Preliminary Phytochemical analysis of methanolic extracts showed presence of terpenoids, flavonoids, and sterols. Maximum inhibition (54.63 % was obtained at the dose of 100 mg/kg after 3 hrs of drug treatment in carrageenan induced paw oedema, whereas indomethacin produced 57.65 % of inhibition. In the chronic model, 300 mg/kg of MEIF like indomethacin and dexamethasone standard drug decreased formation of granuloma tissue by 22.64, 29.63 % and 34.84 % respectively.  The successive methanol re-extract of Ichnocarpus frutescens root (MEIF exhibited strong scavenging effects on 2, 2-diphenyl-2-picryl hydroxyl (DPPH free radical, nitric oxide, super oxide anion, hydroxyl radical and inhibition of lipid peroxidation. These results clearly indicate strong anti-inflammatory and antioxidant properties of Ichnocarpus frutescens root.

  6. Pharmacological interactions of anti-inflammatory-analgesics in odontology.

    Science.gov (United States)

    Gómez-Moreno, Gerardo; Guardia, Javier; Cutando, Antonio; Calvo-Guirado, José Luis

    2009-02-01

    In this second article we describe the more interesting pharmacological interactions in dental practice based on the prescription of analgesic narcotics, paracetamol and non-selective non-steroid anti-inflammatory drugs (NSAI) (which inhibit cyclooxigenase 1 -COX 1- and cyclooxigenase 2 -COX 2-) and selective NSAIs (COX 2 inhibitors). The importance of preventing the appearance of these pharmacological interactions is because these are medicaments prescribed daily in odontology for moderate pain treatment and inflammation in the oral cavity. Paracetamol can interact with warfarin and therefore care should be taken with chronic alcoholic patients. All NSAIs reduce renal blood flow and consequently are capable of reducing the efficacy of medicaments used for treating arterial hypertension, which act via a renal mechanism. Especial attention should be taken considering the risk of interaction between the antagonists of AT1 receptors of angiostensin II (ARAII) and the NSAIs.

  7. 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

    Institute of Scientific and Technical Information of China (English)

    徐迎阳; 支玉香

    2014-01-01

    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.

  8. USE OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS FOR THE TREATMENT OF AXIAL SPONDYLOARTHRITIS, INCLUDING ANKYLOSING SPONDYLITIS, MONITORING THEIR EFFICACY AND SAFETY (DRAFT GUIDELINES OF THE EXPERT SPONDYLOARTHRITIS DIAGNOSIS AND TREATMENT GROUP

    Directory of Open Access Journals (Sweden)

    I. Z. Gaidukova

    2016-01-01

    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.

  9. Medicinal Plants of the Australian Aboriginal Dharawal People Exhibiting Anti-Inflammatory Activity

    Science.gov (United States)

    Akhtar, Most A.; Raju, Ritesh; Beattie, Karren D.; Bodkin, Frances

    2016-01-01

    Chronic inflammation contributes to multiple ageing-related musculoskeletal and neurodegenerative diseases, cardiovascular diseases, asthma, rheumatoid arthritis, and inflammatory bowel disease. More recently, chronic neuroinflammation has been attributed to Parkinson's and Alzheimer's disease and autism-spectrum and obsessive-compulsive disorders. To date, pharmacotherapy of inflammatory conditions is based mainly on nonsteroidal anti-inflammatory drugs which in contrast to cytokine-suppressive anti-inflammatory drugs do not influence the production of cytokines such as tumour necrosis factor-α or nitric oxide. However, their prolonged use can cause gastrointestinal toxicity and promote adverse events such as high blood pressure, congestive heart failure, and thrombosis. Hence, there is a critical need to develop novel and safer nonsteroidal anti-inflammatory drugs possessing alternate mechanism of action. In this study, plants used by the Dharawal Aboriginal people in Australia for the treatment of inflammatory conditions, for example, asthma, arthritis, rheumatism, fever, oedema, eye inflammation, and inflammation of bladder and related inflammatory diseases, were evaluated for their anti-inflammatory activity in vitro. Ethanolic extracts from 17 Eucalyptus spp. (Myrtaceae) were assessed for their capacity to inhibit nitric oxide and tumor necrosis factor-α production in RAW 264.7 macrophages. Eucalyptus benthamii showed the most potent nitric oxide inhibitory effect (IC50  5.57 ± 1.4 µg/mL), whilst E. bosistoana, E. botryoides, E. saligna, E. smithii, E. umbra, and E. viminalis exhibited nitric oxide inhibition values between 7.58 and 19.77 µg/mL. PMID:28115968

  10. Medicinal Plants of the Australian Aboriginal Dharawal People Exhibiting Anti-Inflammatory Activity.

    Science.gov (United States)

    Akhtar, Most A; Raju, Ritesh; Beattie, Karren D; Bodkin, Frances; Münch, Gerald

    2016-01-01

    Chronic inflammation contributes to multiple ageing-related musculoskeletal and neurodegenerative diseases, cardiovascular diseases, asthma, rheumatoid arthritis, and inflammatory bowel disease. More recently, chronic neuroinflammation has been attributed to Parkinson's and Alzheimer's disease and autism-spectrum and obsessive-compulsive disorders. To date, pharmacotherapy of inflammatory conditions is based mainly on nonsteroidal anti-inflammatory drugs which in contrast to cytokine-suppressive anti-inflammatory drugs do not influence the production of cytokines such as tumour necrosis factor-α or nitric oxide. However, their prolonged use can cause gastrointestinal toxicity and promote adverse events such as high blood pressure, congestive heart failure, and thrombosis. Hence, there is a critical need to develop novel and safer nonsteroidal anti-inflammatory drugs possessing alternate mechanism of action. In this study, plants used by the Dharawal Aboriginal people in Australia for the treatment of inflammatory conditions, for example, asthma, arthritis, rheumatism, fever, oedema, eye inflammation, and inflammation of bladder and related inflammatory diseases, were evaluated for their anti-inflammatory activity in vitro. Ethanolic extracts from 17 Eucalyptus spp. (Myrtaceae) were assessed for their capacity to inhibit nitric oxide and tumor necrosis factor-α production in RAW 264.7 macrophages. Eucalyptus benthamii showed the most potent nitric oxide inhibitory effect (IC50  5.57 ± 1.4 µg/mL), whilst E. bosistoana, E. botryoides, E. saligna, E. smithii, E. umbra, and E. viminalis exhibited nitric oxide inhibition values between 7.58 and 19.77 µg/mL.

  11. Medicinal Plants of the Australian Aboriginal Dharawal People Exhibiting Anti-Inflammatory Activity

    Directory of Open Access Journals (Sweden)

    Most A. Akhtar

    2016-01-01

    Full Text Available Chronic inflammation contributes to multiple ageing-related musculoskeletal and neurodegenerative diseases, cardiovascular diseases, asthma, rheumatoid arthritis, and inflammatory bowel disease. More recently, chronic neuroinflammation has been attributed to Parkinson’s and Alzheimer’s disease and autism-spectrum and obsessive-compulsive disorders. To date, pharmacotherapy of inflammatory conditions is based mainly on nonsteroidal anti-inflammatory drugs which in contrast to cytokine-suppressive anti-inflammatory drugs do not influence the production of cytokines such as tumour necrosis factor-α or nitric oxide. However, their prolonged use can cause gastrointestinal toxicity and promote adverse events such as high blood pressure, congestive heart failure, and thrombosis. Hence, there is a critical need to develop novel and safer nonsteroidal anti-inflammatory drugs possessing alternate mechanism of action. In this study, plants used by the Dharawal Aboriginal people in Australia for the treatment of inflammatory conditions, for example, asthma, arthritis, rheumatism, fever, oedema, eye inflammation, and inflammation of bladder and related inflammatory diseases, were evaluated for their anti-inflammatory activity in vitro. Ethanolic extracts from 17 Eucalyptus spp. (Myrtaceae were assessed for their capacity to inhibit nitric oxide and tumor necrosis factor-α production in RAW 264.7 macrophages. Eucalyptus benthamii showed the most potent nitric oxide inhibitory effect (IC50  5.57±1.4 µg/mL, whilst E. bosistoana, E. botryoides, E. saligna, E. smithii, E. umbra, and E. viminalis exhibited nitric oxide inhibition values between 7.58 and 19.77 µg/mL.

  12. Simultaneous analysis of non-steroidal anti-inflammatory drugs using electrochemically controlled solid-phase microextraction based on nanostructure molecularly imprinted polypyrrole film coupled to ion mobility spectrometry.

    Science.gov (United States)

    Ameli, Akram; Kalhor, Hamideh; Alizadeh, Naader

    2013-06-01

    A simple, rapid, and highly sensitive method for simultaneous analysis of anti-inflammatory drugs (naproxen, ibuprofen, and mefenamic acid) in diluted human serum was developed using the electrochemically controlled solid-phase microextraction coupled to ion mobility spectrometry. A conducting molecularly imprinted polymer film based on polypyrrole was synthesized for the selective uptake and release of drugs. The film was prepared by incorporation of a template molecule (naproxen) during the electropolymerization of pyrrole onto a platinum electrode using cyclic voltammetry method. The measured ion mobility spectrometry intensity was related to the concentration of analytes taken up into the films. The calibration graphs (naproxen, ibuprofen, and mefenamic acid) were linear in the range of 0.1-30 ng/mL and detection limits were 0.07-0.37 ng/mL and relative standard deviation was lower than 6%. On the basis of the results obtained in this work, the conducting molecularly imprinted polymer films as absorbent have been applied in the electrochemically controlled solid-phase microextraction and ion mobility spectrometry system for the selective clean-up and quantification of trace amounts of anti-inflammatory drugs in human serum samples. Scanning electron microscopy has confirmed the nano-structure morphology of the polypyrrole film.

  13. Anti-inflammatory activity of red and white lotus seeds (Nelumbo nucifera in albino rats

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    P. Vikrama Chakravarthi

    2010-08-01

    Full Text Available The present study was carried out to evaluate the anti-inflammatory activity of red and white lotus seeds in albino rats. The Carrageenin induced paw edema model was used for studying the anti-inflammatory activity. The cyclooxygenase-2 (COX-2 enzyme inhibition assay was carried out in spectrophotometer to identify the specific mode of action. Forty eight adult Sprague-Dawley rats were used in this experiment. They were divided into six groups of eight each and maintained under ideal laboratory conditions. Group I was taken as control and group II treated with the standard drug diclofenac potassium @ 3mg/kg/celecoxib @ 10mg/kg (in case of COX–2 assay on 7th day of study. The methanolic extract of Nelumbo nucifera seeds of red and white varieties @ 400mg/kg and 600mg/kg were fed to group III, IV, V and VI respectively, for 7 days. All groups of lotus seed extracts were revealed anti-inflammatory activity in Carragenin induced inflammation as well as in COX-2 enzyme inhibition assay. While comparing all groups, the higher dose group of white lotus seed extracts, exhibited more pronounced inhibition than other groups. [Vet World 2010; 3(4.000: 157-159

  14. Anti-oxidant and anti-inflammatory activity of leaf extracts and fractions of Mangifera indica

    Institute of Scientific and Technical Information of China (English)

    Mohan CG; Deepak M; Viswanatha GL; Savinay G; Hanumantharaju V; Rajendra CE; Praveen D Halemani

    2013-01-01

    Objective: To evaluate the anti-oxidant and anti-inflammatory activity of leaf extracts and fractions of Mangifera indica in in vitro conditions. Methods: In vitro DPPH radical scavenging activity and lipoxygenase (LOX) inhibition assays were used to evaluate the anti-oxidant and anti-inflammatory activities respectively. Methanolic extract (MEMI), successive water extract (SWMI) and ethyl acetate fraction (EMEMI), n-butanol fraction (BMEMI) and water soluble fraction (WMEMI) of methanolic extract were evaluated along with respective reference standards. Results: In in vitro DPPH radical scavenging activity, the MEMI, EMEMI and BMEMI have offered significant antioxidant activity with IC50 values of 13.37, 3.55 and 14.19 μg/mL respectively. Gallic acid, a reference standard showed significant antioxidant activity with IC50 value of 1.88 and found to be more potent compared to all the extracts and fractions. In in vitro LOX inhibition assay, the MEMI, EMEMI and BMEMI have showed significant inhibition of LOX enzyme activity with IC50 values of 96.71, 63.21 and 107.44 μg/mL respectively. While, reference drug Indomethacin also offered significant inhibition against LOX enzyme activity with IC50 of 57.75. Furthermore, MEMI was found to more potent than SWMI and among the fractions EMEMI was found to possess more potent antioxidant and anti-inflammatory activity. Conclusions: These findings suggest that the MEMI and EMEMI possess potent anti-oxidant and anti-inflammatory activities in in vitro conditions.

  15. Agreement between patients' self-report and physicians' prescriptions on nonsteroidal anti-inflammatory drugs and other drugs used in musculoskeletal disorders: the international Pharmacoepidemiologic General Research eXtension database.

    Science.gov (United States)

    Grimaldi-Bensouda, Lamiae; Rossignol, Michel; Aubrun, Elodie; Benichou, Jacques; Abenhaim, Lucien

    2012-07-01

    PURPOSE: The use of prescription records for the assessment of exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) does not capture over-the-counter drug use. This study compared patients' self-reported use to physician's prescriptions for NSAIDs and other drugs used to treat musculoskeletal disorders (MSDs). METHODS: The international Pharmacoepidemiologic General Research eXtension database includes a network of general practitioners recruiting patients without reference to diagnoses or prescriptions. Data on all drug use across France within the 2 years preceding the date of inclusion (index date) were obtained from both patients' self-reports (PSRs) and physicians' prescription reports (PPRs). Patients' reports were obtained using a structured telephone interview combined with an interview guide containing a list of drugs commonly used. Comparisons were made on exposure to four categories of MSD drugs and three time windows up to 24 months before the index date. RESULTS: Agreement between physician and patient reports was assessed on 4152 patient-physician pairs. Bias- and prevalence-adjusted kappa values showed fair agreement for nonaspirin NSAIDs, moderate to fair for nonnarcotic analgesics, high for osteoarthritis and moderate to substantial for muscle relaxants. Over-the-counter drug use was associated with greater disagreement (OR = 2.21, 95%CI = 1.05-1.38). Age was not associated with disagreement. CONCLUSION: Differences between PSR and PPR in estimating the prevalence of MSD drug use varied by the type of drug and the elapsed time from the index date. The patient-assisted interview method used in this study showed better agreement with PPR compared with standard interviews, especially for long time windows and patients older than 65 years. Copyright © 2012 John Wiley & Sons, Ltd.

  16. IL-35 is a novel responsive anti-inflammatory cytokine--a new system of categorizing anti-inflammatory cytokines.

    Science.gov (United States)

    Li, Xinyuan; Mai, Jietang; Virtue, Anthony; Yin, Ying; Gong, Ren; Sha, Xiaojin; Gutchigian, Stefanie; Frisch, Andrew; Hodge, Imani; Jiang, Xiaohua; Wang, Hong; Yang, Xiao-Feng

    2012-01-01

    It remains unknown whether newly identified anti-inflammatory/immunosuppressive cytokine interleukin-35 (IL-35) is different from other anti-inflammatory cytokines such as IL-10 and transforming growth factor (TGF)-β in terms of inhibition of inflammation initiation and suppression of full-blown inflammation. Using experimental database mining and statistical analysis methods we developed, we examined the tissue expression profiles and regulatory mechanisms of IL-35 in comparison to other anti-inflammatory cytokines. Our results suggest that in contrast to TGF-β, IL-35 is not constitutively expressed in human tissues but it is inducible in response to inflammatory stimuli. We also provide structural evidence that AU-rich element (ARE) binding proteins and microRNAs target IL-35 subunit transcripts, by which IL-35 may achieve non-constitutive expression status. Furthermore, we propose a new system to categorize anti-inflammatory cytokines into two groups: (1) the house-keeping cytokines, such as TGF-β, inhibit the initiation of inflammation whereas (2) the responsive cytokines including IL-35 suppress inflammation in full-blown stage. Our in-depth analyses of molecular events that regulate the production of IL-35 as well as the new categorization system of anti-inflammatory cytokines are important for the design of new strategies of immune therapies.

  17. In Vivo Anti-inflammatory Activity of Lipoic Acid Derivatives in Mice 

    Directory of Open Access Journals (Sweden)

    Brunon Kwiecień

    2013-04-01

    Full Text Available Background: In mammals lipoic acid (LA and its reduced form dihydrolipoic acid (DHLA function as cofactors for multienzymatic complexes catalyzing the decarboxylation of α-ketoacids. Moreover, LA is used as a drug in a variety of diseases including inflammatory diseases. The aim of the study was to examine anti-inflammatory properties of LA metabolites.Material/methods:The present paper reports the chemical synthesis of 2,4-bismethylthio-butanoic acid (BMTBA and tetranor-dihydrolipoic acid (tetranor-DHLA. BMTBA is one of the biotransformation products of LA, while tetranor-DHLA is an analogue of DHLA. Structural identity of these compounds was confirmed by 1H NMR. These compounds were assessed for their anti-inflammatory activity in mice. For this purpose, the zymosan-induced peritonitis and the carrageenan-induced hind paw edema animal models were applied.Results/conclusions: The obtained results indicated that the early vascular permeability measured at 30 min of zymosan-induced peritonitis was significantly inhibited in groups receiving BMTBA (10, 30, 50 mg/kg. The early infiltration of neutrophils measured at 4 hours of zymosan-induced peritonitis was inhibited in the group receiving BMTBA (50 mg/kg and tetranor-DHLA (50 mg/kg. The results indicated that the increase in paw edema was significantly inhibited in the groups receiving BMTBA (50, 100 mg/kg and tetranor-DHLA (30, 50 mg/kg. In summary, the present studies clearly demonstrated that both BMTBA and tetranor-DHLA were able to act as anti-inflammatory agents. This is the first study examining in vivo the anti-inflammatory properties of LA metabolites.

  18. Anti-inflammatory activity of the essential oil obtained from Ocimum basilicum complexed with β-cyclodextrin (β-CD) in mice.

    Science.gov (United States)

    Rodrigues, Lindaiane Bezerra; Martins, Anita Oliveira Brito Pereira Bezerra; Ribeiro-Filho, Jaime; Cesário, Francisco Rafael Alves Santana; E Castro, Fyama Ferreira; de Albuquerque, Thaís Rodrigues; Fernandes, Maria Neyze Martins; da Silva, Bruno Anderson Fernandes; Quintans Júnior, Lucindo José; Araújo, Adriano Antunes de Sousa; Menezes, Paula Dos Passos; Nunes, Paula Santos; Matos, Isabella Gonçalves; Coutinho, Henrique Douglas Melo; Goncalves Wanderley, Almir; de Menezes, Irwin Rose Alencar

    2017-02-22

    Cyclodextrins (CDs) are cyclic oligosaccharides can enhance the bioavailability of drugs. Ocimum basilicum is an aromatic plant found in Brazil used in culinary. The essential oil of this plant presents anti-edematogenic and anti-inflammatory activities in acute and chronic inflammation. The aim of this study was to investigate the anti-inflammatory effects of the essential oil obtained from O. basilicum complexed with β - cyclodextrin (OBEO/β-CD) in mice. The complexation with β-cyclodextrin (β-CD) was performed by different methods and analyzed by differential scanning calorimetry (DSC), thermogravimetry (TG) and scanning electron microscopy (SEM). The anti-inflammatory activity was evaluated using mice models of paw edema induced by carrageenan, dextran, histamine and arachidonic acid (AA); vascular permeability and peritonitis induced by carrageenan and granuloma induced by cotton block introduction. The DSC, TG and SEM analysis indicated that the OBEO was successfully complexed with β-CD. The oral administration of OEOB/β-CD prevented paw edema formation by decreasing vascular permeability in vivo, inhibited leukocyte recruitment to the peritoneal cavity, and inhibited granuloma formation in mice. Our results indicate that conjugation with β-CD improves the anti-inflammatory effects of OBEO in mice models of acute and chronic inflammation, indicating that this complex can be used in anti-inflammatory drug development.

  19. Degradable magnesium-based implant materials with anti-inflammatory activity.

    Science.gov (United States)

    Peng, Qiuming; Li, Kun; Han, Zengsheng; Wang, Erde; Xu, Zhigang; Liu, Riping; Tian, Yongjun

    2013-07-01

    The objective of this study was to prepare a new biodegradable Mg-based biomaterial, which provides good mechanical integrity in combination with anti-inflammatory function during the degradation process. The silver element was used, because it improved the mechanical properties as an effective grain refiner and it is also treated as a potential anti-inflammatory core. The new degradable Mg-Zn-Ag biomaterial was prepared by zone solidification technology and extrusion. The mechanical properties were mostly enhanced by fine grain strengthening. In addition, the alloys exhibited good cytocompatibility. The anti-inflammatory function of degradation products was identified by both interleukin-1α and nitric oxide modes. The anti-inflammatory impact was significantly associated with the concentration of silver ion. It was demonstrated that Mg-Zn-Ag system was a potential metallic stent with anti-inflammatory function, which can reduce the long-term dependence of anti-inflammatory drug after coronary stent implantation.

  20. Topical anti-inflammatory activity of yacon leaf extracts

    Directory of Open Access Journals (Sweden)

    Rejane B. Oliveira

    2013-06-01

    Full Text Available Smallanthus sonchifolius (Poepp. H. Rob. , Asteraceae, known as yacon, is an herb that is traditionally used for the treatment of diabetes in folk medicine. However, recent studies have demonstrated that this plant has other interesting properties such as anti-microbial and anti-inflammatory actions. Thus, the purpose of this study was to evaluate the topical anti-inflammatory property of different extracts prepared from yacon leaves and analyze the role of different chemical classes in this activity. Three yacon leaf extracts were obtained: aqueous extract, where chlorogenic acid derivatives and sesquiterpene lactones were detected; leaf rinse extract, rich in sesquiterpene lactones; and polar extract, rich in chlorogenic acid derivatives. All the extracts exhibited anti-edematogenic activity in vivo (aqueous extract: 25.9% edema inhibition at 0.50 mg/ear; polar extract: 42.7% inhibition at 0.25 mg/ear; and leaf rinse extract: 44.1% inhibition at 0.25 mg/ear. The leaf rinse extract furnished the best results regarding neutrophil migration inhibition, and NO, TNF-α and PGE2 inhibition. These data indicate that both sesquiterpene lactones and chlorogenic acid derivatives contribute to the anti-inflammatory action, although sesquiterpene lactones seem to have more pronounced effects. In conclusion, yacon leaf extracts, particularly the sesquiterpene lactone-rich extract, has potential use as topical anti-inflammatory agent.

  1. Anti-inflammatory role of obestatin in autoimmune myocarditis.

    Science.gov (United States)

    Pamukcu, Ozge; Baykan, Ali; Bayram, Latife Cakir; Narin, Figen; Cetin, Nazmi; Narin, Nazmi; Argun, Mustafa; Ozyurt, Abdullah; Uzum, Kazim

    2016-01-01

    Obestatin is a popular endogeneous peptide, known to have an autoimmune regulatory effect on energy metabolism and the gastrointestinal system. Studies regarding the anti-inflammatory effects of obestatin are scarce. The aim of this study was to show the anti-inflammatory effect of obestatin in an experimental model of autoimmune myocarditis in rats. Experimental autoimmune myocarditis was induced in Lewis rats by immunization with subcutaneous administration of porcine cardiac myosin, twice at 7-day intervals. Intraperitoneal pretreatment with obestatin (50 μg/kg) was started before the induction of myocarditis and continued for 3 weeks. The severity of myocarditis was evidenced by clinical, echocardiographic and histological findings. In addition, by-products of neutrophil activation, lipid peroxidation, inflammatory and anti-inflammatory cytokines were measured in serum. Obestatin significantly ameliorated the clinical and histopathological severity of autoimmune myocarditis. Therapeutic effects of obestatin in myocarditis were associated with reduced lipid peroxidation, suppression of polymorphonuclear leukocyte infiltration and enhancement of glutathione synthesis, inhibition of serum inflammatory and activation of anti-inflammatory cytokines. Histopathologically, the left ventricle was significantly dilated, and its wall thickened, along with widespread lymphocytic and histocytic infiltration. The myocardium was severely infiltrated with relatively large mononuclear cells. These histopathological changes were observed in lesser degrees in obestatin-treated rats. This study demonstrated a novel anti-inflammatory effect of obestatin in an experimental model of autoimmune myocarditis. Consequently, obestatin administration may represent a promising therapeutic approach for myocarditis and dilated cardiomyopathy in the future.

  2. Leaves extract of Murraya Koenigii linn for anti--inflammatory and analgesic activity in animal models

    Directory of Open Access Journals (Sweden)

    Shailly Gupta

    2010-01-01

    Full Text Available This work has been done for the investigation of the anti-inflammatory and analgesic activity of methanol extract of dried leaves of Murraya koenigii Linn by oral administration at dose of 100, 200 and 400 mg/kg body weight, to healthy animals. Extract was studied for its anti-inflammatory activity by using carrageenan-induced hind paw edema in albino rats and the mean increase in paw volume and % inhibition in paw volume were measured plethysmometrically at different time intervals after carrageenan (1% w/v injection. Extract was also evaluated for analgesic activity using Eddy′s hot plate method and formalin induced paw licking method in albino rats. The methanol extract showed significant (P < 0.001 reduction in the carrageenan-induced paw edema and analgesic activity evidenced by increase in the reaction time by eddy′s hot plate method and percentage increase in pain in formalin test. The methanol extract showed anti-inflammatory and analgesic effect in dose dependent manner when compared with the control and standard drug, diclofenac sodium (10mg/kg, p.o. These inhibitions were statistically significant (P < 0.05. Thus our investigation suggests a potential benefit of Murraya koenigii in treating conditions associated with inflammatory pain.

  3. Evaluating Anti-Inflammatory activity of aqueous root extract of Strophanthus hispidus DC. (Apocynaceae

    Directory of Open Access Journals (Sweden)

    E O Agbaje

    2012-01-01

    Full Text Available Summary: The present study explored the anti-inflammatory potential of aqueous root extract of Strophanthus hispidus (SPH DC (Apocynaceae in rodents, using standard laboratory models. Doses of 50, 100, 500 and 1000 mg/kg of aqueous SPH were administered orally in carrageenan-induced rat hind paw oedema, xylene-induced ear oedema in mice, and formalin-induced mice hind paw oedema (sub-acute 6 days, using indomethacin (10 mg/kg, dexamethasone 1 mg/kg and acetylsalicylic acid (Aspirin, 100 mg/kg respectively as standard drugs. The study further explored the effect of the herbal drug on some inflammatory mediators-histamine, serotonin and prostaglandin, using only the highest dose of SPH. Results obtained showed that the extract exerted a dose-dependent and significant (p<0.05 anti-inflammatory activity, which compared favourably with the positive control.  Significant inhibitions of mediators were also recorded; however, the least inhibition (42.8 % was produced in the serotonin model. Phytochemical analysis indicated the presence of flavonoids, cardiac glycosides, tannins, and anthraquinones.  It is also noteworthy that zinc, copper, manganese, lead, and chromium were the elemental constituents in the aqueous extract of SPH, some of which have been reported to possess anti-inflammatory property. While 2 g/kg of SPH administered orally did not produce any mortality, the median lethal dose by i.p route was 39.81 mg/kg, and it is thought that the lead contribute to the toxicity recorded. The pH of the herbal drug was 6.7. Our findings substantiate the local use of SPH in the treatment of acute and sub-acute inflammatory conditions, while it also suggests some possible pathways for its anti-inflammatory activity.  Lastly, since the herbal drug is liable to producing toxic effects, it must be used with caution. Industrial relevance: Herbal remedies continue to serve as an important source of conventional therapies for diverse disease conditions

  4. Anti-inflammatory and analgesic activities of SKLJI, a highly purified and injectable herbal extract of Lonicera japonica.

    Science.gov (United States)

    Ryu, Keun Ho; Rhee, Hae In; Kim, Joo Hyon; Yoo, Hunseung; Lee, Bong Yong; Um, Key-An; Kim, Keunyoung; Noh, Ji-Yoon; Lim, Kyung-Min; Chung, Jin-Ho

    2010-01-01

    The parenteral route has many merits over the oral route, including greater predictability, reproducibility of absorption, and rapid drug action, but injectable phytomedicines are uncommon due to protein precipitating tannin and hemolytic saponin components. In this study, in an effort to develop a safe injectable analgesic phytomedicine, we prepared a tannin and saponin-free Lonicera japonica extract, SKLJI, through fractionation and column purification, and evaluated its anti-inflammatory and analgesic activities in in vivo experimental models of inflammation and pain. The removal of tannin and saponin resulted in loganin and sweroside-enriched SKLJI and it showed reduced hemolysis and protein precipitation. In efficacy tests, SKLJI inhibited croton oil- and arachidonic acid-induced ear edema, acetic acid-induced writhing, and carrageenan-induced rat hind paw hyperalgesia. Inhibition of cylcooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and 5-lipoxyfenase (5-LO) activities by SKLJI appeared to be the mechanism underlying anti-inflammatory and analgesic efficacy. Loganin and sweroside also showed anti-inflammatory and analgesic activities, suggesting that they might be active principles in the efficacy of SKLJI. These results suggest that SKLJI is a viable candidate for a new anti-inflammatory and analgesic phytomedicine that can be administered by the parenteral route.

  5. Anti-inflammatory activity of probiotic Bifidobacterium:Enhancement of IL-10 production in peripheral blood mononuclear cells from ulcerative colitis patients and inhibition of IL-8 secretion in HT-29 cells

    Institute of Scientific and Technical Information of China (English)

    Akemi Imaoka; Tatsuichiro Shima; Kimitoshi Kato; Shigeaki Mizuno; Toshiki Uehara; Satoshi Matsumoto; Hiromi Setoyama; Taeko Hara; Yoshinori Umesaki

    2008-01-01

    AIM: To determine the anti-inflammatory activity of probiotic Bifidobacteria in Bifidobacteria-fermented milk (BFM) which is effective against active ulcerative colitis (UC) and exacerbations of UC, and to explore the immunoregulatory mechanisms.METHODS: Peripheral blood mononuclear cells (PBMNC)from UC patients or HT-29 cells were co-cultured with heat-killed probiotic bacteria or culture supernatant of Bifidobacterium breve strain Yakult (BbrY) or Bifidobacterium bifidum strain Yakult (BbiY) to estimate the amount of IL-10 or IL-8 secreted.RESULTS: Both strains of probiotic Bifidobacteria contained in the BFM induced IL-10 production in PBMNC from UC patients, though BbrY was more effective than BbiY.Conditioned medium (CM) and DNA of both strains inhibited IL-8 secretion in HT-29 cells stimulated with TNF-α, whereas no such effect was observed with heatkilled bacteria.The inhibitory effect of CM derived from BbiY was greater than that of CM derived from BbrY.DNAs of the two strains had a comparable inhibitory activity against the secretion of IL-8.CM of BbiY induced a repression of IL-8 gene expression with a higher expression of IκB-ζ mRNA 4 h after culture of HT-29 cells compared to that in the absence of CM.CONCLUSION: Probiotic Bifidobacterium strains in BFM enhance IL-10 production in PBMNC and inhibit IL-8 secretion in intestinal epithelial cells, suggesting that BFM has anti-inflammatory effects against ulcerative colitis.

  6. Use of Fixed Dose Combination (FDC Drugs in India: Central Regulatory Approval and Sales of FDCs Containing Non-Steroidal Anti-Inflammatory Drugs (NSAIDs, Metformin, or Psychotropic Drugs.

    Directory of Open Access Journals (Sweden)

    Patricia McGettigan

    2015-05-01

    Full Text Available In 2012, an Indian parliamentary committee reported that manufacturing licenses for large numbers of fixed dose combination (FDC drugs had been issued by state authorities without prior approval of the Central Drugs Standard Control Organization (CDSCO in violation of rules, and considered that some ambiguity until 1 May 2002 about states' powers might have contributed. To our knowledge, no systematic enquiry has been undertaken to determine if evidence existed to support these findings. We investigated CDSCO approvals for and availability of oral FDC drugs in fou