Indomethacin Inhibits Cancer Cell Migration via Attenuation of Cellular Calcium Mobilization

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Ke-Li Tsai

2013-06-01

Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs were shown to reduce the risk of colorectal cancer recurrence and are widely used to modulate inflammatory responses. Indomethacin is an NSAID. Herein, we reported that indomethacin can suppress cancer cell migration through its influence on the focal complexes formation. Furthermore, endothelial growth factor (EGF-mediated Ca2+ influx was attenuated by indomethacin in a dose dependent manner. Our results identified a new mechanism of action for indomethacin: inhibition of calcium influx that is a key determinant of cancer cell migration.

Tryptamine-Gallic Acid Hybrid Prevents Non-steroidal Anti-inflammatory Drug-induced Gastropathy

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Pal, Chinmay; Bindu, Samik; Dey, Sumanta; Alam, Athar; Goyal, Manish; Iqbal, Mohd. Shameel; Sarkar, Souvik; Kumar, Rahul; Halder, Kamal Krishna; Debnath, Mita Chatterjee; Adhikari, Susanta; Bandyopadhyay, Uday

2012-01-01

We have investigated the gastroprotective effect of SEGA (3a), a newly synthesized tryptamine-gallic acid hybrid molecule against non-steroidal anti-inflammatory drug (NSAID)-induced gastropathy with mechanistic details. SEGA (3a) prevents indomethacin (NSAID)-induced mitochondrial oxidative stress (MOS) and dysfunctions in gastric mucosal cells, which play a pathogenic role in inducing gastropathy. SEGA (3a) offers this mitoprotective effect by scavenging of mitochondrial superoxide anion (O2˙̄) and intramitochondrial free iron released as a result of MOS. SEGA (3a) in vivo blocks indomethacin-mediated MOS, as is evident from the inhibition of indomethacin-induced mitochondrial protein carbonyl formation, lipid peroxidation, and thiol depletion. SEGA (3a) corrects indomethacin-mediated mitochondrial dysfunction in vivo by restoring defective electron transport chain function, collapse of transmembrane potential, and loss of dehydrogenase activity. SEGA (3a) not only corrects mitochondrial dysfunction but also inhibits the activation of the mitochondrial pathway of apoptosis by indomethacin. SEGA (3a) inhibits indomethacin-induced down-regulation of bcl-2 and up-regulation of bax genes in gastric mucosa. SEGA (3a) also inhibits indometacin-induced activation of caspase-9 and caspase-3 in gastric mucosa. Besides the gastroprotective effect against NSAID, SEGA (3a) also expedites the healing of already damaged gastric mucosa. Radiolabeled (99mTc-labeled SEGA (3a)) tracer studies confirm that SEGA (3a) enters into mitochondria of gastric mucosal cell in vivo, and it is quite stable in serum. Thus, SEGA (3a) bears an immense potential to be a novel gastroprotective agent against NSAID-induced gastropathy. PMID:22157011

Anti-inflammatory Activity of Methanoilc and Ethanolic Extracts of ...

African Journals Online (AJOL)

ADOWIE PERE

ABSTRACT: Aqueous ethanoic and methanolic extracts of Citrus Sinensis Peel were investigated for anti- inflammatory activity in carrageenan induced paw oedema in wistar rats, and compared to a positive control drug,. Indomethacin. These extracts were given(IP) in a concentration of 20, and 70mg/kg with extract with a ...

Anti-inflammatory polymersomes of redox-responsive polyprodrug amphiphiles with inflammation-triggered indomethacin release characteristics.

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Tan, Jiajia; Deng, Zhengyu; Liu, Guhuan; Hu, Jinming; Liu, Shiyong

2018-03-21

Inflammation serves as a natural defense mechanism to protect living organisms from infectious diseases. Nonsteroidal anti-inflammatory drugs (NSAIDs) can help relieve inflammatory reactions and are clinically used to treat pain, fever, and inflammation, whereas long-term use of NSAIDs may lead to severe side effects including gastrointestinal damage and cardiovascular toxicity. Therefore, it is of increasing importance to configure new dosing strategies and alleviate the side effects of NSAIDs. Towards this goal, glutathione (GSH)-responsive disulfide bonds and hydrogen peroxide (H 2 O 2 )-reactive phenylboronic ester linkages were utilized as triggering moieties in this work to design redox-responsive prodrug monomers and polyprodrug amphiphiles based on indomethacin (IND) drug. Note that IND is a widely prescribed NSAID in the clinic. Starting from three types of redox-reactive IND prodrug monomers, redox-responsive polyprodrug amphiphiles were synthesized through reversible addition-fragmentation chain transfer (RAFT) polymerizations of prodrug monomers using poly(ethylene oxide) (PEO)-based macroRAFT agent. The resultant polyprodrug amphiphiles with high IND loading contents (>33 wt%) could self-assemble into polymersomes with PEO shielding coronas and redox-responsive bilayer membranes composed of IND prodrugs. Upon incubation with GSH or H 2 O 2 , controlled release of intact IND in the active form from polyprodrug polymersomes was actuated by GSH-mediated disulfide cleavage reaction and H 2 O 2 -mediated oxidation of phenylboronic ester moieties, respectively, followed by self-immolative degradation events. Furthermore, in vitro studies at the cellular level revealed that redox-responsive polymersomes could efficiently relieve inflammatory responses induced by lipopolysaccharide (LPS) in RAW264.7 macrophage cells. Copyright © 2018. Published by Elsevier Ltd.

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...... degrees, pH 7.4, in a sodium phosphate buffer, 66 mM, by means of equilibrium dialysis and, in case of salicylic acid, by dialysis rate determinations. Cobinding of each of these drugs with monoacetyl-4,4'-diaminodiphenyl sulfone, warfarin, and diazepam has been studied by measuring dialysis rates...

Toxic effects of non-steroidal anti-inflammatory agents in rats ...

African Journals Online (AJOL)

The toxicosis of some non-steroidal anti-inflammatory drugs, piroxicam, indomethacin, phenylbutazone, and aspirin, which occasionally are locally used in Nigeria as rodenticides have been evaluated in rats using changes in the serum biochemical and haematological parameters as indices of toxicity. In the study, no ...

The anti-inflammatory and analgesic properties of prosopis chilenses in rats.

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Abodola, M A; Lutfi, M F; Bakhiet, A O; Mohamed, A H

2015-07-01

Prosopis chilensis is used locally in Sudan for inflammatory conditions of joints; however, literature lacks scientific evidence for anti-inflammatory effect of this plant. To evaluate anti-inflammatory and analgesic effects of prosopis chilenses. Edema inhibition percent (EI %) and hot plate method were used to evaluate anti-inflammatory and analgesic effects of Prosopis chilenses in Wistar albino rats. Anti-inflammatory and analgesic effects of Prosopis chilenses were compared to indomethacin and acetylsalicylic acid respectively. Ethanolic extract of prosopis chilensis at a dose of 200 and 100mg/kg body weight achieved peak EI% (EI% = 96.1%) and (EI% = 94.4%) three and four hours after oral dosing respectively. The maximum EI% for indomethacin was 97.0% and was recorded after 4 hours following oral administration of the drug at a dose of 5 mg/kg body weight. Prosopis chilensis extracts at doses of 100 and 200 mg/kg body weight significantly increased the rats' response time to hot plate compared to acetylsalicylic acid at a dose rate of 100mg/kg body weight (Pprosopis chilenses. Relevance of these effects to prosopis chilenses phy-to-constituents was discussed.

Autoradiographic and biochemical observations on the distribution of non-steroid anti-inflammatory drugs.

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Rainsford, K D; Schweitzer, A; Brune, K

1981-04-01

A comparison has been made of the distribution of some new radioactively-labelled non-steroid anti-inflammatory (NSAI) drugs or pro-drugs with their respective progenitors and/or standard acidic NSAI drugs (i.e. aspirin, indomethacin and phenylbutazone), using whole body autoradiography and scintillation counting. The object of this study was to establish if the distribution of these new NSAI drugs may contribute to changes in their side-, or therapeutic effects compared with the older drugs. All the NSAI drugs accumulated in those tissues wherein the principle therapeutic and side-effects are manifest. The accumulation in inflamed tissues occurs regardless of the structural type of NSAI drugs, i.e. with specific accumulation occurring in this tissue of the acidic drugs or their acidic metabolites. New aspects of the distribution of the acetyl moiety of aspirin are reported which may be significant in relation to the side-effects induced by this drug.

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

International Nuclear Information System (INIS)

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

1989-01-01

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

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

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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.

Proniosomal formulation of curcumin having anti-inflammatory and anti-arthritic activity in different experimental animal models.

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Kumar, K; Rai, A K

2012-10-01

Curcumin, the active ingredient of the spice turmeric, has a long history as an herbal remedy for a variety of diseases. Transdermal drug delivery has been recognized as an alternative route to oral delivery. Proniosomes offer a versatile vesicle delivery concept with the potential for drug delivery via the transdermal route. In this study, different proniosomal gel bases were prepared by the ether injection method, using Span 60 and Span 80, Tween 20, cholesterol, and formulation PA2. They were characterized by scanning electron microscopy, revealing vesicular structures, and assessed for stability and effect on in vitro skin permeation using rat skin. Anti-inflammatory and anti-arthritic effects of formulation PA2 and PB1 were compared with a standard market product containing indomethacin. The effect of formulation PA2 and PB1 was evaluated for acute inflammation in carrageenan induced rat paw edema and for chronic inflammation in complete Freud's adjuvant (CFA) induced arthritis in rats. Further histopathological and radiographic evaluation was performed. The investigated curcumin loaded proniosomal formula proved to be non-irritant, non-toxic, but had lower anti-inflammatory and anti-arthritic effects than the marketed indomethacin products.

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

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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.

Anti-inflammatory drugs in the 21st century.

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Rainsford, K D

2007-01-01

Historically, anti-inflammatory drugs had their origins in the serendipitous discovery of certain plants and their extracts being applied for the relief of pain, fever and inflammation. When salicylates were discovered in the mid-19th century to be the active components of Willow Spp., this enabled these compounds to be synthesized and from this, acetyl-salicylic acid or Aspirin was developed. Likewise, the chemical advances of the 19th-20th centuries lead to development of the non-steroidal anti-inflammatory drugs (NSAIDs), most of which were initially organic acids, but later non-acidic compounds were discovered. There were two periods of NSAID drug discovery post-World War 2, the period up to the 1970's which was the pre-prostaglandin period and thereafter up to the latter part of the last century in which their effects on prostaglandin production formed part of the screening in the drug-discovery process. Those drugs developed up to the 1980-late 90's were largely discovered empirically following screening for anti-inflammatory, analgesic and antipyretic activities in laboratory animal models. Some were successfully developed that showed low incidence of gastro-intestinal (GI) side effects (the principal adverse reaction seen with NSAIDs) than seen with their predecessors (e.g. aspirin, indomethacin, phenylbutazone); the GI reactions being detected and screened out in animal assays. In the 1990's an important discovery was made from elegant molecular and cellular biological studies that there are two cyclo-oxygenase (COX) enzyme systems controlling the production of prostanoids [prostaglandins (PGs) and thromboxane (TxA2)]; COX-1 that produces PGs and TxA2 that regulate gastrointestinal, renal, vascular and other physiological functions, and COX-2 that regulates production of PGs involved in inflammation, pain and fever. The stage was set in the 1990's for the discovery and development of drugs to selectively control COX-2 and spare the COX-1 that is central to

Kinetic studies of the inhibition of a human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isozyme by bile acids and anti-inflammatory drugs.

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Miyabe, Y; Amano, T; Deyashiki, Y; Hara, A; Tsukada, F

1995-01-01

We have investigated the steady-state kinetics for a cytosolic 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isozyme of human liver and its inhibition by several bile acids and anti-inflammatory drugs such as indomethacin, flufemanic acid and naproxen. Initial velocity and product inhibition studies performed in the NADP(+)-linked (S)-1-indanol oxidation at pH 7.4 were consistent with a sequential ordered mechanism in which NADP+ binds first and leaves last. The bile acids and drugs, competitive inhibitors with respect to the alcohol substrate, exhibited uncompetitive inhibition with respect to the coenzyme, with Ki values less than 1 microM, whereas indomethacin exhibited noncompetitive inhibition (Ki < 24 microM). The kinetics of the inhibition by a mixture of the two inhibitors suggests that bile acids and drugs, except indomethacin, bind to overlapping sites at the active center of the enzyme-coenzyme binary complex.

Possibilities of the combined use of non-steroidal anti-inflammatory drugs and sulfhydryl compounds in radioprotection

International Nuclear Information System (INIS)

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

1991-01-01

The combined preirradiation administration of indomethacin and cystamine was found to enhance synergistically the recovery of hemopoiesis in sublethally gamma-irradiated mice. This effect can be explained by a common operation of two mechanisms of radioprotection, i.e. of an increased survival of hemopoietic stem cells due to cystamine action and of stimulatory effects of indomethacin on the proliferation of surviving cells, mediated by the inhibition of prostaglandin synthesis. Attempts to prove such enhancement of protective effects on irradiated mice in terms of postirradiation lethality were unsuccessful. The reason seems to be the influence of toxic effects of the indomethacin-cystamine combination on the gastrointestinal tract. When using the less toxic combination, i.e. diclofenac and WR-2721, the additivity of protective effects is manifested even in the survival of lethally irradiated mice. The results suggest that under suitable conditions avoiding the unfavourable toxic effects, non-steroidal anti-inflammatory drugs can be successfully used with the aim to enhance the efficiency of sulfhydryl radioprotectors. (orig.) [de

Effects of intrathecal or intracerebroventricular administration of nonsteroidal anti-inflammatory drugs on a C-fiber reflex in rats.

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Bustamante, D; Paeile, C; Willer, J C; Le Bars, D

1997-06-01

A C-fiber reflex elicited by electrical stimulation within the territory of the sural nerve was recorded from the ipsilateral biceps femoris muscle in anesthetized rats. The temporal evolution of the response was studied using a constant stimulus intensity (3 times threshold), and recruitment curves were built by varying the stimulus intensity from 0 to 7 times threshold. The intrathecal (i.t.) but not i.c.v. administration of aspirin, indomethacin, ketoprofen and lysine clonixinate resulted in dose-dependent depressions of the C-fiber reflex. In contrast, saline was ineffective. Regardless of the route of administration, the drugs never produced disturbances in heart rate and/or acid-base equilibrium. When a constant level of stimulation was used, 500 microg of aspirin i.t. induced a blockade of the reflex immediately after the injection, followed by a partial recovery. Indomethacin produced a stable depression, which reached 80 to 90% with an i.t. dose of 500 microg. Ketoprofen and lysine clonixinate produced a more stable effect; the highest doses (500 microg) produced a steady-state depression of approximately 50% for approximately 30 min. When the recruitment curves were built with a range of nociceptive stimulus intensities, all of the drugs except for indomethacin produced a dose-dependent decrease in the slopes and the areas under the recruitment curves without major modifications in the thresholds; indomethacin also induced a significant dose-related increase in the threshold. The orders of potency for both stimulation paradigms with the i.t. route were the same, namely aspirin > indomethacin > lysine clonixinate > or = ketoprofen. It is concluded that nonsteroidal anti-inflammatory drugs elicit significant antinociceptive effects at a spinal level, which do not depend on the existence of a hyperalgesic or inflammatory state. Such effects were not seen after injections within the lateral ventricle.

Anti-Inflammatory Iridoids of Botanical Origin

Science.gov (United States)

Viljoen, A; Mncwangi, N; Vermaak, I

2012-01-01

Inflammation is a manifestation of a wide range of disorders which include; arthritis, atherosclerosis, Alzheimer’s disease, inflammatory bowel syndrome, physical injury and infection amongst many others. Common treatment modalities are usually non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, paracetamol, indomethacin and ibuprofen as well as corticosteroids such as prednisone. These however, may be associated with a host of side effects due to non-selectivity for cyclooxygenase (COX) enzymes involved in inflammation and those with selectivity may be highly priced. Thus, there is a continuing search for safe and effective anti-inflammatory molecules from natural sources. Research has confirmed that iridoids exhibit promising anti-inflammatory activity which may be beneficial in the treatment of inflammation. Iridoids are secondary metabolites present in various plants, especially in species belonging to the Apocynaceae, Lamiaceae, Loganiaceae, Rubiaceae, Scrophulariaceae and Verbenaceae families. Many of these ethnobotanicals have an illustrious history of traditional use alluding to their use to treat inflammation. Although iridoids exhibit a wide range of pharmacological activities such as cardiovascular, hepatoprotection, hypoglycaemic, antimutagenic, antispasmodic, anti-tumour, antiviral, immunomodulation and purgative effects this review will acutely focus on their anti-inflammatory properties. The paper aims to present a summary for the most prominent iridoid-containing plants for which anti-inflammatory activity has been demonstrated in vitro and / or in vivo. PMID:22414102

Indomethacin decreases optic nerve oxygen tension by a mechanism other than cyclo-oxygenase inhibition

DEFF Research Database (Denmark)

Noergaard, M Hove; Pedersen, D Bach; Bang, K

2008-01-01

We investigated the effect of several Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), on the preoptic nerve oxygen tension (ONPO2), as indomethacin previously has demonstrated a strong decreasing effect on ONPO2. We tested whether these NSAIDs, like indomethacin, also reduce the increasing effect...

The nonsteroidal anti-inflammatory drug indomethacin induces heterogeneity in lipid membranes: potential implication for its diverse biological action.

Directory of Open Access Journals (Sweden)

Yong Zhou

2010-01-01

Full Text Available The nonsteroidal anti-inflammatory drug (NSAID, indomethacin (Indo, has a large number of divergent biological effects, the molecular mechanism(s for which have yet to be fully elucidated. Interestingly, Indo is highly amphiphilic and associates strongly with lipid membranes, which influence localization, structure and function of membrane-associating proteins and actively regulate cell signaling events. Thus, it is possible that Indo regulates diverse cell functions by altering micro-environments within the membrane. Here we explored the effect of Indo on the nature of the segregated domains in a mixed model membrane composed of dipalmitoyl phosphatidyl-choline (di16:0 PC, or DPPC and dioleoyl phosphatidyl-choline (di18:1 PC or DOPC and cholesterol that mimics biomembranes.Using a series of fluorescent probes in a fluorescence resonance energy transfer (FRET study, we found that Indo induced separation between gel domains and fluid domains in the mixed model membrane, possibly by enhancing the formation of gel-phase domains. This effect originated from the ability of Indo to specifically target the ordered domains in the mixed membrane. These findings were further confirmed by measuring the ability of Indo to affect the fluidity-dependent fluorescence quenching and the level of detergent resistance of membranes.Because the tested lipids are the main lipid constituents in cell membranes, the observed formation of gel phase domains induced by Indo potentially occurs in biomembranes. This marked Indo-induced change in phase behavior potentially alters membrane protein functions, which contribute to the wide variety of biological activities of Indo and other NSAIDs.

Effect of indomethacin and salt depletion on renal proton MR imaging

International Nuclear Information System (INIS)

Heyman, S.N.; Mammen, M.

1991-01-01

Blockade of the synthesis of vasodilating prostaglandins with non-steroidal anti-inflammatory drugs (NSAID) renders the renal medulla susceptible to hypoxic injury with reduced renal function, especially in clinical conditions characterized by volume depletion. Alterations in renal hemodynamics and urine production may effect renal MR imaging under these circumstances. We injected salt-depleted and control rats undergoing proton MR imaging with indomethacin 10 mg/kg. Indomethacin abolished the cortico-medullary T2-gradient and markedly diminished the overall renal signal in salt-depleted rats only. These changes, which progressed over a period of 40 min after indomethacin was injected, probably result from renal oligemia and decreased urine production, with an associated decrease in T2-values. We suggest that a history of consumption of non-steroidal anti-inflammatory drugs should be obtained and taken into account in the evaluation of renal proton MR imaging, especially in the presence of salt and volume depletion. (orig.)

Thermodynamics of Indomethacin Adsorption to Phospholipid Membranes.

Science.gov (United States)

Fearon, Amanda D; Stokes, Grace Y

2017-11-22

Using second-harmonic generation, we directly monitored adsorption of indomethacin, a nonsteroidal anti-inflammatory drug, to supported lipid bilayers composed of phospholipids of varying phase, cholesterol content, and head group charge without the use of extrinsic labels at therapeutically relevant aqueous concentrations. Indomethacin adsorbed to gel-phase lipids with a high binding affinity, suggesting that like other arylacetic acid-containing drugs, it preferentially interacts with ordered lipid domains. We discovered that adsorption of indomethacin to gel-phase phospholipids was endothermic and entropically driven, whereas adsorption to fluid-phase phospholipids was exothermic and enthalpically driven. As temperature increased from 19 to 34 °C, binding affinities to gel-phase lipids increased by 7-fold but relative surface concentration decreased to one-fifth of the original value. We also compared our results to the entropies reported for indomethacin adsorbed to surfactant micelles, which are used in drug delivery systems, and assert that adsorbed water molecules in the phospholipid bilayer may be buried deeper into the acyl chains and less accessible for disruption. The thermodynamic studies reported here provide mechanistic insight into indomethacin interactions with mammalian plasma membranes in the gastrointestinal tract and inform studies of drug delivery, where indomethacin is commonly used as a prototypical, hydrophobic small-molecule drug.

Alteration of plasma prednisolone levels by indomethacin and naproxen.

OpenAIRE

Rae, S A; Williams, I A; English, J; Baylis, E M

1982-01-01

Eleven patients with stable rheumatoid disease (RD) who were receiving regular corticosteroid therapy (CS) were investigated to discover the effect on plasma prednisolone levels of additional therapy with the non-steroidal anti-inflammatory (NSAI) drugs, indomethacin and naproxen. There was a highly significant (P less than 0.001) increase in free prednisolone levels after concurrent therapy with either indomethacin or naproxen for 2 weeks. Total prednisolone levels were unchanged. These resu...

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

OpenAIRE

Khoeini Sharifabadi, Malihe; Saber-Tehrani, Mohammad; Waqif Husain, Syed; Mehdinia, Ali; Aberoomand-Azar, Parviz

2014-01-01

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 dr...

Ordered cubic nanoporous silica support MCM-48 for delivery of poorly soluble drug indomethacin

Science.gov (United States)

Zeleňák, Vladimír; Halamová, Dáša; Almáši, Miroslav; Žid, Lukáš; Zeleňáková, Adriána; Kapusta, Ondrej

2018-06-01

Ordered MCM-48 nanoporous silica (SBET = 923(3) m2·g-1, VP = 0.63(2) cm3·g-1) with cubic Ia3d symmetry was used as a support for drug delivery of anti-inflammatory poorly soluble drug indomethacin. The delivery from parent, unmodified MCM-48, and 3-aminopropyl modified silica carrier was studied into the simulated body fluids with the pH = 2 and pH = 7.4. The studied samples were characterized by thermal analysis (TG/DTG-DTA), N2 adsorption/desorption, infrared spectroscopy (FT-IR), powder XRD, SEM, HRTEM methods, measurements of zeta potential (ζ) and dynamic light scattering (DLS). The determined content of indomethacin in pure MCM-48 was 21 wt.% and in the amine-modified silica MCM-48A-I the content was 45 wt.%. The release profile of the drug, in the time period up to 72 h, was monitored by TLC chromatographic method. It as shown, that by the modification of the surface, the drug release can be controlled. The slower release of indomethacin was observed from amino modified sample MCM-48A-I in the both types of studied simulated body fluids (slightly alkaline intravenous solution with pH = 7.4 and acidic gastric fluid with pH = 2), which was supported and explained by zeta potential and DLS measurements. The amount of the released indomethacin into the fluids with various pH was different. The maximum released amount of the drug was 97% for sample containing unmodified silica, MCM-48-I at pH = 7.4 and lowest released amount, 57%, for amine modified sample MCM-48A-I at pH = 2. To compare the indomethacin release profile four kinetic models were tested. Results showed, that that the drug release based on diffusion Higuchi model, mainly governs the release.

Morin protects gastric mucosa from nonsteroidal anti-inflammatory drug, indomethacin induced inflammatory damage and apoptosis by modulating NF-κB pathway.

Science.gov (United States)

Sinha, Krishnendu; Sadhukhan, Pritam; Saha, Sukanya; Pal, Pabitra Bikash; Sil, Parames C

2015-04-01

Deregulation in prostaglandin (PG) biosynthesis, severe oxidative stress, inflammation and apoptosis contribute to the pathogenesis of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. Unfortunately, most of the prescribed anti-ulcer drugs generate various side effects. In this scenario, we could consider morin as a safe herbal potential agent against IND-gastropathy and rationalize its action systematically. Rats were pretreated with morin for 30 min followed by IND (48 mgkg(-1)) administration for 4 h. The anti-ulcerogenic nature of morin was assessed by morphological and histological analysis. Its effects on the inflammatory (MPO, cytokines, adhesion molecules), ulcer-healing (COXs, PGE(2)), and signaling parameters (NF-κB and apoptotic signaling) were assessed by biochemical, RP-HPLC, immunoblots, IHC, RT-PCR, and ELISA at the time points of their maximal changes due to IND administration. IND induced NF-κB and apoptotic signaling in rat's gastric mucosa. These increased proinflammatory responses, but reduced the antioxidant enzymes and other protective factors. Morin reversed all the adverse effects to prevent IND-induced gastric ulceration in a PGE2 independent manner. Also, it did not affect the absorption and/or primary pharmacological activity of IND. The gastroprotective action of morin is primarily attributed to its potent antioxidant nature that also helps in controlling several IND-induced inflammatory responses. For the first time, the study reveals a mechanistic basis of morin mediated protective action against IND-induced gastropathy. As morin is a naturally abundant safe antioxidant, future detailed pharmacokinetic and pharmacodynamic studies are expected to establish it as a gastroprotective agent. Copyright © 2015 Elsevier B.V. All rights reserved.

Alteration of plasma prednisolone levels by indomethacin and naproxen.

Science.gov (United States)

Rae, S A; Williams, I A; English, J; Baylis, E M

1982-01-01

Eleven patients with stable rheumatoid disease (RD) who were receiving regular corticosteroid therapy (CS) were investigated to discover the effect on plasma prednisolone levels of additional therapy with the non-steroidal anti-inflammatory (NSAI) drugs, indomethacin and naproxen. There was a highly significant (P less than 0.001) increase in free prednisolone levels after concurrent therapy with either indomethacin or naproxen for 2 weeks. Total prednisolone levels were unchanged. These results could provide an explanation for clinical reports that these two NSAI drugs possess a steroid-sparing effect. PMID:7126420

Non-steroidal anti-inflammatory drugs and cyclooxygenase in Alzheimer's disease

NARCIS (Netherlands)

Hoozemans, Jeroen J. M.; Veerhuis, Robert; Rozemuller, Annemieke J. M.; Eikelenboom, Piet

2003-01-01

Epidemiological studies indicate that anti-inflammatory drugs, especially the non-steroidal anti-inflammatory drugs (NSAIDs), decrease the risk of developing Alzheimer's disease (AD). Their beneficial effects may be due to interference in the chronic inflammatory reaction, that takes place in AD.

Analgesic and Anti-Inflammatory Activity of Pinus roxburghii Sarg.

Directory of Open Access Journals (Sweden)

Dhirender Kaushik

2012-01-01

Full Text Available The Chir Pine, Pinus roxburghii, named after William Roxburgh, is a pine native to the Himalaya. Pinus roxburghii Sarg. (Pinaceae is traditionally used for several medicinal purposes in India. As the oil of the plant is extensively used in number of herbal preparation for curing inflammatory disorders, the present study was undertaken to assess analgesic and anti-inflammatory activities of its bark extract. Dried and crushed leaves of Pinus roxburghii Sarg. were defatted with petroleum ether and then extracted with alcohol. The alcoholic extract at the doses of 100 mg/kg, 300 mg/kg, and 500 mg/kg body weight was subjected to evaluation of analgesic and anti-inflammatory activities in experimental animal models. Analgesic activity was evaluated by acetic acid-induced writhing and tail immersion tests in Swiss albino mice; acute and chronic anti-inflammatory activity was evaluated by carrageenan-induced paw oedema and cotton pellet granuloma in Wistar albino rats. Diclofenac sodium and indomethacin were employed as reference drugs for analgesic and anti-inflammatory studies, respectively. In the present study, the alcoholic bark extract of Pinus roxburghii Sarg. demonstrated significant analgesic and anti-inflammatory activities in the tested models.

Anti-nociceptive and anti-inflammatory properties of the ethanolic ...

African Journals Online (AJOL)

Anti-nociceptive and anti-inflammatory properties of the ethanolic extract of Lagenaria breviflora whole fruit in rat and mice. ... Its effect was comparable especially at 200mg/kg body weight to those of diclofenac, indomethacin and ibuprofen. It could be suggested from the findings of this experiment that the extract may be ...

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

Non-Steroidal Anti Inflammatory Drugs Usage In Orthopaedics And ...

African Journals Online (AJOL)

Background: Non steroidal anti-inflammatory drugs NSAIDs) are a group of heterogeneous compounds with nti inflammatory, analgesic and often times anti pyretic roperties. They are weak organic acids and are the most commonly used drugs in Orthopaedic/Trauma practice. hey provide mild to moderate pain relief.

Aggravation by paroxetine, a selective serotonin reuptake inhibitor, of antral lesions generated by nonsteroidal anti-inflammatory drugs in rats.

Science.gov (United States)

Takeuchi, Koji; Tanaka, Akiko; Nukui, Kazuo; Kojo, Azusa; Gyenge, Melinda; Amagase, Kikuko

2011-09-01

Recent clinical studies have suggested a risk of adverse gastric reactions from the concomitant use of selective serotonin (5-HT) reuptake inhibitors (SSRIs) with nonsteroidal anti-inflammatory drugs (NSAIDs). We examined the adverse effects of SSRIs on antral lesions produced by indomethacin in rats. Rats fasted for 24 h were refed for 1 h, then administered indomethacin (30 mg/kg s.c.) 1 h after the refeeding and killed 6 h later. Paroxetine (1-10 mg/kg) was given orally 30 min before indomethacin. Indomethacin caused antral lesions in refed rats. Paroxetine dose-dependently aggravated these lesions, despite provoking no damage by itself. Similar results were obtained when other NSAIDs such as diclofenac, flurbiprofen, and loxoprofen were coadministered with paroxetine or when indomethacin was coadministered with other antidepressants such as fluvoxamine and milnacipran, but not imipramine or maprotiline. Exogenous 5-HT also worsened the indomethacin-induced antral damage, whereas the aggravating effect of paroxetine was attenuated by ondansetron, a selective 5-HT(3) antagonist, but not antagonists for other 5-HT receptor subtypes. Indomethacin plus paroxetine had no effect on gastric secretion but significantly decreased mucosal superoxide dismutase (SOD) activity as well as GSH content. The antral damage induced by indomethacin plus paroxetine was significantly prevented by antisecretory (acid or pepsin) agents and mucosal protective agents as well as SOD and allopurinol. These results suggest that SSRIs aggravate NSAID-induced antral lesions, probably via the activation of 5HT(3) receptors, and the mechanism of aggravation may involve the corrosive action of acid/pepsin as well as an impaired antioxidative system.

Mast cells and pro-inflammatory cytokines roles in assessment of grape seeds extract anti-inflammatory activity in rat model of carrageenan-induced paw edema

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Amany Ahmed Mohamed Abd-Allah

2018-01-01

Full Text Available Objective(s: Reactive oxygen species (ROS-produced oxidative disorders were involved at the pathophysiology of many inflammatory processes via the generation of pro-inflammatory cytokines and antioxidant defense system suppression. Although herbal antioxidants as mono-therapy relief many inflammatory diseases including, autoimmunity rheumatoid arthritis, but as combination therapy with other proven anti-inflammatory drugs in order to decreasing their toxic impacts has not yet been studied clearly, especially against chemical substances that’s induced local inflammation with characteristic edema. Materials and Methods: Grape seeds extract (GSE at a concentration of 40 mg/kg B. wt alone or in combination with indomethacin (Indo. at a dose of 5 mg/Kg B. wt orally given for 10 days prior (gps VI, VII, VIII or as a single dose after edema induction (gps IX, X, XI in rat's left hind paw by sub-planter single injection of 0.1 carrageenan: saline solution (1% (gp. V to assess the prophylactic and therapeutic anti-inflammatory activities of both through  the estimation of selective inflammatory mediators and oxidative damage-related biomarkers as well as tissue mast cell scoring. Furthermore, both substances were given alone (gps II, III, IV for their  blood, liver and kidney safety evaluation comparing with negative control rats (gp. I which kept without medication. Results: A marked reduction on the inflammatory mediators, edema volume and oxidative byproducts in edema bearing rats' prophylactic and treated with grape seeds extract and indomethacin was observed. Indomethacin found to induce some toxicological impacts which minimized when administered together with GSE. Conclusion: GSE is a safe antioxidant agent with anti-inflammatory property.

Binding of indomethacin methyl ester to cyclooxygenase-2. A computational study.

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Sárosi, Menyhárt-Botond

2018-06-05

Inhibitors selective towards the second isoform of prostaglandin synthase (cyclooxygenase, COX-2) are promising nonsteroidal anti-inflammatory drugs and antitumor medications. Methylation of the carboxylate group in the relatively nonselective COX inhibitor indomethacin confers significant COX-2 selectivity. Several other modifications converting indomethacin into a COX-2 selective inhibitor have been reported. Earlier experimental and computational studies on neutral indomethacin derivatives suggest that the methyl ester derivative likely binds to COX-2 with a similar binding mode as that observed for the parent indomethacin. However, docking studies followed by molecular dynamics simulations revealed two possible binding modes in COX-2 for indomethacin methyl ester, which differs from the experimental binding mode found for indomethacin. Both alternative binding modes might explain the observed COX-2 selectivity of indomethacin methyl ester. Graphical abstract Binding of indomethacin methyl ester to cyclooxygenase-2.

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

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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.

Persistent Adult Neuroimmune Activation and Loss of Hippocampal Neurogenesis Following Adolescent Ethanol Exposure: Blockade by Exercise and the Anti-inflammatory Drug Indomethacin

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Ryan P. Vetreno

2018-03-01

Full Text Available Alcohol abuse and binge drinking are common during adolescence, a developmental period characterized by heightened neuroplasticity. Animal studies reveal that adolescent ethanol exposure decreases hippocampal neurogenesis that persists into adulthood, but the mechanism remains to be fully elucidated. Using a rodent model of adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2-days on/2-days off from postnatal day [P]25 to P55, we tested the hypothesis that AIE-induced upregulation of neuroimmune signaling contributes to the loss of hippocampal neurogenesis in adulthood. We found that AIE caused upregulation of multiple proinflammatory Toll-like receptors (TLRs, increased expression of phosphorylated NF-κB p65 (pNF-κB p65 and the cell death marker cleaved caspase 3, and reduced markers of neurogenesis in the adult (P80 hippocampus, which is consistent with persistently increased neuroimmune signaling reducing neurogenesis. We observed a similar increase of pNF-κB p65-immunoreactive cells in the post-mortem human alcoholic hippocampus, an effect that was negatively correlated with age of drinking onset. Voluntary wheel running from P24 to P80 prevented the AIE-induced loss of neurogenesis markers (i.e., nestin and doublecortin in the adult hippocampus that was paralleled by blockade of increased expression of the cell death marker cleaved caspase 3. Wheel running also prevented the AIE-induced increase of hippocampal pNF-κB p65 and induction of neuroimmune NF-κB target genes, including TNFα and IκBα in the adult brain. Administration of the anti-inflammatory drug indomethacin during AIE prevented the loss of neurogenesis markers (i.e., nestin and doublecortin and the concomitant increase of cleaved caspase 3, an effect that was accompanied by blockade of the increase of pNF-κB p65. Similarly, administration of the proinflammatory TLR4 activator lipopolysaccharide resulted in a loss of doublecortin that was paralleled by increased

Polymer-lipid hybrid nanoparticles as enhanced indomethacin delivery systems.

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Dalmoro, Annalisa; Bochicchio, Sabrina; Nasibullin, Shamil F; Bertoncin, Paolo; Lamberti, Gaetano; Barba, Anna Angela; Moustafine, Rouslan I

2018-05-17

Non-steroidal anti-inflammatory drugs (NSAIDs), i.e. indomethacin used for rheumatoid arthritis and non-rheumatoid inflammatory diseases, are known for their injurious actions on the gastrointestinal (GI) tract. Mucosal damage can be avoided by using nanoscale systems composed by a combination of liposomes and biodegradable natural polymer, i.e. chitosan, for enhancing drug activity. Aim of this study was to prepare chitosan-lipid hybrid delivery systems for indomethacin dosage through a novel continuous method based on microfluidic principles. The drop-wise conventional method was also applied in order to investigate the effect of the two polymeric coverage processes on the nanostructures features and their interactions with indomethacin. Thermal-physical properties, mucoadhesiveness, drug entrapment efficiency, in vitro release behavior in simulated GI fluids and stability in stocking conditions were assayed and compared, respectively, for the uncoated and chitosan-coated nanoliposomes prepared by the two introduced methods. The prepared chitosan-lipid hybrid structures, with nanometric size, have shown high indomethacin loading (about 10%) and drug encapsulation efficiency up to 99%. TEM investigation has highlighted that the developed novel simil-microfluidic method is able to put a polymeric layer, surrounding indomethacin loaded nanoliposomes, thicker and smoother than that achievable by the drop-wise method, improving their storage stability. Finally, double pH tests have confirmed that the chitosan-lipid hybrid nanostructures have a gastro retentive behavior in simulated gastric and intestinal fluids thus can be used as delivery systems for the oral-controlled release of indomethacin. Based on the present results, the simil-microfluidic method, working with large volumes, in a rapid manner, without the use of drastic conditions and with a precise control over the covering process, seems to be the most promising method for the production of suitable

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.

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

International Nuclear Information System (INIS)

Hajjizadeh, M.; Jabbari, A.; Heli, H.; Moosavi-Movahedi, A.A.; Haghgoo, S.

2007-01-01

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

Effect of indomethacin and salt depletion on renal proton MR imaging; An experimental study in the rat

Energy Technology Data Exchange (ETDEWEB)

Heyman, S.N.; Mammen, M. (Harvard Medical School, Boston, MA (United States). Charles A Dana Research Inst. Beth Israel Hospital, Boston, MA (United States))

1991-11-01

Blockade of the synthesis of vasodilating prostaglandins with non-steroidal anti-inflammatory drugs (NSAID) renders the renal medulla susceptible to hypoxic injury with reduced renal function, especially in clinical conditions characterized by volume depletion. Alterations in renal hemodynamics and urine production may effect renal MR imaging under these circumstances. We injected salt-depleted and control rats undergoing proton MR imaging with indomethacin 10 mg/kg. Indomethacin abolished the cortico-medullary T2-gradient and markedly diminished the overall renal signal in salt-depleted rats only. These changes, which progressed over a period of 40 min after indomethacin was injected, probably result from renal oligemia and decreased urine production, with an associated decrease in T2-values. We suggest that a history of consumption of non-steroidal anti-inflammatory drugs should be obtained and taken into account in the evaluation of renal proton MR imaging, especially in the presence of salt and volume depletion. (orig.).

Aspirin and its related non-steroidal anti-inflammatory drugs

African Journals Online (AJOL)

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

Non-steroidal anti-inflammatory drugs and benign oesophageal stricture.

Science.gov (United States)

Heller, S R; Fellows, I W; Ogilvie, A L; Atkinson, M

1982-01-01

Drug histories were obtained from 76 patients at the time of initial Eder-Puestow dilatation for benign oesophageal stricture. Six patients had consumed drugs known to cause oesophageal ulceration (emepronium bromide and potassium preparations). Of the remaining 70 patients, 22 had regularly taken a non-steroidal anti-inflammatory drug before the onset of dysphagia compared with 10 patients in a control group matched for age and sex; this difference was significant (p less than 0.02). Non-steroidal anti-inflammatory drugs may have a causative role in the formation of oesophageal stricture in patients with gastro-oesophageal reflux, in whom they should be prescribed with caution. PMID:6807392

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)....

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. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

Proquazone: a treatment for lymphocytic infiltration of the skin. Comparative study with 2 other nonsteroid anti-inflammatory drugs.

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Johansson, E A

1987-01-01

15 patients with lymphocytic infiltration of the skin (LIS) were treated with the nonsteroid anti-inflammatory (NSAI) drug proquazone [1-isopropyl-4-phenyl-7-methyl-2(IH)]. In contrast to other NSAI drugs proquazone is a nonacidic compound which is known to be a potent prostaglandin synthesis inhibitor. Of the 15 patients 8 were healed completely with proquazone; in half of these patients lesions recurred but healed with reintroduction of the drug. Two patients remained symptom-free with a small maintenance dose. Two patients showed a partial remission. The treatment was discontinued in 3 patients, in 2 of them because of side effects and in 1 because of lack of response. Two other NSAI drugs, both known to be potent prostaglandin synthesis inhibitors, namely indomethacin and ibuprofen, were tried, however without effect. The present study indicates that proquazone should be considered in the treatment of LIS.

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

Science.gov (United States)

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.

Effect of ethamsylate on carrageenan-induced rat paw oedema: a comparison with indomethacin.

Science.gov (United States)

Gard, P R; Trigger, D J

1990-12-01

1. Ethamsylate (diethylammonium 2,5-dihydroxybenzene sulfonate, Dicynene), a systemic haemostatic agent with an unknown mechanism of action, was tested for anti-inflammatory activity using the carrageenan-induced rat paw oedema test. 2. Ethamsylate was shown to be an effective anti-inflammatory agent with a time course and amplitude of effect similar to that of indomethacin, although the potency was only about 4% of that for indomethacin. 3. When ethamsylate and indomethacin were co-administered they did not show additive effects, suggesting that they do not share a common mode of action. It is proposed that ethamsylate, like indomethacin, may inhibit prostaglandin synthesis. Ulceration produced by indomethacin, it is suggested that it may prove to be a useful addition to, or replacement for, indomethacin in the treatment of inflammatory disorders.

No effect of one-year treatment with indomethacin on Alzheimer's disease progression : a randomized controlled trial

NARCIS (Netherlands)

de Jong, Daniëlle; Jansen, René; Hoefnagels, Willibrord; Jellesma-Eggenkamp, Marja; Verbeek, Marcel; Borm, George; Kremer, Berry

2008-01-01

BACKGROUND: The objective of this study was to determine whether treatment with the nonselective nonsteroidal anti-inflammatory drug (NSAID) indomethacin slows cognitive decline in patients with Alzheimer's disease (AD). METHODOLOGY/PRINCIPAL FINDINGS: This double-blind, randomized,

Attenuation of stress induced memory deficits by nonsteroidal anti-inflammatory drugs (NSAIDs) in rats: Role of antioxidant enzymes.

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Emad, Shaista; Qadeer, Sara; Sadaf, Sana; Batool, Zehra; Haider, Saida; Perveen, Tahira

2017-04-01

Repeated stress paradigms have been shown to cause devastating alterations on memory functions. Stress is linked with inflammation. Psychological and certain physical stressors could lead to neuroinflammation. Inflammatory process may occur by release of mediators and stimulate the production of prostaglandins through cyclooxygenase (COX). Treatment with COX inhibitors, which restrain prostaglandin production, has enhanced memory in a number of neuroinflammatory states showing a potential function for raised prostaglandins in these memory shortfalls. In the present study, potential therapeutic effects of indomethacin and diclofenac sodium on memory in both unrestraint and restraint rats were observed. Two components, long term memory and short term memory were examined by Morris water maze (MWM) and elevated plus maze (EPM) respectively. The present study also demonstrated the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on lipid peroxidation (LPO) and activities of antioxidant enzymes along with the activity of acetylcholinesterase (AChE). Results of MWM and EPM showed significant effects of drugs in both unrestraint and restraint rats as escape latency and transfer latency, in respective behavioral models were decreased as compared to that of control. This study also showed NSAIDs administration decreased LPO and increased antioxidant enzymes activity and decreased AChE activity in rats exposed to repeated stress. In conclusion this study suggests a therapeutic potential of indomethacin and diclofenac against repeated stress-induced memory deficits. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Acute oral toxicity and anti-inflammatory activity of hydroalcoholic extract from Lampaya medicinalis Phil in rats.

Science.gov (United States)

Morales, Glauco; Paredes, Adrián; Olivares, Alberto; Bravo, Jaime

2014-03-26

Algesia and inflammation are related with several pathological conditions. It is known that many drugs available for the treatment of these problems cause unwanted side effects. This study was aimed at evaluating acute toxicity and anti-inflammatory activity of Lampaya medicinalis Phil. (Verbenaceae) widely used in the folk medicine of Northern Chile against rheumatism, arthritis and body joints pain. Oral administration of hydroalcoholic extract (HAE) at the highest dose of 3000 mg/ Kg body weight resulted in no mortalities or evidence of significant behavioral changes. Histological examination revealed normal architecture and no significant adverse effects were observed on the liver, kidney, heart, lung or ovaries and testicles. The results suggest that the oral administration of hydroalcoholic extract (HAE) from Lampaya medicinalis did not produce any toxic effect in rats. Hydroalcoholic extract (HAE) significantly inhibited the carrageenan-induced rat paw edema in dose - response relationship, at test doses of 37.5, 75, 150 and 300 mg/Kg body weight. Maximum inhibition (61.98 ± 2.69%) was noted at 300 mg/Kg after 2 h of drug treatment carrageenan induced paw edema, whereas indomethacin produced 47.90 ± 1.16% of inhibition. The inhibitory values of edema at 3 h postcarrageenan were 31.04 ± 0.75%, 40.51 ± 2.36%, 48.97 ± 1.14% and 56.87 ± 0.41% for 37.5, 75, 150, and 300 mg/kg of extract respectively. Indomethacin (10 mg/Kg) gave a percentage inhibition of 49.44 ± 1.44. HAE (300 and 150 mg/kg) induced an anti-inflammatory effect greater than (or comparable) with the effect of indomethacin from 2nd to 4th hours of the experiment. Our results reveal for first time that compounds contained in the hydroalcoholic extract of Lampaya medicinalis Phil exert anti-inflammatory effect and the oral administration is safe and non toxic up to dose level 3000 mg/kg body weight. The anti-inflammatory activity may be associated with the presence of flavonoids. These

N-arylmethylideneaminophthalimide: Design, synthesis and evaluation as analgesic and anti-inflammatory agents.

Science.gov (United States)

Banarouei, Nasimossadat; Davood, Asghar; Shafaroodi, Hamed; Saeedi, Ghazaleh; Shafiee, Abbas

2018-04-23

N-aryl derivatives of phthalimide and 4-nitro phthalimide have demonstrated cyclooxygenase inhibitory activity. Also they possess an excellent analgesic and anti-inflammatory activity. In this work, a new series of N-arylmethylideneamino derivatives of phthalimide and 4-nitro phthalimide were designed and synthesized. The designed compounds were synthesized by condensation of the appropriate aldehyde and N-aminophthalimide in ethanol at room temperature at PH around 3. Their analgesic and anti-inflammatory activity were evaluated by acetic acid-induced pain test and carrageenan-induced paw edema test in mice and rats, respectively. The details of the synthesis and chemical characterization of the analogs are described. In vivo screening showed compounds 3a, 3b, 3f and 3h were the most potent analgesic compounds. In addition compounds 3a, 3c, 3d, 3e and 3j indicated comparable anti-inflammatory activity to indomethacin as reference drug. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Evaluation of the anti-inflammatory activities of Quillaja saponaria Mol. saponin extract in mice

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Sumana Sarkhel

Full Text Available Objective: Quillaja saponaria bark contains a high percentage of triterpene saponins and has been used for centuries as antiinflammatory and analgesic agent in Chilean folk medicine.In the Present study the anti-inflammatory activities of the aqueous extract of commercially partially purified saponin from Quillaja saponaria Mol. in in vivo animal models. Methods & materials:: Aqueous extract of the plant material was prepared by cold maceration. The anti-inflammatory activity of a commercial Quillaja saponaria Mol. (QS saponin extract was investigated by carragenan induced mice paw edema model for acute inflammation (Winter, 1962 [16]. Results: The anti-inflammatory activity was evaluated by carragenan in paw edema model in swiss albino mice (18–20 g. The anti-inflammatory activity was found to be dose dependent in carragenan induced paw edema. QS was found to significantly (p < 0.05 reduce the carragenan induced mice paw edema (38.59%; 20 mg/kg bw as compared to carragenan control. The percentage inhibition of standard anti-inflammatory drug indomethacin was (55%; 10 mg/kg, bw. Conclusion: The results of the present study demonstrate that the aqueous extract of Quillaja saponaria saponins (QS possess significant anti-inflammatory activity. Keywords: Anti-inflammatory activity, Aqueous extract, Paw edema

Osteoarthritis guidelines: a progressive role for topical nonsteroidal anti-inflammatory drugs

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Stanos SP

2013-04-01

Full Text Available Steven P Stanos Rehabilitation Institute of Chicago, Center for Pain Management, Chicago, IL, USA Abstract: Current treatment guidelines for the treatment of chronic pain associated with osteoarthritis reflect the collective clinical knowledge of international experts in weighing the benefits of pharmacologic therapy options while striving to minimize the negative effects associated with them. Consideration of disease progression, pattern of flares, level of functional impairment or disability, response to treatment, coexisting conditions such as cardiovascular disease or gastrointestinal disorders, and concomitant prescription medication use should be considered when creating a therapeutic plan for a patient with osteoarthritis. Although topical nonsteroidal anti-inflammatory drugs historically have not been prevalent in many of the guidelines for osteoarthritis treatment, recent evidence-based medicine and new guidelines now support their use as a viable option for the clinician seeking alternatives to typical oral formulations. This article provides a qualitative review of these treatment guidelines and the emerging role of topical nonsteroidal anti-inflammatory drugs as a therapy option for patients with localized symptoms of osteoarthritis who may be at risk for oral nonsteroidal anti-inflammatory drug-related serious adverse events. Keywords: osteoarthritis, nonsteroidal anti-inflammatory drugs, guidelines, topical analgesics, diclofenac

Macrolide Hybrid Compounds: Drug Discovery Opportunities in Anti- Infective and Anti-inflammatory Area.

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Paljetak, Hana Cipcic; Tomaskovic, Linda; Matijasic, Mario; Bukvic, Mirjana; Fajdetic, Andrea; Verbanac, Donatella; Peric, Mihaela

2017-01-01

Macrolides, polyketide natural products, and their 15-membered semi-synthetic derivatives are composed of substituted macrocyclic lactone ring and used primarily as potent antibiotics. Recently their usefulness was extended to antimalarial and anti-inflammatory area. Hybrid macrolides presented in this article are the next generation semi-synthetic compounds that combine pharmacophores from antibacterial, antimalarial and anti-inflammatory area with 14- and 15-membered azalide scaffolds. Antibacterial azalide hybrids with sulphonamides showed improved activity against resistant streptococci while quinolone conjugates demonstrated full coverage of respiratory pathogens including macrolide resistant strains and their efficacy was confirmed in mouse pneumonia model. Antimalarial macrolide hybrids, mainly involving (chloro)quinoline pharmacophores, showed outstanding activity against chloroquine resistant strains, favourable pharmacokinetics, promising in vivo efficacy as well as encouraging developmental potential. Anti-inflammatory hybrids were obtained by combining macrolides with corticosteroid and non-steroidal anti-inflammatory drugs. They were found active in in vivo animal models of locally induced inflammation, asthma, inflammatory bowel disease and rheumatoid arthritis and demonstrated improved safety over parent steroid drugs. Overall, macrolide hybrids possess significant potential to be developed as potent novel medicines in therapeutic areas of utmost pharmaceutical interest. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Indomethacin causes prostaglandin D(2)-like and eotaxin-like selective responses in eosinophils and basophils.

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Stubbs, Victoria E L; Schratl, Petra; Hartnell, Adele; Williams, Timothy J; Peskar, Bernhard A; Heinemann, Akos; Sabroe, Ian

2002-07-19

We investigated the actions of a panel of nonsteroidal anti-inflammatory drugs on eosinophils, basophils, neutrophils, and monocytes. Indomethacin alone was a potent and selective inducer of eosinophil and basophil shape change. In eosinophils, indomethacin induced chemotaxis, CD11b up-regulation, respiratory burst, and L-selectin shedding but did not cause up-regulation of CD63 expression. Pretreatment of eosinophils with indomethacin also enhanced subsequent eosinophil shape change induced by eotaxin, although treatment with higher concentrations of indomethacin resulted in a decrease in the expression of the major eosinophil chemokine receptor, CCR3. Indomethacin activities and cell selectivity closely resembled those of prostaglandin D(2) (PGD(2)). Eosinophil shape change in response to eotaxin was inhibited by pertussis toxin, but indomethacin- and PGD(2)-induced shape change responses were not. Treatment of eosinophils with specific inhibitors of phospholipase C (U-73122), phosphatidylinositol 3-kinase (LY-294002), and p38 mitogen-activated protein kinase (SB-202190) revealed roles for these pathways in indomethacin signaling. Indomethacin and its analogues may therefore provide a structural basis from which selective PGD(2) receptor small molecule antagonists may be designed and which may have utility in the treatment of allergic inflammatory disease.

Anti-oxidant and anti-inflammatory activity of leaf extracts and fractions of Mangifera indica.

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Mohan, C G; Deepak, M; Viswanatha, G L; Savinay, G; Hanumantharaju, V; Rajendra, C E; Halemani, Praveen D

2013-04-13

To evaluate the anti-oxidant and anti-inflammatory activity of leaf extracts and fractions of Mangifera indica in in vitro conditions. 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. In in vitro DPPH radical scavenging activity, the MEMI, EMEMI and BMEMI have offered significant antioxidant activity with IC(50) values of 13.37, 3.55 and 14.19 μg/mL respectively. Gallic acid, a reference standard showed significant antioxidant activity with IC(50) 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 IC(50) 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 IC(50) 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. These findings suggest that the MEMI and EMEMI possess potent anti-oxidant and anti-inflammatory activities in in vitro conditions. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Indomethacin induces apoptosis via a MRPI-dependent mechanism in doxorubicin-resistant small-cell lung cancer cells overexpressing MRPI

NARCIS (Netherlands)

de Groot, D. J. A.; van der Deen, M.; Le, T. K. P.; Regeling, A.; de Jong, S.; de Vries, E. G. E.

2007-01-01

Small-cell lung cancers (SCLCs) initially respond to chemotherapy, but are often resistant at recurrence. The non-steroidal anti-inflammatory drug indomethacin is an inhibitor of multidrug resistance protein 1 (MRPI) function. The doxorubicin-resistant MRPI-overexpressing human SCLC cell line

[Anti-inflammatory, analgesic and anti-pyretic activities of a non-steroidal anti-inflammatory drug, etofenamate, in experimental animals].

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Nakamura, H; Motoyoshi, S; Imazu, C; Ishii, K; Yokoyama, Y; Seto, Y; Kadokawa, T; Shimizu, M

1982-08-01

Anti-inflammatory, analgesic, and anti-pyretic activities of orally administered etofenamate, the diethylene glycol ester of flufenamic acid, were investigated in experimental animals. Against acetic acid-induced vascular permeability in mice and ultra-violet light-induced erythema in guinea pigs, etofenamate produced a dose related inhibition at doses of 40--320 mg/kg and 5--20 mg/kg, respectively. In rats, felt-pellet-induced granuloma formation and adjuvant-induced arthritis were significantly inhibited by repeated administration of etofenamate at doses of 20 mg/kg/day for 5 days and 40 mg/kg/day for 21 days, respectively. Etofenamate showed an inhibitory activity on the squeak response caused by flexing and extending the silver nitrate-induced arthritic joint in rats; and it produced a dose related anti-writhing activity at doses of 50--300 mg/kg and 10--80 mg/kg in mice and rats, respectively, in the acetic acid-induced writhing test. Etofenamate showed a significant anti-pyretic activity at doses of 0.2 mg/kg or more. These potencies of etofenamate were 0.5 to 1.6 times those of flufenamic acid. In particular, the anti-erythema, anti-arthritis, and anti-pyretic activities of etofenamate were approximately equivalent to or superior to those of flufenamic acid. From these results, it was suggested that etofenamate given orally, like other non-steroidal anti-inflammatory drugs, showed anti-inflammatory, analgesic, and anti-pyretic activities in experimental animals.

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

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

2014-01-01

BACKGROUND: Nonsteroidal anti-inflammatory drugs can increase bleeding and thrombosis, but little is known about the cerebrovascular safety of these drugs, especially among healthy people. AIMS: The aim of this study was to examine the risk of ischemic and hemorrhagic stroke associated with the use...... 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......·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....

Anti-inflammatory activity of animal oils from the Peruvian Amazon.

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Schmeda-Hirschmann, Guillermo; Delporte, Carla; Valenzuela-Barra, Gabriela; Silva, Ximena; Vargas-Arana, Gabriel; Lima, Beatriz; Feresin, Gabriela E

2014-10-28

Animal oils and fats from the fishes Electrophorus electricus and Potamotrygon motoro, the reptiles Boa constrictor, Chelonoidis denticulata (Geochelone denticulata) and Melanosuchus niger and the riverine dolphin Inia geoffrensis are used as anti-inflammatory agents in the Peruvian Amazon. The aim of the study was to assess the topic anti-inflammatory effect of the oils/fats as well as to evaluate its antimicrobial activity and fatty acid composition. The oils/fats were purchased from a traditional store at the Iquitos market of Belen, Peru. The topic anti-inflammatory effect was evaluated by the mice ear edema induced by arachidonic acid (AA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) at the dose of 3mg oil/ear. Indomethacine and nimesulide were used as reference anti-inflammatory drugs. The application resembles the traditional topical use of the oils. The antimicrobial effect of the oils/fats was assessed by the microdilution test against reference strains of Escherichia coli, Staphylococcus aureus and Salmonella enteritidis. The fatty acid composition of the oils/fats (as methyl esters) was determined by GC and GC-MS analysis after saponification. All oils/fats showed topic anti-inflammatory activity, with better effect in the TPA-induced mice ear edema assay. The most active drugs were Potamotrygon motoro, Melanosuchus niger and Geochelone denticulata. In the AA-induced assay, the best activity was found for Potamotrygon motoro and Electrophorus electricus oil. The oil of Electrophorus electricus also showed a weak antimicrobial effect with MIC values of 250 µg/mL against Escherichia coli ATCC 25922 and Salmonella enteritidis-MI. The main fatty acids in the oils were oleic, palmitic and linoleic acids. Topical application of all the oils/fats investigated showed anti-inflammatory activity in the mice ear edema assay. The effect can be related with the identity and composition of the fatty acids in the samples. This study gives support to the traditional

Analgesic, anti-inflammatory and antioxidant properties of Buddleja globosa, Buddlejaceae.

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Backhouse, N; Rosales, L; Apablaza, C; Goïty, L; Erazo, S; Negrete, R; Theodoluz, C; Rodríguez, J; Delporte, C

2008-03-05

Buddleja globosa, known as "matico", is employed in Chile for wound healing. To validate the traditional use of the crude drug through in vivo and in vitro evaluation of the anti-inflammatory, analgesic and antioxidant properties of its extracts. Sequential hexane, dichloromethane, methanol and total methanol extracts were studied using bioguided fractionation. The following activities were investigated: analgesic (writhing test), oral and topic anti-inflammatory (paw- and ear-induced edema), free radical scavenging and antioxidant activities (1,1-diphenyl-2-picrylhydrazyl, DPPH, superoxide anion, lipid peroxidation and xanthine oxidase inhibition). Sodium naproxen, nimesulide, indomethacin were used as reference drugs for in vivo, quercetin and allopurinol for in vitro assays. A mixture of alpha- and beta-amyrins was isolated from the hexane extract that showed 41.2% of analgesic effect at 600 mg/kg, inhibited by 47.7 and 79.0% the arachidonic acid (AA) and 12-deoxyphorbol-13-decanoate (TPA)-induced inflammation at 3mg/20 microL/ear, respectively. A mixture of beta-sitosterol, stigmasterol, stigmastenol, stigmastanol and campesterol was isolated from the fraction CD4-N and beta-sitosterol-glycoside from the fraction CD5-N, reducing TPA-induced inflammation by 78.2 and 83.7% at 1mg/20 microL/ear, respectively. The fraction CD4-N at 300 mg/kg also showed analgesic activity (38.7%). The methanol extract at 600mg/kg per os showed anti-inflammatory effect (61.4%), topic anti-inflammatory (56.7% on TPA) and analgesic activity (38.5%). Verbascoside and luteolin-7-O-glucoside were the major components of the methanol extract; apigenin 7-O-glucoside was also detected. Inhibition of superoxide anion, lipoperoxidation, and DPPH bleaching effect was found in the methanol serial and global extracts. The present report demonstrate the analgesic and anti-inflammatory properties of Buddleja globosa and validate its use in Chilean traditional medicine.

Acute oral toxicity and anti-inflammatory activity of hydroalcoholic extract from Lampaya medicinalis Phil in rats

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Glauco Morales

2014-01-01

Full Text Available BACKGROUND: Algesia and inflammation are related with several pathological conditions. It is known that many drugs available for the treatment of these problems cause unwanted side effects. This study was aimed at evaluating acute toxicity and anti-inflammatory activity of Lampaya medicinalis Phil. (Verbenaceae widely used in the folk medicine of Northern Chile against rheumatism, arthritis and body joints pain. RESULTS: Oral administration of hydroalcoholic extract (HAE at the highest dose of 3000 mg/ Kg body weight resulted in no mortalities or evidence of significant behavioral changes. Histological examination revealed normal architecture and no significant adverse effects were observed on the liver, kidney, heart, lung or ovaries and testicles. The results suggest that the oral administration of hydroalcoholic extract (HAE from Lampaya medicinalis did not produce any toxic effect in rats. Hydroalcoholic extract (HAE significantly inhibited the carrageenan-induced rat paw edema in dose - response relationship, at test doses of 37.5, 75, 150 and 300 mg/Kg body weight. Maximum inhibition (61.98 ± 2.69% was noted at 300 mg/Kg after 2 h of drug treatment carrageenan induced paw edema, whereas indomethacin produced 47.90 ± 1.16% of inhibition. The inhibitory values of edema at 3 h postcarrageenan were 31.04±0.75%, 40.51 ± 2.36%, 48.97 ± 1.14% and 56.87 ± 0.41% for 37.5, 75, 150, and 300 mg/kg of extract respectively. Indomethacin (10 mg/Kg gave a percentage inhibition of 49.44 ± 1.44. HAE (300 and 150 mg/kg induced an anti-inflammatory effect greater than (or comparable with the effect of indomethacin from 2nd to 4th hours of the experiment. CONCLUSIONS: Our results reveal for first time that compounds contained in the hydroalcoholic extract ofLampaya medicinalis Phil exert anti-inflammatory effect and the oral administration is safe and non toxic up to dose level 3000 mg/kg body weight. The anti-inflammatory

Beneficial effect of an omega-6 PUFA-rich diet in non-steroidal anti-inflammatory drug-induced mucosal damage in the murine small intestine.

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Ueda, Toshihide; Hokari, Ryota; Higashiyama, Masaaki; Yasutake, Yuichi; Maruta, Koji; Kurihara, Chie; Tomita, Kengo; Komoto, Shunsuke; Okada, Yoshikiyo; Watanabe, Chikako; Usui, Shingo; Nagao, Shigeaki; Miura, Soichiro

2015-01-07

To investigate the effect of a fat rich diet on non-steroidal anti-inflammatory drug (NSAID)-induced mucosal damage in the murine small intestine. C57BL6 mice were fed 4 types of diets with or without indomethacin. One group was fed standard laboratory chow. The other groups were fed a fat diet consisting of 8% w/w fat, beef tallow (rich in SFA), fish oil, (rich in omega-3 PUFA), or safflower oil (rich in omega-6 PUFA). Indomethacin (3 mg/kg) was injected intraperitoneally from day 8 to day 10. On day 11, intestines and adhesions to submucosal microvessels were examined. In the indomethacin-treated groups, mucosal damage was exacerbated by diets containing beef tallow and fish oil, and was accompanied by leukocyte infiltration (P safflower oil diet than in mice fed the beef tallow or fish oil diet (P safflower oil significantly decreased monocyte and platelet recruitment (P < 0.05). A diet rich in SFA and omega-3 PUFA exacerbated NSAID-induced small intestinal damage via increased leukocyte infiltration. Importantly, a diet rich in omega-6-PUFA did not aggravate inflammation as monocyte migration was blocked.

Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis.

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Trelle, Sven; Reichenbach, Stephan; Wandel, Simon; Hildebrand, Pius; Tschannen, Beatrice; Villiger, Peter M; Egger, Matthias; Jüni, Peter

2011-01-11

To analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs. Network meta-analysis. Bibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data. All large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility. The primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data. 31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death. Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.

[Non-steroidal anti-inflammatory drug induced gastropathy and preventive effects of teprenone on the gastropathy in rats].

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Ma, Juan; Yuan, Gang; Chen, Min-hu

2006-10-31

To construct the model of non-steroidal anti-inflammatory drug (NSAID) induced gastropathy and observe the preventive effects of Teprenone on it in rats. Ninety-one male Sprague-Dawley (SD) rats were divided into normal saline group, model group (I) and prophylaxis group (II). Group I includes four subgroups (Ia, Ib, Ic, Id) treated by indomethacin (5 mgxkg(-1)xd(-1)), combination of indomethacin (5 mgxkg(-1)xd(-1)) and prednisone (10 mgxkg(-1)xd(-1)), celecoxib (100 mgxkg(-1)xd(-1)) and combination of celecoxib (100 mgxkg(-1)xd(-1)) and prednisone (10 mgxkg(-1)xd(-1)) respectively. Group II also includes four subgroups (IIa, IIb, IIc, IId) pretreated by teprenone (12 mgxkg(-1)xd(-1)) compared with group I. Lesion index (LI), pathohistology index, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) mRNA detected by RT-PCR were observed after 4 days. Compared with normal saline group, LI (11.00 (1.00 - 22.5), 8.50 (0.75 - 14.50), 11.00 (3.50 - 14.75), P NSAID. Prednisone could promote the risk in NSAID induced gastropathy. In addition to COX-1 inhibition, other factors might also involved in NSAID induced gastropathy. Teprenone could prevented from NSAID induced gastropathy but the actions might be not associated with COXs.

Tryptamine-gallic acid hybrid prevents non-steroidal anti-inflammatory drug-induced gastropathy: correction of mitochondrial dysfunction and inhibition of apoptosis in gastric mucosal cells.

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Pal, Chinmay; Bindu, Samik; Dey, Sumanta; Alam, Athar; Goyal, Manish; Iqbal, Mohd Shameel; Sarkar, Souvik; Kumar, Rahul; Halder, Kamal Krishna; Debnath, Mita Chatterjee; Adhikari, Susanta; Bandyopadhyay, Uday

2012-01-27

We have investigated the gastroprotective effect of SEGA (3a), a newly synthesized tryptamine-gallic acid hybrid molecule against non-steroidal anti-inflammatory drug (NSAID)-induced gastropathy with mechanistic details. SEGA (3a) prevents indomethacin (NSAID)-induced mitochondrial oxidative stress (MOS) and dysfunctions in gastric mucosal cells, which play a pathogenic role in inducing gastropathy. SEGA (3a) offers this mitoprotective effect by scavenging of mitochondrial superoxide anion (O(2)(·-)) and intramitochondrial free iron released as a result of MOS. SEGA (3a) in vivo blocks indomethacin-mediated MOS, as is evident from the inhibition of indomethacin-induced mitochondrial protein carbonyl formation, lipid peroxidation, and thiol depletion. SEGA (3a) corrects indomethacin-mediated mitochondrial dysfunction in vivo by restoring defective electron transport chain function, collapse of transmembrane potential, and loss of dehydrogenase activity. SEGA (3a) not only corrects mitochondrial dysfunction but also inhibits the activation of the mitochondrial pathway of apoptosis by indomethacin. SEGA (3a) inhibits indomethacin-induced down-regulation of bcl-2 and up-regulation of bax genes in gastric mucosa. SEGA (3a) also inhibits indometacin-induced activation of caspase-9 and caspase-3 in gastric mucosa. Besides the gastroprotective effect against NSAID, SEGA (3a) also expedites the healing of already damaged gastric mucosa. Radiolabeled ((99m)Tc-labeled SEGA (3a)) tracer studies confirm that SEGA (3a) enters into mitochondria of gastric mucosal cell in vivo, and it is quite stable in serum. Thus, SEGA (3a) bears an immense potential to be a novel gastroprotective agent against NSAID-induced gastropathy.

Osteoarthritis guidelines: a progressive role for topical nonsteroidal anti-inflammatory drugs.

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Stanos, Steven P

2013-01-01

Current treatment guidelines for the treatment of chronic pain associated with osteoarthritis reflect the collective clinical knowledge of international experts in weighing the benefits of pharmacologic therapy options while striving to minimize the negative effects associated with them. Consideration of disease progression, pattern of flares, level of functional impairment or disability, response to treatment, coexisting conditions such as cardiovascular disease or gastrointestinal disorders, and concomitant prescription medication use should be considered when creating a therapeutic plan for a patient with osteoarthritis. Although topical nonsteroidal anti-inflammatory drugs historically have not been prevalent in many of the guidelines for osteoarthritis treatment, recent evidence-based medicine and new guidelines now support their use as a viable option for the clinician seeking alternatives to typical oral formulations. This article provides a qualitative review of these treatment guidelines and the emerging role of topical nonsteroidal anti-inflammatory drugs as a therapy option for patients with localized symptoms of osteoarthritis who may be at risk for oral nonsteroidal anti-inflammatory drug-related serious adverse events.

Analgesic and anti-inflammatory effects of honey: the involvement of autonomic receptors.

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Owoyele, Bamidele Victor; Oladejo, Rasheed Olajiire; Ajomale, Kayode; Ahmed, Rasheedat Omotayo; Mustapha, Abdulrasheed

2014-03-01

The use of honey for therapeutic purposes is on the increase and many studies have shown that honey has the ability to influence biological systems including pain transmission. Therefore, this study was designed to investigate the analgesic and anti-inflammatory effects of honey and the effects of concurrent administration of autonomic nervous system blocking drugs. Studies on analgesic activities was carried out using hotplate and formalin-induced paw licking models while the anti-inflammatory activity was by the carrageenan paw oedema method. Animals were distributed into six groups consisting of five animals each. They were administered saline, honey (600 mg/kg), indomethacin (5 mg/kg), autonomic blockers (3 μg/kg of tamsulosin, 20 mg/kg (intraperitoneally) of propranolol, 2 ml/kg of atropine or 10 mg/kg (intra muscularly) of hexamethonium) or honey (200 and 600 mg/kg) with one of the blockers. The results showed that honey reduced pain perception especially inflammatory pain and the administration of tamsulosin and propranolol spared the effect of honey. Hexamethonium also spared the effects of honey at the early and late phases of the test while atropine only inhibited the early phase of the test. However, atropine and hexamethonium spared the anti-inflammatory effects of honey but tamsulosin abolished the effects while propranolol only abolished the anti-inflammatory effects at the peak of the inflammation. The results suggest the involvement of autonomic receptors in the anti-nociceptive and anti-inflammatory effects of honey although the level of involvement depends on the different types of the receptors.

Smoking, caffeine, and nonsteroidal anti-inflammatory drugs in families with Parkinson disease.

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Hancock, Dana B; Martin, Eden R; Stajich, Jeffrey M; Jewett, Rita; Stacy, Mark A; Scott, Burton L; Vance, Jeffery M; Scott, William K

2007-04-01

To assess associations between Parkinson disease (PD) and putatively protective factors-smoking, caffeine (coffee, tea, and soft drinks), and nonsteroidal anti-inflammatory drugs (aspirin, ibuprofen, and naproxen). Family-based case-control study. Academic medical center clinic. A total of 356 case subjects and 317 family controls who self-reported environmental exposures. Associations between PD and environmental measures (history, status, dosage, duration, and intensity) of smoking, coffee, caffeine, nonsteroidal anti-inflammatory drugs, and non-aspirin nonsteroidal anti-inflammatory drugs were examined using generalized estimating equations with an independent correlation matrix while controlling for age and sex. Individuals with PD were significantly less likely to report ever smoking (odds ratio = 0.56; 95% confidence interval, 0.41-0.78). Additional measures of smoking revealed significant inverse associations with PD (Pcoffee drinking was inversely associated with PD (test for trend P = .05). Increasing dosage (trend P = .009) and intensity (trend P = .01) of total caffeine consumption were also inversely associated, with high dosage presenting a significant inverse association for PD (odds ratio = 0.58; 95% confidence interval, 0.34-0.99). There were no significant associations between nonsteroidal anti-inflammatory drugs and PD. Inverse associations of smoking and caffeine were corroborated using families with PD, thus emphasizing smoking and caffeine as important covariates to consider in genetic studies of PD.

Qing Dai attenuates nonsteroidal anti-inflammatory drug-induced mitochondrial reactive oxygen species in gastrointestinal epithelial cells.

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Saito, Rie; Tamura, Masato; Matsui, Hirofumi; Nagano, Yumiko; Suzuki, Hideo; Kaneko, Tsuyoshi; Mizokami, Yuji; Hyodo, Ichinosuke

2015-01-01

Treatments with nonsteroidal anti-inflammatory drugs (NSAIDs) have increased the number of patients with gastrointestinal complications. Qing Dai has been traditionally used in Chinese herbal medicine for various inflammatory diseases such as ulcerative colitis. We previously reported that Qing Dai suppressed inflammations by scavenging reactive oxygen species (ROS) in ulcerative colitis patients. Thus, Qing Dai can attenuate the production of ROS, which play an important role in NSAID-induced gastrointestinal injuries. In this study, we aimed to elucidate whether Qing Dai decreased mitochondrial ROS production in NSAID-treated gastrointestinal cells by examining cellular injury, mitochondrial membrane potentials, and ROS production with specific fluorescent indicators. We also performed electron paramagnetic resonance measurement in isolated mitochondria with a spin-trapping reagent (CYPMPO or DMPO). Treatments with indomethacin and aspirin induced cellular injury and mitochondrial impairment in the gastrointestinal cells. Under these conditions, mitochondrial alterations were observed on electron microscopy. Qing Dai prevented these complications by suppressing ROS production in gastrointestinal cells. These results indicate that Qing Dai attenuated the ROS production from the NSAID-induced mitochondrial alteration in the gastrointestinal epithelial cells. Qing Dai treatment may be considered effective for the prevention NSAID-induced gastrointestinal injury.

Nonsteroidal anti-inflammatory drugs: adverse effects and their prevention.

NARCIS (Netherlands)

Vonkeman, Harald Erwin; van de Laar, 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,

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

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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.

Nonsteroidal anti-inflammatory drugs for treatment of acute gout

NARCIS (Netherlands)

van Durme, Caroline M. P. G.; Wechalekar, Mihir D.; Landewé, Robert B. M.

2015-01-01

Are nonsteroidal anti-inflammatory drugs (NSAIDs) associated with better outcomes than cyclooxygenase inhibitors, glucocorticoids, IL-1 inhibitors or placebo in the treatment of acute gout? NSAIDs are not significantly associated with a difference in pain reduction compared with cyclooxygenase

Structural damage and changes in eicosanoid metabolites in the gastric mucosa of rats and pigs induced by anti-inflammatory drugs of varying ulcerogenicity.

Science.gov (United States)

Rainsford, K D

1986-01-01

The object of the studies reviewed here has been to correlate the time-course of ultrastructural changes induced by oral administration of a range of non-steroidal anti-inflammatory (NSAI) drugs with effects on eicosanoid metabolism and drug absorption, so as to discriminate what biochemical/cellular and pharmacological factors account for their varying ulcerogenicity. Oral administration of highly ulcerogenic drugs (e.g. aspirin, diclofenac, indomethacin, piroxicam) to rats causes rapid damage to surface and gastric mucous cells, selective parietal cell damage, and extensive disruption of endothelial cells of submucosal microcapillaries (especially with aspirin) with accompanying extravasation of blood cell components. These changes are coincident with depressed levels of PGE2/6-keto-PGF1 alpha (measured by GC/MS or RIA) and uptake of the drugs (measured by scintillation counting or HPLC). Low ulcerogenic NSAI drugs (e.g. azapropazone, benoxaprofen and fenclofenac) causes very little damage to the surface mucosal cells. Azapropazone has been found to be well absorbed, and benoxaprofen and fenclofenac somewhat more slowly, so for the latter two drugs their low rate of absorption might also be a factor in their reduced ulcerogenicity. Aspirin, azapropazone and benoxaprofen have been shown to reduce 5-HETE levels (RIA), although the latter two drugs were more effective than aspirin. Thus, they result in the inhibition of PG production, by cyclo-oxygenase inhibition (with potential adverse effects from excess oxyradical and/or production of HETE's) with inhibition of the lipoxygenase pathway. The time-sequence of changes induced by single oral doses of indomethacin or other NSAI drugs on the ultrastructure and the prostanoid metabolism of the pig gastric mucosa parallelled those seen in the rat. Attempts to determine whether co-administration of NSAI drugs might reduce the inhibition of PG cyclo-oxygenase by more potent inhibitors (e.g. indomethacin) have been

Hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs)

DEFF Research Database (Denmark)

Nissen, Christoffer V; Bindslev-Jensen, Carsten; Mørtz, Charlotte G

2015-01-01

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are reported to be the second most common cause of drug hypersensitivity. In 2011, experts from the EAACI/ENDA group and GA(2)LEN proposed a new classification system for NSAID hypersensitivity. The aim of this study was to classify...... responders reacted to non-pyrazolone drugs. Only one patient could not be classified according to the EAACI/ENDA system. An overlap between respiratory and cutaneous symptoms was found in 15/39 (38%) of patients. CONCLUSIONS: All but one of our patients could be classified according to the EAACI...

Sustained-release indomethacin in the management of the acute painful shoulder from bursitis and/or tendinitis.

Science.gov (United States)

Calabro, J J; Londino, A V; Eyvazzadeh, C

1985-10-25

Of all the forms of nonarticular rheumatism, by far the most common are bursitis and tendinitis. Yet, the bursae and neighboring tendon sheaths are the most neglected anatomic structures of the body. Moreover, like the joints, they are lined by synovial membrane, secrete synovial fluid, and are common sites of rheumatic problems. The vast majority of painful shoulder problems are caused by acute subacromial (subdeltoid) bursitis and bicipital tendinitis. In the management of these periarticular disorders, the ultimate goal is to preserve shoulder motion. Although this is accomplished by daily range-of-motion exercises, it is clearly facilitated by suppression of periarticular inflammation and discomfort through the use of nonsteroidal anti-inflammatory drugs. Of these, sustained-release indomethacin provides the anti-inflammatory efficacy of indomethacin and by virtue of its sustained-release formulation, may promote patient compliance since it need be given only once or twice daily.

Anti-inflammatory drugs suppress proliferation and induce apoptosis through altering expressions of cell cycle regulators and pro-apoptotic factors in cultured human osteoblasts

International Nuclear Information System (INIS)

Chang, J.-K.; Li, C.-J.; Liao, H.-J.; Wang, C.-K.; Wang, G.-J.; Ho, M.-L.

2009-01-01

It has been reported that anti-inflammatory drugs (AIDs) inhibited bone repair in animal studies, and suppressed proliferation and induced cell death in rat osteoblast cultures. In this study, we further investigated the molecular mechanisms of AID effects on proliferation and cell death in human osteoblasts (hOBs). We examined the effects of dexamethasone (10 -7 and 10 -6 M), non-selective non-steroidal anti-inflammatory drugs (NSAIDs): indomethacin, ketorolac, piroxicam and diclofenac (10 -5 and 10 -4 M), and COX-2 inhibitor: celecoxib (10 -6 and 10 -5 M) on proliferation, cytotoxicity, cell death, and mRNA and protein levels of cell cycle and apoptosis-related regulators in hOBs. All the tested AIDs significantly inhibited proliferation and arrested cell cycle at G0/G1 phase in hOBs. Celecoxib and dexamethasone, but not non-selective NSAIDs, were found to have cytotoxic effects on hOB, and further demonstrated to induce apoptosis and necrosis (at higher concentration) in hOBs. We further found that indomethacin, celecoxib and dexamethasone increased the mRNA and protein expressions of p27 kip1 and decreased those of cyclin D2 and p-cdk2 in hOBs. Bak expression was increased by celecoxib and dexamethasone, while Bcl-XL level was declined only by dexamethasone. Furthermore, the replenishment of PGE1, PGE2 or PGF2α did not reverse the effects of AIDs on proliferation and expressions of p27 kip1 and cyclin D2 in hOBs. We conclude that the changes in expressions of regulators of cell cycle (p27 kip1 and cyclin D2) and/or apoptosis (Bak and Bcl-XL) by AIDs may contribute to AIDs caused proliferation suppression and apoptosis in hOBs. This effect might not relate to the blockage of prostaglandin synthesis by AIDs

Gastrointestinal Complications Depending on the Selectivity of Non-Steroidal Anti-Inflammatory Drug

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G.V. Dzyak

2013-02-01

Full Text Available The article deals with the problem of gastrointestinal complications during administration of nonsteroidal anti-inflammatory drugs, commonly used to treat a range of conditions, particularly rheumatic diseases. The results of own researches, which served to define the characteristics of changes in the state of gastric secretory function in patients receiving non-selective and selective anti-inflammatory agent and their comparative analysis, are provided. The data obtained demonstrated a certain contribution to the understanding of the mechanism of development of complications from the gastrointestinal tract when taken drugs of above group.

Manganese dioxide-graphene nanocomposite film modified electrode as a sensitive voltammetric sensor of indomethacin detection

Energy Technology Data Exchange (ETDEWEB)

Liu, Yuxia; Zhang, Zhenfa; Zhang, Cuizong; Huang, Wei; Liang, Caiyun; Peng, Jinyun [Guangxi Normal University for Nationalities, Chongzuo (China)

2016-08-15

Excess amount of analgesic and anti-inflammatory drug, such as indomethacin, often leads to serious gastrointestinal complications; therefore, amount of such active compound should be regulated in commercial drugs. This study proposes an efficient analytical technique to detect indomethacin selectively. We prepared and investigated electrochemical properties of a manganese dioxide-graphene nanocomposite film modified glassy carbon electrode (MnO{sub 2}-Gr/GCE). The behavior of the modified electrode as electrocatalyst towards indomethacin oxidation was also examined. The cyclic voltammetric results reveal that the electrocatalytic activity for the oxidation of indomethacin can significantly be enhanced on the MnO{sub 2}-Gr/GCE. Indomethacin exhibited a sensitive anodic peak at about 0.90 V at MnO{sub 2}-Gr/GCE. The data obtained from differential pulse voltammetry showed that the anodic peak currents were linearly dependent on the indomethacin concentrations in the range of 1.0 X 10{sup -7} to 2.5 X 10{sup -5} mol/L with a detection limit of 3.2 X 10{sup -8} mol/L (S/N = 3). Most importantly, the proposed method shows efficient and selective sensing of indomethacin in commercial harmaceutical formulations. This is the first report of a voltammetric sensor for indomethacin using MnO{sub 2}-Gr/GCE. We believe that this new method can be commercialized for routine applications in laboratories.

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

BACKGROUND: Psoriasis is a common disease and is associated with cardiovascular diseases. Systemic anti-inflammatory drugs may reduce risk of cardiovascular events. We therefore examined the rate of cardiovascular events, i.e. cardiovascular death, myocardial infarction and stroke, in patients...... with severe psoriasis treated with systemic anti-inflammatory drugs. METHODS: Individual-level linkage of administrative registries was used to perform a longitudinal nationwide cohort study. Time-dependent multivariable adjusted Cox regression was used to estimate hazard ratios (HRs) with 95% confidence...... 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...

Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain.

Science.gov (United States)

Inage, Kazuhide; Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

2016-08-01

Retrospective study. To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (ppain to chronic low back pain.

Unusual anti-leukemia activity of nanoformulated naproxen and other non-steroidal anti-inflammatory drugs

Energy Technology Data Exchange (ETDEWEB)

Kumar, Raj [School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005 (India); Advanced Material Research Centre, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005 (India); Siril, Prem Felix, E-mail: prem@iitmandi.ac.in [School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005 (India); Advanced Material Research Centre, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005 (India); Javid, Farideh [School of Applied Science, University of Huddersfield, Queensgate, Huddersfield HD1 3DH (United Kingdom)

2016-12-01

The non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used pharmaceuticals worldwide. Interestingly, many of them have significant anticancer properties too. However, the poor water solubility of certain NSAIDs limits their application for cancer treatment. Nanosizing of such drugs can help to improve the solubility and this may result in enhanced anticancer activities too. Moreover, over dosages and the accompanying side effects of NSAIDs can be minimized by improving their solubility and bioavailability. Successful nanoformulation of three NSAIDs: ibuprofen (IBP), ketoprufen (KP) and naproxen (NAP) using a novel evaporation assisted solvent-antisolvent interaction (EASAI) method is reported here. Three water soluble and biocompatible polymers: polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and hydroxypropyl methylcellulose (HPMC) were used to stabilize the drug nanoparticles. Particles having spherical morphology with average size below 30 nm were thoroughly characterized using dynamic light scattering and field emission scanning electron microscopy (FESEM) imaging. The nanoformulation resulted in ten to fifteen fold improvements in the solubility and significant enhancement in the in-vitro drug release profiles of the NSAIDs. Anticancer screening of the nanoformulated NSAIDs against five different cancer cell lines such as MCF-7 (Human breast cancer cell line), (Human pancreatic cancer cell line) MIA-PA-CA-2, (Human colon cancer cell line) HT-29, (Human leukemia cell line) Jurkat and (human ovarian carcinoma cell line) A2780 was performed. All the nanoformulated samples showed improved anticancer activity against the Leukemia cancer cell line, out of which NAP-PVP showed the highest anti-cancer activity. The anti-Leukemia activity of NAP-PVP was more than twice that of doxorubicin which is a standard anticancer drug. - Highlights: • Nanoparticles of three non-steroidal anti-inflammatory drugs were prepared. • Particle sizes were

Unusual anti-leukemia activity of nanoformulated naproxen and other non-steroidal anti-inflammatory drugs

International Nuclear Information System (INIS)

Kumar, Raj; Siril, Prem Felix; Javid, Farideh

2016-01-01

The non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used pharmaceuticals worldwide. Interestingly, many of them have significant anticancer properties too. However, the poor water solubility of certain NSAIDs limits their application for cancer treatment. Nanosizing of such drugs can help to improve the solubility and this may result in enhanced anticancer activities too. Moreover, over dosages and the accompanying side effects of NSAIDs can be minimized by improving their solubility and bioavailability. Successful nanoformulation of three NSAIDs: ibuprofen (IBP), ketoprufen (KP) and naproxen (NAP) using a novel evaporation assisted solvent-antisolvent interaction (EASAI) method is reported here. Three water soluble and biocompatible polymers: polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and hydroxypropyl methylcellulose (HPMC) were used to stabilize the drug nanoparticles. Particles having spherical morphology with average size below 30 nm were thoroughly characterized using dynamic light scattering and field emission scanning electron microscopy (FESEM) imaging. The nanoformulation resulted in ten to fifteen fold improvements in the solubility and significant enhancement in the in-vitro drug release profiles of the NSAIDs. Anticancer screening of the nanoformulated NSAIDs against five different cancer cell lines such as MCF-7 (Human breast cancer cell line), (Human pancreatic cancer cell line) MIA-PA-CA-2, (Human colon cancer cell line) HT-29, (Human leukemia cell line) Jurkat and (human ovarian carcinoma cell line) A2780 was performed. All the nanoformulated samples showed improved anticancer activity against the Leukemia cancer cell line, out of which NAP-PVP showed the highest anti-cancer activity. The anti-Leukemia activity of NAP-PVP was more than twice that of doxorubicin which is a standard anticancer drug. - Highlights: • Nanoparticles of three non-steroidal anti-inflammatory drugs were prepared. • Particle sizes were

Use of non-steroidal anti-inflammatory drugs and nutritional ...

African Journals Online (AJOL)

Background. The use of medications by football players in many populations is known to be high. Data on African players are scarce. Objective. To determine the magnitude of use of non-steroidal anti-inflammatory drugs (NSAIDs) and nutritional supplements by Zimbabwean football players. Methods. We conducted a ...

Anti-inflammatory activity of Lippia dulcis.

Science.gov (United States)

Pérez, S; Meckes, M; Pérez, C; Susunaga, A; Zavala, M A

2005-10-31

Lippia dulcis hexane and ethanol extracts were tested for its anti-inflammatory activity in several animal models. Hexane extract showed to be inactive, but the ethanol extract at doses of 400 mg/kg produced significant inhibition of carrageenan-induced paw oedema and reduced the weight of cotton pellet-induced granuloma, moreover, the topical application of 0.5 mg/ear of this extract inhibited the edema induced with TPA by 49.13%, an effect which is of less intensity than that produced by indomethacine at the same dose.

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

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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.

Differential effects of sulindac and indomethacin on blood pressure in treated essential hypertensive subjects.

Science.gov (United States)

Puddey, I B; Beilin, L J; Vandongen, R; Banks, R; Rouse, I

1985-09-01

Attenuation of the effectiveness of antihypertensive therapy by non-steroidal anti-inflammatory (NSAI) drugs has been attributed to inhibition of systemic or renal vasodilator prostaglandin synthesis, or a combination of both. Indomethacin is a NSAI drug with both renal and extrarenal cyclo-oxygenase inhibition properties. Sulindac is a relatively selective cyclo-oxygenase inhibitor said not to affect urinary prostaglandin excretion. This study examines the relative effect on blood pressure of 4 weeks' treatment, with indomethacin 25 mg three times daily and sulindac 200 mg twice daily, in a randomized placebo controlled trial in 26 hypertensive subjects. In nine patients treated with indomethacin, supine blood pressure rose 11 mmHg systolic and 4 mmHg diastolic by the end of the first week, whereas nine subjects treated with sulindac showed a fall in blood pressure similar to the trend seen in placebo-treated subjects. Indomethacin treatment inhibited renal cyclo-oxygenase with a 78% reduction in urinary prostaglandin E2 excretion and 89% suppression of plasma renin activity. Neither measurement was affected by sulindac. Extrarenal cyclo-oxygenase activity was inhibited by both indomethacin and sulindac with serum thromboxane B2 decreasing by 96% and 69% respectively. The results suggest that the pressor effect of NSAI drugs is predominantly related to renal cyclo-oxygenase inhibition. the lack of effect of sulindac on blood pressure may make it a safer therapeutic option if NSAI drug therapy is necessary in the hypertensive patient.

Assessment Of Pattern Of Non-steroidal Anti-Inflammatory Drugs ...

African Journals Online (AJOL)

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in the treatment of pains. Self-medication is a common practice all over the world. Unwanted effects from use of this class of medication could pose health challenges. This study evaluated the prevalence and pattern of inappropriate use of NSAIDs among ...

[STUDYING GASTRIC ULCERATION EFFECT OF A NEW DRUG INTENDED FOR TREATMENT OF CHRONIC INFLAMMATORY DISEASES OF KIDNEYS AND URINARY TRACT.

Science.gov (United States)

Murashko, T O; Smirnov, I V; Ivanov, A A; Postnikov, P S; Nemtsev, A O; Bondarev, A A; Udut, V V; Prisukhin, A N; Kornaukhov, A N; Sergeev, T S

2016-08-01

Gastric ulceration properties (gastrointestinal toxicity) of the sodium salt of 4-(0-β-D-glucopyranosyloxy) benzoic acid, a new nonsteroidal anti-inflammatory drug (NSAID) intended for the treatment of chronic inflammatory diseases of the kidney and urinary tract, have been tested on laboratory animals. Acute NSAID-induced gastropathy was induced in rats by oral administration of indomethacin, nimesulide, diclofenac, acetylsalicylic acid and the new drug. Test animals were killed by instantaneous decapitation 4 h after treatment and their gastrointestinal tracts were studied by pathomorphological methods on micropreparations and histological sections of gastric mucosa. It was established that the new drug, in contrast to reference NSAIDS, did not exhibit gastropathic action on the gastric mucosa.

Indomethacin promotes apoptosis in gastric cancer cells through concomitant degradation of Survivin and Aurora B kinase proteins.

Science.gov (United States)

Chiou, Shiun-Kwei; Hoa, Neil; Hodges, Amy; Ge, Lishen; Jadus, Martin R

2014-09-01

Regular usage of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with reduced incidence of a variety of cancers. The molecular mechanisms underlying these chemopreventive effects remain poorly understood. This current investigation showed that in gastric cancer cells: (1) Indomethacin treatment enhanced the degradation of chromosomal passenger proteins, Survivin and Aurora B kinase; (2) Indomethacin treatment down-regulated Aurora B kinase activity in a cell cycle-independent fashion; (3) siRNA knockdown of Survivin level promoted Aurora B kinase protein degradation, and vice versa; (4) ectopic overexpression of Survivin blocked reduction of Aurora B kinase level and activity by indomethacin treatment, and vice versa; (5) siRNA knockdown of Aurora B kinase level and AZD1152 inhibition of its activity induced apoptosis, and overexpression of Aurora B kinase inhibited indomethacin-induced apoptosis; (6) indomethacin treatment reduced Aurora B kinase level, coinciding with reduction of Survivin level and induction of apoptosis, in KATO III and HT-29 cells, and in mouse gastric mucosa. A role for Aurora B kinase function in NSAID-induced apoptosis was not previously explored. Thus this report provides better understanding of the molecular mechanisms underlying the anti-cancer effect of NSAIDs by elucidating a significant role for Aurora B kinase in indomethacin-induced apoptosis.

Effectiveness of various non-steroidal anti-inflammatory drugs in ...

African Journals Online (AJOL)

Purpose: To study the effectiveness of various nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with vertebral fractures. Methods: A total of 78 patients (17 males and 61 females) with a mean age of 69.5 years were included. The major inclusion criterion was an osteoporotic vertebral fracture between T7 and L3.

In vitro and in vivo anti-inflammatory active copper(II-lawsone complexes.

Directory of Open Access Journals (Sweden)

Ján Vančo

Full Text Available We report in vitro and in vivo anti-inflammatory activities of a series of copper(II-lawsone complexes of the general composition [Cu(Law2(LNx(H2O(2-x]·yH2O; where HLaw = 2-hydroxy-1,4-naphthoquinone, x = 1 when LN = pyridine (1 and 2-aminopyridine (3 and x = 2 when LN = imidazole (2, 3-aminopyridine (4, 4-aminopyridine (5, 3-hydroxypyridine (6, and 3,5-dimethylpyrazole (7. The compounds were thoroughly characterized by physical techniques, including single crystal X-ray analysis of complex 2. Some of the complexes showed the ability to suppress significantly the activation of nuclear factor κB (NF-κB both by lipopolysaccharide (LPS and TNF-alpha (complexes 3-7 at 100 nM level in the similar manner as the reference drug prednisone (at 1 μM level. On the other hand, all the complexes 1-7 decreased significantly the levels of the secreted TNF-alpha after the LPS activation of THP-1 cells, thus showing the anti-inflammatory potential via both NF-κB moderation and by other mechanisms, such as influence on TNF-alpha transcription and/or translation and/or secretion. In addition, a strong intracellular pro-oxidative effect of all the complexes has been found at 100 nM dose in vitro. The ability to suppress the inflammatory response, caused by the subcutaneous application of λ-carrageenan, has been determined by in vivo testing in hind-paw edema model on rats. The most active complexes 1-3 (applied in a dose corresponding to 40 μmol Cu/kg, diminished the formation of edema simalarly as the reference drug indomethacine (applied in 10 mg/kg dose. The overall effect of the complexes, dominantly 1-3, shows similarity to anti-inflammatory drug benoxaprofen, known to induce intracellular pro-oxidative effects.

In vitro efficacy and release study with anti-inflammatory drugs incorporated in adhesive transdermal drug delivery systems.

Science.gov (United States)

Meyer, Stefanie; Peters, Nils; Mann, Tobias; Wolber, Rainer; Pörtner, Ralf; Nierle, Jens

2014-04-01

The topical application of two different anti-inflammatory extracts incorporated in adhesive transdermal drug delivery systems (TDDSs) was investigated. Therefore, anti-inflammatory properties and percutaneous absorption behavior of adhesive TDDSs were characterized in vitro conducting experiments with a dermatologically relevant human skin model. Anti-inflammatory efficacy against UV irradiation of both TDDSs was determined in vitro with EpiDerm™. The reduction of the release of proinflammatory cytokines by topically applied TDDSs was compared with the reduction during the presence of the specific cyclooxygenase inhibitor diclofenac in the culture medium. A similar anti-inflammatory efficacy of the topically applied TDDSs in comparison with the use of diclofenac in the culture medium should be achieved. Furthermore, percutaneous absorption in efficacy tests was compared with percutaneous absorption in diffusion studies with porcine cadaver skin. Both the topically applied TDDSs showed a significant anti-inflammatory activity. Permeation coefficients through the stratum corneum and the epidermis gained from the release studies on porcine cadaver skin (Magnolia: 2.23·10(-5) cm/h, licorice: 4.68·10(-6) cm/h) were approximately five times lower than the permeation coefficients obtained with the EpiDerm™ skin model (Magnolia: 9.48·10(-5) cm/h, licorice: 24.0·10(-6) cm/h). Therefore, an adjustment of drug doses during experiments with the EpiDerm™ skin model because of weaker skin barrier properties should be considered.

Investigation on the anti- inflammatory and analgesic effects of Olea europaea L. metanolic extract on male NMRI mouse

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Elaheh Tekye

2012-04-01

Full Text Available Background: Different mediators are involved in pain and edema induction during different stages of inflammation. Then, treatment of them encounters some difficulties. Medicinal plants are an important source of substances which are claimed to induce anti-inflammatory effects. This study was aimed to investigate anti-inflammatory and analgesic effects of Olea europaea L.methanolic extract on male NMRI mouse. Methods: Methanolic extraction was done for leaf of Olea europaea L. and different doses (200, 300 and 400 mg/kg were intraperitoneally (i.p. adminstered to male NMRI mice. Analgesic and anti-inflammatory effects of extract was measured during both phases of Formalin test, Acetic acid induced visceral pain and xylene inflammation tests. A standard analgesic and anti-inflammatory drug such as indomethacin, dexamethasone and morphine were administered in positive control groups where appropriates. Results: Results indicated significant dose-dependent analgesic and anti-inflammatory effects of methanolic extract of Olea europaea L. leaf on pain which induced by formalin (both phase and acetic acid, and inflammation caused by xylene. Conclusion: Our findings Showed that administration of methanolic extract of Olea europaea L.leaf can suppress pain and inflammation dose dependently which, may mediate via different components of extract. However, more investigations need to be done.

Central and peripheral haemodynamic effects of non-steroidal anti-inflammatory drugs in man.

Science.gov (United States)

Wennmalm, A; Carlsson, I; Edlund, A; Eriksson, S; Kaijser, L; Nowak, J

1984-01-01

The haemodynamic effects of non-steroidal anti-inflammatory (NSAI) drugs can be attributed either to their common property of inhibiting the formation of prostaglandins (PG) in the cardiovascular system, or to direct actions on the tone and sensitivity of the resistance vessels in various regions. Indomethacin (IND) is the most frequently studied NSAI drug, in animals and in man. Its cardiovascular effects differ somewhat from those of other NSAI, due to the fact that, besides inhibiting PG formation, IND acts as a direct vasoconstrictor. The stimulatory effect of IND in vascular smooth muscle results in an increased systemic vascular resistance which, although partially compensated by a decreased cardiac output, gives rise to a moderate increase in systemic blood pressure. The vasoconstrictor effect of IND is of particular interest in patients with ischemic heart disease, since it lowers their already decreased coronary flow, and may thereby accentuate the risk of myocardial infarction. Administration of IND also leads to a decreased blood flow in the splanchnic region, the kidneys, and the brain. The cerebral blood flow is lowered by 25-35%; in addition, IND almost entirely erases the hyperemic flow response to hypercapnia. Of other NSAI drugs, at least aspirin and naproxen are completely devoid of such actions on the cerebral circulation. A common vascular effect of all NSAI drugs is a diminution of reactive hyperemia, the local hyperemia that develops in a tissue subjected to a short period of arterial occlusion. Part of this hyperemic response is dependent on an intact vascular PG formation and consequently it is inhibited when PG formation is blocked. In contrast, NSAI drugs do not affect the functional increase in the blood flow in working skeletal muscle.

A gastroenterologist and arheumatologist answer the questions on the use ofnon-steroidal anti-inflammatory drugs raised by primary care physicians

Directory of Open Access Journals (Sweden)

Przemysław Dyrla

2016-03-01

Full Text Available Non-steroidal anti-inflammatory drugs are drugs of choice for chronic pain, which is most common in chronic conditions, rheumatism in particular. According to  current recommendations, these medications should be used continuously or intermittently, and their choice should be tailored to each patient. Unfortunately, non-steroidal anti-inflammatory drugs have multiple adverse effects ranging from the most insignificant dyspepsia to severe upper gastrointestinal bleeding. Therefore, gastroscopy and, in the case of confirmed Helicobacter pylori infection, eradication is advisable for planned long-term treatment with these agents. Long-term use of proton pump inhibitors is recommended in rheumatic patients chronically receiving non-selective non-steroidal anti-inflammatory drugs, while celecoxib (a selective COX-2 inhibitor combined with proton pump inhibitor should be administered in patients at high risk of gastrointestinal complications. In rheumatic patients, the type of non-steroidal anti-inflammatory drug and the route of its administration should be tailored to each patient in terms of strength and duration of drug action, the type of disease and comorbidities as well as contraindications. Adverse gastrointestinal effects are due to the mechanism of action of non-steroidal anti-inflammatory drugs, and therefore independent of the route of administration. The use of proton pump inhibitors with cardioprotective doses of aspirin should be limited to patients with risk factors for gastrointestinal complications. High non-steroidal anti-inflammatory drug doses are limited to gout attack, acute pain and axial spondyloarthropathy showing high clinical activity. In other cases, the lowest effective non-steroidal anti-inflammatory drug dose is recommended. Advancing age is characterised by impairment in the function of all organs, therefore elderly patients should receive lower non-steroidal anti-inflammatory drug

Inhibition of amyloidogenesis by non-steroidal anti-inflammatory drugs and their hybrid nitrates

Science.gov (United States)

Schiefer, Isaac T.; Abdul-Hay, Samer; Wang, Huali; Vanni, Michael; Qin, Zhihui; Thatcher, Gregory R. J.

2011-01-01

Poor blood-brain barrier penetration of non-steroidal anti-inflammatory drugs (NSAIDs) has been blamed for the failure of the selective amyloid lowering agent (SALA) R-flurbiprofen in phase 3 clinical trials for Alzheimer’s disease (AD). NO-donor NSAIDs (NO-NSAIDs) provide an alternative, gastric-sparing approach to NSAID SALAs, which may improve bioavailability. NSAID analogs were studied for anti-inflammatory activity and for SALA activity in N2a neuronal cells transfected with human amyloid precursor protein (APP). Flurbiprofen (1) analogs were obtained with enhanced anti-inflammatory and anti-amyloidogenic properties compared to 1, however, esterification led to elevated Aβ1–42 levels. Hybrid nitrate prodrugs possessed superior anti-inflammatory activity and reduced toxicity relative to the parent NSAIDs, including clinical candidate, CHF5074. Although hybrid nitrates elevated Aβ1–42 at higher concentration, SALA activity was observed at low concentrations (≤ 1 µM): both Aβ1–42 and the ratio of Aβ1–42/Aβ1–40 were lowered. This biphasic SALA activity was attributed to the intact nitrate drug. For several compounds the selective modulation of amyloidogenesis was tested using an immunoprecipitation MALDI-TOF approach. These data support the development of NO-NSAIDs as an alternative approach towards a clinically useful SALA. PMID:21405086

Protective Effect of Wheat Peptides against Indomethacin-Induced Oxidative Stress in IEC-6 Cells

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Hong Yin

2014-01-01

Full Text Available Recent studies have demonstrated that wheat peptides protected rats against non-steroidal anti-inflammatory drugs-induced small intestinal epithelial cells damage, but the mechanism of action is unclear. In the present study, an indomethacin-induced oxidative stress model was used to investigate the effect of wheat peptides on the nuclear factor-κB(NF-κB-inducible nitric oxide synthase-nitric oxide signal pathway in intestinal epithelial cells-6 cells. IEC-6 cells were treated with wheat peptides (0, 125, 500 and 2000 mg/L for 24 h, followed by 90 mg/L indomethacin for 12 h. Wheat peptides significantly attenuated the indomethacin-induced decrease in superoxide dismutase and glutathione peroxidase activity. Wheat peptides at 2000 mg/L markedly decreased the expression of the NF-κB in response to indomethacin-induced oxidative stress. This study demonstrated that the addition of wheat peptides to a culture medium significantly inhibited the indomethacin-induced release of malondialdehyde and nitrogen monoxide, and increased antioxidant enzyme activity in IEC-6 cells, thereby providing a possible explanation for the protective effect proposed for wheat peptides in the prevention of indomethacin-induced oxidative stress in small intestinal epithelial cells.

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

Science.gov (United States)

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

2016-11-23

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

Negative effect of non-steroidal anti-inflammatory drugs on the ...

African Journals Online (AJOL)

Ciprofloxacin, a second generation fluoroquinolone is often co-administered with non-steroidal anti-inflammatory drugs (NSAIDs) in life threatening situations in which Staphylococcus aureus infections are accompanied with pain and inflammation. This study was carried out to investigate possible in vitro interactions in co ...

Solid lipid nanoparticles as anti-inflammatory drug delivery system in a human inflammatory bowel disease whole-blood model.

Science.gov (United States)

Serpe, Loredana; Canaparo, Roberto; Daperno, Marco; Sostegni, Raffaello; Martinasso, Germana; Muntoni, Elisabetta; Ippolito, Laura; Vivenza, Nicoletta; Pera, Angelo; Eandi, Mario; Gasco, Maria Rosa; Zara, Gian Paolo

2010-03-18

Standard treatment for inflammatory bowel diseases (IBD) necessitates frequent intake of anti-inflammatory and/or immunosuppressive drugs, leading to significant adverse events. To evaluate the role solid lipid nanoparticles (SLN) play as drug delivery system in enhancing anti-inflammatory activity for drugs such as dexamethasone and butyrate in a human inflammatory bowel diseases whole-blood model. ELISA assay and the peripheral blood mononuclear cell (PBMC) cytokine mRNA expression levels were evaluated by quantitative SYBR Green real-time RT-PCR to determine the IL-1beta, TNF-alpha, IFN-gamma and IL-10 secretion in inflammatory bowel diseases patients' PBMC culture supernatants. There was a significant decrease in IL-1beta (p<0.01) and TNF-alpha (p<0.001) secretion, whilst IL-10 (p<0.05) secretion significantly increased after cholesteryl butyrate administration, compared to that of butyrate alone at the highest concentration tested (100 microM), at 24h exposure. There was a significant decrease in IL-1beta (p<0.01), TNF-alpha (p<0.001) and IL-10 (p<0.001) secretion after dexamethasone loaded SLN administration, compared to dexamethasone alone at the highest concentration tested (250 nM) at 24h exposure. No IFN-gamma was detected under any conditions and no cytotoxic effects observed even at the highest concentration tested. The incorporation of butyrate and dexamethasone into SLN has a significant positive anti-inflammatory effect in the human inflammatory bowel disease whole-blood model. Copyright 2010 Elsevier B.V. All rights reserved.

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

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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.

The influence of anti-inflammatory medication on exercise-induced myogenic precursor cell responses in humans

DEFF Research Database (Denmark)

Mackey, Abigail L; Kjaer, Michael; Dandanell, Sune

2007-01-01

The consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) is widespread among athletes when faced with muscle soreness or injury, but the effects of NSAIDs on satellite cell activity in humans are unknown. To investigate this, 14 healthy male endurance athletes (mean peak oxygen consumption...... 62 ml x kg(-1) x min(-1)) volunteered for the study, which involved running 36 km. They were divided into two groups and received either 100 mg indomethacin per day or placebo. Muscle biopsies collected before the run and on days 1, 3, and 8 afterward were analyzed for satellite cells...

Non-steroidal anti-inflammatory drugs and risk of pulmonary embolism

NARCIS (Netherlands)

Biere-Rafi, Sara; Di Nisio, Marcello; Gerdes, Victor; Porreca, Ettore; Souverein, Patrick; de Boer, Anthonius; Büller, Harry; Kamphuisen, Pieter

2011-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with an increased risk of arterial thrombosis, but their effect on venous thrombotic events is less well established. The study aimed to assess the risk of symptomatic pulmonary embolism (PE) in patients using NSAIDs and to evaluate

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

NARCIS (Netherlands)

W.T.M. Enthoven (Wendy); P.D.D.M. Roelofs (Pepijn); 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

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

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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

Evaluation of synthetic zeolites as oral delivery vehicle for anti-inflammatory drugs

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Elham Khodaverdi

2014-05-01

Full Text Available Objective(s: In this research, zeolite X and zeolite Y were used as vehicle to prepare intestine targeted oral delivery systems of indomethacin and ibuprofen. Materials and Methods: A soaking procedure was implemented to encapsulate indomethacin or ibuprofen within synthetic zeolites. Gravimetric methods and IR spectra of prepared formulations were used to assess drug loading efficiencies into zeolite structures. Scanning Electron Microscopy (SEM was also utilized to determine morphologies changes in synthetic zeolites after drug loading. At the next stage, dissolution studies were used to predict the in vivo performance of prepared formulations at HCl 0.1 N and PBS pH 6.5 as simulated gastric fluid (SGF and simulated intestine fluid (SIF, respectively. Results: Drug loadings of prepared formulations was determined between 24-26 % w/w. Dissolution tests at SGF were shown that zeolites could retain acidic model drugs in their porous structures and can be able to limit their release into the stomach. On the other hand, all prepared formulations completely released model drugs during 3 hr in simulated intestine fluid. Conclusion: Obtained results indicated zeolites could potentially be able to release indomethacin and ibuprofen in a sustained and controlled manner and reduced adverse effects commonly accompanying oral administrations of NSAIDs.

Development and characterisation of cellulose based electrospun mats for buccal delivery of non-steroidal anti-inflammatory drug (NSAID).

Science.gov (United States)

Nazari, Kazem; Kontogiannidou, Eleni; Ahmad, Rita Haj; Gratsani, Aggeliki; Rasekh, Manoochehr; Arshad, Muhammad Sohail; Sunar, Burde Suheyla; Armitage, David; Bouropoulos, Nikolaos; Chang, Ming-Wei; Li, Xiang; Fatouros, Dimitrios G; Ahmad, Zeeshan

2017-05-01

In this study conventional electrospinning (ESp) was used to prepare a series of buccal films containing indomethacin (INDO, a nonsteroidal anti-inflammatory drug), Ethocel (10), hydroxypropylmethylcellulose (HPMC) and Tween ® 80 at various concentrations. The films were characterized using scanning electron microscopy (SEM) and atomic force microscopy (AFM), fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Drug release behaviour was assessed in vitro (buffer pH6.8). SEM revealed film morphology and mean fibre diameter was dependent on the process formulation. INDO was encapsulated in the amorphous state once electrospun as evidenced from DSC and XRD studies. The presence of other excipients within fibrous matrices was confirmed using FTIR and Raman spectroscopy. Loading and release of INDO from filamentous structures was influenced by formulation composition; indicating potential to 'fine-tune' dosage forms. Given that ESp is a one-step preparation method and operational at ambient conditions; an attractive route for engineering tailored film type dosage forms is presented. This is a valuable approach for optimizing dosage forms as needed in a single step for various age groups. Copyright © 2017 Elsevier B.V. All rights reserved.

Consumption and awareness of students about nonsteroidal anti-inflammatory drugs

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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.

Ankle sprain: the effects of non-steroidal anti-inflammatory drugs

NARCIS (Netherlands)

Struijs, Peter A. A.; Kerkhoffs, Gino M. M. J.

2015-01-01

Injury of the lateral ligament complex of the ankle joint occurs in about one in 10,000 people per day, accounting for a quarter of all sports injuries. We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of non-steroidal anti-inflammatory drugs

Lansoprazole prevents experimental gastric injury induced by non-steroidal anti-inflammatory drugs through a reduction of mucosal oxidative damage

Science.gov (United States)

Blandizzi, Corrado; Fornai, Matteo; Colucci, Rocchina; Natale, Gianfranco; Lubrano, Valter; Vassalle, Cristina; Antonioli, Luca; Lazzeri, Gloria; Tacca, Mario Del

2005-01-01

AIM: This study investigated the mechanisms of protection afforded by the proton pump inhibitor lansoprazole against gastric injury induced by different non-steroidal anti-inflammatory drugs (NSAIDs) in rats. METHODS: Male Sprague-Dawley rats were orally treated with indomethacin (100 µmol/kg), diclofenac (60 µmol/kg), piroxicam (150 µmol/kg) or ketoprofen (150 µmol/kg). Thirty minutes before NSAIDs, animals were orally treated with lansoprazole 18 or 90 µmol/kg. Four hours after the end of treatments, the following parameters were assessed: gastric mucosal PGE2, malondialdehyde (MDA), myeloperoxidase (MPO) or non-proteic sulfhydryl compounds (GSH) levels; reverse transcription-polymerase chain reaction (RT-PCR) of mucosal COX-2 mRNA; gastric acid secretion in pylorus-ligated animals; in vitro effects of lansoprazole (1-300 µmol/L) on the oxidation of low density lipoproteins (LDLs) induced by copper sulphate. RESULTS: All NSAIDs elicited mucosal necrotic lesions which were associated with neutrophil infiltration and reduction of PGE2 levels. Increments of MPO and MDA contents, as well as a decrease in GSH levels were detected in the gastric mucosa of indomethacin- or piroxicam-treated animals. Indomethacin enhanced mucosal cyclooxygenase-2 expression, while not affecting cyclooxygenase-1. At the oral dose of 18 µmol/kg lansoprazole partly counteracted diclofenac-induced mucosal damage, whereas at 90 µmol/kg it markedly prevented injuries evoked by all test NSAIDs. Lansoprazole at 90 µmol/kg reversed also the effects of NSAIDs on MPO, MDA and GSH mucosal contents, without interfering with the decrease in PGE2 levels or indomethacin-induced cyclooxygenase-2 expression. However, both lansoprazole doses markedly inhibited acid secretion in pylorus-ligated rats. Lansoprazole concentration-dependently reduced the oxidation of LDLs in vitro. CONCLUSION: These results suggest that, besides the inhibition of acid secretion, lansoprazole protection against NSAID

Postoperative use of non-steroidal anti-inflammatory drugs in patients with anastomotic leakage requiring reoperation after colorectal resection

DEFF Research Database (Denmark)

Klein, Mads; Gögenur, Ismail; Rosenberg, Jacob

2012-01-01

To evaluate the effect of postoperative use of non-steroidal anti-inflammatory drugs (NSAIDs) on anastomotic leakage requiring reoperation after colorectal resection.......To evaluate the effect of postoperative use of non-steroidal anti-inflammatory drugs (NSAIDs) on anastomotic leakage requiring reoperation after colorectal resection....

Lansoprazole protects and heals gastric mucosa from non-steroidal anti-inflammatory drug (NSAID)-induced gastropathy by inhibiting mitochondrial as well as Fas-mediated death pathways with concurrent induction of mucosal cell renewal.

Science.gov (United States)

Maity, Pallab; Bindu, Samik; Choubey, Vinay; Alam, Athar; Mitra, Kalyan; Goyal, Manish; Dey, Sumanta; Guha, Mithu; Pal, Chinmay; Bandyopadhyay, Uday

2008-05-23

We have investigated the mechanism of antiapoptotic and cell renewal effects of lansoprazole, a proton pump inhibitor, to protect and heal gastric mucosal injury in vivo induced by indomethacin, a non-steroidal anti-inflammatory drug (NSAID). Lansoprazole prevents indomethacin-induced gastric damage by blocking activation of mitochondrial and Fas pathways of apoptosis. Lansoprazole prevents indomethacin-induced up-regulation of proapoptotic Bax and Bak and down-regulation of antiapoptotic Bcl-2 and Bcl(xL) to maintain the normal proapoptotic/antiapoptotic ratio and thereby arrests indomethacin-induced mitochondrial translocation of Bax and collapse of mitochondrial membrane potential followed by cytochrome c release and caspase-9 activation. Lansoprazole also inhibits indomethacin-induced Fas-mediated mucosal cell death by down-regulating Fas or FasL expression and inhibiting caspase-8 activation. Lansoprazole favors mucosal cell renewal simultaneously by stimulating gene expression of prosurvival proliferating cell nuclear antigen, survivin, epidermal growth factor, and basic fibroblast growth factor. The up-regulation of Flt-1 further indicates that lansoprazole activates vascular epidermal growth factor-mediated controlled angiogenesis to repair gastric mucosa. Lansoprazole also stimulates the healing of already formed ulcers induced by indomethacin. Time course study of healing indicates that it switches off the mitochondrial death pathway completely but not the Fas pathway. However, lansoprazole heals mucosal lesions almost completely after overcoming the persisting Fas pathway, probably by favoring the prosurvival genes expression. This study thus provides the detailed mechanism of antiapoptotic and prosurvival effects of lansoprazole for offering gastroprotection against indomethacin-induced gastropathy.

Nuclear magnetic resonance-based metabolomics for prediction of gastric damage induced by indomethacin in rats

Energy Technology Data Exchange (ETDEWEB)

Um, So Young [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); Park, Jung Hyun [Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); Chung, Myeon Woo [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Kim, Kyu-Bong [College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam (Korea, Republic of); Kim, Seon Hwa [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam (Korea, Republic of); Choi, Ki Hwan, E-mail: hyokwa11@korea.kr [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Lee, Hwa Jeong, E-mail: hwalee@ewha.ac.kr [Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of)

2012-04-13

Highlights: Black-Right-Pointing-Pointer NMR based metabolomics - gastric damage by indomethacin. Black-Right-Pointing-Pointer Pattern recognition analysis was performed to biomarkers of gastric damage. Black-Right-Pointing-Pointer 2-Oxoglutarate, acetate, taurine and hippurate were selected as putative biomarkers. Black-Right-Pointing-Pointer The gastric damage induced by NSAIDs can be screened in the preclinical step of drug. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) have side effects including gastric erosions, ulceration and bleeding. In this study, pattern recognition analysis of the {sup 1}H-nuclear magnetic resonance (NMR) spectra of urine was performed to develop surrogate biomarkers related to the gastrointestinal (GI) damage induced by indomethacin in rats. Urine was collected for 5 h after oral administration of indomethacin (25 mg kg{sup -1}) or co-administration with cimetidine (100 mg kg{sup -1}), which protects against GI damage. The {sup 1}H-NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and 36 endogenous metabolites were assigned for targeted profiling. The level of gastric damage in each animal was also determined. Indomethacin caused severe gastric damage; however, indomethacin administered with cimetidine did not. Simultaneously, the patterns of changes in their endogenous metabolites were different. Multivariate data analyses were carried out to recognize the spectral pattern of endogenous metabolites related to indomethacin using partial least square-discrimination analysis. In targeted profiling, a few endogenous metabolites, 2-oxoglutarate, acetate, taurine and hippurate, were selected as putative biomarkers for the gastric damage induced by indomethacin. These metabolites changed depending on the degree of GI damage, although the same dose of indomethacin (10 mg kg{sup -1}) was administered to rats. The results of global and targeted profiling suggest that the gastric damage induced by

Nuclear magnetic resonance-based metabolomics for prediction of gastric damage induced by indomethacin in rats

International Nuclear Information System (INIS)

Um, So Young; Park, Jung Hyun; Chung, Myeon Woo; Kim, Kyu-Bong; Kim, Seon Hwa; Choi, Ki Hwan; Lee, Hwa Jeong

2012-01-01

Highlights: ► NMR based metabolomics – gastric damage by indomethacin. ► Pattern recognition analysis was performed to biomarkers of gastric damage. ► 2-Oxoglutarate, acetate, taurine and hippurate were selected as putative biomarkers. ► The gastric damage induced by NSAIDs can be screened in the preclinical step of drug. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) have side effects including gastric erosions, ulceration and bleeding. In this study, pattern recognition analysis of the 1 H-nuclear magnetic resonance (NMR) spectra of urine was performed to develop surrogate biomarkers related to the gastrointestinal (GI) damage induced by indomethacin in rats. Urine was collected for 5 h after oral administration of indomethacin (25 mg kg −1 ) or co-administration with cimetidine (100 mg kg −1 ), which protects against GI damage. The 1 H-NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and 36 endogenous metabolites were assigned for targeted profiling. The level of gastric damage in each animal was also determined. Indomethacin caused severe gastric damage; however, indomethacin administered with cimetidine did not. Simultaneously, the patterns of changes in their endogenous metabolites were different. Multivariate data analyses were carried out to recognize the spectral pattern of endogenous metabolites related to indomethacin using partial least square-discrimination analysis. In targeted profiling, a few endogenous metabolites, 2-oxoglutarate, acetate, taurine and hippurate, were selected as putative biomarkers for the gastric damage induced by indomethacin. These metabolites changed depending on the degree of GI damage, although the same dose of indomethacin (10 mg kg −1 ) was administered to rats. The results of global and targeted profiling suggest that the gastric damage induced by NSAIDs can be screened in the preclinical stage of drug development using a NMR based metabolomics approach.

Anti-inflammatory and antipyretic effects of Sonchus oleraceus in rats.

Science.gov (United States)

Vilela, Fabiana C; Bitencourt, Andressa D; Cabral, Layla D M; Franqui, Lidiane S; Soncini, Roseli; Giusti-Paiva, Alexandre

2010-02-17

Sonchus oleraceus L. has been used to relieve headaches, general pain, hepatitis, infections, inflammation and rheumatism in Brazilian folk medicine. Nevertheless, scientific information regarding this species is scarce; there are no reports related to its possible anti-inflammatory effects. This study was aimed at evaluating the scientific basis for the traditional use of Sonchus oleraceus using in vivo inflammatory models. Carrageenan-induced paw edema, peritonitis and febrile response induced by lipopolysaccharide tests, as well as fibrovascular tissue growth induced by s.c. cotton pellet implantation were used to investigate the anti-inflammatory activity of Sonchus oleraceus hydroethanolic extract (SoHE) in rats. The SoHE at test doses of 100-300 mg/kg p.o. clearly demonstrated anti-inflammatory effects by reduced paw edema induced by carragenan, inhibited leukocyte recruitment into the peritoneal cavity and reduced LPS-induced febrile response, and in the model of chronic inflammation using the cotton pellet-induced fibrovascular tissue growth in rats, the SoHE significantly inhibited the formation of granulomatous tissue. The extract administered at 300 mg/kg p.o. had a stronger anti-inflammatory effect than indomethacin (10mg/kg) or dexamethasone (1mg/kg). The hydroethanolic extract of Sonchus oleraceus markedly demonstrated anti-inflammatory action in rats, which supports previous claims of its traditional use. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

[Drug eruptions caused by noncorticoid anti-inflammatory agents].

Science.gov (United States)

Roujeau, J C; Guillaume, J C; Revuz, J; Touraine, R

1984-01-01

Non-steroidal anti-inflammatory drugs (NSAI) may elicit various kinds of cutaneous side effects. The commonest ones are non-specific erythematous eruptions, sometimes with a phototoxic distribution, and urticaria. Vasculitis and severe bullous eruptions (Stevens-Johnson's syndrome and Toxic Epidermal Necrolysis) are rare but may have severe outcomes. The overall incidence of cutaneous reactions is about the same for all NSAI, 1 to 3 p. 100, during the clinical studies performed before marketing the drug, but this increases afterwards (up to 45 p. 100 for Benoxaprofen). Drugs with long half-lives may carry a higher risk for severe cutaneous reactions. NSAI are now the main cause of drug induced TEN. Urticarial reactions seem related to pharmacological phenomena while the pathogenic events leading to other kinds of skin reactions remain unknown. An hypersensitivity reaction is postulated. The therapeutic value of corticosteroids for the severe cutaneous side effects of drugs is still controversial.

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.

Hepatotoxicity of Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review of Randomized Controlled Trials

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Pajaree Sriuttha

2018-01-01

Full Text Available Background. Nonsteroidal anti-inflammatory drugs (NSAIDs are the most widely used medication in several countries, including Thailand. NSAIDs have been associated with hepatic side effects; however, the frequency of these side effects is uncertain. Aim of the Review. To systematically review published literature on randomized, controlled trials that assessed the risk of clinically significant hepatotoxicity associated with NSAIDs. Methods. Searches of bibliographic databases EMBASE, PubMed, and the Cochrane Library were conducted up to July 30, 2016, to identify randomized controlled trials of ibuprofen, naproxen, diclofenac, piroxicam, meloxicam, mefenamic acid, indomethacin, celecoxib, and etoricoxib in adults with any disease that provide information on hepatotoxicity outcomes. Results. Among the 698 studies, 18 studies met the selection criteria. However, only 8 studies regarding three NSAIDs (celecoxib, etoricoxib, and diclofenac demonstrated clinically significant hepatotoxic evidence based on hepatotoxicity justification criteria. Of all the hepatotoxicity events found from the above-mentioned three NSAIDs, diclofenac had the highest proportion, which ranged from 0.015 to 4.3 (×10−2, followed by celecoxib, which ranged from 0.13 to 0.38 (×10−2, and etoricoxib, which ranged from 0.005 to 0.930 (×10−2. Conclusion. Diclofenac had higher rates of hepatotoxic evidence compared to other NSAIDs. Hepatotoxic evidence is mostly demonstrated as aminotransferase elevation, while liver-related hospitalization or discontinuation was very low.

Relation between Proepileptic Activity of Indomethacin and AdrenalGland Hormones

OpenAIRE

Hacimuftuoglu, Ahmet; Suleyman, Halis; Cadirci, Elif; Albayrak, Abdulmecit; Polat, Beyzagul; Hakan Alp, Hamit; Halici, Zekai

2012-01-01

The role of inflammation has been shown in the pathogenesis of epilepsy, while glucocorticoids and adrenaline have anti-inflammatory effects. The aim of the present study was to investigate the effects of adrenaline, prednisolone, and indomethacin on caffeine-induced epilepsy (epileptiform activity) in rats and to examine the mechanism of the pro-epileptic effect of indomethacin. The adrenalectomized rats that had been given only adrenaline (the control group) did not die; however, adrenaline...

Microglial responses to amyloid β peptide opsonization and indomethacin treatment

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Leonard Brian

2005-08-01

Full Text Available Abstract Background Recent studies have suggested that passive or active immunization with anti-amyloid β peptide (Aβ antibodies may enhance microglial clearance of Aβ deposits from the brain. However, in a human clinical trial, several patients developed secondary inflammatory responses in brain that were sufficient to halt the study. Methods We have used an in vitro culture system to model the responses of microglia, derived from rapid autopsies of Alzheimer's disease patients, to Aβ deposits. Results Opsonization of the deposits with anti-Aβ IgG 6E10 enhanced microglial chemotaxis to and phagocytosis of Aβ, as well as exacerbated microglial secretion of the pro-inflammatory cytokines TNF-α and IL-6. Indomethacin, a common nonsteroidal anti-inflammatory drug (NSAID, had no effect on microglial chemotaxis or phagocytosis, but did significantly inhibit the enhanced production of IL-6 after Aβ opsonization. Conclusion These results are consistent with well known, differential NSAID actions on immune cell functions, and suggest that concurrent NSAID administration might serve as a useful adjunct to Aβ immunization, permitting unfettered clearance of Aβ while dampening secondary, inflammation-related adverse events.

Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety

OpenAIRE

Roth, Sandford

2011-01-01

Sanford H RothArizona Research and Education, Arthritis Laboratory, Arizona State University, Phoenix, AZ, USAAbstract: Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID) therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less...

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....

Non-steroidal anti-inflammatory drugs (NSAIDs) for axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis)

NARCIS (Netherlands)

Kroon, Feline P. B.; van der Burg, Lennart R. A.; Ramiro, Sofia; Landewé, Robert B. M.; Buchbinder, Rachelle; Falzon, Louise; van der Heijde, Désirée

2015-01-01

Axial spondyloarthritis (axSpA) comprises ankylosing spondylitis (radiographic axSpA) and non-radiographic (nr-)axSpA and is associated with psoriasis, uveitis and inflammatory bowel disease. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line drug treatment. To determine

[Reversible infertility from nonsteroidal anti-inflammatory drugs].

Science.gov (United States)

Skomsvoll, Johan Fredrik; Rødevand, Erik; Koksvik, Hege Svean; Salvesen, Kjell Asmund; von Düring, Vidar; Rygnestad, Tarjei; Østensen, Monika

2005-06-02

Nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 inhibitors may interfere with ovulation and the rupture of the follicle, causing reversible infertility. Literature review. Reversible infertility is shown both in animal and human studies of these drugs. As determined by ultrasound, the drugs may delay or inhibit ovulation. These findings are also confirmed by a few randomized controlled studies showing an increase in time from the luteinizing hormone surge to rupture of the follicle and an increased size of the unruptured follicle. Most of the hormone analyses show values in accordance with the ovulation/menstrual cycle. Also, two epidemiological studies have shown an association between NSAID use and spontaneous abortion. These studies have methodological weaknesses and their findings have to be elucidated in future studies. Women with fertility problems should avoid not only the selective cyclooxygenase-2 inhibitors, but also the traditional NSAIDs. However, women with rheumatic disease responding well to therapy should consult their physicians before stopping treatment. Reduced dose of a NSAID and temporary stop of drug treatment early in the menstrual cycle, or alternative drug treatment, may be a solution. NSAIDs should not be used in the last eight weeks of pregnancy.

Acute nonsteroidal anti-inflammatory drug-induced colitis

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Massimo Tonolini

2013-01-01

Full Text Available Resulting from direct toxicity on the bowel mucosa, nonsteroidal anti-inflammatory drug (NSAID-induced colitis is an underestimated although potentially serious condition. Plain abdominal radiographs and multidetector computed tomography allow to identify a right-sided acute colitis with associated pericolonic inflammation, progressively diminished changes along the descending and sigmoid colon, and rectal sparing, consistent with the hypothesized pathogenesis of NSAID colitis. Increased awareness of this condition should reduce morbidity through both prevention and early recognition. High clinical suspicion and appropriate patient questioning, together with consistent instrumental findings, negative biochemistry, and stool investigations should help physicians not to miss this important diagnosis.

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...

Experimental study of the effect of cisplatin combined with indomethacin and its derivatives for the treatment of lewis lung carcinoma with '18FDG-PET/CT

International Nuclear Information System (INIS)

Gao Jidong; Zhang Caixia; Lu Guoxiu; Xu Weina; Yu Shupeng

2013-01-01

Background: Non-steroidal anti-inflammatory drug Indomethacin have been used in the treatment of fever, pain, inflammation and rheumatic disease. In recent years, some researches have confirmed that Indomethacin have the ability of assistant therapy on many kinds of malignant tumors, such as colon cancer; gastric cancer and lung cancer: Purpose: To evaluate the effect of Cisplatin combined with Indomethacin and Histamine-Indomethacin to Lewis lung cancer. Methods: 40 male Kunming mice were used to establish Lewis lung cancer model. They were randomly divided into four groups: Cisplatin treatment group, Cisplatin+Indomethacin treatment group, Cisplatin+Histamine-Indomethacin treatment group and control group. Each mouse was given the PET/CT imaging and taken orbital blood for 0.2 mL before and after the treatment. Histological detection was given. Results: Ratio of targets were significantly different after the treatment, especially in Cisplatin+Histamine-Indomethacin treatment group. Each group TNF-α levels were increased after treatment and the Cisplatin+Histamine-Indomethacin treatment group was the most obvious. There was no obvious difference in tumor inhibiting rates. Conclusions: The results showed that Cisplatin combined with Histamine-Indomethacin could inhibit tumor growth and promote apoptosis of tumor cells better. The changes of the ratio of targets could reflect the effect of the chemotherapy drugs earlier. (authors)

Anti-Inflammatory Activity of Iridoids and Verbascoside Isolated from Castilleja tenuiflora

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Verónica Rodríguez-López

2013-09-01

Full Text Available Castilleja tenuiflora (Orobanchaceae has been used in Mexican traditional medicine as a treatment for cough, dysentery, anxiety, nausea and vomiting as well as hepatic and gastrointestinal diseases. The ethanolic extract of the aerial parts of Castilleja tenuiflora was separated by silica gel column chromatography. The fractions were evaluated using the induced edema acetate 12-O-tetradecanoylphorbol (TPA anti-inflammatory activity model. The most active fraction was subjected to medium-pressure liquid chromatography (MPLC with UV detection at 206 and 240 nm. The following iridoids were isolated: geniposidic acid, aucubin, bartioside, 8-epi-loganin, mussaenoside, and the phenylpropanoid verbascoside. The most active iridoid was geniposidic acid, which was more active than the control (indomethacin, and the least active iridoid was mussaenoside. 8-epi-Loganin, and mussaenoside have not been previously reported to be anti-inflammatory compounds. The results of these investigations confirm the potential of Mexican plants for the production of bioactive compounds and validate the ethnomedical use of Castilleja tenuiflora-like anti-inflammatory plants.

Non-Steroidal Anti-inflammatory Drugs As Host-Directed Therapy for Tuberculosis : A Systematic Review

NARCIS (Netherlands)

Kroesen, Vera M.; Gröschel, Matthias I.; Martinson, Neil; Zumla, Alimuddin; Maeurer, Markus; van der Werf, Tjip S.; Vilaplana, Cristina

2017-01-01

Lengthy, antimicrobial therapy targeting the pathogen is the mainstay of conventional tuberculosis treatment, complicated by emerging drug resistances. Host-directed therapies, including non-steroidal anti-inflammatory drugs (NSAIDs), in contrast, target host factors to mitigate disease severity. In

Evidence for gastroprotective, anti-inflammatory and antioxidant potential of methanolic extract of Cordia dichotoma leaves on indomethacin and stress induced gastric lesions in Wistar rats.

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Hatware, Ketan Vinayakrao; Sharma, Sanjay; Patil, Kiran; Shete, Meghanath; Karri, Sravani; Gupta, Gaurav

2018-07-01

The Cordia dichotoma (CD) is having anticancer and other pharmacological effects as it contains mainly flavonoids. The present study was aimed to demonstrate the gastroprotective effect of methanolic extract of CD leaves (MECD) obtained using Soxhlet extractor. In this study the qualitative phytochemical analysis of MECD revealed the presence of bioflavonoids and determination of quercetin was confirmed by HPLC analysis. The MECD was administered orally at doses 50 mg/kg, 100 mg/kg and 200 mg/kg against indomethacin induced gastric ulceration and stress-induced gastric ulceration in Wistar rats. Omeprazole at 10 mg/kg orally was used as the reference standard. The various parameters like gastric volume, gastric pH, total acidity, ulcer index, percent protection were estimated for assessment of anti-secretory and gastroprotective effects of MECD. At the same time antioxidant parameters like superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in addition to that inflammatory parameters such as tumor necrosis factor-α (TNF-α), interleukin-6 and interleukin-10 were also estimated according to their respective method of estimation using analyzing kit. The MECD have reduced gastric volume, total acidity and gastric mucosal damage in both the experimental models significantly and dose dependently as compared with control group. Similarly the antioxidant enzymes like SOD and CAT were increased while MDA levels were decreased significantly, at the same time TNF-α and IL-6 levels were decreased and anti-inflammatory IL-10 levels were increased significantly in MECD treated groups. Thus the pretreatment with MECD has shown significant gastroprotective potential probably due to its antioxidant and anti-inflammatory properties. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Inflammatory injury to the neonatal brain – what can we do?

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Noa eOfek-shlomai

2014-04-01

Full Text Available Abstract Perinatal brain damage is one of the leading causes of life long disability. This damage could be hypoxic-ischemic, inflammatory or both.This mini-review discusses different interventions aiming at minimizing inflammatory processes in the neonatal brain, both before and after insult. Current options of anti-inflammatory measures for neonates remain quite limited. We describe current anti-inflammatory intervention strategies such as avoiding perinatal infection and inflammation, and reducing exposure to inflammatory processes. We describe the known effects of anti-inflammatory drugs such as steroids, antibiotics, and indomethacin, and the possible anti-inflammatory role of other substances such as IL-1receptor antagonists, erythropoietin, caffeine, estradiol, insulin like growth factor and melatonin as well as endogenous protectors, and genetic regulation of inflammation. If successful, these may decrease mortality and long term morbidity among term and preterm infants.

Complex compounds of terbium(III) with some nonsteroidal anti-inflammatory drugs and their analytical applications

International Nuclear Information System (INIS)

Teslyuk, O.I.; Egorova, A.V.; Yagodkin, B.N.; Bel'tyukova, S.V.

2007-01-01

Luminescence properties of the complexes of terbium(III) with nonsteroidal anti-inflammatory drugs (ibuprofen and orthofen) were studied. It was demonstrated that in the presence of organic bases (2,2'-dipyridyl and 1,10-phenanthroline) mixed-ligand complexes are formed and the luminescence intensity of terbium(III) increases by a factor of up to 250. The optimum complexation conditions were determined. It was proposed to use these complexes as analytical forms for the luminescence determination of nonsteroidal anti-inflammatory drugs (ibuprofen and orthofen) in pharmaceutical dosage forms. The detection limits are 2 and 0.05 μg/ml, respectively [ru

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.

Clinical pharmacology of indomethacin in preterm infants: implications in patent ductus arteriosus closure.

Science.gov (United States)

Pacifici, Gian Maria

2013-10-01

Indomethacin is a non-steroidal anti-inflammatory drug that is a potent inhibitor of prostaglandin E(2) synthesis. After birth, the ductus arteriosus closes spontaneously within 2-4 days in term infants. The major factor closing the ductus arteriosus is the tension of oxygen, which increases significantly after birth. Prostaglandin E(2) has the opposite effect to that of oxygen; it relaxes smooth muscle and tends to inhibit the closure of the ductus arteriosus. In preterm infants with respiratory distress syndrome, the ductus arteriosus fails to close (patent ductus arteriosus [PDA]) because the concentration of prostaglandin E2 is relatively high. PDA occurs in more than 70 % of neonates weighing less than 1,500 g at birth. The aim of this article was to review the published data on the clinical pharmacology of indomethacin in preterm infants in order to provide a critical analysis of the literature and a useful tool for physicians. The bibliographic search was performed electronically using the PubMed and EMBASE databases as search engines and February 2012 was the cutoff point. A remarkable interindividual variability was observed for the half-life (t(½)), clearance (CL), and volume of distribution (V(d)) of indomethacin. Prophylactic indomethacin consists of a continuous infusion of low levels of indomethacin and may be useful in preterm infants. Extremely preterm infants are less likely to respond to indomethacin. Infants with a postnatal age of 2 months do not respond to treatment with indomethacin. Indomethacin has several adverse effects, the most common of which is renal failure. An increase in serum creatinine of ≥0.5 % mg/dL after indomethacin was observed in about 10-15 % of the patients and creatinine returns to a normal level about 1 week after cessation of therapy. Indomethacin should be administered intravenously by syringe pump for at least 30 min to minimize adverse effects on cerebral, gastrointestinal, and renal blood flow velocities. A

The anti-inflammatory activity of dillapiole and some semisynthetic analogues.

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Parise-Filho, Roberto; Pastrello, Michelli; Pereira Camerlingo, Carla Emygdio; Silva, Gisele Juni; Agostinho, Leonardo Aguiar; de Souza, Thaís; Motter Magri, Fátima Maria; Ribeiro, Roberto Rodrigues; Brandt, Carlos Alberto; Polli, Michelle Carneiro

2011-11-01

Piper aduncum L. (Piperaceae) produces an essential oil (dillapiole) with great exploitative potential and it has proven effects against traditional cultures of phytopathogens, such as fungi, bacteria and mollusks, as well as analgesic action with low levels of toxicity. This study investigated the in vivo anti-inflammatory activity of dillapiole. Furthermore, in order to elucidate its structure-anti-inflammatory activity relationship (SAR), semisynthetic analogues were proposed by using the molecular simplification strategy. Dillapiole and safrole were isolated and purified using column chromatography. The semisynthetic analogues were obtained by using simple organic reactions, such as catalytic reduction and isomerization. All the analogues were purified by column chromatography and characterized by (1)H and (13)C NMR. The anti-inflammatory activities of dillapiole and its analogues were studied in carrageenan-induced rat paw edema model. Dillapiole and di-hydrodillapiole significantly (p<0.05) inhibited rat paw edema. All the other substances tested, including safrole, were less powerful inhibitors with activities inferior to that of indomethacin. These findings showed that dillapiole and di-hydrodillapiole have moderate anti-phlogistic properties, indicating that they can be used as prototypes for newer anti-inflammatory compounds. Structure-activity relationship studies revealed that the benzodioxole ring is important for biological activity as well as the alkyl groups in the side chain and the methoxy groups in the aromatic ring.

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

Anti-inflammatory management for tendon injuries - friends or foes?

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Chan Kai-Ming

2009-10-01

Full Text Available Abstract Acute and chronic tendon injuries are very common among athletes and in sedentary population. Most physicians prescribe anti-inflammatory managements to relieve the worst symptoms of swelling and pain, including non-steroidal anti-inflammatory drugs, corticosteroids and physical therapies. However, experimental research shows that pro-inflammatory mediators such as prostaglandins may play important regulatory roles in tendon healing. Noticeably nearly all cases of chronic tendon injuries we treat as specialists have received non-steroidal anti-inflammatory drugs by their physician, suggesting that there might be a potential interaction in some of these cases turning a mild inflammatory tendon injury into chronic tendinopathy in predisposed individuals. We are aware of the fact that non-steroidal anti-inflammatory drugs and corticosteroids may well have a positive effect on the pain control in the clinical situation whilst negatively affect the structural healing. It follows that a comprehensive evaluation of anti-inflammatory management for tendon injuries is needed and any such data would have profound clinical and health economic importance.

Marine bioactive compounds: stereospecific anti-inflammatory activity of natural and synthetic cordiachromene A.

Science.gov (United States)

Benslimane, A F; Pouchus, Y F; Verbist, J F; Petit, J Y; Khettab, E N; Welin, L; Brion, J D

1992-01-01

A new synthesis is proposed for cordiachromene A (CCA), a bioactive component of the ascidian Aplidium antillense Gravier, using a method producing a racemic mixture. The anti-inflammatory activities of a natural extract and a chemically synthetic form of CCA were assessed in vivo by carrageenan-induced rat-paw edema. The activity of synthetic CCA was confirmed by a test on kaolin-induced granuloma in the rat. Strong activities were measured for both CCA, but comparison of results of the first test suggests that only the natural optically active isomer has an anti-inflammatory effect. CCA is similar to indomethacin in its effect on carrageenan-induced rat-paw edema and ten times as active as phenylbutazone.

Prescription Pattern Analysis of Nonsteroidal Anti-inflammatory Drugs in the Northeastern Iranian Population

NARCIS (Netherlands)

Zeinali, Majid; Tabeshpour, Jamshid; Maziar, Seyed Vahid; Taherzadeh, Zhila; Zirak, Mohammad Reza; Sent, Danielle; Azarkhiavi, Kamal Razavi; Eslami, Saeid

2017-01-01

Inappropriate nonsteroidal anti-inflammatory drugs (NSAIDs) therapy is a common cause of actual and potential adverse effects, such as bleeding and gastrointestinal ulceration, which exacerbates the patient's medical condition and might even be life threatening. We aimed to evaluate and analyze the

Nuclear factor kappa B: a pro-inflammatory, transcription factor-mediated signalling pathway in lung carcinogenesis and its inhibition by nonsteroidal anti-inflammatory drugs.

Science.gov (United States)

Setia, Shruti; Sanyal, Sankar Nath

2012-01-01

9,10-Dimethyl benz(a)anthracene (DMBA), when injected intratracheally once at a dose of 20 mg/kg body weight, is found to induce lung cancer in rats. Two nonsteroidal anti-inflammatory drugs (NSAIDs), indomethacin and etoricoxib, are given orally daily as chemopreventive agents at a dose of 0.6 mg/kg body weight and 2 mg/kg body weight, respectively, along with DMBA. Morphologic and histologic analysis revealed the occurence of tumors and intense cellular proliferation in the DMBA-treated animals, whereas no such features were observed in the other groups. Nuclear factor κB, a nuclear transcription factor, and proliferating cell nuclear antigen, a cell proliferation antigen, were studied by immunoblotting and immunohistochemistry and their levels were markedly elevated in the DMBA group compared with the others. Oxidative stress parameters, as studied by the inducible nitric oxide synthase activity, and the levels of reactive oxygen and nitrogen species were found to be suppressed in the DMBA group. Furthermore, fluorescent staining of the isolated lung cells from bronchoalveolar lavage was performed to study apoptosis and alterations in the mitochondrial membrane potential, and the DMBA-induced lung cancer was found to be associated with high inner mitochondrial membrane potential and a suppressed level of apoptosis.

Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug.

Science.gov (United States)

Dang, Tram T; Thai, Anh V; Cohen, Joshua; Slosberg, Jeremy E; Siniakowicz, Karolina; Doloff, Joshua C; Ma, Minglin; Hollister-Lock, Jennifer; Tang, Katherine M; Gu, Zhen; Cheng, Hao; Weir, Gordon C; Langer, Robert; Anderson, Daniel G

2013-07-01

Immuno-isolation of islets has the potential to enable the replacement of pancreatic function in diabetic patients. However, host response to the encapsulated islets frequently leads to fibrotic overgrowth with subsequent impairment of the transplanted grafts. Here, we identified and incorporated anti-inflammatory agents into islet-containing microcapsules to address this challenge. In vivo subcutaneous screening of 16 small molecule anti-inflammatory drugs was performed to identify promising compounds that could minimize the formation of fibrotic cell layers. Using parallel non-invasive fluorescent and bioluminescent imaging, we identified dexamethasone and curcumin as the most effective drugs in inhibiting the activities of inflammatory proteases and reactive oxygen species in the host response to subcutaneously injected biomaterials. Next, we demonstrated that co-encapsulating curcumin with pancreatic rat islets in alginate microcapsules reduced fibrotic overgrowth and improved glycemic control in a mouse model of chemically-induced type I diabetes. These results showed that localized administration of anti-inflammatory drug can improve the longevity of encapsulated islets and may facilitate the translation of this technology toward a long-term cure for type I diabetes. Published by Elsevier Ltd.

Characteristics of indomethacin-saccharin (IMC-SAC) co-crystals prepared by an anti-solvent crystallization process.

Science.gov (United States)

Chun, Nan-Hee; Wang, In-Chun; Lee, Min-Jeong; Jung, Yun-Taek; Lee, Sangkil; Kim, Woo-Sik; Choi, Guang J

2013-11-01

The creation of co-crystals of various insoluble drug substances has been extensively investigated as a promising approach to improve their pharmaceutical performance. In this study, co-crystal powders of indomethacin and saccharin (IMC-SAC) were prepared by an anti-solvent (water) addition and compared with co-crystals by evaporation method. No successful synthesis of a pharmaceutical co-crystal powder via an anti-solvent approach has been reported. Among solvents examined, methanol was practically the only one that resulted in the formation of highly pure IMC-SAC co-crystal powders by anti-solvent approach. The mechanism of a preferential formation of IMC-SAC co-crystal to IMC was explained with two aspects: phase solubility diagram and solution complexation concept. Accordingly, the anti-solvent approach can be considered as a competitive route for producing pharmaceutical co-crystal powders with acceptable properties. Copyright © 2013 Elsevier B.V. All rights reserved.

TOPICALITY OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS IN TREATMENT OF FEVER IN CHILDREN

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O.A. Mubarakshina

2010-01-01

Full Text Available Nonsteroidal anti-inflammatory drugs are widely used in pediatric practice for the treatment of fever. The choice of the drug from this group must be based on high effectiveness of medication and the lowest risk of adverse events. Only paracetamol and ibuprofen completely fulfill these requirements at the present times. They are officially recommended by WHO for the use as an anti-fever pediatric medication. The article examines advantages of ibuprofen compared to paracetamol on the basis of results of randomized studies. Author describes a safety of ibuprofen and opportunities of combined treatment with ibuprofen and paracetamol.Key words: children, fever, ibuprofen, paracetamol, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(2:156-160

Helicobacter pylori and risk of ulcer bleeding among users of nonsteroidal anti-inflammatory drugs

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...... the role of H. pylori as a cause of bleeding peptic ulcer among NSAID users....

Medicinal chemistry and anti-inflammatory activity of nitric oxide-releasing NSAI drugs.

Science.gov (United States)

Koç And, Esra; Küçükgüzel, S Güniz

2009-05-01

Nitric Oxide, which acts as a non-specific cytotoxic mediator and a biological messenger on immunological competence, has been gaining significantly increasing importance. As an alternative to conventional NSAIDs having significant side effects, pharmacologically improved and therapeutically enhanced NO releasing non-steroidal anti-inflammatory drugs with less side effects are being planned to produce.

Anti-inflammatory and analgesic potential of Caesalpinia ferrea

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Sandrine Maria A. Lima

2012-02-01

Full Text Available Caesalpinia ferrea Mart. belongs to the family Fabaceae. Known as pau-ferro and jucá, it is used in folk medicine to treat diabetes, as antipyretic and antirheumatic. This study aimed to evaluate the anti-inflammatory and antinociceptive activities of the ethanol extract of the fruits of C. ferrea (EECf. In the evaluation of anti-inflammatory activity, EECf (50 mg/kg produced significantly inhibition of ear edema by 66.6% compared to control. Indomethacin (10 mg/kg showed inhibition of 83.9% compared to control. EECf (50 mg/kg inhibited of vascular permeability induced by acetic acid and was also able to reduce of cell migration to the peritoneal cavity induced by thioglycolate. In the writhing test induced by acid acetic, EECf (12.5, 25 and 50 mg/kg significantly reduced the number of contortions by 24.9, 46.9 and 74.2%, respectively. In the formalin test, EECf presented effects only in the second phase. The results provided experimental evidence for the effectiveness of the traditional use of C. ferrea in treating various diseases associated with inflammation and pain.

Analgesic and anti-inflammatory effects of Cyphostemma vogelii (Hook

African Journals Online (AJOL)

Rita

2013-04-24

Apr 24, 2013 ... Key words: Analgesic, anti-inflammatory, mice, Cyphostemma vogelii, nociception. ... steroidal anti- inflammatory drugs (NSAIDs) are considered the drugs of ..... 44-55. Hughes H, Lang M (1983). Control of pain in dogs and cats In: Kitchell. R, Erickson H (eds.) Animal pain. Baltimore Waverly press. pp. 207-.

Non-steroidal anti-inflammatory drugs (NSAIDs) for chronic non-cancer pain in children and adolescents.

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Eccleston, Christopher; Cooper, Tess E; Fisher, Emma; Anderson, Brian; Wilkinson, Nick Mr

2017-08-02

Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions.As the leading cause of morbidity in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (that is pain lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications (nociceptive, neuropathic, or idiopathic) from genetic conditions, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, as well as for other unknown reasons.Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat pain, reduce fever, and for their anti-inflammation properties. They are commonly used within paediatric pain management. Non-steroidal anti-inflammatory drugs are currently licensed for use in Western countries, however they are not approved for infants under three months old. The main adverse effects include renal impairment and gastrointestinal issues. Common side effects in children include diarrhoea, headache, nausea, constipation, rash, dizziness, and abdominal pain. To assess the analgesic efficacy and adverse events of NSAIDs used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting. We searched the Cochrane

The effect of a non-steroidal anti-inflammatory drug on two important predictors for accidental falls: postural balance and manual reaction time. A randomized, controlled pilot study.

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Hegeman, Judith; Nienhuis, Bart; van den Bemt, Bart; Weerdesteyn, Vivian; van Limbeek, Jacques; Duysens, Jacques

2011-04-01

Accidental falls in older individuals are a major health and research topic. Increased reaction time and impaired postural balance have been determined as reliable predictors for those at risk of falling and are important functions of the central nervous system (CNS). An essential risk factor for falls is medication exposure. Amongst the medications related to accidental falls are the non-steroidal anti-inflammatory drugs (NSAIDs). About 1-10% of all users experience CNS side effects. These side effects, such as dizziness, headaches, drowsiness, mood alteration, and confusion, seem to be more common during treatment with indomethacin. Hence, it is possible that maintenance of (static) postural balance and swift reactions to stimuli are affected by exposure to NSAIDs, indomethacin in particular, consequently putting older individuals at a greater risk for accidental falls. The present study investigated the effect of a high indomethacin dose in healthy middle-aged individuals on two important predictors of falls: postural balance and reaction time. Twenty-two healthy middle-aged individuals (59.5 ± 4.7 years) participated in this double-blind, placebo-controlled, randomized crossover trial. Three measurements were conducted with a week interval each. A measurement consisted of postural balance as a single task and while concurrently performing a secondary cognitive task and reaction time tasks. For the first measurement indomethacin 75 mg (slow-release) or a visually identical placebo was randomly assigned. In total, five capsules were taken orally in the 2.5 days preceding assessment. The second measurement was without intervention, for the final one the first placebo group got indomethacin and vice versa. Repeated measures GLM revealed no significant differences between indomethacin, placebo, and baseline in any of the balance tasks. No differences in postural balance were found between the single and dual task conditions, or on the performance of the dual task

Role of Non-Steroidal Anti-Inflammatory Drugs in Gynecology

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Anna Livshits

2010-07-01

Full Text Available This review summarizes the current use of non-steroidal anti-inflammatory drugs (NSAIDs in obstetrics, gynecology and infertility. These medications are commonly used in different fields of reproductive medicine, for pain management after operative procedures and to relieve dysmenorrhea. In addition to their analgesic effect, NSAIDs are helpful in the management of menorrhagia by decreasing menstrual blood loss. NSAIDs alleviate pain associated with medical abortion, assist in undertaking natural cycle in-vitro fertilization by preventing follicular rupture and reducing premature ovulation, and serve as tocolytics in preterm labor. New NSAIDs may have a growing role in management of women's health.

Indomethacin treatment prior to pentylenetetrazole-induced seizures downregulates the expression of il1b and cox2 and decreases seizure-like behavior in zebrafish larvae.

Science.gov (United States)

Barbalho, Patrícia Gonçalves; Lopes-Cendes, Iscia; Maurer-Morelli, Claudia Vianna

2016-03-09

It has been demonstrated that the zebrafish model of pentylenetetrazole (PTZ)-evoked seizures and the well-established rodent models of epilepsy are similar pertaining to behavior, electrographic features, and c-fos expression. Although this zebrafish model is suitable for studying seizures, to date, inflammatory response after seizures has not been investigated using this model. Because a relationship between epilepsy and inflammation has been established, in the present study we investigated the transcript levels of the proinflammatory cytokines interleukin-1 beta (il1b) and cyclooxygenase-2 (cox2a and cox2b) after PTZ-induced seizures in the brain of zebrafish 7 days post fertilization. Furthermore, we exposed the fish to the nonsteroidal anti-inflammatory drug indomethacin prior to PTZ, and we measured its effect on seizure latency, number of seizure behaviors, and mRNA expression of il1b, cox2b, and c-fos. We used quantitative real-time PCR to assess the mRNA expression of il1b, cox2a, cox2b, and c-fos, and visual inspection was used to monitor seizure latency and the number of seizure-like behaviors. We found a short-term upregulation of il1b, and we revealed that cox2b, but not cox2a, was induced after seizures. Indomethacin treatment prior to PTZ-induced seizures downregulated the mRNA expression of il1b, cox2b, and c-fos. Moreover, we observed that in larvae exposed to indomethacin, seizure latency increased and the number of seizure-like behaviors decreased. This is the first study showing that il1b and cox-2 transcripts are upregulated following PTZ-induced seizures in zebrafish. In addition, we demonstrated the anticonvulsant effect of indomethacin based on (1) the inhibition of PTZ-induced c-fos transcription, (2) increase in seizure latency, and (3) decrease in the number of seizure-like behaviors. Furthermore, anti-inflammatory effect of indomethacin is clearly demonstrated by the downregulation of the mRNA expression of il1b and cox2b. Our results

Anti-metastatic Action of Non-steroidal Anti-inflammatory Drugs

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Wen-Chun Hung

2008-08-01

Full Text Available Epidemiological studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs reduce the incidence and mortality of several types of human cancer. However, the molecular mechanisms by which NSAIDs exert their chemopreventive and anticancer effects are not fully understood. Cyclooxygenase 1 (COX-1 and COX-2 are the main targets for NSAIDs. Recent studies demonstrate that COX-2 is overexpressed in many human cancers and may promote tumorigenesis via: (1 stimulation of cancer cell proliferation; (2 increase of tumor angiogenesis; (3 prevention of cancer cell apoptosis; (4 modulation of immunoregulatory reactions; and (5 enhancement of tumor metastasis. NSAIDs may target the signaling molecules (from upstream activators to downstream effectors involved in these mechanisms to attenuate the development and progression of cancer. In this review, we discuss the recent findings with regard to the mechanisms by which NSAIDs inhibit tumorigenesis and will specifically focus on the elucidation of NSAID-induced inhibition of tumor metastasis.

Phenotypic changes in neutrophils related to anti-inflammatory therapy.

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Barton, A E; Bayley, D L; Mikami, M; Llewellyn-Jones, C G; Stockley, R A

2000-01-03

Previous work from the group has shown that non-steroidal anti-inflammatory agents given to volunteers and patients inhibit PMN function possibly by affecting the developing neutrophil during the differentiation process. In this study indomethacin treatment in vivo reduced neutrophil chemotaxis and proteolytic degradation of fibronectin, with a maximal effect after 14 days. Stimulated neutrophil adherence to fibronectin was also reduced but this was not due to quantitative changes in beta(2) integrin expression or function. L-Selectin expression on resting and stimulated neutrophils was increased after 14 days and there was a small decrease in plasma levels of soluble L-selectin. These effects, however, could not be reproduced by treatment of neutrophils with indomethacin in vitro, suggesting they are due to effects on differentiating/maturing PMNs. In an attempt to interpret these changes, studies were performed with dexamethasone, which is known to alter neutrophil function and kinetics. Dexamethasone treatment reduced chemotaxis and increased superoxide generation after 1 day and was associated with increased expression of activated beta(2) integrins and reduced L-selectin expression on resting neutrophils. This suggests the appearance of mainly 'activated' cells as a result of demargination and indicates that the effects of indomethacin are distinctive and not related to changes in compartmentalisation.

Anti-inflammatory effects of insulin.

Science.gov (United States)

Dandona, Paresh; Chaudhuri, Ajay; Mohanty, Priya; Ghanim, Husam

2007-07-01

This review deals with the recent observations on the pro-inflammatory effects of glucose and the anti-inflammatory actions of insulin. Apart from being novel, they are central to our understanding of why hyperglycemia is a prognosticator of bad clinical outcomes including patients with acute coronary syndromes, stroke and in patients in the intensive care unit. The pro-inflammatory effect of glucose as well as that of other macronutrients including fast food meals provides the basis of chronic oxidative stress and inflammation in the obese and their propensity to atherosclerotic disease. The anti-inflammatory action of insulin provides a neutralizing effect to balance macronutrient induced inflammation on the one hand and the possibility of using insulin as an anti-inflammatory drug on the other. The actions of macronutrients and insulin described above explain why insulin resistant states like obesity and type 2 diabetes are associated with oxidative stress, inflammation and atherosclerosis. They also suggest that insulin may be antiatherogenic.

Non-steroidal anti-inflammatory drugs and antibiotics prescription trends at a central west bank hospital.

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Tayem, Yasin I; Qubaja, Marwan M; Shraim, Riyad K; Taha, Omar B; Abu Shkheidem, Imadeddin A; Ibrahim, Murad A

2013-11-01

We aimed to reliably describe the pattern of outpatient prescription of non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics (ATBs) at a central hospital in the West Bank, Palestine. This was a retrospective, cross-sectional study investigating a cohort of 2,208 prescriptions ordered by outpatient clinics and the emergency room over one year in Beit Jala Hospital in Bethlehem, West Bank. The orders were analysed for the rate and types of NSAIDs and ATBs utilised, and the appropriateness of these drugs to the diagnosis. Of the total prescriptions, 410 contained NSAIDs (18.6%), including diclofenac (40.2%), low dose aspirin (23.9%), ibuprofen (17.8%) and indomethacin (15.1%). A minority of these prescriptions contained a combination of these agents (2.5%). Only one prescription contained cyclooxyeganse-2 inhibitors (0.2%). The appropriateness of NSAID use to the diagnosis was as follows: appropriate (58.3%), inappropriate (14.4%) and difficult to tell (27.3%). The rate of ATB use was 30.3% (669 prescriptions). The ATBs prescribed were amoxicillin (23.3%), augmentin (14.3%), quinolones (12.7%), first and second generation cephalosporins (9.4% and 12.7%, respectively) and macrolides (7.2%). ATB combinations were identified in 9.4%, with the most common being second-generation cephalopsorins and metronidazole (4.3%). Regarding the appropriateness of prescribing ATBs according to the diagnosis, it was appropriate in 44.8%, inappropriate in 20.6% and difficult to tell in 34.6% of the prescriptions. These findings revealed a relatively large number and inappropriate utilisation of ATBs and NSAIDs. An interventional programme needs to be adopted to reinforce physicians' knowledge of the rational prescription of these agents.

Conservative Nonhormonal Options for the Treatment of Male Infertility: Antibiotics, Anti-Inflammatory Drugs, and Antioxidants.

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Calogero, Aldo E; Condorelli, Rosita A; Russo, Giorgio Ivan; La Vignera, Sandro

2017-01-01

The nonhormonal medical treatment can be divided into empirical, when the cause has not been identified, and nonempirical, if the pathogenic mechanism causing male infertility can be solved or ameliorated. The empirical nonhormonal medical treatment has been proposed for patients with idiopathic or noncurable oligoasthenoteratozoospermia and for normozoospermic infertile patients. Anti-inflammatory, fibrinolytic, and antioxidant compounds, oligo elements, and vitamin supplementation may be prescribed. Infection, inflammation, and/or increased oxidative stress often require a specific treatment with antibiotics, anti-inflammatory drugs, and/or antioxidants. Combined therapies can contribute to improve sperm quality.

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

Topical Anti-Inflammatory and Analgesic Effects of Multiple Applications of S(+)-Flurbiprofen Plaster (SFPP) in a Rat Adjuvant-Induced Arthritis Model.

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Sugimoto, Masanori; Toda, Yoshihisa; Hori, Miyuki; Mitani, Akiko; Ichihara, Takahiro; Sekine, Shingo; Kaku, Shinsuke; Otsuka, Noboru; Matsumoto, Hideo

2016-06-01

Preclinical Research The aim of this study was to evaluate the efficacy of multiple applications of S(+)-flurbiprofen plaster (SFPP), a novel Nonsteroidal anti-inflammatory drug (NSAID) patch, for the alleviation of inflammatory pain and edema in rat adjuvant-induced arthritis (AIA) model as compared to other NSAID patches. The AIA model was induced by the injection of Mycobacterium butyricum and rats were treated with a patch (1.0 cm × 0.88 cm) containing each NSAID (SFP, ketoprofen, loxoprofen, diclofenac, felbinac, flurbiprofen, or indomethacin) applied to the paw for 6 h per day for 5 days. The pain threshold was evaluated using a flexion test of the ankle joint, and the inflamed paw edema was evaluated using a plethysmometer. cyclooxygenase (COX)-1 and COX-2 inhibition was evaluated using human recombinant proteins. Multiple applications of SFPP exerted a significant analgesic effect from the first day of application as compared to the other NSAID patches. In terms of paw edema, SFPP decreased edema from the second day after application, Multiple applications of SFPP were superior to those of other NSAID patches, in terms of the analgesic effect with multiple applications. These results suggest that SFPP may be a beneficial patch for providing analgesic and anti-inflammatory effects clinically. Drug Dev Res 77 : 206-211, 2016. © 2016 The Authors Drug Development Research Published by Wiley Periodicals, Inc. © 2016 The Authors Drug Development Research Published by Wiley Periodicals, Inc.

Drug-induced liver injury due to antimicrobials, central nervous system agents, and nonsteroidal anti-inflammatory drugs.

Science.gov (United States)

Devarbhavi, Harshad; Andrade, Raúl J

2014-05-01

Antimicrobial agents including antituberculosis (anti-TB) agents are the most common cause of idiosyncratic drug-induced liver injury (DILI) and drug-induced liver failure across the world. Better molecular and genetic biomarkers are acutely needed to help identify those at risk of liver injury particularly for those needing antituberculosis therapy. Some antibiotics such as amoxicillin-clavulanate and isoniazid consistently top the lists of agents in retrospective and prospective DILI databases. Central nervous system agents, particularly antiepileptics, account for the second most common class of agents implicated in DILI registries. Hepatotoxicity from older antiepileptics such as carbamazepine, phenytoin, and phenobarbital are often associated with hypersensitivity features, whereas newer antiepileptic drugs have a more favorable safety profile. Antidepressants and nonsteroidal anti-inflammatory drugs carry very low risk of significant liver injury, but their prolific use make them important causes of DILI. Early diagnosis and withdrawal of the offending agent remain the mainstays of minimizing hepatotoxicity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug

OpenAIRE

Dang, Tram T.; Thai, Anh V.; Cohen, Joshua; Slosberg, Jeremy E.; Siniakowicz, Karolina; Doloff, Joshua C.; Ma, Minglin; Hollister-Lock, Jennifer; Tang, Katherine; Gu, Zhen; Cheng, Hao; Weir, Gordon C.; Langer, Robert; Anderson, Daniel G.

2013-01-01

Immuno-isolation of islets has the potential to enable the replacement of pancreatic function in diabetic patients. However, host response to the encapsulated islets frequently leads to fibrotic overgrowth with subsequent impairment of the transplanted grafts. Here, we identified and incorporated anti-inflammatory agents into islet-containing microcapsules to address this challenge. In vivo subcutaneous screening of 16 small molecule anti-inflammatory drugs was performed to identify promising...

Anti-inflammatory homoeopathic drug dilutions restrain lipopolysaccharide-induced release of pro-inflammatory cytokines: In vitro and in vivo evidence

Directory of Open Access Journals (Sweden)

Umesh B Mahajan

2017-01-01

Full Text Available Context: The lipopolysaccharide (LPS-induced cytokine release and oxidative stress are validated experimental parameters used to test anti-inflammatory activity. We investigated the effects of homoeopathic mother tinctures, 6 CH, 30 CH and 200 CH dilutions of Arnica montana, Thuja occidentalis and Bryonia alba against LPS (1 μg/ml-induced cytokine release from RAW-264.7 cells and human whole-blood culture. Materials and Methods: For in vivo evaluations, mice were orally treated with 0.1 ml drug dilutions twice a day for 5 days followed by an intraperitoneal injection of 0.5 mg/kg LPS. After 24 h, the mice were sacrificed and serum levels of pro-inflammatory cytokines and nitric oxide were determined. The extent of oxidative stress was determined in the liver homogenates as contents of reduced glutathione, malondialdehyde, superoxide dismutase and catalase. Results: The tested drug dilutions significantly reduced in vitro LPS-induced release of tumour necrosis factor-α, interleukin-1 (IL-1 and IL-6 from the RAW-264.7 cells and human whole blood culture. Similar suppression of cytokines was evident in mice serum samples. These drugs also protected mice from the LPS-induced oxidative stress in liver tissue. Conclusions: Our findings substantiate the protective effects of Arnica, Thuja and Bryonia homoeopathic dilutions against LPS-induced cytokine elevations and oxidative stress. This study authenticates the claims of anti-inflammatory efficacy of these homoeopathic drugs.

Concentrated Phosphatidic Acid in Cereal Brans as Potential Protective Agents against Indomethacin-Induced Stomach Ulcer.

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Afroz, Sheuli; Ikoma, Teru; Yagi, Ayano; Kogure, Kentaro; Tokumura, Akira; Tanaka, Tamotsu

2016-09-21

One of complications associated with long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is peptic ulcer. Recently, we found that orally administered phosphatidic acid (PA) ameliorated aspirin-induced stomach lesions in mice. In this study, we identified PA-rich food sources and examined the effects of the food materials on indomethacin-induced stomach ulcer. Among examined, buckwheat (Fagopyrum esculentum) bran contained the highest level of PA (188 mg/100 g). PA was the richest phospholipid (25%) in the lipid fraction of the buckwheat bran. Administration of the lipid extracts of buckwheat bran significantly ameliorated indomethacin-induced stomach lesions in mice. In contrast, wheat (Triticum durum) bran lipids (PA, 4%) and soybean (Glycine max) lipids (PA, 3%) were not associated with ameliorative effects. These results indicated that PA-rich lipids can be used as an effective supplement for prevention of NSAID-induced stomach ulcer.

Synthesis and anti-angiogenic effect of conjugates between serum albumin and non-steroidal anti-inflammatory drugs

DEFF Research Database (Denmark)

Kjær, Birgitte; Struve, Casper; Friis, Tina

2010-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit tumor growth and angiogenesis. Covalent linkage of naproxen to human serum albumin (HSA) has been shown to target it efficiently to the liver and this may potentially be exploited for liver-selective inhibition of angiogenesis. With the aim...... effect on endothelial cells at or above the level of the non-conjugated NSAIDs in an in vitro angiogenesis assay....

Effect of indomethacin and lactoferrin on human tenocyte proliferation and collagen formation in vitro

International Nuclear Information System (INIS)

Zhang, Yaonan; Wang, Xiao; Qiu, Yiwei; Cornish, Jillian; Carr, Andrew J.; Xia, Zhidao

2014-01-01

Highlights: • Indomethacin, a classic NSAID, inhibited human tenocyte proliferation at high concentration (100 µM). • Lactoferrin at 50-100 µg/ml promoted human tenocyte survival, proliferation and collagen synthesis. • Lactoferrin is anabolic to human tenocytes in vitro and reverses potential inhibitory effects of NSAIDs on human tenocytes. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in patients with injuries and inflammation of tendon and ligament, and as post-surgical analgesics. The aim of this study is to investigate the effect of indomethacin, a classic NSAID and its combinational effect with an anabolic agent of skeletal tissue, lactoferrin, on the proliferation and collagen formation of human tenocytes in vitro. A factorial experimental design was employed to study the dose-dependent effect of the combination of indomethacin and lactoferrin. The results showed that indomethacin at high concentration (100 μM) inhibited human tenocyte proliferation in culture medium with 1–10% fetal bovine serum (FBS) in vitro. Also, high dose of indomethacin inhibited the collagen formation of human tenocytes in 1% FBS culture medium. Lactoferrin at 50–100 μg/ml promoted human tenocyte survival in serum-free culture medium and enhanced proliferation and collagen synthesis of human tenocytes in 1% FBS culture medium. When 50–100 μg/ml lactoferrin was used in combination with 100–200 μM indomethacin, it partially rescued the inhibitory effects of indomethacin on human tenocyte proliferation, viability and collagen formation. To our knowledge, it is the first evidence that lactoferrin is anabolic to human tenocytes in vitro and reverses potential inhibitory effects of NSAIDs on human tenocytes

Effect of indomethacin and lactoferrin on human tenocyte proliferation and collagen formation in vitro

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yaonan [Centre for Nanohealth, College of Medicine, Swansea University, Singleton Park, Swansea, UK SA2 8PP (United Kingdom); Department of Orthopaedic, Beijing Hospital of Ministry of Public Health, Beijing, China 100730 (China); Wang, Xiao; Qiu, Yiwei [Centre for Nanohealth, College of Medicine, Swansea University, Singleton Park, Swansea, UK SA2 8PP (United Kingdom); Cornish, Jillian [Department of Medicine, University of Auckland, Private Bag 92019, Auckland (New Zealand); Carr, Andrew J. [Centre for Nanohealth, College of Medicine, Swansea University, Singleton Park, Swansea, UK SA2 8PP (United Kingdom); Xia, Zhidao, E-mail: z.xia@swansea.ac.uk [Centre for Nanohealth, College of Medicine, Swansea University, Singleton Park, Swansea, UK SA2 8PP (United Kingdom)

2014-11-14

Highlights: • Indomethacin, a classic NSAID, inhibited human tenocyte proliferation at high concentration (100 µM). • Lactoferrin at 50-100 µg/ml promoted human tenocyte survival, proliferation and collagen synthesis. • Lactoferrin is anabolic to human tenocytes in vitro and reverses potential inhibitory effects of NSAIDs on human tenocytes. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in patients with injuries and inflammation of tendon and ligament, and as post-surgical analgesics. The aim of this study is to investigate the effect of indomethacin, a classic NSAID and its combinational effect with an anabolic agent of skeletal tissue, lactoferrin, on the proliferation and collagen formation of human tenocytes in vitro. A factorial experimental design was employed to study the dose-dependent effect of the combination of indomethacin and lactoferrin. The results showed that indomethacin at high concentration (100 μM) inhibited human tenocyte proliferation in culture medium with 1–10% fetal bovine serum (FBS) in vitro. Also, high dose of indomethacin inhibited the collagen formation of human tenocytes in 1% FBS culture medium. Lactoferrin at 50–100 μg/ml promoted human tenocyte survival in serum-free culture medium and enhanced proliferation and collagen synthesis of human tenocytes in 1% FBS culture medium. When 50–100 μg/ml lactoferrin was used in combination with 100–200 μM indomethacin, it partially rescued the inhibitory effects of indomethacin on human tenocyte proliferation, viability and collagen formation. To our knowledge, it is the first evidence that lactoferrin is anabolic to human tenocytes in vitro and reverses potential inhibitory effects of NSAIDs on human tenocytes.

Radioiodination and bio-evaluation of some anti-inflammatory drugs

International Nuclear Information System (INIS)

Mohamed, H.H.

2009-01-01

This thesis deals with the electrophilic substitution radioiodination reaction of non-steroidal anti-inflammatory drugs namely, Piroxicam (Pirox), Meloxicam (Melox), Etodolac and Naproxen for using them as anti-inflammatory imaging agent. The factors affecting the percent of radiochemical yields such as drug concentration, ph of the reaction mixtures, different oxidizing agents, reaction time, temperature and different organic media were studied. We can divide the objective of this thesis into three parts: First part performs to compare the electrophilic substitution radioiodination reaction of Piroxicam (Pirox) and Meloxicam (Melox) with Iodine-125 where both chloramine-T (CAT) and iodogen were used as oxidizing agents. The maximum radiochemical yield of 125 I-Piroxicam ( 125 I-Pirox) was (94%) using 3.7 MBq of Na 125 I, 0.4 mM of Pirox as substrate, 3.6 mM of chloramine-T (CAT) as oxidizing agent in acetone at neutral ph=7 at 60 degree C within 20 min where the maximum radiochemical yield of ( 125 I-Melox) was (92%) using 0.7 mM of Melox as substrate, 0.62 mM of iodogen as oxidizing agent in acetone at neutral ph=7 at 25 degree C within 30 min. The radiochemical yields were determined by TLC using methylene chloride: ethyl acetate (3: 7 v/v) as a developing system and by high-pressure liquid chromatography (HPLC) using reversed phase RP-18 column and methanol: water (70: 30 v/v) as mobile phase at flow rate (1 ml/min). Tracers showed good localization in inflamed muscle either (septic or sterile). The collected data indicates that Pirox can be used as anti-inflammatory imaging agent at 24 h post injection however Melox can be used as anti-inflammatory imaging agent at 2 h due to its shorter biological half life (t 1/2 ) compared with Pirox. Second part describes a fast and efficient method for radiolabeling of etodolac with iodine-125, where both chloramine-T and iodogen were used as oxidizing agents. The labeling reaction was carried out via electrophilic

Postoperative non-steroidal anti-inflammatory drugs and colorectal anastomotic leakage

DEFF Research Database (Denmark)

Klein, Mads; Gögenur, Ismail; Rosenberg, Jacob

2012-01-01

Anastomotic leakage (AL) is the most important and one of the most serious complications after colorectal resections with primary anastomosis. Any factors that contribute to increase the risk of AL should be identified and - if possible - eliminated. Non-steroidal anti-inflammatory drugs (NSAIDs......) are often used for treating pain after surgical procedures, among these also colorectal resections. The objective of this Ph.d. thesis was to investigate whether the use of NSAIDs in the postoperative period increases the risk of AL, and investigate the effect on pathophysiological mechanisms. In order...

Anti-inflammatory effects and anti-oxidant capacity of Myrathius arboreus (Cecropiaceae) in experimental models.

Science.gov (United States)

Oluwole, Oluwafemi Gabriel; Ologe, Olufunmilayo; Alabi, Akinyinka; Tunde Yusuf, Ganiyu; Umukoro, Solomon

2017-11-27

Inflammation is involved in various diseases; search for safe treatments is warranted. Anti-inflammatory effects of ethanol extract of Myrathius arboreus (EEMa) were studied in carrageenan-induced model, formaldehyde sub-acute-induced model, and in 48 h lipopolysaccharide-induced air pouch model of inflammation. EEMa membrane-stabilizing activities and anti-oxidant capacity were determined in vitro. In the carrageenan model EEMa (125, 250, or 500 mg/kg), indomethacin (5 mg/kg), or vehicle 3 mL/kg was administered orally in rats (n=5). After 1 h, 0.1 mL of 1% carrageenan was injected into the right hind paw of rats. Change in edema sizes was measured for 3 h with plethysmometer. One-tenth milliliter (0.1 mL) of 2.5% formaldehyde was injected into the rat paw on the first day and the third day to induce sub-acute inflammation; changes in the edema sizes were determined, and percentages of inhibitions were calculated. Anti-inflammatory effects of EEMa were further examined in lipopolysaccharide (LPS)-induced air-pouch based on leukocytes count, volume of exudates, levels of malondialdehyde, glutathione, superoxide dismutase, nitric oxides, and tumor necrosis factor released into the inflammatory fluids. EEMa-free radicals scavenging activities were studied in DPPH and reducing power tests. Membrane-stabilizing activities of EEMa were evaluated in the red blood cell lysis induced by thermal and hypotonic solution. EEMa (250, 500 mg/kg) produced significant (p<0.001; p<0.05) inhibition of inflammation when compared with vehicle. Also, EEMa (250, 500, or 1000 μg/mL) significantly stabilized membrane and produced free radical scavenging activities. M. arboreus possesses anti-inflammatory and the anti-oxidant properties that might benefit translational medicine.

Evaluation of a bioceramic-based nanocomposite material for controlled delivery of a non-steroidal anti-inflammatory drug.

Science.gov (United States)

Hesaraki, S; Moztarzadeh, F; Nezafati, N

2009-12-01

In this study, nanocomposite of 50wt% calcium sulfate and 50wt% nanocrystalline apatite was produced and its biocompatibility, physical and structural properties were compared with pure calcium sulfate (CS) cement. Indomethacin (IM), a non-steroidal anti-inflammatory drug, was also loaded on both CS and nanocomposite cements and its in vitro release was evaluated over a period of time. The effect of the loaded IM on basic properties of the cements was also investigated. Biocompatibility tests showed a partial cytotoxicity in CS cement due to the reduced number of viable mouse fibroblast L929 cells in contact with the samples as well as spherical morphologies of the cells. However, no cytotoxic effect was observed for nanocomposite cement and no significant difference was found between the number of the cells seeded in contact with this specimens and culture plate as control. Other results showed that the setting time and injectability of the nanocomposite cement was much higher than those of CS cement, whereas reverse result obtained for compressive strength. In addition, incorporation of IM into compositions slightly increased the initial setting time and injectability of the cements and did not change their compressive strength. While a fast IM release was observed from CS cement in which about 97% of the loaded drug was released during 48h, nanocomposite cement showed a sustained release behavior in which 80% of the loaded IM was liberated after 144h. Thus, the nanocomposite can be a more appropriate carrier than CS for controlled release of IM in bone defect treatments.

Topical anti-inflammatory activity of Calea prunifolia HBK (Asteraceae) in the TPA model of mouse ear inflammation

International Nuclear Information System (INIS)

Gomez, Milton; Gil, Juan F.

2011-01-01

Phytochemical study of Calea prunifolia HBK identified two compounds derived from p-hydroxyacetophenone, the 1-(2-hydroxy-5-(1-methoxyethyl)phenyl)-3-methylbut-2.en-1-one showed a satisfactory anti-inflammatory activity (58.33%), when considering that this is a natural product. Although the two derived compounds are structurally similar, the anti-inflammatory activity of 1-(2-hydroxy-5-methoxyphenyl)-3-methylbut-2-en-1-one was not significant (2.08%). The test was conducted in a model of inflammation induced by topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) in the ear of mice. The positive control was tested with indomethacin and the negative control was done only with vehicle. These results allow the identification of a pharmacophore group that through molecular modeling studies and organic synthesis can result in compounds with improved anti-inflammatory activity. (author)

Topical anti-inflammatory activity of Calea prunifolia HBK (Asteraceae) in the TPA model of mouse ear inflammation

Energy Technology Data Exchange (ETDEWEB)

Gomez, Milton; Gil, Juan F., E-mail: miltongoba@uniquindio.edu.co [Grupo de Busqueda de Principios Bioactivos, Programa de Quimica, Universidad del Quindio, Armenia (Colombia)

2011-09-15

Phytochemical study of Calea prunifolia HBK identified two compounds derived from p-hydroxyacetophenone, the 1-(2-hydroxy-5-(1-methoxyethyl)phenyl)-3-methylbut-2.en-1-one showed a satisfactory anti-inflammatory activity (58.33%), when considering that this is a natural product. Although the two derived compounds are structurally similar, the anti-inflammatory activity of 1-(2-hydroxy-5-methoxyphenyl)-3-methylbut-2-en-1-one was not significant (2.08%). The test was conducted in a model of inflammation induced by topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) in the ear of mice. The positive control was tested with indomethacin and the negative control was done only with vehicle. These results allow the identification of a pharmacophore group that through molecular modeling studies and organic synthesis can result in compounds with improved anti-inflammatory activity. (author)

Potential Impact of Diet on Treatment Effect from Anti-TNF Drugs in Inflammatory Bowel Disease

DEFF Research Database (Denmark)

Andersen, Vibeke; Hansen, Axel Kornerup; Heitmann, Berit Lilienthal

2017-01-01

We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such invest...... inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in prospective observational, animal and interventional studies are warranted.......We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies......% CI: 1.73-4.31, p impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic...

Assessment of anti-inflammatory potential of Sesbania bispinosa ...

African Journals Online (AJOL)

Aim and objectives: Leaf extracts and fractions of S. bispinosa were evaluated for anti-inflammatory activity in mice using acute and chronic anti-inflammatory models with aspirin as a reference drug. Materials and methods: Methanol, chloroform and hexane were used to prepare leaf extracts by soxhlet extraction method, ...

Regression of sporadic intra-abdominal desmoid tumour following administration of non-steroidal anti-inflammatory drug

Directory of Open Access Journals (Sweden)

Fujiwara Yoshinori

2008-02-01

Full Text Available Abstract Background Desmoid tumours or fibromatoses are rare entities characterized by the benign proliferation of fibroblasts, which can be life-threatening due to their locally aggressive properties. Surgery is widely accepted as the first line of treatment for extra-abdominal desmoids; however, it is not recommended for intra-abdominal desmoids because of the high-risk of recurrence and difficulties with the operation. Here, we report on a patient with sporadic intra-abdominal desmoid tumours, who showed partial response following the intake of non-steroidal anti-inflammatory drugs. Case presentation A 73-year-old man presented with swelling and pain of the right leg. Computed tomography showed an abnormal multilocular soft-tissue mass (95 × 70 mm in the right pelvis, which was revealed by biopsy to be a desmoid tumour. Immunohistochemical analysis showed that the tumour cells expressed vimentin, but not smooth-muscle actin, CD34, or desmin. Very few Ki-67-positive cells were found. Non-cytotoxic treatment with etodolac (200 mg/day was chosen because of the patient's age, lack of bowel obstruction, and the likelihood of prostate cancer. Two years after the commencement of non-steroidal anti-inflammatory drug administration, computed tomography showed a decrease in tumour size (63 × 49 mm, and the disappearance of intratumoural septa. Conclusion Our case report suggests that non-steroidal anti-inflammatory drug treatment should be taken into consideration for use as first-line treatment in patients with sporadic intra-abdominal desmoid tumours.

Regression of sporadic intra-abdominal desmoid tumour following administration of non-steroidal anti-inflammatory drug

Science.gov (United States)

Tanaka, Keita; Yoshikawa, Reigetsu; Yanagi, Hidenori; Gega, Makoto; Fujiwara, Yoshinori; Hashimoto-Tamaoki, Tomoko; Hirota, Syozo; Tsujimura, Tohru; Tomita, Naohiro

2008-01-01

Background Desmoid tumours or fibromatoses are rare entities characterized by the benign proliferation of fibroblasts, which can be life-threatening due to their locally aggressive properties. Surgery is widely accepted as the first line of treatment for extra-abdominal desmoids; however, it is not recommended for intra-abdominal desmoids because of the high-risk of recurrence and difficulties with the operation. Here, we report on a patient with sporadic intra-abdominal desmoid tumours, who showed partial response following the intake of non-steroidal anti-inflammatory drugs. Case presentation A 73-year-old man presented with swelling and pain of the right leg. Computed tomography showed an abnormal multilocular soft-tissue mass (95 × 70 mm) in the right pelvis, which was revealed by biopsy to be a desmoid tumour. Immunohistochemical analysis showed that the tumour cells expressed vimentin, but not smooth-muscle actin, CD34, or desmin. Very few Ki-67-positive cells were found. Non-cytotoxic treatment with etodolac (200 mg/day) was chosen because of the patient's age, lack of bowel obstruction, and the likelihood of prostate cancer. Two years after the commencement of non-steroidal anti-inflammatory drug administration, computed tomography showed a decrease in tumour size (63 × 49 mm), and the disappearance of intratumoural septa. Conclusion Our case report suggests that non-steroidal anti-inflammatory drug treatment should be taken into consideration for use as first-line treatment in patients with sporadic intra-abdominal desmoid tumours. PMID:18257933

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.

Determination of residual nonsteroidal anti-inflammatory drugs in aqueous sample using magnetic nanoparticles modified with cetyltrimethylammonium bromide by high performance liquid chromatography.

Science.gov (United States)

Khoeini Sharifabadi, Malihe; Saber-Tehrani, Mohammad; Waqif Husain, Syed; Mehdinia, Ali; Aberoomand-Azar, Parviz

2014-01-01

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 (R (2) > 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.

Biotin-Pt (IV)-indomethacin hybrid: A targeting anticancer prodrug providing enhanced cancer cellular uptake and reversing cisplatin resistance.

Science.gov (United States)

Hu, Weiwei; Fang, Lei; Hua, Wuyang; Gou, Shaohua

2017-10-01

A Pt(IV) prodrug (2) composed of cancer-targeting biotin and nonsteroidal anti-inflammatory drug indomethacin in the axial positions of the six-coordinated octahedral geometry derived from cisplatin was developed, which could be highly accumulated in cancer cells more than normal ones and activated by endogenous reducing molecules to release cisplatin and indomethacin moieties simultaneously to inhibit tumor progression synergistically. In vitro assays revealed that 2 exhibited significantly selective inhibition to the tested cancer cell lines and sensitivity to cisplatin resistant cancer cells. Moreover, 2 presented cyclooxygenases inhibition properties to reduce tumor-associated inflammation, reduced the invasiveness of the highly aggressive PC-3 cells, and disrupted capillary-like tube formation in EA.hy926 cells. In all, this study offers a new strategy to enhance sensitivity and reduce toxicity of cisplatin. Copyright © 2017 Elsevier Inc. All rights reserved.

Morphine Suppository versus Indomethacin Suppository in the Management of Renal Colic: Randomized Clinical Trial

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Forough Zamanian

2016-01-01

Full Text Available Background. Renal colic is a medical emergency due to the rapid onset and devastating nature of its pain. Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs are both used as first-line choices in its management. Aim. This study aimed to compare the efficacy and safety of opioids and NSAIDs in the management of acute renal colic. Methods. One hundred and fifty-eight patients were divided into two groups (n=79 and received either 10 mg morphine or 100 mg indomethacin suppositories. The severity of pain was measured using verbal numeric rating scale at baseline and 20, 40, 60, and 90 minutes after the administration of analgesics. Drug side effects as well as patients’ vital signs were also recorded. Results. The mean decrease in the pain score during the first 20 minutes was significantly higher among those who received morphine suppository. However, no significant difference was observed between the two groups regarding the mean decrease in pain score during the first 40, 60, and 90 minutes after the admission. Prevalence of drug side effects or changes in the vital signs was not significantly different between the two groups. Conclusions. Morphine suppositories seem to be more efficient in achieving rapid pain relief comparing to indomethacin.

Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug

OpenAIRE

Dang, Tram T.; Thai, Anh V.; Cohen, Joshua; Slosberg, Jeremy E.; Siniakowicz, Karolina; Doloff, Joshua C.; Ma, Minglin; Hollister-Lock, Jennifer; Tang, Katherine M.; Gu, Zhen; Cheng, Hao; Weir, Gordon C.; Langer, Robert; Anderson, Daniel Griffith; Tang, Katherine

2013-01-01

Immuno-isolation of islets has the potential to enable the replacement of pancreatic function in diabetic patients. However, host response to the encapsulated islets frequently leads to fibrotic overgrowth with subsequent impairment of the transplanted grafts. Here, we identified and incorporated anti-inflammatory agents into islet-containing microcapsules to address this challenge. In vivo subcutaneous screening of 16 small molecule anti-inflammatory drugs was performed to identify promising...

Nonsteroidal anti-inflammatory drug use in patients with chronic kidney disease

OpenAIRE

Heleniak, Zbigniew; Cieplińska, Magdalena; Szychliński, Tomasz; Rychter, Dymitr; Jagodzińska, Kalina; Kłos, Alicja; Kuźmiuk, Izabela; Tylicka, Marzena Jakimowicz; Tylicki, Leszek; Rutkowski, Bolesław; Dębska-Ślizień, Alicja

2016-01-01

Aims Nonsteroidal anti-inflammatory drugs (NSAIDs) are the cornerstone of pain management. There are no detailed data on NSAIDs use in Poland, especially in patients with chronic kidney disease (CKD). The aim of this study was to evaluate the frequency, circumstances, and causes of NSAIDs use as well as knowledge of their side-effects in patients with CKD. Method This cross-sectional study was conducted in 972 individuals with CKD, enrolled in a written survey originally developed by the auth...

Diagnosis and Management of Gastroenteropathy Asssociated to Non-steroidal Anti-Inflammatory Drugs

Directory of Open Access Journals (Sweden)

Stella Ilone

2016-09-01

Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs is a group of drugs used to treat pain, inflammation, and fever. High consumption of NSAIDs associated with high gastrointestinal side effects. Common complaint from patients, which ranging from mild heartburn to the onset of gastrointestinal bleeding, often complicates the adequate administration of NSAIDs. Various methods have been developed to reduce the likelihood of gastroenteropathy complication. Early diagnosis, appropriate prompt treatment, as well as adequate monitoring will reduce morbidity and mortality from complications due to NSAIDs. This paper will discuss the diagnosis and management of gastro-enteropathy NSAID through approaching the underlying pathophysiology.

Use of nonsteroidal anti-inflammatory drugs and renal failure in nursing home residents-results of the study "Inappropriate Medication in Patients with Renal Insufficiency in Nursing Homes".

Science.gov (United States)

Dörks, Michael; Herget-Rosenthal, Stefan; Schmiemann, Guido; Hoffmann, Falk

2016-04-01

Use of potentially inappropriate medications may result in increased morbidity, mortality and resource utilisation. Due to polypharmacy and age-related decline in renal function the elderly population is at particular risk. Therefore, the Beers Criteria include use of nonsteroidal anti-inflammatory drugs in chronic renal failure stage 4 and 5 as these drugs may worsen renal function. According to the summary of product characteristics, the nonsteroidal anti-inflammatory drugs ibuprofen and diclofenac are contraindicated in these patients. Objective was to assess the extent of nonsteroidal anti-inflammatory drug use in nursing homes with a focus on residents with severe renal failure. Multi-centre cross-sectional study in 21 German nursing homes. The study population comprised residents for whom at least one serum creatinine value and information about sex were available, so that creatinine clearance rate could be estimated. In all, 685 of 852 residents were included as they fulfilled the abovementioned criteria. Renal failure was severe (estimated creatinine clearance rate renal failure (20.8 %). With one exception, all residents prescribed nonsteroidal anti-inflammatory drugs with severe renal failure were treated with at least one nonsteroidal anti-inflammatory drug that was contraindicated due to the underlying renal function. Notwithstanding their classification as potentially inappropriate medications and underlying contraindications, use of nonsteroidal anti-inflammatory drugs is common among nursing home residents with severe renal failure.

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

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Chang-Chuan Guo

2011-08-01

Full Text Available 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. Keywords: Protein binding, Non-steroidal anti-inflammatory drugs, Enantiomer, Stereoselectivity, Human serum albumin

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

OpenAIRE

Chalelgn Kassaw; Nasir Tajure Wabe

2012-01-01

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 pr...

A binding site for non-steroidal anti-inflammatory drugs in FAAH

Science.gov (United States)

Bertolacci, Laura; Romeo, Elisa; Veronesi, Marina; Magotti, Paola; Albani, Clara; Dionisi, Mauro; Lambruschini, Chiara; Scarpelli, Rita; Cavalli, Andrea; Vivo, Marco De; Piomelli, Daniele; Garau, Gianpiero

2013-01-01

In addition to inhibiting the cyclooxygenasemediated biosynthesis of prostanoids, various widely used non-steroidal anti-inflammatory drugs (NSAIDs) enhance endocannabinoid signaling by blocking the anandamidedegrading membrane enzyme, fatty acid amide hydrolase (FAAH). The X-ray structure of FAAH in complex with the NSAID carprofen, along with studies of site-directed mutagenesis, enzyme activity assays, and nuclear magnetic resonance, now reveal the molecular details of this interaction, providing information that may guide the design of dual FAAH-cyclooxygenase inhibitors with superior analgesic efficacy. PMID:23240907

Anti-inflammatory and Antihistaminic Study of a Unani Eye Drop Formulation.

Science.gov (United States)

Abdul, Latif; Abdul, Razique; Sukul, R R; Nazish, Siddiqui

2010-01-01

The Unani eye drop is an ophthalmic formulation prepared for its beneficial effects in the inflammatory and allergic conditions of the eyes. In the present study, the Unani eye drop formulation was prepared and investigated for its anti-inflammatory and antihistaminic activity, using in vivo and in vitro experimental models respectively. The Unani eye drop formulation exhibited significant anti-inflammatory activity in turpentine liniment-induced ocular inflammation in rabbits. The preparation also showed antihistaminic activity in isolated guinea-pig ileum. The anti-inflammatory and antihistaminic activity of eye drop may be due to presence of active ingredients in the formulation. Although there are many drugs in Unani repository which are mentioned in classical books or used in Unani clinical practice effectively in treatment of eye diseases by various Unani physicians. Inspite of the availability of vast literature, there is a dearth of commercial Unani ocular preparations. So, keeping this in mind, the eye drop formulation was prepared and its anti-inflammatory and antihistaminic activity was carried out in animal models. Thus, in view of the importance of alternative anti-inflammatory and antiallergic drugs, it becomes imperative to bring these indigenous drugs to the front foot and evaluate their activities.

Mechanism of inhibition of myeloperoxidase by anti-inflammatory drugs.

Science.gov (United States)

Kettle, A J; Winterbourn, C C

1991-05-15

Hypochlorous acid (HOCl) is the most powerful oxidant produced by human neutrophils, and should therefore be expected to contribute to the damage caused by these inflammatory cells. It is produced from H2O2 and Cl- by the heme enzyme myeloperoxidase (MPO). We used a H2O2-electrode to assess the ability of a variety of anti-inflammatory drugs to inhibit conversion of H2O2 to HOCl. Dapsone, mefenamic acid, sulfapyridine, quinacrine, primaquine and aminopyrine were potent inhibitors, giving 50% inhibition of the initial rate of H2O2 loss at concentrations of about 1 microM or less. Phenylbutazone, piroxicam, salicylate, olsalazine and sulfasalazine were also effective inhibitors. Spectral investigations showed that the inhibitors acted by promoting the formation of compound II, which is an inactive redox intermediate of MPO. Ascorbate reversed inhibition by reducing compound II back to the active enzyme. The characteristic properties that allowed the drugs to inhibit MPO reversibly were ascertained by determining the inhibitory capacity of related phenols and anilines. Inhibition increased as substituents on the aromatic ring became more electron withdrawing, until an optimum reduction potential was reached. Beyond this optimum, their inhibitory capacity declined. The best inhibitor was 4-bromoaniline which had an I50 of 45 nM. An optimum reduction potential enables inhibitors to reduce MPO to compound II, but prevents them from reducing compound II back to the active enzyme. Exploitation of this optimum reduction potential will help in targeting drugs against HOCl-dependent tissue damage.

Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety.

Science.gov (United States)

Roth, Sanford H

2011-01-01

Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID) therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy. Topical NSAID formulations deliver effective doses of analgesics directly to the affected joints, thereby limiting systemic exposure and potentially the risk of systemic adverse events, such as gastropathy and serious cardiovascular events. There are currently two topical NSAIDs approved by the US Food and Drug Administration for osteoarthritis-associated pain, as well as for the signs and symptoms of osteoarthritis. This review discusses the relative safety, and the gastrointestinal, cardiovascular, and renal risks of chronic oral or systemic NSAID therapy and topical NSAID formulations in patients with osteoarthritis.

No effect of one-year treatment with indomethacin on Alzheimer's disease progression: a randomized controlled trial.

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Daniëlle de Jong

2008-01-01

Full Text Available The objective of this study was to determine whether treatment with the nonselective nonsteroidal anti-inflammatory drug (NSAID indomethacin slows cognitive decline in patients with Alzheimer's disease (AD.This double-blind, randomized, placebo-controlled trial was conducted between May 2000 and September 2005 in two hospitals in the Netherlands. 51 patients with mild to moderate AD were enrolled into the study. Patients received 100 mg indomethacin or placebo daily for 12 months. Additionally, all patients received omeprazole. The primary outcome measure was the change from baseline after one year of treatment on the cognitive subscale of the AD Assessment Scale (ADAS-cog. Secondary outcome measures included the Mini-Mental State Examination, the Clinician's Interview Based Impression of Change with caregiver input, the noncognitive subscale of the ADAS, the Neuropsychiatric Inventory, and the Interview for Deterioration in Daily life in Dementia. Considerable recruitment problems of participants were encountered, leading to an underpowered study. In the placebo group, 19 out of 25 patients completed the study, and 19 out of 26 patients in the indomethacin group. The deterioration on the ADAS-cog was less in the indomethacin group (7.8+/-7.6, than in the placebo group (9.3+/-10.0. This difference (1.5 points; CI -4.5-7.5 was not statistically significant, and neither were any of the secondary outcome measures.The results of this study are inconclusive with respect to the hypothesis that indomethacin slows the progression of AD.

Anti-inflammatory and Antihistaminic Study of a Unani Eye Drop Formulation

Directory of Open Access Journals (Sweden)

Latif Abdul

2010-03-01

Full Text Available The Unani eye drop is an ophthalmic formulation prepared for its beneficial effects in the inflammatory and allergic conditions of the eyes. In the present study, the Unani eye drop formulation was prepared and investigated for its anti-inflammatory and antihistaminic activity, using in vivo and in vitro experimental models respectively. The Unani eye drop formulation exhibited significant anti-inflammatory activity in turpentine liniment-induced ocular inflammation in rabbits. The preparation also showed antihistaminic activity in isolated guinea-pig ileum. The anti-inflammatory and antihistaminic activity of eye drop may be due to presence of active ingredients in the formulation. Although there are many drugs in Unani repository which are mentioned in classical books or used in Unani clinical practice effectively in treatment of eye diseases by various Unani physicians. Inspite of the availability of vast literature, there is a dearth of commercial Unani ocular preparations. So, keeping this in mind, the eye drop formulation was prepared and its anti-inflammatory and antihistaminic activity was carried out in animal models. Thus, in view of the importance of alternative anti-inflammatory and anti- allergic drugs, it becomes imperative to bring these indigenous drugs to the front foot and evaluate their activities.

Synthesis of novel 1,2,3-triazole based benzoxazolinones: their TNF-α based molecular docking with in-vivo anti-inflammatory, antinociceptive activities and ulcerogenic risk evaluation.

Science.gov (United States)

Haider, Saqlain; Alam, M Sarwar; Hamid, Hinna; Shafi, Syed; Nargotra, Amit; Mahajan, Priya; Nazreen, Syed; Kalle, Arunasree M; Kharbanda, Chetna; Ali, Yakub; Alam, Aftab; Panda, Amulya K

2013-01-01

A library of novel bis-heterocycles containing benzoxazolinone based 1,2,3-triazoles has been synthesized using click chemistry approach. The compound 3f exhibited potent selective COX-2 inhibition of 59.48% in comparison to standard drug celecoxib (66.36% inhibition). The compound 3i showed significant (p < 0.001, 50.95%), TNF-α inhibitory activity as compared to indomethacin (p < 0.001, 64.01%). The results of the carrageenan induced hind paw oedema showed that compounds 3a, 3f, 3i, 3o, and 3e exhibited potent anti-inflammatory activity in comparison to Indomethacin. The molecular docking studies revealed that 3i exhibits strong inhibitory effect due to the extra stability of the complex because of an extra π-π bond. The histopathology report showed that none of the compounds caused gastric ulceration. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Uric acid ameliorates indomethacin-induced enteropathy in mice through its antioxidant activity.

Science.gov (United States)

Yasutake, Yuichi; Tomita, Kengo; Higashiyama, Masaaki; Furuhashi, Hirotaka; Shirakabe, Kazuhiko; Takajo, Takeshi; Maruta, Koji; Sato, Hirokazu; Narimatsu, Kazuyuki; Yoshikawa, Kenichi; Okada, Yoshikiyo; Kurihara, Chie; Watanabe, Chikako; Komoto, Shunsuke; Nagao, Shigeaki; Matsuo, Hirotaka; Miura, Soichiro; Hokari, Ryota

2017-11-01

Uric acid is excreted from blood into the intestinal lumen, yet the roles of uric acid in intestinal diseases remain to be elucidated. The study aimed to determine whether uric acid could reduce end points associated with nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy. A mouse model of NSAID-induced enteropathy was generated by administering indomethacin intraperitoneally to 8-week-old male C57BL/6 mice, and then vehicle or uric acid was administered orally. A group of mice treated with indomethacin was also concurrently administered inosinic acid, a uric acid precursor, and potassium oxonate, an inhibitor of uric acid metabolism, intraperitoneally. For in vitro analysis, Caco-2 cells treated with indomethacin were incubated in the presence or absence of uric acid. Oral administration of uric acid ameliorated NSAID-induced enteropathy in mice even though serum uric acid levels did not increase. Intraperitoneal administration of inosinic acid and potassium oxonate significantly elevated serum uric acid levels and ameliorated NSAID-induced enteropathy in mice. Both oral uric acid treatment and intraperitoneal treatment with inosinic acid and potassium oxonate significantly decreased lipid peroxidation in the ileum of mice with NSAID-induced enteropathy. Treatment with uric acid protected Caco-2 cells from indomethacin-induced oxidative stress, lipid peroxidation, and cytotoxicity. Uric acid within the intestinal lumen and in serum had a protective effect against NSAID-induced enteropathy in mice, through its antioxidant activity. Uric acid could be a promising therapeutic target for NSAID-induced enteropathy. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Non-steroidal anti-inflammatory drug use and risk of endometrial cancer

DEFF Research Database (Denmark)

Verdoodt, Freija; Friis, Søren; Dehlendorff, Christian

2016-01-01

OBJECTIVE: Non-steroidal anti-inflammatory drug (NSAID) use has been linked to a reduction in the risk of several cancer types. For endometrial cancer, however, results have been inconsistent. To summarize the available evidence on the risk of endometrial cancer associated with use of aspirin...... a random effects model. RESULTS: Six case-control and seven cohort studies were found eligible for our meta-analysis. We observed risk reductions in endometrial cancer associated with regular use of aspirin (case-control: 11%, cohort: 8%) and NA-NSAIDs (case-control: 9%, cohort: 6%), compared to non...

Hemostimulating efficiency of non-steroid anti-inflammatory drugs under modified irradiation conditions

International Nuclear Information System (INIS)

Zhvoronkov, L.P.; Sklobovskaya, I.Eh.

1988-01-01

Non-steroid anti-inflammatory drugs (NSAID) were found to have hemostimulating effect in mice after irradiation. This effect was rather definite under irradiation conditions modified by dose fractioning or radioprotective chemicals. NSAID application during fractionated irradiation with midlethal integral dose leads to almost complete recovery of bone marrow hemopoiesis by the 9th day of radiation illness. NSAID usage combined with chemical radioprotectors provides effective hemopoiesis stimulation leading to survival increase in animals, irradiated with absolutely lethal doses. (author)

Rectally administered indomethacin to prevent post-ESWL-pancreatitis (RIPEP): study protocol for a randomized controlled trial.

Science.gov (United States)

Qian, Yang-Yang; Chen, Hui; Tang, Xin-Ying; Jiang, Xi; Qian, Wei; Zou, Wen-Bin; Xin, Lei; Li, Bo; Qi, Yan-Fen; Hu, Liang-Hao; Zou, Duo-Wu; Jin, Zhen-Dong; Wang, Dong; Du, Yi-Qi; Wang, Luo-Wei; Liu, Feng; Li, Zhao-Shen; Liao, Zhuan

2017-11-02

Pancreatic extracorporeal shock wave lithotripsy (P-ESWL) is the first-line therapy for large pancreatic duct stones. Although it is a highly effective and safe procedure for the fragmentation of pancreatic stones, it is still not complication-free. Just like endoscopic retrograde cholangiopancreatography (ERCP), pancreatitis is the most common complication. To date, nonsteroidal anti-inflammatory drugs (NSAIDs) have proven to be the only effective prophylactic medication for post-ERCP pancreatitis and the European, American and Japanese Society for Gastrointestinal Endoscopy guidelines have recommended prophylactic rectally administered indomethacin for all patients undergoing ERCP. Given the little research about effective prevention for post P-ESWL pancreatitis, we aim to determine whether rectally administered indomethacin can reduce post-ESWL-pancreatitis. The RIPEP study is a prospective, randomized, double-blinded, placebo-controlled trial. One thousand three hundred and seventy patients with chronic pancreatitis and pancreatic stones (>5 mm in diameter) treated with P-ESWL at Changhai Hospital will be randomly allocated to rectally administered indomethacin or placebo therapy before the procedure. The primary endpoint is the incidence of post-ESWL pancreatitis. Secondary endpoints include the severity of pancreatitis, occurrence rate of asymptomatic hyperamylasemia and other complications. The RIPEP trial is designed to show that rectally administered indomethacin reduces the development and severity of post-ESWL pancreatitis and benefits patients treated with P-ESWL. ClinicalTrials.gov, ID: NCT02797067 . Registered on 17 November 2016.

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...

Anti-inflammatory and Antihistaminic Study of a Unani Eye Drop Formulation

Directory of Open Access Journals (Sweden)

Latif Abdul

2010-01-01

Full Text Available The Unani eye drop is an ophthalmic formulation prepared for its beneficial effects in the inflammatory and allergic conditions of the eyes. In the present study, the Unani eye drop formulation was prepared and investigated for its anti-inflammatory and antihistaminic activity, using in vivo and in vitro experimental models respectively. The Unani eye drop formulation exhibited significant anti-inflammatory activity in turpentine liniment-induced ocular inflammation in rabbits. The preparation also showed antihistaminic activity in isolated guinea-pig ileum. The anti-inflammatory and antihistaminic activity of eye drop may be due to presence of active ingredients in the formulation. Although there are many drugs in Unani repository which are mentioned in classical books or used in Unani clinical practice effectively in treatment of eye diseases by various Unani physicians. Inspite of the availability of vast literature, there is a dearth of commercial Unani ocular preparations. So, keeping this in mind, the eye drop formulation was prepared and its anti-inflammatory and antihistaminic activity was carried out in animal models. Thus, in view of the importance of alternative anti-inflammatory and antiallergic drugs, it becomes imperative to bring these indigenous drugs to the front foot and evaluate their activities.

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

Antinociceptive and anti-inflammatory kaempferol glycosides from Sedum dendroideum.

Science.gov (United States)

De Melo, Giany O; Malvar, David do C; Vanderlinde, Frederico A; Rocha, Fabio F; Pires, Priscila Andrade; Costa, Elson A; de Matos, Lécia G; Kaiser, Carlos R; Costa, Sônia S

2009-07-15

To identify the compounds responsible for the antinociceptive and anti-inflammatory effects previously described for Sedum dendroideum, through bioassay-guided fractionation procedures. Antinociceptive activity was evaluated through mouse acetic acid-induced writhing model. The anti-inflammatory activity was assessed through croton oil-induced mouse ear oedema and carrageenan-induced peritonitis. The Sedum dendroideum juice afforded seven known flavonoids identified with basis on NMR data. The oral administration of the major kaempferol glycosides kaempferitrin [1] (17.29 micromol/kg), kaempferol 3-O-beta-glucopyranoside-7-O-alpha-rhamnopyranoside [2] (16.82 micromol/kg), kaempferol 3-O-neohesperidoside-7-O-alpha-rhamnopyranoside [3] (13.50 micromol/kg) or alpha-rhamnoisorobin [5] (23.13 micromol/kg) inhibited by 47.3%, 25.7%, 60.2% and 58.0%, respectively, the acetic acid-induced nociception (indomethacin: 27.95 micromol/kg, p.o.; 68.9%). Flavonoids 1, 2, 3 or 5, at the same doses, reduced by 39.5%, 46.5%, 35.6% and 33.3%, respectively, the croton oil-induced oedema (dexamethasone: 5.09 micromol/kg, s.c.; 83.7%) and impaired leukocyte migration by 42.9%, 46.3%, 50.4% and 49.6%, respectively (dexamethasone: 5.09 micromol/kg, s.c.; 66.1%). Our findings show that the major kaempferol glycosides may account for the renowned medicinal use of Sedum dendroideum against pain and inflammatory troubles.

Is there a future for andrographolide to be an anti-inflammatory drug? Deciphering its major mechanisms of action.

Science.gov (United States)

Tan, W S Daniel; Liao, Wupeng; Zhou, Shuo; Wong, W S Fred

2017-09-01

Andrographis paniculata has long been part of the traditional herbal medicine system in Asia and in Scandinavia. Andrographolide was isolated as a major bioactive constituent of A. paniculata in 1951, and since 1984, andrographolide and its analogs have been scrutinized with modern drug discovery approach for anti-inflammatory properties. With this accumulated wealth of pre-clinical data, it is imperative to review and consolidate different sources of information, to decipher the major anti-inflammatory mechanisms of action in inflammatory diseases, and to provide direction for future studies. Andrographolide and its analogs have been shown to provide anti-inflammatory benefits in a variety of inflammatory disease models. Among the diverse signaling pathways investigated, inhibition of NF-κB activity is the prevailing anti-inflammatory mechanism elicited by andrographolide. There is also increasing evidence supporting endogenous antioxidant defense enhancement by andrographolide through Nrf2 activation. However, the exact pathway leading to NF-κB and Nrf2 activation by andrographolide has yet to be elucidated. Validation and consensus on the major mechanistic actions of andrographolide in different inflammatory conditions are required before translating current findings into clinical settings. There are a few clinical trials conducted using andrographolide in fixed combination formulation which have shown anti-inflammatory benefits and good safety profile. A concerted effort is definitely needed to identify potent andrographolide lead compounds with improved pharmacokinetics and toxicological properties. Taken together, andrographolide and its analogs have great potential to be the next new class of anti-inflammatory agents, and more andrographolide molecules are likely moving towards clinical study stage in the near future. Copyright © 2017 Elsevier Inc. All rights reserved.

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

2017-01-01

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...

Sub-chronic indomethacin treatment and its effect on the male reproductive system of albino rats: possible protective role of black tea extract.

Science.gov (United States)

Bagoji, Ishwar B; Hadimani, Gavishiddappa A; Yendigeri, Saeed M; Das, Kusal K

2017-05-01

Indomethacin is commonly used as a nonsteroidal anti-inflammatory drug (NSAID) to treat inflammation, arthritis and joint pains. Unfortunately, it has a wide range of adverse effects on the physiological system, including gonads. This study aimed to assess possible beneficial effects of black tea extract (BTE) against indomethacin-induced alteration of gonadal hormone levels in male rats. Adult male rats were divided into Group I (control), Group II (indomethacin, 5 mg/kg body weight [bwt.]; i.p., 21 days), Group III (BTE, 2.5 g tea leaf/dL of water, i.e. 2.5% of aqueous BTE, orally, 21 days) and Group IV (indomethacin+BTE, 21 days). Sperm count and motility, serum luteinising hormone (LH), follicle-stimulating hormone (FSH) and testosterone, along with histopathology of testes were studied. One-way ANOVA, followed by post-hoc t-test were conducted. Indomethacin-treated rats showed significant decrease in testicular weight, sperm count, sperm motility, serum gonadotropins and testosterone concentrations. Histopathology of the testes showed tortuous and distorted seminiferous tubules, marked thickening of the tubular basement membrane, reduced spermatogenesis process (>30%) and marked decrease in the number of interstitial cells of Leydig in indomethacin-treated rats. Interestingly, rats supplemented with BTE showed remarkable improvements in testicular weight gain, sperm count and motility, serum gonadotropins and testosterone concentrations, along with testicular histopathology. The results suggest that BTE might have potential ameliorative effects against sub-chronic indomethacin-induced alteration of gonadal hormone levels in male albino rats.

Assessment of topical non-steroidal anti-inflammatory drugs in animal models.

Science.gov (United States)

Hiramatsu, Y; Akita, S; Salamin, P A; Maier, R

1990-10-01

Four commercial gel preparations of topical anti-inflammatory agents have been assessed in six animal models commonly used to determine the biological activity of non-steroidal anti-inflammatory agents for systemic administration. Only UV-induced erythema of the skin, adjuvant induced arthritis and the measurement of vascular permeability proved suitable for differentiation of the potency of the four topical agents. Carrageenin-induced paw oedema, the cotton pellet test and the assessment of the pain threshold according to Randall and Selitto were of little value. The effects of the gel preparation of diclofenac (CAS 15307-86-5) diethylammonium (Voltaren Emulgel) were comparable to two preparations containing 1% and 5% active ingredient, respectively. Gel 4 showed low overall activity. The experiments demonstrated that some of the models used for the assessment of anti-inflammatory agent for systemic administration proved suitable for the testing of topical preparations and that percutaneous absorption was insufficient to elicit anti-inflammatory effect in the animals at sites remote from the site of application.

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

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...

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

Science.gov (United States)

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

1987-01-01

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

Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis

Science.gov (United States)

Chmiel, James F.; Konstan, Michael W.; Elborn, J. Stuart

2013-01-01

Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from 38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed. PMID:23880054

A Novel Tetrasubstituted Imidazole as a Prototype for the Development of Anti-inflammatory Drugs.

Science.gov (United States)

Nascimento, Marcus Vinicius P S; Munhoz, Antonio C M; Theindl, Lais C; Mohr, Eduarda Talita B; Saleh, Najla; Parisotto, Eduardo B; Rossa, Thaís A; Zamoner, Ariane; Creczynski-Pasa, Tania B; Filippin-Monteiro, Fabíola B; Sá, Marcus M; Dalmarco, Eduardo Monguilhott

2018-04-14

Although inflammation is a biological phenomenon that exists to protect the host against infections and/or related problems, its unceasing activation results in the aggravation of several medical conditions. Imidazoles, whether natural or synthetic, are molecules related to a broad spectrum of biological effects, including anti-inflammatory properties. In this study, we screened eight novel small molecules of the imidazole class synthesized by our research group for their in vitro anti-inflammatory activity. The effect of the selected molecules was confirmed in an in vivo inflammatory model. We also analyzed whether the effects were caused by inhibition of nuclear factor kappa B (NF-κB) transcription factor transmigration. Of the eight imidazoles tested, methyl 1-allyl-2-(4-fluorophenyl)-5-phenyl-1H-imidazole-4-acetate (8) inhibited nitric oxide metabolites and pro-inflammatory cytokine (TNF-α, IL-6, and IL-1β) secretion in J774 macrophages stimulated with LPS. It also attenuated leukocyte migration and exudate formation in the pleural cavity of mice challenged with carrageenan. Furthermore, imidazole 8 reverted the oxidative stress pattern triggered by carrageenan in the pleural cavity by diminishing myeloperoxidase, superoxide dismutase, catalase, and glutathione S-transferase activities and reducing the production of nitric oxide metabolites and thiobarbituric acid-reactive substances. Finally, these effects can be attributed, at least in part, to the ability of this compound to prevent NF-κB transmigration. In this context, our results demonstrate that imidazole 8 has promising potential as a prototype for the development of a new anti-inflammatory drug to treat inflammatory conditions in which NF-κB and oxidative stress play a prominent role. Graphical Abstract ᅟ.

Conservative Secondary Shell Substitution In Cyclooxygenase-2 Reduces Inhibition by Indomethacin Amides and Esters via Altered Enzyme Dynamics

Science.gov (United States)

2015-01-01

The cyclooxygenase enzymes (COX-1 and COX-2) are the therapeutic targets of nonsteroidal anti-inflammatory drugs (NSAIDs). Neutralization of the carboxylic acid moiety of the NSAID indomethacin to an ester or amide functionality confers COX-2 selectivity, but the molecular basis for this selectivity has not been completely revealed through mutagenesis studies and/or X-ray crystallographic attempts. We expressed and assayed a number of divergent secondary shell COX-2 active site mutants and found that a COX-2 to COX-1 change at position 472 (Leu in COX-2, Met in COX-1) reduced the potency of enzyme inhibition by a series of COX-2-selective indomethacin amides and esters. In contrast, the potencies of indomethacin, arylacetic acid, propionic acid, and COX-2-selective diarylheterocycle inhibitors were either unaffected or only mildly affected by this mutation. Molecular dynamics simulations revealed identical equilibrium enzyme structures around residue 472; however, calculations indicated that the L472M mutation impacted local low-frequency dynamical COX constriction site motions by stabilizing the active site entrance and slowing constriction site dynamics. Kinetic analysis of inhibitor binding is consistent with the computational findings. PMID:26704937

Effects of indomethacin suppositories on serum amylase, inflammatory factors and immune function after endoscopic retrograde cholangiopancreatography

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Xiao-Bin Peng

2016-10-01

Full Text Available Objective: To explore the effects of indomethacin suppositories on serum amylase, inflammatory factors and immune function after endoscopic retrograde cholangiopancreatography (ERCP. Methods: A total of 85 patients with common bile duct stones or obstructive jaundice were divided into the observation group (n=45 and the control group (n=40 according to the different treatment methods, both two groups patients were treated with ERCP, patients in the observation group was given indomethacin suppositories 50 mg preoperative 30 min. Serum amylase, inflammatory factors and T cell subsets were detected preoperative, postoperative 6 h and postoperative 24 h. Inflammatory factors including interleukin -10 (IL-10, interleukin -6 (IL-6, tumor necrosis factor alpha (TNF-α and interleukin-4 (IL-4. T cell subsets including CD3+ , CD4+ , CD8+ and calculated CD4+ / CD8+ . Results: In both two groups, postoperative 6 h, 24 h serum amylase were significantly higher than before surgery; in the observation group, the postoperative 6 h, 24 h serum amylase were significantly lower than in the control group at the same time point and the differences were statistically significant (P<0.05. Both two groups’ postoperative 6 h, 24 h serum proinflammatory factor IL-6 and TNF-α increased first and then decreased, both were significantly higher than before surgery; both two groups’ postoperative 6 h, 24 h serum anti-inflammatory factor IL-10 and IL-4 gradually increased, both were significantly higher than before surgery, and the differences were statistically significant (P<0.05; In the observation group, antiinflammatory factor IL-10 and IL-4 significantly increased while pro-inflammatory factor IL-6 and TNF-α significantly decreased compared with the control group at the same time point 6 h and 24 h after surgery, the difference between the two groups was statistically significant (P<0.05. Both two groups’ postoperative 6 h, 24 h T cell subsets CD3+ , CD4+ , CD4

Long-Term Safety of In Utero Exposure to Anti-TNFα Drugs for the Treatment of Inflammatory Bowel Disease

DEFF Research Database (Denmark)

Chaparro, M; Verreth, A; Lobaton, T

2018-01-01

OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs...... in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non......-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox...

Indomethacin induced gastropathy in CD18, intercellular adhesion molecule 1, or P-selectin deficient mice

Science.gov (United States)

Morise, Z; Granger, D; Fuseler, J; Anderson, D; Grisham, M

1999-01-01

BACKGROUND—Neutrophil-endothelial cell interactions are thought to play a critical role in the pathophysiology of non-steroidal anti-inflammatory drug (NSAID) induced gastropathy.
AIMS—To optimise a mouse model of NSAID induced gastropathy and to evaluate the importance of adhesion molecules using adhesion molecule deficient mice.
METHODS—Gastropathy was induced in C57BL/6 mice or their adhesion molecule deficient counterparts via oral administration of indomethacin (20 mg/kg). Lesion scores, mucosal permeability, and histopathology were used to assess gastric mucosal injury.
RESULTS—Intragastric administration of indomethacin induced linear haemorrhagic mucosal lesions, primarily in the corpus of the stomach that were first observed at six hours. These lesions continued to develop over the next six hours with maximal lesion scores and mucosal permeabilities at 12 hours. When indomethacin was administered to mice deficient in CD18, intercellular adhesion molecule 1 (ICAM-1), or P-selectin, there were significant decreases in lesion scores compared with their C57BL/6 controls. In addition, mucosal permeabilities were found to be significantly lower in CD18 or ICAM-1 deficient mice observed at 12 hours.
CONCLUSION—Certain leucocyte and endothelial cell adhesion molecules are important determinants for full expression of indomethacin induced gastropathy. It is proposed that this modification of the mouse model may be useful for the investigation of other pathophysiological mechanisms of NSAID induced gastropathy.


Keywords: indomethacin; gastropathy; cyclooxygenase; intercellular adhesion molecule; VCAM; vascular cell adhesion molecule; P-selectin PMID:10486359

The hidden mechanism beyond ginger (Zingiber officinale Rosc.) potent in vivo and in vitro anti-inflammatory activity.

Science.gov (United States)

Ezzat, Shahira M; Ezzat, Marwa I; Okba, Mona M; Menze, Esther T; Abdel-Naim, Ashraf B

2018-03-25

Ginger (Zingiber officinale Roscoe) is a well known anti-inflammatory drug in the Egyptian, Indian and Chinese folk medicines, yet its mechanism of action is unclear. To explore its mechanism of action and to correlate it to its biophytochemicals. Various extracts viz. water, 50%, 70%, 80%, and 90% ethanol were prepared from ginger rhizomes. Fractionation of the aqueous extract (AE) was accomplished using Diaion HP-20. In vitro anti-inflammatory activity of the different extracts and isolated compounds was evaluated using protein denaturation inhibition, membrane stabilization, protease inhibition, and anti-lipoxygenase assays. In vivo anti-inflammatory activity of AE was estimated using carrageenan-induced rat paw edema in rats at doses 25, 50, 100 and 200mg/kg b.wt. All the tested extracts showed significant (p< 0.1) in vitro anti-inflammatory activities. The strongest anti-lipoxygenase activity was observed for AE that was more significant than that of diclofenac (58% and 52%, respectively) at the same concentration (125μg/ml). Purification of AE led to the isolation of 6-poradol (G1), 6-shogaol (G2); methyl 6- gingerol (G3), 5-gingerol (G4), 6-gingerol (G5), 8-gingerol (G6), 10-gingerol (G7), and 1-dehydro-6-gingerol (G8). G1, G2 and G8 exhibited potent activity in all the studied assays, while G4 and G5 exhibited moderate activity. In vivo administration of AE ameliorated rat paw edema in a dose-dependent manner. AE (at 200mg/kg) showed significant reduction in production of PGE2, TNF-α, IL-6, monocyte chemoattractant protein-1 (MCP-1), regulated upon activation, normal T-cell expressed and secreted (RANTES), myeloperoxidase (MPO) activity by 60%, 57%, 60%, 41%, 32% and 67%, respectively. AE at 100 and 200mg/kg was equipotent to indomethacin in reduction of NO x level and in increasing the total antioxidant capacity (TAC). Histopathological examination revealed very few inflammatory cells infiltration and edema after administration of AE (200mg/kg) prior to

Compensatory Cellular Reactions to Nonsteroidal Anti-Inflammatory Drugs on Osteogenic Differentiation in Canine Bone Marrow-Derived Mesenchymal Stem Cells

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OH, Namgil; KIM, Sangho; HOSOYA, Kenji; OKUMURA, Masahiro

2014-01-01

ABSTRACT The suppressive effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the bone healing process have remained controversial, since no clinical data have clearly shown the relationship between NSAIDs and bone healing. The aim of this study was to assess the compensatory response of canine bone marrow-derived mesenchymal stem cells (BMSCs) to several classes of NSAIDs, including carprofen, meloxicam, indomethacin and robenacoxib, on osteogenic differentiation. Each of the NSAIDs (10 µM) was administered during 20 days of the osteogenic process with human recombinant IL-1β (1 ng/ml) as an inflammatory stimulator. Gene expression of osteoblast differentiation markers (alkaline phosphatase and osteocalcin), receptors of PGE2 (EP2 and EP4) and enzymes for prostaglandin (PG) E2 synthesis (COX-1, COX-2, cPGES and mPGES-1) was measured by using quantitative reverse transcription-polymerase chain reaction. Protein production levels of alkaline phosphatase, osteocalcin and PGE2 were quantified using an alkaline phosphatase activity assay, osteocalcin immunoassay and PGE2 immunoassay, respectively. Histologic analysis was performed using alkaline phosphatase staining, von Kossa staining and alizarin red staining. Alkaline phosphatase and calcium deposition were suppressed by all NSAIDs. However, osteocalcin production showed no significant suppression by NSAIDs. Gene expression levels of PGE2-related receptors and enzymes were upregulated during continuous treatment with NSAIDs, while certain channels for PGE2 synthesis were utilized differently depending on the kind of NSAIDs. These data suggest that canine BMSCs have a compensatory mechanism to restore PGE2 synthesis, which would be an intrinsic regulator to maintain differentiation of osteoblasts under NSAID treatment. PMID:24419976

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

Prevention of nonsteroidal anti-inflammatory drug-induced gastropathy.

Science.gov (United States)

Schlansky, Barry; Hwang, Joo Ha

2009-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their analgesic, antipyretic, and antiinflammatory properties, and aspirin is increasingly employed in the primary and secondary prevention of cardiovascular disease and ischemic stroke. Despite undisputed therapeutic efficacy for these indications, all NSAIDs impart a considerable risk of peptic ulcer disease and upper gastrointestinal hemorrhage. A growing body of evidence supports an association between non-aspirin NSAIDs and acute coronary syndromes, and an expanding understanding of the gastroduodenal effects of aspirin, COX-2 selective agents, clopidogrel, and Helicobacter pylori synergism fuel controversies in NSAID use. In this review, we discuss risk stratification of patients taking NSAIDs and the appropriate application of proven gastro-protective strategies to decrease the incidence of gastrointestinal hemorrhage based upon an individualized assessment of risk for potential toxicities. Prevention of NSAID-related gastropathy is an important clinical issue, and therapeutic strategies for both the primary and secondary prevention of adverse events are continually evolving.

Different activities of Schinus areira L.: anti-inflammatory or pro-inflammatory effect.

Science.gov (United States)

Davicino, R; Mattar, A; Casali, Y; Anesini, C; Micalizzi, B

2010-12-01

The anti-inflammatory drugs possess many serious side effects at doses commonly prescribed. It is really important to discover novel regulators of inflammation from natural sources with minimal adverse effects. Schinus areira L. is a plant native from South America and is used in folk medicine as an anti-inflammatory herb. For this study, the activity of aqueous extracts on inflammation and the effect on superoxide anion production in mice macrophages were assayed. Aqueous extracts were prepared by soaking herbs in cold water (cold extract), boiling water (infusion), and simmering water (decoction). Cold extract possess an anti-inflammatory activity. Decoction and infusion showed pro-inflammatory activity. Cold extract increased the production of superoxide anion. It has been proposed to use diverse methods to obtain extracts of S. areira L. with different effects. Cold extract, decoction, and infusion could be utilized as extracts or as pharmacological preparations for topical application.

The impact of non-steroidal anti-inflammatory drugs on the small intestinal epithelium

OpenAIRE

Handa, Osamu; Naito, Yuji; Fukui, Akifumi; Omatsu, Tatsushi; Yoshikawa, Toshikazu

2013-01-01

The small intestine has been called as a dark continent of digestive tract and it had been very difficult to diagnose or treat the disease of small intestine. However recent technological development including video capsule endoscopy or balloon-assisted endoscopy has made us to aware the various diseases of small intestine. By using capsule endoscopy, many researchers reported that more than 70% of patients treated continuously with non-steroidal anti-inflammatory drugs (NSAID) exhibit the mu...

Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease.

Science.gov (United States)

Bornebroek, Marjolijn; de Lau, Lonneke M L; Haag, Mendel D M; Koudstaal, Peter J; Hofman, Albert; Stricker, Bruno H C; Breteler, Monique M B

2007-01-01

Several lines of evidence suggest a role of inflammatory processes in Parkinson disease, although it is still unclear whether inflammation is a cause or rather a consequence of neurodegeneration. In a prospective population-based cohort study among 6,512 participants aged >or=55 years, with repeated in-person examination, we evaluated the association between cumulative use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of Parkinson disease. Complete information on filled prescriptions was available from automated pharmacy records. Data were analyzed by means of Cox proportional hazards regression analysis, adjusted for age, sex, smoking habits and coffee consumption. After an average 9.4 years of follow-up, 88 new cases of Parkinson disease were detected. No association was found between use of NSAIDs and the risk of Parkinson disease (adjusted hazard ratio for any NSAID use, 1.50; 95% confidence interval, 0.95-2.37). Our findings do not support the hypothesis that NSAIDs might decrease the risk of Parkinson disease. (c) 2007 S. Karger AG, Basel.

Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs: risks versus benefits.

Science.gov (United States)

Gwee, Kok Ann; Goh, Vernadine; Lima, Graca; Setia, Sajita

2018-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are often coadministered with proton-pump inhibitors (PPIs) to reduce NSAID-induced gastrointestinal (GI) adverse events. This coadministration is generally regarded as safe, and is included in many of the guidelines on NSAID prescription. However, recent evidence indicates that the GI risks associated with NSAIDs can be potentiated when they are combined with PPIs. This review discusses the GI effects and complications of NSAIDs and how PPIs may potentiate these effects, options for prevention of GI side effects, and appropriate use of PPIs in combination with NSAIDs.

Apple Polyphenol Suppresses Indomethacin-Induced Gastric Damage in Experimental Animals by Lowering Oxidative Stress Status and Modulating the MAPK Signaling Pathway.

Science.gov (United States)

Lee, Yi-Chen; Cheng, Chun-Wen; Lee, Huei-Jane; Chu, Huei-Chuien

2017-11-01

Indomethacin is a nonsteroid anti-inflammatory drug (NSAID) that is used to alleviate pain and inflammation in clinical medicine. Previous studies indicated that NSAIDs can cause gastrointestinal mucosal complications, and it is associated with mucosal lipid peroxidation and oxidative damage. Based on the evidences, decreasing oxidative stress may be an ideal therapeutic strategy for preventing gastrointestinal ulcer. Apple (Rosaceae Malus sp.) is one of the most commonly consumed fruits worldwide. The abundant polyphenolic constituents have received increasing attention for decades. In both in vivo and in vitro studies, the reports showed that apple polyphenol (AP) seems to provide an indirect antioxidant protection by activating cellular antioxidant enzymes to defend against oxidative stress. To address this issue and develop AP into a healthy improvement supplement, we studied the effect and potential mechanisms of AP in indomethacin-treated animal. The results showed AP can decelerate the gastric lesion, significantly suppress lipid peroxidation, increase the level of glutathione and the activity of catalase, and regulate the MAPK signaling proteins. These findings imply that AP protects the gastric mucosa from indomethacin-caused lesions and the protection is at least partially attributable to its antioxidative properties. This alternative medical function of AP may be a safe and effective intervention for preventing indomethacin-induced gastric complications.

PRESCRIBING TRENDS OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS IN A TERTIARY CARE HOSPITAL IN THE MIDDLE ANATOLIA

OpenAIRE

Elif Borekci

2017-01-01

Background: Non-steroidal anti-inflammatory (NSAI) drugs are widely used for their analgesic, antipyretic and antiinflammatory effects. The aim of this study is to evaluate the prescribing trends of NSAI drugs among the doctors working the outpatients clinics in our hospital. Materials and methods: Questionnaires consisting of 10 questions related to analgesic and NSAI drug preferences were applied to the doctors working the medical and surgery outpatient clinics in a tertiary care hospita...

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.

Gelatin-carboxymethyl tamarind gum biocomposites: In vitro characterization & anti-inflammatory pharmacodynamics

Energy Technology Data Exchange (ETDEWEB)

Jana, Sougata, E-mail: janapharmacy@rediffmail.com; Banerjee, Abhisek; Sen, Kalyan Kumar; Maiti, Sabyasachi

2016-12-01

In this study, gelatin and carboxymethyl tamarind gum (CTG) were chemically cross-linked to control the delivery of aceclofenac from their interpenetrating network (IPNs). Infrared spectra, thermal and X-ray data supported that drug and polymer was compatible in the composite hydrogels. Irregularly shaped IPN microstructures were seen under field emission scanning electron microscope (FE-SEM). IPN system was capable of entrapping about 96% of the drug fed. CTG in IPN structures suppressed the drug release rate in HCl solution (pH 1.2); however extended the same in phosphate buffer solution (pH 6.8). The drug release was controlled by polymer chain relaxation/swelling and simple diffusion in vitro. The anti-inflammatory activity of drug-loaded biocomposites lasted over 7 h in albino rats, thus suggesting their potential as an anti-inflammatory therapeutics. - Highlights: • Novel gelatin-carboxymethyl tamarind gum biocomposites was synthesized. • FTIR, thermal and X-ray study ensured compatibility between drug and polymers. • FE-SEM image revealed irregular shape of the IPN microstructures. • In vivo anti-inflammatory pharmacodynamics in rat model was encouraging.

Anti-Helicobacter pylori and antiulcerogenic activity of Aframomum pruinosum seeds on indomethacin-induced gastric ulcer in rats.

Science.gov (United States)

Kouitcheu Mabeku, Laure Brigitte; Nanfack Nana, Blandine; Eyoum Bille, Bertrand; Tchuenteu Tchuenguem, Roland; Nguepi, Eveline

2017-12-01

Peptic ulcer is one of the most common diseases affecting mankind. Although there are many products used for its treatment, most of these products produce severe adverse reactions requiring the search for novel compounds. Some Afromomum species are used traditionally to cure acute gastritis. To evaluate the antiulcer activity of the methanol extract of Aframomum pruinosum Gagnepain (Zingiberaceae) seeds against two major etiologic agents of peptic ulcer disease; Helicobacter pylori and non-steroidal anti-inflammatory drugs. The anti-Helicobacter activity of A. pruinosum was evaluated using the broth microdilution method. After oral administration of indomethacin (5 mg/kg) for 5 consecutive days, gastric ulcerated animals were divided into control group and five other groups: three groups that recieved respectively 125, 250 and 500 mg/kg of plant extract, the fourth group received Maalox (50 mg/kg) and the fifth group, Misoprostol (100 μg/kg), respectively, for 5 days. Ulcer areas, gastric mucus content and nitric oxide gastric levels of animals were assessed 24 h after this treatment. A. pruinosum extract shows a moderate anti-Helicobacter activity with an MIC value of 128 μg/mL. A. pruinosum extract, like Misoprostol and Maalox, markedly reduces the % of ulcerated area from 8.15 ± 0.33 to 1.71 ± 0.44% (500 mg/kg). It also increased significantly mucus and NO gastric production with respective values of 4.44 ± 1.35 and 965.81 ± 106.74 μmol/g (500 mg/kg). These findings suggest that A. pruinosum methanol extract possesses antiulcer properties as ascertained by the comparative decreases in ulcer areas, increase of mucus and NO gastric production.

[Indomethacin (indocollyre) versus diclofenac (voltarene) for the control of pain following excimer photoablation].

Science.gov (United States)

Cochener, B; Kling, F; Savary-Le Floch, G; Colin, J

2000-06-01

To compare effect of two topical non steroidal anti-inflammatory (NSAI) drugs: Indomethacin (Indocollyre)0.1 %, Chauvin Inc.) and Diclofenac (Voltaren 0.1%, Cibavision) on postoperative pain and epithelial regrowth following surface excimer photoablation. Eighty-six excimer operated patients, were divided in two similar groups depending on the NSAI instilled postoperatively and for 3 days (4 drops daily). No patient was informed of any other available drug. Pain intensity was quantified between 1 and 10 according to an analog scale (reported from 1 to 10 hours, then 4 times a day during 7 days). Complementary medications and functional symptoms were also notified. Biomicroscopic evaluation using fluorescein test was performed to assess reepithelialization. In term of pain, no significative difference was observed between the two groups concerning intensity, associated medications, or numbers of days of discomfort. Controversially, retreated eyes might induce more pain than initial treatments. No delay in epithelial regrowth was noted and the difference between the two groups in functional complaints was no statistically significant. Pain appears to be not related to ablation depth. DISCUSSION- CONCLUSION: Our results are correlated to literature reported data. Introduction of NSAI constitutes a real advent in the care of excimer postoperative pain. Effect of indomethacin seems comparable to diclofenac effect, but might be of interest because of no anesthetic property that might guarantee of no delay in wound healing response.

Lung abscess complicating pneumococcal pneumonia: a causal role of non-steroidal anti-inflammatory drugs?

OpenAIRE

Gibelin, Aude; de Prost, Nicolas; Brun-Buisson, Christian

2013-01-01

Pulmonary abscess is a distinctly uncommon complication of pneumococcal pneumonia in immunocompetent adults that has recently been reported to occur following administration of non-steroidal anti-inflammatory drugs (NSAIDs). We report herein the case of a 24-year-old patient with no predisposing risk factor who developed a lung abscess after NSAIDs exposure, further illustrating this potentially severe complication of NSAIDs use, especially in the absence of associated antibiotic therapy.

Lung abscess complicating pneumococcal pneumonia: a causal role of non-steroidal anti-inflammatory drugs?

Science.gov (United States)

Gibelin, Aude; de Prost, Nicolas; Brun-Buisson, Christian

2013-08-20

Pulmonary abscess is a distinctly uncommon complication of pneumococcal pneumonia in immunocompetent adults that has recently been reported to occur following administration of non-steroidal anti-inflammatory drugs (NSAIDs). We report herein the case of a 24-year-old patient with no predisposing risk factor who developed a lung abscess after NSAIDs exposure, further illustrating this potentially severe complication of NSAIDs use, especially in the absence of associated antibiotic therapy.

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

Energy Technology Data Exchange (ETDEWEB)

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

1991-09-01

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

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

International Nuclear Information System (INIS)

Gross, N.J.; Holloway, N.O.; Narine, K.R.

1991-01-01

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

An analysis of the gastro-intestinal side-effects of non-steroidal anti-inflammatory drugs, with particular reference to comparative studies in man and laboratory species.

Science.gov (United States)

Rainsford, K D

1982-01-01

A critical analysis has been performed of reports published on the incidence of gastro-intestinal (GI) side-effects found in arthritic patients being treated with non-steroid anti-inflammatory (NSAI) drugs. The results show the following: 1. The incidence of GI ulceration (as revealed by gastroscopy) and haemorrhage in arthritic patients taking NSAI drugs may be higher than suspected from clinical trial data. 2. Incidence of all GI side-effects (including ulceration and haemorrhage) may be lower with some of the new NSAI drugs than with traditional drugs (e.g. aspirin, indomethacin and phenylbutazone). 3. Arthritic patients may be more susceptible to the ulcerogenic actions of NSAI drugs. Experiments with animals, together with evidence from clinical studies, indicate that stress factors and the presence of decreased mucosal resistance in the diseased state may contribute to the enhanced susceptibility of the GI tract towards the ulcerogenicity of NSAI drugs. 4. Comparison of data on gastroscopic observations in man with the author's data on the effects of NSAI drugs in stress-sensitized rats shows the latter technique appears to be a useful means of predicting the ulcerogenic potential of NSAI drugs in man. The comparison has also been used to predict the ulcerogenicity of drug - alcohol combinations; alcohol being a common ulcerogen consumed by many patients. Some NSAI drugs with low ulcerogenic activity (i.e. azapropazone, benoxaprofen and fenclofenac) in the stressed-rat assay show little or no interaction with alcohol. These studies using laboratory animals show the importance of employing conditions to mimic environmental factors (e.g. stress and alcohol consumption) which might predispose individuals to ulcerogenic or other side-effects of NSAI drugs. From these studies it appears possible to construct 'predictive profiles' of the relative ulcerogenicity of NSAI drugs which may be applicable to the clinical situation in man.

New approaches to reduce ulcerogenity of nonsteroidal anti-inflammatory drugs: achievements, unsolved issues and ways to optimize

Directory of Open Access Journals (Sweden)

F. V. Hladkykh

2014-04-01

Full Text Available Analysis of the domestic and foreign literature sources devoted to the study of pathogenetic mechanisms of gastropathy caused by non-steroidal anti-inflammatory drugs was done. Current approaches of prevention and treatment of NSAID-induced gastropathy were lined. The appropriateness of drugs with polytropic pharmacological properties (Quercetin, Vinboron and Tiotriazolin to eliminate the side effects of NSAIDs, including ultserogenesis was discusses.

Role of non-steroidal anti-inflammatory drugs on intestinal permeability and nonalcoholic fatty liver disease.

Science.gov (United States)

Utzeri, Erika; Usai, Paolo

2017-06-14

The use of non-steroidal anti-inflammatory drugs (NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of non-alcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.

Inflammation in Depression and the Potential for Anti-Inflammatory Treatment

DEFF Research Database (Denmark)

Kohler, Ole; Krogh, Jesper; Mors, Ole

2016-01-01

Accumulating evidence supports an association between depression and inflammatory processes, a connection that seems to be bidirectional. Clinical trials have indicated antidepressant treatment effects for anti-inflammatory agents, both as add-on treatment and as monotherapy. In particular......, nonsteroidal anti-inflammatory drugs (NSAIDs) and cytokine-inhibitors have shown antidepressant treatment effects compared to placebo, but also statins, poly-unsaturated fatty acids, pioglitazone, minocycline, modafinil, and corticosteroids may yield antidepressant treatment effects. However, the complexity...... of the inflammatory cascade, limited clinical evidence, and the risk for side effects stress cautiousness before clinical application. Thus, despite proof-of-concept studies of anti-inflammatory treatment effects in depression, important challenges remain to be investigated. Within this paper, we review...

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

DEFF Research Database (Denmark)

Kristensen, Søren Lund; Fosbøl, Emil L; Kamper, Anne-Lise

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...

Synthesis of non-steroidal anti-inflammatory drug analogues for selective studies on the COX-II enzyme

International Nuclear Information System (INIS)

Fleming, S.A.; Ridges, M.D.; Jensen, A.W.

1996-01-01

Synthesis of the azido substituted non-steroidal anti-inflammatory drug 2-(2,6-dichloroanilino)phenylacetic acid and isotope labeling of this compound have been performed and are described. Initial evaluation of the binding ability and photoreactivity indicates that this compound has potential for photoaffinity labeling as well as enzyme selectivity studies. (author)

[Meloxicam: the golden mean of nonsteroidal anti-inflammatory drugs].

Science.gov (United States)

Karateev, A E

2014-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are most commonly used to treat acute and chronic pain in locomotor system (LMS) diseases. However, their administration may be accompanied by the development of dangerous complications as organic and functional disorders of the cardiovascular system (CVS) and gastrointestinal tract (GIT). Physicians have currently a wide range of NSAIDs at their disposal; but none of the representatives of this group can be considered the best. Thus, highly selective cyclooxygenase-2 inhibitors (Coxibs) are substantially safer for GIT; however, their use is clearly associated with the increased risk of severe cardiovascular events. Nonselective NSAIDs, such as naproxen or ketoprofen, are safer for CVS, but more frequently cause significant GIT organic and functional disorders. Moderately selective NSAIDs, such as meloxicam (movalis), conceivably could be the most acceptable choice for treating the majority of patients in this situation. This drug has been long and extensively used in global clinical practice and has gained the confidence of physicians and patients. The major benefits of meloxicam are its proven efficacy, convenient treatment regimen, relatively low risk of complications as organic and functional disorders of the GIT and CVD and good compatibility with low-dose aspirin.

Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety

Directory of Open Access Journals (Sweden)

Roth SH

2011-05-01

Full Text Available Sanford H RothArizona Research and Education, Arthritis Laboratory, Arizona State University, Phoenix, AZ, USAAbstract: Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy. Topical NSAID formulations deliver effective doses of analgesics directly to the affected joints, thereby limiting systemic exposure and potentially the risk of systemic adverse events, such as gastropathy and serious cardiovascular events. There are currently two topical NSAIDs approved by the US Food and Drug Administration for osteoarthritis-associated pain, as well as for the signs and symptoms of osteoarthritis. This review discusses the relative safety, and the gastrointestinal, cardiovascular, and renal risks of chronic oral or systemic NSAID therapy and topical NSAID formulations in patients with osteoarthritis.Keywords: NSAIDs, osteoarthritis, topical administration, synovial fluid, peptic ulcer, Helicobacter pylori

Anti-inflammatory activity of leaf essential oil from Cinnamomum longepaniculatum (Gamble) N. Chao.

Science.gov (United States)

Du, Yong-Hua; Feng, Rui-Zhang; Li, Qun; Wei, Qin; Yin, Zhong-Qiong; Zhou, Li-Jun; Tao, Cui; Jia, Ren-Yong

2014-01-01

The anti-inflammatory activity of the essential oil from C. longepaniculatum was evaluated by three experimental models including the dimethyl benzene-induced ear edema in mice, the carrageenan-induced paw edema in rat and the acetic acid-induced vascular permeability in mice. The influence of the essential oil on histological changes and prostaglandin E2 (PGE2), histamine and 5-hydroxytryptamine (5-HT) production associated with carrageenan-induced rat paw edema was also investigated. The essential oil (0.5, 0.25, 0.13 ml/kg b.w.) showed significantly inhibition of inflammation along with a dose-dependent manner in the three experimental models. The anti-inflammatory activity of essential oil was occurred both in early and late phase and peaked at 4 h after carrageenan injection. The essential oil resulted in a dose dependent reduction of the paw thickness, connective tissue injury and the infiltration of inflammatory cell. The essential oil also significantly reduced the production of PGE2, histamine and 5-HT in the exudates of edema paw induced by carrageenan. Both the essential oil and indomethacin resulted relative lower percentage inhibition of histamine and 5-HT than that of PGE2 at 4 h after carrageenan injection.

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

Directory of Open Access Journals (Sweden)

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.

Topical nonsteroidal anti-inflammatory drugs for management of osteoarthritis in long-term care patients

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Argoff CE

2011-09-01

Full Text Available Charles E Argoff1, F Michael Gloth2 1Albany Medical College and Comprehensive Pain Center, Albany Medical Center, Albany, NY, USA; 2Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: Osteoarthritis is common in patients ≥65 years of age. Although nonsteroidal anti-inflammatory drugs (NSAIDs are often prescribed for osteoarthritis pain, they pose age-related cardiovascular, renal, and gastrointestinal risks. Two topical NSAIDs, diclofenac sodium 1% gel (DSG and diclofenac sodium 1.5% in 45.5% dimethylsulfoxide solution (D-DMSO, are approved in the US for the treatment of osteoarthritis pain. Topical NSAIDs have shown efficacy and safety in knee (DSG, D-DMSO and hand (DSG osteoarthritis. Analyses of data from randomized controlled trials of DSG in hand and knee osteoarthritis demonstrate significant improvement of pain and function in both younger patients (<65 years and older patients (≥65 years and suggest good safety and tolerability. However, long-term safety data in older patients are limited. Topical NSAIDs can ease medication administration and help address barriers to pain management in older patients, such as taking multiple medications and inability to swallow, and are a valuable option for long-term care providers. Keywords: nonsteroidal anti-inflammatory drugs, long-term care, nursing homes, chronic pain, topical analgesics

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

2011-01-01

Petersen SG, Beyer N, Hansen M, Holm L, Aagaard P, Mackey AL, Kjaer M. Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients.......Petersen SG, Beyer N, Hansen M, Holm L, Aagaard P, Mackey AL, Kjaer M. Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients....

Neostigmine interactions with non steroidal anti-inflammatory drugs.

Science.gov (United States)

Miranda, Hugo F; Sierralta, Fernando; Pinardi, Gianni

2002-04-01

1. The common mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of the enzyme cyclo-oxygenase (COX), however, this inhibition is not enough to completely account for the efficacy of these agents in several models of acute pain. 2. It has been demonstrated that cholinergic agents can induce antinociception, but the nature of the interaction between these agents and NSAIDs drugs has not been studied. The present work evaluates, by isobolographic analysis, the interactions between the cholinergic indirect agonist neostigmine (NEO) and NSAIDs drugs, using a chemical algesiometric test. 3. Intraperitoneal (i.p.) or intrathecal (i.t.) administration of NEO and of the different NSAIDs produced dose-dependent antinociception in the acetic acid writhing test of the mouse. 4. The i.p. or i.t. co-administration of fixed ratios of ED(50) fractions of NSAIDs and NEO, resulted to be synergistic or supra-additive for the combinations ketoprofen (KETO) and NEO, paracetamol (PARA) and NEO) and diclofenac (DICLO) and NEO administered i.p. However, the same combinations administered i.t. were only additive. In addition, the combinations meloxicam (MELO) and NEO and piroxicam (PIRO) and NEO, administered either i.p. or i.t., were additive. 5. The results suggest that the co-administration of NEO with some NSAIDs (e.g. KETO, PARA or DICLO) resulted in a synergistic interaction, which may provide evidence of supraspinal antinociception modulation by the increased acetylcholine concentration in the synaptic cleft of cholinergic interneurons. The interaction obtained between neostigmine and the NSAIDs could carry important clinical implications.

Direct medical costs of serious gastrointestinal ulcers attributable to non steroidal anti-inflammatory drugs in the Netherlands

NARCIS (Netherlands)

Vonkeman, Harald E.; Klok, Rogier M.; Postma, Maarten J.; Brouwers, Jacobus R.B.J.; van de Laar, Mart A.F.J.

2006-01-01

Purpose: The occurrence and prevention of gastrointestinal ulcers attributable to the use of non-steroidal anti-inflammatory drugs (NSAIDs) has become a major health care issue. Analysis of cost effectiveness of preventive strategies has been hampered by a lack of recent cost of illness studies. The

Indomethacin reduces glomerular and tubular damage markers but not renal inflammation in chronic kidney disease patients: a post-hoc analysis.

Directory of Open Access Journals (Sweden)

Martin H de Borst

Full Text Available Under specific conditions non-steroidal anti-inflammatory drugs (NSAIDs may be used to lower therapy-resistant proteinuria. The potentially beneficial anti-proteinuric, tubulo-protective, and anti-inflammatory effects of NSAIDs may be offset by an increased risk of (renal side effects. We investigated the effect of indomethacin on urinary markers of glomerular and tubular damage and renal inflammation. We performed a post-hoc analysis of a prospective open-label crossover study in chronic kidney disease patients (n = 12 with mild renal function impairment and stable residual proteinuria of 4.7±4.1 g/d. After a wash-out period of six wks without any RAAS blocking agents or other therapy to lower proteinuria (untreated proteinuria (UP, patients subsequently received indomethacin 75 mg BID for 4 wks (NSAID. Healthy subjects (n = 10 screened for kidney donation served as controls. Urine and plasma levels of total IgG, IgG4, KIM-1, beta-2-microglobulin, H-FABP, MCP-1 and NGAL were determined using ELISA. Following NSAID treatment, 24 h -urinary excretion of glomerular and proximal tubular damage markers was reduced in comparison with the period without anti-proteinuric treatment (total IgG: UP 131[38-513] vs NSAID 38[17-218] mg/24 h, p<0.01; IgG4: 50[16-68] vs 10[1-38] mg/24 h, p<0.001; beta-2-microglobulin: 200[55-404] vs 50[28-110] ug/24 h, p = 0.03; KIM-1: 9[5]-[14] vs 5[2]-[9] ug/24 h, p = 0.01. Fractional excretions of these damage markers were also reduced by NSAID. The distal tubular marker H-FABP showed a trend to reduction following NSAID treatment. Surprisingly, NSAID treatment did not reduce urinary excretion of the inflammation markers MCP-1 and NGAL, but did reduce plasma MCP-1 levels, resulting in an increased fractional MCP-1 excretion. In conclusion, the anti-proteinuric effect of indomethacin is associated with reduced urinary excretion of glomerular and tubular damage markers, but not with reduced excretion of renal

[Non-selective and selective non-steroidal anti-inflammatory drugs, administration in pregnancy and breast feeding].

Science.gov (United States)

Fardet, Laurence; Nizard, Jacky; Généreau, Thierry

2002-09-28

THE FACTS: Non steroidal anti-inflammatory drugs (NSAI), except aspirin, are classically contraindicated during pregnancy. Nevertheless, they are widely used, in particular by the obstetricians. During pregnancy, the potential toxicity of these drugs is double, maternal and fetal. The maternal toxicity is comparable to that, already known in adults, with however, some particularities at the time of labor and delivery. The fetal toxicity is mainly renal and cardiovascular, with the NSAI responsible for oligoamniosis and premature closure of the arterial canal of the fetus. On the other hand, the use of these molecules during breast-feeding does not seem source of adverse events, notably in the newborn. THE VARIOUS MOLECULES: Among the family of non-selective non-steroidal anti-inflammatories, indications and adverse events of the various molecules differ considerably. Moreover, whereas the majority of these molecules are non-selective, i.e. inhibiting the two isoforms of cyclooxygenase, new therapeutics, specifically inhibiting cyclooxygenase-2, are now available. Few studies have been published concerning their prescription during pregnancy and breast-feeding and their maternal and fetal side effects remain ignored by most of the practitioners.

Decreasing Skin Graft Contraction through Topical Wound Bed Preparation with Anti-Inflammatory Agents

Science.gov (United States)

2017-10-01

Award Number: W81XWH-14-2-0153 TITLE: Decreasing Skin Graft Contraction through Topical Wound Bed Preparation with Anti-Inflammatory Agents...09/14/2017 4. TITLE AND SUBTITLE “Decreasing Skin Graft Contraction through Topical Wound Bed Preparation with Anti-Inflammatory Agents” 5a...of a specific topical anti-inflammatory drug that will reduce and shorten the inflammatory state of the recipient wound bed and thus, skin graft

Anti-inflammatory activity of Shirishavaleha: An Ayurvedic compound formulation.

Science.gov (United States)

Yadav, Shyamlal Singh; Galib; Ravishankar, B; Prajapati, P K; Ashok, B K; Varun, B

2010-10-01

The purpose of the present study was to evaluate the anti-inflammatory activity of Shirishavaleha prepared from two different parts of Shirisha (Albizia lebbeck Benth.), viz. the bark (Twak) and the heartwood (Sara). The activity was screened in the carrageenan-induced rat paw edema model in albino rats. The raw materials were collected and authenticated in the university and the trial formulations were prepared by following standard classical guidelines. Randomly selected animals were divided into four groups of six animals each. The test drugs were administered orally at a dose of 1.8 g/kg for 5 days. Phenylbutazone was used as the standard anti-inflammatory drug for comparison. Between the two different test samples studied, the formulation made from heartwood showed a weak anti-inflammatory activity in this model while that made from the bark produced a considerable suppression of edema after 6 h. It appears that the bark sample would be preferable for clinical use.

Studies on anti-inflammatory and analgesic properties of Lactobacillus rhamnosus in experimental animal models.

Science.gov (United States)

Amdekar, Sarika; Singh, Vinod

2016-06-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used for the treatment of inflammatory diseases. However, constant use of NSAID may lead to some side effects like gastrointestinal ulcers, bleeding and renal disorders. This study evaluates analgesic and anti-inflammatory activities of Lactobacillus rhamnosus in female Wistar rats. Diclofenac sodium was used as a standard drug for comparison. L. rhamnosus, drugs and vehicle were administered orally. Acetic acid-induced writhing test and carrageenan-induced paw edema model were used for evaluation. Paw edema and number of writhes were measured subsequently. Pro-inflammatory (interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α and IL-17) and anti-inflammatory (IL-4 and IL-10) cytokines were estimated in serum after 24 h. Results showed that L. rhamnosus significantly decreased the paw thickness at t=24 h by 28.66 % while drug decreased by 19.33 %. Also, L. rhamnosus treatment and standard drug showed a protection of 66.66 % and 41.66 %, respectively. L. rhamnosus and diclofenac sodium treatment significantly down-regulated pro-inflammatory and up-regulated anti-inflammatory cytokines at prhamnosus was more pronounced in comparison to diclofenac sodium. The present study clearly suggests that L. rhamnosus suppressed carrageenan-induced paw edema after second phase and decreased the acetic acid-induced writhings. It ameliorated the inflammatory pathways by down-regulating pro-inflammatory cytokines. However, additional clinical investigations are needed to prove the efficacy of L. rhamnosus in treatment/management of inflammatory joint diseases.

New heparin–indomethacin conjugate with an ester linkage: Synthesis, self aggregation and drug delivery behavior

Energy Technology Data Exchange (ETDEWEB)

Li, Nan-Nan; Zheng, Bing-Na [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Lin, Jian-Tao [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Guangdong Medical College, Dongguan 523808 (China); Zhang, Li-Ming, E-mail: ceszhlm@mail.sysu.edu.cn [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China)

2014-01-01

New heparin–indomethacin conjugate with an ester linkage was prepared by the carbodiimide-mediated condensation reaction, and then characterized by FTIR and {sup 1}HNMR analyses. Due to its amphiphilic character, such a conjugate could self-aggregate into spherical nanoparticles in aqueous system, as confirmed by fluorescence spectroscopy, dynamic light scattering and transmission electron microscopy. By the in vitro drug release tests, the resultant conjugate nanoparticles were found to have a sustained and esterase-sensitive release behavior for conjugated indomethacin. In addition, the uptake of these conjugate nanoparticles into human nasopharyngeal carcinoma CNE1 cells was confirmed by fluorescence microscopy. - Highlights: • New heparin–indomethacin conjugate with an ester linkage was prepared. • Such a conjugate could self-aggregate into spherical nanoparticles in aqueous system. • The resultant conjugate nanoparticles exhibited an esterase-sensitive drug release behavior. • The resultant conjugate nanoparticles showed the cellular uptake ability in CNE1 cells.

Protective effects of escin against indomethacin-induced gastric ulcer in mice.

Science.gov (United States)

Wang, Tian; Zhao, Shanshan; Wang, Yucun; Yang, Yujiao; Yao, Le; Chu, Liuxiang; Du, Hanhan; Fu, Fenghua

2014-12-01

Escin, a natural mixture of triterpenoid saponin isolated from the seed of the horse chestnut, is reported to have a potent antiulcer activity against ethanol-induced gastric mucosal lesions. This study investigated the possible mechanisms underlying the gastroprotective effect of escin against indomethacin-induced gastric ulcer in mice. Gastric ulceration was induced by a single intragastric administration of indomethacin (18 mg/kg). The mice underwent intragastric treatment with escin at doses of 0.45, 0.9 or 1.8 mg/kg. Gastric lesion was estimated morphometrically and histopathologically 6 h after the indomethacin administration. The antioxidative parameters in gastric mucosa were measured. Moreover, the activity of myeloperoxidase and the contents of TNF-α, P-selectin and VCAM-1 in gastric tissues were determined. The results showed that escin protected gastric tissues against indomethacin-induced gastropathy as demonstrated from a reduction in the ulcer index and an attenuation of histopathologic changes. Escin caused significant reductions of the contents of malondialdehyde, TNF-α, P-selectin, VCAM-1 and myeloperoxidase activity. The altered activities of superoxide dismutase, catalase and glutathione peroxidase in the stomach tissues were also ameliorated by escin treatment. The present study demonstrated that escin had a protective effect against indomethacin-induced gastric ulcer in mice, not only by virtue of its antioxidant potential, but also due to its anti-inflammatory effect.

Oxovanadium(IV) complexes of non-steroidal anti-inflammatory drugs: synthesis, spectroscopy, and antimicrobial activity

International Nuclear Information System (INIS)

Muhammad, N.; Ali, S.; Shahzadi, S.; Khan, A.N.

2008-01-01

Oxovanadium(IV) complexes with four different non-steroidal anti-inflammatory drugs have been synthesized. These complexes were characterized by different analytical techniques such as CHN, IR, UV-Vis spectroscopy, and mass spectrometry. The IR data show the bidentate nature of the ligands and reveal hexacoordinate geometry in the solid state. The complexes were tested for their biological activity against six different bacterial strains and plant pathogens, and all complexes showed good biological activity with few exceptions [ru

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

Energy Technology Data Exchange (ETDEWEB)

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

1988-11-01

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

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

International Nuclear Information System (INIS)

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

1988-01-01

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

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

Nonsteroidal Anti-Inflammatory Drugs and Analgesics Use by Kidney Transplant Recipients.

Science.gov (United States)

Mulka-Gierek, Maria; Foroncewicz, Bartosz; Pączek, Leszek; Wawiórko, Elżbieta; Kamińska, Joanna; Kosieradzki, Maciej; Małkowski, Piotr; Małczuk, Bianka; Nazarewski, Sławomir; Mucha, Krzysztof

2018-03-02

BACKGROUND Nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics are the most commonly used drugs and are increasingly available over-the-counter (OTC). In certain groups of patients, including kidney transplant recipients, their use may be complicated by adverse effects or drug interactions. The aim of our study was to assess the causes and frequency of OTC NSAIDs or analgesics use, as well as the awareness of related side effects. MATERIAL AND METHODS We enrolled 94 randomly selected kidney transplant recipients, who represented 5% of all kidney transplant recipients at our center. An anonymous survey consisting of 23 multiple-choice questions was administered voluntarily and anonymously. RESULTS In all, 63% of study patients confirmed taking the OTC painkillers; 22% of these patients took these drugs at least several times a week, and 4% took these drugs daily. For 38% of the study kidney transplant recipients, NSAIDs or analgesics were reported to be the only way to manage their pain. In addition, 30% of study patients were unaware of the risks associated with these drugs, despite the fact that 89% of the study patients consider physicians the best source of information. CONCLUSIONS Our study found that 63% of kidney transplant recipients regularly took OTC painkillers and 30% were unaware of the potential adverse effects. This necessitates continuous, ongoing education of kidney transplant recipients about the risks of OTC NSAIDs or analgesics use.

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

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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.

Recent considerations in nonsteroidal anti-inflammatory drug gastropathy.

Science.gov (United States)

Singh, G

1998-07-27

Conservative calculations estimate that approximately 107,000 patients are hospitalized annually for nonsteroidal anti-inflammatory drug (NSAID)-related gastrointestinal (GI) complications and at least 16,500 NSAID-related deaths occur each year among arthritis patients alone. The figures for all NSAID users would be overwhelming, yet the scope of this problem is generally under-appreciated. The Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS) Post-Marketing Surveillance Program (PMS) has prospectively followed patient status and outcomes, drug side effects, and the economic impact of illness for >11,000 arthritis patients at 8 participating institutions in the United States and Canada. Analysis of these data indicates that: (1) osteoarthritis (OA) and rheumatoid arthritis (RA) patients are 2.5-5.5 times more likely than the general population to be hospitalized for NSAID-related GI events; (2) the absolute risk for serious NSAID-related GI toxicity remains constant and the cumulative risk increases over time; (3) there are no reliable warning signals- >80% of patients with serious GI complications had no prior GI symptoms; (4) independent risk factors for serious GI events were age, prednisone use, NSAID dose, disability level, and previous NSAID-induced GI symptoms; and (5) antacids and H2 antagonists do not prevent NSAID-induced gastric ulcers, and high-risk NSAID users who take gastro-protective drugs are more likely to have serious GI complications than patients not taking such medications. Currently, limiting NSAID use is the only way to decrease the risk of NSAID-related GI events. Ongoing ARAMIS research is aimed at developing a simple point-score system for estimating individual risks of developing serious NSAID-related GI complications.

[Upper gastrointestinal hemorrhage caused by anti-inflammatory agents].

Science.gov (United States)

Duhamel, C; Czernichow, P; Dechelotte, P; Ducrotte, P; Lerebours, E; Colin, R

1989-03-01

The aim of this study was to describe the clinical and evolutive characteristics of gastroduodenal bleeding occurring in patients receiving nonsteroidal anti-inflammatory (NSAI) drugs, containing salicylates or not, and to determine the relative toxicity of the NSAI drugs without salicylates. Eight hundred and fourty-five consecutive patients with upper gastrointestinal bleeding related to endoscopically proven peptic ulcer or gastroduodenal erosions were admitted between 1983 and June 1987 to an intensive care unit for digestive tract hemorrhage. Of these, 267 were using anti-inflammatory drugs; 151 (56 p. 100) were taking NSAI drugs other than salicylates, 97 salicylates (36 p. 100) and 10, steroids (4 p. 100). Patients taking nonsteroidal drugs without or with salicylates were compared with patients bleeding from gastroduodenal ulcer or erosion not receiving anti-inflammatory therapy. Patients receiving nonsteroidal drugs not containing salicylates were older (70 p. 100 over 65 years of age vs 46 p. 100, p less than 0.001) and the proportion of female patients was greater (54 p. 100 vs 33 p. 100, p less than 0.001) than in the other group. No significant difference was observed with regard to the following parameters: percentage of gastric lesions, concomitant anticoagulant therapy, need for surgical hemostasis, or mortality. Patients taking aspirin had more gastric lesions (75 p. 100 vs 64 p. 100, p less than 0.05) and less need for surgical hemostasis (7 p. 100 vs 15 p. 100, p less than 0.05); the other parameters did not differ. NSAI drugs other than salicylates were taken more often for osteoarthritis than salicylates (33.6 p. 100 vs 17.4 p. 100, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrasound-enhanced delivery of antibiotics and anti-inflammatory drugs into the eye.

Science.gov (United States)

Nabili, Marjan; Patel, Hetal; Mahesh, Sankaranarayana P; Liu, Ji; Geist, Craig; Zderic, Vesna

2013-04-01

Delivery of sufficient amounts of therapeutic drugs into the eye is often a challenging task. In this study, ultrasound application (frequencies of 400 KHz to 1 MHz, intensities of 0.3-1.0 W/cm(2) and exposure duration of 5 min) was investigated to overcome the barrier properties of cornea, which is a typical route for topical administration of ophthalmic drugs. Permeability of ophthalmic drugs, tobramycin and dexamethasone and sodium fluorescein, a drug-mimicking compound, was studied in ultrasound- and sham-treated rabbit corneas in vitro using a standard diffusion cell setup. Light microscopy observations were used to determine ultrasound-induced structural changes in the cornea. For tobramycin, an increase in permeability for ultrasound- and sham-treated corneas was not statistically significant. Increase of 46%-126% and 32%-109% in corneal permeability was observed for sodium fluorescein and dexamethasone, respectively, with statistical significance (p anti-inflammatory ocular drug dexamethasone. Future investigations are needed to determine the effectiveness and safety of this application in in vivo long-term survival studies. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Development of hydroethanolic extract of Ipomoea pes-caprae using factorial design followed by antinociceptive and anti-inflammatory evaluation

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Daniela Vieira

2012-11-01

Full Text Available Ipomoea pes-caprae (L. R. Br., Convolvulaceae, is a medicinal plant that grows abundantly as a pan-tropical stand plant. The 3² (two factors and three levels factorial design, was applied to determine the best time and drug/solvent proportion to maximize the flavonoid content in the hydroethanolic extract by maceration process. The antinociceptive and anti-inflammatory effects were studied at 5-20 mg/kg, i.p., using the writhing test and carrageenan-induced pleurisy models in mice. The optimized extract was able to inhibit more than 50% of abdominal writhing at 20 mg/kg, with 55.88%±2.4 of maximum inhibition. Indomethacin, used as positive control, inhibited 64.86% at 10 mg/kg. In the pleurisy model, the extract produced dose-dependent inhibition of the first phase of inflammation (4 h in the pleural cavity induced by injection of carrageenan (1% in mice. It inhibited 50%±0.82 (p<0.01 of exudation induced by carrageenan, and 60.88%±0.14 (p<0.01 of leukocyte migration to the pleural cavity. In conclusion, the results validate the technological conditions of the maceration process to produce an optimized bioactive herb extract for the development of analgesic and anti-inflammatory phytopharmaceuticals using 70 ºGL ethanol, a plant to solvent ratio of 12.5% (w/v, and ten days of maceration.

Long-term cardiovascular risk of nonsteroidal anti-inflammatory drug use according to time passed after first-time myocardial infarction

DEFF Research Database (Denmark)

Olsen, Anne-Marie Schjerning; Fosbøl, Emil L; Lindhardsen, Jesper

2012-01-01

The cardiovascular risk after the first myocardial infarction (MI) declines rapidly during the first year. We analyzed whether the cardiovascular risk associated with using nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with the time elapsed following first-time MI....

Synthesis, Analgesic, Anti-inflammatory and Antimicrobial Activities ...

African Journals Online (AJOL)

Purpose: Microbial infections often produce pain and inflammation. Chemotherapeutic, analgesic and anti-inflammatory drugs are prescribed simultaneously in normal practice. The compound possessing all three activities is not common.The purpose of the present study was to examine whether molecular modification ...

Contribution of Helicobacter pylori infection to the risk of peptic ulcer bleeding in patients on nonsteroidal anti-inflammatory drugs, antiplatelet agents, anticoagulants, corticosteroids and selective serotonin reuptake inhibitors.

Science.gov (United States)

Venerito, M; Schneider, C; Costanzo, R; Breja, R; Röhl, F-W; Malfertheiner, P

2018-06-01

Nonsteroidal anti-inflammatory drugs, low-dose aspirin, non-aspirin antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors and corticosteroids increase the risk of gastroduodenal bleeding. To determine in a retrospective cohort study the contribution of Helicobacter pylori infection to the risk of peptic ulcer bleeding in patients taking these drugs. Among patients with peptic ulcer disease diagnosed by endoscopy from 01/2004 to 12/2014 (N = 1719, 60% males, age 65.8 ± 14.5), 56.9% had peptic ulcer bleeding (cases) and 43.1% uncomplicated peptic ulcer disease (controls). Demographics, intake of nonsteroidal anti-inflammatory drugs, aspirin, non-aspirin antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors, proton pump inhibitors and corticosteroids were documented. H. pylori status was determined by histology, rapid urease test or serology. Adjusted odds ratios (OR) were estimated by logistic regression analysis. Helicobacter pylori infection increased the risk of peptic ulcer bleeding in nonsteroidal anti-inflammatory drug and aspirin users (OR = 2.91, 95% CI = 1.71-4.98 and OR = 2.23, 95% CI = 1.52-3.28, respectively), but not in patients on anticoagulants, selective serotonin reuptake inhibitor or corticosteroid therapy. H. pylori-positive status substantially increased the risk of peptic ulcer bleeding in patients on non-aspirin antiplatelet agents (OR = 4.37, 95% CI = 1.28-14.99), concomitant aspirin/nonsteroidal anti-inflammatory drug intake (OR = 5.85, 95% CI = 1.68-20.36) and combined antiplatelet therapy (OR = 8.43, 95% CI = 1.09-65.17). After further adjustment for proton pump inhibitor intake, H. pylori infection was still a risk factor for peptic ulcer bleeding in nonsteroidal anti-inflammatory drug and aspirin users. Helicobacter pylori infection increases the risk of peptic ulcer bleeding in peptic ulcer disease patients on nonsteroidal anti-inflammatory drugs, aspirin and non

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

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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.

Experimental evaluation of anti-inflammatory, antinociceptive and antipyretic activities of clove oil in mice

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Yousef A. Taher

2015-09-01

Full Text Available Background: Clove oil of Eugenia caryophyllata (Myrtaceae is a light yellowish fluid obtained from dried flower buds. Clove oil is used traditionally to relieve toothache. Aim: The aim of the present work was to study the anti-inflammatory, antinociceptive and antipyretic potential of clove oil in mice. Methods: Analgesic activity was examined using acetic-acid-induced abdominal constrictions and the hot plate test. Carrageenan-induced paw edema and brewer's-yeast-induced pyrexia were used to investigate the anti-inflammatory activity and the antipyretic effects, respectively. The oil was administered intraperitoneally (i.p. at a dose of 33 mg/kg body weight and the effects were compared with reference drugs. Results: In the antinociceptive test, mice treated with clove oil exhibited significantly decreased acetic-acid-induced writhing movements by a maximum of 87.7% (p<0.01 compared with a decrease of 77.7% (p<0.01 in response to aspirin injection (100 mg/kg, intraperitoneal, i.p.. Similarly, in the hot plate test, clove oil significantly increased the reaction latency to pain after 60 min by 82.3% (p<0.05 compared with morphine value of 91.7% (p<0.01. In addition, clove oil and indomethacin produced anti-inflammatory effects, as demonstrated by respectively 50.6% (p<0.05 and 70.4% (p<0.01 inhibition of mouse paw edema induced by carrageenan. Furthermore, clove oil significantly attenuated the hyperthermia induced by yeast at ΔT-max by 2.7°C (p<0.001, and time of peak effects was 30–180 min compared with a paracetamol value ΔT-max of 3.2°C (p<0.001. The estimated i.p. LD50 of clove oil was 161.9 mg/kg. Phytochemical screening of the oil showed the presence of eugenol. Conclusion: The present findings demonstrate the potential pharmacological properties of clove oil and provide further a support for its reported use in folk medicine.

Fenspiride: an anti-inflammatory drug with potential benefits in the treatment of endotoxemia.

Science.gov (United States)

De Castro, C M; Nahori, M A; Dumarey, C H; Vargaftig, B B; Bachelet, M

1995-12-29

Using a model of endotoxemia triggered by the intravenous injection of bacterial lipopolysaccharide (0.1 and 1 mg/kg) to guinea-pigs, we investigated the interference of fenspiride, an anti-inflammatory drug recommended for the treatment of inflammatory diseases of the upper respiratory tract. Administered orally at 60 mg/kg, fenspiride reduced the lipopolysaccharide-induced early rise of tumor necrosis factor concentrations in serum (4.2 +/- 0.9 vs. 2.3 +/- 0.5 ng/ml, P fenspiride (1551.5 +/- 183.7 vs. 771.5 +/- 237.5 pg/mu g protein, P fenspiride reduced the increased serum concentrations of extracellular type II phospholipase A2 (3.9 +/- 1.2 vs. 1.2 +/- 0.1 nmol/ml per min, P fenspiride may result from the inhibition of the formation of tumor necrosis factor, a major mediator of the effects of lipopolysaccharide.

Avicenna's Canon of Medicine: a review of analgesics and anti-inflammatory substances

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Shahla Mahdizadeh

2015-04-01

Full Text Available Naturally occurring substances mentioned in medieval medical literatures currently have, and will continue to have, a crucial place in drug discovery. Avicenna was a Persian physician who is known as the most influential medical writers in the Middle ages. Avicenna`s Canon of Medicine, the most famous books in the history of medicine, presents a clear and organized summary of all the medical knowledge of the time, including a long list of drugs. Several hundred substances and receipts from different sources are mentioned for treatment of different illnesses in this book. The aim of the present study was to provide a descriptive review of all anti-inflammatory and analgesic drugs presented in this comprehensive encyclopedia of medicine. Data for this review were provided by searches of different sections of this book. Long lists of anti-inflammatory and analgesic substances used in the treatment of various diseases are provided. The efficacy of some of these drugs, such as opium, willow oil, curcuma, and garlic, was investigated by modern medicine; pointed to their potent anti-inflammatory and analgesic properties. This review will help further research into the clinical benefits of new drugs for treatment of inflammatory diseases and pain.

Nonsteroidal Anti-Inflammatory Drug Hypersensitivity in Preschool Children

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Kidon Mona

2007-12-01

Full Text Available Although extensively studied in adults, nonsteroidal anti-inflammatory drug (NSAID hypersensitivity in children, especially in young children, remains poorly defined. Pediatricians, prescribing antipyretics for children, rarely encounter significant problems, but the few epidemiologic studies performed show conflicting results. Although it is clear that some patients with acetylsalicylic acid (ASA-sensitive asthma have their clinical onset of disease in childhood and bronchoconstriction after ASA challenge is seen in 0 to 22% of asthmatic children so challenged, ibuprofen at antipyretic doses may cause acute respiratory problems only in a very small number of mild to moderate asthmatics. The recently elucidated mechanism of action of acetaminophen may explain some occurrences of adverse reactions in patients with cross-reactive NSAID hypersensitivity on the basis of its inhibitory activity on the newly described enzyme, cyclooxygenase (COX-3. This nonspecific sensitivity to inhibition of COX is most likely genetically determined and shows a remarkable association with atopic disease even in the very young age group and possibly an increased predilection in specific ethnic groups. This review summarizes state-of-the-art published data on NSAID hypersensitivity in preschool children.

Previous use of non-steroidal anti-inflammatory drugs and anticoagulants: the influence on clinical outcome of bleeding gastroduodenal ulcers

NARCIS (Netherlands)

Vreeburg, E. M.; de Bruijne, H. W.; Snel, P.; Bartelsman, J. W.; Rauws, E. A.; Tytgat, G. N.

1997-01-01

To evaluate the relationship between prior non-steroidal anti-inflammatory drug (NSAID) or anticoagulant use and clinical outcome in bleeding gastric and duodenal ulcer patients. Prospective cohort-study. All patients (n = 132) admitted because of upper gastrointestinal bleeding during 3 months in

Design, Synthesis, Antinociceptive and Anti-Inflammatory Activities of Novel Piroxicam Analogues

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Eliezer J. Barreiro

2012-11-01

Full Text Available In this paper we report the design, synthesis, antinociceptive and anti-inflammatory activities of a series of benzothiazine N-acylhydrazones 14a–h, planned by structural modification of piroxicam (1, a non steroidal anti-inflammatory drug. Among the synthesized analogues, compounds 14f (LASSBio-1637 and 14g (LASSBio-1639 were identified as novel antinociceptive and anti-inflammatory prototypes, active by oral administration, acting by a mechanism of action that seems to be different from that of piroxicam, since they were inactive as an inhibitor of cyclooxygenase (COX-1 and COX-2 at concentrations of 10 mM.

Design, synthesis, antinociceptive and anti-inflammatory activities of novel piroxicam analogues.

Science.gov (United States)

de Miranda, Amanda Silva; Bispo Júnior, Walfrido; da Silva, Yolanda Karla Cupertino; Alexandre-Moreira, Magna Suzana; Castro, Rosane de Paula; Sabino, José Ricardo; Lião, Luciano Morais; Lima, Lídia Moreira; Barreiro, Eliezer J

2012-11-28

In this paper we report the design, synthesis, antinociceptive and anti-inflammatory activities of a series of benzothiazine N-acylhydrazones 14a–h, planned by structural modification of piroxicam (1), a non steroidal anti-inflammatory drug. Among the synthesized analogues, compounds 14f (LASSBio-1637) and 14g (LASSBio-1639) were identified as novel antinociceptive and anti-inflammatory prototypes, active by oral administration, acting by a mechanism of action that seems to be different from that of piroxicam, since they were inactive as an inhibitor of cyclooxygenase (COX-1 and COX-2) at concentrations of 10 mM.

The prevention of gastropathy and upper abdominal symptoms caused by nonsteroidal anti-inflammatory drugs.

Science.gov (United States)

Vakil, Nimish

2006-01-01

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is increasing, primarily due to arthritis in the aging population. This article reviews current data on the risk of gastrointestinal complications related to NSAIDs and strategies to manage risk in patients taking these agents. Risks of NSAID use include gastrointestinal ulceration, hemorrhage, or perforation; renal dysfunction; death; and dyspepsia. Alternate therapies include use of non-NSAID analgesics; low-dose NSAIDs; and concurrent administration of cytoprotective agents with NSAIDs, acid inhibitors, proton pump inhibitors, and COX-2 agents.

Evaluation of anti-inflammatory effect of statins in chronic periodontitis

OpenAIRE

Snophia Suresh; Satya Narayana; P Jayakumar; Uma Sudhakar; V Pramod

2013-01-01

Objectives: Statins are the group of lipid-lowering drugs commonly used to control cardiovascular and cerebrovascular diseases. Statins have potential anti-inflammatory effect by blocking the intermediate metabolites of the mevalonate pathway. The objective of this study was to evaluate the anti-inflammatory effect of statin medication in chronic periodontitis patients. Materials and Methods: Thirty patients of age group between 40 and 60 years were selected from the outpatient pool of De...

Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline.

Science.gov (United States)

Lee, Dong-Won; Shirley, Shawna A; Lockey, Richard F; Mohapatra, Shyam S

2006-08-24

Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs) can enhance theophylline's capacity to alleviate allergic asthma. A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA) and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL) fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in treating asthma may be enhanced through the use of this novel drug delivery

Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline

Directory of Open Access Journals (Sweden)

Mohapatra Shyam S

2006-08-01

Full Text Available Abstract Background Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. Objectives We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs can enhance theophylline's capacity to alleviate allergic asthma. Methods A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Results Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Conclusion Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in

Alleviating Promotion of Inflammation and Cancer Induced by Nonsteroidal Anti-Inflammatory Drugs

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Anthony M. Kyriakopoulos

2017-01-01

Full Text Available Clinical Relevance. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs including aspirin are of intensive use nowadays. These drugs exert their activity via the metabolism of arachidonic acid (AA by cyclooxygenase inhibition. Though beneficial for health in some instances, both unspecific and specific cyclooxygenase inhibitor activity interfere with AA metabolism producing also proinflammatory lipids that may promote cancer. Materials and Methods. This review is based on available literature on clinical uses, biochemical investigations, molecular medicine, pharmacology, toxicity, and epidemiology-clinical studies on NSAIDs and other drugs that may be used accordingly, which was collected from electronic (SciFinder, Medline, Science Direct, and ACS among others and library searches of books and journals. Results. Relevant literature supports the notion that NDSAID use may also promote proinflammatory biochemical events that are also related to precancerous predisposition. Several agents are proposed that may be employed in immediate future to supplement and optimize treatment with NSAIDs. In this way serious side effects arising from promotion of inflammation and cancer, especially in chronic NSAID users and high risk groups of patients, could be avoided.

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

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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.

3-Aminothiophene-2-Acylhydrazones: Non-Toxic, Analgesic and Anti-Inflammatory Lead-Candidates

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Yolanda Karla Cupertino da Silva

2014-06-01

Full Text Available Different chemotypes are described as anti-inflammatory. Among them the N-acylhydrazones (NAH are highlighted by their privileged structure nature, being present in several anti-inflammatory drug-candidates. In this paper a series of functionalized 3-aminothiophene-2-acylhydrazone derivatives 5a–i were designed, synthesized and bioassayed. These new derivatives showed great anti-inflammatory and analgesic potency and efficacy. Compounds 5a and 5d stand out in this respect, and were also active in CFA-induced arthritis in rats. After daily treatment for seven days with 5a and 5d (50 µmol/Kg, by oral administration, these compounds were not renal or hepatotoxic nor immunosuppressive. Compounds 5a and 5d also displayed good drug-scores and low risk toxicity calculated in silico using the program OSIRIS Property Explorer.

The effects of lycopene on DNA damage and oxidative stress on indomethacin-induced gastric ulcer in rats.

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Boyacioglu, Murat; Kum, Cavit; Sekkin, Selim; Yalinkilinc, Hande Sultan; Avci, Hamdi; Epikmen, Erkmen Tugrul; Karademir, Umit

2016-04-01

Lycopene, the main antioxidant compound present in tomatoes, has high singlet oxygen- and peroxyl radicals-quenching ability, resulting in protection against oxidative damage in aerobic cell. Indomethacin is a nonsteroidal anti-inflammatory drug, and can promote oxidative damage in gastric tissue. The aim of this study was to investigate the protective effects of lycopene on an indomethacin-induced gastric ulcer model. A total of 42 adult male Wistar rats were divided into six groups of seven animals as follows: control, indomethacin, lansoprazole, lycopene 10 mg/kg, lycopene 50 mg/kg and lycopene 100 mg/kg. Gastric ulcers were induced by oral administration of indomethacin, after which the differing doses of lycopene were administered by oral gavage. The efficacy of lycopene was compared with lansoprazole. DNA damage of lymphocytes was measured by comet assay. Activities of superoxide dismutase, catalase and myeloperoxidase, as well as malondialdehyde and glutathione levels were determined in stomach tissue. This tissue was also taken for pathological investigations. The TUNEL method was used to detect apoptotic cells in paraffin sections. The results showed that 100 mg/kg lycopene administration significantly decreased % Tail DNA and Mean Tail Moment in the gastric ulcer group, compared with the other treatment groups. This same dose of lycopene also significantly decreased high malondialdehyde level and myeloperoxidase activity, and increased the activity of antioxidant enzymes (with the exception of catalase) in tissue. Apoptosis rates in the stomachs of the rats correlated with the biochemical and histopathological findings. These results indicated that lycopene might have a protective effect against indomethacin-induced gastric ulcer and oxidative stress in rats. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Anti-inflammatory effects of octadecylamine-functionalized nanodiamond on primary human macrophages.

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Pentecost, A E; Witherel, C E; Gogotsi, Y; Spiller, K L

2017-09-26

Chronic inflammatory disorders such as rheumatoid arthritis are characterized by excessive pro-inflammatory or "M1" activation of macrophages, the primary cells of the innate immune system. Current treatments include delivery of glucocorticoids (e.g. dexamethasone - Dex), which reduce pro-inflammatory M1 behaviour in macrophages. However, these treatments have many off-target effects on cells other than macrophages, resulting in broad immunosuppression. To limit such side effects, drug-incorporated nano- and microparticles may be used to selectively target macrophages via phagocytosis, because of their roles as highly effective phagocytes in the body. In this study, surface-modified nanodiamond (ND) was explored as a platform for the delivery of dexamethasone to macrophages because of ND's rich surface chemistry, which contributes to ND's high potential as a versatile drug delivery platform. After finding that octadecylamine-functionalized nanodiamond (ND-ODA) enhanced adsorption of Dex compared to carboxylated ND, the effects of Dex, ND-ODA, and Dex-adsorbed ND-ODA on primary human macrophage gene expression were characterized. Surprisingly, even in the absence of Dex, ND-ODA had strong anti-inflammatory effects, as determined by multiplex gene expression via NanoString and by protein secretion analysis via ELISA. ND-ODA also inhibited expression of M2a markers yet increased the expression of M2c markers and phagocytic receptors. Interestingly, the adsorption of Dex to ND-ODA further increased some anti-inflammatory effects, but abrogated the effect on phagocytic receptors, compared to its individual components. Overall, the ability of ND-ODA to promote anti-inflammatory and pro-phagocytic behaviour in macrophages, even in the absence of loaded drugs, suggests its potential for use as an anti-inflammatory therapeutic to directly target macrophages through phagocytosis.

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

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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.

Anti-inflammatory and anti-oxidative effects of herbal preparation EM 1201 in adjuvant arthritic rats

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Laimis Akramas

2015-01-01

Conclusions: The present study suggests that EM 1201 has protective activity against arthritis and demonstrated its potential beneficiary effect analogical to diclofenac. Anti-inflammatory and anti-oxidative effect of EM 1201 in rats with AA support the need of further investigations by using it as supplementary agent alone or together with other anti-arthritic drugs in the treatment of rheumatoid arthritis.

The stimulatory effect of single-dose pre-irradiation administration of indomethacin and diclofenac on haemopoietic recovery in the spleen of gamma-irradiated mice

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

1989-01-01

The aim of the work was to examine the effect of the single-dose pre-irradiation administration of non-steroid anti-inflammatory drugs, i.e. indomethacin (0.15 mg/mouse) and diclofenac (0.6 mg/mouse) on the recovery of haemopoiesis in the spleen of whole-body irradiated male mice (CBA x C57BL/10)F 1 . It was shown that the administation of these substances 1-24 h prior to sublethal irradiation stimulates the recovery of the proliferation activity of the spleen and the formation of endogenous spleen colonies. These results can be explained as the inhibitory effect of the substances administered on biosynthesis of prostaglandins. (author)

Indomethacin counteracts the effects of chronic social defeat stress on emotional but not recognition memory in mice.

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Duque, Aránzazu; Vinader-Caerols, Concepción; Monleón, Santiago

2017-01-01

We have previously observed the impairing effects of chronic social defeat stress (CSDS) on emotional memory in mice. Given the relation between stress and inflammatory processes, we sought to study the effectiveness of the anti-inflammatory indomethacin in reversing the detrimental effects of CSDS on emotional memory in mice. The effects of CSDS and indomethacin on recognition memory were also evaluated. Male CD1 mice were randomly divided into four groups: non-stressed + saline (NS+SAL); non-stressed + indomethacin (NS+IND); stressed + saline (S+SAL); and stressed + indomethacin (S+IND). Stressed animals were exposed to a daily 10 min agonistic confrontation (CSDS) for 20 days. All subjects were treated daily with saline or indomethacin (10 mg/kg, i.p.). 24 h after the CSDS period, all the mice were evaluated in a social interaction test to distinguish between those that were resilient or susceptible to social stress. All subjects (n = 10-12 per group) were then evaluated in inhibitory avoidance (IA), novel object recognition (NOR), elevated plus maze and hot plate tests. As in control animals (NS+SAL group), IA learning was observed in the resilient groups, as well as in the susceptible mice treated with indomethacin (S+IND group). Recognition memory was observed in the non-stressed and the resilient mice, but not in the susceptible animals. Also, stressed mice exhibited higher anxiety levels. No significant differences were observed in locomotor activity or analgesia. In conclusion, CSDS induces anxiety in post-pubertal mice and impairs emotional and recognition memory in the susceptible subjects. The effects of CSDS on emotional memory, but not on recognition memory and anxiety, are reversed by indomethacin. Moreover, memory impairment is not secondary to the effects of CSDS on locomotor activity, emotionality or pain sensitivity.

Indomethacin counteracts the effects of chronic social defeat stress on emotional but not recognition memory in mice.

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Aránzazu Duque

Full Text Available We have previously observed the impairing effects of chronic social defeat stress (CSDS on emotional memory in mice. Given the relation between stress and inflammatory processes, we sought to study the effectiveness of the anti-inflammatory indomethacin in reversing the detrimental effects of CSDS on emotional memory in mice. The effects of CSDS and indomethacin on recognition memory were also evaluated. Male CD1 mice were randomly divided into four groups: non-stressed + saline (NS+SAL; non-stressed + indomethacin (NS+IND; stressed + saline (S+SAL; and stressed + indomethacin (S+IND. Stressed animals were exposed to a daily 10 min agonistic confrontation (CSDS for 20 days. All subjects were treated daily with saline or indomethacin (10 mg/kg, i.p.. 24 h after the CSDS period, all the mice were evaluated in a social interaction test to distinguish between those that were resilient or susceptible to social stress. All subjects (n = 10-12 per group were then evaluated in inhibitory avoidance (IA, novel object recognition (NOR, elevated plus maze and hot plate tests. As in control animals (NS+SAL group, IA learning was observed in the resilient groups, as well as in the susceptible mice treated with indomethacin (S+IND group. Recognition memory was observed in the non-stressed and the resilient mice, but not in the susceptible animals. Also, stressed mice exhibited higher anxiety levels. No significant differences were observed in locomotor activity or analgesia. In conclusion, CSDS induces anxiety in post-pubertal mice and impairs emotional and recognition memory in the susceptible subjects. The effects of CSDS on emotional memory, but not on recognition memory and anxiety, are reversed by indomethacin. Moreover, memory impairment is not secondary to the effects of CSDS on locomotor activity, emotionality or pain sensitivity.

Coming to terms with nonsteroidal anti-inflammatory drug gastropathy.

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Roth, Sanford H

2012-05-07

Despite well known complications, oral nonsteroidal anti-inflammatory drugs (NSAIDs) remain the most commonly prescribed medications in the US for musculoskeletal disorders such as osteoarthritis. Although there has been a recent focus on the cardiovascular and renal complications associated with these agents, NSAID gastropathy continues to be a particular concern in many patients, especially those at increased risk for serious adverse events, including the elderly. Complicating the diagnosis of NSAID gastropathy is its silent course, which, up to half of the time, is asymptomatic. Several strategies are currently employed by physicians to mitigate the risk of serious gastrointestinal events. These include either addition of a proton pump inhibitor to current nonselective NSAID therapy or the use of a cyclo-oxygenase-2-selective NSAID. Although these agents are effective at mitigating the overall risk of gastrointestinal adverse events, they fail to address NSAID-related cardiovascular and renal risks. Due to their reduced systemic absorption, topical NSAIDs may present a viable option for patients at increased risk for serious NSAID-related adverse events, including gastropathy.

COMPARISON OF ANTI - INFLAMMATORY ACTIVITY OF ALPINIA GALANGAL IN THREE EXPERIMENTAL ANIMAL MODELS

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Venuturumilli Lakshmi

2015-05-01

Full Text Available Inflammation is not a disease but a non - specific response of the body defence 1 . Anti - inflammatory drugs have become popular because of their ability in controlling the inflammatory reaction and mitigating the suffering in such clinical situations. Edema represents the early phase of inflammation. 2 In the present study acute and subacute experimental methods were compared with standard drug Indomethacin. R at hind paw edema, formalin induced peritonitis in mice were used as acute methods, paper disc induced granuloma in rats was used as subacute method. Institutional animal ethics committee permission was taken for all the methods as per CPCSEA guide lines. Inflammation was induced by the following 3 methods: i Hind paw edema was produced by sub plantar injection of 0.1ml of1% carrageenin 3 and paw volume was measured by digital plethysmometer at 0, 3hours. ii Intraperitoneal injection of 1.5% formalin 3 was given to albino mice in peritonitis method and ascitic fluid was measured after 6hours by sacrificing the animals. iii Under ether anesthesia, sterilized &weighed paper discs were implanted subcutaneously in each axilla and groin of male wistar rats sutur ed under sterilized conditions in granuloma 4 method. The discs were cleared of extraneous tissue, dried and weighed on the 5 th day by sacrificing the animals. In all the methods 6 animals in each group (test, standard and control were taken. Results were tabulated in each method separately and statistical analysis was done by student t test. P value < 0.05 considered significant. Percentage inhibition in each method was calculated.

Cooling Crystallization of Indomethacin: Effect of Supersaturation, Temperature and Seeding on Polymorphism and Crystal Size Distribution

DEFF Research Database (Denmark)

Malwade, Chandrakant Ramkrishna; Qu, Haiyan

2018-01-01

In this work, effect of crystallization parameters i.e., supersaturation, seeding, and temperature on polymorphism and crystal size of a non-steroidal anti-inflammatory drug, indomethacin (IMC), was investigated. Firstly, several crystallization solvents (ethanol, methanol, ethyl acetate, acetone...... of IMC from ethanol confirmed that the supersaturation, operating temperature and seeding does affect the polymorphism as well as crystal size distribution of IMC. Fine needle shaped crystals of metastable α-IMC were obtained at 5 °C with high supersaturation even in presence of γ-IMC seeds, while...... rhombic plates like crystals of thermodynamically stable γ-IMC were obtained in remaining experiments. The amount of seed loading only marginally influenced the crystal growth rate and median particle diameter (d50). Particle size analysis of crystals obtained showed bimodal distribution in all...

Anti-inflammatory effects of exercise

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Pedersen, Bente Klarlund

2017-01-01

and IL-10 is provoked by exercise and exerts direct anti-inflammatory effects by an inhibition of TNF-α and by stimulating IL-1ra, thereby limiting IL-1β signalling. Moreover, muscle-derived IL-6 appears to have direct anti-inflammatory effects and serves as a mechanism to improve glucose tolerance....... In addition, indirect anti-inflammatory effects of long-term exercise are mediated via improvements in body composition. CONCLUSION: Physical activity represents a natural, strong anti-inflammatory strategy with minor side effects and should be integrated in the management of patients with cardiometabolic...

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

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E. A. Spiridonov

2015-01-01

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

Potentiometric determination of ibuprofen, indomethacin and naproxen using an artificial neural network calibration

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A. HAKAN AKTAŞ

2008-01-01

Full Text Available In this study, three anti-inflammatory agents, namely ibuprofen, indomethacin and naproxen, were titrated potentiometrically using tetrabutylammonium hydroxide in acetonitrile solvent under a nitrogen atmosphere at 25 °C. MATLAB 7.0 software was applied for data treatment as a multivariate calibration tool in the potentiometric titration procedure. An artificial neural network (ANN was used as a multivariate calibration tool in the potentiometric titration to model the complex non-linear relationship between ibuprofen, indomethacin and naproxen concentrations and the millivolt (mV of the solutions measured after the addition of different volumes of the titrant. The optimized network predicted the concentrations of agents in synthetic mixtures. The results showed that the employed ANN can precede the titration data with an average relative error of prediction of less than 2.30 %.

Anti-inflammatory properties of desipramine and fluoxetine

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Portet Karine

2007-05-01

Full Text Available Abstract Background Antidepressants are heavily prescribed drugs and have been shown to affect inflammatory signals. We examined whether these have anti-inflammatory properties in animal models of septic shock and allergic asthma. We also analysed whether antidepressants act directly on peripheral cell types that participate in the inflammatory response in these diseases. Methods The antidepressants desipramine and fluoxetine were compared in vivo to the glucocorticoid prednisolone, an anti-inflammatory drug of reference. In a murine model of lipopolysaccharides (LPS-induced septic shock, animals received the drugs either before or after injection of LPS. Circulating levels of tumour necrosis factor (TNF-α and mortality rate were measured. In ovalbumin-sensitized rats, the effect of drug treatment on lung inflammation was assessed by counting leukocytes in bronchoalveolar lavages. Bronchial hyperreactivity was measured using barometric plethysmography. In vitro production of TNF-α and Regulated upon Activation, Normal T cell Expressed and presumably Secreted (RANTES from activated monocytes and lung epithelial cells, respectively, was analysed by immunoassays. Reporter gene assays were used to measure the effect of antidepressants on the activity of nuclear factor-κB and activator protein-1 which are involved in the control of TNF-α and RANTES expression. Results In the septic shock model, all three drugs given preventively markedly decreased circulating levels of TNF-α and mortality (50% mortality in fluoxetine treated group, 30% in desipramine and prednisolone treated groups versus 90% in controls. In the curative trial, antidepressants had no statistically significant effect, while prednisolone still decreased mortality (60% mortality versus 95% in controls. In ovalbumin-sensitized rats, the three drugs decreased lung inflammation, albeit to different degrees. Prednisolone and fluoxetine reduced the number of macrophages, lymphocytes

Evaluation of matrix type mucoadhesive tablets containing indomethacin for buccal application.

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Ikeuchi-Takahashi, Yuri; Sasatsu, Masanaho; Onishi, Hiraku

2013-09-10

Nonsteroidal anti-inflammatory drugs (NSAIDs) are administered for pain relief from oral mucositis. However, the systemic administration of NSAIDs is limited due to systemic side effects. To avoid these side effects and treat local lesions effectively, a matrix type mucoadhesive tablet was developed. A mixture of hard fat, ethylcellulose (EC) and polyethylene glycol (PEG) was used as a matrix base, and indomethacin (IMC) was used as the principal agent. In tablets consisting of hard fat, EC and IMC, the drug release was sustained. In tablets consisting of hard fat, EC, considerable amounts of PEG and IMC, the drug release was relatively increased and IMC existed as the molecular phase or in an amorphous state. The in vitro adhesive force of the tablets consisting of hard fat, EC, considerable amounts of PEG and IMC was significantly increased as compared with the tablets consisting of hard fat and IMC. A significantly high tissue concentration and significantly low plasma concentration were observed after buccal administration of this matrix type mucoadhesive tablet as compared with that after oral administration of IMC. Thus, the matrix type mucoadhesive tablet has good potential as a preparation for the treatment of pain due to oral aphtha. Copyright © 2013 Elsevier B.V. All rights reserved.

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

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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.

Chemical composition and anti-inflammatory evaluation of essential oils from leaves and stem barks from Drimys brasiliensis Miers (Winteraceae)

International Nuclear Information System (INIS)

Lago, Joao Henrique G.; Carvalho, Larissa A.C.; Silva, Flavia S. da; Romoff, Paulete; Toyama, Daniela de O.; Favero, Oriana A.

2010-01-01

The essential oils from leaves and stem barks from Drimys brasiliensis Miers (Winteraceae) were individually obtained by hydrodistillation and their compounds characterized by use of GC/FID and GC/MS. The main identified derivatives were monoterpenes (leaves 4.31% and stem barks 90.02%) and sesquiterpenes (leaves 52.31% and stem barks 6.35%). Additionally, the sesquiterpene polygodial was isolated from hexane extract from stem barks of D. brasiliensis after chromatographic steps and characterized by spectroscopic means, mainly NMR. Aiming the evaluation of anti-inflammatory potential, the crude essential oils and the sesquiterpene polygodial were subjected to bioassays to evaluate the acute toxicity of these compounds as well as the anti-inflammatory and antinociceptive activities induced by carrageenan and formalin in mice. Ours results showed that essential oil obtained from the stem barks significantly reduced the oedema induced by carrageenan. The anti-inflammatory effect induced by stem barks oil (at 200 mg kg -1 ) was similar to observed for indomethacin (at 10 mg kg -1 ) and superior for polygodial (at 200 mg kg -1 ) in 30 and 60 min after the administration of essential oils. The inflammatory response induced by formalin was effective to the stem barks oil (62.5%) in comparison to polygodial (50.0%). (author)

Chemical composition and anti-inflammatory evaluation of essential oils from leaves and stem barks from Drimys brasiliensis Miers (Winteraceae)

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Lago, Joao Henrique G., E-mail: joao.lago@unifesp.b [Universidade Federal de Sao Paulo (UNIFESP-EPM), Diadema, SP (Brazil). Dept. de Ciencias Exatas e da Terra; Carvalho, Larissa A.C.; Silva, Flavia S. da; Romoff, Paulete [Universidade Presbiteriana Mackenzie, Sao Paulo, SP (Brazil). Centro de Ciencias e Humanidades; Toyama, Daniela de O.; Favero, Oriana A. [Universidade Presbiteriana Mackenzie, Sao Paulo, SP (Brazil). Centro de Ciencias Biologicas e da Saude

2010-07-01

The essential oils from leaves and stem barks from Drimys brasiliensis Miers (Winteraceae) were individually obtained by hydrodistillation and their compounds characterized by use of GC/FID and GC/MS. The main identified derivatives were monoterpenes (leaves 4.31% and stem barks 90.02%) and sesquiterpenes (leaves 52.31% and stem barks 6.35%). Additionally, the sesquiterpene polygodial was isolated from hexane extract from stem barks of D. brasiliensis after chromatographic steps and characterized by spectroscopic means, mainly NMR. Aiming the evaluation of anti-inflammatory potential, the crude essential oils and the sesquiterpene polygodial were subjected to bioassays to evaluate the acute toxicity of these compounds as well as the anti-inflammatory and antinociceptive activities induced by carrageenan and formalin in mice. Ours results showed that essential oil obtained from the stem barks significantly reduced the oedema induced by carrageenan. The anti-inflammatory effect induced by stem barks oil (at 200 mg kg{sup -1}) was similar to observed for indomethacin (at 10 mg kg{sup -1}) and superior for polygodial (at 200 mg kg{sup -1}) in 30 and 60 min after the administration of essential oils. The inflammatory response induced by formalin was effective to the stem barks oil (62.5%) in comparison to polygodial (50.0%). (author)

Indomethacin treatment prevents high fat diet-induced obesity and insulin resistance but not glucose intolerance in C57BL/6J Mice

DEFF Research Database (Denmark)

Fjære, Even; Aune, Ulrike Liisberg; Røen, Kristin

2014-01-01

Chronic low grade inflammation is closely linked to obesity-associated insulin resistance. To examine how administration of the anti-inflammatory compound indomethacin, a general cyclooxygenase inhibitor, affected obesity development and insulin sensitivity, we fed obesity-prone male C57BL/6J mice...... a high fat/high sucrose (HF/HS) diet or a regular diet supplemented or not with indomethacin (±INDO) for 7 weeks. Development of obesity, insulin resistance, and glucose intolerance was monitored, and the effect of indomethacin on glucose-stimulated insulin secretion (GSIS) was measured in vivo...... and in vitro using MIN6 β-cells. We found that supplementation with indomethacin prevented HF/HS-induced obesity and diet-induced changes in systemic insulin sensitivity. Thus, HF/HS+INDO-fed mice remained insulin-sensitive. However, mice fed HF/HS+INDO exhibited pronounced glucose intolerance. Hepatic glucose...

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

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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.

[Cyclooxygenase inhibitors and antiplatelet effect of acetylsalicylic acid. selective approach to nonsteroidal anti-inflammatory drugs in cardiological practice].

Science.gov (United States)

Lomakin, N V; Gruzdev, A K

2011-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) represent class of medicines which is wide concerning chemical structure and mechanism of action. In the light of contradictory data on efficacy and safety of NSAID in cardiovascular patients selection of most appropriate NSAID (basing on profile of efficacy and safety) in patients receiving continuous therapy with low dose aspirin appears to be a problem. In this paper we discuss peculiarities of drug interaction between cyclooxygenase inhibitors and acetylsalicylic acid, and principles of selection of adequate NSAI.

Screening of Bauhinia purpurea Linn. for analgesic and anti-inflammatory activities

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Shreedhara, C.S.; Vaidya, V.P.; Vagdevi, H.M.; Latha, K.P.; Muralikrishna, K.S.; Krupanidhi, A.M.

2009-01-01

Objectives: Ethanol extract of the stem of Bauhinia purpurea Linn. was subjected to analgesic and anti-inflammatory activities in animal models. Materials and Methods: Albino Wistar rats and mice were the experimental animals respectively. Different CNS depressant paradigms like analgesic activity (determined by Eddy's hot plate method and acetic acid writhing method) and anti-inflammatory activity determined by carrageenan induced paw edema using plethysmometer in albino rats) were carried out, following the intra-peritoneal administration of ethanol extract of Bauhinia purpurea Linn. (BP) at the dose level of 50 mg/kg and 100 mg/kg. Results: The analgesic and anti-inflammatory activities of ethanol extracts of BP were significant (P Bauhinia purpurea has shown significant analgesic and anti-inflammatory activities at the dose of 100 mg/kg and was comparable with corresponding standard drugs. The activity was attributed to the presence of phytoconstituents in the tested extract. PMID:20336222

Development and application of SPE/CZE method for detection and determination of selected non-steroidal anti-inflammatory drugs in wastewater

Czech Academy of Sciences Publication Activity Database

Čapka, Lukáš; Lacina, P.; Vávrová, M.

2012-01-01

Roč. 21, 11A (2012), s. 3312-3317 ISSN 1018-4619 Institutional research plan: CEZ:AV0Z40310501 Keywords : Non-steroidal anti-inflammatory drugs * capillary zone electrophoresis * solid phase extraction * wastewater Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 0.641, year: 2012

Bio-Electro-Fenton process for the degradation of Non-Steroidal Anti-Inflammatory Drugs in wastewater

DEFF Research Database (Denmark)

Nadais, Helena; Li, Xiaohu; Alves, Nadine

2018-01-01

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are ubiquitous municipal wastewater pollutants of which several are resistant to degradation in conventional wastewater treatment, and represent a major environmental health concern worldwide. An alternative treatment, the bio-electro-Fenton process......, has received increasing attention in past years. In this process the strong oxidant •HO is formed using the electrons derived from bacterial oxidation of organic substrate. In this work, a laboratory scale microbial electrolysis cell based bio-electro-Fenton process was developed for the treatment...

Preparation and in-vitro evaluation of indomethacin nanoparticles

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A Rezaei Mokarram

2010-09-01

Full Text Available "nBackground and the purpose of the study: During the last two decades one of the most important problems in drug formulations has been low aqueous solubility of new molecules. However, numerous techniques, such as milling, co-solvent solubilization and solid dispersion have been used conventionally for aqueous solubility enhancement and the rate of solubility. Recently, nanoparticle engineering processes have been developed and reported for pharmaceutical applications to increase the dissolution rate of low-soluble drugs which in turn may leads to substantial increases in bioavailability. In this study, a controlled precipitation method was used to produce indomethacin nano-solid suspension in a polymeric matrix (as a model, in order to increase the solubility and rate of the dissolution of poorly soluble model drug. "nMethods: Nano-solid suspension of indomethacin in polyvinyl pyrrolidine (PVP was prepared by controlled precipitation technique, characterized by differential scanning calorimetry (DSC, X-ray diffraction (XRD, Fourier Transform Infrared Spectroscopy (FTIR and evaluated for in vitro solubility and dissolution rate. Results and major conclusion:Absence of thermal and diffractional peaks in DSC and XRD studies indicated that indomethacin interacts with PVP in solid phase. The solubility of indomethacin in nano-solid suspension compared to crystalline form was increased to about four-fold. It was found that particle size distribution depend to the polymer MW and drug: polymer ratios. Spectroscopy methods and Transmission Electron Microscopy (TEM images showed that indomethacin dispersed as amorphous nanosize particles in freeze dried powder. Enhanced solubility and dissolution rate of indomethacin compared to physical mixtures and crystalline form of indomethacin (polymorph I, demonstrated that it interacts with PVP via hydrogen bond and probably forming eutectic mixture.

Anti-inflammatory effects of ursodeoxycholic acid by lipopolysaccharide-stimulated inflammatory responses in RAW 264.7 macrophages.

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Wan-Kyu Ko

Full Text Available The aim of this study was to investigate the anti-inflammatory effects of Ursodeoxycholic acid (UDCA in lipopolysaccharide (LPS-stimulated RAW 264.7 macrophages.We induced an inflammatory process in RAW 264.7 macrophages using LPS. The anti-inflammatory effects of UDCA on LPS-stimulated RAW 264.7 macrophages were analyzed using nitric oxide (NO. Pro-inflammatory and anti-inflammatory cytokines were analyzed by quantitative real time polymerase chain reaction (qRT-PCR and enzyme-linked immunosorbent assay (ELISA. The phosphorylations of extracellular signal-regulated kinase (ERK, c-Jun N-terminal kinase (JNK, and p38 in mitogen-activated protein kinase (MAPK signaling pathways and nuclear factor kappa-light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα signaling pathways were evaluated by western blot assays.UDCA decreased the LPS-stimulated release of the inflammatory mediator NO. UDCA also decreased the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α, interleukin 1-α (IL-1α, interleukin 1-β (IL-1β, and interleukin 6 (IL-6 in mRNA and protein levels. In addition, UDCA increased an anti-inflammatory cytokine interleukin 10 (IL-10 in the LPS-stimulated RAW 264.7 macrophages. UDCA inhibited the expression of inflammatory transcription factor nuclear factor kappa B (NF-κB in LPS-stimulated RAW 264.7 macrophages. Furthermore, UDCA suppressed the phosphorylation of ERK, JNK, and p38 signals related to inflammatory pathways. In addition, the phosphorylation of IκBα, the inhibitor of NF-κB, also inhibited by UDCA.UDCA inhibits the pro-inflammatory responses by LPS in RAW 264.7 macrophages. UDCA also suppresses the phosphorylation by LPS on ERK, JNK, and p38 in MAPKs and NF-κB pathway. These results suggest that UDCA can serve as a useful anti-inflammatory drug.

Anti-ulcerogenic mechanism of magnesium in indomethacin ...

African Journals Online (AJOL)

olayemitoyin

laxatives and antacids have been reported to prevent ulcer formation but the mechanisms underlying this potential is unknown. ..... quantity (Figure 3D) even though the indomethacin ... Barragan-Roddiguez, L., (2008): Efficacy and safety.

Protective effect of nonsteroidal anti-inflammatory drugs on colorectal adenomas is modified by a polymorphism in peroxisome proliferator-activated receptor [Delta

NARCIS (Netherlands)

Siezen, C.L.E.; Tijhuis, M.J.; Kram, N.R.; Soest, van E.M.; Jong, de D.J.; Fodde, R.; Kranen, H.J.; Kampman, E.

2006-01-01

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a decreased risk of colorectal tumors. Single nucleotide polymorphisms (SNPs) in target genes of NSAID action, and their haplotypes, might modulate this protective effect. METHODS: A case-control study including 724 cases

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.

Study on analgesic and anti-inflammatory properties of Cordia myxa fruit hydro-alcoholic extract.

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Ranjbar, Mohammadmehdi; Varzi, Hossein Najafzadeh; Sabbagh, Atefeh; Bolooki, Adeleh; Sazmand, Alireza

2013-12-15

Cordia myxa is a plant which is used in tropical regions of the world. Analgesic and anti-inflammatory effect of fruit of this medicinal plant was investigated in mice. Hydro-alcoholic extract of it was prepared by maceration method. Formalin test was conducted in six groups of mice (6 animals in each group) and acetic acid test in another six groups (6 mice). Groups one to six in each test were administered normal saline, oral indomethacin, intraperitoneal tramadol, 100 mg kg(-1) oral extract, 200 mg kg(-1) oral extract and 100 mg kg(-1) intraperitoneal extract, respectively. The duration of foot lickings were calculated in formalin- administered (1st) group within min 0 to 5 (acute phase) and 15 to 25 (chronic phase). Acetic acid-induced writhings were counted within 10 min in the 2nd group. The results showed that hydro-alcoholic extract of Cordia myxa fruit was considerably effective in formalin test. Also, analgesic and anti-inflammatory properties of this plant's fruit in both acute and chronic phase are somewhat similar to these properties in the study on animal model of experimental colitis.

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...... a protective effect against CRC. Further studies of the effective dose of aspirin and the potential interaction between NSAID use and BMI are warranted....

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.

Resistance Training with Co-ingestion of Anti-inflammatory Drugs Attenuates Mitochondrial Function

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Daniele A. Cardinale

2017-12-01

Full Text Available Aim: The current study aimed to examine the effects of resistance exercise with concomitant consumption of high vs. low daily doses of non-steroidal anti-inflammatory drugs (NSAIDs on mitochondrial oxidative phosphorylation in skeletal muscle. As a secondary aim, we compared the effects of eccentric overload with conventional training.Methods: Twenty participants were randomized to either a group taking high doses (3 × 400 mg/day of ibuprofen (IBU; 27 ± 5 year; n = 11 or a group ingesting a low dose (1 × 75 mg/day of acetylsalicylic acid (ASA; 26 ± 4 year; n = 9 during 8 weeks of supervised knee extensor resistance training. Each of the subject's legs were randomized to complete the training program using either a flywheel (FW device emphasizing eccentric overload, or a traditional weight stack machine (WS. Maximal mitochondrial oxidative phosphorylation (CI+IIP from permeabilized skeletal muscle bundles was assessed using high-resolution respirometry. Citrate synthase (CS activity was assessed using spectrophotometric techniques and mitochondrial protein content using western blotting.Results: After training, CI+IIP decreased (P < 0.05 in both IBU (23% and ASA (29% with no difference across medical treatments. Although CI+IIP decreased in both legs, the decrease was greater (interaction p = 0.015 in WS (33%, p = 0.001 compared with FW (19%, p = 0.078. CS activity increased (p = 0.027 with resistance training, with no interactions with medical treatment or training modality. Protein expression of ULK1 increased with training in both groups (p < 0.001. The increase in quadriceps muscle volume was not correlated with changes in CI+IIP (R = 0.16.Conclusion: These results suggest that 8 weeks of resistance training with co-ingestion of anti-inflammatory drugs reduces mitochondrial function but increases mitochondrial content. The observed changes were not affected by higher doses of NSAIDs consumption, suggesting that the resistance training

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

Science.gov (United States)

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

2000-12-01

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 signalling of these possible interactions, which are often not explicitly reported, utilising reports of adverse drug reactions in data sets of SRS. As an example, the influence of concomitant use of diuretics and non-steroidal anti-inflammatory drugs (NSAIDs) on symptoms indicating a decreased efficacy of diuretics was examined using reports received by the Netherlands Pharmacovigilance Foundation Lareb. Reports received between 1 January 1990 and 1 January 1999 of patients older than 50 years were included in the study. Cases were defined as reports with symptoms indicating a decreased efficacy of diuretics, non-cases as all other reports. Exposure categories were the use of NSAIDs or diuretics versus the use of neither of these drugs. The influence of the combined use of both drugs was examined using logistic regression analysis. The odds ratio of the statistical interaction term of the combined use of both drugs was increased [adjusted odds ratio 2.0, 95% confidence interval (CI) 1.1-3.7], which may indicate an enhanced effect of concomitant drug use. The findings illustrate that spontaneous reporting systems have a potential for signal detection and the analysis of possible drug-drug interactions. The method described may enable a more active approach in the detection of drug-drug interactions after marketing.

Anti-inflammatory activity of Ambrosia artemisiaefolia and Rhoeo spathacea.

Science.gov (United States)

Pérez G, R M

1996-09-01

Alcoholic extracts of the leaves of Ambrosia artemisiaefolia and Rhoeo spathacea have been investigated for anti-inflammatory activity using various experimental models of inflammation (croton oil ear oedema, carrageenan-induced edema, cotton pellet granuloma and formaldehyde induced arthritis) and the results compared with phenylbutazone and bethamethasone, standard anti-inflammatory drugs. These extracts at doses of 50, 100 and 150mg/kg of A. artemisiaefolia and R. spathacea, showed significant inhibition of acute oedema in rats and mice induced by the phlogistic agents, carrageenan and croton oil, in a dose-dependant manner. The ethanol extracts reduced cotton pellet granuloma and caused a statistically significant inhibitory effect on edema in the chronic model of formaldehyde arthritis in rats. Since Ambrosia artemisiaefolia and Rhoeo spathacea were found to be effective in both acute and chronic phases of inflammation they can be considered as general anti-inflammatory agents. Copyright © 1996 Gustav Fischer Verlag · Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.

Anti-inflammatory Activity of Epimedium brevicornu Maxim Ethanol Extract.

Science.gov (United States)

Huang, Shan; Meng, Ning; Chang, Bingquan; Quan, Xianghua; Yuan, RuiYing; Li, Bin

2018-04-05

Epimedium brevicornu Maxim has been used as a traditional herbal drug in China. In this study, the anti-inflammatory effects of E. brevicornu Maxim ethanol extract (EBME) were investigated in RAW264.7 macrophages and mice challenged with lipopolysaccharide (LPS). Results showed that EBME attenuated inflammation by decreasing the production of several proinflammatory mediators, such as nitric oxide (NO), prostaglandin (PG) E 2 , inducible nitric oxide synthase, and cyclooxygenase-2, in LPS-stimulated RAW264.7 macrophages. EBME increased the expression of heme oxygenase-1 (HO-1) and promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2. The inhibitory effects of EBME on LPS-stimulated NO and PGE 2 expression were partially reversed by HO-1 inhibitor. EBME also elicited an anti-inflammatory effect by inhibiting the production of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in LPS-induced peritonitis. Therefore, EBME exhibited anti-inflammatory effects in vitro and in vivo.

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

Science.gov (United States)

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. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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)

Herraez-Hernandez, R.; van de Merbel, N.C.; Brinkman, U.A.T.

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

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

Anti-Inflammatory and Antinociceptive Effects of Salbutamol on Acute and Chronic Models of Inflammation in Rats: Involvement of an Antioxidant Mechanism

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Hulya Uzkeser

2012-01-01

Full Text Available The possible role of β-2 adrenergic receptors in modulation of inflammatory and nociceptive conditions suggests that the β-2 adrenergic receptor agonist, salbutamol, may have beneficial anti-inflammatory and analgesic effects. Therefore, in this study, we induced inflammatory and nociceptive responses with carrageenan-induced paw edema or cotton-pellet-induced granuloma models, both of which result in oxidative stress. We hypothesized that salbutamol would prevent inflammatory and nociceptive responses by stimulating β-2 adrenergic receptors and the prevention of generation of ROS during the acute inflammation process in rats. Both doses of salbutamol used in the study (1 and 2 mg/kg effectively blocked the acute inflammation and inflammatory nociception induced by carrageenan. In the cotton-pellet-induced granuloma test, both doses of salbutamol also significantly decreased the weight of granuloma tissue on the cotton pellets when compared to the control. Anti-inflammatory and analgesic effects of salbutamol were found to be comparable with those of indomethacin. Salbutamol decreased myeloperoxidase (MPO activity and lipid peroxidation (LPO level and increased the activity of superoxide dismutase (SOD and level of glutathione (GSH during the acute phase of inflammation. In conclusion, salbutamol can decrease acute and chronic inflammation, possibly through the stimulation of β-2 adrenergic receptors. This anti-inflammatory effect may be of significance in asthma treatment, where inflammation also takes part in the etiopathology. This study reveals that salbutamol has significant antioxidative effects, which at least partially explain its anti-inflammatory capabilities. These findings presented here may also shed light on the roles of β-2 adrenergic receptors in inflammatory and hyperalgesic conditions.

Study of evaluation of anti-inflammatory activity of macrolide antibiotics in rats: an experimental study

OpenAIRE

Punam A. Gosavi; Jugalkishore B. Jaju; Vishal M. Ubale; Ganesh R. Pawar; Shrikant C. Dharmadhikari

2015-01-01

Background: Inflammation is a complex and dynamic condition in which many changes take place at the site of inflammation, as well as systemically. In general, inflammatory response acts to protect the host, but many times it goes unchecked with tissue destruction leading to a spectrum of inflammatory disorders. Anti-inflammatory drugs have long been used to treat spectrum of inflammatory conditions. Anti-inflammatory agents, in use today, though have efficacy, cause a variety of side effects ...

Pharmacokinetic equivalence study of nonsteroidal anti-inflammatory drug etoricoxib

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Tjandrawinata RR

2018-04-01

drug/reference drug were 103.40% (98.70%–108.32% for AUC0-72h and 109.26% (100.18%–119.18% for Cmax. No clinically significant differences in tmax and t½values were found between the test drug and the reference drug. No adverse events were experienced by the subjects during this study.Conclusion: The present study demonstrated that the evaluated generic etoricoxib 120 mg film-coated tablets were bioequivalent to the reference drug. Keywords: bioavailability, bioequivalence, etoricoxib, nonsteroidal anti-inflammatory drug, selective cyclooxygenase-2 inhibitor 

[Peroral and transdermal application of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of regional musculoskeletal pain syndromes].

Science.gov (United States)

Hodinka, László; Bálint, Géza; Budai, Erika; Géher, Pál; Papp, Renáta; Somogyi, Péter; Szántó, Sándor; Vereckei, Edit

2017-12-01

In this review the available evidences regarding the most frequently applied medication (peroral and transdermal non-steroidal anti-inflammatory agents) for the most frequent musculoskeletal complaints (regional pain syndromes) have been collected for the appropriate medical professionals who are most frequently faced with these conditions (general practitioners, rheumatologists, orthopedics, occupational and sports medicine experts). The special population at risk (with repeated and high energy overuse because of occupational or sport activities) and the pathology of their syndromes are identified. Mode of action, pharmacological properties of the non-steroidal anti-inflammatory drugs and the unwanted effects of their application especially in infants and elderly are highlighted. Recommendations of the general and specific pain management guidelines have been selected and listed in the review. Orv Hetil. 2017; 158(Suppl. 3): 3-30.

Selective micellar electrokinetic chromatographic method for simultaneous determination of some pharmaceutical binary mixtures containing non-steroidal anti-inflammatory drugs

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Michael E. El-Kommos

2013-02-01

Full Text Available A simple and selective micellar electrokinetic chromatographic (MEKC method has been developed for the analysis of five pharmaceutical binary mixtures containing three non-steroidal anti-inflammatory drugs (NSAIDs. The investigated mixtures were Ibuprofen (IP–Paracetamol (PC, Ibuprofen (IP–Chlorzoxazone (CZ, Ibuprofen (IP–Methocarbamol (MC, Ketoprofen (KP–Chlorzoxazone (CZ and Diclofenac sodium (DS–Lidocaine hydrochloride (LC. The separation was run for all mixtures using borate buffer (20 mM, pH 9 containing 15% (v/v methanol and 100 mM sodium dodecyl sulphate (SDS at 15 kV and the components were detected at 214 nm. Different factors affecting the electrophoretic mobility of the seven investigated drugs were studied and optimized. The method was validated according to international conference of harmonization (ICH guidelines and United States pharmacopoeia (USP. The method was applied to the analysis of five pharmaceutical binary mixtures in their dosage forms. The results were compared with other reported high performance liquid chromatographic methods and no significant differences were observed. Keywords: Capillary electrophoresis, Micellar electrokinetic chromatographic method, Non-steroidal anti-inflammatory drugs, Pharmaceutical binary mixtures, Pharmaceutical analysis

Evaluation of in vivo anti-inflmmatory and analgesic activity of Dillenia indica f. elongata (Miq. Miq. and Shorea robusta stem bark extracts

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Preet Amol Singh

2016-01-01

Full Text Available Objective: To evaluate the in vivo anti-inflammatory and analgesic potential of stem bark extract of Dillenia indica f. elongata (Miq. Miq. (D. indica f. elongata and its comparison with Shorea robusta Gaertn. (S. robusta and respective standard drugs in experimental animals. Methods: Analgesic models (hot plate, tail flick and formalin induced paw licking along with acute (carrageenan-induced and chronic (formalin-induced models of inflammation were evaluated for analgesic and anti-inflammatory potential of the plant extracts. Results: The results of the study showed that the ethyl acetate extracts of D. indica f. elongata (100 and 300 mg/kg and S. robusta (100 and 300 mg/kg possessed good central as well as peripheral analgesic activity as compared with pentazocine and indomethacin (10 mg/kg respectively. The extracts showed significant (P < 0.01 activity in carrageenan- and formalininduced chronic inflammation models by using indomethacin (8 mg/kg and diclofenac (13.5 mg/kg as standard drugs respectively. Conclusions: It can be concluded that the presence of major constituents like flavonoids, tannins and phenols in the ethyl acetate extracts of stem bark of D. indica f. elongata (100 and 300 mg/kg and S. robusta (100 and 300 mg/kg may be responsible for its analgesic and antiinflammatory activity.

Determining the Molecular Pathways Underlying the Protective Effect of Non-Steroidal Anti-Inflammatory Drugs for Alzheimer's Disease: A Bioinformatics Approach

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Alejo J Nevado-Holgado

Full Text Available Alzheimer's disease (AD represents a substantial unmet need, due to increasing prevalence in an ageing society and the absence of a disease modifying therapy. Epidemiological evidence shows a protective effect of non steroidal anti inflammatory (NSAID drugs, and genome wide association studies (GWAS show consistent linkage to inflammatory pathways; both observations suggesting anti-inflammatory compounds might be effective in AD therapy although clinical trials to date have not been positive.In this study, we use pathway enrichment and fuzzy logic to identify pathways (KEGG database simultaneously affected in both AD and by NSAIDs (Sulindac, Piroxicam, Paracetamol, Naproxen, Nabumetone, Ketoprofen, Diclofenac and Aspirin. Gene expression signatures were derived for disease from both blood (n = 344 and post-mortem brain (n = 690, and for drugs from immortalised human cell lines exposed to drugs of interest as part of the Connectivity Map platform. Using this novel approach to combine datasets we find striking overlap between AD gene expression in blood and NSAID induced changes in KEGG pathways of Ribosome and Oxidative Phosphorylation. No overlap was found in non NSAID comparison drugs. In brain we find little such overlap, although Oxidative Phosphorylation approaches our pre-specified significance level.These findings suggest that NSAIDs might have a mode of action beyond inflammation and moreover that their therapeutic effects might be mediated in particular by alteration of Oxidative Phosphorylation and possibly the Ribosome pathway. Mining of such datasets might prove increasingly productive as they increase in size and richness. Keywords: Alzheimer's disease, NSAID, Inflammation, Fuzzy logic, Ribosome

Anti-inflammatory and antipyretic activities of artesunate in experimental animals

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Ette Ettebong

2016-09-01

Full Text Available Objective: To evaluate the anti-inflammatory and antipyretic potentials of artesunate in albino wistar mice and rats respectively. Methods: For the anti-inflammatory activity, artesunate (5 mg/kg was administered orally against egg albumin- and xylene-induced inflammation in mice using ibuprofen (50 mg/kg as standard drug. To assess antipyretic activity, artesunate (5 mg/kg was administered orally against amphetamine- and 2, 4-dinitrophenol-induced pyrexia in rats using ibuprofen (15 mg/ kg as standard drug. Results: The result showed that artesunate significantly (P < 0.001–0.010 reduced inflammation induced by egg albumin and xylene in a time-dependent manner. It also significantly (P < 0.001–0.050 and time-dependently reduced pyrexia induced by amphetamine and 2, 4-dinitrophenol. These reductions were similar to those produced by the standard drug ibuprofen, and thereby demonstrating that artesunate possesses antiinflammatory and antipyretic activities. Conclusions: These results further support the rationale for the use of artesunate in the treatment of malaria, a disease characterized by fever and inflammation and open up possibilities of its usefulness in other inflammatory and feverish diseases.

[Recommendation for the prevention and treatment of non-steroidal anti-inflammatory drug-induced gastrointestinal ulcers and its complications].

Science.gov (United States)

2017-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are a broad class of non glucocorticoid drugs which are extensively used in anti-inflammatory, analgesic, and antipyretic therapies. However, NSAIDs may cause many side effects, most commonly in gastrointestinal(GI) tract. Cardiovascular system, kidney, liver, central nervous system and hematopoietic system are also involved. NSAID-induced GI side effects not only endanger the patients' health, increase mortality, but also greatly increase the cost of medical care. Therefore, how to reduce GI side effects is of particular concern to clinicians. The Chinese Rheumatism Data Center(CRDC) and Chinese Systemic Lupus Erythematosus Treatment and Research Group(CSTAR) compose a "Recommendation for the prevention and treatment of non-steroidal anti-inflammatory drug-induced gastrointestinal ulcers and its complications" , as following: (1) GI lesions are the most common side effects of NSAIDs. (2) NSAID-induced GI side effects include gastritis, esophagitis, gastric and duodenal ulcers, bleeding, perforation and obstruction. (3) With the application of capsule endoscopy and small intestinal endoscopy, growing attention is being paid to the NASID-induced small intestine mucosa damage, which is mainly erosion and ulcer. (4) Risk factors related to NSAID-induced GI ulcers include: Helicobacter pylori (Hp) infection, age> 65 years, past history of GI ulcers, high doses of NSAIDs, multiple-drug combination therapy, and comorbidities, such as cardiovascular disease and nephropathy.(5) GI and cardiovascular function should be evaluated before using NSAIDs and gastric mucosal protective agents. (6) The risk of GI ulcers and complications caused by selective cyclooxygenase-2 (COX-2) inhibitors is less than that of non-selective COX-2 inhibitors. (7)Hp eradication therapy helps to cure GI ulcers and prevent recurrence when Hp infection is positive in NSAID-induced ulcers. (8) Proton pump inhibitor (PPI) is the first choice for the

"Smart tattoo" glucose biosensors and effect of coencapsulated anti-inflammatory agents.

Science.gov (United States)

Srivastava, Rohit; Jayant, Rahul Dev; Chaudhary, Ayesha; McShane, Michael J

2011-01-01

Minimally invasive glucose biosensors with increased functional longevity form one of the most promising techniques for continuous glucose monitoring. In the present study, we developed a novel nanoengineered microsphere formulation comprising alginate microsphere glucose sensors and anti-inflammatory-drug-loaded alginate microspheres. The formulation was prepared and characterized for size, shape, in vitro drug release, biocompatibility, and in vivo acceptability. Glucose oxidase (GOx)- and Apo-GOx-based glucose sensors were prepared and characterized. Sensing was performed both in distilled water and simulated interstitial body fluid. Layer-by-layer self-assembly techniques were used for preventing drug and sensing chemistry release. Finally, in vivo studies, involving histopathologic examination of subcutaneous tissue surrounding the implanted sensors using Sprague-Dawley rats, were performed to test the suppression of inflammation and fibrosis associated with glucose sensor implantation. The drug formulation showed 100% drug release with in 30 days with zero-order release kinetics. The GOx-based sensors showed good enzyme retention and enzyme activity over a period of 1 month. Apo-GOx-based visible and near-infrared sensors showed good sensitivity and analytical response range of 0-50 mM glucose, with linear range up to 12 mM glucose concentration. In vitro cell line studies proved biocompatibility of the material used. Finally, both anti-inflammatory drugs were successful in controlling the implant-tissue interface by suppressing inflammation at the implant site. The incorporation of anti-inflammatory drug with glucose biosensors shows promise in improving sensor biocompatibility, thereby suggesting potential application of alginate microspheres as "smart tattoo" glucose sensors with increased functional longevity. © 2010 Diabetes Technology Society.

Antipyretic, analgesic and anti-inflammatory activity of Viola betonicifolia whole plant.

Science.gov (United States)

Muhammad, Naveed; Saeed, Muhammad; Khan, Haroon

2012-05-02

Pyrexia, algesia and inflammation are associated with several pathological conditions. Synthetic drugs available for the treatment of these conditions cause multiple unwanted effects. Several studies are ongoing worldwide to find natural healing agents with better safety profile. The current study was thus aimed at evaluating antipyretic, analgesic and anti-inflammatory activities of the methanolic extract of whole plant of V. betonicifolia (VBME). VBME was employed to assess antipyretic activity in yeast induced hyperthermia. Analgesic profile was ascertained in acetic acid induced writhing, hot plat and tail immersion test. Nevertheless, the anti-inflammatory activity was tested in carrageenan induced paw edema and histamine induced inflammatory tests. BALB/c mice were used at test doses of 100, 200 and 300 mg/kg body weight intra peritoneally (i.p). In yeast induced pyrexia, VBME demonstrated dose dependently (78.23%) protection at 300 mg/kg, similar to standard drug, paracetamol (90%) at 150 mg/kg i.p. VBME showed a dose dependent analgesia in various pain models i.e. acetic acid, hot plat and tail immersion having 78.90%, 69.96% and 68.58% protection respectively at 300 mg/kg. However, the analgesic action of VBME was completely antagonized by the injection of naloxone like opiate antagonists. Similarly carrageenan and histamine induces inflammation was significantly antagonized by VBME, 66.30% and 60.80% respectively at 300 mg/kg. It is concluded that VBME has marked antipyretic, analgesic and anti-inflammatory activities in various animal models and this strongly supports the ethnopharmacological uses of Viola betonicifolia as antipyretic, analgesic and anti-inflammatory plant.

Inflammation in Depression and the Potential for Anti-Inflammatory Treatment

DEFF Research Database (Denmark)

Köhler, Karl Ole; Krogh, Jesper; Mors, Ole

2016-01-01

, nonsteroidal anti-inflammatory drugs (NSAIDs) and cytokine-inhibitors have shown antidepressant treatment effects compared to placebo, but also statins, poly-unsaturated fatty acids, pioglitazone, minocycline, modafinil, and corticosteroids may yield antidepressant treatment effects. However, the complexity...

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...... 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...... associated with low-dose aspirin use among nulliparous women (OR 0.82, 95 % CI 0.70-0.95) and with non-aspirin NSAID use among women having used HRT (OR 0.90, 95 % CI 0.82-0.99). CONCLUSIONS: We found no association between use of NSAIDs and endometrial cancer risk overall, although there were some...

Are anti-inflammatory agents effective in treating gingivitis as solo or adjunct therapies? A systematic review.

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Polak, David; Martin, Conchita; Sanz-Sánchez, Ignacio; Beyth, Nurit; Shapira, Lior

2015-04-01

Systematically review the scientific evidence for efficiency of anti-inflammatory agents against gingivitis, either as solo treatments or adjunctive therapies. A protocol was developed aimed to answer the following focused question: "Are anti-inflammatory agents effective in treating gingivitis as solo or adjunct therapies?" RCTs and cohort studies on anti-inflammatory agents against gingivitis studies were searched electronically. Screening, data extraction and quality assessment were conducted. The primary outcome measures were indices of gingival inflammation. A sub-analysis was performed dividing the active agents into anti-inflammatory and other drugs. The search identified 3188 studies, of which 14 RCTs met the inclusion criteria. The use of anti-inflammatory or other agents, in general showed a higher reduction in the test than in the control in terms of gingival indexes and bleeding scores. Only two RCTs on inflammatory drugs could be meta-analysed, showing a statistically significant reduction in the GI in the experimental group [WMD = -0.090; 95% CI (-0.105; -0.074); p = 0.000]. However, the contribution of both studies to the global result was unbalanced (% weight: 99.88 and 0.12 respectively). Most of the tested material showed beneficial effect as anti-inflammatory agents against gingivitis, either as a single treatment modality or as an adjunctive therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Inhibition of the development of myringosclerosis by local administration of fenspiride, an anti-inflammatory drug.

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Mattsson, C; Hellström, S

1997-01-01

Earlier studies have revealed a relationship between the development of myringosclerosis and oxygen-derived free radicals. The latter can be blocked by the anti-inflammatory drug fenspiride. The present study was undertaken to test the ability of fenspiride to prevent myringosclerosis from developing during healing of the tympanic membrane. Myringotomized rats were treated with either topical applications or intraperitoneal injections of fenspiride for 12 days, after which the tympanic membranes were examined by otomicroscopy and studied histologically by light microscopy. Topically applied fenspiride was found to inhibit the development of sclerotic lesions, whereas intraperitoneal injections were ineffective.

Anti-inflammatory Effect of Sodium Valproate on Carrageenan-Induced Paw Edema in Male Rat

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mj Khoshnood

2008-12-01

Full Text Available ABESTRACT: Introduction & objective: Inflammation is a body defensive response to the endogenous and exogenous stimulators such as chemical, radiation, trauma and invasive microorganism, which result pain and tissue necrosis. There are many natural and synthetic drugs for treatment of inflammation and lot of them are under investigation. Sodium valporate is an antiepileptic drug used particularly in the treatment of primary generalized seizure notably absence, myocolonic seizure, acute manic phase of bipolar disorder and prophylaxis of migraine. The previous observations showed sodium valporate increases level of gamma amino butyric acid (GABA in the central and peripheral nervous system. In acute inflammation, GABA showed a significant attenuation of paw edema and nociception. The aim of this study was evaluation of anti-inflammatory effect of sodium valporate. Materials & Methods: In order to evaluated the anti-inflammatory and antiexudative of sodium valporate doses of 200,400 and 600 mg/kg were investigated on rat paw edema that induced by carrageenan. In addition, the plasma leakage in the inflamed tissue was evaluated by application of trypan blue as intravenous injection. Dexamethason was used as positive control. Results: Results showed sodium valporate doses of 400 and 600 mg/kg decreased inflammatory and exudative effect as compared to control group. Conclusion: Although the anti-inflammatory mechanisms of this drug were not evident but we can say sodium valporate in addition to already proved effects has anti-inflammatory effect.

Plant-Derived Anti-Inflammatory Compounds: Hopes and Disappointments regarding the Translation of Preclinical Knowledge into Clinical Progress

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Robert Fürst

2014-01-01

Full Text Available Many diseases have been described to be associated with inflammatory processes. The currently available anti-inflammatory drug therapy is often not successful or causes intolerable side effects. Thus, new anti-inflammatory substances are still urgently needed. Plants were the first source of remedies in the history of mankind. Since their chemical characterization in the 19th century, herbal bioactive compounds have fueled drug development. Also, nowadays, new plant-derived agents continuously enrich our drug arsenal (e.g., vincristine, galantamine, and artemisinin. The number of new, pharmacologically active herbal ingredients, in particular that of anti-inflammatory compounds, rises continuously. The major obstacle in this field is the translation of preclinical knowledge into evidence-based clinical progress. Human trials of good quality are often missing or, when available, are frequently not suitable to really prove a therapeutical value. This minireview will summarize the current situation of 6 very prominent plant-derived anti-inflammatory compounds: curcumin, colchicine, resveratrol, capsaicin, epigallocatechin-3-gallate (EGCG, and quercetin. We will highlight their clinical potential and/or pinpoint an overestimation. Moreover, we will sum up the planned trials in order to provide insights into the inflammatory disorders that are hypothesized to be beneficially influenced by the compound.

Anti-inflammatory and anti-oxidant activities of Secamone afzelii ...

African Journals Online (AJOL)

. This study re-ports the anti-inflammatory and antioxidant properties of S. afzelii. The anti-inflammatory activity was determined by the carrageenan-induced paw oedema method in 7 day old chicks and antioxi-dant property by the 2 ...

Effects of drugs on platelet function.

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Morse, E E

1977-01-01

Numerous drugs and chemicals affect the function of human blood platelets. The mechanism of action of some medications is partly understood. Aspirin is the most frequently involved drug. It appears to interfere with the platelet release reaction by acetylation of a platelet membrane protein which may be involved in the synthesis of prostaglandins. Other anti-inflammatory drugs, including indomethacin, phenylbutazone, ibuprophen (Motrin) and clonixin, also interfere with the release reaction but have a shorter acting course than aspirin. Some drugs stimulate adenylcyclase (gliclazide) or block phosphodiesterase, (dipyridamole, caffeine) both of which actions lead to an increase in adenosine cyclic 3':5' monophosphate (cAMP) and decrease aggregation by adenosine diphosphate (ADP). These interactions should be known to clinical scientists since patients using these medicaments may manifest abnormal platelet function tests in the laboratory and mild hemorrhagic syndromes in the clinic.

Antipyretic, analgesic and anti-inflammatory activity of Viola betonicifolia whole plant

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Muhammad Naveed

2012-05-01

Full Text Available Abstract Background Pyrexia, algesia and inflammation are associated with several pathological conditions. Synthetic drugs available for the treatment of these conditions cause multiple unwanted effects. Several studies are ongoing worldwide to find natural healing agents with better safety profile. The current study was thus aimed at evaluating antipyretic, analgesic and anti-inflammatory activities of the methanolic extract of whole plant of V. betonicifolia (VBME. Methods VBME was employed to assess antipyretic activity in yeast induced hyperthermia. Analgesic profile was ascertained in acetic acid induced writhing, hot plat and tail immersion test. Nevertheless, the anti-inflammatory activity was tested in carrageenan induced paw edema and histamine induced inflammatory tests. BALB/c mice were used at test doses of 100, 200 and 300mg/kg body weight intra peritoneally (i.p. Results In yeast induced pyrexia, VBME demonstrated dose dependently (78.23% protection at 300mg/kg, similar to standard drug, paracetamol (90% at 150mg/kg i.p. VBME showed a dose dependent analgesia in various pain models i.e. acetic acid, hot plat and tail immersion having 78.90%, 69.96% and 68.58% protection respectively at 300mg/kg. However, the analgesic action of VBME was completely antagonized by the injection of naloxone like opiate antagonists. Similarly carrageenan and histamine induces inflammation was significantly antagonized by VBME, 66.30% and 60.80% respectively at 300mg/kg. Conclusions It is concluded that VBME has marked antipyretic, analgesic and anti-inflammatory activities in various animal models and this strongly supports the ethnopharmacological uses of Viola betonicifolia as antipyretic, analgesic and anti-inflammatory plant.

Structural and physicochemical characterization of pyridine derivative salts of anti-inflammatory drugs

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Nechipadappu, Sunil Kumar; Trivedi, Darshak R.

2017-08-01

Salts of common anti-inflammatory drugs mefenamic acid (MFA), tolfenamic acid (TFA) and naproxen (NPX) with various pyridine derivatives (4-amino pyridine (4AP), 4-dimethylaminopyridine (DMAP) and 2-amino pyridine (2AP)) were synthesized by crystal engineering approach based on the pKa values of API's and the salt former. All the salts were characterized systematically by various spectroscopic methods including FT-IR and 1H NMR and the crystal structure was determined by single-crystal X-ray diffraction techniques (SCXRD). DMAP salt of NPX and 2AP salts of MFA and TFA were not obtained in the salt screening experiments. All the molecular salts exhibited 1:1 molecular stoichiometry in the asymmetric unit and except NPX-2AP salt, all the molecular salts included a water molecule in the crystal lattice. Physicochemical and structural properties between drug-drug molecular salts of MFA-4AP, TFA-4AP and NPX-4AP have been evaluated and it was found that these molecular salts were found to be stable for a time period of six months at ambient condition and further hydration of molecular salts were not observed even at accelerated humid conditions (∼75% RH). It was found that 4AP salts of MFA and TFA and DMAP salts of MFA and TFA are isostructural.

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...

Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs: risks versus benefits

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Gwee KA

2018-02-01

Full Text Available Kok Ann Gwee,1 Vernadine Goh,2 Graca Lima,3 Sajita Setia4 1Stomach, Liver, and Bowel Centre, Gleneagles Hospital, 2Department of Pharmacy, National University of Singapore, Singapore; 3Global Medical Affairs, Asia-Pacific Region, Pfizer, Hong Kong; 4Medical Affairs, Pfizer, Singapore Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs are often coadministered with proton-pump inhibitors (PPIs to reduce NSAID-induced gastrointestinal (GI adverse events. This coadministration is generally regarded as safe, and is included in many of the guidelines on NSAID prescription. However, recent evidence indicates that the GI risks associated with NSAIDs can be potentiated when they are combined with PPIs. This review discusses the GI effects and complications of NSAIDs and how PPIs may potentiate these effects, options for prevention of GI side effects, and appropriate use of PPIs in combination with NSAIDs. Keywords: PPIs, COX2 inhibitors, NSAIDs, enteropathy, gastrointestinal

In-vitro antioxidant and in-vivo anti-inflammatory activities of aerial parts of Cassia species

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Jignasu P. Mehta

2017-05-01

The antioxidant activity of the extracts was measured using scavenging of 2,2′-Diphenyl-1-picrylhydrazyl hydrate (DPPH, bleaching of β-carotene and % inhibition of H2O2. The anti-inflammatory activity was evaluated using carrageenan induced paw edema method on Wistar albino rats. The etahnolic extracts of aerial parts of C. siamea and C. javanica were evaluated for in vivo anti-inflammatory activity against the animal model of female Wistar albino rats. Ethanol extracts showed significant and dose-dependent anti-inflammatory effects. The contents of flavonoids and total phenolic compounds could be correlated with the antioxidant and anti-inflammatory activities observed for C. siamea and C. javanica. Our findings suggest that aerial parts of C. siamea and C. javanica contain potential antioxidant and anti-inflammatory compounds, which could be tested as drug candidates against oxidative and inflammation-related pathological processes in medicinal chemistry studies.

Cytoprotective and enhanced anti-inflammatory activities of liposomal piroxicam formulation in lipopolysaccharide-stimulated RAW 264.7 macrophages.

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Chiong, Hoe Siong; Yong, Yoke Keong; Ahmad, Zuraini; Sulaiman, Mohd Roslan; Zakaria, Zainul Amiruddin; Yuen, Kah Hay; Hakim, Muhammad Nazrul

2013-01-01

Liposomal drug delivery systems, a promising lipid-based nanoparticle technology, have been known to play significant roles in improving the safety and efficacy of an encapsulated drug. Liposomes, prepared using an optimized proliposome method, were used in the present work to encapsulate piroxicam, a widely prescribed nonsteroidal anti-inflammatory drug. The cytotoxic effects as well as the in vitro efficacy in regulation of inflammatory responses by free-form piroxicam and liposome-encapsulated piroxicam were evaluated using a lipopolysaccharide-sensitive macrophage cell line, RAW 264.7. Cells treated with liposome-encapsulated piroxicam demonstrated higher cell viabilities than those treated with free-form piroxicam. In addition, the liposomal piroxicam formulation resulted in statistically stronger inhibition of pro-inflammatory mediators (ie, nitric oxide, tumor necrosis factor-α, interleukin-1β, and prostaglandin E2) than piroxicam at an equivalent dose. The liposome-encapsulated piroxicam also caused statistically significant production of interleukin-10, an anti-inflammatory cytokine. This study affirms the potential of a liposomal piroxicam formulation in reducing cytotoxicity and enhancing anti-inflammatory responses in vitro.

Anti-inflammatory activity of Ruta graveolens Linn on carrageenan ...

African Journals Online (AJOL)

Aqueous, ethanolic and methanolic extracts of Ruta graveolens were investigated for anti-inflammatory activity in carrageenan induced paw edema in wistar male rats, and compared to a positive control drug, Voveran. These extracts were given (ip) in a concentration of 20 and 50 mg/kg b.w. before carrageenan injection.

Structural basis of non-steroidal anti-inflammatory drug diclofenac binding to human serum albumin.

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Zhang, Yao; Lee, Philbert; Liang, Shichu; Zhou, Zuping; Wu, Xiaoyang; Yang, Feng; Liang, Hong

2015-11-01

Human serum albumin (HSA) is the most abundant protein in plasma, which plays a central role in drug pharmacokinetics because most compounds bound to HSA in blood circulation. To understand binding characterization of non-steroidal anti-inflammatory drugs to HSA, we resolved the structure of diclofenac and HSA complex by X-ray crystallography. HSA-palmitic acid-diclofenac structure reveals two distinct binding sites for three diclofenac in HSA. One diclofenac is located at the IB subdomain, and its carboxylate group projects toward polar environment, forming hydrogen bond with one water molecule. The other two diclofenac molecules cobind in big hydrophobic cavity of the IIA subdomain without interactive association. Among them, one binds in main chamber of big hydrophobic cavity, and its carboxylate group forms hydrogen bonds with Lys199 and Arg218, as well as one water molecule, whereas another diclofenac binds in side chamber, its carboxylate group projects out cavity, forming hydrogen bond with Ser480. © 2015 John Wiley & Sons A/S.

Non-Steroidal Anti-inflammatory Drugs As Host-Directed Therapy for Tuberculosis: A Systematic Review

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Vera M. Kroesen

2017-06-01

Full Text Available Lengthy, antimicrobial therapy targeting the pathogen is the mainstay of conventional tuberculosis treatment, complicated by emerging drug resistances. Host-directed therapies, including non-steroidal anti-inflammatory drugs (NSAIDs, in contrast, target host factors to mitigate disease severity. In the present Systematic Review, we investigate whether NSAIDs display any effects as therapy of TB and discuss possible mechanisms of action of NSAIDs as adjunctive therapy of TB. Ten studies, seven preclinical studies in mice and three clinical trials, were included and systematically reviewed. Our results point toward a beneficial effect of NSAIDs as adjunct to current TB therapy regimens, mediated by decreased lung pathology balancing host-immune reaction. The determination of the best timing for their administration in order to obtain the potential beneficial effects needs further investigation. Even if the preclinical evidence requires clinical evaluation, NSAIDs might represent a potential safe, simple, and cheap improvement in therapy of TB.

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

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

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Nørgård, Bente Mertz

2011-12-01

The clinical epidemiological studies included in this thesis fall into three parts. The first part includes studies on birth outcome in women with ulcerative colitis. The second part includes pharmacoepidemiological studies on birth outcome after anti-inflammatory drug therapy in pregnancy, including patients with ulcerative colitis and Crohn's disease. The third part (and the latest publications) includes birth outcome in women with Crohn's disease; and the methods of cohort establishment in these studies are developed and improved due to the knowledge gathered from conducting the earlier studies. The birth outcomes in women with ulcerative colitis are examined in a nationwide, Danish, cohort of women based on data from the Danish National Hospital Discharge Registry and the Danish Medical Birth Registry, and within a Hungarian case-control data set. Our data suggest: 1) Significantly increased risk of preterm birth when women give birth 0-6 months after establishment of the diagnosis. It is considered whether the increased risk may be influenced by disease activity around the time of establishing the diagnosis. 2) No increased risk of giving birth to children with low birth weight, intrauterine growth retardation or congenital abnormalities (evaluated overall). 3) Significantly increased risk of some selected congenital abnormalities (limb deficiencies, obstructive urinary and multiple congenital abnormalities). No other studies have examined the risk of selected congenital abnormalities in children born by women with ulcerative colitis. The pharmacoepidemiological studies on birth outcomes after use of anti-inflammatory drug therapy in pregnancy, including women with ulcerative colitis and Crohn's disease, are based on data from the Hungarian case-control data set, a countywide Danish prescription Database, the Danish National Hospital Discharge Registry, the Danish Medical Birth Registry, and review of selected medical records. After exposure to sulfasalazine

Solubility of ocular therapeutic agents in self-emulsifying oils. I. Self-emulsifying oils for ocular drug delivery: solubility of indomethacin, aciclovir and hydrocortisone.

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Czajkowska-Kośnik, Anna; Sznitowska, Małgorzata

2009-01-01

Self-emulsifying drug delivery systems (SEDDS) were prepared by dissolving Cremophor EL, Tween 20, Tween 80 and Span 80 (1% or 5%) in oils (Miglyol 812 or castor oil). Solubilities of three ophthalmic drugs, namely aciclovir, hydrocortisone and indomethacin were determined in these systems. In addition, the effect of a small amount of water (0.5% and 2%) on solubilization properties of the systems was estimated. Of the three substances, indomethacin showed the best solubility in Miglyol while aciclovir was practically insoluble in this oil. The surfactants usually increased drug solubility in the oily phase. Only Tween 20 was found to decrease the solubility of aciclovir and hydrocortisone in Miglyol. Addition of a small amount of water to the oil/surfactant system increased solubility of hydrocortisone, but not of indomethacin. The results of the current study may be utilized to design a suitable composition of SEDDS and allow continuation of research on this type of drug carriers.

Antibacterial, anti-inflammatory and neuroprotective layer-by-layer coatings for neural implants

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Zhang, Zhiling; Nong, Jia; Zhong, Yinghui

2015-08-01

Objective. Infection, inflammation, and neuronal loss are common issues that seriously affect the functionality and longevity of chronically implanted neural prostheses. Minocycline hydrochloride (MH) is a broad-spectrum antibiotic and effective anti-inflammatory drug that also exhibits potent neuroprotective activities. In this study, we investigated the development of biocompatible thin film coatings capable of sustained release of MH for improving the long term performance of implanted neural electrodes. Approach. We developed a novel magnesium binding-mediated drug delivery mechanism for controlled and sustained release of MH from an ultrathin hydrophilic layer-by-layer (LbL) coating and characterized the parameters that control MH loading and release. The anti-biofilm, anti-inflammatory and neuroprotective potencies of the LbL coating and released MH were also examined. Main results. Sustained release of physiologically relevant amount of MH for 46 days was achieved from the Mg2+-based LbL coating at a thickness of 1.25 μm. In addition, MH release from the LbL coating is pH-sensitive. The coating and released MH demonstrated strong anti-biofilm, anti-inflammatory, and neuroprotective potencies. Significance. This study reports, for the first time, the development of a bioactive coating that can target infection, inflammation, and neuroprotection simultaneously, which may facilitate the translation of neural interfaces to clinical applications.

Two cases of corneal perforation after oral administration of nonsteroidal anti-inflammatory drugs: oral NSAID-induced corneal damage.

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Masuda, Ikuya; Matsuo, Toshihiko; Okamoto, Kazuo; Matsushita, Kyoko; Ohtsuki, Hiroshi

2010-01-01

To report 2 cases of corneal perforation associated with the use of oral nonsteroidal anti-inflammatory drugs (NSAIDs). In a 62-year-old woman and a 79-year-old woman, corneal perforation occurred after 7 days and 5 months of oral NSAIDs administration, respectively. After NSAIDs were discontinued, the cornea epithelialized and the anterior chamber formed within 14 and 10 days, respectively. It is well known that topical NSAIDs cause corneal perforation. Observations in the present cases suggest that the oral administration of NSAIDs may also cause corneal damage, and hence, medical professionals should consider the risk of damage to the cornea when administering these drugs orally.

Zinc salt enhances gastroprotective activity of risperidone in indomethacin-induced gastric ulcer.

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Oluwole, F S; Onwuchekwa, C

2016-09-01

Zinc has been reported to mediate cellular responses to injury by producing cytoprotection via the scavenging of reactive oxygen species. Anti-stress medications are generally anti-psychotic drugs and anti- depressants. Some Anti-psychotic drugs such as risperidone have been reported to possess anti-ulcer activity. Risperidone as an antipsychotic drug blocks several neurotransmitter systems including dopaminergic, adrenergic, histaminergic and serotonergic pathways. The study investigated the antiulcer activity of Zinc Chloride (ZnCl(2)) in combination with risperidone in male Wistar rats. The animals were divided into two groups of twenty animals each for ZnCl(2) and risperidone groups. Each group was further divided into four subgroups. ZnCl(2) was administered orally at 20mg/kg, 40mg/kg and 80mg/kg to a subgroup, while 80mg/kg of ZnCl(2) was administered in combination with risperidone (0.1mg/kg, 0.3mg/kg and 0.5mg/kg) orally once daily for 21 days. The controls were treated with distilled water. Ulcer was induced using indomethacin. Histology of the stomach tissues was prepared with PAS and H& E stains. Ulcer score and ulcer area were assessed using standard methods. Data were analysed using student t-test and Graphpad Prism 5. There were decreases in ulcer scores using the different doses of ZnCl, (20mg/kg, 40mg/kg and 80mg/kg). Also using the highest dose ZnCl(2) (80mg/ kg) and different doses of risperidone there were decreases in ulcer scores compared to the control. This effect of the risperidone showed a significant dose- dependent reduction. The effect ZnCl(2), and risperidone were also reflected in the ulcer area and in the histology. These findings suggest that ZnCl(2), enhances the gastroprotective activity ofrisperidone in indomethacin- induced gastric ulcer. However, more detailed studies are necessary to confirm the relevance of this finding and its implications in clinical settings.

Clinical Drug-Drug Pharmacokinetic Interaction Potential of Sucralfate with Other Drugs

DEFF Research Database (Denmark)

Sulochana, Suresh P; Syed, Muzeeb; Chandrasekar, Devaraj V

2016-01-01

of drugs. This review covers several category of drugs such as non-steroidal anti-inflammatory drugs, fluoroquinolones, histamine H2-receptor blockers, macrolides, anti-fungals, anti-diabetics, salicylic acid derivatives, steroidal anti-inflammatory drugs and provides pharmacokinetic data summary along...

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

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

2013-01-01

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 5 mg/kg) or carprofen (15 or 25 mg/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, P carprofen: Z = 2.58, P = 0.010) in induced birds. Saline-induced birds also had significantly lower TT than saline-sham birds (Z = −2.17, P = 0.030). This study found direct evidence of an association between inflammatory arthropathies and thermal hyperalgesia, and showed that NSAID treatment maintained baseline thermal sensitivity (via anti-nociception). 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. PMID:24129110

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.

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

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McGettigan, Patricia; Roderick, Peter; Mahajan, Rushikesh; Kadam, Abhay; Pollock, Allyson M.

2015-01-01

Background 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 four therapeutic areas: analgesia (non-steroidal anti-inflammatory drugs [NSAIDs]), diabetes (metformin), depression/anxiety (anti-depressants/benzodiazepines), and psychosis (anti-psychotics). Methods and Findings This was an ecologic study with a time-trend analysis of FDC sales volumes (2007–2012) and a cross-sectional examination of 2011–2012 data to establish the numbers of formulations on the market with and without a record of CDSCO approval (“approved” and “unapproved”), their branded products, and sales volumes. Data from the CDSCO on approved FDC formulations were compared with sales data from PharmaTrac, a database of national drug sales. We determined the proportions of FDC sales volumes (2011–2012) arising from centrally approved and unapproved formulations and from formulations including drugs banned/restricted internationally. We also determined the proportions of centrally approved and unapproved formulations marketed before and after 1 May 2002, when amendments were made to the drug rules. FDC approvals in India, the United Kingdom (UK), and United States of America (US) were compared. For NSAID FDCs, 124 formulations were marketed, of which 34 (27%) were centrally approved and 90 (73%) were unapproved; metformin: 25 formulations, 20 (80%) approved, five (20%) unapproved; anti-depressants/benzodiazepines: 16 formulations, three (19%) approved, 13 (81%) unapproved

Nicolau Syndrome after Intramuscular Injection of Non-Steroidal Anti-Inflammatory Drugs (NSAID

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Mehmet Dadaci

2015-01-01

Full Text Available Nicolau syndrome is a rare complication of intramuscular injection that leads to local ischemic necrosis of the skin and adipose tissue. In this paper, we discuss etiologies, risk factors, and treatment options for gluteal Nicolau syndrome referring to patients treated in our hospital. Our study includes 17 women who visited our clinic with symptoms of gluteal necrosis secondary to intramuscular injection. The following variables were taken into account: injection site, drug administered, frequency of injections, the person who administered the injections, needle size, and needle tip color. Magnetic resonance images obtained in the aftermath of intramuscular injection application were carefully analyzed for presence of necrosis, cyst formation and the thickness of the gluteal fat tissue layer. Drugs that had been received in intramuscular injection were exclusively non-steroidal anti-inflammatory drugs. Mean patient BMI was 41.8 (all patients were considered as obese, and mean gluteal fat thickness was 54 mm. Standard length of needles (3.8 cm had been used in procedures. The wounds were treated with primary closure in 11 patients and with local flap therapy in 6 patients. The observed necrosis was a consequence of misplaced gluteal injection, where drugs were injected into the adipose tissue instead of the muscle due to the extreme thickness of the fat layer, on one hand, and the inappropriate length of standard needles, on the other hand. Intramuscular injection should be avoided in obese patients whenever possible: if it is necessary, proper injection technique should be used.

Propolis: a review of its anti-inflammatory and healing actions

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A. F. N. Ramos

2007-01-01

Full Text Available Tissue healing is an adaptive biological response by which the organism repairs damaged tissue. The initial stage of healing is represented by an acute inflammatory reaction, in which inflammatory cells migrate to damaged tissue and phagocyte debris. At a later stage, fibroblasts and endothelial cells proliferate and generate a scar. The occurrence of inflammatory processes and healing imperfections have been a concern for hundreds of years, especially for individuals with healing difficulties, such as diabetics and carriers of peripheral circulation deficiencies. A wide variety of natural products have been used as anti-inflammatory and healing agents, with propolis being a remarkable option. Propolis has been used in popular medicine for a very long time; however, it is not a drug intended for all diseases. Currently, the determination of quality standards of propolis-containing products is a major problem due to their varying pharmacological activities and chemical compositions. The aim of this review is to discuss the use of propolis with emphasis on its anti-inflammatory and healing properties.

A comparative study of renal dysfunction in patients with inflammatory arthropathies: strong association with cardiovascular diseases and not with anti-rheumatic therapies, inflammatory markers or duration of arthritis.

LENUS (Irish Health Repository)

Haroon, Muhammad

2012-02-01

AIMS: The aim of this study was to investigate the prevalence of chronic kidney disease (CKD) among comparable patients with rheumatoid arthritis (RA) and seronegative inflammatory arthritis, and to explore any predictive factors for renal impairment. METHODS: Consecutive patients with peripheral joint disease (oligo and polyarthritis) were recruited from our inflammatory arthritis clinics. We divided patients in two groups: RA group and seronegative inflammatory arthritis group. The cohort consisted of 183 patients (RA = 107, seronegative arthritis = 76 [psoriatic arthritis = 69, undifferentiated oligoarthritis = 7]). Estimated glomerular filtration rate (eGFR) was calculated using the established Modification of Diet in Renal Disease equation. Demographic details, disease-specific characteristics, anti-rheumatic drugs and the presence of cardiovascular diseases were recorded. RESULTS: In total, 17.48% (n = 32) of the cohort had CKD. There was no statistically significant variation between the two groups as regards baseline demographics, disease characteristics, use of anti-rheumatic drugs and the presence of individual cardiovascular diseases. We found that eGFR and the presence of CKD were similar among these groups. Among patients with CKD, 72% had undiagnosed CKD. No association of statistical significance was noted between CKD and the use of corticosteroids, disease-modifying antirheumatic drugs and anti-tumor necrosis factor agents. The association of cardiovascular diseases with CKD remained significant after adjusting for confounders (age, gender, duration of arthritis, high C-reactive protein, use of anti-rheumatic drugs). CONCLUSIONS: Patients with inflammatory arthritis are more prone to have CKD. This could have serious implications, as the majority of rheumatology patients use non-steroidal anti-inflammatory drugs and different immunosuppressives, such as methotrexate. No association of kidney dysfunction was noted with inflammatory disease

Use of Nonsteroidal Anti-Inflammatory Drugs for Symptomatic Treatment of Episodic Headache.

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Affaitati, Giannapia; Martelletti, Paolo; Lopopolo, Mariangela; Tana, Claudio; Massimini, Francesca; Cipollone, Francesco; Lapenna, Domenico; Giamberardino, Maria Adele; Costantini, Raffaele

2017-03-01

Primary headaches have high epidemiologic impact but their symptomatic treatment often remains problematic. Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used, but their modality of employment and efficacy/differential efficacy are highly variable. This study investigated current NSAID use for episodic headache at an Italian headache center (January 2000 to February 2013). A retrospective evaluation was performed on 6,443 patient records: migraine (n = 2,330), tension-type headache (TTH; n = 807), and migraine plus TTH (n = 3,306). Among migraine patients, 80% had used NSAIDs in the past year. Preferences were: nimesulide (57%), ketoprofen (25%), and ibuprofen (24%); complete efficacy was significantly higher than incomplete/absent efficacy (P headache was higher than could be hypothesized based on guidelines, with NSAID preferences not entirely coinciding with international recommendations. This outcome suggests the need for greater awareness of all treatment options in headache by both patients and physicians. © 2016 World Institute of Pain.

Controlled release from aspirin based linear biodegradable poly(anhydride esters) for anti-inflammatory activity.

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Dasgupta, Queeny; Movva, Sahitya; Chatterjee, Kaushik; Madras, Giridhar

2017-08-07

This work reports the synthesis of a novel, aspirin-loaded, linear poly (anhydride ester) and provides mechanistic insights into the release of aspirin from this polymer for anti-inflammatory activity. As compared to conventional drug delivery systems that rely on diffusion based release, incorporation of bioactives in the polymer backbone is challenging and high loading is difficult to achieve. In the present study, we exploit the pentafunctional sugar alcohol (xylitol) to provide sites for drug (aspirin) attachment at its non-terminal OH groups. The terminal OH groups are polymerized with a diacid anhydride. The hydrolysis of the anhydride and ester bonds under physiological conditions release aspirin from the matrix. The resulting poly(anhydride ester) has high drug loading (53%) and displays controlled release kinetics of aspirin. The polymer releases 8.5 % and 20%, of the loaded drug in one and four weeks, respectively and has a release rate constant of 0.0035h -0.61 . The release rate is suitable for its use as an anti-inflammatory agent without being cytotoxic. The polymer exhibits good cytocompatibility and anti-inflammatory properties and may find applications as injectable or as an implantable bioactive material. The physical insights into the release mechanism can provide development of other drug loaded polymers. Copyright © 2017 Elsevier B.V. All rights reserved.

[Cost-effectiveness analysis of celecoxib versus non-selective non-steroidal anti-inflammatory drug therapy for the treatment of osteoarthritis in Spain: A current perspective].

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De Lossada, A; Oteo-Álvaro, Á; Giménez, S; Oyagüez, I; Rejas, J

2016-01-01

To assess the cost-effectiveness of celecoxib and non-selective non-steroidal anti-inflammatory drugs for the treatment of osteoarthritis in clinical practice in Spain. A decision-tree model using distribution, doses, treatment duration and incidence of GI and CV events observed in the pragmatic PROBE-designed «GI-Reasons» trial was used for cost-effectiveness. Effectiveness was expressed in terms of event averted and quality-adjusted life-years (QALY) gained. QALY were calculated based on utility decrement in case of any adverse events reported in GI-Reasons trial. The National Health System perspective in Spain was applied; cost calculations included current prices of drugs plus cost of adverse events occurred. The analysis was expressed as an incremental cost-effectiveness ratio per QALY gained and per event averted. One-way and probabilistic analyses were performed. Compared with non-selective non-steroidal anti-inflammatory drugs, at current prices, celecoxib treatment had higher overall treatment costs €201 and €157, respectively. However, celecoxib was associated with a slight increase in QALY gain and significantly lower incidence of gastrointestinal events (pcost-effectiveness ratio of €13,286 per QALY gained and €4,471 per event averted. Sensitivity analyses were robust, and confirmed the results of the base case. Celecoxib at current price may be considered as a cost-effective alternative vs. non-selective non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis in daily practice in the Spanish NHS. Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

A study of the energy absorption and exposure buildup factors of some anti-inflammatory drugs

International Nuclear Information System (INIS)

Ekinci, Neslihan; Kavaz, Esra; Özdemir, Yüksel

2014-01-01

Human radiation exposure is increasing due to radiation development in science and technology. The development of radioprotective agents is important for protecting patients from the side effects of radiotherapy and for protecting the public from unwanted irradiation. Radioprotective agents are used to reduce the damage caused by radiation in healthy tissues. There are several classes of radioprotective compounds that are under investigation. Analgesics and anti-inflammatory compounds are being considered for treating or preventing the effects of damage due to radiation exposure, or for increasing the chance of survival after exposure to a high dose of radiation. In this study, we investigated the radioprotective effects of some analgesic and anti-inflammatory compounds by evaluating buildup factors. The gamma ray energy absorption (EABF) and exposure buildup factors (EBF) were calculated to select compounds in a 0.015–15 MeV energy region up to a penetration depth of 40 mfp (mean free path). Variations of EABF and EBF with incident photon energy and penetration depth elements were also investigated. Significant variations in both EABF and EBF values were observed for several compounds at the moderate energy region. At energies below 0.15 MeV, EABF and EBF values increased with decreasing equivalent atomic number (Z eq ) of the samples. In addition, EABF and EBF were the largest for ibuprofen, aspirin, paracetamol, naproxen and ketoprofen at 0.05 and 0.06 MeV, respectively, and the EABF value was 0.1 MeV for aceclofenac. From these results, we concluded that the buildup of photons is less for aceclofenac compared to other materials. - Highlights: • Buildup factors of anti-inflammatory drugs have been calculated by a G-P fitting method. • Z eff of diclofenac was observed higher than other compounds. • It was found that buildup of photons is less for aceclofenac and diclofenac. • It would be appealing to use aceclofenac and diclofenac as radioprotective

Evolving guidelines in the use of topical nonsteroidal anti-inflammatory drugs in the treatment of osteoarthritis.

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Balmaceda, Casilda M

2014-01-21

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a standard treatment for osteoarthritis (OA), but the use of oral NSAIDs has been linked to an elevated risk for cardiovascular and gastrointestinal adverse events and renal toxicity. Topical NSAIDs are thought to afford efficacy that is comparable to oral formulations while reducing widespread systemic drug exposure, which may provide a benefit in terms of safety and tolerability. As a result, European treatment guidelines have, for many years, recommended the use of topical NSAIDs as a safe and effective treatment option for OA. Following the recent approval of several topical NSAID formulations by the US Food and Drug Administration, US treatment guidelines are increasingly recommending the use of topical NSAIDs as an alternative therapy and, in some cases, as a first-line option for OA. This commentary summarizes OA treatment guidelines that are currently available and discusses their potential evolution with regard to the increased inclusion of topical NSAIDs.

The pattern of use of non-steroidal anti-inflammatory drugs (NSAIDs) from 1997 to 2005: a nationwide study on 4.6 million people

DEFF Research Database (Denmark)

Fosbøl, Emil Loldrup; Gislason, Gunnar H; Jacobsen, Søren

2008-01-01

PURPOSE: To describe the nationwide pattern of use of non-steroidal anti-inflammatory drugs (NSAIDs) in the Danish population. METHODS: All Danish citizens aged 10 or above 1 January 1997 were included in the study. The national prescription registry was used to identify all claimed prescriptions...

Effects of Non-Steroidal Anti-Inflammatory Drugs onFlexor Tendon Rehabilitation after Repair

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Alireza Rouhani

2013-09-01

Full Text Available   Background: Peritendinous adhesions after repairing an injury to the digital flexor tendons are a major problem in hand surgery. Non-steroidal anti-inflammatory drug therapy may affect tendon healing and the development of peritendinous adhesions. The aim of this study was to evaluate ibuprofen effect in patients function after flexor tendon surgical repair.   Method: Thirty-five patients, who had sharp-edge lacerations of hand-zone II requiring flexor tendons repair, participated in this randomized double-blind clinical trial study. The patients were randomly classified into two parallel and matched groups (21 patients in the intervention group and 14 patients in the control group. The groups were matched considering age, gender, and laceration size. The control group received a placebo with the same appearance and dosage. In the intervention group, ibuprofen was prescribed at a high dosage (2400 mg/day. The range of motion improvement rate of the involved fingers and the patients’ performance after their follow-up period were compared. Results: There was a statistically significant difference between the two groups for range of motion of the involved finger joints (P=0.03. According to the DASH score, there was a statistically significant difference between the final performance of the patients, such that it was 11±2.4 and 18.4±6.3 in the intervention and control groups, respectively (P=0.01. There was not any case of re-tear or need to re-operate in the intervention and control groups. Conclusion: Our findings reveal that ibuprofen with an anti-inflammatory dose was effective in improving the range of motion of the involved fingers joints after flexor tendon injury.

Effects of Non-Steroidal Anti-Inflammatory Drugs onFlexor Tendon Rehabilitation after Repair

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Alireza Rouhani

2013-09-01

Full Text Available Background: Peritendinous adhesions after repairing an injury to the digital flexor tendons are a major problem in hand surgery. Non-steroidal anti-inflammatory drug therapy may affect tendon healing and the development of peritendinous adhesions. The aim of this study was to evaluate ibuprofen effect in patients function after flexor tendon surgical repair.   Method: Thirty-five patients, who had sharp-edge lacerations of hand-zone II requiring flexor tendons repair, participated in this randomized double-blind clinical trial study. The patients were randomly classified into two parallel and matched groups (21 patients in the intervention group and 14 patients in the control group. The groups were matched considering age, gender, and laceration size. The control group received a placebo with the same appearance and dosage. In the intervention group, ibuprofen was prescribed at a high dosage (2400 mg/day. The range of motion improvement rate of the involved fingers and the patients’ performance after their follow-up period were compared. Results: There was a statistically significant difference between the two groups for range of motion of the involved finger joints (P=0.03. According to the DASH score, there was a statistically significant difference between the final performance of the patients, such that it was 11±2.4 and 18.4±6.3 in the intervention and control groups, respectively (P=0.01. There was not any case of re-tear or need to re-operate in the intervention and control groups. Conclusion: Our findings reveal that ibuprofen with an anti-inflammatory dose was effective in improving the range of motion of the involved fingers joints after flexor tendon injury.

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

OpenAIRE

Lionberger, David

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...

Evaluation of anti-inflammatory effect of statins in chronic periodontitis.

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Suresh, Snophia; Narayana, Satya; Jayakumar, P; Sudhakar, Uma; Pramod, V

2013-01-01

Statins are the group of lipid-lowering drugs commonly used to control cardiovascular and cerebrovascular diseases. Statins have potential anti-inflammatory effect by blocking the intermediate metabolites of the mevalonate pathway. The objective of this study was to evaluate the anti-inflammatory effect of statin medication in chronic periodontitis patients. Thirty patients of age group between 40 and 60 years were selected from the outpatient pool of Department of Periodontics, Thaimoogambigai Dental College and Hospital, Chennai. Thirty patients selected were grouped into two groups, Group-I consists of patients with generalized chronic periodontitis and on statin medication and Group-II consists of patients with generalized chronic periodontitis. Clinical parameters were recorded and gingival crevicular fluid (GCF) samples were analyzed for interleukin (IL)-1β using commercially available enzyme-linked immunosorbent assay. The mean GCF IL-1β levels in generalized chronic periodontitis patients who are on statin medication (Group-I) were lower than the generalized chronic periodontitis patients without statin medication (Group-II). Reduction of GCF IL-1β levels in statin users indicate that statins have anti-inflammatory effect on periodontal disease.

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

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Marcio A. R. Araujo

2011-09-01

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.

Evaluation of anti-inflammatory activity, effect on blood pressure & gastric tolerability of antidepressants

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Preeta Kaur Chugh

2013-01-01

Full Text Available Background & objectives: Antidepressants are being used as analgesics for various pain related disorders like neuropathic and non neuropathic pain. Although their analgesic activity is well recognized but anti-inflammatory potential of antidepressants is still inconclusive. Since the antidepressants are used for longer duration, it becomes important to elucidate effect of anti-depressants on blood pressure and gastric mucosa. This study was undertaken to evaluate the anti-inflammatory potential of various antidepressant drugs as well as their effect on blood pressure and gastric tolerability on chronic administration in rats. Methods: Rat paw oedema model was used for studying anti-inflammatory activity, single dose of test drug (venlafaxine 20 and 40 mg/kg, amitryptline 25 mg/kg, fluoxetine 20 mg/kg was administered intraperitoneally 45 min prior to administration of 0.1 ml of 1 per cent carrageenan in sub-planter region. Oedema induced in test group was compared with normal saline treated control group. For studying effect on blood pressure and gastric tolerability, test drugs were administered for 14 days. Blood pressure was recorded on days 0, 7 and 14 using tail cuff method. On day 14, 4 h after drug administration, rats were sacrificed and stomach mucosa was examined for ulcerations. Results: Pretreatment of rats with venlafaxine (40 mg/kg resulted in a significant decrease in paw oedema as compared to control (2.4 ± 0.15 to 1.1 ± 0.16 ml, P<0.01. Similarly, in the group pretreated with fluoxetine, significant decrease in paw oedema was observed in comparison to control (P<0.05. Significant change in mean blood pressure was seen in rats pretreated with venlafaxine 40 mg/kg (126.7 ± 4.2 to 155.2 ± 9.7, P<0.05 and fluoxetine (143.5 ± 2.6 to 158.3 ± 1.2, P<0.05 on day 7. No significant difference with regard to gastric tolerability was observed among groups. Interpretation & conclusions: Our findings showed significant anti-inflammatory

Chemicals Compositions, Antioxidant and Anti-Inflammatory Activity of Cynara scolymus Leaves Extracts, and Analysis of Major Bioactive Polyphenols by HPLC

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Maryem Ben Salem

2017-01-01

Full Text Available Objective. Artichoke (Cynara scolymus L. was one of the plant remedies for primary health care. The present study was focused on the determination of chemical composition, antioxidant activities, and anti-inflammatory activity and on analyzing its major bioactive polyphenols by HPLC. Methods. Artichoke Leaves Extracts (ALE were analyzed for proximate analysis and phytochemical and antioxidant activity by several methods such as DDPH, ABTS, FRAP, and beta-carotene bleaching test. The carrageenan (Carr model induced paw oedema in order to investigate the anti-inflammatory activity. Identification and quantification of bioactive polyphenols compounds were done by HPLC method. The oxidative stress parameters were determined; CAT, SOD, GSH, MDA, and AOPP activities and the histopathological examination were also performed. Results. It was noted that EtOH extract of ALE contained the highest phenolic, flavonoid, and tannin contents and the strongest antioxidants activities including DDPH (94.23%, ABTS (538.75 mmol, FRAP assay (542.62 umol, and β-carotene bleaching (70.74% compared to the other extracts of ALE. Administration of EtOH extract at dose 400 mg/kg/bw exhibited a maximum inhibition of inflammation induced by Carr for 3 and 5 hours compared to reference group Indomethacin (Indo. Conclusion. ALE displayed high potential as natural source of minerals and phytochemicals compounds with antioxidant and anti-inflammatory properties.

Barriers to physician adherence to nonsteroidal anti-inflammatory drug guidelines: a qualitative study.

Science.gov (United States)

Cavazos, J M; Naik, A D; Woofter, A; Abraham, N S

2008-09-15

Despite wide availability of physician guidelines for safer use of nonsteroidal anti-inflammatory drugs (NSAIDs) and widespread use of these drugs in the US, NSAID prescribing guidelines have been only modestly effective. To identify and describe comprehensively barriers to provider adherence to NSAID prescribing guidelines. We conducted interviews with 25 physicians, seeking to identify the major influences explaining physician non-adherence to guidelines. Interviews were standardized and structured probes were used for clarification and detail. All interviews were audio-taped and transcribed. Three independent investigators analysed the transcripts, using the constant-comparative method of qualitative analysis. Our analysis identified six dominant physician barriers explaining non-adherence to established NSAID prescribing guidelines. These included (i) lack of familiarity with guidelines, (ii) perceived limited validity of guidelines, (iii) limited applicability of guidelines among specific patients, (iv) clinical inertia, (v) influences of prior anecdotal experiences and (vi) medical heuristics. A heterogeneous set of influences are barriers to physician adherence to NSAID prescribing guidelines. Suggested measures for improving guideline-concordant prescribing should focus on measures to improve physician education and confidence in guidelines, implementation of physician/pharmacist co-management strategies and expansion of guideline scope.

Ursolic Acid and Oleanolic Acid: Pentacyclic Terpenoids with Promising Anti-Inflammatory Activities.

Science.gov (United States)

Kashyap, Dharambir; Sharma, Ajay; Tuli, Hardeep S; Punia, Sandeep; Sharma, Anil K

2016-01-01

Plant derived products are not only served as dietary components but also used to treat and prevent the inflammatory associated diseases like cancer. Among the natural products pentacyclic terpenoids including ursolic acid and oleanolic acid are considered as the promising anti-inflammatory therapeutic agents. The current review extensively discusses the anti-inflammatory therapeutic potential of these pentacyclic moieties along with their proposed mechanisms of action. Furthermore, the relevant patents have also been listed to present the health benefits of these promising therapeutic agents to pin down the inflammatory diseases. Expert opinion: Pentacyclic terpenoids are known to negatively down-regulate a variety of extracellular and intracellular molecular targets associated with disease progression. The major anti-inflammatory effects of these molecules have been found to be mediated via inactivation of NFkB, STAT3/6, Akt/mTOR pathways. A number of patents on UA & OA based moieties have been reported between 2010 and 2016. Still there have been only a few compounds which meet the need of sufficient hydro solubility and bioavailability along with higher anti-inflammatory activities. Thus, it is essential to develop novel derivatives of terpenpoids which may not only overcome the solubility issues but also may improve their therapeutic effects. In addition, scientific community may utilize nanotechnology based drug delivery systems so as to increase the bio-availability, selectivity and dosages related problems.

Curcumin: an anti-inflammatory molecule from a curry spice on the path to cancer treatment.

Science.gov (United States)

Basnet, Purusotam; Skalko-Basnet, Natasa

2011-06-03

Oxidative damage and inflammation have been pointed out in preclinical studies as the root cause of cancer and other chronic diseases such as diabetes, hypertension, Alzheimer's disease, etc. Epidemiological and clinical studies have suggested that cancer could be prevented or significantly reduced by treatment with anti-oxidant and anti-inflammatory drugs, therefore, curcumin, a principal component of turmeric (a curry spice) showing strong anti-oxidant and anti-inflammatory activities, might be a potential candidate for the prevention and/or treatment of cancer and other chronic diseases. However, curcumin, a highly pleiotropic molecule with an excellent safety profile targeting multiple diseases with strong evidence on the molecular level, could not achieve its optimum therapeutic outcome in past clinical trials, largely due to its low solubility and poor bioavailability. Curcumin can be developed as a therapeutic drug through improvement in formulation properties or delivery systems, enabling its enhanced absorption and cellular uptake. This review mainly focuses on the anti-inflammatory potential of curcumin and recent developments in dosage form and nanoparticulate delivery systems with the possibilities of therapeutic application of curcumin for the prevention and/or treatment of cancer.

Curcumin: An Anti-Inflammatory Molecule from a Curry Spice on the Path to Cancer Treatment

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Purusotam Basnet

2011-06-01

Full Text Available Oxidative damage and inflammation have been pointed out in preclinical studies as the root cause of cancer and other chronic diseases such as diabetes, hypertension, Alzheimer’s disease, etc. Epidemiological and clinical studies have suggested that cancer could be prevented or significantly reduced by treatment with anti-oxidant and anti-inflammatory drugs, therefore, curcumin, a principal component of turmeric (a curry spice showing strong anti-oxidant and anti-inflammatory activities, might be a potential candidate for the prevention and/or treatment of cancer and other chronic diseases. However, curcumin, a highly pleiotropic molecule with an excellent safety profile targeting multiple diseases with strong evidence on the molecular level, could not achieve its optimum therapeutic outcome in past clinical trials, largely due to its low solubility and poor bioavailability. Curcumin can be developed as a therapeutic drug through improvement in formulation properties or delivery systems, enabling its enhanced absorption and cellular uptake. This review mainly focuses on the anti-inflammatory potential of curcumin and recent developments in dosage form and nanoparticulate delivery systems with the possibilities of therapeutic application of curcumin for the prevention and/or treatment of cancer.

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...

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

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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.

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.

The Effect of DA-6034 on Intestinal Permeability in an Indomethacin-Induced Small Intestinal Injury Model.

Science.gov (United States)

Kwak, Dong Shin; Lee, Oh Young; Lee, Kang Nyeong; Jun, Dae Won; Lee, Hang Lak; Yoon, Byung Chul; Choi, Ho Soon

2016-05-23

DA-6034 has anti-inflammatory activities and exhibits cytoprotective effects in acute gastric injury models. However, explanations for the protective effects of DA-6034 on intestinal permeability are limited. This study sought to investigate the effect of DA-6034 on intestinal permeability in an indomethacin-induced small intestinal injury model and its protective effect against small intestinal injury. Rats in the treatment group received DA-6034 from days 0 to 2 and indomethacin from days 1 to 2. Rats in the control group received indomethacin from days 1 to 2. On the fourth day, the small intestines were examined to compare the severity of inflammation. Intestinal permeability was evaluated by using fluorescein isothiocyanate-labeled dextran. Western blotting was performed to confirm the association between DA-6034 and the extracellular signal-regulated kinase (ERK) pathway. The inflammation scores in the treatment group were lower than those in the control group, but the difference was statistically insignificant. Hemorrhagic lesions in the treatment group were broader than those in the control group, but the difference was statistically insignificant. Intestinal permeability was lower in the treatment group than in the control group. DA-6034 enhanced extracellular signal-regulated kinase expression, and intestinal permeability was negatively correlated with ERK expression. DA-6034 may decrease intestinal permeability in an indomethacin-induced intestinal injury model via the ERK pathway.

Ethanolic leaf extract of Langenaria breviflora (bitter gourd) inhibits ...

African Journals Online (AJOL)

SARAH

2015-01-30

Jan 30, 2015 ... ABSTRACT. Objective: Gastrointestinal toxicity remains a barrier to applications of non-steroidal anti-inflammatory drugs in ... acetaminophen, ibuprofen, aspirin and indomethacin ..... Hepatic and Renal Function of Rats. IOSR.

[Trends of non-steroidal anti-inflammatory drugs use in Spain, 1990 through 2003].

Science.gov (United States)

de Abajo, F J; del Pozo, J García; del Pino, A

2005-11-01

To know the trends of supply, consumption and pattern of use of non-steroidal anti-inflammatory drugs (NSAIDs) in Spain from 1990 through 2003, as well as their costs. Drug utilization study. National Health System, outpatient setting. Information on drug utilization was obtained from the ALHAQUEM database of the Spanish Ministry of Health, which contains the number of packages sold in community pharmacies and charged to the National Health System. Data were expressed in defined daily doses (DDD) per 1000 inhabitants per day (DHD). NSAIDs consumption in Spain increased from 23.67 DHD in 1990 to 45.82 DHD in 2003 (a 93.6% increase). Ibuprofen was the NSAID which showed the greatest increase (15.33 DHD in 2003). The consumption of coxibs reached a maximum of 7.74 DHD in 2001, but decreased to 3.59 DHD in 2003 once prior-authorization programs were set up. Over the study period the share of NSAIDs use with a low gastrointestinal risk increased from 29% to 59%. Overall costs of NSAIDs increased from 117 million euro in 1990 to 329 million euro in 2003. Over the study period the consumption of NSAIDs in Spain has increased twofold while costs increased threefold. The pattern of use has remarkably changed showing an increasing use of NSAIDs with a better gastrointestinal profile. The impact of coxibs marketing has been moderate.

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

International Nuclear Information System (INIS)

Al-Rajab, Abdul Jabbar; Sabourin, Lyne; Lapen, David R.; Topp, Edward

2010-01-01

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. 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 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.

Potential Impact of Diet on Treatment Effect from Anti-TNF Drugs in Inflammatory Bowel Disease

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Vibeke Andersen

2017-03-01

Full Text Available We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD, to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had no dietary restrictions (78% versus 67%, p = 0.51. A meta-analysis of 295 patients found higher odds of achieving clinical remission and remaining in clinical remission among patients on combination therapy with specialised enteral nutrition and Infliximab (IFX compared with IFX monotherapy (OR 2.73; 95% CI: 1.73–4.31, p < 0.01, OR 2.93; 95% CI: 1.66–5.17, p < 0.01, respectively. In conclusion, evidence-based knowledge on impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in prospective observational, animal and interventional studies are warranted.

Comparison of different zeolite framework types as carriers for the oral delivery of the poorly soluble drug indomethacin.

Science.gov (United States)

Karavasili, Christina; Amanatiadou, Elsa P; Kontogiannidou, Eleni; Eleftheriadis, Georgios K; Bouropoulos, Nikolaos; Pavlidou, Eleni; Kontopoulou, Ioanna; Vizirianakis, Ioannis S; Fatouros, Dimitrios G

2017-08-07

Microporous zeolites of distinct framework types, textural properties and crystal morphologies namely BEA, ZSM and NaX, have been employed as carriers to assess their effect on modulating the dissolution behavior of a BCS II model drug (indomethacin). Preparation of the loaded carriers via the incipient wetness method induced significant drug amorphization for the BEA and NaX samples, as well as high drug payloads. The stability of the amorphous drug content was retained after stressing test evaluation of the porous carriers. The dissolution profile of loaded indomethacin was evaluated in simulated gastric fluid (pH 1.2) and simulated intestinal fluids FaSSIF (fasted) and FeSSIF (fed state) conditions and was found to be dependent on the aluminosilicate ratio of the zeolites and the degree of crystalline drug content. The feasibility of the zeolitic particles as oral drug delivery systems was appraised with cytocompatibility and cellular toxicity studies in Caco-2 cultures in a time- and dose-dependent manner by means of the MTT assay and flow cytometry analysis, respectively. Intracellular accumulation of the zeolite particles was observed with no apparent cytotoxic effects at the lower concentrations tested, rendering such microporous zeolites pertinent candidates in oral drug delivery applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of cytokine-suppressive anti-inflammatory drugs on inflammatory activation in ex vivo human and ovine fetal membranes.

Science.gov (United States)

Stinson, Lisa F; Ireland, Demelza J; Kemp, Matthew W; Payne, Matthew S; Stock, Sarah J; Newnham, John P; Keelan, Jeffrey A

2014-03-01

Intrauterine infection and inflammation are responsible for the majority of early (PTBs). Anti-inflammatory agents, delivered intra-amniotically together with antibiotics, may be an effective strategy for preventing PTB. In this study, the effects of four cytokine-suppressive anti-inflammatory drugs (CSAIDs: N-acetyl cysteine (NAC), SB239063, TPCA-1 and NEMO binding domain inhibitor (NBDI)) were assessed on human and ovine gestational membrane inflammation. Full-thickness membranes were collected from healthy, term, human placentas delivered by Caesarean section (n=5). Using a Transwell model, they were stimulated ex vivo with γ-irradiation-killed Escherichia coli applied to the amniotic face. Membranes from near-term, ovine placentas were stimulated in utero with lipopolysaccharide, Ureaplasma parvum or saline control and subjected to explant culture. The effects of treatment with CSAIDs or vehicle (1% DMSO) on accumulation of PGE2 and cytokines (human interleukin 6 (IL6), IL10 and TNFα; ovine IL8 (oIL8)) were assessed in conditioned media at various time points (3-20  h). In human membranes, the IKKβ inhibitor TPCA-1 (7  μM) and p38 MAPK inhibitor SB239063 (20  μM) administered to the amniotic compartment were the most effective in inhibiting accumulation of cytokines and PGE2 in the fetal compartment. NAC (10  mM) inhibited accumulation of PGE2 and IL10 only; NBDI (10  μM) had no significant effect. In addition to the fetal compartment, SB239063 also exerted consistent and significant inhibitory effects in the maternal compartment. TPCA-1 and SB239063 suppressed oIL8 production, while all CSAIDs tested suppressed ovine PGE2 production. These results support the further investigation of intra-amniotically delivered CSAIDs for the prevention of inflammation-mediated PTB.

Anti-inflammatory effects of nitric oxide-releasing hydrocortisone NCX 1022, in a murine model of contact dermatitis.

Science.gov (United States)

Hyun, Eric; Bolla, Manlio; Steinhoff, Martin; Wallace, John L; Soldato, Piero Del; Vergnolle, Nathalie

2004-11-01

1 The concept that nitric oxide (NO) release can be beneficial in inflammatory conditions has raised more attention in the recent years, particularly with the development of nitric oxide-releasing anti-inflammatory drugs. There is considerable evidence that NO is capable of enhancing the anti-inflammatory benefits of conventional anti-inflammatory drugs. 2 Since hydrocortisone is the most widely used anti-inflammatory drug for the treatment of skin inflammation, we compared the anti-inflammatory effects of hydrocortisone to an NO-releasing derivative of hydrocortisone, NCX 1022, in a murine model of irritant contact dermatitis, induced by epidermal application of benzalkonium chloride. 3 Topical pre- and post-treatment with NCX 1022 (3 nmol) in C57BL6 mice not only reduced ear oedema formation in a dose-dependent manner, but also was significantly more effective than the parent compound during the initial stages of inflammation (from 1 to 5 h). NCX 1022, but not hydrocortisone, significantly inhibited granulocyte recruitment (tissue myeloperoxidase activity). Histological samples of mouse ears treated with NCX 1022 showed significant reduction in both the number of infiltrated cells and disruption of the tissue architecture compared to hydrocortisone-treated tissues. 4 With intravital microscopy, we observed that both pre- and post-treatments with NCX 1022 were more effective than hydrocortisone in terms of inhibiting benzalkonium chloride-induced leukocyte adhesion to the endothelium, without affecting the flux of rolling leukocytes or venule diameter. 5 These results suggest that by releasing NO, NCX 1022 modulates one of the early events of skin inflammation: the recruitment of leukocytes to the site of inflammation. Overall, we have shown that NO-hydrocortisone provided faster and greater protective effects, reducing major inflammatory parameters (leukocyte adhesion and recruitment, oedema formation, tissue disruption) compared to its parental compound.

Bioactivity screening of microalgae for antioxidant, anti-inflammatory, anticancer, anti-diabetes and antibacterial activities

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Chiara eLauritano

2016-05-01

Full Text Available Marine microalgae are considered a potentially new and valuable source of biologically active molecules for applications in the food industry as well as in the pharmaceutical, nutraceutical and cosmetic sectors. They can be easily cultured, have short generation times and enable an environmentally-friendly approach to drug discovery by overcoming problems associated with the over-utilization of marine resources and the use of destructive collection practices. In this study, 21 diatoms, 7 dinoflagellates and 4 flagellate species were grown in three different culturing conditions and the corresponding extracts were tested for possible antioxidant, anti-inflammatory, anticancer, anti-diabetes, antibacterial and anti-biofilm activities. In addition, for two diatoms we also tested two different clones to disclose diversity in clone bioactivity. Six diatom species displayed specific anti-inflammatory, anticancer (blocking human melanoma cell proliferation and anti-biofilm (against the bacteria Staphylococcus epidermidis activities whereas, none of the other microalgae were bioactive against the conditions tested for. Furthermore, none of the 6 diatom species tested were toxic on normal human cells. Culturing conditions (i.e. nutrient starvation conditions greatly influenced bioactivity of the majority of the clones/species tested. This study denotes the potential of diatoms as sources of promising bioactives for the treatment of human pathologies.

Virtual Dual inhibition of COX-2 / 5-LOX enzymes based on binding properties of alpha-amyrins, the anti-inflammatory compound as a promising anti-cancer drug

Science.gov (United States)

Ranjbar, Mohammad Mehdi; Assadolahi, Vahideh; Yazdani, Mohsen; Nikaein, Donya; Rashidieh, Behnam

2016-01-01

Hydro-alcoholic fruit extract of Cordia myxa was considerably effective on curing acute inflammation in mouse model. Previous studies suggested significant anti-inflammatory activities as well as potential anticancer agent of α-amyrins in seeds. Inhibition of Cyclooxygenase-2 (COX-2) and 5-Lipooxygenase (5-LOX) is significant in cancer prevention and therapeutics although this inhibition with chemo-drugs has its own side-effects. It is shown that these enzymes pathways are related to several cancers including colon, breast and lung cancer. This study was conducted based on Cordia species' α-amyrins as a safer natural anti-cancer compound for inhibition of COX-2 and 5-LOX enzymes by molecular docking. The X-ray crystal structure of COX2 / 5-LOX enzymes and α-amyrins was retrieved and energetically minimized respectively. The binding site and surface of enzymes were detected. Docking studies were performed by AutoDock 4.2 using Lamarckian genetic algorithm (LGA). Finally drug likeness, molecular pharmacokinetic properties and toxicity of α-amyrins was calculated. Molecular Docking revealed hydrogen and hydrophobic interactions between α-amyrins with both active sites of COX-2 and 5-LOX enzymes. Interestingly, it covalently bonded to Fe cofactor of 5-LOX enzyme and chelated this molecule. Base on binding energies (∆G) α-amyrin has more inhibitory effects on 5-LOX (-10.45 Kcal/mol) than COX-2 (-8.02 Kcal/mol). Analysis of molecular pharmacokinetic parameters suggested that α-amyrins complied with most sets of Lipinski's rules, and so it could be a suitable ligand for docking studies. Eventually, bioactivity score showed α-amyrins possess considerable biological activities as nuclear receptor, enzyme inhibitor, GPCR and protease inhibitor ligand. These results clearly demonstrate that α-amyrins could act as potential highly selective COX-/5-LOX inhibitor. Also, it is a safe compound in comparison with classical non-steroidal anti-inflammatory drugs (NSAIDs

Anti-inflammatory actions of acupuncture

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Freek J. Zijlstra

2003-01-01

Full Text Available Acupuncture has a beneficial effect when treating many diseases and painful conditions, and therefore is thought to be useful as a complementary therapy or to replace generally accepted pharmacological intervention. The attributive effect of acupuncture has been investigated in inflammatory diseases, including asthma, rhinitis, inflammatory bowel disease, rheumatoid arthritis, epicondylitis, complex regional pain syndrome type 1 and vasculitis. Large randomised trials demonstrating the immediate and sustained effect of acupuncture are missing. Mechanisms underlying the ascribed immunosuppressive actions of acupuncture are reviewed in this communication. The acupuncture-controlled release of neuropeptides from nerve endings and subsequent vasodilative and anti-inflammatory effects through calcitonine gene-related peptide is hypothesised. The complex interactions with substance P, the analgesic contribution of β-endorphin and the balance between cell-specific pro-inflammatory and anti-inflammatory cytokines tumour necrosis factor-α and interleukin-10 are discussed.

The Role of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs in the Management of the Post-Embolization Symptoms after Uterine Artery Embolization

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Tiago Bilhim

2010-05-01

Full Text Available Uterine artery embolization (UAE is usually a very painful procedure. Although pain after the procedure can occur as a single symptom, it usually is associated with other symptoms such as nausea, vomiting, pelvic pain, general malaise, fever and leukocytosis that characterize the post-embolization syndrome. Management of the post-embolization symptoms and of pain in particular, is paramount if UAE is to be performed as an outpatient procedure. Different protocols have used analgesic and/or anti-inflammatory agents to control these symptoms. Nonsteroidal anti-inflammatory drugs (NSAIDs are frequently used in association with analgesic drugs to control post-embolization symptoms. In our institution the patients start oral medication with NSAIDs the day before the procedure and continue it during and after UAE. We also mix NSAIDs with the embolizing particles. This enables a reduction in the inflammation present in the uterine fibroids and helps controlling the pain. The purpose of this paper is to review the importance of NSAIDs in the management of the post-embolization symptoms. We describe the protocol that we use in our institution that enables us to perform the procedure on an outpatient basis with same day discharge and good control of the post-embolization symptoms with oral NSAIDs and analgesics.

Analgesic and anti-inflammatory controlled-released injectable microemulsion: Pseudo-ternary phase diagrams, in vitro, ex vivo and in vivo evaluation.

Science.gov (United States)

Pineros, Isabel; Slowing, Karla; Serrano, Dolores R; de Pablo, Esther; Ballesteros, Maria Paloma

2017-04-01

Development of analgesic and anti-inflammatory controlled-released injectable microemulsions utilising lysine clonixinate (LC) as model drug and generally regarded as safe (GRAS) excipients. Different microemulsions were optimised through pseudo-ternary phase diagrams and characterised measuring droplet size, viscosity, ex vivo haemolytic activity and in vitro drug release. The anti-inflammatory and analgesic activity was tested in mice (Hot plate test) and rats (Carrageenan-induced paw edema test) respectively and their activity was compared to an aqueous solution of LC salt. The aqueous solution showed a faster and shorter response whereas the optimised microemulsion increased significantly (p<0.01) the potency and duration of the analgesic and anti-inflammatory activity after deep intramuscular injection. The droplet size and the viscosity were key factors to control the drug release from the systems and enhance the effect of the formulations. The microemulsion consisting of Labrafil®/Lauroglycol®/Polysorbate 80/water with LC (56.25/18.75/15/10, w/w) could be a promising formulation after buccal surgery due to its ability to control the drug release and significantly achieve greater analgesic and anti-inflammatory effect over 24h. Copyright © 2016. Published by Elsevier B.V.

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.

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.

Effects of nonsteroidal anti-inflammatory meloxicam on stomach, kidney, and liver of rats.

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Burukoglu, Dilek; Baycu, Cengiz; Taplamacioglu, Fulya; Sahin, Erhan; Bektur, Ezgi

2016-06-01

Nonsteroidal anti-inflammatory (NSAI) drugs are the most commonly used group of drugs today. Increase in the use of standard NSAI for treating pain and inflammation was restricted by the fact that these drugs were proven to possibly cause gastrointestinal and renal toxicity. Meloxicam is a NSAI that has anti-inflammatory, analgesic, and antipyretic effects. This study aims to investigate the effects of meloxicam on stomach, kidney, and liver of rats under light microscopy level. Based on the light microscopic observations, mononuclear cell infiltration and pseudolobular formation was established in liver samples of animals in the experimental group. Metaplasia in surface and glandular epithelia and atrophy were observed in stomach samples. Glomerular stasis-related hypertrophy and focal interstitial nephritis were found in kidneys. It was concluded in this study that meloxicam might cause hepatotoxicity, nephrotoxicity, and gastric metaplasia in rats at a used dose and duration. © The Author(s) 2014.

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

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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.

Anti-inflammatory effects of chronic aspirin on brain arachidonic acid metabolites

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Basselin, Mireille; Ramadan, Epolia; Chen, Mei; Rapoport, Stanley I.

2010-01-01

Pro-inflammatory and anti-inflammatory mediators derived from arachidonic acid (AA) modulate peripheral inflammation and its resolution. Aspirin (ASA) is a unique non-steroidal anti-inflammatory drug, which switches AA metabolism from prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) to lipoxin A4 (LXA4) and 15-epi-LXA4. However it is unknown whether chronic therapeutic doses of ASA are anti-inflammatory in the brain. We hypothesized that ASA would dampen increases in brain concentrations of AA metabolites in a rat model of neuroinflammation, produced by a 6-day intracerebroventricular infusion of bacterial lipopolysaccharide (LPS). In rats infused with LPS (0.5 ng/h) and given ASA-free water to drink, concentrations in high-energy microwaved brain of PGE2, TXB2 and leukotriene B4 (LTB4) were elevated. In rats infused with artificial cerebrospinal fluid, 6 weeks of treatment with a low (10 mg/kg/day) or high (100 mg/kg/day) ASA dose in drinking water decreased brain PGE2, but increased LTB4, LXA4 and 15-epi-LXA4 concentrations. Both doses attenuated the LPS effects on PGE2, and TXB2. The increments in LXA4 and 15-epi-LXA4 caused by high-dose ASA were significantly greater in LPS-infused rats. The ability of ASA to increase anti-inflammatory LXA4 and 15-epi-LXA4 and reduce pro-inflammatory PGE2 and TXB2 suggests considering aspirin further for treating clinical neuroinflammation. PMID:20981485

Anti-inflammatory, gastroprotective and anti-ulcerogenic effects of red algae Gracilaria changii (Gracilariales, Rhodophyta) extract

Science.gov (United States)

2013-01-01

Background Gracilaria changii (Xia et Abbott) Abbott, Zhang et Xia, a red algae commonly found in the coastal areas of Malaysia is traditionally used for foods and for the treatment of various ailments including inflammation and gastric ailments. The aim of the study was to investigate anti-inflammatory, gastroprotective and anti-ulcerogenic activities of a mass spectrometry standardized methanolic extract of Gracilaria changii. Methods Methanolic extract of Gracilaria changii (MeOHGCM6 extract) was prepared and standardized using mass spectrometry (MS). Anti-inflammatory activities of MeOHGCM6 extract were examined by treating U937 cells during its differentiation with 10 μg/ml MeOHGCM6 extract. Tumour necrosis factors-α (TNF-α) response level and TNF-α and interleukin-6 (IL-6) gene expression were monitored and compared to that treated by 10 nM betamethasone, an anti-inflammatory drug. Gastroprotective and anti-ulcerogenic activities of MeOHGCM6 extract were examined by feeding rats with MeOHGCM6 extract ranging from 2.5 to 500 mg/kg body weight (b.w.) following induction of gastric lesions. Production of mucus and gastric juice, pH of the gastric juice and non-protein sulfhydryls (NP-SH) levels were determined and compared to that fed by 20 mg/kg b.w. omeprazole (OMP), a known anti-ulcer drug. Results MS/MS analysis of the MeOHGCM6 extracts revealed the presence of methyl 10-hydroxyphaeophorbide a and 10-hydroxypheophytin a, known chlorophyll proteins and several unidentified molecules. Treatment with 10 μg/ml MeOHGCM6 extract during differentiation of U937 cells significantly inhibited TNF-α response level and TNF-α and IL-6 gene expression. The inhibitory effect was comparable to that of betamethasone. No cytotoxic effects were recorded for cells treated with the 10 μg/ml MeOHGCM6 extract. Rats fed with MeOHGCM6 extract at 500 mg/kg b.w. showed reduced absolute ethanol-induced gastric lesion sizes by > 99% (p < 0.05). This protective

Anti-inflammatory effects of methylthiouracil in vitro and in vivo

Energy Technology Data Exchange (ETDEWEB)

Ku, Sae-Kwang [Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 712-715 (Korea, Republic of); Baek, Moon-Chang, E-mail: mcbaek@knu.ac.kr [Department of Molecular Medicine, CMRI, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Bae, Jong-Sup, E-mail: baejs@knu.ac.kr [College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of)

2015-11-01

The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new treatments for human diseases. Here, methylthiouracil (MTU), an antithyroid drug, was examined for its effects on lipopolysaccharide (LPS)-mediated vascular inflammatory responses. The anti-inflammatory activities of MTU were determined by measuring permeability, human neutrophil adhesion and migration, and activation of pro-inflammatory proteins in LPS-activated human umbilical vein endothelial cells and mice. We found that post-treatment with MTU inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion/transendothelial migration of human neutrophils to human endothelial cells. MTU induced potent inhibition of LPS-induced endothelial cell protein C receptor (EPCR) shedding. It also suppressed LPS-induced hyperpermeability and neutrophil migration in vivo. Furthermore, MTU suppressed the production of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, and the activation of nuclear factor-κB (NF-κB) and extracellular regulated kinases (ERK) 1/2 by LPS. Moreover, post-treatment with MTU resulted in reduced LPS-induced lethal endotoxemia. These results suggest that MTU exerts anti-inflammatory effects by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases. - Highlights: • MTU reduced LPS-mediated hyperpermeability in vitro and in vivo. • MTU inhibited LPS-mediated leukocyte adhesion and migration. • MTU inhibited LPS-mediated production of IL-6 and TNF-α. • MTU reduced LPS-mediated mortality and lung injury.

Anti-inflammatory effects of methylthiouracil in vitro and in vivo

International Nuclear Information System (INIS)

Ku, Sae-Kwang; Baek, Moon-Chang; Bae, Jong-Sup

2015-01-01

The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new treatments for human diseases. Here, methylthiouracil (MTU), an antithyroid drug, was examined for its effects on lipopolysaccharide (LPS)-mediated vascular inflammatory responses. The anti-inflammatory activities of MTU were determined by measuring permeability, human neutrophil adhesion and migration, and activation of pro-inflammatory proteins in LPS-activated human umbilical vein endothelial cells and mice. We found that post-treatment with MTU inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion/transendothelial migration of human neutrophils to human endothelial cells. MTU induced potent inhibition of LPS-induced endothelial cell protein C receptor (EPCR) shedding. It also suppressed LPS-induced hyperpermeability and neutrophil migration in vivo. Furthermore, MTU suppressed the production of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, and the activation of nuclear factor-κB (NF-κB) and extracellular regulated kinases (ERK) 1/2 by LPS. Moreover, post-treatment with MTU resulted in reduced LPS-induced lethal endotoxemia. These results suggest that MTU exerts anti-inflammatory effects by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases. - Highlights: • MTU reduced LPS-mediated hyperpermeability in vitro and in vivo. • MTU inhibited LPS-mediated leukocyte adhesion and migration. • MTU inhibited LPS-mediated production of IL-6 and TNF-α. • MTU reduced LPS-mediated mortality and lung injury.

Anti-inflammatory and neuropharmacological activities of ...

African Journals Online (AJOL)

The crude methanolic extracts of leaves of Caesalpinia pulcherrima were evaluated for its anti-inflammatory and neuropharmacological activities. When given orally to rats at dose of 200 and 400 mg/kg, the extract showed a significant (P<0.001) anti-inflammatory activity against carrageenin induced paw edema in rats ...

An anti-inflammatory principle from cactus.

Science.gov (United States)

Park, E H; Kahng, J H; Lee, S H; Shin, K H

2001-03-01

In previous studies, the ethanol extract of cactus (Opuntia ficus-indica) showed potent anti-inflammatory action. In the present study, following fractionation of the methanol extract of cactus stems guided by adjuvant-induced chronic inflammation model in mice, an active anti-inflammatory principle has been isolated and identified as beta-sitosterol.

Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthritis.

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Al-Okbi, Sahar Y

2014-09-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by elevated oxidative stress and inflammatory biomarkers. The severe side effects of drug used during such disease necessitate the search for new and safe approaches. Food is a rich source of antioxidants and anti-inflammatory bioactive constituents including phenolic compounds, polyunsaturated fatty acids, phytosterols, toccopherols, and carotenoids. We have a series of publications dealing with the anti-inflammatory activity of different food extracts (as nutraceuticals) in experimental animals (acute and chronic inflammation model) and in clinical study (RA patients). Fish oil, primrose oil, extracts of black cumin, fenugreek, liquorice, coriander, tomato, carrot, sweet potato, broccoli, green tea, rosemary, hazelnut, walnut, wheat germ, and date in addition to the probiotic Bifidobacterium bifidum were the nutraceuticals studied. During these studies, changes in inflammatory biomarkers (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), seromucoids, fibrinogen, tumor necrosis factor-α (TNF-α), prostaglandin E2), oxidative stress (malondialdehyde), antioxidant status (total antioxidant capacity, vitamin C, vitamin E, retinol, β-carotene), the level of copper (Cu) and zinc (Zn) and colonic microflora in response to the administration of nutraceuticals have been assessed. Results of these studies showed that the majority of nutraceuticals studied possess beneficial effect toward chronic inflammatory diseases, which might be due to the presence of one or more of the above-mentioned phytochemicals. Anti-inflammatory and antioxidant nutraceuticals may serve as complementary medicine for the management of RA. © The Author(s) 2012.

Therapeutic effects of date fruits (Phoenix dactylifera) in the prevention of diseases via modulation of anti-inflammatory, anti-oxidant and anti-tumour activity.

Science.gov (United States)

Rahmani, Arshad H; Aly, Salah M; Ali, Habeeb; Babiker, Ali Y; Srikar, Sauda; Khan, Amjad A

2014-01-01

The current mode of treatment of various diseases based on synthetic drugs is expensive, alters genetic and metabolic pathways and also shows adverse side effects. Thus, safe and effective approach is needed to prevent the diseases development and progression. In this vista, Natural products are good remedy in the treatment/management of diseases and they are affordable and effective without any adverse effects. Dates are main fruit in the Arabian Peninsula and are considered to be one of the most significant commercial crops and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that constituents of dates act as potent antioxidant, anti-tumour as well as anti-inflammatory, provide a suitable alternative therapy in various diseases cure. In this review, dates fruits has medicinal value are summarized in terms of therapeutic implications in the diseases control through anti-oxidant, anti-inflammatory, anti-tumour and ant-diabetic effect.

Effect of nonsteroidal anti-inflammatory drugs on colorectal distension-induced visceral pain

Science.gov (United States)

Baskın, Veysel; Bilge, S. Sırrı; Bozkurt, Ayhan; Akyüz, Bahar; Ağrı, Arzu Erdal; Güzel, Hasan; İlkaya, Fatih

2016-01-01

Objectives: To investigate nonsteroidal anti-inflammatory drugs effectiveness in colorectal distension (CRD)-induced visceral pain model. Materials and Methods: Male Sprague–Dawley (250–300 g) rats were anesthetized with ketamine (50 mg/kg, intraperitoneally [i.p.]) and chlorpromazine (25 mg/kg, i.p.). Two bipolar Teflon-coated Ni/Cr wire electrodes (80-M diameter) were placed in the abdominal external oblique muscle for the recording of electromyography. Jugular vein catheter was placed for the administration of drugs. CRD method was applied to evaluate of visceral pain. All drugs (paracetamol, meloxicam, metamizole, and dexketoprofen) administered intravenously. Results: Paracetamol 200, 400, and 600 mg/kg did not change the visceromotor response (VMR) when compare with the control group. Meloxicam 2 and 4 mg/kg showed no effect but at doses of 6 mg/kg meloxicam significantly ([51.9 ± 6.4%] [P Dexketoprofen 2 and 4 mg/kg did not cause a change in VMR but 6 mg/kg dose significantly reduced response compared with the control group ([43.9 ± 3.9%, 36.8 ± 2.8%, 34.8 ± 2.5%, 42.1 ± 4.8%, 40.7 ± 3.5%, 36.4 ± 2.7%, and 26.1 ± 2.2%]; from 10 min to 70 min, respectively, [P dexketoprofen and meloxicam show antinociceptive effect with different duration of action on CRD-induced visceral pain model. This condition can be explained due to different chemical structures and different mechanisms which play a role in modulation of pain. PMID:27114637

Anti-inflammatory Activity of Methanoilc and Ethanolic Extracts of ...

African Journals Online (AJOL)

Aqueous ethanoic and methanolic extracts of Citrus Sinensis Peel were investigated for antiinflammatory activity in carrageenan induced paw oedema in wistar rats, and compared to a positive control drug, Indomethacin. These extracts were given(IP) in a concentration of 20, and 70mg/kg with extract with a concentration ...

Potential impact of diet on treatment effect from anti-TNF drugs in inflammatory bowel disease

DEFF Research Database (Denmark)

Andersen, Vibeke; Hansen, Axel Kornerup; Heitmann, Berit Lilienthal

2017-01-01

We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such invest......We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies...... for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had......% CI: 1.73–4.31, p diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic...

Do nonsteroidal anti-inflammatory drugs affect the outcome of arthroscopic Bankart repair?

Science.gov (United States)

Blomquist, J; Solheim, E; Liavaag, S; Baste, V; Havelin, L I

2014-12-01

To achieve pain control after arthroscopic shoulder surgery, nonsteroidal anti-inflammatory drugs (NSAIDs) are a complement to other analgesics. However, experimental studies have raised concerns that these drugs may have a detrimental effect on soft tissue-to-bone healing and, thus, have a negative effect on the outcome. We wanted to investigate if there are any differences in the clinical outcome after the arthroscopic Bankart procedure for patients who received NSAIDs prescription compared with those who did not. 477 patients with a primary arthroscopic Bankart procedure were identified in the Norwegian shoulder instability register and included in the study. 32.5% received prescription of NSAIDs post-operatively. 370 (78%) of the patients answered a follow-up questionnaire containing the Western Ontario Shoulder Instability index (WOSI). Mean follow-up was 21 months. WOSI at follow-up were 75% in the NSAID group and 74% in the control group. 12% of the patients in the NSAID group and 14% in the control group reported recurrence of instability. The reoperation rate was 5% in both groups. There were no statistically significant differences between the groups. Prescription of short-term post-operative NSAID treatment in the post-operative period did not influence on the functional outcome after arthroscopic Bankart procedures. © 2014 The Authors. Scandinavian Journal of Medicine & Science in Sports published by John Wiley & Sons Ltd.

Amorphous formulations of indomethacin and griseofulvin prepared by electrospinning.

Science.gov (United States)

Lopez, Felipe L; Shearman, Gemma C; Gaisford, Simon; Williams, Gareth R

2014-12-01

Following an array of optimization experiments, two series of electrospun polyvinylpyrrolidone (PVP) fibers were prepared. One set of fibers contained various loadings of indomethacin, known to form stable glasses, and the other griseofulvin (a poor glass former). Drug loadings of up to 33% w/w were achieved. Electron microscopy data showed the fibers largely to comprise smooth and uniform cylinders, with evidence for solvent droplets in some samples. In all cases, the drug was found to exist in the amorphous physical state in the fibers on the basis of X-ray diffraction and differential scanning calorimetry (DSC) measurements. Modulated temperature DSC showed that the relationship between a formulation's glass transition temperature (Tg) and the drug loading follows the Gordon-Taylor equation, but not the Fox equation. The results of Gordon-Taylor analysis indicated that the drug/polymer interactions were stronger with indomethacin. The interactions between drug and polymer were explored in more detail using molecular modeling simulations and again found to be stronger with indomethacin; the presence of significant intermolecular forces was further confirmed using IR spectroscopy. The amorphous form of both drugs was found to be stable after storage of the fibers for 8 months in a desiccator (relative humidity <25%). Finally, the functional performance of the fibers was studied; in all cases, the drug-loaded fibers released their drug cargo very rapidly, offering accelerated dissolution over the pure drug.

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.

Anti-inflammatory and antinociceptive activities of Rhipicephalus microplus saliva

Directory of Open Access Journals (Sweden)

D F Buccini

2018-01-01

Full Text Available Objective: To evaluate the antinociceptive and anti-inflammatory activities and the toxic effects of Rhipicephalus microplus saliva for elucidating the modulation mechanism between arthropod saliva and host. Methods: For saliva collection, engorged ticks were obtained from a controlled bovine infestation and collected by natural fall. The ticks were fixed and injected pilocarpine 0.2% for induction of salivation. Saliva was collected, lyophilized and stored at - 80 °C. Cytotoxic activity was assessed by the hemolysis method (25, 50, 100, 200 and 300 μ g/mL and MTT cell viability assay (2.5, 5, 10, 20 and 40 μ g/mL for 24, 48 and 72 h. Anti-inflammatory activity was evaluated using the method of neutrophil migration to the peritoneal cavity of mice at doses of 10, 15 and 20 mg/kg; antinociceptive activity was assessed using the acetic acid-induced writhing test, and formalin-induced paw-licking in mice at dose of 15 mg/kg. Results: Saliva did not cause erythrocytes hemolysis at any concentration tested, as well as did not decrease cell viability in the MTT assay. Saliva inhibited neutrophil migration by 87% and 73% at doses of 15 and 20 mg/kg, respectively. In the nociceptive tests, saliva presented analgesic activity of 69.96% in the abdominal writhing test, and of 84.41% in the formalin test. Conclusions: The study proves that Rhipicephalus microplus saliva has significant in vivo anti-inflammatory and antinociceptive activities. The data presented herein support the development of further studies to elucidate the active principles of Rhipicephalus microplus saliva and its mechanism of action and, in future, to develop novel anti-inflammatory and analgesic drugs.

Anti-inflammatory Chitosan/Poly-γ-glutamic acid nanoparticles control inflammation while remodeling extracellular matrix in degenerated intervertebral disc.

Science.gov (United States)

Teixeira, Graciosa Q; Leite Pereira, Catarina; Castro, Flávia; Ferreira, Joana R; Gomez-Lazaro, Maria; Aguiar, Paulo; Barbosa, Mário A; Neidlinger-Wilke, Cornelia; Goncalves, Raquel M

2016-09-15

Intervertebral disc (IVD) degeneration is one of the most common causes of low back pain (LBP), the leading disorder in terms of years lived with disability. Inflammation can play a role in LPB, while impairs IVD regeneration. In spite of this, different inflammatory targets have been purposed in the context of IVD regeneration. Anti-inflammatory nanoparticles (NPs) of Chitosan and Poly-(γ-glutamic acid) with a non-steroidal anti-inflammatory drug, diclofenac (Df), were previously shown to counteract a pro-inflammatory response of human macrophages. Here, the effect of intradiscal injection of Df-NPs in degenerated IVD was evaluated. For that, Df-NPs were injected in a bovine IVD organ culture in pro-inflammatory/degenerative conditions, upon stimulation with needle-puncture and interleukin (IL)-1β. Df-NPs were internalized by IVD cells, down-regulating IL-6, IL-8, MMP1 and MMP3, and decreasing PGE2 production, compared with IL-1β-stimulated IVD punches. Interestingly, at the same time, Df-NPs promoted an up-regulation of extracellular matrix (ECM) proteins, namely collagen type II and aggrecan. Allover, this study suggests that IVD treatment with Df-NPs not only reduces inflammation, but also delays and/or decreases ECM degradation, opening perspectives to new intradiscal therapies for IVD degeneration, based on the modulation of inflammation. Degeneration of the IVD is an age-related progressive process considered to be the major cause of spine disorders. The pro-inflammatory environment and biomechanics of the degenerated IVD is a challenge for regenerative therapies. The novelty of this work is the intradiscal injection of an anti-inflammatory therapy based on Chitosan (Ch)/Poly-(γ-glutamic acid) (γ-PGA) nanoparticles (NPs) with an anti-inflammatory drug (diclofenac, Df), previously developed by us. This drug delivery system was tested in a pro-inflammatory/degenerative intervertebral disc ex vivo model. The main findings support the success of an anti-inflammatory