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

PubMed Central

Lionberger, David R; Brennan, Michael J

2010-01-01

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 acute soft tissue injuries was included. Relevant literature was identified on MEDLINE using the search terms topical NSAIDs, diclofenac, diclofenac epolamine, acute pain, sports injury, soft tissue injury, strain, sprain, and contusion, and from citations in retrieved articles covering the years 1978–2008. Review of published, randomized clinical trials and meta-analyses shows that topical NSAIDs are significantly more effective than placebo in relieving acute pain; the pooled average relative benefit was 1.7 (95% confidence interval, 1.5–1.9). In a limited number of comparisons, topical and oral NSAIDs provided comparable pain relief, but the use of topical agents produced lower plasma drug concentrations and fewer systemic adverse events (AEs). The physical–chemical properties of diclofenac epolamine make it well suited for topical use. In patients with acute soft tissue injuries treated with DETP, clinical data report an analgesic benefit within hours of the first application, and significant pain relief relative to placebo within 3 days. Moreover, DETP displayed tolerability comparable with placebo; the most common AEs were pruritus and other application site reactions. Review of published literature suggests that DETP is generally safe and well tolerated, clinically efficacious, and a rational treatment option for patients experiencing acute pain associated with strains, sprains, and contusions, and other localized painful conditions. PMID:21197326

Use of Non-Steroidal Anti-Inflammatory Drugs That Elevate Cardiovascular Risk: An Examination of Sales and Essential Medicines Lists in Low-, Middle-, and High-Income Countries

PubMed Central

McGettigan, Patricia; Henry, David

2013-01-01

Background Certain non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., rofecoxib [Vioxx]) increase the risk of heart attack and stroke and should be avoided in patients at high risk of cardiovascular events. Rates of cardiovascular disease are high and rising in many low- and middle-income countries. We studied the extent to which evidence on cardiovascular risk with NSAIDs has translated into guidance and sales in 15 countries. Methods and Findings Data on the relative risk (RR) of cardiovascular events with individual NSAIDs were derived from meta-analyses of randomised trials and controlled observational studies. Listing of individual NSAIDs on Essential Medicines Lists (EMLs) was obtained from the World Health Organization. NSAID sales or prescription data for 15 low-, middle-, and high-income countries were obtained from Intercontinental Medical Statistics Health (IMS Health) or national prescription pricing audit (in the case of England and Canada). Three drugs (rofecoxib, diclofenac, etoricoxib) ranked consistently highest in terms of cardiovascular risk compared with nonuse. Naproxen was associated with a low risk. Diclofenac was listed on 74 national EMLs, naproxen on just 27. Rofecoxib use was not documented in any country. Diclofenac and etoricoxib accounted for one-third of total NSAID usage across the 15 countries (median 33.2%, range 14.7–58.7%). This proportion did not vary between low- and high-income countries. Diclofenac was by far the most commonly used NSAID, with a market share close to that of the next three most popular drugs combined. Naproxen had an average market share of less than 10%. Conclusions Listing of NSAIDs on national EMLs should take account of cardiovascular risk, with preference given to low risk drugs. Diclofenac has a risk very similar to rofecoxib, which was withdrawn from worldwide markets owing to cardiovascular toxicity. Diclofenac should be removed from EMLs. Please see later in the article for the Editors' Summary PMID:23424288

Use of non-steroidal anti-inflammatory drugs that elevate cardiovascular risk: an examination of sales and essential medicines lists in low-, middle-, and high-income countries.

PubMed

McGettigan, Patricia; Henry, David

2013-01-01

Certain non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., rofecoxib [Vioxx]) increase the risk of heart attack and stroke and should be avoided in patients at high risk of cardiovascular events. Rates of cardiovascular disease are high and rising in many low- and middle-income countries. We studied the extent to which evidence on cardiovascular risk with NSAIDs has translated into guidance and sales in 15 countries. Data on the relative risk (RR) of cardiovascular events with individual NSAIDs were derived from meta-analyses of randomised trials and controlled observational studies. Listing of individual NSAIDs on Essential Medicines Lists (EMLs) was obtained from the World Health Organization. NSAID sales or prescription data for 15 low-, middle-, and high-income countries were obtained from Intercontinental Medical Statistics Health (IMS Health) or national prescription pricing audit (in the case of England and Canada). Three drugs (rofecoxib, diclofenac, etoricoxib) ranked consistently highest in terms of cardiovascular risk compared with nonuse. Naproxen was associated with a low risk. Diclofenac was listed on 74 national EMLs, naproxen on just 27. Rofecoxib use was not documented in any country. Diclofenac and etoricoxib accounted for one-third of total NSAID usage across the 15 countries (median 33.2%, range 14.7-58.7%). This proportion did not vary between low- and high-income countries. Diclofenac was by far the most commonly used NSAID, with a market share close to that of the next three most popular drugs combined. Naproxen had an average market share of less than 10%. Listing of NSAIDs on national EMLs should take account of cardiovascular risk, with preference given to low risk drugs. Diclofenac has a risk very similar to rofecoxib, which was withdrawn from worldwide markets owing to cardiovascular toxicity. Diclofenac should be removed from EMLs.

Nanostructured lipid carriers to enhance transdermal delivery and efficacy of diclofenac.

PubMed

Nguyen, Chien Ngoc; Nguyen, Thi Thuy Trang; Nguyen, Hanh Thuy; Tran, Tuan Hiep

2017-10-01

Lipid carrier-mediated transdermal drug delivery offers several advantages because it is non-irritating and non-toxic, provides effective control of drug release, and forms an adhesive film that hydrates the outer skin layers. However, to penetrate the deeper skin layers, these formulations need to overcome several barriers in the stratum corneum. This study evaluates factors influencing particle size and drug-loading capacity, which play a key role in drug permeation and efficacy. Diclofenac sodium was chosen as the model drug. The fabrication of diclofenac sodium-loaded lipid nanoparticles was optimized by modulating several parameters, including the lipids and surfactants employed, the drug/lipid ratio, and the pH of the aqueous phase. The physical properties and loading efficiencies of the nanoparticles were characterized. The optimized formulation was then dispersed into a polymer solution to form a gel, which demonstrated a sustained ex vivo permeation of diclofenac sodium over 24 h through excised rat skin and a higher drug penetrating capacity than that of a commercially available gel. In vivo anti-inflammatory activity was assessed in a rat carrageenan-induced paw edema model; the anti-edema effects of the prepared gel and commercially available gel over 24 h were comparable. The present findings indicate the effects of particle size and drug loading on the ability of nanostructured lipid carrier preparations to provide transdermal drug delivery.

Lipid nanostructured Hydrogels for Topical Delivery of Anti-inflammatory Drugs: Preparation and Characterization

NASA Astrophysics Data System (ADS)

Acevedo-Robles, Noelia

Diclofenac sodium is a nonsteroidal anti-inflammatory drugs (NSAID) used to treat sign or symptoms of osteoarthritis and rheumatoid arthritis. However, its clinical usage is limited to some extent due to its toxicity and systemic side effects, including gastrointestinal lesions. The development of lipid nanostructured hydrogel for topical application will solve the problems of first pass metabolism minimize systemic side effect of the anti-inflammatory drugs. Two types of nanotechnologies were used: Lipid Nanostructured Lipid carrier (NLC) and Solid Lipid Nanoparticles (SLN). The difference between both nanotechnologies is that NLC carrier contain liquid and solid lipid, however, the SLN contains solid lipid. Both nanostructured lipid carrier is prepared by high pressure micro-fluidizer technology avoiding solvents use. The use of liquid lipid with solid lipid leads us to imperfection in the matrix which can provide more space for the accommodation of the drug, therefore NLC is the more efficient formulation in drug entrapment.

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

PubMed Central

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

2013-01-01

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

Anti-inflammatory Chitosan/Poly-γ-glutamic acid nanoparticles control inflammation while remodeling extracellular matrix in degenerated intervertebral disc.

PubMed

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 therapy for degenerated IVD that not only reduces inflammation but also promotes native IVD matrix production. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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".

PubMed

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 < 30 ml/min) in 106 residents (15.5 %). Approximately one-fifth was treated with at least one nonsteroidal anti-inflammatory drug in both the total study population (20.3 %) and that with severe 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.

A Review of Topical Diclofenac Use in Musculoskeletal Disease

PubMed Central

Nair, Bindu; Taylor-Gjevre, Regina

2010-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed medications for the treatment of musculoskeletal disorders. Osteoarthritis is the most common form of arthritis in humans and its prevalence rises with age. Oral NSAIDs have potential associated toxicities that must be monitored for and can limit the use of these drugs in certain populations including people of older age. Topical NSAIDs are now being recognized as an option for the treatment strategy of osteoarthritis. We review the efficacy and safety of one of the most common topical NSAIDS, topical diclofenac, for the treatment of osteoarthritis. PMID:27713334

Disparate effects of non-steroidal anti-inflammatory drugs on apoptosis in guinea-pig gastric mucous cells: inhibition of basal apoptosis by diclofenac

PubMed Central

Ashton, Miranda; Hanson, Peter J

2002-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) induce apoptosis in gastrointestinal cancer cell lines. Similar actions on normal gastric epithelial cells could contribute to NSAID gastropathy. The present work therefore compared the actions of diclofenac, ibuprofen, indomethacin, and the cyclo-oxygenase-2 selective inhibitor, NS-398, on a primary culture of guinea-pig gastric mucous epithelial cells. Cell number was assessed by staining with crystal violet. Apoptotic activity was determined by condensation and fragmentation of nuclei and by assay of caspase-3-like activity. Necrosis was evaluated from release of cellular enzymes. Ibuprofen (250 μM for 24 h) promoted cell loss, and apoptosis, under both basal conditions and when apoptosis was increased by 25 μM N-Hexanoyl-D-sphingosine (C6-ceramide). Diclofenac (250 μM for 24 h) reduced the proportion of apoptotic nuclei from 5.2 to 2.1%, and caused inhibition of caspase-3-like activity, without causing necrosis under basal conditions. No such reduction in apoptotic activity was evident in the presence of 25 μM C6-ceramide. The inhibitory effect of diclofenac on basal caspase-3-like activity was also exhibited by the structurally similar mefenamic and flufenamic acids (1–250 μM), but not by niflumic acid. Inhibition of superoxide production by the cells increased caspase-3-like activity, but the inhibitory action of diclofenac on caspase activity remained. Diclofenac did not affect superoxide production. Diclofenac inhibited caspase-3-like activity in cell homogenates and also inhibited human recombinant caspase-3. In conclusion, NSAIDs vary in their effect on apoptotic activity in a primary culture of guinea-pig gastric mucous epithelial cells, and the inhibitory effect of diclofenac on basal apoptosis could involve an action on caspase activity. PMID:11815376

Efficacy and Safety Profile of Diclofenac/Cyclodextrin and Progesterone/Cyclodextrin Formulations: A Review of the Literature Data.

PubMed

Scavone, Cristina; Bonagura, Angela Colomba; Fiorentino, Sonia; Cimmaruta, Daniela; Cenami, Rosina; Torella, Marco; Fossati, Tiziano; Rossi, Francesco

2016-06-01

According to health technology assessment, patients deserve the best medicine. The development of drugs associated with solubility enhancers, such as cyclodextrins, represents a measure taken in order to improve the management of patients. Different drugs, such as estradiol, testosterone, dexamethasone, opioids, non-steroidal anti-inflammatories (NSAIDs; i.e. diclofenac), and progesterone are associated with cyclodextrins. Products containing the association of diclofenac/cyclodextrins are available for subcutaneous, intramuscular, and intravenous administration in doses that range from 25 to 75 mg. Medicinal products containing the association of progesterone/cyclodextrins are indicated for intramuscular and subcutaneous injection at a dose equal to 25 mg. The effects of cyclodextrins have been discussed in the solubility profile and permeability through biological membranes of drug molecules. A literature search was performed in order to give an overview of the pharmacokinetic characteristics, and efficacy and safety profiles of diclofenac/hydroxypropyl-β-cyclodextrin (HPβCD) and progesterone/HPβCD associations. The results of more than 20 clinical studies were reviewed. It was suggested that the new diclofenac/HPβCD formulation gives a rapid and effective response to acute pain and, furthermore, has pharmacokinetic and efficacy/safety profiles comparable to other medicinal products not containing cyclodextrins. One of the principal aspects of these new diclofenac formulations is that in lowering the dose (lower than 50 mg) the drugs could be more tolerable, especially in patients with comorbid conditions. Moreover, results of studies investigating the characteristics of progesterone and cyclodextrins showed that the new formulation (progesterone/HPβCD 25 mg solution) has the same bioavailability as other products containing progesterone. It is more rapidly absorbed and allows the achievement of peak plasma concentrations in a shorter time. Finally, the new formulation of progesterone was shown to be safe and not inferior to other products already on the market, with the exception of progesterone administered vaginally. As shown by the results of clinical studies presented in this review, the newly approved medicines containing cyclodextrins have been found to be as effective and as well-tolerated as other medicinal products that do not contain cyclodextrins. Moreover, the newly approved lower dose of diclofenac associated with cyclodextrins is consistent with the European Medicines Agency recommendations reported in the revision of the Assessment Report for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Cardiovascular Risk. Finally, the use of cyclodextrins led to significant increases in solubility and bioavailability of drugs, such as diclofenac and progesterone, and improvement in the efficacy and safety of these drugs.

Synergistic effect of the interaction between curcumin and diclofenac on the formalin test in rats.

PubMed

De Paz-Campos, Marco A; Ortiz, Mario I; Chávez Piña, Aracely E; Zazueta-Beltrán, Liliana; Castañeda-Hernández, Gilberto

2014-10-15

The association of non-steroidal anti-inflammatory drugs with certain plant extracts can increase antinociceptive activity, permitting the use of lower doses and thus limiting side effects. Therefore, the aim objective of the current study was to examine the effects of curcumin on the nociception and pharmacokinetics of diclofenac in rats. Antinociception was assessed using the formalin test. Diluted formalin was injected subcutaneously into the dorsal surface of the right hind paw. Nociceptive behavior was quantified as the number of flinches of the injected paw during 60 min after injection, and a reduction in formalin-induced flinching was interpreted as an antinociceptive response. Rats were treated with oral diclofenac (1-31 mg/kg), curcumin (3.1-100 mg/kg) or the diclofenac-curcumin combination (2.4-38.4 mg/kg). To determine the possibility of a pharmacokinetic interaction, the oral bioavailability of diclofenac (10 mg/kg) was studied in presence and the absence of curcumin (31 mg/kg). Diclofenac, curcumin, or diclofenac-curcumin combination produced an antinociceptive effect on the formalin test. ED30 values were estimated for the individual drugs, and an isobologram was constructed. The derived theoretical ED30 for the antinociceptive effect (19.2 mg/kg) was significantly different from the observed experimental ED30 value (9.8 mg/kg); hence, the interaction between diclofenac and curcumin that mediates the antinociceptive effect was synergistic. Notwithstanding, the interaction does not appear to involve pharmacokinetic mechanisms, as oral curcumin failed to produce any significant alteration in oral diclofenac bioavailability. Data suggest that the diclofenac-curcumin combination can interact at the systemic level and may have therapeutic advantages for the clinical treatment of inflammatory pain. Copyright © 2014 Elsevier GmbH. All rights reserved.

Diclofenac poisoning is widespread in declining vulture populations across the Indian subcontinent.

PubMed

Shultz, Susanne; Baral, Hem Sagar; Charman, Sheonaidh; Cunningham, Andrew A; Das, Devojit; Ghalsasi, G R; Goudar, Mallikarjun S; Green, Rhys E; Jones, Ainsley; Nighot, Prashant; Pain, Deborah J; Prakash, Vibhu

2004-12-07

Recent declines in the populations of three species of vultures in the Indian subcontinent are among the most rapid ever recorded in any bird species. Evidence from a previous study of one of these species, Gyps bengalensis, in the Punjab province of Pakistan, strongly implicates mortality caused by ingestion of residues of the veterinary non-steroidal anti-inflammatory drug diclofenac as the major cause of the decline. We show that a high proportion of Gyps bengalensis and G. indicus found dead or dying in a much larger area of India and Nepal also have residues of diclofenac and visceral gout, a post-mortem finding that is strongly associated with diclofenac contamination in both species. Hence, veterinary use of diclofenac is likely to have been the major cause of the rapid vulture population declines across the subcontinent.

Topical diclofenac epolamine patch 1.3% for treatment of acute pain caused by soft tissue injury

PubMed Central

McCarberg, B H; Argoff, C E

2010-01-01

Acute pain caused by musculoskeletal disorders is very common and has a significant negative impact on quality-of-life and societal costs. Many types of acute pain have been managed with traditional oral non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 inhibitors (coxibs). Data from prospective, randomised controlled clinical trials and postmarketing surveillance indicate that use of oral traditional NSAIDs and coxibs is associated with an elevated risk of developing gastrointestinal, renovascular and/or cardiovascular adverse events (AEs). Increasing awareness of the AEs associated with NSAID therapy, including coxibs, has led many physicians and patients to reconsider use of these drugs and look for alternative treatment options. Treatment with NSAIDs via the topical route of administration has been shown to provide clinically effective analgesia at the site of application while minimising systemic absorption. The anti-inflammatory and analgesic potency of the traditional oral NSAID diclofenac, along with its physicochemical properties, makes it well suited for topical delivery. Several topical formulations of diclofenac have been developed. A topical patch containing diclofenac epolamine 1.3% (DETP, FLECTOR® Patch), approved for use in Europe in 1993, has recently been approved for use in the United States and is indicated for the treatment of acute pain caused by minor strains, sprains and contusions. In this article, we review the available clinical trial data for this product in the treatment of pain caused by soft tissue injury. PMID:20666849

Risk of single and combined exposure of birds to non-steroidal anti-inflammatory drugs and lead.

PubMed

Osickova, Jitka; Skochova, Hana; Ondracek, Karel; Kral, Jiri; Damkova, Veronika; Peckova, Lucie; Pohanka, Miroslav; Vitula, Frantisek; Bandouchova, Hana; Pikula, Jiri

2012-01-01

Pharmaceuticals and heavy metals such as diclofenac and lead, respectively, have been identified as environmental contaminants toxic to birds and posing serious threats to declining populations of raptors worldwide. The aim of the present study was to test the hypothesis that a sublethal combination of non-steroidal anti-inflammatory drugs and lead induces more pronounced effects than single exposures in birds. A total of 40 Japanese quails (Coturnix coturnix japonica) at the age of 2 months and average weight of 180g were on a random basis divided into four experimental groups of 10 specimens (i.e., control, diclofenac, lead, and lead+diclofenac exposures). Six lead shots in the total weight of 1.5 grams were inserted into the crop on day 0 of the experiment, while a total of 5 mg/kg of diclofenac administered intramuscularly were divided into treatments on days 0 and 5. Group responses were compared using haematology and biochemistry after 10 days. There was no mortality in control and both single and combined diclofenac and lead exposure groups, nor did the birds show any clinical signs of intoxication. Univariate analyses of blood parameters yielded a decrease in haematocrit in birds exposed to both substances when compared with the control, a lower haemoglobin level of the lead-exposed group, increased activity of aspartate aminotransferase in the NSAIDs-exposed group, increased activity of alkaline phosphatase in birds exposed to a combination of diclofenac and lead, and a higher phosphorus level in the lead-exposed group. The principal component analysis revealed no multivariate pattern of responses of blood parameters and did not allow separation of exposure groups from controls when the variables and samples were projected onto a two dimensional space. Results of the present study can enhance understanding of combination toxicity of veterinary drugs and heavy metals in birds, i.e. a scenario that has become environmentally relevant in recent decades. Fortunately, individual blood parameter effects prevailed and no joint mortal effects were recognised in Japanese quails exposed to a combination of sublethal doses of diclofenac and lead.

Effect of different penetration enhancers on diclofenac permeation across horse skin.

PubMed

Ferrante, M; Andreeta, A; Landoni, M F

2010-12-01

Diclofenac is a hydrophilic non-steroidal anti-inflammatory drug widely used in humans and animals. Previous reports have shown that this compound has low percutaneous absorption in horses. The effect of five penetration enhancers (10% urea, 15% and 20% oleic acid and 5% and 10% d-limonene) on the percutaneous absorption of diclofenac diethylamine through horse skin was evaluated in vitro using Franz-type diffusion cells. All tested penetration enhancers induced a significant increase in diclofenac diethylamine permeation, with limonene showing the highest enhancing effect at the lowest concentration (5%) applied. The presence of the permeation enhancers did not affect lag-time. This is the first in vitro study of the effects of penetration enhancers on transdermal permeation of diclofenac diethylamine across horse skin. The results suggested that urea, limonene and 5% oleic acid were useful for enhancing the transdermal absorption of diclofenac diethylamine and may assist in the development of a transdermal formulation of diclofenac diethylamine for use in horses. Copyright © 2009. Published by Elsevier Ltd.

Ecotoxicogenomic assessment of diclofenac toxicity in soil.

PubMed

Chen, Guangquan; den Braver, Michiel W; van Gestel, Cornelis A M; van Straalen, Nico M; Roelofs, Dick

2015-04-01

Diclofenac is widely used as nonsteroidal anti-inflammatory drug leaving residues in the environment. To investigate effects on terrestrial ecosystems, we measured dissipation rate in soil and investigated ecotoxicological and transcriptome-wide responses in Folsomia candida. Exposure for 4 weeks to diclofenac reduced both survival and reproduction of F. candida in a dose-dependent manner. At concentrations ≥ 200 mg/kg soil diclofenac remained stable in the soil during a 21-day incubation period. Microarrays examined transcriptional changes at low and high diclofenac exposure concentrations. The results indicated that development and growth were severely hampered and immunity-related genes, mainly directed against bacteria and fungi, were significantly up-regulated. Furthermore, neural metabolic processes were significantly affected only at the high concentration. We conclude that diclofenac is toxic to non-target soil invertebrates, although its mode of action is different from the mammalian toxicity. The genetic markers proposed in this study may be promising early markers for diclofenac ecotoxicity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Immunogenomics reveal molecular circuits of diclofenac induced liver injury in mice

PubMed Central

Lee, Eun-Hee; Oh, Jung-Hwa; Selvaraj, Saravanakumar; Park, Se-Myo; Choi, Mi-Sun; Spanel, Reinhard

2016-01-01

Diclofenac is a non-steroidal anti-inflammatory drug and its use can be associated with severe adverse reactions, notably myocardial infarction, stroke and drug-induced liver injury (DILI). In pursue of immune-mediated DILI mechanisms an immunogenomic study was carried out. Diclofenac treatment of mice at 30 mg/kg for 3 days caused significant serum ALT and AST elevations, hepatomegaly and degenerative changes including hepatic glycogen depletion, hydropic swelling, cholesterolosis and eosinophilic hepatocytes with one animal presenting subsegmental infarction due to portal vein thrombosis. Furthermore, portal/periportal induction of the rate limiting enzyme in ammonia detoxification, i.e. carbamoyl phosphate synthetase 1 was observed. The performed microarray studies informed on > 600 differential expressed genes of which 35, 37 and 50 coded for inflammation, 51, 44 and 61 for immune and 116, 129 and 169 for stress response, respectively after single and repeated dosing for 3 and 14 days. Bioinformatic analysis defined molecular circuits of hepatic inflammation with the growth hormone (Ghr)− and leptin receptor, the protein-tyrosine-phosphatase, selectin and the suppressor-of-cytokine-signaling (Socs) to function as key nodes in gene regulatory networks. Western blotting confirmed induction of fibronectin and M-CSF to hallmark tissue repair and differentiation of monocytes and macrophages. Transcript expression of the macrophage receptor with collagenous structure increased > 7-fold and immunohistochemistry of CD68 evidenced activation of tissue-resident macrophages. Importantly, diclofenac treatment prompted strong expression of phosphorylated Stat3 amongst individual animals and the associated 8- and 4-fold Soc3 and Il-6 induction reinforced Ghr degradation as evidenced by immunoblotting. Moreover, immunohistochemistry confirmed regulation of master regulatory proteins of diclofenac treated mice to suggest complex pro-and anti-inflammatory reactions in immune-mediated hepatic injury. The findings encourage translational research. PMID:26934552

Discovery of new class of methoxy carrying isoxazole derivatives as COX-II inhibitors: Investigation of a detailed molecular dynamics study

NASA Astrophysics Data System (ADS)

Joy, Monu; Elrashedy, Ahmed A.; Mathew, Bijo; Pillay, Ashona Singh; Mathews, Annie; Dev, Sanal; Soliman, Mahmoud E. S.; Sudarsanakumar, C.

2018-04-01

Two novel isoxazole derivatives were synthesized and characterized by NMR and single crystal X-ray crystallography techniques. The methoxy and dimethoxy functionalized variants of isoxazole were screened for its anti-inflammatory profile using cyclooxygenase fluorescent inhibitor screening assay methods along with standard drugs, Celecoxib and Diclofenac. The potent and selective nature of the two isoxazole derivatives on COX-II isoenzyme with a greater magnitude of inhibitory concentration, as compared to the standard drugs and further exploited through molecular dynamics (MD) simulation. Classical, accelerated and multiple MD simulations were performed to investigate the actual binding mode of the two non-steroidal anti-inflammatory drug candidates and addressed their functional selectivity towards COX-II enzyme inhibitory nature.

Selection of non-steroidal anti-inflammatory drug and treatment regimen for sulfur mustard-induced cutaneous lesions.

PubMed

Plahovinsak, Jennifer L; Buccellato, Matthew A; Reid, Frances M; Graham, John S

2016-09-01

The inflammatory process plays an important role in sulfur mustard (HD) injury and HD pathogenesis, suggesting that anti-inflammatory treatments applied as soon as possible following HD injury may reduce tissue damage and accelerate healing. This study used the HD dermal weanling swine model to investigate the efficacy of two non-steroidal anti-inflammatory drugs, capsaicin and diclofenac, when applied in combination with the steroid, clobetasol. The therapeutic regimen was also investigated with respect to initiation of treatment post-exposure, frequency and duration. Yorkshire-cross pigs were randomly assigned to experimental groups, corresponding to all combinations of treatment (capsaicin with clobetasol or diclofenac with clobetasol), onset time (1, 2 or 4 h post-exposure), treatment duration (1, 3 or 5 days) and frequency of applications (2, 3 or 4 per day). For each animal, two sites on the ventral abdomen were exposed to 400 μL of neat HD for 8 min to achieve superficial dermal (SD) lesions and two sites were exposed to 400 μL neat HD for 30 min to achieve deep dermal (DD) lesions. Each treatment regimen was tested against a SD and a DD injury. Untreated SD and DD lesion sites served as within-animal controls. Assessments, up to one week post-challenge, included digital photographs, clinical assessments (lesion size measurements and modified Draize scoring), transepidermal water loss (TEWL), reflectance colorimetry and histopathologic evaluations that included an estimate for depth of injury and wound healing parameters. Diclofenac plus clobetasol treatment resulted in significant reductions in lesion contracture and modified Draize scores, increased barrier function (decreased TEWL), and increased healing as determined by histopathology for both SD and DD injury when compared with untreated sites and sites treated with capsaicin plus clobetasol. An increased duration of treatment from 1 to 5 days was most commonly associated with decreased clinical assessment and histopathological severity scores. Therefore, a combination of diclofenac and clobetasol application, when administered for at least five days, shows promise in ameliorating HD-induced lesions.

[Efficiency of famotidin in prophylaxis of NSAIDs-induced gastropathy: result of multicenter research ZASLON-1 (protection of gastric mucosa from non-steroidal anti-inflammatory drugs].

PubMed

Lazebnik, L B; Drozdov, V N; Kim, V A

2009-01-01

This article presents results of the first Russian randomized study of NSAID-gastropaty prevention at patients receiving NSAIDS. Results of clinical and endoscopic monitoring of two groups of patients: 1st - 108 patients with AA or RA treated with diclofenac and famotidin and 2nd--116 patients with AA or RA receiving diclofenac treatment only. It was shown that combined use of diclofenac and famotidin reduces to 2.6 times frequency and significantly reduces severity of painful dyspepsia symptoms and antipain manifestations reduces more than twice frequency of erosive-ulcerous lesions of gastric mucosa and duodenum.

Development of gellan gum containing formulations for transdermal drug delivery: Component evaluation and controlled drug release using temperature responsive nanogels.

PubMed

Carmona-Moran, Carlos A; Zavgorodnya, Oleksandra; Penman, Andrew D; Kharlampieva, Eugenia; Bridges, S Louis; Hergenrother, Robert W; Singh, Jasvinder A; Wick, Timothy M

2016-07-25

Enhancing skin permeation is important for development of new transdermal drug delivery formulations. This is particularly relevant for non-steroidal anti-inflammatory drugs (NSAIDs). To address this, semisolid gel and solid hydrogel film formulations containing gellan gum as a gelling agent were developed and the effects of penetration enhancers (dimethyl sulfoxide, isopropyl alcohol and propylene glycol) on transport of the NSAID diclofenac sodium was quantified. A transwell diffusion system was used to accelerate formulation development. After 4h, diclofenac flux from a superior formulation of the semisolid gel or the solid hydrogel film was 130±11μg/cm(2)h and 108±7μg/cm(2)h, respectively, and significantly greater than that measured for a currently available diclofenac sodium topical gel (30±4μg/cm(2)h, p<0.05) or solution formulation (44±6μg/cm(2)h, p<0.05) under identical conditions. Over 24h diclofenac transport from the solid hydrogel film was greater than that measured for any new or commercial diclofenac formulation. Entrapment of temperature-responsive nanogels within the solid hydrogel film provides temperature-activated prolonged release of diclofenac. Diclofenac transport was minimal at 22°C, when diclofenac is entrapped within temperature-responsive nanogels incorporated into the solid hydrogel film, but increased 6-fold when the temperature was increased to skin surface temperature of 32°C. These results demonstrate the feasibility of the semisolid gel and solid hydrogel film formulations that can include thermo-responsive nanogels for development of transdermal drug formulations with adjustable drug transport kinetics. Copyright © 2016 Elsevier B.V. All rights reserved.

Metabolism of diclofenac in plants--hydroxylation is followed by glucose conjugation.

PubMed

Huber, Christian; Bartha, Bernadett; Schröder, Peter

2012-12-01

Pharmaceuticals from human or veterinary medication form a new class of micropollutants that poses a serious threat to our aquatic environment and its organisms. The intensively used nonsteroidal anti-inflammatory drug diclofenac is found in the environment worldwide due to its poor elimination during waste water treatment processes. In order to test phytoremediation as a tool for the removal of this drug from waste water, the uptake of the compound into plant tissues and its metabolic pathway was addressed using Hordeum vulgare (barley) and a hairy root cell culture of Armoracia rusticana (horse radish) as model species. Diclofenac is taken up by plants and undergoes rapid metabolization; already after 3h of exposure the drug and its metabolites could be detected in the plant tissues. Similar to its fate in mammalian cells the drug is activated in a phase I reaction resulting in the hydroxylated metabolite 4'OH-diclofenac which is conjugated subsequently in phase II to a glucopyranoside, a typical plant specific metabolite. After exposure to 10 and 100 μM diclofenac a concentration dependent formation of the hydroxylated metabolite was observed, while the formation of the phase II metabolite OH-diclofenac glucopyranoside was not positively affected by the higher concentration. To our knowledge this is the first time these two human painkiller metabolites are shown to occur in plant tissues. Copyright © 2012 Elsevier B.V. All rights reserved.

Comparison of the effects of chronic intra-articular administration of tenoxicam, diclofenac, and methylprednisolone in healthy rats.

PubMed

Orak, Mehmet Müfit; Ak, Dursun; Midi, Ahmet; Laçin, Berna; Purisa, Sevim; Bulut, Güven

2015-01-01

Lyophilized drug manufacturing and intra-articular (IA) applications have increased to address gastrointestinal side effects resulting from chronic treatment with non-steroidal anti-inflammatory drugs (NSAIDs) for degenerative joint disease. Accordingly, we histologically examined joint and stomach tissues from rats to determine and compare the effects of long-term treatment with an IA corticosteroid (methylprednisolone acetate), lyophilized NSAID (tenoxicam), and non-lyophilized NSAID (diclofenac) following application to the knee joint. One hundred Wistar albino rats were divided into 4 groups of 25 rats: control, methylprednisolone, tenoxicam, and diclofenac. Ten IA injections were administered at 1-week intervals. Rats were sacrificed at 48 h and 1, 2, 4, and 8 weeks after the tenth injection. Histomorphologically, knee joint samples were examined for osteoarthritic changes and stomach tissue samples for gastric changes. Unlike methylprednisolone, diclofenac and tenoxicam caused increased fibrosis and fibroblast production; furthermore, chronic methylprednisolone use had no negative effects on the synovium or cartilage. Chronic tenoxicam and diclofenac use affects joints more negatively than chronic steroid treatment.

Repurposing Drugs in Oncology (ReDO)—diclofenac as an anti-cancer agent

PubMed Central

Pantziarka, Pan; Sukhatme, Vidula; Bouche, Gauthier; Meheus, Lydie; Sukhatme, Vikas P

2016-01-01

Diclofenac (DCF) is a well-known and widely used non-steroidal anti-inflammatory drug (NSAID), with a range of actions which are of interest in an oncological context. While there has long been an interest in the use of NSAIDs in chemoprevention, there is now emerging evidence that such drugs may have activity in a treatment setting. DCF, which is a potent inhibitor of COX-2 and prostaglandin E2 synthesis, displays a range of effects on the immune system, the angiogenic cascade, chemo- and radio-sensitivity and tumour metabolism. Both pre-clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. Based on this evidence the case is made for further clinical investigation of the anticancer effects of DCF, particularly in combination with other agents - with a range of possible multi-drug and multi-modality combinations outlined in the supplementary materials accompanying the main paper. PMID:26823679

Three Newly Approved Analgesics: An Update

PubMed Central

Saraghi, Mana; Hersh, Elliot V.

2013-01-01

Since 2008, three new analgesic entities, tapentadol immediate release (Nucynta) diclofenac potassium soft gelatin capsules (Zipsor), and bupivacaine liposome injectable suspension (EXPAREL) were granted US Food and Drug Administration (FDA) approval to treat acute pain. Tapentadol immediate-release is a both a mu-opioid agonist and a norepinephrine reuptake inhibitor, and is indicated for the treatment of moderate to severe pain. Diclofenac potassium soft gelatin capsules are a novel formulation of diclofenac potassium, which is a nonsteroidal anti-inflammatory drug (NSAID), and its putative mechanism of action is through inhibition of cyclooxygenase enzymes. This novel formulation of diclofenac allows for improved absorption at lower doses. Liposomal bupivacaine is a new formulation of bupivacaine intended for single-dose infiltration at the surgical site for postoperative analgesia. Bupivacaine is slowly released from this liposomal vehicle and can provide prolonged analgesia at the surgical site. By utilizing NSAIDs and local anesthetics to decrease the transmission of afferent pain signals, less opioid analgesics are needed to achieve analgesia. Since drug-related adverse events are frequently dose related, lower doses from different drug classes may be employed to reduce the incidence of adverse effects, while producing synergistic analgesia as part of a multimodal analgesic approach to acute pain. PMID:24423420

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

PubMed

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.

Effects of photobiomodulation therapy and topical non-steroidal anti-inflammatory drug on skeletal muscle injury induced by contusion in rats-part 2: biochemical aspects.

PubMed

Tomazoni, Shaiane Silva; Frigo, Lúcio; Dos Reis Ferreira, Tereza Cristina; Casalechi, Heliodora Leão; Teixeira, Simone; de Almeida, Patrícia; Muscara, Marcelo Nicolas; Marcos, Rodrigo Labat; Serra, Andrey Jorge; de Carvalho, Paulo de Tarso Camillo; Leal-Junior, Ernesto Cesar Pinto

2017-11-01

Muscle injuries trigger an inflammatory process, releasing important biochemical markers for tissue regeneration. The use of non-steroidal anti-inflammatory drugs (NSAIDs) is the treatment of choice to promote pain relief due to muscle injury. NSAIDs exhibit several adverse effects and their efficacy is questionable. Photobiomodulation therapy (PBMT) has been demonstrated to effectively modulate inflammation induced from musculoskeletal disorders and may be used as an alternative to NSAIDs. Here, we assessed and compared the effects of different doses of PBMT and topical NSAIDs on biochemical parameters during an acute inflammatory process triggered by a controlled model of contusion-induced musculoskeletal injury in rats. Muscle injury was induced by trauma to the anterior tibial muscle of rats. After 1 h, rats were treated with PBMT (830 nm, continuous mode, 100 mW of power, 35.71 W/cm 2 ; 1, 3, and 9 J; 10, 30, and 90 s) or diclofenac sodium (1 g). Our results demonstrated that PBMT, 1 J (35.7 J/cm 2 ), 3 J (107.1 J/cm 2 ), and 9 J (321.4 J/cm 2 ) reduced the expression of tumor necrosis factor alpha (TNF-α) and cyclooxygenase-2 (COX-2) genes at all assessed times as compared to the injury and diclofenac groups (p < 0.05). The diclofenac group showed reduced levels of COX-2 only in relation to the injury group (p < 0.05). COX-2 protein expression remained unchanged with all therapies except with PBMT at a 3-J dose at 12 h (p < 0.05 compared to the injury group). In addition, PBMT (1, 3, and 9 J) effectively reduced levels of cytokines TNF-α, interleukin (IL)-1β, and IL-6 at all assessed times as compared to the injury and diclofenac groups (p < 0.05). Thus, PBMT at a 3-J dose was more effective than other doses of PBMT and topical NSAIDs in the modulation of the inflammatory process caused by muscle contusion injuries.

Regioselective preparation of 5-hydroxypropranolol and 4´-hydroxydiclofenac with a fungal peroxygenase

Treesearch

Matthias Kinne; Marzena Poraj-Kobielska; Elisabet Aranda; Rene Ullrich; Kenneth E. Hammel; Katrin Scheibner; Martin Hofrichter

2009-01-01

An extracellular peroxygenase of Agrocybe aegerita catalyzed the H2O2-dependent hydroxylation of the multi-function beta-adrenergic blocker propranolol (1-naphthalen-1-yloxy-3-(propan-2-ylamino)-propan-2-ol) and the non-steroidal anti-inflammatory drug diclofenac (2-[2-[(2,6-dichloro-phenyl)amino]phenyl]acetic acid) to give...

Adsorption and co-adsorption of diclofenac and Cu(II) on calcareous soils.

PubMed

Graouer-Bacart, Mareen; Sayen, Stéphanie; Guillon, Emmanuel

2016-02-01

Pharmaceuticals are emerging contaminants and their presence in different compartments of the environment has been detected in many countries. In this study, laboratory batch experiments were conducted to characterize the adsorption of diclofenac, a widely used non-steroidal anti-inflammatory drug, on six calcareous soils. The adsorption of diclofenac was relatively low, which may lead to a risk of groundwater contamination and plant uptake. A correlation between the soil-water distribution coefficient Kd and soil characteristics has been highlighted. Indeed, diclofenac adsorption as a function of soil organic matter content (% OM) and Rt=% CaCO3/% OM was successfully described through a simple empirical model, indicating the importance of considering the inhibiting effect of CaCO3 on OM retention properties for a better assessment of diclofenac fate in the specific case of calcareous soils. The simultaneous co-adsorption of diclofenac and copper - a ubiquitous pollutant in the environment - at the water/soil interface, was also investigated. It appeared quite unexpectedly that copper did not have a significant influence on diclofenac retention. Copyright © 2015 Elsevier Inc. All rights reserved.

Diclofenac Does Not Reduce the Risk of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis in Low-Risk Units.

PubMed

Rainio, Mia; Lindström, Outi; Udd, Marianne; Louhimo, Johanna; Kylänpää, Leena

2017-08-01

Nonsteroidal anti-inflammatory drugs have an inhibitory role in pathogenesis of pancreatitis. Guidelines from the European Society of Gastrointestinal Endoscopy recommend routine rectal administration of 100 mg of diclofenac or indomethacin immediately before or after ERCP for all patients without contraindications. Our aim was to evaluate the effect of diclofenac in preventing post-ERCP pancreatitis (PEP) in a high-volume, low-PEP-risk ERCP unit. The rate and severity of PEP were compared in groups of 1000 historical controls prior to the routine use of diclofenac and in 1000 patients receiving 100 mg diclofenac before ERCP. PEP occurred in 56 (2.8%) of the 2000 patients, and the rate of the pancreatitis was 2.8% in control group and 2.8% in diclofenac group (p = 1.000). The PEP rate among the native papilla patients was 3.9% in control group and 3.6% in diclofenac group (p = 0.803). In subgroup analysis of patients with a high risk of PEP, diclofenac neither prevented PEP nor made its course milder. In an unselected patient population in a center with a low incidence of PEP, diclofenac seems to have no beneficial effect.

Mucosal protective agents prevent exacerbation of NSAID-induced small intestinal lesions caused by antisecretory drugs in rats.

PubMed

Satoh, Hiroshi; Amagase, Kikuko; Takeuchi, Koji

2014-02-01

Antisecretory drugs such as histamine H₂-receptor antagonists and proton pump inhibitors are commonly used for the treatment of upper gastrointestinal mucosal lesions induced by nonsteroidal anti-inflammatory drugs (NSAIDs). However, it has recently been reported that these drugs exacerbate NSAID-induced small intestinal lesions in rats. Unfortunately, there are few effective agents for the treatment of this complication. We examined the effects of mucosal protective agents (MPAs) (misoprostol, irsogladine, and rebamipide) and mucin of porcine stomach on diclofenac-induced intestinal lesions and the exacerbation of the lesions by ranitidine or omeprazole. The effects of the drugs on intestinal motility and mucus distribution/content were also examined. Male Wistar rats (180-220 g) were used. Each drug was administered orally under fed conditions. Diclofenac (1-10 mg/kg) produced multiple lesions in the small intestine dose-dependently. Both ranitidine (30 mg/kg) and omeprazole (100 mg/kg) significantly increased the intestinal lesions induced by low doses (3 and 6 mg/kg) of diclofenac. Misoprostol (0.03-0.3 mg/kg), irsogladine (3-30 mg/kg), and rebamipide (30-300 mg/kg), as well as mucin (30-300 mg/kg) inhibited the formation of intestinal lesions caused by a high dose (10 mg/kg) of diclofenac alone and prevented the exacerbation of diclofenac-induced lesions by antisecretory drugs. Diclofenac (10 mg/kg) markedly increased the intestinal motility and decreased the mucosal mucus, and the decrease of mucus was significantly inhibited by the MPAs. These results indicate the usefulness of the MPAs for the treatment of intestinal lesions induced by NSAIDs alone or by coadministration with antisecretory drugs, and suggest that mucus plays an important role in the protection of intestinal mucosa by the MPAs.

Comparison of skin permeability for three diclofenac topical formulations: an in vitro study.

PubMed

Folzer, E; Gonzalez, D; Singh, R; Derendorf, H

2014-01-01

Diclofenac is a hydrophilic non-steroidal anti-inflammatory drug (NSAID) widely used in humans and animals. There are limited published studies evaluating diclofenac's skin permeation following topical administration. The aim of our study was to evaluate and compare the in vitro permeation of three different diclofenac-containing formulations (patch, gel, solution) over 24 hours. These formulations were applied (n = 6 per formulation) to pig skin sandwiched between the two chambers in a static Franz diffusion cell and aliquots from the receptor medium were sampled at pre-defined time points. An HPLC method with UV detection was developed and validated with the aim of characterizing the transepidermal penetration in the in vitro system. Using this assay to determine the permeation parameters, results at 24 hours showed that the Flector patch released the highest drug amount (54.6%), whereas a lower drug amount was delivered with the Voltaren Emulgel (38.2%) and the solution (34.4%). The commercial gel showed the highest flux (39.9 +/- 0.9 microg/cm2/h) and the shortest lag-time (1.97 +/- 0.02 h). Based on these in vitro results using pig skin, the transdermal patch resulted in a long-lasting controlled release of diclofenac, while the gel had the shortest lag-time.

Phytochemicals enhance antioxidant enzyme expression to protect against NSAID-induced oxidative damage of the gastrointestinal mucosa.

PubMed

Cheng, Yu-Ting; Lu, Chi-Cheng; Yen, Gow-Chin

2017-06-01

The gastrointestinal (GI) mucosa provides the first protective barrier for digested food and xenobiotics, which are easily attacked by toxic substances. Nonsteroidal anti-inflammatory drugs, including aspirin, diclofenac, indomethacin, and ketoprofen, are widely used in clinical medicine, but these drugs may cause oxidative stress, leading to GI damage such as ulcers. Lansoprazol, omeprazole, and other clinical drugs are widely used to treat duodenal and gastric ulcers and have been shown to have multiple biological functions, such as antioxidant activity and the ability to upregulate antioxidant enzymes in vivo. Therefore, the reduction of oxidative stress may be an effective curative strategy for preventing and treating nonsteroidal anti-inflammatory drug induced ulcers of the GI mucosa. Phytochemicals, such as dietary phenolic compounds, phenolic acids, flavan-3-ols, flavonols, flavonoids, gingerols, carotenes, and organosulfur, are common antioxidants in fruits, vegetables, and beverages. A large amount of evidence has demonstrated that natural phytochemicals possess bioactivity and potential health benefits, such as antioxidant, anti-inflammatory, and antibacterial benefits, and they can prevent digestive disease processes. In this review, we summarize the literature on phytochemicals with biological effects, such as angiogenic, antioxidant, antiapoptotic, anti-inflammatory, and antiulceration effects, and their related mechanisms are also discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rectal Diclofenac Versus Rectal Paracetamol: Comparison of Antipyretic Effectiveness in Children.

PubMed

Sharif, Mohammad Reza; Haji Rezaei, Mostafa; Aalinezhad, Marzieh; Sarami, Golbahareh; Rangraz, Masoud

2016-01-01

Fever is the most common complaint in pediatric medicine and its treatment is recommended in some situations. Paracetamol is the most common antipyretic drug, which has serious side effects such as toxicity along with its positive effects. Diclofenac is one of the strongest non-steroidal anti-inflammatory (NSAID) drugs, which has received little attention as an antipyretic drug. This study was designed to compare the antipyretic effectiveness of the rectal form of Paracetamol and Diclofenac. This double-blind controlled clinical trial was conducted on 80 children aged six months to six years old. One group was treated with rectal Paracetamol suppositories at 15 mg/kg dose and the other group received Diclofenac at 1 mg/kg by rectal administration (n = 40). Rectal temperature was measured before and one hour after the intervention. Temperature changes in the two groups were compared. The average rectal temperature in the Paracetamol group was 39.6 ± 1.13°C, and 39.82 ± 1.07°C in the Diclofenac group (P = 0.37). The average rectal temperature, one hour after the intervention, in the Paracetamol and the Diclofenac group was 38.39 ± 0.89°C and 38.95 ± 1.09°C, respectively (P = 0.02). Average temperature changes were 0.65 ± 0.17°C in the Paracetamol group and 1.73 ± 0.69°C in the Diclofenac group (P < 0.001). In the first one hour, Diclofenac suppository is able to control the fever more efficient than Paracetamol suppositories.

Muscovite is protective against non-steroidal anti-inflammatory drug-induced small bowel injury

PubMed Central

Huang, Chen; Lu, Bin; Fan, Yi-Hong; Zhang, Lu; Jiang, Ning; Zhang, Shuo; Meng, Li-Na

2014-01-01

AIM: To evaluate the effect of muscovite in preventing small bowel injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: We recruited and screened thirty-two healthy volunteers who were randomly allocated equally into two groups: an NSAID control group, who received 75 mg slow-release diclofenac, twice daily for 14 d; and an NSAID-muscovite group, who received 3 g of muscovite in addition to the 75 mg of slow-release diclofenac, twice daily for 14 d. For gastroprotection, both groups were administered 20 mg/d of the proton pump inhibitor omeprazole. All eligible subjects underwent video capsule endoscopy (CE) prior to and 14 d after treatment. RESULTS: Thirty subjects (NSAID-muscovite group, n =16; NSAID control group, n =14) finally completed the whole trail. At the baseline CE examination, no statistically significant differences between the two groups have been observed. However, after 14 d of drug treatment, a significant difference was observed in the percentage of subjects with mucosal breaks when comparing the NSAID-muscovite group with the NSAID control group. While 71.4% (10/14) of subjects in the NSAID control group had at least one mucosal break, co-administration of muscovite in the NSAID-muscovite group reduced the rate to 31.3% (5/16) (P = 0.028). Moreover, higher number of mucosal breaks was found in the NSAID control group vs that in the NSAID-muscovite group (P < 0.05). CONCLUSION: Muscovite co-therapy reduced the incidence of small intestinal injury after 14 d of diclofenac administration. PMID:25152605

Avian scavengers and the threat from veterinary pharmaceuticals

PubMed Central

Cuthbert, Richard J.; Taggart, Mark A.; Prakash, Vibhu; Chakraborty, Soumya S.; Deori, Parag; Galligan, Toby; Kulkarni, Mandar; Ranade, Sachin; Saini, Mohini; Sharma, Anil Kumar; Shringarpure, Rohan; Green, Rhys E.

2014-01-01

Veterinary use of the non-steroidal anti-inflammatory drug diclofenac on domesticated ungulates caused populations of resident Gyps vultures in the Indian sub-continent to collapse. The birds died when they fed on carrion from treated animals. Veterinary diclofenac was banned in 2006 and meloxicam was advocated as a ‘vulture-safe’ alternative. We examine the effectiveness of the 2006 ban, whether meloxicam has replaced diclofenac, and the impact of these changes on vultures. Drug residue data from liver samples collected from ungulate carcasses in India since 2004 demonstrate that the prevalence of diclofenac in carcasses in 2009 was half of that before the ban and meloxicam prevalence increased by 44%. The expected vulture death rate from diclofenac per meal in 2009 was one-third of that before the ban. Surveys at veterinary clinics show that diclofenac use in India began in 1994, coinciding with the onset of rapid Gyps declines ascertained from measured rates of declines. Our study shows that one pharmaceutical product has had a devastating impact on Asia's vultures. Large-scale research and survey were needed to detect, diagnose and quantify the problem and measure the response to remedial actions. Given these difficulties, other effects of pharmaceuticals in the environment may remain undetected. PMID:25405963

Avian scavengers and the threat from veterinary pharmaceuticals.

PubMed

Cuthbert, Richard J; Taggart, Mark A; Prakash, Vibhu; Chakraborty, Soumya S; Deori, Parag; Galligan, Toby; Kulkarni, Mandar; Ranade, Sachin; Saini, Mohini; Sharma, Anil Kumar; Shringarpure, Rohan; Green, Rhys E

2014-11-19

Veterinary use of the non-steroidal anti-inflammatory drug diclofenac on domesticated ungulates caused populations of resident Gyps vultures in the Indian sub-continent to collapse. The birds died when they fed on carrion from treated animals. Veterinary diclofenac was banned in 2006 and meloxicam was advocated as a 'vulture-safe' alternative. We examine the effectiveness of the 2006 ban, whether meloxicam has replaced diclofenac, and the impact of these changes on vultures. Drug residue data from liver samples collected from ungulate carcasses in India since 2004 demonstrate that the prevalence of diclofenac in carcasses in 2009 was half of that before the ban and meloxicam prevalence increased by 44%. The expected vulture death rate from diclofenac per meal in 2009 was one-third of that before the ban. Surveys at veterinary clinics show that diclofenac use in India began in 1994, coinciding with the onset of rapid Gyps declines ascertained from measured rates of declines. Our study shows that one pharmaceutical product has had a devastating impact on Asia's vultures. Large-scale research and survey were needed to detect, diagnose and quantify the problem and measure the response to remedial actions. Given these difficulties, other effects of pharmaceuticals in the environment may remain undetected. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Diclofenac toxicity in Gyps vulture is associated with decreased uric acid excretion and not renal portal vasoconstriction.

PubMed

Naidoo, V; Swan, G E

2009-04-01

Diclofenac (DF), a non-steroidal anti-inflammatory drug (NSAID), is largely regarded as one of the most devastating environmental toxicant in recent times, after accidental exposure via their food-chain lead to massive mortalities in three vulture species on the Asian subcontinent. Although the use of diclofenac was recently banned on the Indian subcontinent, following the favourable safety profile of meloxicam, its mechanism of toxicity remains unknown. In an attempt to establish this mechanism, we test three hypotheses using models established from either the domestic chicken (Gallus domesticus) or the African White-backed vulture (Gyps africanus). We demonstrate that both DF and meloxicam are toxic to renal tubular epithelial (RTE) cells following 12 h of exposure, due to an increase in production of reactive oxygen species (ROS), which could be temporarily ameliorated by pre-incubation with uric acid (UA). When cultures were incubated with either drug for only 2 h, meloxicam showed no toxicity in contrast to diclofenac. In both cases no increase in ROS production was evident. In addition, diclofenac decreased the transport of uric acid, by interfering with the p-amino-hippuric acid (PAH) channel. We conclude that vulture susceptibility to diclofenac results from a combination of an increased ROS, interference with UA transport and the duration of exposure.

The anti-inflammatory drugs diclofenac, naproxen and ibuprofen are found in the bile of wild fish caught downstream of a wastewater treatment plant.

PubMed

Brozinski, Jenny-Maria; Lahti, Marja; Meierjohann, Axel; Oikari, Aimo; Kronberg, Leif

2013-01-02

Pharmaceutical residues are ubiquitous in rivers, lakes, and at coastal waters affected by discharges from municipal wastewater treatment plants. In this study, the presence of 17 different pharmaceuticals and six different phase I metabolites was determined in the bile of two wild fish species, bream (Abramis brama) and roach (Rutilus rutilus). The fish were caught from a lake that receives treated municipal wastewater via a small river. Prior to analyses, the bile content was enzymatically hydrolyzed to convert the glucuronide metabolites into the original pharmaceuticals or phase I metabolites. The solid phase extracts of hydrolyzates were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the multiple reaction monitoring mode. The anti-inflammatory drug naproxen could be detected in all the six bream and roach bile samples. Diclofenac was found in five of the bream and roach samples, while ibuprofen was detected in three bream and two roach samples. The observed bile concentrations of diclofenac, naproxen, and ibuprofen in bream ranged from 6 to 95 ng mL(-1), 6 to 32 ng mL(-1), and 16 to 34 ng mL(-1), respectively. The corresponding values in roach samples ranged from 44 to 148 ng mL(-1), 11 to 103 ng mL(-1) and 15 to 26 ng mL(-1), respectively. None of the other studied compounds could be detected. The study shows that pharmaceuticals originating from wastewater treatment plant effluents can be traced to the bile of wild bream and roach living in a lake where diclofenac, naproxen, and ibuprofen are present as pollutants.

Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen, naproxen, and acetylsalicylic acid.

PubMed

Cleuvers, Michael

2004-11-01

The ecotoxicity of the nonsteroidal anti-inflammatory drugs (NSAIDs) diclofenac, ibuprofen, naproxen, and acetylsalicylic acid (ASA) has been evaluated using acute Daphnia and algal tests. Toxicities were relatively low, with half-maximal effective concentration (EC50) values obtained using Daphnia in the range from 68 to 166 mg L(-1) and from 72 to 626 mg L(-1) in the algal test. Acute effects of these substances seem to be quite improbable. The quantitative structure-activity relationships (QSAR) approach showed that all substances act by nonpolar narcosis; thus, the higher the n-octanol/water partitioning coefficient (log Kow) of the substances, the higher is their toxicity. Mixture toxicity of the compounds could be accurately predicted using the concept of concentration addition. Toxicity of the mixture was considerable, even at concentrations at which the single substances showed no or only very slight effects, with some deviations in the Daphnia test, which could be explained by incompatibility of the very steep dose-response curves and the probit analysis of the data. Because pharmaceuticals in the aquatic environment occur usually as mixtures, an accurate prediction of the mixture toxicity is indispensable for environmental risk assessment.

Removal of selected non-steroidal anti-inflammatory drugs (NSAIDs), gemfibrozil, carbamazepine, beta-blockers, trimethoprim and triclosan in conventional wastewater treatment plants in five EU countries and their discharge to the aquatic environment.

PubMed

Paxéus, N

2004-01-01

The removal of commonly used pharmaceuticals (ibuprofen, naproxen, diclofenac, gemfibrozil, carbamazepine, atenolol, metoprolol and trimethoprim) and a biocide (triclosan) in operating wastewater treatment plants in five EU countries has been studied. Under normal operating conditions the acidic drugs and triclosan were partially removed with removal rates varying from ca. 20 to >95%. The highest removal rate was found for ibuprofen and triclosan (>90%) followed by naproxen (80%), gemfibrozil (55%) and diclofenac (39%). Ibuprofen undergoes an oxidative transformation to corresponding hydroxy- and carboxy-metabolites, which contributes to its high removal rate. Disturbances in the activated sludge process resulted in lower removal rates for all acidic drugs, mostly for diclofenac (<10% removed) but also for ibuprofen (<60% removed). The treatment of wastewaters by activated sludge usually did not result in any practical removal (<10%) of neutral carbamazepine or basic atenolol, metoprolol and trimethoprim. The removal rates of the investigated drugs and triclosan are discussed in terms of mechanisms responsible for their removal. Discharges of carbamazepine, diclofenac, gemfibrozil, naproxen, triclosan and trimethoprim from WWTPs to the aquatic environment, expressed as the average concentration in the effluent and the daily discharged quantity per person served by WWTPs were assessed.

Peripheral analgesic sites of action of anti-inflammatory drugs.

PubMed

Ferreira, S H

2002-07-01

Inflammatory signs and symptoms of redness, swelling, heat and pain are due to the effects of inflammatory mediators released during the inflammatory response. Depending on the type of injurious stimuli and the tissue involved, the array of mediators may differ but eicosanoids are involved in the genesis of inflammatory pain. They are responsible for the hypersensitisation of the nociceptors (allodynialhyperalgesia). The basic mechanism of analgesic action of nonsteroidal anti-inflammatory drugs results from the inhibition of prostaglandin synthesis (prostacyclin or PGE2), thus preventing nociceptor threshold lowering. Because there is a temporal hierarchy in the release of inflammatory mediators, there are several targets for the action of peripheral acting analgesics before and after the inhibition of prostaglandin synthesis. Blockade of the release and inhibition of inducible cyclooxygenase explain the analgesic action of glucocorticoids. Nimesulide also has an inhibitory action on the cascade of hypersensitising cytokines. Some analgesics, such as dipyrone, flurbiprofen or diclofenac, act directly upon ongoing inflammatory hypersensitisation. Those analgesics restore the nociceptor by stimulating the arginine/NO/cGMP/K(ATP) channel pathway.

Microneedle pretreatment enhances the percutaneous permeation of hydrophilic compounds with high melting points

PubMed Central

2012-01-01

Background Two commercially available microneedle rollers with a needle length of 200 μm and 300 μm were selected to examine the influence of microneedle pretreatment on the percutaneous permeation of four non-steroidal anti-inflammatory drugs (diclofenac, ibuprofen, ketoprofen, paracetamol) with different physicochemical drug characteristics in Franz-type diffusion cells. Samples of the receptor fluids were taken at predefined times over 6 hours and were analysed by UV–VIS high-performance liquid-chromatography. Histological examinations after methylene blue application were additionally performed to gather information about barrier disruption. Results Despite no visible pores in the stratum corneum, the microneedle pretreatment resulted in a twofold (200 μm) and threefold higher (300 μm) flux through the pretreated skin samples compared to untreated skin samples for ibuprofen and ketoprofen (LogKow > 3, melting point < 100°C). The flux of the hydrophilic compounds diclofenac and paracetamol (logKow < 1, melting point > 100°C) increased their amount by four (200 μm) to eight (300 μm), respectively. Conclusion Commercially available microneedle rollers with 200–300 μm long needles enhance the drug delivery of topically applied non-steroidal anti-inflammatory drugs and represent a valuable tool for percutaneous permeation enhancement particularly for substances with poor permeability due to a hydrophilic nature and high melting points. PMID:22947102

The effects of the topical administration of non-steroidal anti-inflammatory drugs on corneal epithelium and corneal sensitivity in normal subjects.

PubMed

Aragona, P; Tripodi, G; Spinella, R; Laganà, E; Ferreri, G

2000-04-01

To study the changes in the corneal epithelium and corneal sensitivity of healthy subjects after the topical administration of non-steroidal anti-inflammatory drugs (NSAIDs; diclofenac, indomethacin, flurbiprofen and ketorolac) frequently used in ocular therapy. A double-masked parallel clinical study was undertaken on 90 subjects (45 men, 45 women; Caucasian; age 21-46 years, mean +/- SD 27.1 +/- 5 years). The subjects were divided into six groups: group 1 was treated with placebo, group 2 with 0.1% diclofenac, group 3 with 0.1% indomethacin, group 4 with 0.03% flurbiprofen, group 5 with 0.5% ketorolac and group 6 with 0.4% oxybuprocaine. One eye was randomly treated with the study drug and the fellow eye was treated with placebo. The medications were instilled four times, at 5 min intervals. Assessment of the corneal epithelium was carried out by vital fluorescein stain before instillation and 5, 15, 30 and 60 min after instillation of the last drop. Subjective burning sensation was assessed by asking participants to rate burning on a scale from 0 (none) to 3 (severe). After 1 week, assessment of corneal sensitivity was carried out by the Cochet-Bonnet method, repeating the above scheme of instillation and measurement times. None of the study drugs, with the exception of oxybuprocaine, produced evident epithelial damage. All the drugs caused a mean burning sensation greater than the placebo. The diclofenac-treated group showed a statistically significant decrease in corneal sensitivity (p < 0.001) at the measurement carried out 15 min after instillation of the last drop and lasting up to the end of the study, when the corneal anaesthesia was similar to that induced by the topical anaesthetic treatment. No significant changes were demonstrated for the other NSAIDs when compared either with the placebo-treated eyes or with the fellow eyes. Despite a similar mechanism of action and analgesic activity to the other NSAIDs tested, diclofenac was able to induce a reduction in corneal sensitivity. More studies are needed to determine the mechanism of action responsible for this effect.

Comparison of Clinical Efficacies of Preoperatively Initiated Naproxen Sodium-Codeine Phosphate in Combination, Diclofenac Potassium, and Benzydamine Hydrochloride for Pain, Edema, and Trismus After Extraction of Impacted Lower Third Molar: A Randomized Double-Blind Study.

PubMed

Cigerim, Levent; Eroglu, Cennet Neslihan

2018-03-01

The aim of this study was to compare the clinical efficacies of naproxen sodium-codeine phosphate in combination, benzydamine hydrochloride, and diclofenac potassium for pain, edema, and trismus after lower third molar extraction. Ninety healthy volunteers in whom impacted third molar extraction was indicated were randomly distributed into 3 groups. One hour before the tooth-extraction process, patients were administered one of the following drugs: naproxen sodium, 550 mg, and codeine phosphate, 30 mg, in a tablet; diclofenac potassium, 50 mg, in a coated pill; or benzydamine hydrochloride, 50 mg, in a coated pill. Pain assessment was conducted via a visual analog scale; edema assessment, by measuring the distances between predetermined facial landmarks; and trismus assessment, by measuring interincisal distance. Regarding rescue analgesics (paracetamol, 500 mg), the number and time of use by patients were recorded. Naproxen sodium-codeine phosphate was more effective for pain, edema, and trismus than diclofenac potassium and benzydamine hydrochloride (P < .05). Benzydamine hydrochloride yielded similar clinical responses to diclofenac potassium (P > .05). No drug-related side effects were observed. Naproxen sodium-codeine phosphate constitutes the drug of choice after the extraction of a patient's impacted lower third molar. Benzydamine hydrochloride has similar efficacy to diclofenac potassium, and it can be used as a nonsteroidal anti-inflammatory analgesic drug. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Effect of rubbing on the in vitro skin permeation of diclofenac-diethylamine 1.16% gel.

PubMed

Hasler-Nguyen, Nathalie; Fotopoulos, Grigorios

2012-06-21

Rubbing a topical NSAID (non steroidal anti-inflammatory drug) on the skin may increase local drug permeation, affecting its distribution to the site of pain and inflammation. The present study evaluates this hypothesis, by assessing in vitro the effect on skin permeation of applying diclofenac-dieythylamine 1.16% gel with or without rubbing. A single dose of 5 mg/cm2 diclofenac-diethylamine 1.16% gel was applied on excised human skin mounted in Franz-type diffusion cells without or with rubbing for 45 s. Drug penetration into the skin layers was determined after 1 h using the tape stripping technique. In vitro cutaneous permeation into the receptor fluid of the diffusion chamber was measured up to 24 h. Skin electrical resistance was also recorded. Application of diclofenac-diethylamine 1.16% gel with rubbing resulted to a 5-fold higher flux of diclofenac through the skin than when applied without rubbing at 8 h (P = 0.04). Skin rubbing for 45 s decreased by 2-fold skin electrical resistance when compared to the standard application. Application of diclofenac-diethylamine 1.16% gel with rubbing tended to result in higher accumulation in the stripped skin vs. the superficial skin layers when applied without rubbing (P = 0.2). These results suggest that rubbing may alter the superficial skin layer resulting in a transient faster initial diffusion of topically applied diclofenac through the stratum corneum into the deeper skin layer of the dermis to the tissue target.

Effect of rubbing on the in vitro skin permeation of diclofenac-diethylamine 1.16% gel

PubMed Central

2012-01-01

Background Rubbing a topical NSAID (non steroidal anti-inflammatory drug) on the skin may increase local drug permeation, affecting its distribution to the site of pain and inflammation. The present study evaluates this hypothesis, by assessing in vitro the effect on skin permeation of applying diclofenac-dieythylamine 1.16% gel with or without rubbing. Methods A single dose of 5 mg/cm2 diclofenac-diethylamine 1.16% gel was applied on excised human skin mounted in Franz-type diffusion cells without or with rubbing for 45 s. Drug penetration into the skin layers was determined after 1 h using the tape stripping technique. In vitro cutaneous permeation into the receptor fluid of the diffusion chamber was measured up to 24 h. Skin electrical resistance was also recorded. Results Application of diclofenac-diethylamine 1.16% gel with rubbing resulted to a 5-fold higher flux of diclofenac through the skin than when applied without rubbing at 8 h (P = 0.04). Skin rubbing for 45 s decreased by 2-fold skin electrical resistance when compared to the standard application. Application of diclofenac-diethylamine 1.16% gel with rubbing tended to result in higher accumulation in the stripped skin vs. the superficial skin layers when applied without rubbing (P = 0.2). Conclusion These results suggest that rubbing may alter the superficial skin layer resulting in a transient faster initial diffusion of topically applied diclofenac through the stratum corneum into the deeper skin layer of the dermis to the tissue target. PMID:22720797

Different cellular effects of four anti-inflammatory eye drops on human corneal epithelial cells: independent in active components.

PubMed

Qu, Mingli; Wang, Yao; Yang, Lingling; Zhou, Qingjun

2011-01-01

To evaluate and compare the cellular effects of four commercially available anti-inflammatory eye drops and their active components on human corneal epithelial cells (HCECs) in vitro. The cellular effects of four eye drops (Bromfenac Sodium Hydrate Eye Drops, Pranoprofen Eye Drops, Diclofenac Sodium Eye Drops, and Tobramycin & Dex Eye Drops) and their corresponding active components were evaluated in an HCEC line with five in vitro assays. Cell proliferation and migration were measured using 3-(4,5)-dimethylthiahiazo (-z-y1)-3 5-di-phenytetrazoliumromide (MTT) assay and transwell migration assay. Cell damage was determined with the lactate dehydrogenase (LDH) assay. Cell viability and median lethal time (LT₅₀) were measured by 7-amino-actinomycin D (7-AAD) staining and flow cytometry analysis. Cellular effects after exposure of HCECs to the four anti-inflammatory eye drops were concentration dependent. The differences of cellular toxicity on cell proliferation became significant at lower concentrations (<0.002%). Diclofenac Sodium Eye Drops showed significant increasing effects on cell damage and viability when compared with the other three solutions. Tobramycin & Dex Eye Drops inhibited the migration of HCECs significantly. Tobramycin & Dex Eye Drops showed the quickest effect on cell viability: the LT₅₀ was 3.28, 9.23, 10.38, and 23.80 min for Tobramycin & Dex Eye Drops, Diclofenac Sodium Eye Drops, Pranoprofen Eye Drops, and Bromfenac Sodium Hydrate Eye Drops, respectively. However, the comparisons of cellular toxicity revealed significant differences between the eye drops and their active components under the same concentration. The corneal epithelial toxicity differences among the active components of the four eye drops became significant as higher concentration (>0.020%). The four anti-inflammatory eye drops showed different cellular effects on HCECs, and the toxicity was not related with their active components, which provides new reference for the clinical application and drug research and development.

In vitro drug interaction of levocetirizine and diclofenac: Theoretical and spectroscopic studies.

PubMed

Abo Dena, Ahmed S; Abdel Gaber, Sara A

2017-06-15

Levocetirizine dihydrochloride is known to interact with some anti-inflammatory drugs. We report here a comprehensive integrated theoretical and experimental study for the in vitro drug interaction between levocetirizine dihydrochloride (LEV) and diclofenac sodium (DIC). The interaction of the two drugs was confirmed by the molecular ion peak obtained from the mass spectrum of the product. Moreover, FTIR and 1 HNMR spectra of the individual drugs and their interaction product were inspected to allocate the possible sites of interaction. In addition, quantum mechanical DFT calculations were performed to search for the interaction sites and to verify the types of interactions deduced from the spectroscopic studies such as charge-transfer and non-bonding π-π interactions. It was found that the studied drugs interact with each other in aqueous solution via four types of interactions, namely, ion-pair formation, three weak hydrogen bonds, non-bonding π-π interactions and charge-transfer from DIC to LEV. Copyright © 2017 Elsevier B.V. All rights reserved.

Anti-inflammatory, anti-bacterial activity and structure-activity relationships of substitutions on 4-thiazolidinone derivatives - Part-1.

PubMed

Naeem, Muhammad; Chadhury, Muhammad Nawaz; Amjad, Rana; Rehaman, Salma; Khan, Kahlida

2012-10-01

Environmentally benign and economically feasible procedures have been adopted for the synthesis of novel biologically potential 4-thiazolidinone derivatives. Purpose built microwave oven and ionic liquids (PTCs) showed wrack improvements in yield, time and cost. The yield of 1st series (01-08) obtained in the ranged from 82.4-94.2% and for 2nd series (09-16) obtained 80.6-92.8%. The compounds (01-16) were applied for anti-inflammatory activity at concentrations of 0.5 and 01 mg/kg in carrageenan induced acute and formalin induced chronic inflammatory procedures in mice and better results were obtained at 0.5 mg/kg dose. Some of the compounds 03, 04, 07, 12, 13 showed remarkable anti-inflammatory activity in both procedures as compared to the standard reference drug 2-(2,6-dichloranilino) phenyl acetic acid (diclofenac). Particularly compound 12 and 13 may be used as a non-steroidal anti-inflammatory drug (NSAID) to reduce inflammation. The compounds (01-16) were screened for their antimicrobial activity (in-vivo) and found that the compounds 12, 13 and 14 exhibited comparable or higher antibacterial activity then ciprofloxacin (standard) against E. coli, S. enteritidis, P. aeruginosa, S. aureus and B. subtilis. The compounds of series-2 showed significant activity as compared with ciprofloxacin. These compounds could be lead to the selection and use as efficient antimicrobial agents, especially for the treatment of multi-drug resistant infections.

Oxidation of non-steroidal anti-inflammatory drugs with aqueous permanganate.

PubMed

Rodríguez-Álvarez, Tania; Rodil, Rosario; Quintana, José Benito; Triñanes, Sara; Cela, Rafael

2013-06-01

Potassium permanganate is a strong oxidant widely used in drinking water treatment, that can react with organic micropollutants. Thus, the oxidation kinetics and transformation route of seven non-steroidal anti-inflammatory drugs (NSAIDs) upon reaction with potassium permanganate was investigated. A liquid chromatography-quadrupole-time-of-flight-mass spectrometry (LC-Q-TOF-MS) system was used to follow the time course of pharmaceuticals concentrations and for the identification of their by-products. Under strong oxidation conditions (2 mg L(-1) KMnO4, 24 h), only two NSAIDs were significantly degraded: indomethacine and diclofenac. The degradation kinetics of these two drugs was investigated at different concentrations of permanganate, chlorides, phosphates and sample pH by means of a full factorial experimental design. Depending on these factors, half-lives were in the range: 2-270 h for indomethacine and 3-558 h for diclofenac, equivalent to apparent second order constants between 0.65 and 9.5 M(-1) s(-1) and 0.27 and 7.4 M(-1) s(-1), respectively. Permanganate concentration was the most significant factor on NSAIDs oxidation kinetics, but the pH also played a significant role in diclofenac reaction, being faster at acidic pH. In the case of indomethacine, the dose of permanganate seemed also to play an autocatalytic effect. The use of an accurate-mass high resolution LC-Q-TOF-MS system permitted the identification of a total of 13 by-products. The transformation path of these drugs consisted mainly of hydroxylations, decarboxylations and oxidation of aromatic double bonds, with ring opening. The software predicted toxicity of these products indicates that they are expected not to be more toxic than the NSAIDs, with the exception of two indomethacine by-products. Reaction in real samples was slower and/or incomplete for both pharmaceuticals, depending on the organic matter content of the sample. However, still all transformation products could be detected for indomethacine in permanganate treated surface water samples, and two out of five in the case of diclofenac. Copyright © 2013 Elsevier Ltd. All rights reserved.

Anti-inflammatory activity of Achillea and Ruscus topical gel on carrageenan-induced paw edema in rats.

PubMed

Maswadeh, Hamzah M; Semreen, Mohammad H; Naddaf, Ahmad R

2006-01-01

The anti-inflammatory activity of Achillea and Ruscus extracts was studied in comparison with diclofenac sodium topical gel (diclosal Emulgel), using the carrageenan induced paw edema model in Albino rats. Gel formulation was prepared containing 6% of each extract in gel base, namely sodium carboxymethylcellulose (NaCMC). The kinetics of drug release from the prepared formulation was studied separately in each case. Results showed that the release follows the Higuchi square root equation. The pharmacological screening revealed that the percent reduction of edema for Achillea extract and Ruscus extract were 48.1% and 18.8%, respectively, while diclosal Emulgel produced 47% reduction of edema.

The efficacy of Curcuma Longa L. extract as an adjuvant therapy in primary knee osteoarthritis: a randomized control trial.

PubMed

Pinsornsak, Piya; Niempoog, Sunyarn

2012-01-01

Nonsteroidal anti-inflammatory Drugs (NSAIDs) is one of the most commonly use medication for treatment of knee osteoarthritis which has the analgesic and anti-inflammation by inhibition of prostaglandin synthesis via COX-1 and COX-2 isoenzyme. The problem of prolong using NSAIDs has side effect on kidney, liver and GI system. Curcumin longa extract Curcumin) is the Asian herbal medicine that has the anti-inflammatory effect by down regulate activation of NF-kappaB and proinflammatory cytokines such as Tumor Necrotic Factor-alpha, Interleukin-1, Interleukin-8, and Nitric Oxide Syntase. Many research data had advocate for the combination therapy which can increase safety and efficacy with less side effect compare with monotherapy regimen especially when the medicine has the different mechanism of action. The present study is the double blind prospective randomized control trial to evaluate the efficacy of curcumin as an adjuvant therapy of diclofenac in primary knee osteoarthritis. 44 patients were randomized to take NSAIDs (diclofenac) 75 mg/d with placebo and the other 44 took NSAIDs (diclofenac) 75 mg/d with curcumin 1,000 mg/d for 3 months. The authors evaluated the Visual Analog Scale (VAS) for pain and Knee Injury and Osteoarthritis Outcome Score (KOOS) every month for 3 months. At the end of study 36 patients were completed for the first group and 37 for the study group. There was no difference in VAS [p-value = 0.923 (F = 0.009)]. The KOOS was analyzed in 5 categories symptom, pain, function in daily living, function in sport and recreation and knee related quality of life. The curcumin with diclofenac group had tendency to be better in Pain and Function in daily living, but there were no statistic different in all group [p-value = 0.412 (F = 0.683), p-value = 0.814 (F = 0.056), p-value = 0.446 (F = 0.589), p-value = 0.224 (F = 1.511) and p-value = 0.938 (F = 0.006)]. In conclusion, the adjuvant therapy ofcurcumin with diclofenac has the potential beneficial effect in comparison with diclofenac alone, but no statistical significance.

Rate of Decline of the Oriental White-Backed Vulture Population in India Estimated from a Survey of Diclofenac Residues in Carcasses of Ungulates

PubMed Central

Green, Rhys E.; Taggart, Mark A.; Senacha, Kalu Ram; Raghavan, Bindu; Pain, Deborah J.; Jhala, Yadvendradev; Cuthbert, Richard

2007-01-01

The non-steroidal anti-inflammatory drug diclofenac is a major cause of the rapid declines in the Indian subcontinent of three species of vultures endemic to South Asia. The drug causes kidney failure and death in vultures. Exposure probably arises through vultures feeding on carcasses of domesticated ungulates treated with the drug. However, before the study reported here, it had not been established from field surveys of ungulate carcasses that a sufficient proportion was contaminated to cause the observed declines. We surveyed diclofenac concentrations in samples of liver from carcasses of domesticated ungulates in India in 2004–2005. We estimated the concentration of diclofenac in tissues available to vultures, relative to that in liver, and the proportion of vultures killed after feeding on a carcass with a known level of contamination. We assessed the impact of this mortality on vulture population trend with a population model. We expected levels of diclofenac found in ungulate carcasses in 2004–2005 to cause oriental white-backed vulture population declines of 80–99% per year, depending upon the assumptions used in the model. This compares with an observed rate of decline, from road transect counts, of 48% per year in 2000–2003. The precision of the estimate based upon carcass surveys is low and the two types of estimate were not significantly different. Our analyses indicate that the level of diclofenac contamination found in carcasses of domesticated ungulates in 2004–2005 was sufficient to account for the observed rapid decline of the oriental white-backed vulture in India. The methods we describe could be used again to assess changes in the effect on vulture population trend of diclofenac and similar drugs. In this way, the effectiveness of the recent ban in India on the manufacture and importation of diclofenac for veterinary use could be monitored. PMID:17668064

Occurrence of neutral and acidic drugs in the effluents of Canadian sewage treatment plants.

PubMed

Metcalfe, Chris D; Koenig, Brenda G; Bennie, Don T; Servos, Mark; Ternes, Thomas A; Hirsch, Roman

2003-12-01

Samples of influent (untreated) and effluent (treated) from 18 sewage treatment plants (STPs) in 14 municipalities in Canada were analyzed for residues of selected prescription and nonprescription drugs. Several neutral and acidic drugs were detected in effluents, including analgesic/anti-inflammatory agents, lipid regulators, and an antiepileptic drug, carbamazepine. Residues were extracted from effluents by solid-phase extraction, followed by either methylation and analysis of acidic drugs by gas chromatography/mass spectrometry or direct analysis of neutral drugs by liquid chromatography/tandem mass spectrometry. Analgesic/anti-inflammatory drugs such as ibuprofen and naproxen, as well as the metabolite of acetylsalicyclic acid, salicylic acid, were often detected in final effluents at microg/L concentrations. The acidic lipid regulator, clofibric acid, and the analgesic/anti-inflammatory drug diclofenac were not detected in any final effluent samples, which is not consistent with data from Europe. The precursor to clofibric acid, clofibrate, is not widely prescribed as a lipid regulator in Canada. However, the lipid regulators bezafibrate and gemfibrozil were detected in some samples of influent and effluent. The chemotherapy drugs ifosfamide and cyclophosphamide and the anti-inflammatory phenazone were not detected in influent or effluent samples, but the vasodilator drug pentoxyfylline was detected at ng/L concentrations in some final effluents. The widespread occurrence of carbamazepine at concentrations as high as 2.3 microg/L may be explained by use of this drug for other therapeutic purposes besides treatment of epilepsy and its resistance to elimination in STPs. The rates of elimination of ibuprofen and naproxen appeared to be elevated in STPs with hydraulic retention times for sewage greater than 12 h.

Sorption and degradation of wastewater-associated non-steroidal anti-inflammatory drugs and antibiotics in soils.

PubMed

Lin, Kunde; Gan, Jay

2011-04-01

Presence of pharmaceuticals at trace levels in recycled water is an emerging issue impacting the beneficial reuse of treated wastewater, including practices such as irrigation and groundwater recharge in arid and semi-arid regions. To assess the environmental risks of irrigation with recycled water containing such micropollutants, in this study we evaluated sorption and degradation of five pharmaceuticals that are antibiotic and anti-inflammatory drugs in two soils collected from arid regions. Naproxen and trimethoprim showed moderate to strong sorption, while the sorption of diclofenac, ibuprofen and sulfamethoxazole was negligible in both soils. Under aerobic conditions, the studied compounds were susceptible to microbial degradation with half-lives varying from 4.8 to 69.3d. Apart from sulfamethoxazole, the other compounds were relatively persistent under anaerobic conditions as indicated by a negligible loss over 84d of incubation or half-lives >50d. The degradation of the selected pharmaceuticals was influenced by microbial activities, oxygen status in the soil, soil type and compound characteristics. The poor sorption and relative persistence of diclofenac and ibuprofen under anaerobic conditions suggest that the two chemicals may pose a high leaching risk when using recycled for irrigation or groundwater replenishment. Copyright © 2010 Elsevier Ltd. All rights reserved.

A Multicenter, Prospective, Randomized Controlled Trial Evaluating the Efficacy of Rectal Diclofenac and Sublingual Nitroglycerin as a Combined Prophylactic Treatment for Post-ERCP Pancreatitis.

PubMed

Tomoda, Takeshi; Kato, Hironari; Mizukawa, Sho; Muro, Shinichiro; Akimoto, Yutaka; Uchida, Daisuke; Matsumoto, Kazuyuki; Yamamoto, Naoki; Horiguchi, Shigeru; Tsutsumi, Koichiro; Okada, Hiroyuki

2016-01-01

Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP). A preliminary research suggested that the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) with nitroglycerin might reduce the incidence of post-ERCP pancreatitis (PEP) more effectively than NSAIDs alone. We conduct a two-arm, multicenter, prospective, randomized, superiority trial to evaluate the additional effect of nitroglycerin for prevention of PEP. A total of 900 patients randomly receive 50 mg diclofenac suppository either alone or with 5 mg isosorbide dinitrate sublingual tablet. The primary endpoint is the occurrence of PEP. This study will clarify whether NSAIDs plus nitroglycerin can prevent PEP.

The pathogenesis of diclofenac induced immunoallergic hepatitis in a canine model of liver injury

PubMed Central

Selvaraj, Saravanakumar; Oh, Jung-Hwa; Spanel, Reinhard; Länger, Florian; Han, Hyoung-Yun; Lee, Eun-Hee; Yoon, Seokjoo; Borlak, Jürgen

2017-01-01

Hypersensitivity to non-steroidal anti-inflammatory drugs is a common adverse drug reaction and may result in serious inflammatory reactions of the liver. To investigate mechanism of immunoallergic hepatitis beagle dogs were given 1 or 3 mg/kg/day (HD) oral diclofenac for 28 days. HD diclofenac treatment caused liver function test abnormalities, reduced haematocrit and haemoglobin but induced reticulocyte, WBC, platelet, neutrophil and eosinophil counts. Histopathology evidenced hepatic steatosis and glycogen depletion, apoptosis, acute lobular hepatitis, granulomas and mastocytosis. Whole genome scans revealed 663 significantly regulated genes of which 82, 47 and 25 code for stress, immune response and inflammation. Immunopathology confirmed strong induction of IgM, the complement factors C3&B, SAA, SERPING1 and others of the classical and alternate pathway. Alike, marked expression of CD205 and CD74 in Kupffer cells and lymphocytes facilitate antigen presentation and B-cell differentiation. The highly induced HIF1A and KLF6 protein expression in mast cells and macrophages sustain inflammation. Furthermore, immunogenomics discovered 24, 17, 6 and 11 significantly regulated marker genes to hallmark M1/M2 polarized macrophages, lymphocytic and granulocytic infiltrates; note, the latter was confirmed by CAE staining. Other highly regulated genes included alpha-2-macroglobulin, CRP, hepcidin, IL1R1, S100A8 and CCL20. Diclofenac treatment caused unprecedented induction of myeloperoxidase in macrophages and oxidative stress as shown by SOD1/SOD2 immunohistochemistry. Lastly, bioinformatics defined molecular circuits of inflammation and consisted of 161 regulated genes. Altogether, the mechanism of diclofenac induced liver hypersensitivity reactions involved oxidative stress, macrophage polarization, mastocytosis, complement activation and an erroneous programming of the innate and adaptive immune system. PMID:29296203

Adsorption of non-steroidal anti-inflammatory drugs from aqueous solution using activated carbons: Review.

PubMed

Ahmed, Muthanna J

2017-04-01

Pharmaceutical pollutants are of significant effect on the environment, so that their treatments have been addressed in many studies. Activated carbon (AC) adsorbent shows best attraction for these compounds due to its unique characteristics represented by high capacity and porosity. In this article, the adsorption performance of AC towards non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, ketoprofen, naproxen, and diclofenac were reviewed. According to collected data, maximum adsorption capacities of 417, 25, 290, and 372 mg/g were obtained from Langmuir isotherm for these drugs, respectively. The values of 1/n for Freundlich isotherm were lower than unity for all studied drugs, confirming the nonlinear and favorable adsorption. In addition, kinetics data were well represented by the pseudo-second-order model and mechanism was not controlled by the pore diffusion step alone. AC adsorption demonstrated superior performance for all selected NSAIDs, thus being efficient technology for treatment of these pharmaceutical pollutants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Low-dose rectal diclofenac for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a randomized controlled trial.

PubMed

Otsuka, Taiga; Kawazoe, Seiji; Nakashita, Shunya; Kamachi, Saori; Oeda, Satoshi; Sumida, Chinatsu; Akiyama, Takumi; Ario, Keisuke; Fujimoto, Masaru; Tabuchi, Masanobu; Noda, Takahiro

2012-08-01

Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography (ERCP). Rectal nonsteroidal anti-inflammatory drugs (specifically, 100 mg of diclofenac or indomethacin) have shown promising prophylactic activity in post-ERCP pancreatitis (PEP). However, the 100-mg dose is higher than that ordinarily used in Japan. We performed a prospective randomized controlled study to evaluate the efficacy of low-dose rectal diclofenac for the prevention of PEP. Patients who were scheduled to undergo ERCP were randomized to receive a saline infusion either with 50 mg of rectal diclofenac (diclofenac group) or without (control group) 30 min before ERCP. The dose of diclofenac was reduced to 25 mg in patients weighing <50 kg. The primary outcome measure was the occurrence of PEP. Enrollment was terminated early because the planned interim analysis found a statistically significant intergroup difference in the occurrence of PEP. A total of 104 patients were eligible for this study; 51 patients received rectal diclofenac. Twelve patients (11.5%) developed PEP: 3.9% (2/51) in the diclofenac group and 18.9% (10/53) in the control group (p = 0.017). After ERCP, the incidence of hyperamylasemia was not significantly different between the two groups. Post-ERCP pain was significantly more frequent in the control group than in the diclofenac group (37.7 vs. 7.8%, respectively; p < 0.001). There were no adverse events related to diclofenac. Low-dose rectal diclofenac can prevent PEP.

Combined effects of aging and in vitro non-steroid anti-inflammatory drugs on kidney and liver mitochondrial physiology.

PubMed

Rocha-Rodrigues, Sílvia; Santos-Alves, Estela; Coxito, Pedro M; Marques-Aleixo, Inês; Passos, Emanuel; Guimarães, João T; Martins, Maria J; Oliveira, Paulo J; Magalhães, José; Ascensão, António

2013-09-03

Aging and drug-induced side effects may contribute to deteriorate mitochondrial bioenergetics in many tissues, including kidney and liver. One possibility is that the combination of both aging and drug toxicity accelerates the process of mitochondrial degradation, leading to progressive bioenergetic disruption. We therefore analyzed in vitro kidney (KM) and liver (LM) mitochondrial response to salicylate and diclofenac in old and adult animals. Male-Wistar adult (19-wks) and aged (106-wks) rats were used. In vitro endpoints of oxygen consumption and membrane potential were evaluated in non-treated conditions (vehicle) and in the presence of salicylate (0.5mM) and diclofenac (50μM). The susceptibility to calcium-induced permeability transition pore (MPTP) was assessed. Aconitase and C, -SH and MDA contents were measured. Apoptotic signaling was followed by measuring caspase 3, 8 and 9 activities, Bax, Bcl2 and CypD expression. ANT content was semi-quantified. In general, animal age alone compromised KM state 3 and LM ADP lag phase while resulting in decreased resistance to the MPTP. Aging decreased LM CypD and increased Mn-SOD. Kidney caspase 9-like activity was lower in aged group. Salicylate and diclofenac induced KM and LM dysfunction. ADP lag phase in KM was further increased in the aged group in the presence of diclofenac. No further impairments were observed regarding drug toxicity adding to the aging process. Aging impaired KM and LM function despite no detected alterations on oxidative stress and apoptosis. However, aging did not further exacerbate KM and LM frailty induced by salicylate and diclofenac. © 2013.

The Effectiveness of the Rectal Administration of Low-dose Diclofenac for the Prevention of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis.

PubMed

Okuno, Mitsuru; Shiroko, Junko; Taguchi, Daisuke; Yamaguchi, Kimihiro; Takada, Jun; Imai, Susumu; Sato, Hiroyuki; Thanabashi, Shinobu

2018-03-30

Objective A 50-100-mg rectal dose of nonsteroidal anti-inflammatory drugs (NSAIDs; diclofenac or indomethacin) has been shown to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, this is higher than the recommended 25-mg dose that is commonly administered to Japanese patients. The objective of this study was to evaluate the safety and efficacy of 25-mg rectal dose of diclofenac in preventing PEP. Methods Between January 2016 and March 2017, a total of 147 patients underwent ERCP with or without the rectal administration of diclofenac (25 mg) 20 min before the procedure. A retrospective analysis was conducted to evaluate the efficacy and safety of this dose in preventing PEP. Results Thirteen patients (8.8%) developed PEP: 3 patients (4.1%) in the diclofenac group and 10 (13.7%) in the control group (p=0.0460). After ERCP, there were no cases of gastrointestinal hemorrhage, ulceration, acute renal failure, or death. A multivariate logistic regression analysis revealed that the non-administration of rectal diclofenac was a risk factor for PEP (odds ratio=3.530; 95% confidence interval=1.017-16.35; p=0.0468). Conclusions A 25-mg rectal dose of diclofenac might prevent PEP.

Multifunctional medicated lyophilised wafer dressing for effective chronic wound healing.

PubMed

Pawar, Harshavardhan V; Boateng, Joshua S; Ayensu, Isaac; Tetteh, John

2014-06-01

Wafers combining weight ratios of Polyox with carrageenan (75/25) or sodium alginate (50/50) containing streptomycin and diclofenac were prepared to improve chronic wound healing. Gels were freeze-dried using a lyophilisation cycle incorporating an annealing step. Wafers were characterised for morphology, mechanical and in vitro functional (swelling, adhesion, drug release in the presence of simulated wound fluid) characteristics. Both blank (BLK) and drug-loaded (DL) wafers were soft, flexible, elegant in appearance and non-brittle in nature. Annealing helped to improve porous nature of wafers but was affected by the addition of drugs. Mechanical characterisation demonstrated that the wafers were strong enough to withstand normal stresses but also flexible to prevent damage to newly formed skin tissue. Differences in swelling, adhesion and drug release characteristics could be attributed to differences in pore size and sodium sulphate formed because of the salt forms of the two drugs. BLK wafers showed relatively higher swelling and adhesion than DL wafers with the latter showing controlled release of streptomycin and diclofenac. The optimised dressing has the potential to reduce bacterial infection and can also help to reduce swelling and pain associated with injury due to the anti-inflammatory action of diclofenac and help to achieve more rapid wound healing. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Pes Anserine Bursitis in Symptomatic Osteoarthritis Patients: A Mesotherapy Treatment Study

PubMed Central

Di Stefano, Alexandra; Dodaj, Ira; Scarcello, Laura; Bellomo, Rosa Grazia

2015-01-01

Abstract Background: Pes anserine bursitis strongly affects quality of life in patients with osteoarthritis. Treatment includes nonsteroidal anti-inflammatory drugs (NSAIDs), physiotherapy, and injections of corticosteroid, with highly variable responses; recovery can take 10 days to 36 months. Mesotherapy is a minimally invasive technique consisting of subcutaneous injections of bioactive substances. The goal is to modulate the pharmacokinetics of the injected substance and prolong the effects at a local level. Objective: To evaluate the effects of mesotherapy with diclofenac for anserine bursitis associated with knee osteoarthritis. Methods: One hundred and seventeen patients with anserine bursitis associated with grade II Kellgren-Lawrence knee osteoarthritis, assessed by clinical, radiographic, and ultrasonographic examination, were evaluated and treated. They were randomly divided into two groups (A, mesotherapy; B, control). Group A completed nine sessions of mesotherapy with sodium diclofenac (25 mg/1 mL; Akis®, IBSA, Lugano, Switzerland), 1 mL for each session, three times per week. Group B received 21 oral administrations of sodium diclofenac (50 mg; Voltaren®, Novartis, Parsippany, NJ), once a day for 3 weeks. Primary outcome measures were pain intensity assessed by visual analogue scale (VAS), along with ability to perform activities of daily living, ability to participate in sports, level of pain, symptoms, and quality of life, as assessed by the Knee injury and Osteoarthritis Outcome Score. These measures were performed before and after the treatment period and at 30 and 90 days' follow up. Results: In both groups pain level decreased significantly after the treatment period. Ultrasonography showed a reduction of the hypoechoic area related to anserine bursitis only in group A. Conclusion: Administration of conventional NSAIDs (diclofenac) by mesotherapy is effective in managing anserine bursitis in knee osteoarthritis in the short term and mid-term. These observations could be of interest for efforts to reduce the adverse effects of oral administration of anti-inflammatory drugs. PMID:26083769

Pes Anserine Bursitis in Symptomatic Osteoarthritis Patients: A Mesotherapy Treatment Study.

PubMed

Saggini, Raoul; Di Stefano, Alexandra; Dodaj, Ira; Scarcello, Laura; Bellomo, Rosa Grazia

2015-08-01

Pes anserine bursitis strongly affects quality of life in patients with osteoarthritis. Treatment includes nonsteroidal anti-inflammatory drugs (NSAIDs), physiotherapy, and injections of corticosteroid, with highly variable responses; recovery can take 10 days to 36 months. Mesotherapy is a minimally invasive technique consisting of subcutaneous injections of bioactive substances. The goal is to modulate the pharmacokinetics of the injected substance and prolong the effects at a local level. To evaluate the effects of mesotherapy with diclofenac for anserine bursitis associated with knee osteoarthritis. One hundred and seventeen patients with anserine bursitis associated with grade II Kellgren-Lawrence knee osteoarthritis, assessed by clinical, radiographic, and ultrasonographic examination, were evaluated and treated. They were randomly divided into two groups (A, mesotherapy; B, control). Group A completed nine sessions of mesotherapy with sodium diclofenac (25 mg/1 mL; Akis®, IBSA, Lugano, Switzerland), 1 mL for each session, three times per week. Group B received 21 oral administrations of sodium diclofenac (50 mg; Voltaren®, Novartis, Parsippany, NJ), once a day for 3 weeks. Primary outcome measures were pain intensity assessed by visual analogue scale (VAS), along with ability to perform activities of daily living, ability to participate in sports, level of pain, symptoms, and quality of life, as assessed by the Knee injury and Osteoarthritis Outcome Score. These measures were performed before and after the treatment period and at 30 and 90 days' follow up. In both groups pain level decreased significantly after the treatment period. Ultrasonography showed a reduction of the hypoechoic area related to anserine bursitis only in group A. Administration of conventional NSAIDs (diclofenac) by mesotherapy is effective in managing anserine bursitis in knee osteoarthritis in the short term and mid-term. These observations could be of interest for efforts to reduce the adverse effects of oral administration of anti-inflammatory drugs.

Anti-Inflammatory and Antioxidant Activities of Salvia fruticosa: An HPLC Determination of Phenolic Contents

PubMed Central

Boukhary, Rima; Ghoneim, Asser I.; Aboul-Ela, Maha; El-Lakany, Abdalla

2016-01-01

Objectives. Salvia fruticosa Mill. (S. fruticosa) is widely used in folk medicine. Accordingly, the present study was designed to evaluate the antioxidant and anti-inflammatory activities of S. fruticosa, and to determine the phenolic constituents of its extracts. Methods. The antioxidant activity was determined using 2,2-diphenylpicrylhydrazyl assay. Total phenolic contents were estimated using Folin-Ciocalteu reagent, and high-performance liquid chromatography was performed to identify phenolic constituents. To evaluate the anti-inflammatory activity, carrageenan-induced mouse paw edema was determined plethysmographically. Key Findings. Different plant extracts demonstrated strong radical scavenging activity, where the ethyl acetate extract had the highest value in the roots and the lowest in the aerial parts. This antioxidant activity was correlated to the total phenolic content of different extracts, where rutin and luteolin were the most abundant constituents. Interestingly, both the roots and aerial parts revealed a significant anti-inflammatory activity comparable to diclofenac. Conclusions. This study is the first to demonstrate pharmacologic evidence of the potential anti-inflammatory activity of S. fruticosa. This activity may partly be due to the radical scavenging effects of its polyphenolic contents. These findings warrant the popular use of the East Mediterranean sage and highlight the potential of its active constituents in the development of new anti-inflammatory drugs. PMID:26881007

Estimation of total phenolic content, in-vitro antioxidant and anti-inflammatory activity of flowers of Moringa oleifera

PubMed Central

Alhakmani, Fatma; Kumar, Sokindra; Khan, Shah Alam

2013-01-01

Objective To evaluate and compare the antioxidant potential and anti-inflammatory activity of ethanolic extract of flowers of Moringa oleifera (M. oleifera) grown in Oman. Methods Flowers of M. oleifera were collected in the month of December 2012 and identified by a botanist. Alcoholic extract of the dry pulverized flowers of M. oleifera were obtained by cold maceration method. The ethanolic flower extract was subjected to preliminary phytochemical screening as the reported methods. Folin-Ciocalteu reagent was used to estimate total phenolic content. DPPH was used to determine in-vitro antioxidant activity and anti-inflammatory activity of flowers was investigated by protein denaturation method. Results Phytochemical analysis of extract showed presence of major classes of phytochemicals such as tannins, alkaloids, flavonoids, cardiac glycosides etc. M. oleifera flowers were found to contain 19.31 mg/g of gallic acid equivalent of total phenolics in dry extract but exhibited moderate antioxidant activity. The anti-inflammatory activity of plant extract was significant and comparable with the standard drug diclofenac sodium. Conclusions The results of our study suggest that flowers of M. oleifera possess potent anti-inflammatory activity and are also a good source of natural antioxidants. Further study is needed to identify the chemical compounds responsible for their anti-inflammatory activity. PMID:23905019

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

PubMed Central

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 < 0.001). The maximum analgesic effect was observed at 120 min at the dose of 100 mg/kg (i.p.) and was comparable to that of standard analgin (150 mg/kg) and the percentage of edema inhibition effect was 46.4% and 77% for 50 mg/kg and 100 mg/kg (i.p) respectively. Anti-inflammatory activity was compared with standard Diclofenac sodium (5 mg/kg). Conclusion: Ethanol extract of 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

Metabolism of aceclofenac in cattle to vulture-killing diclofenac.

PubMed

Galligan, T H; Taggart, M A; Cuthbert, R J; Svobodova, D; Chipangura, J; Alderson, D; Prakash, V M; Naidoo, V

2016-10-01

The nonsteroidal anti-inflammatory drug (NSAID) diclofenac is highly toxic to Gyps vultures, and its recent widespread use in South Asia caused catastrophic declines in at least 3 scavenging raptors. The manufacture of veterinary formulations of diclofenac has since been banned across the region with mixed success. However, at least 12 other NSAIDs are available for veterinary use in South Asia. Aceclofenac is one of these compounds, and it is known to metabolize into diclofenac in some mammal species. The metabolic pathway of aceclofenac in cattle, the primary food of vultures in South Asia, is unknown. We gave 6 cattle the recommended dose of aceclofenac (2 mg/kg), collected blood thereafter at intervals for up to 12 h, and used liquid chromatography with mass spectrometry in a pharmacokinetic analysis of aceclofenac and diclofenac in the plasma. Nearly all the aceclofenac administered to the cattle was very rapidly metabolized into diclofenac. At 2 h, half the aceclofenac had been converted into diclofenac, and at 12 h four-fifths of the aceclofenac had been converted into diclofenac. Therefore, administering aceclofenac to livestock poses the same risk to vultures as administering diclofenac to livestock. This, coupled with the risk that aceclofenac may replace diclofenac in the veterinary market, points to the need for an immediate ban on all aceclofenac formulations that can be used to treat livestock. Without such a ban, the recovery of vultures across South Asia will not be successful. © 2016 Society for Conservation Biology.

Isolation, identification and molecular docking as cyclooxygenase (COX) inhibitors of the main constituents of Matricaria chamomilla L. extract and its synergistic interaction with diclofenac on nociception and gastric damage in rats.

PubMed

Ortiz, Mario I; Fernández-Martínez, Eduardo; Soria-Jasso, Luis Enrique; Lucas-Gómez, Isaac; Villagómez-Ibarra, Roberto; González-García, Martha P; Castañeda-Hernández, Gilberto; Salinas-Caballero, Mireya

2016-03-01

Chamomile (Matricaria chamomilla L., Asteraceae) is a medicinal plant widely used as remedy for pain and gastric disorders. The association of non-steroidal anti-inflammatory drugs (NSAIDs) with medicinal plant extracts may increase its antinociceptive activity, permit the use of lower doses and limit side effects. The aim was to isolate and identify the main chemical constituents of Matricaria chamomilla ethanolic extract (MCE) as well as to explore their activity as cyclooxygenase (COX) inhibitors in silico; besides, to examine the interaction between MCE and diclofenac on nociception in the formalin test by isobolographic analysis, and to determine the level of gastric injury in rats. Three terpenoids, α-bisabolol, bisabolol oxide A, and guaiazulene, were isolated and identified by (1)H NMR. Docking simulation predicted COX inhibitory activity for those terpenoids. Diclofenac, MCE, or their combinations produced an antinociceptive effect. The sole administration of diclofenac and the highest combined dose diclofenac-MCE produced significant a gastric damage, but that effect was not seen with MCE alone. An isobologram was constructed and the derived theoretical ED35 for the antinociceptive effect was significantly different from the experimental ED35; hence, the interaction between diclofenac and MCE that mediates the antinociceptive effect is synergist. The MCE contains three major terpenoids with plausible COX inhibitory activity in silico, but α-bisabolol showed the highest affinity. Data suggest that the diclofenac-MCE combination can interact at the systemic level in a synergic manner and may have therapeutic advantages for the clinical treatment of inflammatory pain. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Effects of the pharmaceuticals gemfibrozil and diclofenac on the marine mussel (Mytilus spp.) and their comparison with standardized toxicity tests.

PubMed

Schmidt, Wiebke; O'Rourke, Kathleen; Hernan, Robert; Quinn, Brian

2011-07-01

Human pharmaceuticals, like the lipid lowering agent gemfibrozil and the non-steroidal anti-inflammatory drug diclofenac are causing environmental concern. In this study, the marine mussel (Mytilus spp.) was exposed by injection to environmentally relevant and elevated (1 μg/L and 1000 μg/L) concentrations of both compounds and biomarker expression was observed. Gemfibrozil exposure induced biomarkers of stress (glutathione S-transferase and metallothionein) at both concentrations 24h and 96 h after exposure, respectively. Biomarkers of damage (lipid peroxidation (LPO) and DNA damage) were significantly affected, as well as the biomarker for reproduction, alkali-labile phosphate assay, indicating the potential oxidative stress and endocrine disrupting effect of gemfibrozil. Diclofenac significantly induced LPO after 96 h indicating tissue damage. Additionally standard toxicity tests using the marine species Vibrio fischeri, Skeletonema costatum and Tisbe battagliai showed differences in sensitivity to both drugs in the mg/L range. Results indicate a suite of tests should be used to give accurate information for regulation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Non-Steroidal Anti-Inflammatory Drug Use and the Risk of Acute Myocardial Infarction in the General German Population: A Nested Case-Control Study.

PubMed

Thöne, Kathrin; Kollhorst, Bianca; Schink, Tania

2017-09-01

Use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with an increased relative risk of acute myocardial infarction (AMI), but the label warnings refer particularly to patients with cardiovascular risk factors. The magnitude of relative AMI risk for patients with and without cardiovascular risk factors varies between studies depending on the drugs and doses studied. The aim of our study was to estimate population-based relative AMI risks for individual and widely used NSAIDs, for a cumulative amount of NSAID use, and for patients with and without a prior history of cardiovascular risk factors. Based on data from the German Pharmacoepidemiological Research Database (GePaRD) of about 17 million insurance members from four statutory health insurance providers, for the years 2004-2009, a nested case-control study was conducted within a cohort of 3,476,931 new NSAID users classified into current, recent, or past users. Up to 100 controls were matched to each case by age, sex, and length of follow-up using risk set sampling. Multivariable conditional logistic regression was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Duration of NSAID use was calculated by the cumulative amount of dispensed defined daily doses (DDDs), and stratified analyses were conducted for potential effect modifiers. Overall, 17,236 AMI cases were matched to 1,714,006 controls. Elevated relative AMI risks were seen for current users of fixed combinations of diclofenac with misoprostol (OR 1.76, 95% CI 1.26-2.45), indometacin (1.69, 1.22-2.35), ibuprofen (1.54, 1.43-1.65), etoricoxib (1.52, 1.24-1.87), and diclofenac (1.43, 1.34-1.52) compared with past use. A low cumulative NSAID amount was associated with a higher relative AMI risk for ibuprofen, diclofenac, and indometacin. The relative risk associated with current use of diclofenac, fixed combinations of diclofenac with misoprostol, etoricoxib, and ibuprofen was highest in the younger age group (<60 years) and similar for patients with or without major cardiovascular risk factors. Relative AMI risk estimates differed among the 15 investigated individual NSAIDs. Diclofenac and ibuprofen, the most frequently used NSAIDs, were associated with a 40-50% increased relative risk of AMI, even for low cumulative NSAID amounts. The relative AMI risk in patients with and without cardiovascular risk factors was similarly elevated.

C-reactive protein estimation: a quantitative analysis for three nonsteroidal anti-inflammatory drugs: a randomized control trial.

PubMed

Salgia, Gaurav; Kulkarni, Deepak G; Shetty, Lakshmi

2015-01-01

C-reactive protein (CRP) estimation for quantitative analysis to assess anti-inflammatory action of nonsteroidal anti-inflammatory drugs (NSAIDs) after surgery in maxillofacial surgery. This study was to evaluate the efficacy of CRP as a quantitative analysis for objective assessment of efficacy of three NSAIDs in postoperative inflammation and pain control. The parallel study group design of randomization was done. Totally 60 patients were divided into three groups. CRP was evaluated at baseline and postoperatively (immediate and 72 h) after surgical removal of impacted lower third molar. The respective group received the drugs by random coding postoperatively. The assessment of pain control and inflammation using NSAIDs postoperatively after surgical removal of impacted lower third molar was qualitatively and quantitatively assessed with CRP levels. The blood sample of the patient was assessed immediate postoperatively and after 72 h. The visual analog scale (VAS) was used for assessment of pain and its correlation with CRP levels. Comparison of difference in levels of CRP levels had P < 0.05 with immediate postoperative and baseline levels. The duration of surgery with association of CRP levels P = 0.425 which was nonsignificant. The pain score was increased with mefenamic acid (P = 0.003), which was significant on VAS. Diclofenac had the best anti-inflammatory action. There was a significant increase in CRP levels in immediate postoperative values and 72 h. CRP test proved to be a useful indicator as a quantitative assessment tool for monitoring postsurgical inflammation and therapeutic effects of various anti-inflammatory drugs. CRP test is a useful indicator for quantitative assessment for comparative evaluation of NSAIDs.

A comparison of preservative-free diclofenac and preserved diclofenac eye drops after cataract surgery in patients with diabetic retinopathy.

PubMed

Yasuda, Kanako; Miyazawa, Akiko; Shimura, Masahiko

2012-06-01

The aim of this study was to compare the anti-inflammatory efficacy of preservative-free and preserved 0.1% diclofenac eye drops for the management of postoperative inflammation after cataract surgery in patients with nonproliferative diabetic retinopathy and in normal controls. Forty-two diabetic patients and 50 normal control patients who underwent small-incision phacoemulsification cataract surgery bilaterally received topical preservative-free diclofenac in 1 eye and preserved diclofenac in the other eye. The corrected distance visual acuity (CDVA) as determined by a logarithm of the minimum angle of resolution (logMAR) chart, intraocular pressure (IOP), foveal thickness (FT) using optical coherence tomography (OCT), and the anterior chamber flare (ACF) score measured with a laser flare cell meter were monitored for 12 weeks after surgery. In the eyes with diabetic retinopathy, there were no significant differences in CDVA, IOP, FT, and ACF score between the right and left eyes at the initial exam. After cataract surgery, changes in CDVA, IOP, and FT were not influenced by the preservative in the diclofenac eye drops. In contrast, the ACF score in the eyes treated with preserved diclofenac showed slower recovery from postoperative inflammation than the eyes treated with preservative-free diclofenac. In the normal control eyes, similar but milder changes were observed in each of the clinical parameters. Because preservative suppressed the anti-inflammatory efficacy of topical diclofenac after cataract surgery, preservative-free diclofenac may have an improved safety profile during postoperative treatment, especially in patients with diabetic retinopathy.

Sorption and desorption of selected non-steroidal anti-inflammatory drugs in an agricultural loam-textured soil.

PubMed

Zhang, Y; Price, G W; Jamieson, R; Burton, D; Khosravi, K

2017-05-01

Non-steroidal, anti-inflammatory drugs (NSAIDs) are widely used pharmaceutical products with analgesic and anti-inflammatory effects that are consistently detected in municipal wastewater systems and in municipal biosolids. Land application of biosolids and irrigation with reclaimed wastewater introduces these compounds into agricultural environments, which is an emerging issue of concern for ecosystem health. In this study, the sorption-desorption behaviour of four commonly consumed NSAIDs, including naproxen (NPX), ibuprofen (IBU), ketoprofen (KTF), and diclofenac (DCF), was examined in a loam textured soil exposed to either an individual-compound or a mixture of the four NSAIDs. The proportion of NSAIDs adsorbed to the soil in the mixture-compound system was 72%, 55%, 50% and 45%, for diclofenac, naproxen, ketoprofen, and ibuprofen, respectively, and differed slightly from the individual compound adsorption. Diclofenac displayed strong sorption and low desorption in both the individual-compound and mixture-compound systems. Naproxen and ibuprofen exhibited significant differences between the adsorption isotherms of the individual-compound and mixture-compound systems. Results of this study highlight differences in the sorption behaviour of NSAIDs, when present as mixtures, possibly through multilayer bonding effects or complexation with cationic metals or organo-clays from the soil. Soil organic matter (SOM) may have played a role in determining some of the interactions between the compounds but other factors associated with the mixture-compound system, such as cation bridging or multilayer cooperative adsorption. Desorption data suggests that the mechanisms involved in binding NSAIDs to the soil surface are also influence by the presence of other compounds in a mixture. A reduction in desorption was observed for all four NSAIDs in the mixture-compound system relative to the individual-compound system, but were greatest for naproxen and ibuprofen. The sorption-desorption hysteresis increased for naproxen and ibuprofen in the mixture-compound system. This study suggests that cooperative adsorption plays a role in the interaction of NSAIDs when present as mixtures rather than as individual compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis, spectroscopic and thermal studies of Mg(II), Ca(II), Sr(II) and Ba(II) diclofenac sodium complexes as anti-inflammatory drug and their protective effects on renal functions impairment and oxidative stress

NASA Astrophysics Data System (ADS)

El-Megharbel, Samy M.; Hamza, Reham Z.; Refat, Moamen S.

2015-01-01

The main task of our present study is the preparation of newly complexes of Mg(II), Ca(II), Sr(II) and Ba(II) with diclofenac which succeeded to great extent in alleviating the side effects of diclofenac alone and ameliorating the kidney function parameters and antioxidant capacities with respect to diclofenac treated group alone. The Mg(II), Ca(II), Sr(II) and Ba(II) with diclofenac have been synthesized and characterized using infrared, electronic and 1H NMR spectral, thermogravimetric and conductivity measurements. The diclofenac ligand has been found to act as bidentate chelating agent. Diclofenac complexes coordinate through the oxygen's of the carboxyl group. The molar ratio chelation is 1:2 (M2+-dic) with general formula [M(dic)2(H2O)2]ṡnH2O. Antibacterial screening of the alkaline earth metal complexes against Escherichia coli (Gram - ve), Bacillus subtilis (Gram + ve) and anti-fungal (Asperagillus oryzae, Asperagillus niger, Asperagillus flavus) were investigated. The kidney functions in male albino rats were ameliorated upon treatment with metal complexes of dic, which are represented by decreasing the levels of urea and uric acid to be located within normal values. The other looks bright spot in this article is the assessment of antioxidant defense system including SOD, CAT and MDA with the help of Sr2+, Mg2+ and Ca2+-dic complexes. The hormones related to kidney functions and stresses have been greatly ameliorated in groups treated with dic complexes in comparable with dic treated group.

Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal β-glucuronidase activity

PubMed Central

Zhong, Ze-yu; Sun, Bin-bin; Shu, Nan; Xie, Qiu-shi; Tang, Xian-ge; Ling, Zhao-li; Wang, Fan; Zhao, Kai-jing; Xu, Ping; Zhang, Mian; Li, Ying; Chen, Yang; Liu, Li; Xia, Lun-zhu; Liu, Xiao-dong

2016-01-01

Aim: Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), which may cause serious intestinal adverse reactions (enteropathy). In this study we investigated whether co-administration of ciprofloxacin affected the pharmacokinetics of diclofenac and diclofenac-induced enteropathy in rats. Methods: The pharmacokinetics of diclofenac was assessed in rats after receiving diclofenac (10 mg/kg, ig, or 5 mg/kg, iv), with or without ciprofloxacin (20 mg/kg, ig) co-administered. After receiving 6 oral doses or 15 intravenous doses of diclofenac, the rats were sacrificed, and small intestine was removed to examine diclofenac-induced enteropathy. β-Glucuronidase activity in intestinal content, bovine liver and E coli was evaluated. Results: Following oral or intravenous administration, the pharmacokinetic profile of diclofenac displayed typical enterohepatic circulation, and co-administration of ciprofloxacin abolished the enterohepatic circulation, resulted in significant reduction in the plasma content of diclofenac. In control rats, β-glucuronidase activity in small intestinal content was region-dependent: proximal intestine

Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal β-glucuronidase activity.

PubMed

Zhong, Ze-Yu; Sun, Bin-Bin; Shu, Nan; Xie, Qiu-Shi; Tang, Xian-Ge; Ling, Zhao-Li; Wang, Fan; Zhao, Kai-Jing; Xu, Ping; Zhang, Mian; Li, Ying; Chen, Yang; Liu, Li; Xia, Lun-Zhu; Liu, Xiao-Dong

2016-07-01

Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), which may cause serious intestinal adverse reactions (enteropathy). In this study we investigated whether co-administration of ciprofloxacin affected the pharmacokinetics of diclofenac and diclofenac-induced enteropathy in rats. The pharmacokinetics of diclofenac was assessed in rats after receiving diclofenac (10 mg/kg, ig, or 5 mg/kg, iv), with or without ciprofloxacin (20 mg/kg, ig) co-administered. After receiving 6 oral doses or 15 intravenous doses of diclofenac, the rats were sacrificed, and small intestine was removed to examine diclofenac-induced enteropathy. β-Glucuronidase activity in intestinal content, bovine liver and E coli was evaluated. Following oral or intravenous administration, the pharmacokinetic profile of diclofenac displayed typical enterohepatic circulation, and co-administration of ciprofloxacin abolished the enterohepatic circulation, resulted in significant reduction in the plasma content of diclofenac. In control rats, β-glucuronidase activity in small intestinal content was region-dependent: proximal intestine

Selective adsorption of oppositely charged PNIPAAM on halloysite surfaces: a route to thermo-responsive nanocarriers.

PubMed

Cavallaro, Giuseppe; Lazzara, Giuseppe; Lisuzzo, Lorenzo; Milioto, Stefana; Parisi, Filippo

2018-08-10

Halloysite nanotubes were functionalized with stimuli-responsive macromolecules to generate smart nanohybrids. Poly(N-isopropylacrylamide)-co-methacrylic acid (PNIPAAM-co-MA) was selectively adsorbed into halloysite lumen by exploiting electrostatic interactions. Amine-terminated PNIPAAM polymer was also investigated that selectively interacts with the outer surface of the nanotubes. The adsorption site has a profound effect on the thermodynamic behavior and therefore temperature responsive features of the hybrid material. The drug release kinetics was investigated by using diclofenac as a non-steroidal anti-inflammatory drug model. The release kinetics depends on the nanoarchitecture of the PNIPAAM/halloysite based material. In particular, diclofenac release was slowed down above the LCST for PNIPAAM-co-MA/halloysite. Opposite trends occurred for halloysite functionalized with PNIPAAM at the outer surface. This work represents a further step toward the opportunity to extend and control the delivery conditions of active species, which represent a key point in technological applications.

Diclofenac residues as the cause of vulture population decline in Pakistan

USGS Publications Warehouse

Oaks, J.L.; Gilbert, M.; Virani, M.Z.; Watson, R.T.; Meteyer, C.U.; Rideout, B.A.; Shivaprasad, H.L.; Ahmed, S.; Chaudhry, M.J.I.; Arshad, M.; Mahmood, S.; Ali, A.; Khan, A.A.

2004-01-01

The Oriental white-backed vulture (OWBV; Gyps bengalensis) was once one of the most common raptors in the Indian subcontinent. A population decline of >95%, starting in the 1990s, was first noted at Keoladeo National Park, India. Since then, catastrophic declines, also involving Gyps indicus and Gyps tenuirostris, have continued to be reported across the subcontinent. Consequently these vultures are now listed as critically endangered by BirdLife International. In 2000, the Peregrine Fund initiated its Asian Vulture Crisis Project with the Ornithological Society of Pakistan, establishing study sites at 16 OWBV colonies in the Kasur, Khanewal and Muzaffargarha??Layyah Districts of Pakistan to measure mortality at over 2,400 active nest sites5. Between 2000 and 2003, high annual adult and subadult mortality (5a??86%) and resulting population declines (34a??95%) (ref. 5 and M.G., manuscript in preparation) were associated with renal failure and visceral gout. Here, we provide results that directly correlate residues of the anti-inflammatory drug diclofenac with renal failure. Diclofenac residues and renal disease were reproduced experimentally in OWBVs by direct oral exposure and through feeding vultures diclofenac-treated livestock. We propose that residues of veterinary diclofenac are responsible for the OWBV decline.

Diclofenac enables unprecedented week-long microneedle-enhanced delivery of a skin impermeable medication in humans

PubMed Central

Brogden, Nicole K.; Banks, Stan L.; Crofford, Leslie J.; Stinchcomb, Audra L.

2013-01-01

Microneedles applied to the skin create micropores, allowing transdermal drug delivery of skin-impermeable compounds. The first human study with this technique demonstrated delivery of naltrexone (an opioid antagonist) for two to three days. Rapid micropore closure, however, blunts the delivery window. Application of diclofenac (an anti-inflammatory) allows seven days of naltrexone delivery in animals. Purpose the purpose of the current work was to demonstrate delivery of naltrexone for seven days following one microneedle treatment in humans. Methods Human subjects were treated with microneedles, diclofenac (or placebo), and naltrexone. Impedance measurements were used as a surrogate marker to measure micropore formation, and plasma naltrexone concentrations were measured for seven days post-microneedle application. Results Impedance dropped significantly from baseline to post-microneedle treatment, confirming micropore formation. Naltrexone was detected for seven days in Group 1 (diclofenac + naltrexone, n = 6), vs. 72 hours in Group 2 (placebo + naltrexone, n = 2). At study completion, a significant difference in impedance was observed between intact and microneedle-treated skin in Group 1 (confirming the presence of micropores). Conclusion This is the first study demonstrating week-long drug delivery after one microneedle application, which would increase patient compliance and allow delivery of therapies for chronic diseases. PMID:23761054

Release study of diclofenac from new carbomer gels.

PubMed

Bregni, Carlos; Chiappetta, Diego; Faiden, Natalia; Carlucci, Adriana; García, Roberto; Pasquali, Ricardoc

2008-01-01

Carbopol gels were prepared using a traditional polymer with mucoadhesive properties (974P). A new Carbomer derivative Ultrez 21 was also evaluated. Mineral oil, as occlusive ingredient, glycerol as humectant and ethanol were included in all the compositions. The feasibility of preparing these formulations with or without a bioadhesive polymer (Polycarbophil AA-1) and a second oil phase with enhancer activity (Miglyol 840) was evaluated. Further characterization including physical stability during a year was carried out. In vitro release behaviour of diclofenac sodium in Franz diffusion cell was evaluated with some selected formulations using an ethanol-water (50% w/w) solution as receptor medium. Addition of Polycarbophil AA-1 increased formulation viscosity and decreased drug release. These types of topical dosage forms could give sustained delivery of drug onto the skin, could tolerate the incorporation of an enhancer, a humectant and an occlusive phase, so they are interesting promises to improve skin absorption of nonsteroidal anti-inflammatory drugs and to prevent side effects associated.

Biophysical study of the non-steroidal anti-inflammatory drugs (NSAID) ibuprofen, naproxen and diclofenac with phosphatidylserine bilayer membranes.

PubMed

Manrique-Moreno, Marcela; Heinbockel, Lena; Suwalsky, Mario; Garidel, Patrick; Brandenburg, Klaus

2016-09-01

Non-steroidal anti-inflammatory drugs (NSAIDs) represent an effective pain treatment option and therefore one of the most sold therapeutic agents worldwide. The study of the molecular interactions responsible for their physiological activity, but also for their side effects, is therefore important. This report presents data on the interaction of the most consumed NSAIDs (ibuprofen, naproxen and diclofenac) with one main phospholipid in eukaryotic cells, dimyristoylphosphatidylserine (DMPS). The applied techniques are Fourier-transform infrared spectroscopy (FTIR), with which in transmission the gel to liquid crystalline phase transition of the acyl chains in the absence and presence of the NSAID are monitored, supplemented by differential scanning calorimetry (DSC) data on the phase transition. FTIR in reflection (ATR, attenuated total reflectance) is applied to record the dependence of the interactions of the NSAID with particular functional groups observed in the DMPS spectrum such as the ester carbonyl and phosphate vibrational bands. With Förster resonance energy transfer (FRET) a possible intercalation of the NSAID into the DMPS liposomes and with isothermal titration calorimetry (ITC) the thermodynamics of the interaction are monitored. The data show that the NSAID react in a particular way with this lipid, but in some parameters the three NSAID clearly differ, with which now a clear picture of the interaction processes is possible. Copyright © 2016 Elsevier B.V. All rights reserved.

Inhibition of striatal cholinergic interneuron activity by the Kv7 opener retigabine and the nonsteroidal anti-inflammatory drug diclofenac.

PubMed

Paz, Rodrigo Manuel; Tubert, Cecilia; Stahl, Agostina; Díaz, Analía López; Etchenique, Roberto; Murer, Mario Gustavo; Rela, Lorena

2018-05-11

Striatal cholinergic interneurons provide modulation to striatal circuits involved in voluntary motor control and goal-directed behaviors through their autonomous tonic discharge and their firing "pause" responses to novel and rewarding environmental events. Striatal cholinergic interneuron hyperactivity was linked to the motor deficits associated with Parkinson's disease and the adverse effects of chronic antiparkinsonian therapy like l-DOPA-induced dyskinesia. Here we addressed whether Kv7 channels, which provide negative feedback to excitation in other neuron types, are involved in the control of striatal cholinergic interneuron tonic activity and response to excitatory inputs. We found that autonomous firing of striatal cholinergic interneurons is not regulated by Kv7 channels. In contrast, Kv7 channels limit the summation of excitatory postsynaptic potentials in cholinergic interneurons through a postsynaptic mechanism. Striatal cholinergic interneurons have a high reserve of Kv7 channels, as their opening using pharmacological tools completely silenced the tonic firing and markedly reduced their intrinsic excitability. A strong inhibition of striatal cholinergic interneurons was also observed in response to the anti-inflammatory drugs diclofenac and meclofenamic acid, however, this effect was independent of Kv7 channels. These data bring attention to new potential molecular targets and pharmacological tools to control striatal cholinergic interneuron activity in pathological conditions where they are believed to be hyperactive, including Parkinson's disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evaluation of Anti-inflammatory and Antimicrobial Activity of AHPL/AYCAP/0413 Capsule.

PubMed

Nipanikar, Sanjay; Chitlange, Sohan; Nagore, Dheeraj

2017-01-01

Conventional therapeutic agents used for treatment of Acne are associated with various adverse effects necessitating development of safe and effective alternative therapeutic agents. In this context, a polyherbal formulation AHPL/AYCAP/0413 was developed for treatment of Acne. To evaluate Anti-inflammatory and antimicrobial activity of AHPL/AYCAP/0413. 1) Anti-inflammatory activity: Anti-inflammatory activity of AHPL/AYCAP/0413 in comparison with Diclofenac was assessed in carrageenan induced rat Paw edema model. 2) Anti-microbial activity for P. acne : Propionibacterium acnes were incubated under anaerobic conditions. Aliquots of molten BHI with glucose agar were used as the agar base. Formulation and clindamycin (10 μg/ml) were introduced in to the Agar wells randomly. 3) Anti-microbial activity for Staphylococcus epidermidis and Staphylococcus aureus : Staphylococcus epidermidis and Staphylococcus aureus were incubated under aerobic conditions at 37°C. TSB with glucose agar was used as the agar base. 0.5ml of formulation and clindamycin (10 μg/ml) were introduced in to the wells randomly. The antibacterial activity was evaluated by measuring zones of inhibition (in mm). Significant reduction in rat paw edema (51% inhibition) was observed with formulation AHPL/AYCAP/0413 which was also comparable to that of Diclofenac (58% inhibition). Zone of inhibition for formulation was 18.33 mm, 19.20 mm and 26.30 mm for P. acnes , S. epidermidis and S. aureus respectively. This activity was also comparable to that of Clindamycin. AHPL/AYCAP/0413 capsule possesses significant Anti-inflammatory and Anti-microbial activities which further justifies its role in the management of Acne vulgaris. Anti-inflammatory and antimicrobial activities of polyherbal formulation AHPL/AYCAP/0413 were evaluatedAHPL/AYCAP/0413 contains Guduchi extract ( Tinospora cordifolia ), Manjishtha extract ( Rubia cordifolia ), Sariva extract ( Hemidesmus indicus ), Nimba extract ( Azardirachta indica ), Khadira extract ( Acacia catechu ) and Kakmachi extract ( Solanum nigrum )Anti-inflammatory activity of AHPL/AYCAP/0413 in comparison with Diclofenac was assessed in carrageenan induced rat Paw edema model. Significant reduction in rat paw edema (51% inhibition) was observed with formulation AHPL/AYCAP/0413 which was also comparable to that of Diclofenac (58% inhibition)Anti-microbial activity of AHPL/AYCAP/0413 was assessed against Propionibacterium acnes , Staphylococcus epidermidis and Staphylococcus aureus . Zone of inhibition for formulation was 18.33 mm, 19.20 mm and 26.30 mm for P. acnes , S. epidermidis and S. aureus respectively indicating 68.42%, 85.71% and 81.17% activity. This activity was also comparable to that of ClindamycinTherefore it is evident that, AHPL/AYCAP/0413 capsule possesses significant Anti-inflammatory and Anti-microbial activities which further justifies its role in the management of Acne vulgaris. Abbreviations Used : mg: Milligram, kg: Kilogram, w/v: Weight by volume, ml: Milliliters, h: Hour, BHI: Brain Heart Infusion, CFU: Colony forming units, μg: Microgram, A.I.: Activity index, P.I.: Percent inhibition, TSB: Trypticsoy Broth, mm: millimeters, P. acnes : Propionibacterium acnes , S. epidermidis : Staphylococcus epidermidis, S. aureus : Staphylococcus aureus.

Assessment of phytochemicals, antioxidant, and anti-inflammatory potential of Boerhavia procumbens Banks ex Roxb.

PubMed

Bokhari, Jasia; Khan, Muhammad Rashid; Haq, Ihsan Ul

2016-08-01

Boerhavia procumbens is traditionally used in the treatment of various disorders including jaundice and gonorrhea, is a refrigerant, and exhibits anti-inflammatory and antispasmodic activities. The purpose of this study was to determine the phytochemical classes, antioxidant and anti-inflammatory activities of methanol extract (BPME) and different fractions (n-hexane (BPHE), ethyl acetate (BPEE), n-butanol (BPBE), and residual aqueous fraction (BPAE)) of B. procumbens against carrageenan-induced paw edema in rats. To assess the anti-inflammatory effects of B. procumbens, 42 Sprague Dawley male rats (150-200 g) were randomly divided into seven groups. Group I received distilled water and group II was treated with diclofenac potassium (10 mg/kg) body weight (bw) orally. Groups III, IV, V, VI, and VII were administered BPME, BPHE, BPEE, BPBE, and BPAE (200 mg/kg bw) orally, 1 h before the treatment with carrageenan (10 mg/kg bw) in rats. Anti-inflammatory effects of B. procumbens were determined by estimating the inhibition of edema at 1st, 2nd, and 3rd hour after carrageenan injection. Qualitative analysis of methanol extract indicated the composition of diverse classes, namely, flavonoids, tannins, saponins, phlobatannins, cardiac glycosides, alkaloids, terpenoids, and anthraquinones. Quantitative determination illustrated that BPBE and BPEE possessed the highest concentration of total phenolic (60.45 ± 2.1 mg gallic acid equivalent per gram sample) and total flavonoid content (68.05 ± 2.3 mg rutin equivalent per gram sample), respectively. A dose-dependent response for antioxidant activity was exhibited by all the samples. The sample with the highest aptitude for antioxidant activity was the BPBE for 2,2-azobis,3-ethylbenzothiozoline-6-sulfonic acid radical scavenging and total antioxidant capacity. Carrageenan-induced paw edema was significantly (p < 0.05) inhibited by BPBE and BPME at the 1st, 2nd, and 3rd hour and was comparable to control drug diclofenac potassium. Results revealed that various fractions of B. procumbens manifested the antioxidant and anti-inflammatory potential and accredit the local use of B. procumbens in various disorders. © The Author(s) 2015.

Dermatomyositis-like syndrome induced by nonsteroidal anti-inflammatory agents.

PubMed

Grob, J J; Collet, A M; Bonerandi, J J

1989-01-01

A dermatomyositis-like syndrome developed in a patient treated with a nonsteroidal anti-inflammatory agent (NSAI), niflumic acid, and regressed after the cessation of treatment. Previously an eruption had occurred under treatment with another NSAI, diclofenac. Our report shows that NSAI can induce not only lupus-like syndromes but also other connective tissue disorders.

Can Rectal Diclofenac Prevent Post Endoscopic Retrograde Cholangiopancreatography Pancreatitis?

PubMed

Lua, Guan Way; Muthukaruppan, Raman; Menon, Jayaram

2015-10-01

Non steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the incidence of post endoscopic retrograde cholangiopancreatography pancreatitis (PEP). There were various trials using different routes and dosages of NSAIDs but meta-analysis revealed inconsistent results. The aims of this study were to determine the efficacy of rectal diclofenac in preventing PEP and to evaluate any adverse events. This was a randomized, open-label, two-arm, prospective clinical trial. Only patients at high risk of developing PEP were recruited. They received 100 mg rectal diclofenac or no intervention immediately after ERCP. The patients were reviewed 30 days after discharge to evaluate any adverse event. Among 144 recruited patients, 69 (47.9%) received diclofenac and 75 (52.1%) had no intervention. Eleven patients (7.6%) developed PEP, in which seven were from the diclofenac group and four were in the control group. Eight cases of PEP (5.5%) were mild and three cases (2.1%) were moderate. The differences in pancreatitis incidence and severity between both groups were not statistically significant. There were 11 adverse events reported. Clinically significant bleeding happened in four patients (2.8%): one from the diclofenac group and three from the control group. Other events included cholangitis: two patients (2.9%) from the diclofenac group and four (5.3%) from the control group. One patient from the diclofenac group (1.4%) had a perforation which was treated conservatively. In summary, prophylactic rectal diclofenac did not significantly decrease the incidence of PEP among patients at high risk for developing PEP. However, the administration of diclofenac was fairly safe with few clinical adverse events.

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

PubMed

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.

Synthesis, molecular docking, and biological evaluation of some novel hydrazones and pyrazole derivatives as anti-inflammatory agents.

PubMed

Mohammed, Khaled O; Nissan, Yassin M

2014-10-01

2-Hydrazinyl-N-(4-sulfamoylphenyl)acetamide 3 was the key intermediate for the synthesis of novel hydrazones 4-10 and pyrazole derivatives 11-17. All compounds were tested for their in vivo anti-inflammatory activity and their ability to inhibit the production of PGE(2) in serum samples of rats. IC(50) values for the most active compounds for inhibition of COX-1 and COX-2 enzymes were determined in vitro, and they were also tested for their ulcerogenic effect. Molecular docking was performed on the active site of COX-2 to predict their mode of binding to the amino acids. Most of the synthesized compounds showed good anti-inflammatory activity especially compounds 3, 4, 8, 9, 15, and 17 which showed better activity than diclofenac as the reference drug. Compounds 3, 8, 9, 13, and 15-17 were less ulcerogenic than indomethacine as the reference drug. Most of the synthesized compounds interacted with Tyr 385 and Ser 530 in molecular docking study with additional hydrogen bond for compound 17. Compound 17 showed good selectivity index value of 11.1 for COX-1/COX-2 inhibition in vitro. © 2014 John Wiley & Sons A/S.

Improving sustained drug delivery from ophthalmic lens materials through the control of temperature and time of loading.

PubMed

Topete, Ana; Oliveira, Andreia S; Fernandes, A; Nunes, T G; Serro, A P; Saramago, B

2018-05-30

Although the possibility of using drug-loaded ophthalmic lens to promote sustained drug release has been thoroughly pursued, there are still problems to be solved associated to the different alternatives. In this work, we went back to the traditional method of drug loading by soaking in the drug solution and tried to optimize the release profiles by changing the temperature and the time of loading. Two materials commercially available under the names of CI26Y and Definitive 50 were chosen. CI26Y is used for intraocular lenses (IOLs) and Definitive 50 for soft contact lenses (SCLs). Three drugs were tested: an antibiotic, moxifloxacin, and two anti-inflammatories, diclofenac and ketorolac. Sustained drug release from CI26Y disks for, at least 15 days, was obtained for moxifloxacin and diclofenac increasing the loading temperature up to 60 °C or extending the loading time till two months. The sustained release of ketorolac was limited to about 8 days. In contrast, drug release from Definitive 50 disks could not be improved by changing the loading conditions. An attempt to interpret the impact of the loading conditions on the drug release behavior was done using solid-state NMR and differential scanning calorimetry. These studies suggested the establishment of reversible, endothermic interactions between CI26Y and the drugs, moxifloxacin and diclofenac. The loading temperature had a slight effect on the mechanical and optical properties of drug loaded CI26Y samples, which still kept adequate properties to be used as IOL materials. The in vivo efficacy of CI26Y samples, drug loaded at 60 °C for two weeks, was predicted using a simplified mathematical model to estimate the drug concentration in the aqueous humor. The estimated concentrations were found to comply with the therapeutic needs, at least, for moxifloxacin and diclofenac. Copyright © 2018 Elsevier B.V. All rights reserved.

Bax-mediated mitochondrial outer membrane permeabilization (MOMP), distinct from the mitochondrial permeability transition, is a key mechanism in diclofenac-induced hepatocyte injury: Multiple protective roles of cyclosporin A

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

Siu, W.P.; Pun, Pamela Boon Li; Latchoumycandane, Calivarathan

2008-03-15

Diclofenac, a widely used nonsteroidal anti-inflammatory drug, has been associated with rare but severe cases of clinical hepatotoxicity. Diclofenac causes concentration-dependent cell death in human hepatocytes (after 24-48 h) by mitochondrial permeabilization via poorly defined mechanisms. To explore whether the cyclophilin D (CyD)-dependent mitochondrial permeability transition (mPT) and/or the mitochondrial outer membrane permeabilization (MOMP) was primarily involved in mediating cell death, we exposed immortalized human hepatocytes (HC-04) to apoptogenic concentrations of diclofenac (> 500 {mu}M) in the presence or absence of inhibitors of upstream mediators. The CyD inhibitor, cyclosporin A (CsA, 2 {mu}M) fully inhibited diclofenac-induced cell injury, suggesting thatmore » mPT was involved. However, CyD gene silencing using siRNA left the cells susceptible to diclofenac toxicity, and CsA still protected the CyD-negative cells from lethal injury. Diclofenac induced early (9 h) activation of Bax and Bak and caused mitochondrial translocation of Bax, indicating that MOMP was involved in cell death. Inhibition of Bax protein expression by using siRNA significantly protected HC-04 from diclofenac-induced cell injury. Diclofenac also induced early Bid activation (tBid formation, 6 h), which is an upstream mechanism that initiates Bax activation and mitochondrial translocation. Bid activation was sensitive to the Ca{sup 2+} chelator, BAPTA. In conclusion, we found that Bax/Bak-mediated MOMP is a key mechanism of diclofenac-induced lethal cell injury in human hepatocytes, and that CsA can prevent MOMP through inhibition of Bax activation. These data support our concept that the Ca{sup 2+}-Bid-Bax-MOMP axis is a critical pathway in diclofenac (metabolite)-induced hepatocyte injury.« less

Effects of rebamipide on nephrotoxicity associated with selected NSAIDs in rats.

PubMed

Wood, Robert C; Wyatt, Jarrett E; Bullins, Kenny W; Hanley, Angela V; Hanley, Gregory A; Denham, James W; Panus, Peter C; Harirforoosh, Sam

2013-11-15

Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is primarily limited by renal and gastrointestinal adverse effects. Rebamipide suppresses gastric mucosal injury when administered with NSAIDs. This study aimed to determine rebamipide's influence upon renal effects following concomitant use with celecoxib or diclofenac. On day 0, rats were randomly divided into 6 groups (n≥6). On days 1 and 2, three groups received placebo and three groups were administered rebamipide (30 mg/kg) twice daily. On day 3, the rats treated with placebo received another dose of placebo and ten minutes later a single dose of celecoxib (40 mg/kg), diclofenac (10mg/kg), or placebo, respectively. The rats treated with rebamipide received one more dose of rebamipide and ten minutes later one single dose of celecoxib, diclofenac, or placebo, respectively. Urine and blood samples were collected on days 0, 2, and 3. Sodium and potassium excretion rates decreased significantly in the rats treated with celecoxib, diclofenac, rebamipide plus celecoxib, or rebamipide plus diclofenac on day 3. Blood urea nitrogen (BUN) levels significantly increased in placebo plus diclofenac and rebamipide plus diclofenac groups on day 3. Comparing the two groups, the levels of BUN was significantly higher in the rebamipide plus diclofenac group compared to that of placebo plus diclofenac group. Concomitant administration of rebamipide with either NSAID caused a rise in concentrations of urinary kidney injury molecule-1. Histopathological evaluations revealed an intensified NSAID-induced tubular necrosis by rebamipide. Based upon the results obtained, concomitant administration of rebamipide with NSAIDs enhances the effect of NSAIDs on tubular injury. © 2013 Elsevier B.V. All rights reserved.

Antioxidant, Anti-Inflammatory, and Antitumor Activities of Cultured Mycelia and Fruiting Bodies of the Elm Oyster Mushroom, Hypsizygus ulmarius (Agaricomycetes).

PubMed

Greeshma, Panavalappil; Ravikumar, Korattuvalappil S; Neethu, Mangalathmelathil N; Pandey, Meera; Zuhara, Karattuthodi Fathimathu; Janardhanan, Kainoor K

2016-01-01

Ethanoic extracts from the fruiting bodies and mycelia of the elm oyster mushroom, Hypsizygus ulmarius, were evaluated for their antioxidant, anti-inflammatory, and antitumor properties. Ethnolic extracts of fruiting body and mycelia showed 88%, 85%, 71%, and 85%, 65%, 70% 2,2-diphenyl-1-picrylhydrazyl, hydroxyl (DPPH) and 2,2'-azinobis (3-ethyl benzothiazolin-6-sulfonic acid) (ABTS) radical-scavenging activities, respectively, at a concentration of 1000 µg/mL. The anti-inflammatory activity was determined using carrageenan- and formalin- induced paw edema models. Diclofenac was used as the standard drug. In both models, the mycelia extract showed higher activity than the fruiting body extract. The antitumor effect of the extracts against Dalton's Lymphoma Ascites cell-line-induced tumors showed significant antitumor activity. Mycochemical analysis confirmed the presence of many pharmacologically active compounds such as phenol, alkaloids, proteins, tannins, and polysaccharides. Among these, polysaccharides and phenolic compounds were present at a higher concentration in both extracts. These compounds might be largely responsible for the mushroom's medicinal properties. The results of this study indicate that H. ulmarius possesses significant antioxidant, anti-inflammatory, and antitumor properties.

Design and characterization of diclofenac diethylamine transdermal patch using silicone and acrylic adhesives combination.

PubMed

Panchaxari, Dandigi M; Pampana, Sowjanya; Pal, Tapas; Devabhaktuni, Bhavana; Aravapalli, Anil Kumar

2013-01-07

The objective of the study was to develop and characterize Diclofenac Diethylamine (DDEA) transdermal patch using Silicone and acrylic adhesives combination. Modified solvent evaporation method was employed for casting of film over Fluoropolymer coated polyester release liner. Initial studies included solubilization of drug in the polymers using solubilizers. The formulations with combination of adhesives were attempted to combine the desirable features of both the adhesives. The effect of the permeation enhancers on the drug permeation were studied using pig ear skin. All the optimized patches were subjected to adhesion, dissolution and stability studies. A 7-day skin irritancy test on albino rabbits and an in vivo anti-inflammatory study on wistar rats by carrageenan induced paw edema method were also performed. The results indicated the high percent drug permeation (% CDP-23.582) and low solubility nature (1%) of Silicone adhesive and high solubility (20%) and low% CDP (10.72%) of acrylic adhesive. The combination of adhesives showed desirable characteristics for DDEA permeation with adequate % CDP and sufficient solubility. Release profiles were found to be dependent on proportion of polymer and type of permeation enhancer. The anti-inflammatory study revealed the sustaining effect and high percentage inhibition of edema of C4/OLA (99.68%). The acute skin irritancy studies advocated the non-irritant nature of the adhesives used. It was concluded that an ideal of combination of adhesives would serve as the best choice, for fabrication of DDEA patches, for sustained effect of DDEA with better enhancement in permeation characteristics and robustness.

Design and characterization of diclofenac diethylamine transdermal patch using silicone and acrylic adhesives combination

PubMed Central

2013-01-01

Background and purpose of the study The objective of the study was to develop and characterize Diclofenac Diethylamine (DDEA) transdermal patch using Silicone and acrylic adhesives combination. Methods Modified solvent evaporation method was employed for casting of film over Fluoropolymer coated polyester release liner. Initial studies included solubilization of drug in the polymers using solubilizers. The formulations with combination of adhesives were attempted to combine the desirable features of both the adhesives. The effect of the permeation enhancers on the drug permeation were studied using pig ear skin. All the optimized patches were subjected to adhesion, dissolution and stability studies. A 7-day skin irritancy test on albino rabbits and an in vivo anti-inflammatory study on wistar rats by carrageenan induced paw edema method were also performed. Results The results indicated the high percent drug permeation (% CDP-23.582) and low solubility nature (1%) of Silicone adhesive and high solubility (20%) and low% CDP (10.72%) of acrylic adhesive. The combination of adhesives showed desirable characteristics for DDEA permeation with adequate % CDP and sufficient solubility. Release profiles were found to be dependent on proportion of polymer and type of permeation enhancer. The anti-inflammatory study revealed the sustaining effect and high percentage inhibition of edema of C4/OLA (99.68%). The acute skin irritancy studies advocated the non-irritant nature of the adhesives used. Conclusion It was concluded that an ideal of combination of adhesives would serve as the best choice, for fabrication of DDEA patches, for sustained effect of DDEA with better enhancement in permeation characteristics and robustness. PMID:23351568

Diclofenac-Induced Photo-Onycholysis

PubMed Central

Al-Kathiri, Lutfi; Al-Asmaili, Abla

2016-01-01

Onycholysis is the detachment of the nail plate from the nail bed. If drug-induced, it can be an isolated phenomenon, but it may also accompany or follow a cutaneous phototoxicity reaction due to drug intake and exposure to ultraviolet irradiation. Photo-onycholysis is a rare photosensitivity reaction due to exposure to either a natural or artificial source of light. Many drugs are responsible for this phototoxic reaction, especially tetracyclines, psoralens, chloramphenicol, non-steroidal anti-inflammatory drugs, fluoroquinolones, and, rarely, doxycycline. Any patient given enough of a therapeutic dose of an inducing drug and sufficient light irradiation can develop phototoxic reactions. While there is no need to avoid these drugs completely, precautions should be taken. Here we have reported the case of a patient who developed onycholysis of his fingernails with sparing of the toenails following administration of diclofenac therapy for lower back pain. The onycholysis was associated with a phototoxic reaction. The swellings resolved totally within two days, and the patient started to notice the separation of all fingernail plates from their nail beds. The patient was treated symptomatically. On follow-up, onycholysis had regressed slowly, and the condition recovered totally within three months without any sequelae. PMID:26816569

Comparison of Intravitreal Bevacizumab and Intravitreal Diclofenac in the Treatment of Diabetic Macular Edema: a 6-month Follow-up

PubMed Central

FAGHIHI, Hooshang; YAHYAPOUR, Hanif; MAHMOUDZADEH, Raziyeh; FAGHIHI, Shahin

2017-01-01

The aim of this study was to compare the effect of intravitreal diclofenac, a non-steroidal anti-inflammatory drug (NSAID), with that of bevacizumab, a well-known anti-vascular endothelial growth factor (VEGF) drug, in the treatment of diabetic macular edema (DME). Diclofenac was chosen in this study because it has both features of NSAIDs and corticosteroids by inhibiting the cyclooxygenase (COX) and lipoxygenase pathways, respectively. In this non-randomized comparative interventional case series, 64 eyes from 32 patients with bilateral naïve DME were selected and every eye was randomly assigned to intravitreal injection of bevacizumab (IVB) or diclofenac (IVD). After exclusion of some patients because of short follow-up duration or less than two intravitreal injections, finally, 52 eyes from 26 patients were analyzed. Of those, 26 eyes received 500 µg/0.1 mL IVD and 26 eyes received 1.25 mg IVB. After 6 months of follow-up, the results indicated that visual acuity was significantly improved from 0.50 ± 0.13 in IVB and 0.52 ± 0.12 LogMAR in IVD at baseline to 0.2 ± 0.1 and 0.29 ± 0.07, respectively. Central macular thickness (CMT) and macular volume were measured based on spectral-domain optical coherence tomography (OCT) at month 1, 3, and 6. Both groups showed a significant reduction in CMT and macular volume from baseline but there was no significant difference between the IVB and IVD groups. Interestingly, IVD, but not IVB, decreased intraocular pressure (IOP), which is a desirable effect. There was no serious complication due to injections. This study sheds light into the long-term effects of NSAIDs and may support the idea that inflammation suppression by NSAIDs may have the same results as anti-VEGF administration. PMID:29392145

Comparison of Intravitreal Bevacizumab and Intravitreal Diclofenac in the Treatment of Diabetic Macular Edema: a 6-month Follow-up.

PubMed

Faghihi, Hooshang; Yahyapour, Hanif; Mahmoudzadeh, Raziyeh; Faghihi, Shahin

2017-01-01

The aim of this study was to compare the effect of intravitreal diclofenac, a non-steroidal anti-inflammatory drug (NSAID), with that of bevacizumab, a well-known anti-vascular endothelial growth factor (VEGF) drug, in the treatment of diabetic macular edema (DME). Diclofenac was chosen in this study because it has both features of NSAIDs and corticosteroids by inhibiting the cyclooxygenase (COX) and lipoxygenase pathways, respectively. In this non-randomized comparative interventional case series, 64 eyes from 32 patients with bilateral naïve DME were selected and every eye was randomly assigned to intravitreal injection of bevacizumab (IVB) or diclofenac (IVD). After exclusion of some patients because of short follow-up duration or less than two intravitreal injections, finally, 52 eyes from 26 patients were analyzed. Of those, 26 eyes received 500 µg/0.1 mL IVD and 26 eyes received 1.25 mg IVB. After 6 months of follow-up, the results indicated that visual acuity was significantly improved from 0.50 ± 0.13 in IVB and 0.52 ± 0.12 LogMAR in IVD at baseline to 0.2 ± 0.1 and 0.29 ± 0.07, respectively. Central macular thickness (CMT) and macular volume were measured based on spectral-domain optical coherence tomography (OCT) at month 1, 3, and 6. Both groups showed a significant reduction in CMT and macular volume from baseline but there was no significant difference between the IVB and IVD groups. Interestingly, IVD, but not IVB, decreased intraocular pressure (IOP), which is a desirable effect. There was no serious complication due to injections. This study sheds light into the long-term effects of NSAIDs and may support the idea that inflammation suppression by NSAIDs may have the same results as anti-VEGF administration.

A Study on Factors Affecting Low Back Pain and Safety and Efficacy of NSAIDs in Acute Low Back Pain in a Tertiary Care Hospital of Western Nepal

PubMed Central

Bhattarai, Srijana; Chhetri, Himal Paudel; Alam, Kadir; Thapa, Pabin

2013-01-01

Introduction: Low back pain is characterized by a range of symptoms which include pain, muscle tension or stiffness, and is localized between the shoulder blades and the folds of the buttocks, with or without spreading to the legs. Non-Steroidal Anti Inflammatory Drugs (NSAIDs) are the drugs of choice which provide an analgesic effect for acute low back pain. Aim: To study the factors affecting low back pain, efficacy and safety of different non-steroidal anti-inflammatory drugs (aceclofenac, diclofenac, naproxen and nimesulide) in low back pain. Methodology: Data collection form and numeric pain rating scale were used as study tools for studying patients’ demographies and severities of pain respectively. Patients prescribed with aceclofenac 100 mg , diclofenac 100 mg, naproxen 500 mg and nimesulide 100 mg for acute low back pain at Orthopaedics Outpatients Department of Manipal Teaching Hospital, Nepal, were enrolled in this study. The decrease in pain scores was recorded on 5th and 10th days of follow-up and pain scores were calculated. Descriptive statistics and Kruskal Wallis non parametric test were used for analysis. Results: Among 150 patients, 67.3% were females (n=101). Low back pain was more prevalent (24.7%) in age-group of 59-68 years and a positive correlation was seen. Similarly, low back pain was found to be high among people involved in agriculture, heavy weight lifters and non smokers. The decrease in average pain scores was more in the patients treated with aceclofenac (4.83 ± 0.537), followed by that in those who were treated with naproxen (4.13 ± 0.067) and diclofenac (3.84 ± 0.086). The decrease in pain scores was found to be lowest among patients who were treated with nimesulide (2.11 ± 0.148). Nimesulide presented more number of side-effects than the comparative drugs. Conclusion: Different factors affect low back pain, such as age, gender, personal habit, posture, occupation, weight lifting. Aceclofenac showed greater decrease in pain scores with lesser number of side-effects. PMID:24551630

Patterns of analgesic and anti-inflammatory medicine use by Australian veterans.

PubMed

Pearson, S-A; Ringland, C; Kelman, C; Mant, A; Lowinger, J; Stark, H; Nichol, G; Day, R; Henry, D

2007-12-01

We examined analgesic and anti-inflammatory medicine use by Australian veterans before and after the introduction of selective Cox-2 inhibitors. We studied cohorts of Gold Card-holding veterans using prescription data held by the Department of Veterans' Affairs for the period 1 July 1998 to 30 June 2004. Outcomes were volume dispensed, average daily quantity and cumulative incidence of use of paracetamol-containing and aspirin-containing medicines, non-selective and Cox-2-selective non-steroidal anti-inflammatory drugs (NSAIDs), tramadol and dextropropoxyphene. Overall, we found high levels of use of analgesic and anti-inflammatory medicines, which increased by 43% over the study period. Use of paracetamol-containing medicines was overtaken by NSAIDs in 1999/2000, corresponding to the introduction of the Cox-2-selective agents. Between 12 and 17% of Cox-2-selective medicine recipients were supplied amounts indicative of continuous use in relatively high doses and 51% of veterans received at least one relatively Cox-2-selective medicine (celecoxib, rofecoxib, meloxicam, diclofenac) by the end of the study period. Dextropropoxyphene use declined during the study and tramadol use increased 10-fold. This study shows very high levels of Cox-2 inhibitor use during the 6-year period. Cox-2-selective agents were more likely to be taken continuously and at higher doses than non-selective NSAIDs. This is relevant in view of the cardiovascular toxicity of this group of medicines. The study shows the value of using unit record dispensing data to assess drug use patterns. Linking dispensing records to hospital separation and mortality data will further enhance our ability to monitor drug safety.

Removing the Threat of Diclofenac to Critically Endangered Asian Vultures

PubMed Central

Swan, Gerry; Naidoo, Vinasan; Cuthbert, Richard; Pain, Deborah J; Swarup, Devendra; Prakash, Vibhu; Taggart, Mark; Bekker, Lizette; Das, Devojit; Diekmann, Jörg; Diekmann, Maria; Killian, Elmarié; Meharg, Andy; Patra, Ramesh Chandra; Saini, Mohini; Wolter, Kerri

2006-01-01

Veterinary use of the nonsteroidal anti-inflammatory (NSAID) drug diclofenac in South Asia has resulted in the collapse of populations of three vulture species of the genusGyps to the most severe category of global extinction risk. Vultures are exposed to diclofenac when scavenging on livestock treated with the drug shortly before death. Diclofenac causes kidney damage, increased serum uric acid concentrations, visceral gout, and death. Concern about this issue led the Indian Government to announce its intention to ban the veterinary use of diclofenac by September 2005. Implementation of a ban is still in progress late in 2005, and to facilitate this we sought potential alternative NSAIDs by obtaining information from captive bird collections worldwide. We found that the NSAID meloxicam had been administered to 35 captiveGyps vultures with no apparent ill effects. We then undertook a phased programme of safety testing of meloxicam on the African white-backed vultureGyps africanus, which we had previously established to be as susceptible to diclofenac poisoning as the endangered AsianGyps vultures. We estimated the likely maximum level of exposure (MLE) of wild vultures and dosed birds by gavage (oral administration) with increasing quantities of the drug until the likely MLE was exceeded in a sample of 40G. africanus. Subsequently, sixG. africanus were fed tissues from cattle which had been treated with a higher than standard veterinary course of meloxicam prior to death. In the final phase, ten Asian vultures of two of the endangered species(Gyps bengalensis,Gyps indicus) were dosed with meloxicam by gavage; five of them at more than the likely MLE dosage. All meloxicam-treated birds survived all treatments, and none suffered any obvious clinical effects. Serum uric acid concentrations remained within the normal limits throughout, and were significantly lower than those from birds treated with diclofenac in other studies. We conclude that meloxicam is of low toxicity toGyps vultures and that its use in place of diclofenac would reduce vulture mortality substantially in the Indian subcontinent. Meloxicam is already available for veterinary use in India. PMID:16435886

Conjunctival Goblet Cell Density Following Cataract Surgery With Diclofenac Versus Diclofenac and Rebamipide: A Randomized Trial.

PubMed

Kato, Kumiko; Miyake, Kensaku; Kondo, Nagako; Asano, Sayaka; Takeda, Junko; Takahashi, Akiko; Takashima, Yuko; Kondo, Mineo

2017-09-01

To determine the effects of topical diclofenac or betamethasone with concomitant application of topical rebamipide on the conjunctival goblet cell density in eyes after cataract surgery. Randomized clinical trial. Eighty patients who were scheduled for cataract surgery. Patients were randomized into 4 groups according to the postoperative topical drugs to be given; Group A, diclofenac alone; Group B, diclofenac and rebamipide; Group C, betamethasone alone; and Group D, betamethasone and rebamipide. Impression cytology was performed before and at 1 month after the surgery, and the mean density of goblet cells was determined. The mean (± SD) density of goblet cells before the surgery in Group A was 257.0 ± 188.7 cells/mm 2 , and it decreased significantly to 86.5 ± 76.7 cells/mm 2 at 1 month after the surgery (P = .002). In Group B, the goblet cell density was not statistically different between before (238.5 ± 116.6 cells/mm 2 ) and at 1 month after the surgery (211.3 ± 184.4 cells/mm 2 , P = .55). In Groups C and D, the mean density of goblet cells was decreased at 1 month after the surgery, but the decreases were not significant (P = .11 and P = .52, respectively). After cataract surgery with postoperative topical diclofenac, the conjunctival goblet cell density was significantly reduced, and this reduction was blocked by the concomitant use of topical rebamipide. These results suggest that the concomitant use of topical rebamipide with nonsteroidal anti-inflammatory drugs is beneficial, especially in cases with postoperative dry eyes. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Celecoxib or diclofenac hepatic status in the presence or absence of rebamipide.

PubMed

Murrell, D E; Rahmasari, Y; Denham, J W; Panus, P C; Harirforoosh, S

2015-09-01

Utilization of nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, can produce gastrointestinal ulceration. Thus, cyclooxygenase-2-selective inhibitors, such as celecoxib, and protective agents (e.g. rebamipide) have been employed to alleviate harmful NSAID effects. This study sought to explore the influence of rebamipide on the hepatic outcomes following administration of two commonly prescribed NSAIDs. Rats were given either vehicle or rebamipide (30 mg/kg) orally twice daily for two days, then on the third day respective groups were dosed with either vehicle, celecoxib (40 mg/kg), or diclofenac (10 mg/kg) in addition to a respective dose of vehicle or rebamipide. Livers were collected on day 4 following euthanasia. Hepatic tissue was examined via histopathology and assayed for oxidative stress and specific NSAID concentration. The liver sections were found to be free from structural changes. Oxidative stress biomarkers, reduced glutathione and malondialdehyde, were discovered to be unaltered among the groups tested. The hepatic NSAID concentrations were not significantly affected by the presence of rebamipide. The concomitant administration of rebamipide does not influence the hepatic condition of rats administered either celecoxib or diclofenac at the dosages and over the time course examined.

A comprehensive strategy in the development of a cyclodextrin-modified microemulsion electrokinetic chromatographic method for the assay of diclofenac and its impurities: Mixture-process variable experiments and quality by design.

PubMed

Orlandini, S; Pasquini, B; Caprini, C; Del Bubba, M; Squarcialupi, L; Colotta, V; Furlanetto, S

2016-09-30

A comprehensive strategy involving the use of mixture-process variable (MPV) approach and Quality by Design principles has been applied in the development of a capillary electrophoresis method for the simultaneous determination of the anti-inflammatory drug diclofenac and its five related substances. The selected operative mode consisted in microemulsion electrokinetic chromatography with the addition of methyl-β-cyclodextrin. The critical process parameters included both the mixture components (MCs) of the microemulsion and the process variables (PVs). The MPV approach allowed the simultaneous investigation of the effects of MCs and PVs on the critical resolution between diclofenac and its 2-deschloro-2-bromo analogue and on analysis time. MPV experiments were used both in the screening phase and in the Response Surface Methodology, making it possible to draw MCs and PVs contour plots and to find important interactions between MCs and PVs. Robustness testing was carried out by MPV experiments and validation was performed following International Conference on Harmonisation guidelines. The method was applied to a real sample of diclofenac gastro-resistant tablets. Copyright © 2016 Elsevier B.V. All rights reserved.

Nonsteroidal Anti-inflammatory Drugs (NSAIDS) Inhibit the Growth and Reproduction of Chaetomium globosum and Other Fungi Associated with Water-Damaged Buildings.

PubMed

Dalmont, Kelsey; Biles, Charles L; Konsure, Heather; Dahal, Sujita; Rowsey, Tyler; Broge, Matthew; Poudyal, Shubhra; Gurung, Tara; Shrestha, Sabina; Biles, Caleb L; Cluck, Terry; Howard, Alisha

2017-12-01

Indoor mold due to water damage causes serious human respiratory disorders, and the remediation to homes, schools, and businesses is a major expense. Prevention of mold infestation of building materials would reduce health problems and building remediation costs. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit yeasts and a limited number of filamentous fungi. The purpose of this research was to determine the possible inhibitory activity of nonsteroidal anti-inflammatory drugs (NSAIDs) on germination, fungal growth, and reproduction of Chaetomium globosum and other important filamentous fungi that occur in water-damaged buildings. Several NSAIDs were found to inhibit C. globosum germination, growth, and reproduction. The most effective NSAIDs inhibiting C. globosum were ibuprofen, diflunisal, and diclofenac. Fusarium oxysporum, Fusarium solani, Aspergillus niger, and Stachybotrys atra were also tested on the various media with similar results obtained. However, F. oxysporum and A. niger exhibited a higher level of resistance to aspirin and NaSAL when compared to the C. globosum isolates. The inhibition exhibited by NSAIDs was variable depending on growth media and stage of fungal development. These compounds have a great potential of inhibiting fungal growth on building materials such as gypsum board. Formulations of sprays or building materials with NSAID-like chemical treatments may hold promise in reducing mold in homes and buildings.

Selective scavenging of intra-mitochondrial superoxide corrects diclofenac-induced mitochondrial dysfunction and gastric injury: A novel gastroprotective mechanism independent of gastric acid suppression.

PubMed

Mazumder, Somnath; De, Rudranil; Sarkar, Souvik; Siddiqui, Asim Azhar; Saha, Shubhra Jyoti; Banerjee, Chinmoy; Iqbal, Mohd Shameel; Nag, Shiladitya; Debsharma, Subhashis; Bandyopadhyay, Uday

2016-12-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat multiple inflammatory diseases and pain but severe gastric mucosal damage is the worst outcome of NSAID-therapy. Here we report that mitoTEMPO, a mitochondrially targeted superoxide (O 2 - ) scavenger protected as well as healed gastric injury induced by diclofenac (DCF), the most commonly used NSAID. Common existing therapy against gastric injury involves suppression of gastric acid secretion by proton pump inhibitors and histamine H 2 receptor antagonists; however, dyspepsia, vitamin B12 deficiency and gastric microfloral dysbalance are the major drawbacks of acid suppression. Interestingly, mitoTEMPO did not inhibit gastric acid secretion but offered gastroprotection by preventing DCF-induced generation of O 2 - due to mitochondrial respiratory chain failure and by preventing mitochondrial oxidative stress (MOS)-mediated mitopathology. MitoTEMPO even restored DCF-stimulated reduced fatty acid oxidation, mitochondrial depolarization and bioenergetic crisis in gastric mucosa. MitoTEMPO also prevented the activation of mitochondrial pathway of apoptosis and MOS-mediated proinflammatory signaling through NF-κB by DCF. Furthermore, mitoTEMPO when administered in rats with preformed gastric lesions expedited the healing of gastric injury and the healed stomach exhibited its normal physiology as evident from gastric acid and pepsin secretions under basal or stimulated conditions. Thus, in contrast to the existing antiulcer drugs, mitochondrially targeted O 2 - scavengers like mitoTEMPO may represent a novel class of gastroprotective molecules that does not affect gastric acid secretion and may be used in combination with DCF, keeping its anti-inflammatory action intact, while reducing its gastrodamaging effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Analgesic and anti-inflammatory activities of 80% methanol root extract of Jasminum abyssinicum Hochst. ex. Dc. (Oleaceae) in mice.

PubMed

Tadiwos, Yohannes; Nedi, Teshome; Engidawork, Ephrem

2017-04-18

Pain and inflammation are associated with the pathophysiology of various clinical conditions. Most analgesic and anti-inflammatory drugs available in the market present a wide range of problems. The current study was aimed at investigating the analgesic and anti-inflammatory activity of 80% methanol extract of J. abyssinicum root. The analgesic activity was determined using tail-flick test and acetic acid induced writhing, whereas anti-inflammatory activity was determined by carrageenan induced paw edema and formalin induced pedal edema, carried out in vivo. The test group received three different doses of the extract (50mg/kg, 100mg/kg and 200mg/kg) orally. The positive control group received diclofenac (10mg/kg), aspirin (100mg/kg or 150mg/kg) or morphine (20mg/kg) orally. The negative control group received vehicle (2% Tween 80, 10ml/kg) orally. Furthermore, preliminary phytochemical screening was carried out. Oral administration of J. abbysinicum 80% methanol extract (at all doses) significantly (p<0.001) inhibit pain sensation in the pain models. Similarly, the extract demonstrated anti-inflammatory effect in the inflammation models in mice. Preliminary phytochemical screening showed the presence of saponins, flavonoids, terpenoids, triterpenens and glycosides. The data obtained from the present study indicates that the extract possessed a significant analgesic and anti-inflammatory activity, upholding the folkloric use of the plant. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Bioequivalence of diclofenac sodium 2% and 1.5% topical solutions relative to oral diclofenac sodium in healthy volunteers.

PubMed

Holt, Robert J; Taiwo, Tolu; Kent, Jeffrey D

2015-08-01

Topical formulations of nonsteroidal anti-inflammatory drugs (NSAIDs) are generally considered to be safer alternatives to oral NSAIDs due to lower systemic absorption. We conducted randomized, crossover studies that compared the pharmacokinetics (PK), bioequivalence and safety of topical diclofenac sodium 2% twice daily (BID), diclofenac sodium 1.5% four times daily (QID) and oral diclofenac sodium in healthy subjects. The results of three bioequivalence studies are reviewed. Healthy adult subjects (n = 76) applied topical diclofenac sodium 2% solution (40.4 mg/2 mL) BID; or 1.5% solution (19.3 mg/40 drops) QID to each knee for 7.5 consecutive days separated by a washout period. Subjects (n = 22) in one study also received oral diclofenac sodium 75 mg BID for 7.5 days. Plasma diclofenac concentrations were determined from serial blood samples collected on Days 1 and 8 (steady state), and diclofenac PK parameters were estimated by noncompartmental methods. The studies demonstrated comparable bioequivalence between the 2% and 1.5% topical solutions as well as lower systemic exposure compared to oral dosing (approximately 93% less). Daily systemic exposure was comparable between the two formulations with only a 12% difference in the AUCss(0-24) (p = 0.140). Furthermore, both topical solutions demonstrated delayed elimination with a t(1/2) of 4- to 6-fold longer, as compared to oral diclofenac. The 2% solution provided more consistent dosing relative to the 1.5% solution when comparing AUCss(0-24) and Cmaxss across studies. Mild application site reactions were the most common treatment-emergent adverse event reported with topical diclofenac. The steady-state PK profile of topical diclofenac 2% solution administered BID is similar to that of the 1.5% solution administered QID. Systemic exposure to diclofenac is substantially lower after topical application as compared to oral administration. (Study 2 was registered with ClinicalTrials.gov; NCT01202799; https://clinicaltrials.gov/ct2/results?term=01202799&Search=Search).

Phytochemical Composition, Antioxidant, Antimicrobial and in Vivo Anti-inflammatory Activity of Traditionally Used Romanian Ajuga laxmannii (Murray) Benth. (“Nobleman’s Beard” – Barba Împăratului)

PubMed Central

Toiu, Anca; Mocan, Andrei; Vlase, Laurian; Pârvu, Alina E.; Vodnar, Dan C.; Gheldiu, Ana-Maria; Moldovan, Cadmiel; Oniga, Ilioara

2018-01-01

In the Romanian folk medicine, aerial parts of Ajuga laxmannii (“nobleman’s beard,” Romanian – “barba boierului” or “avrămească” or “creştinească”) are traditionally used as galactagogue and anti-inflammatory agents. The present study aimed to evaluate the chemical composition (polyphenols, iridoids, and phytosterols), antioxidant, antimicrobial and in vivo anti-inflammatory activity of different extracts of A. laxmannii aerial parts. The major identified bioactive compounds were rutin, 8-O-acetylharpagide and β-sitosterol. The antioxidant activity of A. laxmannii extracts was evaluated using several methods, and the results showed good antiradical effects. Moreover, the antimicrobial evaluation showed a potent antifungal activity against C. albicans and P. funiculosum. Furthermore, the anti-inflammatory effect was determined by monitoring some parameters involved in the inflammatory process. The results obtained showed differences between the analyzed extracts; and therefore the importance of choosing the best solvent in order to extract the appropriate amount of bioactive compounds. A. laxmannii ethanol extract showed an anti-inflammatory effect by reducing total leukocytes, PMN, phagocytosis, and oxidative stress. Compared to diclofenac, only the 50 mg/mL A. laxmannii extract had better anti-inflammatory and anti-oxidative stress effects, and this could justify the importance of a correlation between the activity and the used concentration. These findings strongly suggest that A. laxmannii could be considered as a valuable source of bioactive compounds, which could be further valued as anti-inflammatory agents in the composition of several herbal drugs. PMID:29551972

Antinociceptive, anti-inflammatory and antidiabetic effects of Bryophyllum pinnatum (Crassulaceae) leaf aqueous extract.

PubMed

Ojewole, John A O

2005-05-13

In order to scientifically appraise some of the ethnomedical uses of Bryophyllum pinnatum leaves, the present study was undertaken to investigate the antinociceptive, anti-inflammatory and antidiabetic properties of the plant's leaf aqueous extract in experimental animal models. The antinociceptive effect of the herb's leaf extract was evaluated by the 'hot-plate' and 'acetic acid' test models of pain in mice. The anti-inflammatory and antidiabetic effects of the plant's extract were investigated in rats, using fresh egg albumin-induced pedal (paw) oedema, and streptozotocin (STZ)-induced diabetes mellitus. Diclofenac (DIC, 100 mg/kg) and chlorpropamide (250 mg/kg) were used respectively as reference drugs for comparison. Bryophyllum pinnatum leaf aqueous extract (BPE, 25-800 mg/kg i.p.) produced significant (P<0.05-0.001) antinociceptive effects against thermally- and chemically-induced nociceptive pain stimuli in mice. The plant extract (BPE, 25-800 mg/kg p.o. or i.p.) also significantly (P<0.05-0.001) inhibited fresh egg albumin-induced acute inflammation and caused significant (P<0.05-0.001) hypoglycaemia in rats. The results of this experimental animal study suggest that Bryophyllum pinnatum leaf aqueous extract possesses antinociceptive, anti-inflammatory and hypoglycaemic properties. The different flavonoids, polyphenols, triterpenoids and other chemical constituents of the herb are speculated to account for the observed antinociceptive, anti-inflammatory and antidiabetic properties of the plant.

Pentadecapeptide BPC 157 and its effects on a NSAID toxicity model: diclofenac-induced gastrointestinal, liver, and encephalopathy lesions.

PubMed

Ilic, Spomenko; Drmic, Domagoj; Franjic, Sandra; Kolenc, Danijela; Coric, Marijana; Brcic, Luka; Klicek, Robert; Radic, Bozo; Sever, Marko; Djuzel, Viktor; Filipovic, Marinko; Djakovic, Zeljko; Stambolija, Vasilije; Blagaic, Alenka Boban; Zoricic, Ivan; Gjurasin, Miroslav; Stupnisek, Mirjana; Romic, Zeljko; Zarkovic, Kamelija; Dzidic, Senka; Seiwerth, Sven; Sikiric, Predrag

2011-03-14

We attempted to fully antagonize the extensive toxicity caused by NSAIDs (using diclofenac as a prototype). Herein, we used the stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419), an anti-ulcer peptide shown to be efficient in inflammatory bowel disease clinical trials (PL 14736) and various wound treatments with no toxicity reported. This peptide was given to antagonize combined gastrointestinal, liver, and brain toxicity induced by diclofenac (12.5mg/kg intraperitoneally, once daily for 3 days) in rats. Already considered a drug that can reverse the toxic side effects of NSAIDs, BPC 157 (10 μg/kg, 10 ng/kg) was strongly effective throughout the entire experiment when given (i) intraperitoneally immediately after diclofenac or (ii) per-orally in drinking water (0.16 μg/mL, 0.16 ng/mL). Without BPC 157 treatment, at 3h following the last diclofenac challenge, we encountered a complex deleterious circuit of diclofenac toxicity characterized by severe gastric, intestinal and liver lesions, increased bilirubin, aspartate transaminase (AST), alanine transaminase (ALT) serum values, increased liver weight, prolonged sedation/unconsciousness (after any diclofenac challenge) and finally hepatic encephalopathy (brain edema particularly located in the cerebral cortex and cerebellum, more in white than in gray matter, damaged red neurons, particularly in the cerebral cortex and cerebellar nuclei, Purkinje cells and less commonly in the hippocampal neurons). The very extensive antagonization of diclofenac toxicity achieved with BPC 157 (μg-/ng-regimen, intraperitoneally, per-orally) may encourage its further use as a therapy to counteract diclofenac- and other NSAID-induced toxicity. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of anti-inflammatory compounds on sulfur mustard injured cells: Recommendations and caveats suggested by in vitro cell culture models.

PubMed

Menacher, Georg; Steinritz, Dirk; Schmidt, Annette; Popp, Tanja; Worek, Franz; Gudermann, Thomas; Thiermann, Horst; Balszuweit, Frank

2018-09-01

Sulfur mustard (SM) is a vesicant agent who had its first military use 100 years ago, in Ypres. Since then it has been used in several conflicts like the Iran-Iraq war in the 1980s. The use of SM in Syria 2015 indicated the still existing threat. Despite decades of research no causal antidote against SM intoxication is available, so far. A SM intoxication is accompanied by necrosis, apoptosis and inflammation. To counteract the SM-induced inflammation, glucocorticoids and non-steroidal anti-inflammatory compounds (NSAIDs) are recommended. Aim of this study was to evaluate the efficacy of the anti-inflammatory compounds dexamethasone, ibuprofen and diclofenac in vitro. For that purpose, two different cell culture models were used. Firstly, a monoculture of keratinocytes (HaCaT) and secondly, an established co-culture of keratinocytes (HaCaT) and immunocompetent cells (THP-1) to identify the role of immune cells in the process and to mimic the dermal physiology more closely. Both models were challenged with different SM concentrations (100, 200 and 300μM) and treated with different anti-inflammatory compounds one hour after the SM exposure. Analytical analysis of necrosis (ToxiLight), apoptosis (CDDE) and inflammation (IL-6 and -8 ELISAs) followed 24h thereafter. Dexamethasone provided small but consistent protective effects in the monoculture. For the reduction of apoptosis, 3μM dexamethasone was sufficient. The most effective reduction regarding interleukin (IL) production was found with 6μM dexamethasone. Protective effects were less pronounced in co-culture, which implies, that the protective effects of dexamethasone are rather generic and not due to a modulation of the immune cells. Against our expectations, ibuprofen strongly amplified apoptosis and necrosis in SM exposed cells in the monoculture as well as the co-culture. Therefore, use of ibuprofen for treatment of SM intoxication should at least be considered most critically, if not even regarded as harmful. Diclofenac significantly reduced necrosis, apoptosis and inflammation in the co-culture in a dose-dependent manner. The greatest benefit regarding cell survival and reduction of the inflammation-marker IL-6 after a SM treatment was observed after diclofenac treatment. The protective effects of diclofenac were less pronounced in the monoculture which suggests, that diclofenac can modify the response of immune cells to SM. In conclusion, the results of our experiments, showing a benefit for diclofenac after SM exposure are in line with in vivo data of other researchers. Though, our in vitro results suggest the preferred use of diclofenac over ibuprofen. The benefit of dexamethasone is still equivocal, but low concentrations seem to have some positive effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of photobiomodulation therapy and topical non-steroidal anti-inflammatory drug on skeletal muscle injury induced by contusion in rats-part 1: morphological and functional aspects.

PubMed

Tomazoni, Shaiane Silva; Frigo, Lúcio; Dos Reis Ferreira, Tereza Cristina; Casalechi, Heliodora Leão; Teixeira, Simone; de Almeida, Patrícia; Muscara, Marcelo Nicolas; Marcos, Rodrigo Labat; Serra, Andrey Jorge; de Carvalho, Paulo de Tarso Camillo; Leal-Junior, Ernesto Cesar Pinto

2017-12-01

Musculoskeletal injuries are very frequent and are responsible for causing pain and impairment of muscle function, as well as significant functional limitations. In the acute phase, the most prescribed treatment is with non-steroidal anti-inflammatory drugs (NSAIDs), despite their questionable effectiveness. However, the use of photobiomodulation therapy (PBMT) in musculoskeletal disorders has been increasing in the last few years, and this therapy appears to be an interesting alternative to the traditional drugs. The objective of the present study was to evaluate and compare the effects of PBMT, with different application doses, and topical NSAIDs, under morphological and functional parameters, during an acute inflammatory process triggered by a controlled model of musculoskeletal injury induced via contusion in rats. Muscle injury was induced by means of a single trauma to the animals' anterior tibialis muscle. After 1 h, the rats were treated with PBMT (830 nm; continuous mode, with a power output of 100 mW; 3.57 W/cm 2 ; 1 J-35.7 J/cm 2 , 3 J-107.1 J/cm 2 , and 9 J-321.4 J/cm 2 ; 10, 30, and 90 s) or diclofenac sodium for topical use (1 g). Morphological analysis (histology) and functional analysis (muscle work) were performed, 6, 12, and 24 h after induction of the injury. PBMT, with all doses tested, improved morphological changes caused by trauma; however, the 9 J (321.4 J/cm 2 ) dose was the most effective in organizing muscle fibers and cell nuclei. On the other hand, the use of diclofenac sodium produced only a slight improvement in morphological changes. Moreover, we observed a statistically significant increase of muscle work in the PBMT 3 J (107.1 J/cm 2 ) group in relation to the injury group and the diclofenac group (p < 0.05). The results of the present study indicate that PBMT, with a dose of 3 J (107.1 J/cm 2 ), is more effective than the other doses of PBMT tested and NSAIDs for topical use as a means to improve morphological and functional alterations due to muscle injury from contusion.

Pregnant women and non-steroidal anti-inflammatory drugs: knowledge, perception and drug consumption pattern during pregnancy in ethiopia.

PubMed

Kassaw, Chalelgn; Wabe, Nasir Tajure

2012-02-01

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. The study was a cross sectional study on women waiting for a consultation in the selected maternity hospitals in Addis Ababa, Ethiopia. The pregnant women were selected randomly and then interviewed by using standardized questionnaires. A total of 224 pregnant women were involved in the study. Out of those, 203 (90.6%) of them have taken NSAIDs since the beginning of their pregnancy. About 201 (89.7%), 198 (88.4%) and 189 (84.4%) of the pregnant women considered that ibuprofen, diclofenac and aspirin are not NSAIDs respectively. Regarding analgesic effect of NSAIDs, 97 (43.3%) of the pregnant women believed that NSAIDs are effective for treating pain. Acetaminophen was considered as the most effective treatment for pain by 84 (37.50%) of the patients. Acetaminophen is the most common analgesic that was taken by most pregnant women. The knowledge of pregnant women about NSAIDs is poor.

Effects of ibuprofen, diclofenac and paracetamol on hatch and motor behavior in developing zebrafish (Danio rerio).

PubMed

Xia, Liang; Zheng, Liang; Zhou, Jun Liang

2017-09-01

Non-steroidal anti-inflammatory drugs (NSAIDs) which are widely used as pain relief medicines are causing increasing environmental concern due to their incomplete removal in wastewater treatment plant and potential toxicity on endocrine, kidney and reproduction in teleost fish. This study focused on the effects of widely used ibuprofen, diclofenac and paracetamol on the hatch and motor ability of early-stage zebrafish, by exposing embryos to the target chemicals at 5, 50 and 500 μg/L starting from 6 h postfertilization (hpf). A significant reduction in hatch rate at 55 hpf was caused by both ibuprofen (-63%) and diclofenac (-58%) at 500 μg/L. Exposure to high concentration of ibuprofen significantly decreased the spontaneous movement by 25%, and reduced the free swimming distance, duration and speed under dark condition by 41%, 29% and 30%, respectively. High concentration of diclofenac also caused 23% decrease in spontaneous movement, and reduced the swimming distance as well as active duration by 17% and 13% under light stimulation. In comparison, the exposure to paracetamol did not cause any notable effect. Among neuron related genes tested, the expression of neurog1 was down-regulated from ibuprofen and diclofenac exposure by 19% and 26%, while the expression of neurod1 was up-regulated only by ibuprofen (31%). These findings indicated that ibuprofen and diclofenac significantly affected embryo locomotivity and were potentially neurotoxic, thus posing threats to zebrafish development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pathology and proposed pathophysiology of diclofenac poisoning in free-living and experimentally exposed oriental white-backed vultures (Gyps bengalensis)

USGS Publications Warehouse

Meteyer, C.U.; Rideout, B.A.; Gilbert, M.; Shivaprasad, H.L.; Oaks, J.L.

2005-01-01

Oriental white-backed vultures (Gyps bengalensis; OWBVs) died of renal failure when they ingested diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), in tissues of domestic livestock. Acute necrosis of proximal convoluted tubules in these vultures was severe. Glomeruli, distal convoluted tubules, and collecting tubules were relatively spared in the vultures that had early lesions. In most vultures, however, lesions became extensive with large urate aggregates obscuring renal architecture. Inflammation was minimal. Extensive urate precipitation on the surface and within organ parenchyma (visceral gout) was consistently found in vultures with renal failure. Very little is known about the physiologic effect of NSAIDs in birds. Research in mammals has shown that diclofenac inhibits formation of prostaglandins. We propose that the mechanism by which diclofenac induces renal failure in the OWBV is through the inhibition of the modulating effect of prostaglandin on angiotensin II-mediated adrenergic stimulation. Renal portal valves open in response to adrenergic stimulation, redirecting portal blood to the caudal vena cava and bypassing the kidney. If diclofenac removes a modulating effect of prostaglandins on the renal portal valves, indiscriminant activation of these valves would redirect the primary nutrient blood supply away from the renal cortex. Resulting ischemic necrosis of the cortical proximal convoluted tubules would be consistent with our histologic findings in these OWBVs.

A RP-HPLC method for quantification of diclofenac sodium released from biological macromolecules.

PubMed

Bhattacharya, Shiv Sankar; Banerjee, Subham; Ghosh, Ashoke Kumar; Chattopadhyay, Pronobesh; Verma, Anurag; Ghosh, Amitava

2013-07-01

Interpenetrating network (IPN) microbeads of sodium carboxymethyl locust bean gum (SCMLBG) and sodium carboxymethyl cellulose (SCMC) containing diclofenac sodium (DS), a nonsteroidal anti-inflammatory drug, were prepared by single water-in-water (w/w) emulsion gelation process using AlCl3 as cross-linking agent in a complete aqueous environment. Pharmacokinetic study of these IPN microbeads was then carried out by a simple and feasible high-performance liquid chromatographic method with UV detection which was developed and validated for the quantification of diclofenac sodium in rabbit plasma. The chromatographic separation was carried out in a Hypersil BDS, C18 column (250 mm × 4.6 mm; 5 m). The mobile phase was a mixture of acetonitrile and methanol (70:30, v/v) at a flow rate of 1.0 ml/min. The UV detection was set at 276 nm. The extraction recovery of diclofenac sodium in plasma of three quality control (QC) samples was ranged from 81.52% to 95.29%. The calibration curve was linear in the concentration range of 20-1000 ng/ml with the correlation coefficient (r(2)) above 0.9951. The method was specific and sensitive with the limit of quantification of 20 ng/ml. In stability tests, diclofenac sodium in rabbit plasma was stable during storage and assay procedure. Copyright © 2013. Published by Elsevier B.V.

Rational Design and Synthesis of Biologically Active Disubstituted 2(3H) Furanones and Pyrrolone Derivatives as Potent and Safer Non Steroidal Anti-inflammatory Agents.

PubMed

Khokra, S L; Khan, S A; Choudhary, D; Hasan, S M; Ahmad, A; Husain, Asif

2016-01-01

Furanone and pyrrolone heterocyclic ring system represent important and interesting classes of bioactive compounds. Medicinal chemists use these heterocycyclic moieties as scaffolds in drug design and discovery. A series of 3-arylidene-5-(naphthalene-2-yl)-furan-2(3H)-ones (2a-j) were synthesized by incorporating pharmacophore of COX-2 inhibitor rofecoxib and naphthyl ring of naproxen as potential non steroidal anti-inflammatory agents. These furanone derivatives were subsequently reacted with dry ammonia gas and benzylamine to furnish corresponding 3-arylidene-5-(naphthlen-2-yl)-1H-pyrrol-2(3H)-ones (3a-e) and 3-arylidene-1-benzyl-5- (naphthalene-2-yl)-1H-pyrrol-2(3H)-ones (4a-e), respectively. The newly prepared heterocyclics were screened for their expected in-vivo biological activities including anti-inflammatory, analgesic and ulcerogenic actions in rodents. The COX-2 inhibitory behavior of synthesized compounds was also assessed via automated docking studies. The chemical structure of the synthesized compounds was characterized by using modern spectroscopic techniques. Result of in-vivo pharmacological studies demonstrated that almost all N-Benzyl-pyrrol-2(3H)-ones (4a-e) showed better anti-inflammatory and analgesic activities in comparison with the other two series of furan-2(3H)-ones and pyrrol- 2(3H)-ones. The moldock score value of the tested compounds was found in the range of -116.66 to -170.328 and was better than the standard drug. Among all the synthesized compounds, only nine compounds (2d, 2g, 2h, 3d, 4a, 4b, 4c, 4d and 4e) exhibited potent anti-inflammatory and analgesic activities with significantly reduced gastrointestinal toxicity in various animal models in comparison to standard drug, diclofenac. Therefore, it is recommended to explore the potential of the synthesized compounds as lead candidates for the development of new therapeutic agents.

Critical role of free cytosolic calcium, but not uncoupling, in mitochondrial permeability transition and cell death induced by diclofenac oxidative metabolites in immortalized human hepatocytes

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

Lim, M.S.; Lim, Priscilla L.K.; Gupta, Rashi

2006-12-15

Diclofenac is a widely used nonsteroidal anti-inflammatory drug that has been associated with rare but serious hepatotoxicity. Experimental evidence indicates that diclofenac targets mitochondria and induces the permeability transition (mPT) which leads to apoptotic cell death in hepatocytes. While the downstream effector mechanisms have been well characterized, the more proximal pathways leading to the mPT are not known. The purpose of this study was to explore the role of free cytosolic calcium (Ca{sup 2+} {sub c}) in diclofenac-induced cell injury in immortalized human hepatocytes. We show that exposure to diclofenac caused time- and concentration-dependent cell injury, which was prevented bymore » the specific mPT inhibitor cyclosporin A (CsA, 5 {mu}M). At 8 h, diclofenac caused increases in [Ca{sup 2+}]{sub c} (Fluo-4 fluorescence), which was unaffected by CsA. Combined exposure to diclofenac/BAPTA (Ca{sup 2+} chelator) inhibited cell injury, indicating that Ca{sup 2+} plays a critical role in precipitating mPT. Diclofenac decreased the mitochondrial membrane potential, {delta}{psi}{sub m} (JC-1 fluorescence), even in the presence of CsA or BAPTA, indicating that mitochondrial depolarization was not a consequence of the mPT or elevated [Ca{sup 2+}]{sub c}. The CYP2C9 inhibitor sulphaphenazole (10 {mu}M) protected from diclofenac-induced cell injury and prevented increases in [Ca{sup 2+}]{sub c}, while it had no effect on the dissipation of the {delta}{psi}{sub m}. Finally, diclofenac exposure greatly increased the mitochondria-selective superoxide levels secondary to the increases in [Ca{sup 2+}]{sub c}. In conclusion, these data demonstrate that diclofenac has direct depolarizing effects on mitochondria which does not lead to cell injury, while CYP2C9-mediated bioactivation causes increases in [Ca{sup 2+}]{sub c}, triggering the mPT and precipitating cell death.« less

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

PubMed Central

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

2012-01-01

Objective To evaluate anti-inflammatory potential of leaf extract of Skimmia anquetilia by in-vitro and in-vivo anti-inflammatory models. Methods Acute toxicity study was carried out to determine the toxicity level of different extract using acute toxic class method as described in Organization of Economic Co-operation and Development Guidelines No.423. Carrageenan (1% w/w) was administered and inflammation was induced in rat paw. The leaf extracts of Skimmia anquetilia were evaluated for anti-inflammatory activity by in-vitro human red blood cell (HRBC) membrane stabilization method and in-vivo carrangeenan-induced rat paw edema method. Results The in-vitro membrane stabilizing test showed petroleum ether (PE), chloroform (CE), ethyl acetate (EE), methanol (ME) and aqueous extracts (AE) showed 49.44%, 59.39%, 60.15%, 68.40% and 52.18 % protection, respectively as compared to control groups. The in-vivo results of CE, EE and ME showed 58.20%, 60.17% and 67.53% inhibition of inflammation after 6h administration of test drugs in albino rats. The potency of the leaf extracts of Skimmia anquetilia were compared with standard diclofenac (10 mg/kg) which showed 74.18% protection in in-vitro HRBC membrane stabilization test and 71.64% inhibition in in-vivo carrangeenan-induced rat paw edema model. The ME showed a dose dependent significant (P< 0.01) anti-inflammatory activity in human red blood cell membrane stabilization test and reduction of edema in carrageenan induced rat paw edema. Conclusions The present investigation has confirmed the anti-inflammatory activity of Skimmia anquetilia due to presence of bioactive phytoconstitutes for the first time and provide the pharmacological evidence in favor of traditional claim of Skimmia anquetilia as an anti- inflammatory agent. PMID:23569983

Soluble Dietary Fiber Can Protect the Gastrointestinal Mucosa Against Nonsteroidal Anti-Inflammatory Drugs in Mice.

PubMed

Satoh, Hiroshi; Urushidani, Tetsuro

2016-07-01

Nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal damage is a serious problem in patients, but effective therapy is not available at present. The effects of feeding conditions and dietary fiber (DF) on NSAID-induced gastrointestinal lesions were examined in mice. NSAIDs (indomethacin, diclofenac, loxoprofen, aspirin) were administered to male mice in various feeding conditions. Gastrointestinal lesions were examined 24 h after NSAID dosing. Regular diets, dietary-fiber-free diet (FFD), and diets supplemented with various types of DF were given to mice. NSAIDs produced marked ulcers and perforations selectively in the gastric antrum when they were administered after feeding of regular diet for 2 h after a 22-h fast. When NSAIDs, except for aspirin, were administered in unfasted conditions, they caused marked lesions in the small intestine. When mice were given FFD, antral ulcers and intestinal lesions induced by indomethacin (30 mg/kg, s.c.) markedly decreased, but when cellulose, an insoluble DF, was added to FFD, the lesions appeared again. The addition of pectin, a soluble DF, to regular diet containing 4.1 % crude fiber significantly inhibited the formation of antral ulcers as well as intestinal lesions caused by indomethacin or diclofenac (100 mg/kg, s.c.). The results indicated that NSAIDs given after feeding of diet produced ulcers selectively in the gastric antrum. The severity of the gastrointestinal lesions depended on the concentration of soluble or insoluble DF in food. Our results suggest that soluble DF such as pectin may be a safe means for protecting the gastrointestinal mucosa against NSAIDs.

Metabolic and Co-Metabolic Transformation of Diclofenac by Enterobacter hormaechei D15 Isolated from Activated Sludge.

PubMed

Aissaoui, Salima; Ouled-Haddar, Houria; Sifour, Mohamed; Harrouche, Kamel; Sghaier, Haitham

2017-03-01

The presence of non-steroidal anti-inflammatory drugs, such as diclofenac (DCF), in the environment, is an emerging problem due to their harmful effects on non-target organisms, even at low concentrations. We studied the biodegradation of DCF by the strain D15 of Enterobacter hormaechei. The strain was isolated from an activated sludge, and identified as E. hormaechei based on its physiological characteristics and its 16 S RNA sequence. Using HPTLC and GC-MS methods, we demonstrated that this strain metabolized DCF at an elimination rate of 52.8%. In the presence of an external carbon source (glucose), the elimination rate increased to approximately 82%. GC-MS analysis detected and identified one metabolite as 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one; it was produced as a consequence of dehydration and lactam formation reactions.

[Antioxidant and anti-inflammatory activities of Moroccan Erica arborea L].

PubMed

Amezouar, F; Badri, W; Hsaine, M; Bourhim, N; Fougrach, H

2013-12-01

The present study was carried out to evaluate the antioxidant and anti-inflammatory capacity, and acute toxicity of Moroccan Erica arborea leaves. Antioxidant capacity was assessed by diphenyle-picryl-hydrazyl (DPPH), phosphomolybdate (PPM) and ferric reducing antioxidant power (FRAP) tests and anti-inflammatory capacity was evaluated by hind paw oedema model using carrageenan-induced inflammation in rat. The acute toxicity was evaluated using mice. Acute toxicity of ethanolic extract of E. arborea showed no sign of toxicity at dose of 5 g/kg B.W. Our extracts have important antioxidant properties. The efficient concentration of the ethanolic extract (10.22 μg/ml) required for decreasing initial DPPH concentration by 50% was comparable to that of standard solution butyl-hydroxy-toluene (BHT) (8.87 μg/ml). The administration of ethanolic extract at doses of 200 and 400mg/kg B.W. was able to prevent plantar oedema and exhibited a significant inhibition against carrageenan-induced inflammation when compared to the control group (NaCl 0.9%) but comparable to those of diclofenac (reference drug). Our results show that the leaves of E. arborea may contain some bioactive compounds which are responsible for the antioxidant and anti-inflammatory activities observed here. Our finding may indicate the possibility of using the extracts of this plant to prevent the antioxidant and inflammatory processes. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Skin permeability and local tissue concentrations of nonsteroidal anti-inflammatory drugs after topical application.

PubMed

Singh, P; Roberts, M S

1994-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are being administered increasingly by transdermal drug delivery for the treatment of local muscle inflammation. The human epidermal permeabilities of different NSAIDs (salicylic acid, diethylamine salicylate, indomethacin, naproxen, diclofenac and piroxicam) from aqueous solutions is dependent on the drug's lipophilicity. A parabolic relationship was observed when the logarithms of NSAID permeability coefficients were plotted against the logarithms of NSAID octanol-water partition coefficients (log P), the optimum log P being around 3. The local tissue concentrations of these drugs after dermal application in aqueous solutions were then determined in a rat model. The extent of local, as distinct from systemic delivery, for each NSAID was assessed by comparing the tissue concentrations obtained below a treated site to those in contralateral tissues. Local direct penetration was evident for all NSAIDs up to a depth of about 3 to 4 mm below the applied site, with distribution to deeper tissues being mainly through the systemic blood supply. A comparison of the predicted tissue concentrations of each NSAID after its application to human epidermis was then made by a convolution of the epidermal and underlying tissue concentration-time profiles. The estimated tissue concentrations after epidermal application of NSAIDs could be related to their maximal fluxes across epidermis from an applied vehicle.

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

PubMed Central

Boukhatem, Mohamed Nadjib; Ferhat, Mohamed Amine; Kameli, Abdelkrim; Saidi, Fairouz; Kebir, Hadjer Tchoketch

2014-01-01

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 the treatment of fungal infections and skin inflammation that should be explored in future studies. PMID:25242268

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

PubMed

Boukhatem, Mohamed Nadjib; Ferhat, Mohamed Amine; Kameli, Abdelkrim; Saidi, Fairouz; Kebir, Hadjer Tchoketch

2014-01-01

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 the treatment of fungal infections and skin inflammation that should be explored in future studies.

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

PubMed

Boukhatem, Mohamed Nadjib; Ferhat, Mohamed Amine; Kameli, Abdelkrim; Saidi, Fairouz; Kebir, Hadjer Tchoketch

2014-01-01

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. 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. 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. 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. RESULTS of the present study indicate that LGEO has a noteworthy potential for the development of drugs for the treatment of fungal infections and skin inflammation that should be explored in future studies.

Solid Lipid Nanoparticles of Guggul Lipid as Drug Carrier for Transdermal Drug Delivery

PubMed Central

Gaur, Praveen Kumar; Mishra, Shikha; Purohit, Suresh

2013-01-01

Diclofenac sodium loaded solid lipid nanoparticles (SLNs) were formulated using guggul lipid as major lipid component and analyzed for physical parameters, permeation profile, and anti-inflammatory activity. The SLNs were prepared using melt-emulsion sonication/low temperature-solidification method and characterized for physical parameters, in vitro drug release, and accelerated stability studies, and formulated into gel. Respective gels were compared with a commercial emulgel (CEG) and plain carbopol gel containing drug (CG) for ex vivo and in vivo drug permeation and anti-inflammatory activity. The SLNs were stable with optimum physical parameters. GMS nanoparticle 1 (GMN-1) and stearic acid nanoparticle 1 (SAN-1) gave the highest in vitro drug release. Guggul lipid nanoparticle gel 3 (GLNG-3) showed 104.68 times higher drug content than CEG in receptor fluid. The enhancement ratio of GLNG-3 was 39.43 with respect to CG. GLNG-3 showed almost 8.12 times higher C max than CEG at 4 hours. The AUC value of GLNG-3 was 15.28 times higher than the AUC of CEG. GLNG-3 showed edema inhibition up to 69.47% in the first hour. Physicochemical properties of major lipid component govern the properties of SLN. SLN made up of guggul lipid showed good physical properties with acceptable stability. Furthermore, it showed a controlled drug release profile along with a promising permeation profile. PMID:24058913

Photodegradation kinetics, transformation, and toxicity prediction of ketoprofen, carprofen, and diclofenac acid in aqueous solutions.

PubMed

Li, Jian; Ma, Li-Yun; Li, Lu-Shuang; Xu, Li

2017-12-01

Photodegradation of 3 commonly used nonsteroidal anti-inflammatory drugs, ketoprofen, carprofen, and diclofenac acid, was conducted under ultraviolet (UV) irradiation. The kinetic results showed that the 3 pharmaceuticals obeyed the first-order reaction with decreasing rate constants of 1.54 × 10 -4 , 5.91 × 10 -5 , and 7.78 × 10 -6  s -1 for carprofen, ketoprofen, and diclofenac acid, respectively. Moreover, the main transformation products were identified by ion-pair liquid-liquid extraction combined with injection port derivatization-gas chromatography-mass spectrometry and high-performance liquid chromatography-quadrupole-time of flight mass spectrometric analysis. There were 8, 3, and 6 transformation products identified for ketoprofen, carprofen, and diclofenac acid, respectively. Decarboxylation, dechlorination, oxidation, demethylation, esterification, and cyclization were proposed to be associated with the transformation of the 3 pharmaceuticals. Toxicity prediction of the transformation products was conducted on the EPI Suite software based on ECOSAR model, and the results indicate that some of the transformation products were more toxic than the parent compounds. The present study provides the foundation to understand the transformation behavior of the studied pharmaceuticals under UV irradiation. Environ Toxicol Chem 2017;36:3232-3239. © 2017 SETAC. © 2017 SETAC.

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

PubMed

McGettigan, Patricia; Henry, David

2011-09-01

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. 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 cardiovascular disease and rose early in the course of treatment. This review suggests that among widely used NSAIDs, naproxen and low-dose ibuprofen are least likely to increase cardiovascular risk. Diclofenac in doses available without prescription elevates risk. The data for etoricoxib were sparse, but in pair-wise comparisons this drug had a significantly higher RR than naproxen or ibuprofen. Indomethacin is an older, rather toxic drug, and the evidence on cardiovascular risk casts doubt on its continued clinical use. Please see later in the article for the Editors' Summary.

Non-steroidal Anti-inflammatory Drugs in Raptors

USGS Publications Warehouse

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.

The extraction of aromatic carboxylic acids by the copper complex with Curtis macrocyclic tetramine and its utilization for photometric determination of nonsteroidal anti-inflammatory drugs.

PubMed

Zseltvay, Ivan; Zheltvay, Olga; Antonovich, Valerij

2011-01-01

Copper complex with Curtis macrocyclic tetramine is offered as reagent for extraction-photometric determination of nonsteroidal anti-inflammatory drugs (NSAIDs), belonging to the class of aromatic carboxylic acids. The studies indicate that this method is suitable for quantitative determination of NSAIDs, which have the constant distribution in the system chloroform/water (log P) no less than 3 and dissolubility in chloroform (S) no less than 10 mg/mL. Under optimum conditions, there are liner relationships between the absorption of chloroform extracts and concentration of NSAID in the range of 0.2-4 mg/mL for indometacin (Ind), 0.2-3 mg/mL for mefenamic acid (Mef) and 0.5-3 mg/mL for diclofenac (Dic). The detection limits (S/N = 3) of Ind, Mef and Dic are 0.2, 0.1 and 0.15 mg/mL, respectively. With the help of calculating method (SPARC V4.2) it was predicted the possibility of utilization of this method for extractive-photometric determination of its detached specimen NSAID.

[Consumption of nonsteroidal anti-inflammatory agents in primary care in Costa Rica: changing patterns and geographical variability].

PubMed

Morera Salas, Melvin; Aparicio Llanos, Amada; Xirinachs Salazar, Yanira; Barber Pérez, Patricia

2007-01-01

To determine changing patterns and variability in consumption of classic nonsteroidal anti-inflammatory drugs (NSAIDs) among the health areas in Costa Rica between 2000 and 2005. The drugs studied were ibuprofen, indomethacin, penicillamine, sulindac, tenoxicam, and diclofenac sodium. To measure consumption, we used the defined daily dose per 1,000 inhabitants per day (DID). To analyze variability, the coefficient of variation weighed by the population size (CVw), extremal ratio, interquartile ratio, dot plot and map graphs were used. From 2000-2005, NSAID consumption increased by 48% and the annual cost rose by 184%. The drugs with greatest consumption and participation in cost were sulindac and indomethacin. NSAID consumption varied between 0.1 and 61.8 DID according to health areas, with a CVw of 66.8%. Variability was greatest with penicillamine (CVw = 449.89%) and tenoxicam (CVw = 315.26%). Clearly differentiated geographical patterns in NSAID consumption were found in Costa Rica, with very different rates within the same region. According to the results obtained, two factors associated with this variability were the supply of health services and the percentage of the population aged 65 years or more within the catchment area.

Grafting of GMA and some comonomers onto chitosan for controlled release of diclofenac sodium.

PubMed

Sharma, Rajeev Kr; Lalita; Singh, Anirudh P; Chauhan, Ghanshyam S

2014-03-01

In order to develop pH sensitive hydrogels for controlled drug release we have graft copolymerized glycidyl methacrylate (GMA) with comonomers acrylic acid, acrylamide and acrylonitrile, onto chitosan (Ch) by using potassium persulphate (KPS) as free radical initiator in aqueous solution. The optimum percent grafting for GMA was recorded for 1g chitosan at [KPS]=25.00 × 10(-3)mol/L, [GMA]=0.756 × 10(-3)mol/L, reaction temperature=60 °C and reaction time=1h in 20 mL H2O. Binary monomers were grafted for five different concentrations at optimum grafting conditions evaluated for GMA alone onto chitosan. The graft copolymers were characterized by FTIR, XRD, TGA and SEM. The swelling properties of chitosan and graft copolymers were investigated at different pH to define their end uses in sustained release of an anti-inflammatory drug, diclofenac sodium. Percent drug release w.r.t. drug loaded in polymeric sample was studied as function of time in buffer solutions of pH 2.0 and 7.4. In vitro release data was analyzed using Fick's Law. Chitosan grafted with binary monomers, GMA-co-AAm and GMA-co-AN showed very good results for sustained release of drug at 7.4 pH. Copyright © 2014 Elsevier B.V. All rights reserved.

Development of reconstitutable suspensions containing diclofenac sodium-loaded microspheres for pediatric delivery.

PubMed

Oz, Umut Can; Devrim, Burcu; Bozkır, Asuman; Canefe, Kandemir

2015-01-01

Effective clinical utilisation of non-steroidal anti-inflammatory drugs, such as diclofenac sodium (DS) is significantly limited by their ulcerogenic potential and poor bioavailability after oral administration. The objective of this work was to develop reconstitutable pediatric suspensions of DS-loaded microspheres prepared with an acrylic polymer (Eudragit RS) for improved pediatric delivery of DS. The microspheres were prepared by the water-in-oil-in-water or solid-in-oil-in-water emulsion techniques. Enviromental scanning electron microscopy observations clearly showed that microspheres have spherical shape. The drug entrapment efficiency of these microspheres was found 47.96 ± 0.79% to 88.57 ± 0.59% and their average particle sizes were 23.94-60.78 µm, which are within the desired range for the development of suspension formulation. The in vitro dissolution indicated prolonged sustained release of DS over 8 h. The results of preliminary characterisation studies of suspensions show that a liquid pharmaceutical preparation for oral administration capable of providing a sustained release of DS was successfully obtained.

Novel chitosan/diclofenac coatings on medical grade stainless steel for hip replacement applications

NASA Astrophysics Data System (ADS)

Finšgar, Matjaž; Uzunalić, Amra Perva; Stergar, Janja; Gradišnik, Lidija; Maver, Uroš

2016-05-01

Corrosion resistance, biocompatibility, improved osteointegration, as well the prevention of inflammation and pain are the most desired characteristics of hip replacement implants. In this study we introduce a novel multi-layered coating on AISI 316LVM stainless steel that shows promise with regard to all mentioned characteristics. The coating is prepared from alternating layers of the biocompatible polysaccharide chitosan and the non-steroid anti-inflammatory drug (NSAID), diclofenac. Electrochemical methods were employed to characterize the corrosion behavior of coated and uncoated samples in physiological solution. It is shown that these coatings improve corrosion resistance. It was also found that these coatings release the incorporated drug in controlled, multi-mechanism manner. Adding additional layers on top of the as-prepared samples, has potential for further tailoring of the release profile and increasing the drug dose. Biocompatibility was proven on human-derived osteoblasts in several experiments. Only viable cells were found on the sample surface after incubation of the samples with the same cell line. This novel coating could prove important for prolongation of the application potential of steel-based hip replacements, which are these days often replaced by more expensive ceramic or other metal alloys.

Novel chitosan/diclofenac coatings on medical grade stainless steel for hip replacement applications

PubMed Central

Finšgar, Matjaž; Uzunalić, Amra Perva; Stergar, Janja; Gradišnik, Lidija; Maver, Uroš

2016-01-01

Corrosion resistance, biocompatibility, improved osteointegration, as well the prevention of inflammation and pain are the most desired characteristics of hip replacement implants. In this study we introduce a novel multi-layered coating on AISI 316LVM stainless steel that shows promise with regard to all mentioned characteristics. The coating is prepared from alternating layers of the biocompatible polysaccharide chitosan and the non-steroid anti-inflammatory drug (NSAID), diclofenac. Electrochemical methods were employed to characterize the corrosion behavior of coated and uncoated samples in physiological solution. It is shown that these coatings improve corrosion resistance. It was also found that these coatings release the incorporated drug in controlled, multi-mechanism manner. Adding additional layers on top of the as-prepared samples, has potential for further tailoring of the release profile and increasing the drug dose. Biocompatibility was proven on human-derived osteoblasts in several experiments. Only viable cells were found on the sample surface after incubation of the samples with the same cell line. This novel coating could prove important for prolongation of the application potential of steel-based hip replacements, which are these days often replaced by more expensive ceramic or other metal alloys. PMID:27215333

Formulation and evaluation of bilayer tablets of metoclopramide hydrochloride and diclofenac sodium.

PubMed

Gattani, Surendra G; Khabiya, Sohan S; Amrutkar, Jitendra R; Kushare, Sachin S

2012-01-01

The main objective of the present research work was to develop a bilayer tablet of metoclopramide hydrochloride (MTH) and diclofenac sodium (DS) in separate layers to avoid incompatibility and thus to maximize the efficacy of both drugs in combination for the effective treatment of migraine headaches. MTH and DS were formulated as immediate and sustained release layers respectively. In vitro dissolution kinetic studies of an optimized (D10) batch of DS in both sustained release layer and bilayer tablet forms show good linearity of regression coefficient 0.9773 (first order equation). The results reveal that an optimized immediate release layer (M5) of MTH and a sustained release layer (D10) of DS might be suitable for the treatment of migraine by sequential release of the two drugs in a bilayer tablet. Migraine is a type of recurring headache of moderate to severe intensity associated with gastrointestinal, neurological, and autonomic symptoms. In migraine, a combination of pretreatment with antiemetics is required for symptomatic treatment, when nausea and vomiting are severe. In our present research, we have selected the metoclopramide hydrochloride (MTH) active ingredient for study because it has an antiemetic effect and is a prokinetic agent. MTH is more effective to counteract gastric stasis associated with migraine, and it enhances the rate of absorption of non-steroidal anti-inflammatory drugs (NSAIDs). In the present investigation we combine MTH and a second active ingredient, diclofenac sodium, as a formulated bilayer tablet to prevent degradation of MTH.

Once-daily, controlled-release tramadol and sustained-release diclofenac relieve chronic pain due to osteoarthritis: A randomized controlled trial

PubMed Central

Beaulieu, André D; Peloso, Paul M; Haraoui, Boulos; Bensen, William; Thomson, Glen; Wade, John; Quigley, Patricia; Eisenhoffer, John; Harsanyi, Zoltan; Darke, Andrew C

2008-01-01

OBJECTIVE: The present study was a randomized, parallel, double-blind comparison between controlled-release (CR) tramadol and sustained-release (SR) diclofenac in patients with chronic pain due to osteoarthritis of the hips and/or knees. METHODS: Patients with at least moderate pain intensity, and having received analgesics over the past three months, underwent a two-to seven-day washout of current analgesics before initiation of 200 mg CR tramadol or 75 mg SR diclofenac. During the eight-week study, patients returned to the clinic biweekly. CR tramadol doses were titrated to a maximum of 200 mg, 300 mg or 400 mg per day. SR diclofenac doses were titrated to 75 mg or 100 mg once daily, or 75 mg twice a day based on pain relief and the presence of side effects. For rescue analgesic, patients took acetaminophen as needed, up to 650 mg three times a day. RESULTS: Forty-five patients on CR tramadol and 52 patients on SR diclofenac were evaluable. Significant improvements from prestudy treatment were shown for visual analogue scale pain (P=0.0001), stiffness (P<0.0005) and physical function (P=0.0001) scores for both treatments. There were no significant differences between the two treatments in the Western Ontario and McMaster Universities subscales, overall pain, pain and sleep, or the clinical effectiveness evaluation. Overall incidence of adverse events was similar in both groups, with more opioid-related adverse events with CR tramadol, and two serious adverse events occurring with the use of SR diclofenac. CONCLUSIONS: CR tramadol is as effective as SR diclofenac in the treatment of pain due to knee or hip osteoarthritis, with the potential for fewer of the serious side effects that characterize nonsteroidal anti-inflammatory drug administration. PMID:18443672

Rectal analgesia for the relief of perineal pain after childbirth: a randomised controlled trial of diclofenac suppositories.

PubMed

Dodd, Jodie M; Hedayati, Hedyeh; Pearce, Elizabeth; Hotham, Neil; Crowther, Caroline A

2004-10-01

To evaluate rectal diclofenac in the relief of perineal pain after trauma during childbirth. A randomised, double-blind trial. Delivery Suite, Women's and Children's Hospital, South Australia. Women with a second-degree (or greater) perineal tear or episiotomy. Women were randomly allocated to either diclofenac or placebo suppositories (Anusol), using a computer-generated randomisation schedule with stratification for parity and mode of birth. Treatment packs contained two x 100 mg diclofenac or two placebo suppositories, the first being inserted when suturing was complete, and the second 12-24 hours after birth. Women were asked to complete questionnaires at 24 and 48 hours after birth relating to their degree of perineal pain using the validated Short Form McGill Pain Questionnaire. Pain scores at 24 and 48 hours after birth. A total of 133 women were recruited, with 67 randomised to diclofenac suppositories and 66 to placebo. Women in the diclofenac group were significantly less likely to experience pain at 24 hours while walking (RR 0.8; 95% CI 0.6 to 1.0), sitting (RR 0.8; 95% CI 0.6 to 1.0), passing urine (RR 0.6; 95% CI 0.4 to 1.0) and on opening their bowels (RR 0.6; 95% CI 0.2 to 0.9) compared with those women who received placebo. These differences were not sustained 48 hours after birth. The use of rectal non-steroidal anti-inflammatory drug suppositories is a simple, effective and safe method of reducing the pain experienced by women following perineal trauma within the first 24 hours after childbirth.

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

PubMed Central

Cong, Lin; Lu, Xuelian

2016-01-01

Increasing drug resistance has brought enormous challenges to the management of Trichosporon spp. infections. The in vitro antifungal activities of non-steroidal anti-inflammatory drugs (NSAIDs) against Candida spp. and Cryptococcus spp. were recently discovered. In the present study, the in vitro interactions between three NSAIDs (aspirin, ibuprofen and diclofenac sodium) and commonly used antifungal agents (fluconazole, itraconazole, voriconazole, caspofungin and amphotericin B) against planktonic and biofilm cells of T. asahii were evaluated using the checkerboard microdilution method. The spectrophotometric method and the XTT reduction assay were used to generate data on biofilm cells. The fractional inhibitory concentration index (FICI) and the ΔE model were compared to interpret drug interactions. Using the FICI, the highest percentages of synergistic effects against planktonic cells (86.67%) and biofilm cells (73.33%) were found for amphotericin B/ibuprofen, and caspofungin/ibuprofen showed appreciable percentages (73.33% for planktonic form and 60.00% for biofilm) as well. We did not observe antagonism. The ΔE model gave consistent results with FICI (86.67%). Our findings suggest that amphotericin B/ibuprofen and caspofungin/ibuprofen combinations have potential effects against T. asahii. Further in vivo and animal studies to investigate associated mechanisms need to be conducted. PMID:27275608

Effects of low-level laser therapy (LLLT) and diclofenac (topical and intramuscular) as single and combined therapy in experimental model of controlled muscle strain in rats.

PubMed

de Paiva Carvalho, Rodrigo Leal; Leal-Junior, Ernesto Cesar Pinto; Petrellis, Maria Carla; Marcos, Rodrigo Labat; de Carvalho, Maria Helena Catelli; De Nucci, Gilberto; Lopes-Martins, Rodrigo Alvaro Brandão

2013-01-01

Muscle injuries represent ca 30% of sports injuries and excessive stretching of muscle causes more than 90% of injuries. Currently the most used treatments are nonsteroidal anti-inflammatory drugs (NSAIDs), however, in last years, low-level laser therapy (LLLT) is becoming an interesting therapeutic modality. The aim of this study was to evaluate the effect of single and combined therapies (LLLT, topical application of diclofenac and intramuscular diclofenac) on functional and biochemical aspects in an experimental model of controlled muscle strain in rats. Muscle strain was induced by overloading tibialis anterior muscle of rats. Injured groups received either no treatment, or a single treatment with topical or intramuscular diclofenac (TD and ID), or LLLT (3 J, 810 nm, 100 mW) 1 h after injury. Walking track analysis was the functional outcome and biochemical analyses included mRNA expression of COX-1 and COX-2 and blood levels of prostaglandin E2 (PGE2 ). All treatments significantly decreased COX-1 and COX-2 gene expression compared with injury group (P < 0.05). However, LLLT showed better effects than TD and ID regarding PGE2 levels and walking track analysis (P < 0.05). We can conclude that LLLT has more efficacy than topical and intramuscular diclofenac in treatment of muscle strain injury in acute stage. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

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

PubMed

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.

Electrochemical incineration of diclofenac in neutral aqueous medium by anodic oxidation using Pt and boron-doped diamond anodes.

PubMed

Brillas, Enric; Garcia-Segura, Sergi; Skoumal, Marcel; Arias, Conchita

2010-04-01

The degradation of diclofenac, a common non-steroidal anti-inflammatory drug, in aqueous medium has been studied by anodic oxidation (AO) using an undivided cell with a Pt or boron-doped diamond (BDD) anode. Operating without pH regulation, AO with Pt acidifies the solution with precipitation of its protonated form, whereas using BDD, the solution becomes alkaline and only attains partial mineralization. Total incineration of low contents of the drug is feasible by AO with BDD in a neutral buffer medium of pH 6.5. Comparative treatment with Pt gives poor decontamination. The diclofenac decay always follows a pseudo first-order reaction. The increase in current for AO with BDD accelerates the degradative process, but decreases its efficiency. 2-Hydroxyphenylacetic acid, 2,5-dihydroxyphenylacetic acid, 2,6-dichloroaniline and 2,6-dichlorohydroquinone have been identified as aromatic intermediates. For AO with Pt, high amounts of malic, succinic, tartaric and oxalic acids are accumulated in the bulk and the N-derivatives produced are rapidly destroyed with loss of NH4+. When BDD is employed, some carboxylic acids are also accumulated in small extent, with a larger persistence of oxalic and oxamic acids. The process involves the formation of different N-derivatives that slowly release NH4+ and NO3(-) ions. Chloride ion is lost in all cases. 2010 Elsevier Ltd. All rights reserved.

Anti-inflammatory effect of ethanolic extract of spine, skin and rind of Jack fruit peel - A comparative study.

PubMed

Meera, M; Ruckmani, A; Saravanan, R; Lakshmipathy Prabhu, R

2017-10-09

The present study was conducted to identify the chemical constituents and evaluate the anti-inflammatory activity of crude ethanolic extracts of spine, skin and rind of jack fruit (Artocarpus heterophyllus) peel. Polyphenol and flavonoid contents were assessed using Folin's Ciocalteu reagent and aluminium chloride methods which revealed 316, 355 and 382 mg tannic acid equivalent/g of polyphenol and 96.7, 131.6 and 164.6 mg quercetin equivalent/g of flavonoid in spine, skin and rind, respectively. Anti-inflammatory activity of all three extracts was comparable to diclofenac in vitro and in vivo studies. Skin exhibited maximum anti-inflammatory activity, rind had preferential inhibition on Cyclooxygenase-2 and spine and skin inhibited both Cyclooxygenase-1 and 2 in vitro.

Synthesis and anti-inflammatory activity of some benzofuran and benzopyran-4-one derivatives.

PubMed

Ragab, Fatma Abd El-Fattah; Eid, Nahed Mahmoud; Hassan, Ghaneya Sayed; Nissan, Yassin Mohammed

2012-01-01

New series of furosalicylic acids 3a-c, furosalicylanilides 6a-n, furobenzoxazines 8a-f, 1-benzofuran-3-arylprop-2-en-1-ones 12a,b, 6-(aryl-3-oxoprop-1-enyl)-4H-chromen-4-ones 16a-c and 6-[6-aryl-2-thioxo-2,5-dihydropyrimidin-4-yl]-4H-chromen-4-ones 17a-c were synthesized. Anti-inflammatory activity evaluation was performed using carrageenan-induced paw edema model in rats and prostaglandin E(2) (PGE(2)) synthesis inhibition activity. Some of the tested compounds revealed comparable activity with less ulcerogenic effect than Diclofenac at a dose 100 mg/kg. All the synthesized compounds were docked on the active site of cyclooxygenase-2 (COX-2) enzyme and most of them showed good interactions with the amino acids of the active site comparable to the interactions exhibited by Diclofenac.

Penetration and pharmacokinetics of non-steroidal anti-inflammatory drugs in rat prostate tissue.

PubMed

Yellepeddi, Venkata K; Radhakrishnan, Jayashree; Radhakrishnan, Rajan

2018-02-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) involves inflammation of the prostate and affects the quality of life of men of all ages. It is well reported in clinical studies that the treatment for CP/CPPS using nonsteroidal anti-inflammatory drugs (NSAIDs) produced favorable outcomes. However, currently, there are no guidelines on choice of the NSAIDs for the treatment of CP/CPPS. Therefore, in the current research study, we evaluated the prostate tissue penetration of four NSAIDs in rats to provide guidance on choice of NSAIDs for the treatment of CP/CPPS. Male Sprague-Dawley rats were administered orally with four NSAIDs viz. celecoxib, diclofenac, ibuprofen, and naproxen at 500 mg/kg dose. The animals were then sacrificed at various time points, and their prostate tissues were harvested. The NSAIDs were then extracted from the prostate tissues using liquid extraction technique, and their concentration in prostate tissue was quantified using high-performance liquid chromatography (HPLC). The prostate tissue penetration and related pharmacokinetic parameters were evaluated by non-compartmental analysis. The HPLC method for quantifying NSAIDs in prostate tissue resulted in single, sharp peaks without any interference and all validation parameters were within limits. Celecoxib showed the highest area under the curve (AUC) [146.50 ± 2.75 μg/mL*h] of all NSAID's. A two-factor analysis of variance (ANOVA) with replication indicated an overall statistically significant difference in the pharmacokinetic parameters for celecoxib, diclofenac, ibuprofen, and naproxen. This study for the first time reported the relative prostate tissue penetration of four NSAIDs. The pharmacokinetic data indicated that celecoxib has the highest penetration and retention in rat prostate tissues. Therefore, celecoxib may be considered as a better choice for the treatment CP/CPPS involving NSAIDs. © 2017 Wiley Periodicals, Inc.

Relative benefit-risk comparing diclofenac to other traditional non-steroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors in patients with osteoarthritis or rheumatoid arthritis: a network meta-analysis.

PubMed

van Walsem, Anneloes; Pandhi, Shaloo; Nixon, Richard M; Guyot, Patricia; Karabis, Andreas; Moore, R Andrew

2015-03-19

There is argument over the benefits and risks of drugs for treating chronic musculoskeletal pain. This study compared the efficacy, safety, and tolerability of diclofenac, ibuprofen, naproxen, celecoxib, and etoricoxib for patients with pain caused by osteoarthritis (OA) or rheumatoid arthritis (RA). A systematic literature review used Medline and EMBASE to identify randomised controlled trials. Efficacy outcomes assessed included: pain relief measured by visual analogue scale (VAS); Western Ontario McMaster Universities Arthritis Index (WOMAC) VAS or WOMAC Likert scale; physical functioning measured by WOMAC VAS or Likert scale; and patient global assessment (PGA) of disease severity measured on VAS or 5-point Likert scale. Safety outcomes included: Antiplatelet Trialists' Collaboration (APTC), major cardiovascular (CV) and major upper gastrointestinal (GI) events, and withdrawals. Data for each outcome were synthesized by a Bayesian network meta-analysis (NMA). For efficacy assessments, labelled doses for OA treatment were used for the base case while labelled doses for RA treatment were also included in the sensitivity analysis. Pooled data across dose ranges were used for safety. Efficacy, safety, and tolerability data were found for 146,524 patients in 176 studies included in the NMA. Diclofenac (150 mg/day) was likely to be more effective in alleviating pain than celecoxib (200 mg/day), naproxen (1000 mg/day), and ibuprofen (2400 mg/day), and similar to etoricoxib (60 mg/day); a lower dose of diclofenac (100 mg/day) was comparable to all other treatments in alleviating pain. Improved physical function with diclofenac (100 and 150 mg/day) was mostly comparable to all other treatments. PGA with diclofenac (100 and 150 mg/day) was likely to be more effective or comparable to all other treatments. All active treatments were similar for APTC and major CV events. Major upper GI events with diclofenac were lower compared to naproxen and ibuprofen, comparable to celecoxib, and higher than etoricoxib. Risk of withdrawal with diclofenac was lower compared to ibuprofen, similar to celecoxib and naproxen, and higher than etoricoxib. The benefit-risk profile of diclofenac was comparable to other treatments used for pain relief in OA and RA; benefits and risks vary in individuals and need consideration when making treatment decisions.

Efficacy of Combined Ultrasound-and-Microbubbles-Mediated Diclofenac Gel Delivery to Enhance Transdermal Permeation in Adjuvant-Induced Rheumatoid Arthritis in the Rat.

PubMed

Liao, Ai-Ho; Chung, Huan-Yu; Chen, Wen-Shiang; Yeh, Ming-Kung

2016-08-01

A previous study that investigated the effect of ultrasound (US) on the transdermal permeation of the non-steroidal anti-inflammatory drug diclofenac found that therapeutic US can increase circulation in an inflamed joint and decrease arthritic pain. Transdermal drug delivery has recently been demonstrated by US combined with microbubbles (MB) contrast agent (henceforth referred to as "US-MB"). The present study evaluated the efficacy of US-MB-mediated diclofenac delivery for treating adjuvant-induced rheumatoid arthritis (RA) in rats. RA was induced by injecting 100 μL of complete Freund's adjuvant into the ankle joint of male Sprague-Dawley rats (250-300 g) that were randomly divided into five treatment groups: (i) carbopol gel alone (the control [group C]), (ii) diclofenac-carbopol gel (group D), (iii) US plus carbopol gel (group U), (iv) US plus diclofenac-carbopol gel (group DU) and (v) US-MB plus diclofenac-carbopol gel (group DUB). The ankle width was measured over 10 d using high-frequency (40-MHz) US B-mode and color Doppler-mode imaging, covering the period before and after treatment. Longitudinal US images of the induced RA showed synovitis and neovascularity. Only a small amount of neovascularity was observed after treatment. The recovery rate on day 10 was significantly higher in group DUB (97.7% ± 2.7%, mean ± standard deviation [SD]) than in groups C (1.0% ± 2.7%), D (37.5% ± 4.6%), U (75.5% ± 4.2%) and DU (87.3% ± 5.2%) (p < 0.05). The results obtained indicate that combining US and MB can increase the skin permeability and thereby enhance the delivery of diclofenac sodium gel and thereby inhibit inflammation of the tissues surrounding the arthritic ankle. Color Doppler-mode imaging revealed that US-MB treatment induced a rapid reduction in synovial neoangiogenesis in the arthritic area. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2016-05-01

In recent years measurable concentrations of non-steroidal anti-inflammatory drugs (NSAIDs) have been shown in the aquatic environment as a result of increasing human consumption. Effects of five frequently used non-steroidal anti-inflammatory drugs (diclofenac, diflunisal, ibuprofen, mefenamic acid and piroxicam in 0.1 mg ml(-1) concentration) in batch cultures of cyanobacteria (Synechococcus elongatus, Microcystis aeruginosa, Cylindrospermopsis raciborskii), and eukaryotic algae (Desmodesmus communis, Haematococcus pluvialis, Cryptomonas ovata) were studied. Furthermore, the effects of the same concentrations of NSAIDs were investigated in natural algal assemblages in microcosms. According to the changes of chlorophyll-a content, unicellular cyanobacteria seemed to be more tolerant to NSAIDs than eukaryotic algae in laboratory experiments. Growth of eukaryotic algae was reduced by all drugs, the cryptomonad C. ovata was the most sensitive to NSAIDs, while the flagellated green alga H. pluvialis was more sensitive than the non-motile green alga D. communis. NSAID treatments had weaker impact in the natural assemblages dominated by cyanobacteria than in the ones dominated by eukaryotic algae, confirming the results of laboratory experiments. Diversity and number of functional groups did not change notably in cyanobacteria dominated assemblages, while they decreased significantly in eukaryotic algae dominated ones compared to controls. The results highlight that cyanobacteria (especially unicellular ones) are less sensitive to the studied, mostly hardly degradable NSAIDs, which suggest that their accumulation in water bodies may contribute to the expansion of cyanobacterial mass productions in appropriate environmental circumstances by pushing back eukaryotic algae. Thus, these contaminants require special attention during wastewater treatment and monitoring of surface waters. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cyto-genotoxicity and oxidative stress in common carp (Cyprinus carpio) exposed to a mixture of ibuprofen and diclofenac.

PubMed

Islas-Flores, Hariz; Manuel Gómez-Oliván, Leobardo; Galar-Martínez, Marcela; Michelle Sánchez-Ocampo, Esmeralda; SanJuan-Reyes, Nely; Ortíz-Reynoso, Mariana; Dublán-García, Octavio

2017-05-01

Thirty million people worldwide consume each day nonsteroidal anti-inflammatory drugs (NSAIDs), a heterogeneous group of pharmaceuticals used for its analgesic, antipyretic, and anti-inflammatory properties. Recent studies report high NSAID concentrations in wastewater treatment plant effluents, in surface, ground, and drinking water, and in sediments. NSAIDs are also known to induce toxicity on aquatic organisms. However, toxicity in natural ecosystems is not usually the result of exposure to a single substance but to a mixture of toxic agents, yet only a few studies have evaluated the toxicity of mixtures. The aim of this study was to evaluate the toxicity induced by diclofenac (DCF), ibuprofen (IBP), and their mixture on a species of commercial interest, the common carp Cyprinus carpio. The median lethal concentration of IBP and DCF was determined, and oxidative stress was evaluated using the following biomarkers: lipid peroxidation and activity of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase. Cyto-genotoxicity was evaluated by micronucleus test, comet assay, and the specific activity of caspase-3. Results show that DCF, IBP, and a mixture of these pharmaceuticals induced free radical production, oxidative stress and cyto-genotoxicity in tissues of C. carpio. However, a greater effect was elicited by the mixture than by either pharmaceutical alone in some biomarkers evaluated, particularly in gill. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1637-1650, 2017. © 2017 Wiley Periodicals, Inc.

The effect of topical diclofenac 3% and calcitriol 3 μg/g on superficial basal cell carcinoma (sBCC) and nodular basal cell carcinoma (nBCC): A phase II, randomized controlled trial.

PubMed

Brinkhuizen, Tjinta; Frencken, Kiki J A; Nelemans, Patty J; Hoff, Marlou L S; Kelleners-Smeets, Nicole W J; Zur Hausen, Axel; van der Horst, Michiel P J; Rennspiess, Dorit; Winnepenninckx, Véronique J L; van Steensel, Maurice A M; Mosterd, Klara

2016-07-01

Nonsteroidal anti-inflammatory drugs and vitamin-D derivatives can target signaling pathways activated in basal cell carcinoma (BCC). We investigated the efficacy of topically applied diclofenac sodium 3% gel, calcitriol 3 μg/g ointment, and a combination of both in superficial BCC (sBCC) and nodular BCC. Patients with a primary, histologically proven sBCC (n = 64) or nodular BCC (n = 64) were randomized to topical diclofenac, calcitriol, combination of both, or no topical treatment (control group). After self-application twice daily under occlusion (8 weeks), tumors were excised. Primary outcome was posttreatment expression levels of proliferation (Ki-67) and antiapoptosis (B-cell lymphoma [Bcl-2]) immunohistochemical markers. Secondary outcomes were histologic clearance, adverse events, application-site reactions, and patient compliance. sBCC treated with diclofenac showed a significant decrease in Ki-67 (P < .001) and Bcl-2 (P = .001), and after combination therapy for Ki-67 (P = .012). Complete histologic tumor regression was seen in 64.3% (P = .0003) of sBCC (diclofenac) and 43.8% (P = .007) of sBCC (combination therapy) compared with 0.0% of controls. No significant changes were found in nodular BCC. Application-site reactions were mostly mild to moderate. The sample size was small. Our results suggest that topical diclofenac is a promising new treatment for sBCC. Its mode of action differs from available noninvasive therapies, and thus has an additive value. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Effects of the pharmaceuticals gemfibrozil and diclofenac on biomarker expression in the zebra mussel (Dreissena polymorpha) and their comparison with standardised toxicity tests.

PubMed

Quinn, Brian; Schmidt, Wiebke; O'Rourke, Kathleen; Hernan, Robert

2011-07-01

Pharmaceuticals, including the lipid regulator gemfibrozil and the non-steroidal anti-inflammatory drug diclofenac have been identified in waste water treatment plant effluents and receiving waters throughout the western world. The acute and chronic toxicity of these compounds was assessed for three freshwater species (Daphnia magna, Pseudokirchneriella subcapitata, Lemna minor) using standardised toxicity tests with toxicity found in the non-environmentally relevant mid mg L(-1) concentration range. For the acute endpoints (IC(50) and EC(50)) gemfibrozil showed higher toxicity ranging from 29 to 59 mg L(-1) (diclofenac 47-67 mg L(-1)), while diclofenac was more toxic for the chronic D. magna 21 d endpoints ranging from 10 to 56 mg L(-1) (gemfibrozil 32-100 mg L(-1)). These results were compared with the expression of several biomarkers in the zebra mussel (Dreissena polymorpha) 24 and 96 h after exposure by injection to concentrations of 21 and 21,000 μg L(-1) corresponding to nominal concentrations of 1 and 1000 μg L(-1). Exposure to gemfibrozil and diclofenac at both concentrations significantly increased the level of lipid peroxidation, a biomarker of damage. At the elevated nominal concentration of 1000 μg L(-1) the biomarkers of defence glutathione transferase and metallothionein were significantly elevated for gemfibrozil and diclofenac respectively, as was DNA damage after 96 h exposure to gemfibrozil. No evidence of endocrine disruption was observed using the alkali-labile phosphate technique. Results from this suite of biomarkers indicate these compounds can cause significant stress at environmentally relevant concentrations acting primarily through oxidation pathways with significant destabilization of the lysosomal membrane and that biomarker expression is a more sensitive endpoint than standardised toxicity tests. Copyright © 2011 Elsevier Ltd. All rights reserved.

Implementing ecopharmacovigilance (EPV) from a pharmacy perspective: A focus on non-steroidal anti-inflammatory drugs.

PubMed

Wang, Jun; He, Bingshu; Yan, Dan; Hu, Xiamin

2017-12-15

Environmental experts have made great efforts to control pharmaceutical pollution. However, the control of emerged environmental problems caused by medicines should draw more attention of pharmacy and pharmacovigilance researchers. Ecopharmacovigilance (EPV) as a kind of pharmacovigilance for the environment is recognized worldwide as crucial to minimize the environmental risk of pharmaceutical pollutants. But continuing to treat the pollution of pharmaceuticals as a group of substances instead of targeting individual pharmaceuticals on a prioritized basis will lead to a significant waste of resources. Considering vulture population decline caused by non-steroidal anti-inflammatory drugs (NSAIDs) residues, we presented a global-scale analysis of 139 reports of NSAIDs occurrence across 29 countries, in order to provide a specific context for implementing EPV. We found a heavy regional bias toward research in Europe, Asia and America. The top 5 most frequently studied NSAIDs included ibuprofen, diclofenac, naproxen, acetaminophen and ketoprofen. The profile of NSAIDs was dominated by acetaminophen in wastewater influents and effluents. Ibuprofen was the most abundant NSAID in surface water. Only 9 NSAIDs were reported in groundwater samples. And majority of NSAIDs were detected in solid matrices at below 1μg/g except for ketoprofen, diclofenac and ibuprofen. From a pharmacy perspective, we get some implication and propose some management practice options for EPV implementation. These include: Further popularizing and applying the concept of EPV, together with developing relevant regulatory guidance, is necessary; More attention should be paid to how to implement EPV for the pollution control of older established drugs; Triggering "a dynamic watch-list mechanism" in conjunction with "source control"; Implementing targeted sewage treatment technologies and strengthening multidisciplinary collaboration; Pharmaceutical levels in aquatic organisms as biological indicators for monitoring pharmaceutical pollution within the water environment; Upgrading drinking water treatment plants with the aim of removing pharmaceutical residues; Paying more attention to EPV for pharmaceuticals in solid matrices. Copyright © 2017 Elsevier B.V. All rights reserved.

Cardiovascular Risk with Non-Steroidal Anti-Inflammatory Drugs: Systematic Review of Population-Based Controlled Observational Studies

PubMed Central

McGettigan, Patricia; Henry, David

2011-01-01

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 cardiovascular disease and rose early in the course of treatment. Conclusions This review suggests that among widely used NSAIDs, naproxen and low-dose ibuprofen are least likely to increase cardiovascular risk. Diclofenac in doses available without prescription elevates risk. The data for etoricoxib were sparse, but in pair-wise comparisons this drug had a significantly higher RR than naproxen or ibuprofen. Indomethacin is an older, rather toxic drug, and the evidence on cardiovascular risk casts doubt on its continued clinical use. Please see later in the article for the Editors' Summary PMID:21980265

Evaluation of anti-inflammatory and antimicrobial activity of AHPL/AYTOP/0213 cream

PubMed Central

Nipanikar, Sanjay U.; Nagore, Dheeraj; Chitlange, Soham S.; Buzruk, Devashree

2017-01-01

Background: Acne vulgaris is almost a widespread disease occurring in all races. Propionibacterium acnes initiate acne and inflammatory mediators aggravate it. Conventional therapies for acne include comedolytic, anti-inflammatory, and anti-biotic agents. Due to adverse effects of these therapies, people are searching for alternative options. In this context, a polyherbal formulation AHPL/AYTOP/0213 cream was developed for the treatment of Acne. Objective: The objective of this study is to study anti-inflammatory and antimicrobial activities of AHPL/AYTOP/0213 cream. Materials and Methods: Skin irritation study was conducted on AHPL/AYTOP/0213 cream as per OECD guidelines. (1) Anti-inflammatory activity: Anti-inflammatory activity of AHPL/AYTOP/0213 cream in comparison with diclofenac sodium cream was assessed in carrageenan-induced rat paw edema model. (2) Antimicrobial activity for P. acnes: P. acnes were incubated under anaerobic conditions. Aliquots of molten brain–heart infusion with glucose agar were used as the agar base. Formulation and clindamycin (10 mg/ml) were introduced in to the Agar wells randomly. (3) Antimicrobial activity for Staphylococcus epidermidis and Staphylococcus aureus: bacteria were incubated under aerobic conditions at 37°C. Tryptic soy broth with glucose agar was used as the agar base. A volume of 0.5 ml of formulation and clindamycin (10 mg/ml) were introduced in to the wells randomly. The antibacterial activity was evaluated by measuring zones of inhibition (in mm). Results: AHPL/AYTOP/0213 cream is nonirritant. Significant reduction in rat paw edema (43%) was observed with AHPL/AYTOP/0213 which was also comparable to diclofenac sodium cream (56.09%). Zone of inhibition for formulation was 20.68 mm, 28.20 mm, and 21.40 mm for P. acnes, S. epidermidis and S. aureus, respectively, which was comparable to clindamycin. The minimum inhibitory concentration of formulation AHPL/AYTOP/0213 obtained in anti-microbial study was 2.5 mg/mL. Conclusion: AHPL/AYTOP/0213 cream is nonirritant and possesses significant anti-inflammatory and antimicrobial activities, which further justifies its role in the management of acne vulgaris. PMID:29861599

Diclofenac affects kidney histology in the three-spined stickleback (Gasterosteus aculeatus) at low μg/L concentrations.

PubMed

Näslund, Johanna; Fick, Jerker; Asker, Noomi; Ekman, Elisabet; Larsson, D G Joakim; Norrgren, Leif

2017-08-01

Diclofenac, a commonly used non-steroidal anti-inflammatory drug, is considered for regulation under the European water framework directive. This is because effects on fish have been reported at concentrations around those regularly found in treated sewage effluents (∼1μg/L). However, a recent publication reports no effects on fish at 320μg/L. In this study, three-spined sticklebacks (Gasterosteus aculeatus) were exposed to 0, 4.6, 22, 82 and 271μg/L diclofenac in flow-through systems for 28days using triplicate aquaria per concentration. At the highest concentration, significant mortalities were observed already after 21days (no mortalities found up to 22μg/L). Histological analysis revealed a significant increase in the proportion of renal hematopoietic tissue (renal hematopoietic hyperplasia) after 28days at the lowest concentration and at all higher concentrations, following a clear dose-response pattern. Skin ulcerations of the jaw were noted by macroscopic observations, primarily at the two highest concentrations. No histological changes were observed in the liver. There was an increase in the relative hepatic mRNA levels of c7 (complement component 7), a gene involved in the innate immune system, at 22μg/L and at all higher concentrations, again following a clear dose-response. The bioconcentration factor was stable across concentrations, but lower than reported for rainbow trout, suggesting lower internal exposure to the drug in the stickleback. In conclusion, this study demonstrates that diclofenac causes histological changes in the three-spined stickleback at low μg/L concentrations, which cause concern for fish populations exposed to treated sewage effluents. Copyright © 2017 Elsevier B.V. All rights reserved.

[Use of topical non-steroidal anti-inflammatory agents in an urban health center. Comparison with the current evidence].

PubMed

Yagüe-Sebastián, M M; Coscollar-Escartín, I; Muñoz-Albadalejo, P; López-Canales, M C; Villaverde-Royo, M V; Gutiérrez-Moreno, F

2013-09-01

To describe the prescribing of topical non-steroidal anti-inflammatory drugs (NSAIDs) in an urban health center (Zaragoza, Spain). A cross-sectional descriptive study was conducted on subjects who belonged to an urban center and were studied during the year 2010. The sample size with a confidence level of 95%, was calculated, a total of 843 prescriptions were analyzed. The sample was single random, and 150 cases were selected. The prevalence and confidence intervals were calculated. The statistical package STATA 9.1 was used for the calculations. The most used drug was diclofenac, in 27.33% (95% CI: 20.65-34.88). NSAIDs were most used in females. In 18% of the cases the area of application was the knee, followed by the 15% in the lower back area (95% CI: 10,22-21,78). There were no adverse reactions. Frequent use is made of topical NSAIDs in a basic health area. Current recommendations support the use in the knee and in the hand, but not in the back, where its use is common. The use of topical NSAIDs decreases side effects and drug interactions, therefore their use is recommended in patients on multiple drug therapy and in the elderly. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Non-steroidal Anti-inflammatory Drugs Attenuate Hyperalgesia and Block Upregulation of Trigeminal Ganglionic Sodium Channel 1.7 after Induction of Temporomandibular Joint Inflammation in Rats.

PubMed

Bi, Rui Yun; Ding, Yun; Gan, Ye Hua

2016-03-01

To investigate the association between the analgesic effect of non-steroidal antiinflammatory drugs (NSAIDs) and sodium channel 1.7 (Nav1.7) expression in the trigeminal ganglion (TG). Temporomandibular joint (TMJ) inflammation was induced by complete Freund's adjuvant (CFA) in female rats. Ibuprofen, diclofenac sodium and meloxicam were given intragastrically before induction of TMJ inflammation. Histopathological evaluation and scoring of TMJ inflammation was used to evaluate the level of inflammation. The head withdrawal threshold and food intake were measured to evaluate TMJ nociceptive responses. The mRNA and protein expression of trigeminal ganglionic Nav1.7 was examined using real-time polymerase chain reaction and western blot. Twenty-four hours after the injection of CFA into the TMJs, NSAIDs attenuated hyperalgesia of inflamed TMJ and simultaneously blocked inflammation-induced upregulation of Nav1.7 mRNA and protein expression in the TG. However, ibuprofen and diclofenac sodium slightly attenuated TMJ inflammation and meloxicam did not affect TMJ inflammation. Attenuation of hyperalgesia of inflamed TMJ by NSAIDs might be associated with their role in blocking upregulation of trigeminal ganglionic Nav1.7.

Preliminary study of highly cross-linked hyaluronic acid-based combination therapy for management of knee osteoarthritis-related pain

PubMed Central

Palmieri, Beniamino; Rottigni, Valentina; Iannitti, Tommaso

2013-01-01

Background Hyaluronic acid has been extensively used for treatment of knee osteoarthritis due to its anti-inflammatory properties and its ability to act as a synovial lubricant. Furthermore, it has found application in combination with other drugs in the dermatological field and in pre-clinical studies in animal models of osteoarthritis. Experimental evidence suggests that a combination of this macromolecule with other drugs may act as a slow-release depot. However, to date, to the best of our knowledge, no one has tested local intra-articular delivery of highly cross-linked hyaluronic acid combined with bisphosphonate or nonsteroidal anti-inflammatory drugs for management of knee osteoarthritis pain in the clinical setting. The aim of the present randomized double-blind study was to investigate, for the first time, the effect of a highly cross-linked hyaluronic acid, Variofill®, alone or in combination with diclofenac sodium or sodium clodronate, for management of bilateral knee osteoarthritis-related pain. Methods Sixty-two patients with symptomatic bilateral medial tibiofemoral knee osteoarthritis (Kellgren–Lawrence grade II and III) and pain in both knees corresponding to a daily visual analog scale (VAS) score ≥ 30 in the month before the beginning of the study were included in this investigation. Patients were divided into three groups: group 1, treated with an injection of hyaluronic acid alone (66 mg) into each knee; group 2, treated with an injection of hyaluronic acid (49.5 mg) plus diclofenac sodium (5 mg) into each knee; group 3, treated with an injection of hyaluronic acid (49.5 mg) plus sodium clodronate (5 mg) into each knee. Patients also underwent blood tests for measurement of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) immediately before and at 6-month follow-up. Results Hyaluronic acid alone and in combination with sodium clodronate or diclofenac sodium produced a significant improvement in mean VAS pain score at 3 and 6-month follow-up. At 6-month follow-up, therapy with hyaluronic acid plus sodium clodronate was the most beneficial in terms of percentage improvement in VAS pain score. A significant improvement in ESR and CRP was observed at 6-month follow-up in each treatment group. No significant difference was observed when the percentage change from baseline related to these parameters was compared among the groups. No dropout was observed in any group. No serious adverse events were observed. Conclusion Further studies are necessary to determine the effect of a therapy based on hyaluronic acid combined with diclofenac sodium or sodium clodronate in larger cohorts of patients affected by knee osteoarthritis and in longer-term follow-up. PMID:23326188

[Effects of lysine clonixinate on platelet function. Comparison with other non-steroidal anti-inflammatory agents].

PubMed

Kramer, E H; Sassetti, B; Kaminker, A J; De Los Santos, A R; Martí, M L; Di Girolamo, G

2001-01-01

One of the mechanisms of action of non steroid antiinflammatory drugs (NSAIDs) consists of inhibition of prostaglandin synthesis. This explains many of the pharmacological effects and adverse events observed in medical practice. Administration of NSAIDs to patients with hemostatic disorders or perioperative conditions entails the risk of bleeding due to inhibition of platelet function. This study deals with platelet changes induced by lysine clonixinate vs diclofenac, ibuprofen and aspirin in classical tests such as platelet count, platelet factor 3 (PF3) activity and platelet aggregation with various inductors and more recent procedures such as P-selectin measurement by flow cytometry. Unlike control drugs, lysine clonixinate did not induce changes in platelet count or function when administered to healthy volunteers at the commonly used therapeutic doses.

Antinociceptive efficacy of lacosamide in the monosodium iodoacetate rat model for osteoarthritis pain

PubMed Central

Beyreuther, Bettina; Callizot, Noëlle; Stöhr, Thomas

2007-01-01

The etiology of osteoarthritis is multifactorial, with inflammatory, metabolic, and mechanical causes. Pain in osteoarthritis is initiated by mild intra-articular inflammation and degeneration of articular cartilage and subchondral bone. The principle of treatment with acetaminophen or non-steroidal anti-inflammatory drugs is to reduce pain and improve joint function. Recently, animal models for osteoarthritic pain behavior have been established. The most frequently used rat model for analyzing properties of drugs on the pathology of osteoarthritis is the injection of the metabolic inhibitor monosodium iodoacetate into the joint, which inhibits the activity of glyceraldehyde-3-phosphate dehydrogenase in chondrocytes. Here, we characterize the effect on pain behavior of lacosamide, a member of a family of functionalized amino acids that are analogues of endogenous amino acids and D-serine, in the monosodium iodoacetate rat model for osteoarthritis in comparison to diclofenac and morphine. Lacosamide (3, 10, and 30 mg/kg) was able to reduce secondary mechanical allodynia and hyperalgesia similarly to morphine (3 mg/kg). In contrast, diclofenac (30 mg/kg) was only effective in reducing secondary mechanical hyperalgesia. During the first week, pain is induced mainly by inflammation in the iodoacetate model, but afterwards inflammation plays only a minor role in pain. Lacosamide was able to inhibit pain at days 3, 7 and 14 after induction of arthritis. This shows that lacosamide is able to reduce pain behavior induced by multiple mechanisms in animals. PMID:17284318

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

PubMed

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 < 0.0001). NSAIDs were replaced with triptans in 53% of patients at first visit; after 1 year there was a spontaneous significant return to NSAIDs (56%; P < 0.0005). Among TTH patients, 90% were NSAID users; preferences were: nimesulide (48%), ketoprofen (47%), and diclofenac (19%), with significantly higher complete vs. incomplete/absent efficacy (nimesulide and ketoprofen, P < 0.02). Replacement with analgesics was performed in 24% of patients; after 1 year, there was a 29% return to NSAIDs. Among migraine plus TTH patients, 89% were NSAID users. Preferences were: nimesulide (44%), ibuprofen (42%), and ketoprofen (38%), with significantly higher complete vs. incomplete/absent efficacy (0.001 < P < 0.0001). Replacement with analgesics was performed in 31% of patients; after 1 year, there was a 37% return to NSAIDs. Nonsteroidal anti-inflammatory drug use in 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.

Efficacy of a comfrey root extract ointment in comparison to a diclofenac gel in the treatment of ankle distortions: results of an observer-blind, randomized, multicenter study.

PubMed

Predel, H G; Giannetti, B; Koll, R; Bulitta, M; Staiger, C

2005-11-01

In the treatment of minor blunt injuries several topical drugs are known to have anti-inflammatory and analgesic properties. They represent, however, two fundamentally different major pharmacological therapy approaches: the "chemical-synthetical" and the "phytotherapeutical" approach. The main objective of this trial (CODEC_2004) was to compare the efficacy and tolerability of an ointment of Comfrey extract (Extr. Rad. Symphyti) with that of a Diclofenac gel in the treatment of acute unilateral ankle sprain (distortion). In a single-blind, controlled, randomized, parallel-group, multicenter and confirmatory clinical trial outpatients with acute unilateral ankle sprains (n=164, mean age 29.0 years, 47.6% female) received either a 6 cm long ointment layer of Kytta-Salbe f (Comfrey extract) (n=82) or of Diclofenac gel containing 1.16 g of diclofenac diethylamine salt (n=82) for 7 +/- 1 days, four times a day. Primary variable was the area-under-the-curve (AUC) of the pain reaction to pressure on the injured area measured by a calibrated caliper (tonometer). Secondary variables were the circumference of the joint (swelling; figure-of-eight method), the individual spontaneous pain sensation at rest and at movement according to a Visual Analogue Scale (VAS), the judgment of impaired movements of the injured joint by the method of "neutral-zero", consumption of rescue medication (paracetamol), as well as the global efficacy evaluation and the global assessment of tolerability (both by physician and patient, 4 ranks). In this study the primary variable was also to be validated prospectively. It was confirmatorily shown that Comfrey extract is non-inferior to diclofenac. The 95% confidence interval for the AUC (Comfrey extract minus Diclofenac gel) was 19.01-103.09h*N/cm2 and was completely above the margin of non-inferiority. Moreover, the results of the primary and secondary variables indicate that Comfrey extract may be superior to Diclofenac gel.

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

PubMed

Fournier, Jean-Pascal; Lapeyre-Mestre, Maryse; Sommet, Agnès; Dupouy, Julie; Poutrain, Jean-Christophe; Montastruc, Jean-Louis

2012-01-01

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

A Double-Blind Placebo-Controlled Comparison of a Novel Formulation of Intravenous Diclofenac and Ketorolac for Postoperative Third Molar Extraction Pain

PubMed Central

Christensen, Kyle; Daniels, Stephen; Bandy, Donald; Ernst, Cynthia C.; Hamilton, Douglas A.; Mermelstein, Fred H.; Wang, Jianyuan; Carr, Daniel B.

2011-01-01

Dyloject is a novel formulation of diclofenac intended for intravenous (IV) administration. This formulation employs the solubilizing agent hydroxypropyl-β-cyclodextrin to permit bolus IV administration. The efficacy and safety of 5 dose levels of IV diclofenac were compared with IV ketorolac and placebo following third molar extraction. This was a single-dose, randomized, double-blind, placebo- and comparator-controlled, parallel-group study. A total of 353 subjects with moderate to severe pain received placebo; ketorolac 30 mg; or IV diclofenac 3.75, 9.4, 18.75, 37.5, or 75 mg (N  =  51 for all groups, except N  =  47 for ketorolac). The primary endpoint was total pain relief over 6 hours (TOTPAR6) as measured by the visual analog scale (VAS). Secondary endpoints included multiple measures of pain intensity and relief; patient global evaluation; and times to pain relief and rescue medication. Dropouts and adverse effects (AEs) were also monitored. IV diclofenac was superior to placebo as measured by TOTPAR6 (P < .0001 for all doses except 3.75 mg, for which P  =  .0341). IV diclofenac 3.75 mg was statistically superior to placebo for TOTPAR2 and TOTPAR4. IV diclofenac at both 37.5 and 75 mg was superior to placebo (P < .05) at the earliest (5 minute) assessments of pain intensity and pain relief, but ketorolac was not. The proportion of patients reporting 30% or greater pain relief at 5 minutes was significantly greater after IV diclofenac 37.5 and 75 mg than after ketorolac 30 mg or placebo. Secondary endpoints confirmed the primary findings. Treatment-related AEs were generally mild to moderate and were typical for nonsteroidal anti-inflammatory drugs (NSAIDs). The more rapid onset of action of IV diclofenac compared with the reference injectable NSAID ketorolac suggests additional clinical benefit. If confirmed in larger series, these findings may improve the safety and efficacy of postoperative NSAID analgesia. PMID:21679043

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

PubMed

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.

Drug switching patterns among patients taking non-steroidal anti-inflammatory drugs: a retrospective cohort study of a general practitioners database in the United Kingdom.

PubMed

Langman, M; Kahler, K H; Kong, S X; Zhang, Q; Finch, E; Bentkover, J D; Stewart, E J

2001-01-01

To examine the frequency and determinants of switching between different non-steroidal anti-inflammatory drugs (NSAIDs) and the relationship with co-prescription of gastro-protective drugs (GPDs). This was an analysis of 30,654 patients receiving a total of 209,140 NSAID prescriptions in the UK from 1 January 1997 to 31 December 1998 identified through the MediPlus database. Analyses examined switching, repeat, termination and GPD co-prescription rates in new and continuing takers according to age and sex. Each patient received an average of 6.8 prescriptions in the year of study. Of the prescriptions 72.2% were for one of three NSAIDs, ibuprofen, diclofenac, or naproxen, and 7.2% of prescriptions were for fixed combination products of an NSAID plus a gastroprotective drug. At least 16.0% of continuing takers, and 28.5% of new takers switched to another NSAID in the review period. On average, new patients switched more frequently than continuing patients (0.39 switches/patient/year versus 0.23 switches/patient/year, p < 0.001). Switching between NSAIDs decreased with age and was less common in women (p < 0.05). Switching was associated with a 24% and 33% increased probability of GPD prescription in new and continuing takers, respectively. The frequency of switching, and of GPD co-prescription at switching, suggest that dissatisfaction with NSAIDs is frequent, and that gastrointestinal intolerance is a common feature of this dissatisfaction.

Effects of exposure to pharmaceuticals (diclofenac and carbamazepine) spiked sediments in the midge, Chironomus riparius (Diptera, Chironomidae).

PubMed

Nieto, Elena; Corada-Fernández, Carmen; Hampel, Miriam; Lara-Martín, Pablo A; Sánchez-Argüello, Paloma; Blasco, Julián

2017-12-31

Human and veterinary pharmaceuticals and degradation products are continuously introduced into the environment. To date, there is a lack of information about the effects of pharmaceuticals in spiked toxicity tests with non-target organisms. In this study, we have evaluated the effects of exposure to two common pharmaceuticals in the midge Chironomus riparius in spiked sediment experiments. The selected pharmaceuticals are the nonsteroidal anti-inflammatory drug (NSAID): diclofenac (DF) and the anti-depressant drug carbamazepine (CBZ). In order to assess the effects of the pharmaceuticals, a chronic toxicity test with the midge was carried out. The endpoints survival, growth and developmental stage by means of biomass, were measured after 10days, and emergence rates and sex-ratio (male/female) were measured after 21days of exposure. Significant mortality was observed in organisms at day 10 with a 40% of larvae surviving in the highest exposure concentration of CBZ. DF decreased the emergence ratio with respect to the controls in organisms exposed at concentrations of 34.0μg·g -1 whereas CBZ reduced the growth of the midges (30,6% with respect to the control) and induced a significant change in sex-ratio at concentrations of 31.4μg·g -1 . The results obtained in the present study indicate possible adverse effects on aquatic invertebrates, which should be taken into account for environmental risk assessment of pharmaceutical compounds in sediments. Copyright © 2017 Elsevier B.V. All rights reserved.

Anti-Inflammatory Activity of Haskap Cultivars is Polyphenols-Dependent.

PubMed

Rupasinghe, H P Vasantha; Boehm, Mannfred M A; Sekhon-Loodu, Satvir; Parmar, Indu; Bors, Bob; Jamieson, Andrew R

2015-06-02

Haskap (Lonicera caerulea L.) berries have long been used for their health promoting properties against chronic conditions. The current study investigated the effect of Canadian haskap berry extracts on pro-inflammatory cytokines using a human monocytic cell line THP-1 derived macrophages stimulated by lipopolysaccharide. Methanol extracts of haskap from different growing locations in Canada were prepared and characterized for their total phenolic profile using colorimetric assays and liquid chromatography-Mass spectrometry (UPLC-MS/MS). Human THP-1 monocytes were seeded in 24-well plates (5 × 10⁵/well) and treated with phorbol 12-myristate 13-acetate (PMA, 0.1 μg/mL) for 48 h to induce macrophage differentiation. After 48 h, the differentiated macrophages were washed with Hank's buffer and treated with various concentrations of test compounds for 4 h, followed by the lipopolysaccharide (LPS)-stimulation (18 h). Borealis cultivar showed the highest phenolic content, flavonoid content and anthocyanin content (p < 0.05). A negative correlation existed between the polyphenol concentration of the extracts and pro-inflammatory cytokines: Interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), prostaglandin (PGE2), and cyclooxygenase-2 (COX-2) enzyme. Borealis exhibited comparable anti-inflammatory effects to COX inhibitory drug, diclofenac. The results showed that haskap berry polyphenols has the potential to act as an effective inflammation inhibitor.

Anti-Inflammatory Activity of Haskap Cultivars is Polyphenols-Dependent

PubMed Central

Rupasinghe, H. P. Vasantha; Boehm, Mannfred M. A.; Sekhon-Loodu, Satvir; Parmar, Indu; Bors, Bob; Jamieson, Andrew R.

2015-01-01

Haskap (Lonicera caerulea L.) berries have long been used for their health promoting properties against chronic conditions. The current study investigated the effect of Canadian haskap berry extracts on pro-inflammatory cytokines using a human monocytic cell line THP-1 derived macrophages stimulated by lipopolysaccharide. Methanol extracts of haskap from different growing locations in Canada were prepared and characterized for their total phenolic profile using colorimetric assays and liquid chromatography—Mass spectrometry (UPLC-MS/MS). Human THP-1 monocytes were seeded in 24-well plates (5 × 105/well) and treated with phorbol 12-myristate 13-acetate (PMA, 0.1 μg/mL) for 48 h to induce macrophage differentiation. After 48 h, the differentiated macrophages were washed with Hank’s buffer and treated with various concentrations of test compounds for 4 h, followed by the lipopolysaccharide (LPS)-stimulation (18 h). Borealis cultivar showed the highest phenolic content, flavonoid content and anthocyanin content (p < 0.05). A negative correlation existed between the polyphenol concentration of the extracts and pro-inflammatory cytokines: Interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), prostaglandin (PGE2), and cyclooxygenase-2 (COX-2) enzyme. Borealis exhibited comparable anti-inflammatory effects to COX inhibitory drug, diclofenac. The results showed that haskap berry polyphenols has the potential to act as an effective inflammation inhibitor. PMID:26043379

Delivering safe and effective analgesia for management of renal colic in the emergency department: a double-blind, multigroup, randomised controlled trial.

PubMed

Pathan, Sameer A; Mitra, Biswadev; Straney, Lahn D; Afzal, Muhammad Shuaib; Anjum, Shahzad; Shukla, Dharmesh; Morley, Kostantinos; Al Hilli, Shatha A; Al Rumaihi, Khalid; Thomas, Stephen H; Cameron, Peter A

2016-05-14

The excruciating pain of patients with renal colic on presentation to the emergency department requires effective analgesia to be administered in the shortest possible time. Trials comparing intramuscular non-steroidal anti-inflammatory drugs with intravenous opioids or paracetamol have been inconclusive because of the challenges associated with concealment of randomisation, small sample size, differences in outcome measures, and inadequate masking of participants and assessors. We did this trial to develop definitive evidence regarding the choice of initial analgesia and route of administration in participants presenting with renal colic to the emergency department. In this three-treatment group, double-blind, randomised controlled trial, adult participants (aged 18-65 years) presenting to the emergency department of an academic, tertiary care hospital in Qatar, with moderate to severe renal colic (Numerical pain Rating Scale ≥ 4) were recruited. With the use of computer-generated block randomisation (block sizes of six and nine), participants were assigned (1:1:1) to receive diclofenac (75 mg/3 mL intramuscular), morphine (0.1 mg/kg intravenous), or paracetamol (1 g/100 mL intravenous). Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants achieving at least a 50% reduction in initial pain score at 30 min after analgesia, assessed by intention-to-treat analysis and per-protocol analysis, which included patients where a calculus in the urinary tract was detected with imaging. This trial is registered with ClinicalTrials.gov, number NCT02187614. Between Aug 5, 2014, and March 15, 2015, we randomly assigned 1645 participants, of whom 1644 were included in the intention-to-treat analysis (547 in the diclofenac group, 548 in the paracetemol group, and 549 in the morphine group). Ureteric calculi were detected in 1316 patients, who were analysed as the per-protocol population (438 in the diclofenac group, 435 in the paracetemol group, and 443 in the morphine group). The primary outcome was achieved in 371 (68%) patients in the diclofenac group, 364 (66%) in the paracetamol group, and 335 (61%) in the morphine group in the intention-to-treat population. Compared to morphine, diclofenac was significantly more effective in achieving the primary outcome (odds ratio [OR] 1·35, 95% CI 1·05-1·73, p=0·0187), whereas no difference was detected in the effectiveness of morphine compared with intravenous paracetamol (1·26, 0·99-1·62, p=0·0629). In the per-protocol population, diclofenac (OR 1·49, 95% CI 1·13-1·97, p=0·0046) and paracetamol (1·40, 1·06-1·85, p=0·0166) were more effective than morphine in achieving the primary outcome. Acute adverse events in the morphine group occurred in 19 (3%) participants. Significantly lower numbers of adverse events were recorded in the diclofenac group (7 [1%] participants, OR 0·31, 95% CI 0·12-0·78, p=0·0088) and paracetamol group (7 [1%] participants, 0·36, 0·15-0·87, p=0·0175) than in the morphine group. During the 2 week follow-up, no additional adverse events were noted in any group. Intramuscular non-steroidal anti-inflammatory drugs offer the most effective sustained analgesia for renal colic in the emergency department and seem to have fewer side-effects. Hamad Medical Corporation Medical Research Center, Doha, Qatar. Copyright © 2016 Elsevier Ltd. All rights reserved.

Widespread pain reliever profile of a flower extract of Tanacetum parthenium.

PubMed

Di Cesare Mannelli, Lorenzo; Tenci, Barbara; Zanardelli, Matteo; Maidecchi, Anna; Lugli, Andrea; Mattoli, Luisa; Ghelardini, Carla

2015-07-15

Tanacetum parthenium L., commonly called Feverfew, is known for anti-inflammatory and anti-migraine properties. Aimed to individuate new therapeutical strategies to control acute and persistent pain induced by different origins we tested two hydroalcoholic extracts obtained from Feverfew flowers and leaves, respectively. Extracts were characterized according to the European Pharmacopoeia monograph. Both the extracts were tested after acute per os administration in the dose range 30-1000 mg kg(-1). The anti-nociceptive properties were evaluated by the Writhing test in mice. The number of abdominal contractions was dose dependently reduced by the flower extract. It reduced mechanical hypersensitivity (Paw pressure test) related to the acute inflammatory phase induced by carrageenan similarly to diclofenac and ibuprofen. In the osteoarthritis model induced by intra articular injection of monoiodoacetate (MIA) the flower extract significantly increased the pain threshold peaking 30 min after treatment. Moreover, it was effective in the chronic constriction injury model of neuropathic pain showing activity similar to the anti-epileptic drug gabapentin. The flower extract activity was confirmed in rat models of chemotherapy-induced neuropathic pain. The mechanical hypersensitivity induced by repeated treatments with the anticancer drug oxaliplatin and with the antiviral dideoxycytidine was significantly reduced after a single injection of Feverfew flower extract. The leaf extract showed lesser efficacy and potency and it was devoid of any effect in carrageenan-, MIA- and chemotherapy-induced pain. The present Feverfew flower extract behaves as a potent pain reliever in acute, inflammatory, articular and neuropathic pain. It appears as a natural strategy potentially suitable for the treatment of different kinds of pain. Copyright © 2015 Elsevier GmbH. All rights reserved.

Single dose oral diclofenac for acute postoperative pain in adults

PubMed Central

Derry, Philip; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

2014-01-01

Background Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), available as a potassium salt (immediate-release) or sodium salt (delayed-release). This review updates an earlier review published in The Cochrane Database of Systematic Reviews (Issue 2, 2004) on ‘Single dose oral diclofenac for postoperative pain’. Objectives To assess single dose oral diclofenac for the treatment of acute postoperative pain. Search methods Cochrane CENTRAL, MEDLINE, EMBASE, Biological Abstracts, the Oxford Pain Relief Database, and reference lists of articles were searched; last search December 2008. Selection criteria Randomised, double-blind, placebo-controlled clinical trials of single dose, oral diclofenac (sodium or potassium) for acute postoperative pain in adults. Data collection and analysis Two review authors independently assessed studies for inclusion and quality, and extracted data. The area under the pain relief versus time curve was used to derive the proportion of participants with at least 50% pain relief over 4 to 6 hours, using validated equations. Relative benefit (risk) and number needed to treat to benefit (NNT) were calculated. Information on adverse events, time to remedication, and participants needing additional analgesia was also collected. Main results Fifteen studies (eight additional studies) with 1512 participants more than doubled the information available at each dose. Overall 50% to 60% of participants experienced at least 50% pain relief over 4 to 6 hours at any dose with diclofenac, compared to 10 to 20% with placebo, giving NNTs of about 2.5 for doses of 25 mg to 100 mg (similar to earlier review); no dose response was demonstrated. At 50 mg and 100 mg, NNTs for diclofenac potassium (2.1 (1.8 to 2.4) and 1.9 (1.7 to 2.2)) were significantly lower (better) than for diclofenac sodium (6.7 (4.2 to 17) and 4.5 (3.2 to 7.7)). The median time to use of rescue medication was 2 hours for placebo, 4.3 hours for diclofenac 50 mg and 4.9 hours for diclofenac 100 mg. Adverse events were reported at a similar rate to placebo, with no serious events. Authors’ conclusions Oral diclofenac is an effective single-dose treatment for moderate to severe postoperative pain. Significantly more participants experienced at least 50% pain relief over 4 to 6 hours with diclofenac potassium than with diclofenac sodium. There was no significant difference between diclofenac and placebo in the incidence of adverse events. PMID:19370609

Topical versus systemic diclofenac in the treatment of temporo-mandibular joint dysfunction symptoms.

PubMed

Di Rienzo Businco, L; Di Rienzo Businco, A; D'Emilia, M; Lauriello, M; Coen Tirelli, G

2004-10-01

The most frequent symptom of craniomandibular dysfunction is pain in the preauricular area or in the temporo-mandibular joint, usually localized at the level of the masticatory musculature. Patients sometimes also complain of reflect otalgia, headaches and facial pain. Osteoarthrosis is a frequent degenerative debilitating chronic disorder that can affect the temporomandibular joint. It causes pain and articular rigidity, a reduction in mobility, and radiological alterations are visible in stratigraphy. The aim of this study was to compare the efficacy of a topically applied non-steroid anti-inflammatory drug that has recently become commercially available (diclofenac sodium in a patented carrier containing dimethyl sulfoxide, that favours transcutaneous absorption) which is commonly used to alleviate pain in knee or elbow joints, versus oral diclofenac, in the treatment of symptoms of temporomandibular joint dysfunction. Dysfunction of the temporomandibular joint was diagnosed in 36 adult patients. The patients were randomized in two age- and gender -matched groups. Group A (18 patients) received oral diclofenac sodium administered after a meal in 50-mg tablets twice a day for 14 days. Group B (18 patients) received 16 mg/ml topical diclofenac (diclofenac topical solution, 10 drops 4 times a day for 14 days). All patients completed a questionnaire at the start and end of therapy. Patients were asked to quantify on a graded visual analogue scale and to reply to questions about the pain and tenderness of the temporomandibular joint and the functional limitation of mouth opening. Patients were also requested to report side-effects of the treatment. All patients showed relief from pain after treatment: the difference between the two groups was not significant (p > 0.05). Post-treatment, 16 patients of group A had epigastralgic symptoms. Three patients treated with topical diclofenac showed a modest irritation of the temporomandibular joint region, and disappeared spontaneously. Our results demonstrate that topically applied diclofenac and oral diclofenac are equally effective in the treatment of temporomandibular joint dysfunction symptoms. Topical diclofenac has the advantage that it does not have adverse systemic effects, whereas oral diclofenac had untoward effects on the gastric apparatus. The efficacy of diclofenac topically applied on the temporomandibular joint region observed in group B is explained by the association of diclofenac with dimethyl-sulfoxide, which enables a rapid effective penetration into the joint tissues. It is noteworthy that dimethyl-sulfoxide favours transuctaneous absorption when used in a multi-dose regime as in our study with 4 doses a day. Thus, single, "as required", applications should be avoided because this practice results in scarce absorption of diclofenac.

Aqueous extract of Codium fragile suppressed inflammatory responses in lipopolysaccharide-stimulated RAW264.7 cells and carrageenan-induced rats.

PubMed

Lee, Seul Ah; Moon, Sung-Min; Choi, Yun Hee; Han, Seul Hee; Park, Bo-Ram; Choi, Mi Suk; Kim, Jae-Sung; Kim, Yong Hwan; Kim, Do Kyung; Kim, Chun Sung

2017-09-01

Codium fragile (Suringar) Hariot has been used in Oriental medicine for the treatment of enterobiasis, dropsy, and dysuria and has been shown to have various biological effects. In this study, we evaluated the anti-inflammatory effects of aqueous extract of C. fragile (AECF) using in vitro and in vivo models. Nitric oxide (NO), prostaglandin E 2 (PGE 2 ), inflammatory-related mRNAs, and proteins were determined using the Griess assay, enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), and western blotting, respectively. Our results indicate that pretreatment of cells with AECF (50, 100 and 200μg/mL) significantly inhibited LPS-induced secretion of NO and PGE 2 in RAW264.7 cells without cytotoxicity. We also found that AECF (100 and 200μg/mL) inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 expression in a dose-dependent manner. Additionally, pretreatment of cells with AECF (100 and 200μg/mL) inhibited LPS-induced production of inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. It also prevented the nuclear translocation of nuclear factor (NF)-κB by suppressing the phosphorylation and degradation of inhibitor of NF-κB (IκB)-α. Furthermore, AECF (100 and 200μg/mL) inhibited the phosphorylation of the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. In addition, orally administered 50, 100, and 200mg/kg body weight of AECF dose-dependently suppressed carrageenan-induced rat paw edema thickness by 6%, 31%, and 50% respectively, after 4h. Furthermore, the anti-inflammatory effect was comparable to that observed in animals treated with the standard drug diclofenac sodium (56%) in vivo. Collectively, our results suggest that AECF exerts potential anti-inflammatory effects by suppressing NF-κB activation and MAPKs pathways in vitro, as well as inhibiting carrageenan-induced rat paw edema thickness in vivo. These findings indicate that AECF could be further developed as an anti-inflammatory drug. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Prescription of nonsteroidal anti-inflammatory drugs and co-prescribed drugs for mucosal protection: analysis of the present status based on questionnaires obtained from orthopedists in Japan.

PubMed

Tsumura, Hidetaka; Tamura, Isamu; Tanaka, Hiroshi; Chinzei, Ryo; Ishida, Tsukasa; Masuda, Atsuhiro; Shiomi, Hideyuki; Morita, Yoshinori; Yoshida, Masaru; Kutsumi, Hiromu; Inokuchi, Hideto; Doita, Minoru; Kurosaka, Masahiro; Azuma, Takeshi

2007-01-01

Recently guidelines for the treatment and prevention of ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs) have been established. The aim of the present study was to examine factors influencing orthopedists in Japan in the use of cytoprotective drugs to prevent NSAID-associated gastrointestinal adverse events. We sent a questionnaire to 402 orthopedists in Hyogo Prefecture. A standardized 10-item questionnaire was used to collect information on NSAID prescriptions (drug name, pharmaceutical form, doses, and duration of use) and associated drugs, especially gastroprotective drugs. Two hundred eight (51.7%) orthopedists returned the questionnaire. The most frequently used NSAIDs, in descending order, were loxoprofen sodium, diclofenac sodium, and etodolac. Most doctors (80%) reported patients with abdominal symptoms associated with NSAIDs. Of these doctors, 59% treated the symptoms by themselves, and prescribed gastroprotective agents (32.2%), histamine H2-receptor antagonists (H2RAs) (26.4%), prostaglandin analogues (PAs) (17.0%), or proton pump inhibitors (PPIs) (16.2%). Sixty-seven percent of doctors reported that those drugs reduced the symptoms. Most orthopedists (96%) prescribed some type of drug to prevent NSAID-associated gastrointestinal events, including gastroprotective drugs (44.6%), H2RAs (19.5%), PAs (17.4%), and PPIs (10.8%). The doctors reported that they prescribed medicines for NSAID-associated gastrointestinal events on the basis of their experience (23%), by considering medical insurance restrictions (17%), and by referring to information provided by pharmaceutical company representatives (16%). Most orthopedists prescribe some type of drug to prevent NSAID-induced ulcers but do not refer to the guidelines. We therefore strongly recommend that the guidelines be made more widely known to gastroenterologists and to physicians in every field of clinical practice, including orthopedics.

Degradation of anti-inflammatory drugs in municipal wastewater by heterogeneous photocatalysis and electro-Fenton process.

PubMed

Villanueva-Rodríguez, Minerva; Bello-Mendoza, Ricardo; Hernández-Ramírez, Aracely; Ruiz-Ruiz, Edgar J

2018-03-01

Non-steroidal anti-inflammatory drugs (NSAID) are compounds frequently found in municipal wastewater and their degradation by conventional wastewater treatment plants (WWTP) is generally incomplete. This study compared the efficiency of two advanced oxidation processes (AOP), namely heterogeneous photocatalysis (HP) and electro-Fenton (EF), in the degradation of a mixture of common NSAID (diclofenac, ibuprofen and naproxen) dissolved in either deionized water or effluent from a WWTP. Both processes were effective in degrading the NSAID mixture and the trend of degradation was as follows, diclofenac > naproxen > ibuprofen. EF with a current density of 40 mA cm -2 and 0.3 mmol Fe 2+  L -1 was the most efficient process to mineralize the organic compounds, achieving up to 92% TOC removal in deionized water and 90% in the WWTP effluent after 3 h of reaction. HP with 1.4 g TiO 2  L -1 at pH 7 under sunlight, produced 85% TOC removal in deionized water and 39% in WWTP effluent also after 3 h treatment. The lower TOC removal efficiency shown by HP with the WWTP effluent was attributed mainly to the scavenging of reactive species by background organic matter in the wastewater. On the contrary, inorganic ions in the wastewater may produce oxidazing species during the EF process, which contributes to a higher degradation efficiency. EF is a promising option for the treatment of anti-inflammatory pharmaceuticals in municipal WWTP at competitive electrical energy efficiencies.

Investigation of pH Influence on Skin Permeation Behavior of Weak Acids Using Nonsteroidal Anti-Inflammatory Drugs.

PubMed

Chantasart, Doungdaw; Chootanasoontorn, Siriwan; Suksiriworapong, Jiraphong; Li, S Kevin

2015-10-01

As a continuing effort to understand the skin permeation behavior of weak acids and bases, the objectives of the present study were to evaluate skin permeation of nonsteroidal anti-inflammatory drugs (NSAIDs) under the influence of pH, investigate the mechanism of pH effect, and examine a previous hypothesis that the effective skin pH for drug permeation is different from donor solution pH. In vitro permeability experiments were performed in side-by-side diffusion cells with diclofenac, ibuprofen, flurbiprofen, ketoprofen, and naproxen and human skin. The donor solution pH significantly affected skin permeation of NSAIDs, whereas no effect of the receiver pH was observed. Similar to previous observations, the apparent permeability coefficient versus donor solution pH relationships deviated from the predictions (fractions of unionized NSAIDs) according to the acid/base theory. The influences of the viable epidermis barrier, polar pathway transport, ion permeation across skin, and effective skin pH were investigated. The effective pH values for skin permeation determined using the NSAIDs (weak acids) in this study were different from those obtained previously with a weak base at the same donor solution pH conditions, suggesting that the observed permeability-pH relationships could not be explained solely by possible pH differences between skin and donor solution. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Efficacy and safety of topical NSAIDs in the management of osteoarthritis: Evidence from real-life setting trials and surveys.

PubMed

Rannou, François; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne

2016-02-01

Topical non-steroidal anti-inflammatory drugs (NSAIDs) are recommended in international and national guidelines as an early treatment option for the symptomatic management of knee and hand osteoarthritis (OA), and may be used ahead of oral NSAIDs due to their superior safety profile. The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm recommends topical NSAIDs for knee OA in addition to the pharmacological background of symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) and rescue analgesia with paracetamol and non-pharmacological treatment, if the patient is still symptomatic. Topical NSAIDs have a moderate effect on pain relief, with efficacy similar to that of oral NSAIDs, with the advantage of a better risk:benefit ratio. In real-life studies, topical and oral NSAIDs demonstrate an equivalent effect on knee pain over 1 year of treatment, with fewer adverse events due to lower systemic absorption of topical NSAIDs compared with oral NSAIDs. As a result, topical NSAIDs may be the preferred treatment option, especially in OA patients aged ≥75 years, and those with co-morbidities or at an increased risk of cardiovascular, gastrointestinal, or renal side effects. Furthermore, using topical NSAIDs in inflammatory rheumatic diseases leads to a 40% reduction in the need for concomitant oral NSAIDs. When selecting a topical NSAID, absorption and bioavailability are important because of heterogeneity among topical drug formulations. Molecules like etofenamate have a bioavailability of >20% and evidence for accumulation in synovial tissues, with efficacy demonstrated as improvement in pain and function in real-life studies of OA patients. Diclofenac also shows good efficacy alongside evidence that diclofenac accumulates in the synovium. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Pharmacokinetic Drug-Drug Interactions Between Vonoprazan and Low-Dose Aspirin or Nonsteroidal Anti-inflammatory Drugs: A Phase 2, Open-Label, Study in Healthy Japanese Men.

PubMed

Sakurai, Yuuichi; Shiino, Madoka; Horii, Sayako; Okamoto, Hiroyuki; Nakamura, Koki; Nishimura, Akira; Sakata, Yukikuni

2017-01-01

Gastroprotective agents are recommended for patients receiving low-dose aspirin (LDA) or nonsteroidal anti-inflammatory drugs (NSAIDs). Vonoprazan is a potassium-competitive acid blocker recently approved for the prevention of peptic ulcer recurrence in patients receiving LDA or NSAIDs. This phase 2, open-label, single-center study in healthy Japanese males evaluated drug-drug interactions between vonoprazan 40 mg and LDA (100 mg) or NSAIDs [loxoprofen sodium (60 mg), diclofenac sodium (25 mg), or meloxicam (10 mg)] and vice versa. Subjects were allocated to one of eight cohorts and received their orally administered treatment regimen (to assess the effect of vonoprazan vs. NSAID or LDA, or vice versa) once daily. Endpoints were the pharmacokinetics of plasma concentrations of the study drugs alone and in combination (primary), safety (secondary), and vonoprazan effects on aspirin-mediated inhibition of platelet-aggregation. Of 109 subjects screened, 64 were assigned to one of eight cohorts (n = 8 per cohort) and received treatment, one subject discontinued due to a treatment-emergent adverse event (TEAE), and 63 completed the study. There were few differences in the pharmacokinetics of vonoprazan when administered with LDA or NSAIDs, and few differences in the pharmacokinetics of LDA or NSAIDs when administered with vonoprazan. The differences were small and not clinically meaningful. Inhibition of arachidonic-induced platelet aggregation by LDA was not influenced by vonoprazan. Six patients experienced a TEAE, all were mild and were deemed unrelated to study drugs. One subject withdrew due to infection (tonsillitis). No clinically meaningful drug-drug interactions were observed and vonoprazan was well tolerated when administered with LDA or NSAIDs. JapicCTI-153100.

In Vitro Anti-inflammatory and Antimicrobial Activities of Azithromycin After Loaded in Chitosan- and Tween 20-Based Oil-in-Water Macroemulsion for Acne Management.

PubMed

Shunmugaperumal, Tamilvanan; Kaur, Varinder

2016-06-01

The objectives of the current investigation are (1) to prepare and characterize (particle size, surface charge (potential zeta), surface morphology by transmission electron microscopy, drug content, and drug release) the azithromycin (AZM, 100 mg)-loaded oil-in-water (o/w) macroemulsion, (2) to assess the toxicity of macroemulsion with or without AZM using RBC lysis test in comparison with AZM in phosphate buffer solution of pH 7.4, (3) to compare the in vitro antimicrobial activity (in Escherichia coli using zone inhibition assay) of AZM-loaded macroemulsion with its aqueous solution, and (4) to assess the in vitro anti-inflammatory effect (using egg albumin denaturation bioassay) of the AZM-loaded macroemulsion in comparison with diclofenac sodium in phosphate buffer solution of pH 7.4. The AZM-loaded macroemulsion possessed the dispersed oil droplets with a mean diameter value of 52.40 ± 1.55 μm. A reversal in the zeta potential value from negative (-2.16 ± 0.75 mV) to positive (+6.52 ± 0.96 mV) was noticed when AZM was added into the macroemulsion. At a 1:5 dilution ratio, 2.06 ± 0.03 mg of drug was released from macroemulsion followed by 1.01 ± 0.01 and 0.25 ± 0.08 mg, respectively, for 1:10 and 1:40 dilution ratios. Antimicrobial activity maintenance and significant reduction of RBC lysis property were noticed for AZM after loaded in the macroemulsion. However, an increment in the absorbance values for emulsion-treated samples in comparison to the control samples was noticed in the anti-inflammatory test. This speculates the potential of the AZM-loaded emulsion to manage inflammatory conditions produced at Acne vulgaris.

[An experimental study of the anti-inflammatory action of noopept and its effect on the level of cytokines].

PubMed

Alekseeva, S V; Kovalenko, L P; Tallerova, A V; Gudasheva, T A; Durnev, A D

2012-01-01

The anti-inflammatory effects of noopept (dipeptide analog of piracetam) upon a single intraperitoneal (i.p.) administration at doses of 1, 5, and 10 mg/kg in comparison to the reference drug diclofenac (10 mg/kg, i.p.) have been studied on a model of acute exudative inflammation induced by carrageenan in outbred rats and concanavalin A (Con A) in CBA mice. The level of cytokines was studied on the lipopolysaccharide (LPS) model (single administration, 100 mg/kg, i.p.) with 5-day administration of noopept at a dose of 5 mg/kg (i.p., before endotoxin injection) in C57BL/6 mice. The administration of noopept led to a significant suppression of the inflammatory response to both carrageenan and Con A. The administration of Con A caused a 16-fold increase in the level of IL-6 interleukin in the blood serum of mice as compared to control. Noopept (5 mg/kg) reduced the level of IL-6 by a factor of 1.8 in the inflammatory response to Con A. The administration of LPS led to pronounced increase in the levels ofpro-inflammatory IL-6 and TNF-alpha in the blood serum of test mice as compared to intact animals. The course administration of noopept (5 mg/kg) significantly decreased the level of IL-6 and reduced by half the level of TNF-alpha.

Polysaccharide peptides from COV-1 strain of Coriolus versicolor induce hyperalgesia via inflammatory mediator release in the mouse.

PubMed

Chan, Siu-Lung; Yeung, John H K

2006-04-18

Polysaccharide peptide (PSP), isolated from Coriolus versicolor COV-1, has been widely used as an adjunct to cancer chemotherapy and as an immuno-stimulator in China. In this study, the anti-nociceptive effects of PSP were investigated in two different pain models in the mouse. In the acetic acid-induced writhing model, initial studies showed that PSP decreased the number of acetic acid-induced writhing by 92.9%, which, by definition, would constitute an analgesic effect. However, further studies showed that PSP itself induced a dose-dependent writhing response. Studies on inflammatory mediator release showed that PSP increased the release of prostaglandin E2, tumor necrosis factor-alpha, interleukin-1beta, and histamine in mouse peritoneal macrophages and mast cells both in vitro and in vivo. The role of inflammatory mediator release in PSP-induced writhing was confirmed when diclofenac and dexamethasone decreased the number of writhing responses by 54% and 58.5%, respectively. Diphenhydramine totally inhibited the PSP-induced writhing. In the hot-plate test, PSP dose-dependently shortened the hind paw withdrawal latency, indicative of a hyperalgesic effect. The hyperalgesic effect was reduced by pretreatment with the anti-inflammatory drugs. In conclusion, the PSP-induced hyperalgesia was related to activation of peritoneal resident cells and an increase in the release of inflammatory mediators.

Physico-chemical characterization and pharmacological evaluation of sulfated polysaccharides from three species of Mediterranean brown algae of the genus Cystoseira.

PubMed

Hadj Ammar, Hiba; Lajili, Sirine; Ben Said, Rafik; Le Cerf, Didier; Bouraoui, Abderrahman; Majdoub, Hatem

2015-01-13

Seaweed polysaccharides are highly active natural substances having valuable applications. The present study was conducted to characterize the physico-chemical properties of sulphated polysaccharides from three Mediterranean brown seaweeds (Cystoseira sedoides, Cystoseira compressa and Cystoseira crinita) and to evaluate their anti-radical, anti-inflammatory and gastroprotective activities. The different rates of neutral sugars, uronic acids, L-fucose and sulphate content were determined by colorimetric techniques. The different macromolecular characteristics of isolated fucoidans were identified by size exclusion chromatography equipped with a triple detection: multiangle light scattering, viscometer and differential refractive index detectors, (SEC/MALS/VD/DRI). Anti-inflammatory activity was evaluated, using the carrageenan-induced rat paw edema test in comparison to the references drugs Acetylsalicylate of Lysine and Diclofenac. The gastroprotective activity was determined using HCl/EtOH induced gastric ulcers in rats and to examine the antioxidant effect of fucoidans in the three species, the free radical scavenging activity was determined using 1,1-diphenyl-2-picrylhydrazyl. The pharmacological evaluation of the isolated fucoidans for their anti-inflammatory, and their gastroprotective effect established that these products from C. sedoides, C. compressa and C. crinita exhibited a significant anti-inflammatory activity at a dose of 50 mg/kg, i.p; the percentages of inhibition of the oedema were 51%, 57% and 58% respectively. And, at the same dose, these fucoidans from C. sedoides and C. compressa showed a significant decrease of the intensity of gastric mucosal damages compared to a control group by 68%, whereas, the fucoidan from C. crinita produced a less gastroprotective effect. Furthermore, the isolated fucoidans exhibited a radical scavenging activity. The comparative study of fucoidans isolated from three species of the genus Cystoseira showed that they have similar chemicals properties and relatives anti-radical, anti-inflammatory and gastroprotective activities which are found to be promising.

Removal of pharmaceutically active compounds in nitrifying-denitrifying plants.

PubMed

Suárez, S; Ramil, M; Omil, F; Lema, J M

2005-01-01

The behaviour of nine pharmaceutically active compounds (PhACs) of different diagnostic groups is studied during a nitrifying-denitrifying process in an activated sludge system. The compounds selected cover a wide range of frequently used substances such as anti-epileptics (carbamazepine), tranquillisers (diazepam), anti-depressants (fluoxetine and citalopram), anti-inflammatories (ibuprofen, naproxen and diclofenac) and estrogens (estradiol and ethinylestradiol). The main objective of this research is to investigate the effect of acclimation of biomass on the removal rates of these compounds, either by maintaining a high sludge retention time or at long-term operation. The removal rates achieved for nitrogen and carbon in the experimental unit exceed 90% and were not affected by the addition of PhACs. Carbamazepine, diazepam and diclofenac were only removed to a small extent. On the other hand, higher removal rates have been observed for naproxen and ibuprofen (68% and 82%), respectively.

Evaluation of Anti-Inflammatory Activity and In-vitro Antioxidant Activity of Indian Mistletoe, the Hemiparasite Dendrophthoe falcate L. F. (Loranthaceae)

PubMed Central

Patil, Satish; Anarthe, Sneha; Jadhav, Ram; Surana, Sanjay

2011-01-01

Methanolic and aqueous extracts of Dendrophthoe falcata Linn. leaves which belongs to the Loranthaceae family, were evaluated through DPPH (1, 1-diphenyl -2-picryl-hydrazyl), antilipid peroxidation and nitric oxide scavenging methods to assess the antioxidant activity. Methanolic and aqueous extracts of Dendrophthoe falcata leaves were also evaluated for their anti-inflammatory activity by carrageenan and cotton pellet induced granuloma tests for their effect on the acute and chronic phase inflammation models in rats. It was found that the methanolic extract of Dendrophthoe falcata leaves demonstrates potent antioxidant activity as compared to aqueous extraction of Dendrophthoe falcata leaves for DPPH (1, 1-diphenyl-2-picryl-hydrazyl) radical scavenging, anti-lipid peroxidation and nitric oxide scavenging activity respectively (having IC50 value 77.8, 79.36 and 86.2, 144, 87, 104). The maximum inhibition for aqueous extract of Dendrophthoe falcata leaves (30.95%) and methanolic extract of Dendrophthoe falcata leaves (23.41%) were obtained at a dose of 300 mg/Kg after 4h of drug treatment in carrageenan induced paw edema, whereas diclofenac sodium (standard drug) produced 42.85% inhibition. In the chronic model (cotton pellet induced granuloma), aqueous extracts of Dendrophthoe falcata leaves and methanolic extracts of Dendrophthoe falcata leaves (at doses of 300 mg/Kg), phenylbutazone as standard drug showed decreased formation of granuloma tissue by 51%, 48%, 53% respectively. In addition, the total phenolic and flavonoid content of aqueous extracts of Dendrophthoe falcata leaves and methanolic extracts of Dendrophthoe falcata leaves were found to be 2.12 % w/w, 4.39 % w/w, 0.31 mg/g and 0.85 mg/g respectively. Thus the results indicate that methanolic and aqueous extracts of Dendrophthoe falcataleaves on animal models have potent anti-inflammatory and in-vitro antioxidant effects. PMID:24250351

Neostigmine interactions with non steroidal anti-inflammatory drugs

PubMed Central

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

2002-01-01

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. 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. 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. The i.p. or i.t. co-administration of fixed ratios of ED50 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. 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. PMID:11934798

Long-term exposure of Mytilus galloprovincialis to diclofenac, Ibuprofen and Ketoprofen: Insights into bioavailability, biomarkers and transcriptomic changes.

PubMed

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

2018-05-01

Non-steroidal anti-inflammatory drugs (NSAIDs) represent a growing concern for marine ecosystems due to their ubiquitous occurrence and documented adverse effects on non-target organisms. Despite the remarkable efforts to elucidate bioaccumulation and ecotoxicological potential under short-term conditions, limited and fragmentary information is available for chronic exposures. In this study bioavailability, molecular and cellular effects of diclofenac (DIC), ibuprofen (IBU) and ketoprofen (KET) were investigated in mussels Mytilus galloprovincialis exposed to the realistic environmental concentration of 2.5 μg/L for up to 60 days. Results indicated a significant accumulation of DIC and IBU but without a clear time-dependent trend; on the other hand, KET concentrations were always below the detection limit. Analyses of a large panel of molecular, biochemical and cellular biomarkers highlighted that all investigated NSAIDs caused alterations of immunological parameters, genotoxic effects, modulation of lipid metabolism and changes in cellular turn-over. This study provided the evidence of long-term ecotoxicological potential of NSAIDs, further unraveling the possible hazard for wild marine organisms. Copyright © 2018 Elsevier Ltd. All rights reserved.

Determination of acidic non-steroidal anti-inflammatory drugs in aquatic samples by liquid chromatography-triple quadrupole mass spectrometry combined with carbon nanotubes-based solid-phase extraction.

PubMed

Reinholds, I; Pugajeva, I; Zacs, Dz; Lundanes, E; Rusko, J; Perkons, I; Bartkevics, V

2017-10-18

A solid-phase extraction (SPE) method based on multi-walled carbon nanotubes (CNT) was developed for the determination of 12 acidic non-steroidal anti-inflammatory drugs (NSAIDs) in surface waters and tap water. Pristine and functionalised CNTs were evaluated as sorbent materials. Batch experiments were used to optimise sorption and desorption conditions (sorbent type and amount, adsorption time, pH). The adsorption equilibrium was reached after 8 to 48 h duration, which increased with the pH of solution. Non-agglomerated pristine CNTs (20 mg) showed the most optimal adsorption (94 to 100%) for all of the analytes after a 30-min contact period in acidified water solutions (100 mL). The compounds retained at those conditions were recovered by 40 to 95% by using 5% ammonium hydroxide in methanol as the desorbing solution at ambient conditions. A comprehensive liquid chromatography coupled to triple quadrupole mass spectrometry (LC-QqQ-MS/MS) was used for the analysis of real water samples. The method showed sufficient recovery (65-125%) and good precision (2-14% relative standard deviation (RSD)). The limits of detection and quantification ranged between 0.01 and 1.3 ng L -1 and 0.04 and 3.9 ng L -1 . Only diclofenac and ibuprofen were found in the analysed surface water samples from Latvia (n = 10) and Norway (n = 14). Diclofenac was found at 1.7-8.4 ng L -1 concentration in two samples of surface waters, whereas the concentrations of ibuprofen ranged between 1.0 and 9.2 ng L -1 in seven samples collected in Norway and 3.9-17 ng L -1 in three samples from Latvia.

Relative efficacy and safety of topical non-steroidal anti-inflammatory drugs for osteoarthritis: a systematic review and network meta-analysis of randomised controlled trials and observational studies.

PubMed

Zeng, Chao; Wei, Jie; Persson, Monica S M; Sarmanova, Aliya; Doherty, Michael; Xie, Dongxing; Wang, YiLun; Li, Xiaoxiao; Li, Jiatian; Long, Huizhong; Lei, Guanghua; Zhang, Weiya

2018-05-01

To compare the efficacy and safety of topical non-steroidal anti-inflammatory drugs (NSAIDs), including salicylate, for the treatment of osteoarthritis (OA). PubMed, Embase, Cochrane Library and Web of Science were searched from 1966 to January 2017. Randomised controlled trials (RCTs) comparing topical NSAIDs with placebo or each other in patients with OA and observational studies comparing topical NSAIDs with no treatment or each other irrespective of disease were included. Two investigators identified studies and independently extracted data. Bayesian network and conventional meta-analyses were conducted. The primary outcomes were pain relief for RCTs and risk of adverse effects (AEs) for observational studies. 43 studies, comprising 36 RCTs (7 900 patients with OA) and seven observational studies (218 074 participants), were included. Overall, topical NSAIDs were superior to placebo for relieving pain (standardised mean difference (SMD)=-0.30, 95% CI -0.40 to -0.20) and improving function (SMD=-0.35, 95% CI -0.45 to -0.24) in OA. Of all topical NSAIDs, diclofenac patches were most effective for OA pain (SMD=-0.81, 95% CI -1.12 to -0.52) and piroxicam was most effective for functional improvement (SMD=-1.04, 95% CI -1.60 to -0.48) compared with placebo. Although salicylate gel was associated with higher withdrawal rates due to AEs, the remaining topical NSAIDs were not associated with any increased local or systemic AEs. Topical NSAIDs were effective and safe for OA. Diclofenac patches may be the most effective topical NSAID for pain relief. No serious gastrointestinal and renal AEs were observed in trials or the general population. However, confirmation of the cardiovascular safety of topical NSAIDs still warrants further observational study. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Magnetic sporopollenin-cyanopropyltriethoxysilane-dispersive micro-solid phase extraction coupled with high performance liquid chromatography for the determination of selected non-steroidal anti-inflammatory drugs in water samples.

PubMed

Abd Wahib, Siti Munirah; Wan Ibrahim, Wan Aini; Sanagi, Mohd Marsin; Kamboh, Muhammad Afzal; Abdul Keyon, Aemi S

2018-01-12

A facile dispersive-micro-solid phase extraction (D-μ-SPE) method coupled with HPLC for the analysis of selected non-steroidal anti-inflammatory drugs (NSAIDs) in water samples was developed using a newly prepared magnetic sporopollenin-cyanopropyltriethoxysilane (MS-CNPrTEOS) sorbent. Sporopollenin homogenous microparticles of Lycopodium clavatum spores possessed accessible functional groups that facilitated surface modification. Simple modification was performed by functionalization with 3-cyanopropyltriethoxysilane (CNPrTEOS) and magnetite was introduced onto the biopolymer to simplify the extraction process. MS-CNPrTEOS was identified by infrared spectrometrywhile the morphology and the magnetic property were confirmed by scanning electron microscopy (SEM) and vibrating sample magnetometer (VSM), respectively. To maximize the extraction performance of ketoprofen, ibuprofen, diclofenac and mefenamic acid using the proposed MS-CNPrTEOS, important D-μ-SPE parameters were comprehensively optimized. The optimum extraction conditions were sorbent amount, 40 mg; extraction time, 5 min; desorption time; 5 min; sample volume, 15 mL; sample pH 2.0; and salt addition, 2.5% (w/v). The feasibility of the developed method was evaluated using spiked tap water, lake water, river water and waste water samples. Results showed that ketoprofen and ibuprofen were linear in the range of 1.0-1000 μg L -1 whilst diclofenac and mefenamic acid were linear in the range 0.8-500 μg L -1 . The results also showed good detection limits for the studied NSAIDs in the range of 0.21-0.51 μg L -1 and good recoveries for spiked water samples in the range of 85.1-106.4%. The MS-CNPrTEOS proved a promising dispersive sorbent and applicable to facile and rapid assay of NSAIDs in water samples. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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

Singh, Deepti; Rawat, Surender; Waseem, Mohd

The YacK gene from Yersinia enterocolitica strain 7, cloned in pET28a vector and expressed in Escherichia coli BL21 (DE3), showed laccase activity when oxidized with 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and guaiacol. The recombinant laccase protein was purified and characterized biochemically with a molecular mass of ≈58 KDa on SDS-PAGE and showed positive zymogram with ABTS. The protein was highly robust with optimum pH 9.0 and stable at 70 °C upto 12 h with residual activity of 70%. Kinetic constants, K{sub m} values, for ABTS and guaiacol were 675 μM and 2070 μM, respectively, with corresponding Vmax values of 0.125 μmol/ml/min and 6500 μmol/ml/min. It also possess antioxidative propertymore » against BSA and Cu{sup 2+}/H{sub 2}O{sub 2} model system. Constant pH MD simulation studies at different protonation states of the system showed ABTS to be most stable at acidic pH, whereas, diclofenac at neutral pH. Interestingly, aspirin drifted out of the binding pocket at acidic and neutral pH, but showed stable binding at alkaline pH. The biotransformation of diclofenac and aspirin by laccase also corroborated the in silico results. This is the first report on biotransformation of non-steroidal anti-inflammatory drugs (NSAIDs) using recombinant laccase from gut bacteria, supported by in silico simulation studies. - Highlights: • Laccase from Yersinia enterocolitica strain 7 was expressed in Escherichia coli BL21 (DE3). • Recombinant laccase was found to be thermostable and alkali tolerant. • The in silico and experimental studied proves the biotransformation of NSAIDs. • Laccase binds to ligands differentially under different protonation state. • Laccase also possesses free radical scavenging property.« less

Relative efficacy and safety of topical non-steroidal anti-inflammatory drugs for osteoarthritis: a systematic review and network meta-analysis of randomised controlled trials and observational studies

PubMed Central

Persson, Monica S M; Sarmanova, Aliya; Doherty, Michael; Xie, Dongxing; Wang, YiLun; Li, Xiaoxiao; Li, Jiatian; Long, Huizhong

2018-01-01

Objectives To compare the efficacy and safety of topical non-steroidal anti-inflammatory drugs (NSAIDs), including salicylate, for the treatment of osteoarthritis (OA). Methods PubMed, Embase, Cochrane Library and Web of Science were searched from 1966 to January 2017. Randomised controlled trials (RCTs) comparing topical NSAIDs with placebo or each other in patients with OA and observational studies comparing topical NSAIDs with no treatment or each other irrespective of disease were included. Two investigators identified studies and independently extracted data. Bayesian network and conventional meta-analyses were conducted. The primary outcomes were pain relief for RCTs and risk of adverse effects (AEs) for observational studies. Results 43 studies, comprising 36 RCTs (7 900 patients with OA) and seven observational studies (218 074 participants), were included. Overall, topical NSAIDs were superior to placebo for relieving pain (standardised mean difference (SMD)=−0.30, 95% CI −0.40 to –0.20) and improving function (SMD=−0.35, 95% CI −0.45 to –0.24) in OA. Of all topical NSAIDs, diclofenac patches were most effective for OA pain (SMD=−0.81, 95% CI −1.12 to –0.52) and piroxicam was most effective for functional improvement (SMD=−1.04, 95% CI −1.60 to –0.48) compared with placebo. Although salicylate gel was associated with higher withdrawal rates due to AEs, the remaining topical NSAIDs were not associated with any increased local or systemic AEs. Conclusions Topical NSAIDs were effective and safe for OA. Diclofenac patches may be the most effective topical NSAID for pain relief. No serious gastrointestinal and renal AEs were observed in trials or the general population. However, confirmation of the cardiovascular safety of topical NSAIDs still warrants further observational study. PMID:29436380

Occurrence and risk assessment of pharmaceutically active compounds in wastewater treatment plants. A case study: Seville city (Spain).

PubMed

Santos, J L; Aparicio, I; Alonso, E

2007-05-01

The occurrence of four anti-inflammatory drugs (diclofenac, ibuprofen, ketoprofen and naproxen), an antiepileptic drug (carbamazepine) and a nervous stimulant (caffeine) in influent and effluent samples from four wastewater treatment plants (WWTPs) in Seville was evaluated. Removal rates in the WWTPs and risk assessment of the pharmaceutically active compounds have been studied. Analytical determination was carried out by high performance liquid chromatography (HPLC) with diode array (DAD) and fluorescence (Fl) detectors after sample clean up and concentration by solid phase extraction. All pharmaceutically active compounds, except diclofenac, were detected not only in wastewater influents but also in wastewater effluents. Mean concentrations of caffeine, carbamazepine, ketoprofen and naproxen ranged between 0.28-11.44 microg l(-1) and 0.21-2.62 microg l(-1) in influent and effluent wastewater, respectively. Ibuprofen was present in the highest concentrations in the range 12.13-373.11 microg l(-1) and 0.78-48.24 microg l(-1) in influent and effluent wastewater, respectively. Removal rates of the pharmaceuticals ranged between 6 and 98%. Risk quotients, expressed as ratios between the measured environmental concentration (MEC) and the predicted no effect concentrations (PNEC) were higher than 1 for ibuprofen and naproxen in influent wastewater and for ibuprofen in effluent wastewater.

Sorption and retention of diclofenac on zeolite in the presence of cationic surfactant.

PubMed

Sun, Ken; Shi, Yan; Wang, Xiaoyu; Li, Zhaohui

2017-02-05

Diclofenac (DC) is one of the most widely prescribed non-steroidal anti-inflammatory drugs and one of the commonly found pharmaceuticals in aquatic environments and wastewater treatment plants. It possesses negative charges when solution pH is greater than its pKa value, while most of the soil components and sediment minerals bear negative charges, too, resulting in a net repulsion between the soil minerals and DC. Surfactant-modified zeolite (SMZ) has been studied extensively over the last 20 years for its effective removal of anionic contaminants tested under different experimental scales. However, its application for the removal of anionic drugs, such as DC, was less reported. This study focused on the sorption of DC by SMZ under different physic-chemical conditions, supplemented with instrumental analyses, in order to elucidate the mechanism of DC sorption by SMZ and to expand the SMZ application further. The results showed that the retention of DC was on the external surfaces of SMZ with extremely fast removal rate. Both anion exchange and partitioning of DC into the adsorbed surfactant micelles (admicelles) were responsible for the extended DC sorption. Interactions of DC with SMZ were facilitated with the benzene ring, the CO, and the CH 2 CH 3 functional groups. Copyright © 2016 Elsevier B.V. All rights reserved.

Rejection of pharmaceuticals in nanofiltration and reverse osmosis membrane drinking water treatment.

PubMed

Radjenović, J; Petrović, M; Ventura, F; Barceló, D

2008-08-01

This paper investigates the removal of a broad range of pharmaceuticals during nanofiltration (NF) and reverse osmosis (RO) applied in a full-scale drinking water treatment plant (DWTP) using groundwater. Pharmaceutical residues detected in groundwater used as feed water in all five sampling campaigns were analgesics and anti-inflammatory drugs such as ketoprofen, diclofenac, acetaminophen and propyphenazone, beta-blockers sotalol and metoprolol, an antiepileptic drug carbamazepine, the antibiotic sulfamethoxazole, a lipid regulator gemfibrozil and a diuretic hydrochlorothiazide. The highest concentrations in groundwater were recorded for hydrochlorothiazide (58.6-2548ngL(-1)), ketoprofen (85%). Deteriorations in retentions on NF and RO membranes were observed for acetaminophen (44.8-73 %), gemfibrozil (50-70 %) and mefenamic acid (30-50%). Furthermore, since several pharmaceutical residues were detected in the brine stream of NF and RO processes at concentrations of several hundreds nanogram per litre, its disposal to a near-by river can represent a possible risk implication of this type of treatment.

Evaluation of the effect of antiarthritic drugs on the secretion of proteoglycans by lapine chondrocytes using a novel assay procedure.

PubMed Central

Collier, S; Ghosh, P

1989-01-01

A new method is described for separating free 35SO4-- from 35SO4 labelled proteoglycans synthesised by rabbit articular chondrocytes cultured in the presence of excess 35SO4--. The procedure uses the low solubility product of barium sulphate to remove, by precipitation, free 35SO4-- from culture medium. Optimum recovery of 35SO4 labelled proteoglycans was achieved after papain digestion to release 35SO4-glycosaminoglycans, and addition of chondroitin sulphate before the precipitation step. Using this assay, we studied the effect of six drugs-indomethacin, diclofenac, sodium pentosan polysulphate, glycosaminoglycan polysulphate ester, tiaprofenic acid, and ketoprofen-on the secretion into the medium of labelled proteoglycans by lapine chondrocytes. The six drugs were tested at 0.1, 1, 10, 50, and 100 micrograms/ml over four consecutive 48 hour culture periods. A consistent concentration-response pattern was found for the four non-steroidal anti-inflammatory drugs (NSAIDs) studied. Generally they inhibited proteoglycan secretion at 50 and 100 micrograms/ml but had no effect at lower concentrations. Inhibition of secretion was strongest with indomethacin and diclofenac at 50 and 100 micrograms/ml. In contrast with the NSAIDs studied, the two sulphated polysaccharides (sodium pentosan polysulphate and glycosaminoglycan polysulphate ester) at low concentrations increased proteoglycan secretion by chondrocytes, with maximal stimulation occurring at 1 microgram/ml. Sodium pentosan polysulphate, but not glycosaminoglycan polysulphate ester, showed inhibitory activity at 50 and 100 micrograms/ml. PMID:2471470

Analysis of the data on pregnancy and lactation provided by patient information leaflets of anti-rheumatic drugs in Argentina.

PubMed

Sabando, Miguel Ormaza; Saavedra, Maira Arias; Sequeira, Gabriel; Kerzberg, Eduardo

2018-04-01

To analyse the level of consistency and updating of the information on pregnancy and lactation provided by patient information leaflets (PILs) of the antirheumatic drugs approved in Argentina. Inconsistencies between the 2016 EULAR Task Force recommendations on the use of anti-rheumatic drugs during pregnancy and lactation and the information provided by PILs of the same drugs approved in Argentina were analysed along with inconsistencies within the PILs of different registered trademarks of these drugs. Eighty-eight PILs of 32 drugs were analysed. Out of the 88 PILs, 50% presented information inconsistencies as to pregnancy. Medications comprised in this group were: hydroxychloroquine, sulfasalazine, azathioprine, tacrolimus, cyclosporine, NSAIDs (during the first two trimesters), celecoxib, some glucocorticoids, colchicine, and some anti-TNF drugs (etanercept, adalimumab and infliximab) during part of the pregnancy. As for lactation, 56% had information inconsistencies. Medications encompassed in this group were: hydroxychloroquine, chloroquine, sulfasalazine, azathioprine, tacrolimus, cyclosporine, NSAIDs, celecoxib, meprednisone, prednisone, colchicine, and anti-TNF drugs. Out of 17 drugs that had more than one registered trademark, information inconsistencies on pregnancy were found in the PILs of sulfasalazine, diclofenac, ibuprofen and methylprednisolone. Concerning lactation, inconsistencies were present in the PILs of hydroxychloroquine, sulfasalazine, diclofenac, ibuprofen, meprednisone, and colchicine. At least half of the PILs of anti-rheumatic drugs analysed in this study had information inconsistencies on pregnancy and lactation. This is a serious state of affairs because the consensual decision-making process between patient and professional may be compromised, which, in turn, may give rise to medical-legal issues.

Laboratory Monitoring of Patients Treated with Antihypertensive Drugs and Newly Exposed to Non Steroidal Anti-Inflammatory Drugs: A Cohort Study

PubMed Central

Fournier, Jean-Pascal; Lapeyre-Mestre, Maryse; Sommet, Agnès; Dupouy, Julie; Poutrain, Jean-Christophe; Montastruc, Jean-Louis

2012-01-01

Background Drug-Drug Interactions between Non Steroidal Anti-Inflammatory Drugs (NSAIDs) and Angiotensin Converting Enzyme Inhibitors (ACEIs), Angiotensin Receptor Blocker (ARBs) or diuretics can lead to renal failure and hyperkalemia. Thus, monitoring of serum creatinine and potassium is recommended when a first dispensing of NSAID occur in patients treated with these drugs. Methods We conducted a pharmacoepidemiological retrospective cohort study using data from the French Health Insurance Reimbursement Database to evaluate the proportion of serum creatinine and potassium laboratory monitoring in patients treated with ACEI, ARB or diuretic and receiving a first dispensing of NSAID. We described the first dispensing of NSAID among 3,500 patients of a 4-year cohort (6,633 patients treated with antihypertensive drugs) and analyzed serum creatinine and potassium laboratory monitoring within the 3 weeks after the first NSAID dispensing. Results General Practitioners were the most frequent prescribers of NSAIDs (85.5%, 95% CI: 84.3–86.6). The more commonly prescribed NSAIDs were ibuprofen (20%), ketoprofen (15%), diclofenac (15%) and piroxicam (12%). Serum creatinine and potassium monitoring was 10.7% (95% CI: 9.5–11.8) in patients treated by ACEIs, ARBs or diuretics. Overall, monitoring was more frequently performed to women aged over 60, treated with digoxin or glucose lowering drugs, but not to patients treated with ACEIs, ARBs or diuretics. Monitoring was more frequent when NSAIDs' prescribers were cardiologists or anesthesiologists. Conclusion Monitoring of serum creatinine and potassium of patients treated with ACEIs, ARBs or diuretics and receiving a first NSAID dispensing is insufficiently performed and needs to be reinforced through specific interventions. PMID:22479557

Oral Versus Topical Diclofenac Sodium in the Treatment of Osteoarthritis.

PubMed

Tieppo Francio, Vinicius; Davani, Saeid; Towery, Chris; Brown, Tony L

2017-06-01

Osteoarthritis (OA) is one of the most common causes of joint pain in the United States and non-steroidal anti-inflammatories (NSAIDs), such as Diclofenac sodium, which is currently available in two main routes of administration; oral and topical distribution have been established as one of the standard treatments for OA. Generally, oral NSAIDs are well tolerated; however our narrative review suggests that the topical solution had a better tolerability property than oral Diclofenac sodium, especially due to side effects of gastrointestinal bleeding with the utilization of the oral format. In addition, the topical route may be considered a reasonable selection by clinicians for management of musculoskeletal pain in those patients with a history of potential risk and adverse side effects. Most studies reviewed comparing oral versus topical solution of Diclofenac sodium revealed comparable efficacy, with minimal side effects utilizing the topical route. The key point of this narrative review is to help clinicians that currently must decide between very inexpensive diclofenac oral presentations and expensive topical presentations especially in the elderly population and the pros and cons of such decision-making process.

Drug-loaded electrospun mats of poly(vinyl alcohol) fibres and their release characteristics of four model drugs

NASA Astrophysics Data System (ADS)

Taepaiboon, Pattama; Rungsardthong, Uracha; Supaphol, Pitt

2006-05-01

Mats of PVA nanofibres were successfully prepared by the electrospinning process and were developed as carriers of drugs for a transdermal drug delivery system. Four types of non-steroidal anti-inflammatory drug with varying water solubility property, i.e. sodium salicylate (freely soluble in water), diclofenac sodium (sparingly soluble in water), naproxen (NAP), and indomethacin (IND) (both insoluble in water), were selected as model drugs. The morphological appearance of the drug-loaded electrospun PVA mats depended on the nature of the model drugs. The 1H-nuclear magnetic resonance results confirmed that the electrospinning process did not affect the chemical integrity of the drugs. Thermal properties of the drug-loaded electrospun PVA mats were analysed by differential scanning calorimetry and thermogravimetric analysis. The molecular weight of the model drugs played a major role on both the rate and the total amount of drugs released from the as-prepared drug-loaded electrospun PVA mats, with the rate and the total amount of the drugs released decreasing with increasing molecular weight of the drugs. Lastly, the drug-loaded electrospun PVA mats exhibited much better release characteristics of the model drugs than drug-loaded as-cast films.

Aqueous solubility of diclofenac diethylamine in the presence of pharmaceutical additives: a comparative study with diclofenac sodium.

PubMed

Khalil, E; Najjar, S; Sallam, A

2000-04-01

Aqueous solubility of diclofenac diethylamine (DDEA), a nonsteroidal anti-inflammatory drug currently formulated as a topical emulgel, was studied in the presence of pharmaceutical additives and compared with diclofenac sodium (DS). Electrolytes at low concentrations exhibited a salting-in effect on DDEA with peak solubility that was attributed to the association of DDEA into micelles, followed by a salting-out effect at higher concentrations, by which structure formation by DDEA molecules increased and precipitation occurred. For DS, which is not capable of forming micelles, the salting-out effect was dominant due to the common ion effect. Cosolvents displayed significant enhancement in solubility of both salts except glycerol, which showed a slight increase in solubility of DDEA and a decrease in solubility of DS due to transformation into the less soluble hydrate form. Ethanol and polyethylene glycol (PEG) 400 cosolvent systems at all concentrations showed positive deviations from the log-linear solubility equation. In the case of propylene glycol (PG) cosolvent systems, negative deviations were observed at low volume fractions of cosolvent, while positive deviations were observed at high volume fractions of cosolvent for DS and DDEA. The parent drug, being less ionizable and highly nonpolar, showed negative deviations up to 90% PG content. Thus, the positive deviations for DS and DDEA could be attributed to the more ionizable carboxylic group and its higher ability for hydrogen bonding at higher fractions of cosolvent. Polyvinylpyrrolidone (PVP) and PEG4000 or PEG6000 enhanced the solubility of DS and DDEA, with PVP exerting higher solubilizing efficiency and DS showing better solubility than DDEA. Solubilities of DS in Tween 80 (T80) and Pluronic F-127 (PF127) aqueous solutions were almost similar, while the solubility of DDEA in the presence of T80 was higher than the solubility in the presence of PF127. DS appeared to be located more in the polyoxyethylene mantle of the micelles, while DDEA was located more in the core of the micelles.

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

Xu, Guang-Lin; Department of Pharmacology, University of Michigan, Ann Arbor; Du, Yi-Fang

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

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

PubMed

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 carrageenan. Ginger anti-inflammatory activity is mediated by inhibiting macrophage and neutrophils activation as well as negatively affecting monocyte and leukocyte migration. This was evidenced by the dose-dependent decrease in pro-inflammatory cytokines and chemokines and replenishment the total antioxidant capacity. Copyright © 2017 Elsevier B.V. All rights reserved.

Pentadecapeptide BPC 157 positively affects both non-steroidal anti-inflammatory agent-induced gastrointestinal lesions and adjuvant arthritis in rats.

PubMed

Sikiric, P; Seiwerth, S; Grabarevic, Z; Rucman, R; Petek, M; Jagic, V; Turkovic, B; Rotkvic, I; Mise, S; Zoricic, I; Konjevoda, P; Perovic, D; Simicevic, V; Separovic, J; Hanzevacki, M; Ljubanovic, D; Artukovic, B; Bratulic, M; Tisljar, M; Rekic, B; Gjurasin, M; Miklic, P; Buljat, G

1997-01-01

Besides a superior protection of the pentadecapeptide BPC 157 (an essential fragment of an organoprotective gastric juice peptide BPC) against different gastrointestinal and liver lesions, an acute anti-inflammatory and analgetic activity was also noted. Consequently, its effect on chronic inflammation lesions, such as adjuvant arthritis, and non-steroidal anti-inflammatory agents (NSAIAs)-induced gastrointestinal lesions was simultaneously studied in rats. In gastrointestinal lesions (indomethacin (30 mg/kg s.c.), aspirin (400 mg/kg i.g.) and diclofenac (125 mg/kg i.p.) studies, BPC 157 (10 micrograms or 10 ng/kg i.p.) was regularly given simultaneously and/or 1 h prior to drug application (indomethacin). In the adjuvant arthritis (tail-application of 0.2 mL of Freund's adjuvant) studies (14 days, 30 days, 1 year) BPC 157 (10 micrograms or 10 ng/kg i.p.), it was given as a single application (at 1 h either before or following the application of Freund's adjuvant) or in a once daily regimen (0-14th day, 14-30th day, 14th day-1 year). Given with the investigated NSAIAs, BPC 157 consistently reduced the otherwise prominent lesions in the stomach of the control rats, as well as the lesions in the small intestine in the indomethacin groups. In the adjuvant arthritis studies, the lesion's development seems to be considerably reduced after single pentadecapeptide medication, and even more attenuated in rats daily treated with BPC 157. As a therapy of already established adjuvant arthritis, its salutary effect consistently appeared already after 2 weeks of medication and it could be clearly seen also after 1 year of application. Taking together all these results, the data likely point to a special anti-inflammatory and mucosal integrity protective effect.

Topical Treatments for Localized Neuropathic Pain.

PubMed

Casale, Roberto; Symeonidou, Z; Bartolo, M

2017-03-01

Topical therapeutic approaches in localized neuropathic pain (LNP) syndromes are increasingly used by both specialists and general practitioners, with a potentially promising effect on pain reduction. In this narrative review, we describe the available compounds for topical use in LNP syndromes and address their potential efficacy according to the literature. Local anaesthetics (e.g., lidocaine, bupivacaine and mepivacaine), as well as general anaesthetic agents (e.g., ketamine), muscle relaxants (e.g., baclofen), capsaicin, anti-inflammatory drugs (e.g., diclofenac), salicylates, antidepressants (e.g., amitriptyline and doxepin), α2 adrenergic agents (e.g., clonidine), or even a combination of them have been tested in various applications for the treatment of LNP. Few of them have reached a sufficient level of evidence to support systematic use as treatment options. Relatively few systemic side effects or drug-drug interactions and satisfactory efficacy seem to be the benefits of topical treatments. More well-organized and tailored studies are necessary for the further conceptualization of topical treatments for LNP.

Neostigmine interactions with non steroidal anti-inflammatory drugs.

PubMed

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.

A proteomic evaluation of the effects of the pharmaceuticals diclofenac and gemfibrozil on marine mussels (Mytilus spp.): evidence for chronic sublethal effects on stress-response proteins.

PubMed

Schmidt, Wiebke; Rainville, Louis-Charles; McEneff, Gillian; Sheehan, David; Quinn, Brian

2014-03-01

Human pharmaceuticals (e.g. the lipid regulator gemfibrozil and the non-steroidal anti-inflammatory drug diclofenac) are an emerging environmental threat in the aquatic environment. This study aimed to evaluate sublethal effects of these two commonly found pharmaceuticals on the protein profiles of marine mussels (Mytilus spp.). Mytilus spp. was exposed to environmentally relevant and elevated concentrations (1 and 1000 µg/l respectively) of both drugs for 14 days. In addition, mussels were maintained for seven days post treatment to examine the potential of blue mussels to recover from such an exposure. Differential protein expression signatures (PES) in the digestive gland of mussels were obtained using two-dimensional gel electrophoresis after 7, 14, and 21 days of exposure. Twelve spots were significantly increased or decreased by gemfibrozil and/or diclofenac, seven of which were successfully identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. These proteins were involved in energy metabolism, oxidative stress response, protein folding, and immune responses. Changes in the PES over time suggested that mussels were still experiencing oxidative stress for up to seven days post exposure. In addition, a suite of biomarkers comprising glutathione transferase, lipid peroxidation, and DNA damage were studied. An oxidative stress response was confirmed by biomarker responses. To our knowledge, this is the first investigation using proteomics to assess the potential effects of human pharmaceuticals on a non-target species in an environmentally-relevant model. The successful application of this proteomic approach supports its potential use in pollution biomonitoring and highlights its ability to aid in the discovery of new biomarkers. Copyright © 2013 John Wiley & Sons, Ltd.

Solar photolysis versus TiO2-mediated solar photocatalysis: a kinetic study of the degradation of naproxen and diclofenac in various water matrices.

PubMed

Kanakaraju, Devagi; Motti, Cherie A; Glass, Beverley D; Oelgemöller, Michael

2016-09-01

Given that drugs and their degradation products are likely to occur as concoctions in wastewater, the degradation of a mixture of two nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac (DCF) and naproxen (NPX), was investigated by solar photolysis and titanium dioxide (TiO2)-mediated solar photocatalysis using an immersion-well photoreactor. An equimolar ratio (1:1) of both NSAIDs in distilled water, drinking water, and river water was subjected to solar degradation. Solar photolysis of the DCF and NPX mixture was competitive particularly in drinking water and river water, as both drugs have the ability to undergo photolysis. However, the addition of TiO2 in the mixture significantly enhanced the degradation rate of both APIs compared to solar photolysis alone. Mineralization, as measured by chemical oxygen demand (COD), was incomplete under all conditions investigated. TiO2-mediated solar photocatalytic degradation of DCF and NPX mixtures produced 15 identifiable degradants corresponding to degradation of the individual NSAIDs, while two degradation products with much higher molecular weight than the parent NSAIDs were identified by liquid chromatography mass spectrometry (LC-MS) and Fourier transform-ion cyclotron resonance-mass spectrometry (FT-ICR-MS). This study showed that the solar light intensity and the water matrix appear to be the main factors influencing the overall performance of the solar photolysis and TiO2-mediated solar photocatalysis for degradation of DCF and NPX mixtures.

Nature is the best source of anti-inflammatory drugs: indexing natural products for their anti-inflammatory bioactivity.

PubMed

Aswad, Miran; Rayan, Mahmoud; Abu-Lafi, Saleh; Falah, Mizied; Raiyn, Jamal; Abdallah, Ziyad; Rayan, Anwar

2018-01-01

The aim was to index natural products for less expensive preventive or curative anti-inflammatory therapeutic drugs. A set of 441 anti-inflammatory drugs representing the active domain and 2892 natural products representing the inactive domain was used to construct a predictive model for bioactivity-indexing purposes. The model for indexing the natural products for potential anti-inflammatory activity was constructed using the iterative stochastic elimination algorithm (ISE). ISE is capable of differentiating between active and inactive anti-inflammatory molecules. By applying the prediction model to a mix set of (active/inactive) substances, we managed to capture 38% of the anti-inflammatory drugs in the top 1% of the screened set of chemicals, yielding enrichment factor of 38. Ten natural products that scored highly as potential anti-inflammatory drug candidates are disclosed. Searching the PubMed revealed that only three molecules (Moupinamide, Capsaicin, and Hypaphorine) out of the ten were tested and reported as anti-inflammatory. The other seven phytochemicals await evaluation for their anti-inflammatory activity in wet lab. The proposed anti-inflammatory model can be utilized for the virtual screening of large chemical databases and for indexing natural products for potential anti-inflammatory activity.

Evaluation of fatty acid amides in the carrageenan-induced paw edema model.

PubMed

Wise, Laura E; Cannavacciulo, Roberta; Cravatt, Benjamin F; Martin, Billy F; Lichtman, Aron H

2008-01-01

While it has long been recognized that Delta(9)-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis, and other cannabinoid receptor agonists possess anti-inflammatory properties, their well known CNS effects have dampened enthusiasm for therapeutic development. On the other hand, genetic deletion of fatty acid amide hydrolase (FAAH), the enzyme responsible for degradation of fatty acid amides, including endogenous cannabinoid N-arachidonoyl ethanolamine (anandamide; AEA), N-palmitoyl ethanolamine (PEA), N-oleoyl ethanolamine (OEA), and oleamide, also elicits anti-edema, but does not produce any apparent cannabinoid effects. The purpose of the present study was to investigate whether exogenous administration of FAAs would augment the anti-inflammatory phenotype of FAAH (-/-) mice in the carrageenan model. Thus, we evaluated the effects of the FAAs AEA, PEA, OEA, and oleamide in wild-type and FAAH (-/-) mice. For comparison, we evaluated the anti-edema effects of THC, dexamethasone (DEX), a synthetic glucocorticoid, diclofenac (DIC), a nonselective cyclooxygenase (COX) inhibitor, in both genotypes. A final study determined if tolerance to the anti-edema effects of PEA occurs after repeated dosing. PEA, THC, DEX, DIC elicited significant decreases in carrageenan-induced paw edema in wild-type mice. In contrast OEA produced a less reliable anti-edema effect than these other drugs, and AEA and oleamide failed to produce any significant decreases in paw edema. Moreover, none of the agents evaluated augmented the anti-edema phenotype of FAAH (-/-) mice, suggesting that maximal anti-edema effects had already been established. PEA was the most effective FAA in preventing paw edema and its effects did not undergo tolerance. While the present findings do not support a role for AEA in preventing carrageenan-induced edema, PEA administration and FAAH blockade elicited anti-edema effects of an equivalent magnitude as produced by THC, DEX, and DIC in this assay.

Establishing Structure Property Relationship in Drug Partitioning into and Release from Niosomes: Physical Chemistry Insights with Anti-Inflammatory Drugs.

PubMed

Dasgupta, Moumita; Kishore, Nand

2017-09-28

Understanding the physical chemistry underlying interactions of drugs with delivery formulations is extremely important in devising effective drug delivery systems. The partitioning and release kinetics of diclofenac sodium and naproxen from Brij 30 and Triton X-100 niosomal formulations have been addressed based on structural characterization, partitioning energetics, and release kinetics, thus establishing a relationship between structures and observed properties. Both the drugs partition in nonpolar regions of TX-100 niosomes via stacking of aromatic rings. The combined effects of interactions of the drugs with polar head groups and the rigidity of the niosome vesicles determine entry and partitioning of drugs into niosomes. The observed slower rate of release of the drugs from the drug encapsulated niosomes of TX-100 than those of Brij 30, suggest stable complexation of drugs in the nonpolar interior of the former. No release of drugs from the niosomes was observed until 24 h even upon varying pH conditions without SDS. However, SDS in drug loaded niosomes led to release of drugs in as early as 6 h. The sustained pattern of in vitro release kinetics of the drugs thus observed from our niosomal preparations suggest these vesicular systems to be promising for pharamaceutical applications as potential drug delivery vehicles.

[Dependence of anti-inflammatory effects of high peak-power pulsed electromagnetic radiation of extremely high frequency on exposure parameters].

PubMed

Gapeev, A B; Mikhaĭlik, E N; Rubanik, A V; Cheremis, N K

2007-01-01

A pronounced anti-inflammatory effect of high peak-power pulsed electromagnetic radiation of extremely high frequency was shown for the first time in a model of zymosan-induced footpad edema in mice. Exposure to radiation of specific parameters (35, 27 GHz, peak power 20 kW, pulse widths 400-600 ns, pulse repetition frequency 5-500 Hz) decreased the exudative edema and local hyperthermia by 20% compared to the control. The kinetics and the magnitude of the anti-inflammatory effect were comparable with those induced by sodium diclofenac at a dose of 3 mg/kg. It was found that the anti-inflammatory effect linearly increased with increasing pulse width at a fixed pulse repetition frequency and had threshold dependence on the average incident power density of the radiation at a fixed pulse width. When animals were whole-body exposed in the far-field zone of radiator, the optimal exposure duration was 20 min. Increasing the average incident power density upon local exposure of the inflamed paw accelerated both the development of the anti-inflammatory effect and the reactivation time. The results obtained will undoubtedly be of great importance in the hygienic standardization of pulsed electromagnetic radiation and in further studies of the mechanisms of its biological action.

Comparison of the Effects of Daily Single-Dose Use of Flurbiprofen, Diclofenac Sodium, and Tenoxicam on Postoperative Pain, Swelling, and Trismus: A Randomized Double-Blind Study.

PubMed

Kaplan, Volkan; Eroğlu, Cennet Neslihan

2016-10-01

The aim of the present study was to compare the effects of daily single-dose use of flurbiprofen, diclofenac sodium, and tenoxicam on pain, swelling, and trismus that occur after surgical extraction of impacted wisdom teeth using local anesthesia. The present study included 3 groups with 30 patients in each group. Those volunteering to participate in this double-blind randomized study (n = 90) were selected from a patient population with an indication for extraction of impacted wisdom teeth. Group 1 patients received 200 mg flurbiprofen, group 2 patients received 100 mg diclofenac sodium, and group 3 patients received 20 mg tenoxicam. All doses were once a day, starting preoperatively. Pain was evaluated postoperatively at 1, 2, 3, 6, 8, and 24 hours and at 2 and 7 days using a visual analog scale (VAS). For comparison with the preoperative measurements, the patients were invited to postoperative follow-up visits 2 and 7 days after extraction to evaluate for swelling and trismus. The statistical analysis was performed using descriptive statistics in SAS, version 9.4 (SAS Institute, Cary, NC), software. Statistical analysis of the pain, swelling, and trismus data was performed using the Kruskal-Wallis, Dunn, and Wilcoxon-Mann-Whitney U tests. The statistical level of significance was accepted at P = .05 and power of 0.80. Clinically, tenoxicam showed better analgesic and anti-inflammatory efficacy compared with diclofenac sodium and, in particular, flurbiprofen. Although the VAS scores in the evaluation of pain showed statistically significant differences at 2 days, no statistically significant difference was found for swelling and trismus. Our study evaluated the analgesic and anti-inflammatory effects with a daily single dose of flurbiprofen, diclofenac sodium, and tenoxicam. Daily 20 mg tenoxicam can be accepted as an adequate and safe option for patients after a surgical procedure. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Analysis of the presence of cardiovascular and analgesic/anti-inflammatory/antipyretic pharmaceuticals in river- and drinking-water of the Madrid Region in Spain.

PubMed

Valcárcel, Y; Alonso, S González; Rodríguez-Gil, J L; Maroto, R Romo; Gil, A; Catalá, M

2011-02-01

Interest in the presence of pharmaceuticals in wastewater, in the water of our rivers and, to a lesser extent, in our drinking water, has been growing in recent decades. Many of these substances, currently classified as "emerging pollutants", are biologically active compounds and continuously released in effluents. As sewage treatment plants (STPs) are not adequately equipped to eliminate all of these substances completely, some are discharged directly into rivers. In Spain, as in most of its neighbouring countries, there is an elevated use of pharmaceuticals for the treatment of cardiovascular diseases (which are extremely prevalent among the older adult population) and anti-inflammatory medications, which are obtainable over the counter without a medical prescription. This study therefore sought to determine to what degree pharmaceuticals with the highest regional prescription and/or use rates, such as cardiovascular and analgesic/anti-inflammatory/antipyretic medications, were present in the principal rivers (Jarama, Manzanares, Guadarrama, Henares and Tagus) and tap-water samples of the Madrid Region (MR). Samples were taken downstream the discharge of 10 of the most important region's STPs and the most frequently used drugs in the region were analysed for. Of the 24 drugs analysed, 21 were detected at concentrations ranging from 2 ng L⁻¹ to 18 μg L⁻¹. The highest drug concentrations corresponded to ibuprofen, diclofenac, naproxen, atenolol, frusemide (furosemide), gemfibrozil and hydrochlorthiazide, and in most cases exceeded the amounts reported in the scientific literature. No traces of these groups of pharmaceuticals were detected in the drinking water analysed. On the basis of the high concentrations detected, we believe that an environmental surveillance system should be implemented to assess the continuous discharge of these pharmaceuticals and their possible ecotoxicological effects. At the same time, efforts to raise the awareness of the public about responsible use and the proper disposal of such substances at purpose-designated collection points should be increased. Furthermore sewage treatment processes should be suitably adapted to increase the rates of removal of these drugs. Copyright © 2010 Elsevier Ltd. All rights reserved.

Physicians' approaches to the use of gastroprotective strategies in low-risk non-steroidal anti-inflammatory drug users.

PubMed

Murthy, S K; Kauldher, S; Targownik, L E

2006-05-01

Many doctors unnecessarily prescribe gastroprotective strategies to non-steroidal anti-inflammatory drugs users at low risk of non-steroidal anti-inflammatory drug-related gastrointestinal complications. To identify factors that predict the overuse of gastroprotective strategies in low-risk non-steroidal anti-inflammatory drug users. We distributed a questionnaire to family doctors and general internists consisting of a clinical vignette describing a low-risk hypothetical patient with osteoarthritis who was a candidate for non-steroidal anti-inflammatory drug therapy. Respondents were asked whether they would prescribe this patient a gastroprotective strategy and to estimate the annual risk of that patient developing a gastrointestinal complication with non-steroidal anti-inflammatory drug use. Respondents inappropriately recommending a gastroprotective strategy were compared with respondents who opted not to use gastroprotection. We received 340 responses (response rate of 28.3%), of which 278 supplied analysable data. Thirty-five percent of respondents inappropriately recommended a gastroprotective strategy for the low-risk subject. Inappropriate prescribers were significantly more likely to overestimate the risk of gastrointestinal complications with traditional non-steroidal anti-inflammatory drugs and this was strongly predictive of gastroprotective strategy recommendation in logistic regression. Many doctors inappropriately recommend gastroprotective strategies in low-risk non-steroidal anti-inflammatory drug users. Improving doctors' awareness of non-steroidal anti-inflammatory drug-associated gastrointestinal risks may lead to a decrease in inappropriate utilization of gastroprotective strategies in low-risk patients.

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

PubMed

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 prescription pattern of NSAIDs in Northeastern Iranian population and also provide suggestions for a more rational prescription behavior for such drugs. In this cross-sectional retrospective study, pattern of 1-year prescriptions was inspected based on 9.3 million prescriptions from two insurance companies. Type of NSAIDs, all dispensed doses and the number of NSAIDs ordered per prescription, and the route of administration for each patient were extracted from the databases. The prescription pattern of NSAIDs was analyzed seasonally. Out of 9,303,585 prescriptions, 19.3% contained at least one NSAID. Diclofenac was the most commonly prescribed NSAID (49.21%). At least two NSAIDs were simultaneously prescribed in 7% of prescriptions. General practitioners prescribed NSAIDs more frequently (67%) than specialists. Orthopedic surgeons and internists more frequently prescribed NSAIDs in comparison with other physicians (6% and 4%, respectively). Gastroprotective agents (GPAs) were coprescribed to only 7.62% of prescriptions. The frequency of NSAIDs prescription was relatively high in Northeast of Iran. A significant number of prescriptions were associated with irrational prescribing in both coadministration of NSAIDs and GPAs and NSAIDs combination. A strategy must be developed and implemented for prescribing and rational use of medications, e.g., continuing medical education regarding the potential risks of NSAIDs, importance of their appropriate and rational use, and necessity of appropriate prescription writing regarding both content and indication.

Genotoxic response and oxidative stress induced by diclofenac, ibuprofen and naproxen in Daphnia magna.

PubMed

Gómez-Oliván, Leobardo Manuel; Galar-Martínez, Marcela; García-Medina, Sandra; Valdés-Alanís, Analleli; Islas-Flores, Hariz; Neri-Cruz, Nadia

2014-10-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used pharmaceuticals in Mexico, but there is not proper regulation on the sale, use and disposal. These drugs can enter water bodies by diverse pathways, attaining significant concentrations and inducing damage on hydrobionts. To evaluate the oxidative stress and consequent damage to genetic material induced by DCF, IBP and NPX on Daphnia magna. The acute toxicity assays were performed to 48-h by nonsteroidal anti-inflammatory drugs evaluated. A sublethal assay were done after 48 h of exposure to DCF, IBP and NPX added to water with the concentration equivalent to the lowest observed adverse effect level (LOAEL), 9.7 mg/L for DCF, 2.9 mg/L for IBP and 0.017 mg/L for NPX. The DNA damage (comet assay) was evaluated at 12, 48 and 96 h. The oxidative biomarkers were evaluated: lipid peroxidation; protein carbonyl content; activity of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase. D. magna exposed to DCF, IBP and NPX showed a significant increase (p < 0.05) with respect to controls in LPX. PCC was increased in IBP exposure. SOD and CAT activity were increased by exposure to IBP and NPX. GPX shows a significant increase with respect to control in IBP and DCF exposure and significant decrease by NPX exposure. DNA damage was observed in 48 and 96 h. DCF, IBP and NPX were responsible of alterations in biochemical biomarkers evaluated and DNA damage.

Bilobalide, a unique constituent of Ginkgo biloba, inhibits inflammatory pain in rats.

PubMed

Goldie, Michelle; Dolan, Sharron

2013-08-01

Standardized Ginkgo biloba extract EGb 761 has been shown to inhibit inflammatory hyperalgesia in rats; however, the mechanism of action is not known. This study set out to investigate the anti-inflammatory and analgesic potential of bilobalide, a unique G. biloba constituent, in three well-characterized models of acute inflammatory pain. The effect of oral, intraplantar or intrathecal administration of bilobalide or drug-vehicle (0.25% agar; 10% ethanol in H2O) on responses to noxious thermal and mechanical stimulation of the hindpaw, and paw oedema were assessed in adult male Wistar rats before and after intradermal hindpaw injection of carrageenan (3%; 50 μl) or capsaicin (10 μg; 50 μl) or after hindpaw incision (n=6-8/group). Oral administration of bilobalide (10-30 mg/kg) significantly inhibited thermal hyperalgesia in response to carrageenan, capsaicin and paw incision, independent of dose, with an efficacy similar to that of diclofenac. In the carrageenan model, mechanical hypersensitivity and paw oedema were also significantly reduced after treatment with bilobalide (10-30 mg/kg). Intrathecal administration of bilobalide (0.5-1 μg) inhibited carrageenan-induced thermal hyperalgesia, but had no effect on mechanical hypersensitivity or paw oedema (application≥2 μg induced adverse effects, precluding testing of higher doses). Intraplantar administration of bilobalide (30-100 μg) had no effect. These data show that bilobalide is a potent anti-inflammatory and antihyperalgesic agent, the therapeutic effects of which are mediated in part through a central site of action, and may account for the therapeutic action of the whole extract G. biloba.

Anti-inflammatory and Analgesic Activities of Topical Formulations of Pterocarpus Santalinus Powder in Rat Model of Chronic Inflammation

PubMed Central

Gupta, Amit O; Jain, Sourav; Dawane, Jayshree Shriram

2017-01-01

Introduction The incidence of arthritis is quite high and there is a need for the search of natural products to halt the progression of disease or provide symptomatic relief without significant adverse effects. Aim This study aimed at evaluating the anti-inflammatory and analgesic activities of topical Pterocarpus santalinus in an animal model of chronic inflammation. Materials and Methods Albino rats of either sex were divided into five groups of six rats each (Group I – Control, Group II –Gel base, Group III –P. santalinus paste, Group IV –P. santalinus gel, Group V– Diclofenac gel). Chronic inflammation was induced on day 0 by injecting 0.1 ml Complete Freund’s Adjuvant (CFA) in sub-plantar tissue of left hind paw of the rats. Topical treatment was started from day 12 till day 28. Body weight and paw volume (Plethysmometer) were assessed on day 0, 12 and 28. Pain assessment was done using Randall and Selitto paw withdrawal method. Data was analysed using GraphPad Prism version 5. Unpaired students t-test and ANOVA followed by Tukey’s test was used for comparison among groups. Results Only topical P.santalinus gel significantly reduced the body weight (p=0.02) due to reduction in inflammatory oedema of the left limb. P. santalinus gel also showed significant reduction (p=0.03) in paw volume of rats compared to the other groups. There was significant reduction in pain threshold (gm/sec) due to chronic inflammation, with all the study drugs (p<0.05) but with P. santalinus gel, this reduction was less (p<0.001). Conclusion Gel showed significant anti-inflammatory and mild analgesic activity on topical application in rat model of chronic inflammation. PMID:28892928

Anti-inflammatory and Analgesic Activities of Topical Formulations of Pterocarpus Santalinus Powder in Rat Model of Chronic Inflammation.

PubMed

Dhande, Priti Pravin; Gupta, Amit O; Jain, Sourav; Dawane, Jayshree Shriram

2017-07-01

The incidence of arthritis is quite high and there is a need for the search of natural products to halt the progression of disease or provide symptomatic relief without significant adverse effects. This study aimed at evaluating the anti-inflammatory and analgesic activities of topical Pterocarpus santalinus in an animal model of chronic inflammation. Albino rats of either sex were divided into five groups of six rats each (Group I - Control, Group II -Gel base, Group III - P. santalinus paste, Group IV - P. santalinus gel, Group V- Diclofenac gel). Chronic inflammation was induced on day 0 by injecting 0.1 ml Complete Freund's Adjuvant (CFA) in sub-plantar tissue of left hind paw of the rats. Topical treatment was started from day 12 till day 28. Body weight and paw volume (Plethysmometer) were assessed on day 0, 12 and 28. Pain assessment was done using Randall and Selitto paw withdrawal method. Data was analysed using GraphPad Prism version 5. Unpaired students t-test and ANOVA followed by Tukey's test was used for comparison among groups. Only topical P.santalinus gel significantly reduced the body weight (p=0.02) due to reduction in inflammatory oedema of the left limb. P. santalinus gel also showed significant reduction (p=0.03) in paw volume of rats compared to the other groups. There was significant reduction in pain threshold (gm/sec) due to chronic inflammation, with all the study drugs (p<0.05) but with P. santalinus gel, this reduction was less (p<0.001). Gel showed significant anti-inflammatory and mild analgesic activity on topical application in rat model of chronic inflammation.

The Ablation or Reduction of Intraoperative Tourniquet Pain with Preoperative Administration of IV Ketorolac Tromethamine

DTIC Science & Technology

1994-08-01

non - steroidal anti - inflammatory drug . Anticipated conclusions of...tromethamine is a nonsteroidal, anti - inflammatory drug (NSAID) that does not have CNS activity. It is a potent analgesic with less anti - inflammatory ...nonsteroidal, anti - inflammatory drug that inhibits prostaglandin production. Administration of ketorolac tromethamine prior to tourniquet inflation

Application of statistical experimental design to the optimisation of microextraction by packed sorbent for the analysis of nonsteroidal anti-inflammatory drugs in human urine by ultra-high pressure liquid chromatography.

PubMed

Magiera, Sylwia; Gülmez, Şefika; Michalik, Aleksandra; Baranowska, Irena

2013-08-23

A new approach based on microextraction by packed sorbent (MEPS) and a reversed-phase ultra-high pressure liquid chromatography (UHPLC) method was developed and validated for the determination and quantification of nonsteroidal anti-inflammatory drugs (NSAIDs) (acetylsalicylic acid, ketoprofen, diclofenac, naproxen and ibuprofen) in human urine. The important factors that could influence the extraction were previously screened using the Plackett-Burman design approach. The optimal MEPS extraction conditions were obtained using C18 phase as a sorbent, small sample volume (20μL) and a short time period (approximately 5min) for the entire sample preparation step. The analytes were separated on a core-shell column (Poroshell 120 EC-C18; 100mm×3.0mm; 2.7μm) using a binary mobile phase composed of aqueous 0.1% trifluoroacetic acid and acetonitrile in the gradient elution mode (4.5min of analysis time). The analytical method was fully validated based on linearity, limits of detection (LOD), limits of quantification (LOQ), inter- and intra-day precision and accuracy, and extraction yield. Under optimised conditions, excellent linearity (R(2)>0.9991), limits of detection (1.07-16.2ngmL(-1)) and precision (0.503-9.15% RSD) were observed for the target drugs. The average absolute recoveries of the analysed compounds extracted from the urine samples were 89.4-107%. The proposed method was also applied to the analysis of NSAIDs in human urine. The new approach offers an attractive alternative for the analysis of selected drugs from urine samples, providing several advantages including fewer sample preparation steps, faster sample throughput and ease of performance compared to traditional methodologies. Copyright © 2013 Elsevier B.V. All rights reserved.

Pharmacokinetics of Diclofenac and Hydroxypropyl‐β‐Cyclodextrin (HPβCD) Following Administration of Injectable HPβCD‐Diclofenac in Subjects With Mild to Moderate Renal Insufficiency or Mild Hepatic Impairment

PubMed Central

Hamilton, Douglas A.; Ernst, Cynthia C.; Kramer, William G.; Madden, Donna; Lang, Eric; Liao, Edward; Lacouture, Peter G.; Ramaiya, Atulkumar

2017-01-01

Abstract Given their established analgesic properties, nonsteroidal anti‐inflammatory drugs (NSAIDs) represent an important postoperative pain management option. This study investigated: (1) the effects of mild or moderate renal insufficiency and mild hepatic impairment on the pharmacokinetics (PK) of diclofenac and hydroxypropyl‐β‐cyclodextrin (HPβCD) following administration of the injectable NSAID HPβCD‐diclofenac; and (2) the PK of HPβCD following administration of HPβCD‐diclofenac and intravenous itraconazole formulated with HPβCD in healthy adults. Diclofenac clearance (CL) and volume of distribution (Vz) tended to increase with decreasing renal function (moderate insufficiency versus mild insufficiency or healthy controls). Regression analysis demonstrated a significant relationship between Vz (but not CL or elimination half‐life, t½) and renal function. HPβCD CL was significantly decreased in subjects with renal insufficiency, with a corresponding increase in t½. There were no significant differences in diclofenac or HPβCD PK in subjects with mild hepatic impairment versus healthy subjects. Exposure to HPβCD in healthy subjects following HPβCD‐diclofenac administration was ∼12% of that with intravenous itraconazole, after adjusting for dosing schedule and predicted accumulation (<5% without adjustment). With respect to PK properties, these results suggest that HPβCD‐diclofenac might be administered to patients with mild or moderate renal insufficiency or mild hepatic impairment without dose adjustment (NCT00805090). PMID:29197175

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

PubMed

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 (p<0.001). Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent the transition of acute low back pain to chronic low back pain.

Synthesis of new bioactive aminophosphonates and study of their antioxidant, anti-inflammatory and antibacterial activities as well the assessment of their toxicological activity

NASA Astrophysics Data System (ADS)

Damiche, Rebiha; Chafaa, Salah

2017-02-01

Two new categories of α-aminophosphonates molecules were synthesized and characterized by UV-Vis, IR, and NMR. Their spectral properties show a perfect convergence. Their biological activities were evaluated. Molecules 1a, 2a, and 1d present a greater antioxidant potential than BHT and vitamin C. The best anti-inflammatory activity is shown by the 2b molecule and that of 1a, 2a, and 2c molecules are closely comparable to that of diclofenac. The antibacterial activity of the synthesized compounds is significantly higher than the antibiotic amoxicillin. The hemolysis rate HR of compounds 1b, 1c, 2b, and 2c was lower than 5%.

A Review of Chronic Musculoskeletal Pain: Central and Peripheral Effects of Diclofenac.

PubMed

Atzeni, Fabiola; Masala, Ignazio Francesco; Sarzi-Puttini, Piercarlo

2018-06-05

Diclofenac is widely used to manage chronic inflammatory and degenerative joint diseases such as osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, and extra-articular rheumatism. Its various mechanisms of action make it particularly effective in treating nociceptive pain, but it is also an alternative for treating spinal and chronic central pain. Osteoarthritis and rheumatoid arthritis are the most frequently encountered arthritic conditions in adults. The management of nociceptive pain requires a sequential hierarchical approach, with the initial NSAID treatment being characterized by the replacement of one drug with another, or complete discontinuation usually because of insufficient pain control. OA- and RA-related pain is complex and multifactorial, and due to physiological interactions between the signaling of the central and peripheral nervous systems. The mechanisms of action of diclofenac make it particularly effective in treating both nociceptive pain and chronic central pain. This review underlines the mechanisms of diclofenac involved in chronic and acute joint pain, the most relevant adverse events.

Ursolic acid rich Ocimum sanctum L leaf extract loaded nanostructured lipid carriers ameliorate adjuvant induced arthritis in rats by inhibition of COX-1, COX-2, TNF-α and IL-1: Pharmacological and docking studies

PubMed Central

Abuzinadah, Mohammed F.; Alkreathy, Huda M.; Banaganapalli, Babajan; Mujeeb, Mohd

2018-01-01

Background Ursolic acid (UA) is a promising molecule with anti-inflammatory, analgesic and potential anti-arthritic activity. Methods This study was undertaken to make formulation and evaluation of Ocimum sanctum L. leaf extract (OLE) loaded nano-structured lipid carriers (OLE-NLCs) for improved transdermal delivery of UA. Different surfactants, solid lipids and liquid lipids were used for the preparation of NLCs. The NLCs were developed using emulsion solvent diffusion and evaporation method. Different physicochemical properties, entrapment efficacy, in vitro release evaluation, and ex vivo permeation studies of the prepared NLCs were carried out. The in vivo anti-arthritic activity of OLE-loaded NLC gel and control gel formulation (OLE free NLC gel) against Complete Freund's Adjuvant (CFA) induced arthritis in wister albino rats was also carried out. Results OLE-NLCs were composed of spherical particles having a mean particle size of ~120 nm, polydispersity index of ~0.162 and zeta potential of ~ -27 mV. The high entrapment efficiency (EE) of UA ~89.56% was attained. The in vitro release study demonstrated a prolonged release of UA from the NLCs up to 12 h. The developed formulation was found to be significantly better with respect to the drug permeation amount with an enhancement ratio of 2.69 as compared with marketed formulation. The in vivo biological activity investigations, studies showed that the newly prepared NLCs formulation of OLE showed excellent anti-arthritic activity and the results were found at par with standard marketed diclofenac gel for its analgesic and anti-arthritic activities. These results were also supported by radiological analysis and molecular docking studies. Conclusion The overall results proved that the prepared OLE-NLCs were very effective for the treatment of arthritis and the results were found at par with standard marketed the standard formulation of diclofenac gel. PMID:29558494

Rifaximin Reduces the Number and Severity of Intestinal Lesions Associated With Use of Nonsteroidal Anti-Inflammatory Drugs in Humans.

PubMed

Scarpignato, Carmelo; Dolak, Werner; Lanas, Angel; Matzneller, Peter; Renzulli, Cecilia; Grimaldi, Maria; Zeitlinger, Markus; Bjarnason, Ingvar

2017-04-01

The intestinal microbiota might contribute to enteropathy associated with use of nonsteroidal anti-inflammatory drugs (NSAIDs), but there have been few human studies of this association. We performed a placebo-controlled study to determine whether a delayed-release antibiotic formulation (rifaximin-extended intestinal release [EIR]) prevents the development of intestinal lesions in subjects taking daily NSAIDs. Sixty healthy volunteers (median age, 26 y; 42% female) were given the NSAID diclofenac (75 mg twice daily) plus omeprazole (20 mg once daily), and either rifaximin-EIR (400 mg) or placebo, twice daily for 14 days. Subjects were assessed by videocapsule endoscopy at baseline and after 2 weeks of treatment. The primary end point was the proportion of subjects developing at least 1 small-bowel mucosal break at week 2. Secondary end points were the change in the mean number of mucosal lesions and the number of subjects with large erosions and/or ulcers after 14 days of exposure. We detected mucosal breaks in 20% of subjects given rifaximin and in 43% of subjects given placebo (P = .05 in the post hoc sensitivity analysis). None of the subjects in the rifaximin group developed large lesions, compared with 9 subjects in the placebo group (P < .001). Our findings indicate that intestinal bacteria contribute to the development of NSAID-associated enteropathy in human beings. Clinical trial no: EudraCT 2013-000730-36. Copyright © 2017. Published by Elsevier Inc.

Exploration of the Anti-Inflammatory Drug Space Through Network Pharmacology: Applications for Drug Repurposing

PubMed Central

de Anda-Jáuregui, Guillermo; Guo, Kai; McGregor, Brett A.; Hur, Junguk

2018-01-01

The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs). In this study, relationships among anti-inflammatory drugs, functional pathways, and ADRs were explored through network models. We integrated structural drug information, experimental anti-inflammatory drug perturbation gene expression profiles obtained from the Connectivity Map and Library of Integrated Network-Based Cellular Signatures, functional pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases, as well as adverse reaction information from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The network models comprise nodes representing anti-inflammatory drugs, functional pathways, and adverse effects. We identified structural and gene perturbation similarities linking anti-inflammatory drugs. Functional pathways were connected to drugs by implementing Gene Set Enrichment Analysis (GSEA). Drugs and adverse effects were connected based on the proportional reporting ratio (PRR) of an adverse effect in response to a given drug. Through these network models, relationships among anti-inflammatory drugs, their functional effects at the pathway level, and their adverse effects were explored. These networks comprise 70 different anti-inflammatory drugs, 462 functional pathways, and 1,175 ADRs. Network-based properties, such as degree, clustering coefficient, and node strength, were used to identify new therapeutic applications within and beyond the anti-inflammatory context, as well as ADR risk for these drugs, helping to select better repurposing candidates. Based on these parameters, we identified naproxen, meloxicam, etodolac, tenoxicam, flufenamic acid, fenoprofen, and nabumetone as candidates for drug repurposing with lower ADR risk. This network-based analysis pipeline provides a novel way to explore the effects of drugs in a therapeutic space. PMID:29545755

Exploration of the Anti-Inflammatory Drug Space Through Network Pharmacology: Applications for Drug Repurposing.

PubMed

de Anda-Jáuregui, Guillermo; Guo, Kai; McGregor, Brett A; Hur, Junguk

2018-01-01

The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs). In this study, relationships among anti-inflammatory drugs, functional pathways, and ADRs were explored through network models. We integrated structural drug information, experimental anti-inflammatory drug perturbation gene expression profiles obtained from the Connectivity Map and Library of Integrated Network-Based Cellular Signatures, functional pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases, as well as adverse reaction information from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The network models comprise nodes representing anti-inflammatory drugs, functional pathways, and adverse effects. We identified structural and gene perturbation similarities linking anti-inflammatory drugs. Functional pathways were connected to drugs by implementing Gene Set Enrichment Analysis (GSEA). Drugs and adverse effects were connected based on the proportional reporting ratio (PRR) of an adverse effect in response to a given drug. Through these network models, relationships among anti-inflammatory drugs, their functional effects at the pathway level, and their adverse effects were explored. These networks comprise 70 different anti-inflammatory drugs, 462 functional pathways, and 1,175 ADRs. Network-based properties, such as degree, clustering coefficient, and node strength, were used to identify new therapeutic applications within and beyond the anti-inflammatory context, as well as ADR risk for these drugs, helping to select better repurposing candidates. Based on these parameters, we identified naproxen, meloxicam, etodolac, tenoxicam, flufenamic acid, fenoprofen, and nabumetone as candidates for drug repurposing with lower ADR risk. This network-based analysis pipeline provides a novel way to explore the effects of drugs in a therapeutic space.

[The assessment of oral NSAID use in patients with rheumatoid arthritis in Hungary--a cross sectional non interventional study].

PubMed

Inotai, András; Rojkovich, Bernadette; Mészáros, Agnes

2010-01-01

Continuous NSAID (nonsteroidal anti-inflammatory drug) therapy is associated with gastrointestinal (GI) and cardiovascular (CV) side effects. In this paper, the oral NSAID use of 143 patients with rheumatoid arthritis was assessed focusing on safety and farmacoeconomic aspects in a cross sectional non interventional study. The most widely used NSAIDs were meloxicam (n = 55, 38.5%) and diclofenac (n = 30, 21%). We found that coxibs were overused (n = 13, 9.1%) compared with the average total coxib consumption in Hungary. According to our results, drugs associated with GI friend side effect profile (meloxicam, celecoxib, etoricoxib) were much preferred in patients with previous GI events, than in patients with low GI risk. The previous occurrence of GI events were significantly higher (p = 0.019) in patients currently treated with safer NSAIDs, probably because of the so-called 'indication bias'. No statistically significant difference in patient's quality of life could be proved between NSAID drug groups. The uses of NSAIDs were considered to be rational concerning CV and GI risk as well as cost-effectiveness.

[Use and potential risks of over-the-counter analgesics].

PubMed

Freytag, A; Quinzler, R; Freitag, M; Bickel, H; Fuchs, A; Hansen, H; Hoefels, S; König, H-H; Mergenthal, K; Riedel-Heller, S G; Schön, G; Weyerer, S; Wegscheider, K; Scherer, M; van den Bussche, H; Haefeli, W E; Gensichen, J

2014-04-01

We investigated the use of prescription and non-prescription (over-the-counter, OTC) analgesics and the associated risks in elderly patients with multiple morbidities. Pain medication use was evaluated from the baseline data (2008/2009) of the MultiCare cohort enrolling elderly patients with multiple morbidities who were treated by primary care physicians (trial registration: ISRCTN89818205). We considered opioids (N02A), other analgesics, and antipyretics (N02B) as well as nonsteroidal anti-inflammatory drugs (NSAIDs; M01A). OTC use, duplicate prescription, dosages, and interactions were examined for acetylsalicylic acid, diclofenac, (dex)ibuprofen, naproxen, and acetaminophen. Of 3,189 patients with multiple morbidities aged 65-85 years, 1,170 patients reported to have taken at least one prescription or non-prescription analgesic within the last 3 months (36.7 %). Of these, 289 patients (24.7 % of 1,170) took at least one OTC analgesic. Duplicate prescription was observed in 86 cases; 15 of these cases took the analgesics regularly. In two cases, the maximum daily dose of diclofenac was exceeded due to duplicate prescription. In 235 cases, patients concurrently took a drug with a potentially clinically relevant interaction. In 43 cases (18.3 % of 235) an OTC analgesic, usually ibuprofen, was involved. About one third of the elderly patients took analgesics regularly or as needed. Despite the relatively high use of OTC analgesics, the proportions of duplicate prescription, medication overdoses, and adverse interactions due to OTC products was low.

Bacterial β-glucuronidase inhibition protects mice against enteropathy induced by indomethacin, ketoprofen or diclofenac: mode of action and pharmacokinetics

PubMed Central

Saitta, Kyle S.; Zhang, Carmen; Lee, Kang Kwang; Fujimoto, Kazunori; Redinbo, Matthew R.; Boelsterli, Urs A.

2014-01-01

We have previously demonstrated that a small molecule inhibitor of bacterial β-glucuronidase (Inh-1; [1-((6,8-dimethyl-2-oxo-1,2-dihydroquinolin-3-yl)-3-(4-ethoxyphenyl)-1-(2-hydroxyethyl)thiourea]) protected mice against diclofenac (DCF)-induced enteropathy. Here we report that Inh-1 was equally protective against small intestinal injury induced by other carboxylic acid-containing non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin (10 mg/kg, ip) and ketoprofen (100 mg/kg, ip).Inh-1 provided complete protection if given prior to DCF (60 mg/kg, ip), and partial protection if administered 3-h post-DCF, suggesting that the temporal window of mucosal protection can be extended for drugs undergoing extensive enterohepatic circulation.Pharmacokinetic analysis of Inh-1 revealed an absolute bioavailability (F) of 21% and a short t1/2 of <1 h. This low F was shown to be due to hepatic first-pass metabolism, as confirmed with the pan-CYP inhibitor, 1-aminobenzotriazole.Using the fluorescent probe 5 (and 6)-carboxy-2′,7′-dichlorofluorescein, we demonstrated that Inh-1 did not interfere with hepatobiliary export of glucuronides in gall bladder-cannulated mice.These data are compatible with the hypothesis that pharmacological inhibition of bacterial β-glucuronidase-mediated cleavage of NSAID glucuronides in the small intestinal lumen can protect against NSAID-induced enteropathy caused by locally high concentrations of NSAID aglycones. PMID:23829165

Non-steroidal anti-inflammatory drugs and gastroprotection with proton pump inhibitors: a focus on ketoprofen/omeprazole.

PubMed

Gigante, Antonio; Tagarro, Ignacio

2012-04-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed agents for rheumatic disorders such as osteoarthritis (OA), rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Despite the known association between NSAID use and gastropathy, however, only around one-third of patients at risk of NSAID-induced gastrointestinal toxicity receive adequate gastroprotection, and as many as 44% of these patients are non-adherent. We review the co-prescription of proton pump inhibitors (PPIs) for the prevention of NSAID-induced gastropathy, with a particular focus on the first fixed-dose NSAID/PPI formulation: ketoprofen/omeprazole modified-release capsules. The ketoprofen/omeprazole fixed-dose combination is available in doses of 100 mg/20 mg, 150 mg/20 mg or 200 mg/20 mg as a single capsule for once-daily administration. Ketoprofen monotherapy has been shown to be generally equivalent to other NSAIDs when used in the treatment of OA. In RA, ketoprofen has demonstrated equivalent efficacy to diclofenac, indometacin, piroxicam, aceclofenac, phenylbutazone, naproxen and flurbiprofen. Studies comparing ketoprofen with ibuprofen and sulindac in patients with RA have, in general, favoured ketoprofen. Studies in AS have generally reported similar efficacy between ketoprofen and phenylbutazone and pirprofen. Prophylaxis with omeprazole is effective for the prevention of gastroduodenal ulcers, maintenance of remission and alleviation of dyspeptic symptoms in NSAID recipients. Omeprazole is well tolerated, and adverse events are generally gastrointestinal in nature. The fixed-dose combination of ketoprofen and omeprazole has demonstrated bioequivalence to the respective monotherapies. The incidence of digestive symptoms and the need for dose reduction was reported to be lower with the combination than with its components. Ketoprofen/omeprazole modified-release capsules are the first fixed-dose NSAID/PPI formulation to be approved. This formulation ensures compliance with the gastroprotective prophylaxis, as whenever the NSAID is taken, the PPI is co-administered. Additionally, the once-daily formulation has the potential to improve adherence to anti-inflammatory therapy. © 2012 Adis Data Information BV. All rights reserved.

Diclofenac rectal suppository: an effective modality for perineal pain.

PubMed

Naz, Shabnam; Memon, Naila Yousuf; Sattar, Asma; Baloch, Rafia

2016-08-01

To determine the frequency of perineal pain after childbirth after a single dose of diclofenac rectal suppository. This cross-sectional study was conducted at Shaikh Zayed Women Hospital, Larkana, Pakistan, from April to September 2014, and comprised patients who were admitted to the labour room for normal vaginal delivery. A single dose of rectal diclofenac suppository of 100mg was given to the patients delivered vaginally or by second-stage emergency Caesarean section. Post-partum pain was noted after 12 and 24 hours of the administration of analgesia. SPSS 16 was used for data analysis. Of the 169 subjects, 63(37.28%) were aged 20 years or less, 85(50.3%) between 21 and 30 years, and 21(12.43%) between 31 and 40 years. Frequency of perineal pain was predominantly mild in 95(56%) patients, moderate in 60(35.5%) and severe in 14(8.28%). The use of non-steroidal anti-inflammatory rectal suppositories was found to be a simple and highly effective modality of reducing the perineal pain.

The efficacy of oral non-steroidal anti-inflammatory drugs for rotator cuff tendinopathy: a systematic review and meta-analysis.

PubMed

Boudreault, Jennifer; Desmeules, François; Roy, Jean-Sébastien; Dionne, Clermont; Frémont, Pierre; Macdermid, Joy C

2014-04-01

To conduct a systematic review and meta-analysis on the efficacy of oral non-steroidal anti-inflammatory drugs for rotator cuff tendinopathy. Systematic review. A literature search was conducted in 4 databases for randomized controlled trials published until 05/2013, comparing the efficacy of oral anti-inflammatory drugs to any other intervention. Studies characteristics were extracted using a standardized form and the methodological quality was evaluated. Results were summarized qualitatively or quantitatively. The mean methodological score of the 12 included studies was 53.6 ± 8.8%. The majority of studies included acute cases and were underpowered to detect differences in adverse events. Compared to a placebo, oral non-steroidal anti-inflammatory drugs were found to provide short-term pain relief (pooled mean difference: -2.69; 95% confidence interval: -1.96 to -3.41) but not function. Oral anti-inflammatory- drugs and corticosteroids injections have similar short-term efficacy in terms of pain reduction as well as in function (pooled standardized mean difference: 0.09; 95% confidence interval: -0.25 to 0.44). Low to moderate grade evidence exists regarding the efficacy of non-steroidal anti-inflammatory drugs for rotator cuff tendinopathy. Oral anti-inflammatory drugs are effective in reducing short-term pain but not function. In terms of pain and function, oral anti-inflammatory drugs in the short term are as effective as corticosteroid injections.

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

PubMed Central

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

2016-01-01

Study Design Retrospective study. Purpose 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. Overview of Literature 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. Methods 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. Results 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 (p<0.001). Conclusions Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent the transition of acute low back pain to chronic low back pain. PMID:27559448

Comparison of the effect of naproxen, etodolac and diclofenac on postoperative sequels following third molar surgery: A randomised, double-blind, crossover study

PubMed Central

Akbulut, Nihat; Atakan, Cemal; Çölok, Gülümser

2014-01-01

Objectives: To compare the three non-steroidal anti-inflammatory agents (NSAIDs) diclofenac potassium, etodolac and naproxen sodium in relation to pain, swelling and trismus following impacted third molar surgery. Study Design: The study was a randomized and a double-blinded study which included 42 healthy young individuals with impacted third molars and bone retention. Patients were randomly assigned to 3 groups (n: 14) to which diclofenac potassium, naproxen sodium and etodolac were administered orally an hour before the operation. Impacted third molars were surgically extracted with local anaesthesia. Visual analog scales (VAS) were used to assess the pain in the 6th, 12th hours and on the 1st, 2nd, 3rd, 5th, and 7th days postoperatively. Swelling was evaluated using ultrasound (US) and mouth opening (trismus) was measured with a composing stick pre and post operatively on the 2nd and 7th days respectively. Results: Regarding pain alleviation, diclofenac potassium was better than naproxen sodium and naproxen sodium was better than etodolac but these differences were not statistically significant. US measurements showed that the swelling on postoperative 2nd day was significantly lowest with diclofenac potassium as compared to others (p= 0.027) while naproxen sodium and etodolac acted similarly (p=0.747). No difference was noted regarding trismus in any of the groups. Conclusions: NSAIDs (diclofenac, naproxen and etodolac) are somehow similarly effective for controlling pain and trismus following extraction of mandibular third molars but diclofenac potassium surpasses others in reduction of swelling. Key words:Diclofenac potassium, naproxen sodium, etodolac, impacted third molar surgery, pain, swelling, trismus. PMID:24316711

Preventive effect of irsogladine or omeprazole on non-steroidal anti-inflammatory drug-induced esophagitis, peptic ulcers, and small intestinal lesions in humans, a prospective randomized controlled study.

PubMed

Kuramoto, Takanori; Umegaki, Eiji; Nouda, Sadaharu; Narabayashi, Ken; Kojima, Yuichi; Yoda, Yukiko; Ishida, Kumi; Kawakami, Ken; Abe, Yosuke; Takeuchi, Toshihisa; Inoue, Takuya; Murano, Mitsuyuki; Tokioka, Satoshi; Higuchi, Kazuhide

2013-05-14

Proton-pump inhibitors such as omeprazole are a standard treatment to prevent non-steroidal anti-inflammatory drug-induced upper gastrointestinal mucosal injuries. However, it is unclear which drugs may protect against all NSAID-induced digestive-tract injuries. Here, we compare the efficacy of the gastromucoprotective drug irsogladine with omeprazole in preventing NSAID-induced esophagitis, peptic ulcers, and small-intestinal mucosal injury in healthy subjects. Thirty-two healthy volunteers were assigned to an irsogladine group (Group I; n = 16) receiving diclofenac sodium 75 mg and irsogladine 4 mg daily for 14 days, or an omeprazole group (Group O; n = 16) receiving diclofenac sodium 75 mg and omeprazole 10 mg daily for 14 days. Esophagitis and peptic ulcers were evaluated by esophagogastroduodenoscopy and small-intestinal injuries by capsule endoscopy, fecal calprotectin, and fecal occult blood before and after treatment. There was no significant difference between Group I and Group O with respect to the change in lesion score in the esophagus, stomach, and duodenum before and after treatment.NSAID treatment significantly increased the number of small intestinal mucosal breaks per subject by capsule endoscopic evaluation, from a basal level of 0.1 ± 0.3 up to 1.9 ± 2.0 lesions in Group O (p = 0.0002). In contrast, there were no significant changes in the mean number of mucosal breaks before and after co-treatment in Group I (0.3 ± 0.8 to 0.5 ± 0.7, p = 0.62), and the between-group difference was significant (p = 0.0040). Fecal calprotectin concentration, when the concentration before treatment was defined as 1, was significantly increased both in Group O (from 1.0 ± 0.0 to 18.1 ± 37.1, p = 0.0002) and Group I (from 1.0 ± 0.0 to 6.0 ± 11.1, p = 0.0280); the degree of increase in Group O was significantly higher compared with that in Group I (p<0.05). In addition, fecal occult blood levels increased significantly in Group O (p = 0.0018), but there was no change in Group I (p = 1.0), and the between-group difference was significant (p = 0.0031). Irsogladine protected against NSAID-induced mucosal injuries throughout the gastrointestinal tract, from esophagus to small intestine, significantly better than omeprazole. This study was registered in the UMIN Clinical Trials Registry (Registry ID number; UMIN000008114).

Syzygium aqueum: A Polyphenol- Rich Leaf Extract Exhibits Antioxidant, Hepatoprotective, Pain-Killing and Anti-inflammatory Activities in Animal Models

PubMed Central

Sobeh, Mansour; Mahmoud, Mona F.; Petruk, Ganna; Rezq, Samar; Ashour, Mohamed L.; Youssef, Fadia S.; El-Shazly, Assem M.; Monti, Daria M.; Abdel-Naim, Ashraf B.; Wink, Michael

2018-01-01

Syzygium aqueum is widely used in folk medicine. A polyphenol-rich extract from its leaves demonstrated a plethora of substantial pharmacological properties. The extract showed solid antioxidant properties in vitro and protected human keratinocytes (HaCaT cells) against UVA damage. The extract also reduced the elevated levels of ALT, AST, total bilirubin (TB), total cholesterol (TC) and triglycerides (TG) in rats with acute CCl4 intoxication. In addition to reducing the high MDA level, the extract noticeably restored GSH and SOD to the normal control levels in liver tissue homogenates and counteracted the deleterious histopathologic changes in liver after CCl4 injection. Additionally, the extract exhibited promising anti-inflammatory activities in vitro where it inhibited LOX, COX-1, and COX-2 with a higher COX-2 selectivity than that of indomethacin and diclofenac and reduced the extent of lysis of erythrocytes upon incubation with hypotonic buffer solution. S. aqueum extract also markedly reduced leukocyte numbers with similar activities to diclofenac in rats challenged with carrageenan. Additionally, administration of the extract abolished writhes induced by acetic acid in mice and prolonged the response latency in hot plate test. Meanwhile, the identified polyphenolics from the extract showed a certain affinity for the active pockets of 5-lipoxygenase (5-LOX), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) explaining the observed anti-inflammatory activities. Finally, 87 secondary metabolites (mostly phenolics) were tentatively identified in the extract based on LC-MS/MS analyses. Syzygium aqueum displays good protection against oxidative stress, free radicals, and could be a good candidate for treating oxidative stress related diseases. PMID:29922158

Nanoemulsion-based gel formulation of diclofenac diethylamine: design, optimization, rheological behavior and in vitro diffusion studies.

PubMed

Hamed, Rania; Basil, Marwa; AlBaraghthi, Tamadur; Sunoqrot, Suhair; Tarawneh, Ola

2016-12-01

Chronic oral administration of the non-steroidal anti-inflammatory drug, diclofenac diethylamine (DDEA), is often associated with gastrointestinal ulcers and bleeding. As an alternative to oral administration, a nanoemulsion-based gel (NE gel) formulation of DDEA was developed for topical administration. An optimized formulation for the o/w nanoemulsion of oil, surfactant and cosurfactant was selected based on nanoemulsion mean droplet size, clarity, stability, and flowability, and incorporated into the gelling agent Carbopol® 971P. Rheological studies of the DDEA NE gel were conducted and compared to those of conventional DDEA gel and emulgel. The three gels exhibited an elastic behavior, where G' dominated G″ at all frequencies, indicating the formation of strong gels. NE gel exhibited higher G' values than conventional gel and emulgel, which indicated the formation of a stronger gel network. Strat-M® membrane, a synthetic membrane with diffusion characteristics that are well correlated to human skin, was used for the in vitro diffusion studies. The release of DDEA from conventional gel, emulgel and NE gel showed a controlled release pattern over 12 h, which was consistent with the rheological properties of the gels. DDEA release kinetics from the three gels followed super case II transport as fitted by Korsmeyer-Peppas model.

Three-dimensional plotted alginate fibers embedded with diclofenac and bone cells coated with chitosan for bone regeneration during inflammation.

PubMed

Lin, Hsin-Yi; Chang, Tsang-Wen; Peng, Tie-Kun

2018-06-01

Alginate hydrogel fibers embedded with bone cells and diclofenac were coated with a layer of chitosan hydrogel and made into a porous scaffold by three-dimensional (3D) printing for drug release and bone regeneration. It was hypothesized that the chitosan coating could improve the scaffold's drug retention and release properties and biocompatibility. Macrophage cells were stimulated and cocultured with the scaffold. Tests were conducted to show how the chitosan coating affected the scaffold's drug release efficacy and how the release efficacy affected the cellular activities of stimulated macrophages and bone cells. The bone cells encapsulated in the coated scaffold demonstrated good viability after the acidic/basic coating process. The coating improved the retention and release efficacy of diclofenac and hence significantly inhibited interleukin-6 and tumor necrosis factor-α secretion from macrophages (p < 0.05). The bone cells in the coated sample mineralized more extensively than the control (p < 0.01). They also more actively expressed genes that produce proteins for extracellular matrix remodeling, MMP13, and interacting with the mineral matrix, OPN (both p < 0.01). It is believed that on days 7 and 10, when diclofenac was depleted and the concentrations of inflammatory compounds surged, the coating effectively blocked the harmful compounds and protected the bone cells within the fibers. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1511-1521, 2018. © 2018 Wiley Periodicals, Inc.

Use of cyclo-oxygenase 2 inhibitors (COX-2) and prescription non-steroidal anti-inflammatory drugs (NSAIDS) in UK and USA populations. Implications for COX-2 cardiovascular profile.

PubMed

Arellano, Félix M; Yood, Marianne Ulcickas; Wentworth, Charles E; Oliveria, Susan A; Rivero, Elena; Verma, Anila; Rothman, Kenneth J

2006-12-01

COX-2 and NSAIDS differ in their gastrointestinal (GI) and cardiovascular (CV) toxicity from pharmacological, clinical and epidemiologic point of views. Describe the patterns of use of NSAIDS and COX-2 in The Health Improvement Network (THIN) database in UK and the PharMetrics database in USA. We examined the experience of 10 distinct cohorts of new users of diclofenac, naproxen, ibuprofen, piroxicam, other NSAIDS, meloxicam, celecoxib, etoricoxib, rofecoxib and valdecoxib. The study period was 1 January 1995 through 2004 (31 March in UK and 28 February in USA). We collected information on covariates including history of upper GI disease, CV disease, hepatic disease, dosage, concomitant medication, and visits to a rheumatologist. We identified 486 076 unique patient-drug pairs in UK and 1 533 239 in USA. In UK population 78 201 (16%) were COX-2 users and in PharMetrics 324 206 (21%) were COX-2 users. Diclofenac and ibuprofen (NSAIDS), and celecoxib and rofecoxib (COX-2) were the agents prescribed most frequently. The duration of therapy was longer among celecoxib and rofecoxib users than among other users. More COX-2 users than NSAIDS users received concomitant gastroprotective agents (GPA), corticosteroids and anti-platelet therapy, and had a history of thromboembolic events and hypertension. PharMetrics patients were prescribed higher doses of NSAIDS and COX-2. The use of any single agent for more than 90 days was uncommon, but more frequent in PharMetrics. Switching was uncommon and was generally to a NSAID. Our results confirm some previous findings from other authors such as the presence of both GI and CV channelling to COX-2 agents but refute others, such as the frequency of drug switching between these agents. The typical use of COX-2 agents in practice is for shorter duration, and at lower doses, than was employed in randomized clinical trials. This difference may help clarify the apparent discrepancy with respect to CV toxicity between the results from clinical trials, which showed a higher CV risk with these drugs, and non-experimental epidemiologic studies, which showed lower or no increase in risk.

Synthesis of 4-substituted pyrido[2,3-d]pyrimidin-4(1H)-one as analgesic and anti-inflammatory agents.

PubMed

El-Gazzar, Abdel-Rahman B A; Hafez, Hend N

2009-07-01

4-Substituted-pyrido[2,3-d]pyrimidin-4(1H)-ones 4a-c were synthesized by oxidation of 4-substituted-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones 3a-c which were in turn prepared from arylidenemalononitriles 1a-c and 6-aminothiouracil 2. The reactivity of compounds 4a-c towards some reagents such as formamide, carbon disulfide, urea, thiourea, formic and acetic acids were studied. All the synthesized compounds were characterized by spectroscopic means and elemental analysis. Compound 4c exhibited 64% and 72% analgesic activity. Also, compound 4b showed 50% and 65% anti-inflammatory activity. Interestingly these compounds showed one-third of ulcer index of the reference aspirin and diclofenac.

Measuring and modeling of binary mixture effects of pharmaceuticals and nickel on cell viability/cytotoxicity in the human hepatoma derived cell line HepG2

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

Rudzok, S., E-mail: susanne.rudzok@ufz.d; Schlink, U., E-mail: uwe.schlink@ufz.d; Herbarth, O., E-mail: olf.herbarth@medizin.uni-leipzig.d

2010-05-01

The interaction of drugs and non-therapeutic xenobiotics constitutes a central role in human health risk assessment. Still, available data are rare. Two different models have been established to predict mixture toxicity from single dose data, namely, the concentration addition (CA) and independent action (IA) model. However, chemicals can also act synergistic or antagonistic or in dose level deviation, or in a dose ratio dependent deviation. In the present study we used the MIXTOX model (EU project ENV4-CT97-0507), which incorporates these algorithms, to assess effects of the binary mixtures in the human hepatoma cell line HepG2. These cells possess a liver-likemore » enzyme pattern and a variety of xenobiotic-metabolizing enzymes (phases I and II). We tested binary mixtures of the metal nickel, the anti-inflammatory drug diclofenac, and the antibiotic agent irgasan and compared the experimental data to the mathematical models. Cell viability was determined by three different methods the MTT-, AlamarBlue (registered) and NRU assay. The compounds were tested separately and in combinations. We could show that the metal nickel is the dominant component in the mixture, affecting an antagonism at low-dose levels and a synergism at high-dose levels in combination with diclofenac or irgasan, when using the NRU and the AlamarBlue assay. The dose-response surface of irgasan and diclofenac indicated a concentration addition. The experimental data could be described by the algorithms with a regression of up to 90%, revealing the HepG2 cell line and the MIXTOX model as valuable tool for risk assessment of binary mixtures for cytotoxic endpoints. However the model failed to predict a specific mode of action, the CYP1A1 enzyme activity.« less

Solid-phase microextraction based on an agarose-chitosan-multiwalled carbon nanotube composite film combined with HPLC-UV for the determination of non-steroidal anti-inflammatory drugs in aqueous samples.

PubMed

Wan Ibrahim, Wan Nazihah; Sanagi, Mohd Marsin; Mohamad Hanapi, Nor Suhaila; Kamaruzaman, Sazlinda; Yahaya, Noorfatimah; Wan Ibrahim, Wan Aini

2018-06-07

We describe the preparation, characterization and application of a composite film adsorbent based on blended agarose-chitosan-multi-walled carbon nanotubes for the preconcentration of selected non-steroidal anti-inflammatory drugs in aqueous samples before determination by high-performance liquid chromatography with UV detection. The composite film showed high surface area (4.0258 m 2 /g) and strong hydrogen bonding between multi-walled carbon nanotubes and agarose/chitosan matrix, which prevent adsorbent deactivation and ensure long-term stability. Several parameters, namely, sample pH, addition of salt, extraction time, desorption solvent and concentration of multi-walled carbon nanotubes in the composite film were optimized using a one-factor-at-time approach. The optimum extraction conditions obtained were as follows: isopropanol as conditioning solvent, 10 mL of sample solution at pH 2, extraction time of 30 min, stirring speed of 600 rpm, 100 μL of isopropanol as desorption solvent, desorption time of 5 min under ultrasonication, and 0.4% w/v of composite film. Under optimized conditions, the calibration curved showed good linearity in the range of 1-500 ng/mL (r 2  = 0.997-0.999), good limits of detection (0.89-8.05 ng/mL) were obtained with good relative standard deviations of < 4.59% (n = 3) for the determination of naproxen, diclofenac sodium salt and mefenamic acid drugs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

PubMed

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.

Pharmacologic targeting of bacterial β-glucuronidase alleviates nonsteroidal anti-inflammatory drug-induced enteropathy in mice.

PubMed

LoGuidice, Amanda; Wallace, Bret D; Bendel, Lauren; Redinbo, Matthew R; Boelsterli, Urs A

2012-05-01

Small intestinal mucosal injury is a frequent adverse effect caused by nonsteroidal anti-inflammatory drugs (NSAIDs). The underlying mechanisms are not completely understood, but topical (luminal) effects have been implicated. Many carboxylic acid-containing NSAIDs, including diclofenac (DCF), are metabolized to acyl glucuronides (AGs), and/or ether glucuronides after ring hydroxylation, and exported into the biliary tree. In the gut, these conjugates are cleaved by bacterial β-glucuronidase, releasing the potentially harmful aglycone. We first confirmed that DCF-AG was an excellent substrate for purified Escherichia coli β-D-glucuronidase. Using a previously characterized novel bacteria-specific β-glucuronidase inhibitor (Inhibitor-1), we then found that the enzymatic hydrolysis of DCF-AG in vitro was inhibited concentration dependently (IC₅₀ ∼164 nM). We next hypothesized that pharmacologic inhibition of bacterial β-glucuronidase would reduce exposure of enterocytes to the aglycone and, as a result, alleviate enteropathy. C57BL/6J mice were administered an ulcerogenic dose of DCF (60 mg/kg i.p.) with or without oral pretreatment with Inhibitor-1 (10 μg per mouse, b.i.d.). Whereas DCF alone caused the formation of numerous large ulcers in the distal parts of the small intestine and increased (2-fold) the intestinal permeability to fluorescein isothiocyanate-dextran, Inhibitor-1 cotreatment significantly alleviated mucosal injury and reduced all parameters of enteropathy. Pharmacokinetic profiling of DCF plasma levels in mice revealed that Inhibitor-1 coadministration did not significantly alter the C(max), half-life, or area under the plasma concentration versus time curve of DCF. Thus, highly selective pharmacologic targeting of luminal bacterial β-D-glucuronidase by a novel class of small-molecule inhibitors protects against DCF-induced enteropathy without altering systemic drug exposure.

Pharmacologic Targeting of Bacterial β-Glucuronidase Alleviates Nonsteroidal Anti-Inflammatory Drug-Induced Enteropathy in Mice

PubMed Central

LoGuidice, Amanda; Wallace, Bret D.; Bendel, Lauren; Redinbo, Matthew R.

2012-01-01

Small intestinal mucosal injury is a frequent adverse effect caused by nonsteroidal anti-inflammatory drugs (NSAIDs). The underlying mechanisms are not completely understood, but topical (luminal) effects have been implicated. Many carboxylic acid-containing NSAIDs, including diclofenac (DCF), are metabolized to acyl glucuronides (AGs), and/or ether glucuronides after ring hydroxylation, and exported into the biliary tree. In the gut, these conjugates are cleaved by bacterial β-glucuronidase, releasing the potentially harmful aglycone. We first confirmed that DCF-AG was an excellent substrate for purified Escherichia coli β-d-glucuronidase. Using a previously characterized novel bacteria-specific β-glucuronidase inhibitor (Inhibitor-1), we then found that the enzymatic hydrolysis of DCF-AG in vitro was inhibited concentration dependently (IC50 ∼164 nM). We next hypothesized that pharmacologic inhibition of bacterial β-glucuronidase would reduce exposure of enterocytes to the aglycone and, as a result, alleviate enteropathy. C57BL/6J mice were administered an ulcerogenic dose of DCF (60 mg/kg i.p.) with or without oral pretreatment with Inhibitor-1 (10 μg per mouse, b.i.d.). Whereas DCF alone caused the formation of numerous large ulcers in the distal parts of the small intestine and increased (2-fold) the intestinal permeability to fluorescein isothiocyanate-dextran, Inhibitor-1 cotreatment significantly alleviated mucosal injury and reduced all parameters of enteropathy. Pharmacokinetic profiling of DCF plasma levels in mice revealed that Inhibitor-1 coadministration did not significantly alter the Cmax, half-life, or area under the plasma concentration versus time curve of DCF. Thus, highly selective pharmacologic targeting of luminal bacterial β-d-glucuronidase by a novel class of small-molecule inhibitors protects against DCF-induced enteropathy without altering systemic drug exposure. PMID:22328575

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

PubMed Central

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

2017-01-01

Objective: 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 prescription pattern of NSAIDs in Northeastern Iranian population and also provide suggestions for a more rational prescription behavior for such drugs. Methods: In this cross-sectional retrospective study, pattern of 1-year prescriptions was inspected based on 9.3 million prescriptions from two insurance companies. Type of NSAIDs, all dispensed doses and the number of NSAIDs ordered per prescription, and the route of administration for each patient were extracted from the databases. The prescription pattern of NSAIDs was analyzed seasonally. Findings: Out of 9,303,585 prescriptions, 19.3% contained at least one NSAID. Diclofenac was the most commonly prescribed NSAID (49.21%). At least two NSAIDs were simultaneously prescribed in 7% of prescriptions. General practitioners prescribed NSAIDs more frequently (67%) than specialists. Orthopedic surgeons and internists more frequently prescribed NSAIDs in comparison with other physicians (6% and 4%, respectively). Gastroprotective agents (GPAs) were coprescribed to only 7.62% of prescriptions. Conclusion: The frequency of NSAIDs prescription was relatively high in Northeast of Iran. A significant number of prescriptions were associated with irrational prescribing in both coadministration of NSAIDs and GPAs and NSAIDs combination. A strategy must be developed and implemented for prescribing and rational use of medications, e.g., continuing medical education regarding the potential risks of NSAIDs, importance of their appropriate and rational use, and necessity of appropriate prescription writing regarding both content and indication. PMID:29417079

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

PubMed

Fosbøl, Emil Loldrup; Gislason, Gunnar H; Jacobsen, Søren; Abildstrom, Steen Z; Hansen, Morten Lock; Schramm, Tina Ken; Folke, Fredrik; Sørensen, Rikke; Rasmussen, Jeppe N; Køber, Lars; Madsen, Mette; Torp-Pedersen, Christian

2008-08-01

To describe the nationwide pattern of use of non-steroidal anti-inflammatory drugs (NSAIDs) in the Danish population. 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 for NSAIDs by the cohort until 2005. By individual-level-linkage of nationwide registries, information was acquired concerning hospitalizations, comorbidity, concomitant pharmacotherapy and socioeconomic factors. The population consisted of 4,614,807 individuals, of which 2,663,706 (57.8%) claimed at least one prescription for NSAID from 1997 to 2005. Ibuprofen and diclofenac were the most frequently used non-selective NSAIDs, whereas rofecoxib and celecoxib were the most frequently used selective cyclooxygenase-2 (COX-2) inhibitors. The usage was similar across all age groups. Female sex and increasing age was associated with increased use of NSAID. Factors predicting extensive NSAID use were: rheumatic disease (odds ratio (OR) = 1.79, 95% confidence interval (CI): 1.69-1.90), gout agents (allopurinol) (OR = 2.54, CI: 2.44-2.64) and other pain medication (OR = 3.27, CI: 3.23-3.31). NSAIDs were most often prescribed for use for one distinct treatment interval and for a short period (overall inter-quartile range [IQR]: 9-66 days). High doses were used in a relatively large proportion of the population (8.9% for etodolac to 19.5% for celecoxib) and 54,373 (2.0%) claimed prescriptions for more than one NSAID at the same time. NSAIDs were commonly used in the Danish population. Since NSAIDs have been associated with increased cardiovascular risk, further research on the overall risk associated with these drugs on a national scale is needed.

Non-Steroidal Anti-Inflammatory Drugs and Antibiotics Prescription Trends at a Central West Bank Hospital

PubMed Central

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

2013-01-01

Objectives: 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. Methods: 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. Results: 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. Conclusion: 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. PMID:24273668

Tunable thermo-responsive hydrogels: synthesis, structural analysis and drug release studies.

PubMed

Cirillo, Giuseppe; Spataro, Tania; Curcio, Manuela; Spizzirri, U Gianfranco; Nicoletta, Fiore Pasquale; Picci, Nevio; Iemma, Francesca

2015-03-01

Thermo-responsive hydrogel films, synthesized by UV-initiated radical polymerization, are proposed as delivery devices for non-steroidal anti-inflammatory drugs (Diclofenac sodium and Naproxen). N-isopropylacrylamide and N,N'-ethylenebisacrylamide were chosen as thermo-sensitive monomer and crosslinker, respectively. Infrared spectroscopy was used to assess the incorporation of monomers into the network, and the network density of hydrogel films was found to strictly depend on both feed composition and film thickness. Calorimetric analyses showed negative thermo-responsive behaviour with shrinking/swelling transition values in the range 32.8-36.1°C. Equilibrium swelling studies around the LCST allowed the correlation between the structural changes and the temperature variations. The mesh size, indeed, rapidly changed from a collapsed to a swollen state, with beneficial effects in applications such as size-selective permeation or controlled drug delivery, while the crosslinking degree, the film thickness, and the loading method deeply influenced the drug release profiles at 25 and 40°C. The analysis of both 3D-network structure, release kinetics and diffusional constraints at different temperatures was evaluated by mathematical modelling. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed

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 explored as a means for reducing the gastric ulcerogenicity of the latter. The results suggest that pharmacokinetic factors may largely account for the reduced ulcerogenicity of these drug mixtures.

Repositioning drugs for inflammatory disease – fishing for new anti-inflammatory agents

PubMed Central

Hall, Christopher J.; Wicker, Sophie M.; Chien, An-Tzu; Tromp, Alisha; Lawrence, Lisa M.; Sun, Xueying; Krissansen, Geoffrey W.; Crosier, Kathryn E.; Crosier, Philip S.

2014-01-01

Inflammation is an important and appropriate host response to infection or injury. However, dysregulation of this response, with resulting persistent or inappropriate inflammation, underlies a broad range of pathological processes, from inflammatory dermatoses to type 2 diabetes and cancer. As such, identifying new drugs to suppress inflammation is an area of intense interest. Despite notable successes, there still exists an unmet need for new effective therapeutic approaches to treat inflammation. Traditional drug discovery, including structure-based drug design, have largely fallen short of satisfying this unmet need. With faster development times and reduced safety and pharmacokinetic uncertainty, drug repositioning – the process of finding new uses for existing drugs – is emerging as an alternative strategy to traditional drug design that promises an improved risk-reward trade-off. Using a zebrafish in vivo neutrophil migration assay, we undertook a drug repositioning screen to identify unknown anti-inflammatory activities for known drugs. By interrogating a library of 1280 approved drugs for their ability to suppress the recruitment of neutrophils to tail fin injury, we identified a number of drugs with significant anti-inflammatory activity that have not previously been characterized as general anti-inflammatories. Importantly, we reveal that the ten most potent repositioned drugs from our zebrafish screen displayed conserved anti-inflammatory activity in a mouse model of skin inflammation (atopic dermatitis). This study provides compelling evidence that exploiting the zebrafish as an in vivo drug repositioning platform holds promise as a strategy to reveal new anti-inflammatory activities for existing drugs. PMID:25038060

Influence of Dosage Form on the Intravitreal Pharmacokinetics of Diclofenac

PubMed Central

Durairaj, Chandrasekar; Kim, Stephen J.; Edelhauser, Henry F.; Shah, Jaymin C.; Kompella, Uday B.

2009-01-01

Purpose To prepare a suspension form of diclofenac and compare the influence of the injected form (suspension versus solution) on the intravitreal pharmacokinetics of diclofenac in Dutch belted pigmented rabbits. Methods Diclofenac acid was prepared and characterized in a suspension formulation. Rabbit eyes were injected with either diclofenac sodium solution (0.3 mg) or diclofenac acid suspension (10 mg) prepared in 0.1 mL balanced salt solution. Rabbits were killed at regular time intervals, the eyes enucleated, and drug content quantified in the vitreous humor and retina-choroid tissue by high-performance liquid chromatography. Pharmacokinetic models were developed for both the dosage forms, and simulations were performed for different doses. Results Diclofenac acid with an approximate 5-μm particle size exhibited 3.5-fold lower solubility in vitreous humor, when compared with its sodium salt. The estimated settling velocity of the suspension in the vitreous humor was 3 cm/h. After diclofenac sodium salt solution injection, drug levels declined rapidly with no drug levels detectable after 24 hours in the vitreous humor and 4 hours in the RC. Throughout the assessed time course, drug levels were higher in the vitreous. However, sustained, high drug levels were observed in both the vitreous humor and the retina-choroid even on day 21 after diclofenac acid suspension injection, with retina-choroid drug levels being higher beginning at 0.25 hour. The elimination half-life of diclofenac suspension was 24 and 18 days in vitreous and retina-choroid, respectively, compared to 2.9 and 0.9 hours observed with diclofenac sodium. The pharmacokinetic models developed indicated a slow-release distribution or depot compartment for the diclofenac acid suspension in the posterior segment. Simulations indicated the inability of a 10-mg dose of diclofenac sodium solution to sustain drug levels in the vitreous beyond 11 days. Conclusions By choosing a less soluble form of a drug such as diclofenac acid, vitreous elimination half-life can be prolonged up to 24 days, potentially resulting in therapeutic levels in the posterior segment tissues for a few months. Higher detectable drug levels in the retina-choroid suggest rapid settling and persistent retention of suspension in retina-choroid tissue. PMID:19516015

Antioxidant, antimicrobial, toxicity and analgesic properties of ethanol extract of Solena amplexicaulis root.

PubMed

Kabir, Md Golam; Rahman, Md Monsor; Ahmed, Nazim Uddin; Fakruddin, Md; Islam, Saiful; Mazumdar, Reaz Mohammad

2014-08-19

This study was subjected to investigate different pharmacological properties of ethanol extract of Solena amplexicaulis root. The extract contains flavonoid, alkaloid, saponin and steroid compounds. The extract exhibited excellent antioxidant activity in DPPH radical scavenging activity. The extract also showed potent activity in brine shrimp lethality bioassay. The LC50 value was found to 44.677 μg/ml. The extract showed better anti-bacterial activity against gram-negative bacteria. In antifungal assay, the maximum 79.31% of anti-mycotic activity was observed against Aspergillus ochraceus while minimum 44.2% against Rhizopus oryzae. MIC value ranged between 1500-3000 μg/ml. The extract was found moderately toxic with a 24-hr LD50 value of 81.47 mg/kg in Swiss albino mice. The degree of inhibition by the ethanolic extract of the root was found less than that of standard analgesic drug diclofenac sodium. The extract also showed moderate anti-inflammatory and antinociceptive activity and anti-diabetic property. Reducing power of the extract was comparable with standard ascorbic acid. Moderate in vitro thrombolytic activity, lipid peroxidation inhibition property, metal chelating ability and stress-protective activity was also observed. Ethanol extract of Solena amplexicaulis root can be valuable for treatment of different diseases.

A simple high performance liquid chromatography method for determination of rebamipide in rat urine.

PubMed

Cooper, Dustin L; Harirforoosh, Sam

2014-01-01

Rebamipide is a mucoprotective agent commonly used to prevent nonsteriodal anti-inflammatory drug-induced gastrointenstinal side effects [1]. Human plasma and urine analysis of rebamipide utilizing high performance liquid chromatography (HPLC) have been reported [2]. Recently, we reported on the plasma levels of rebamipide in presense or absence of celecoxib or diclofenac in rats [3] using a modified HPLC method of detection developed by Jeoung et al. [4]. To tailor the method towards use in urinary rebamipide extraction and analysis, the following modifications were made:•To compensate for high concentrations of rebamipide found in urine, a new rebamipide stock solution was prepared with a final concentration of 50,000 ng/mL.•Rat urine calibration standards were obtained within the range of 50-1000 ng/mL and 1000-50,000 ng/mL.•Plasma samples were replaced with urine samples.

A simple recirculating flow system for the calibration of polar organic chemical integrative samplers (POCIS): effect of flow rate on different water pollutants.

PubMed

Di Carro, Marina; Bono, Luca; Magi, Emanuele

2014-03-01

A calibration system for POCIS was developed and used to calculate the sampling rates of eight analytes belonging to pesticides, non-steroidal anti-inflammatory drugs and perfluorinated compounds: atrazine, propazine, terbutylazine, diclofenac, ibuprofen, ketoprofen, perfluorooctanoic acid and perfluorooctanesulfonate. Experiments with a linear velocity of 2.0, 5.1, 10.2 and 15.3 cm/s were carried out for 96 h using two different analyte concentrations. POCIS extracts were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), using multiple reaction monitoring to maximize sensitivity. Results highlighted that the calculated sampling rates are rather constant at the considered concentrations and flow rates. Obtained values of sampling rates were then employed to calculate Time-Weighted Average concentration of the analytes in river and drinking waters. © 2013 Published by Elsevier B.V.

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

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

Nadanaciva, Sashi; Aleo, Michael D.; Strock, Christopher J.

To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs)more » as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify “toxic” and “non-toxic” drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition. - Highlights: • NSAIDS cause liver and GI toxicity. • Mitochondrial uncoupling contributes to NSAID liver toxicity. • ER stress is a mechanism that contributes to liver toxicity. • Zebrafish and cell based assays are complimentary.« less

Wastewater treatment plants as a pathway for aquatic contamination by pharmaceuticals in the ebro river basin (northeast Spain).

PubMed

Gros, Meritxell; Petrović, Mira; Barceló, Damià

2007-08-01

The occurrence of 28 pharmaceuticals of major human consumption in Spain, including analgesics and anti-inflammatories, lipid regulators, psychiatric drugs, antibiotics, antihistamines, and beta-blockers, was assessed along the Ebro river basin, one of the biggest irrigated lands in that country. Target compounds were simultaneously analyzed by off-line solid-phase extraction, followed by liquid chromatography-tandem mass spectrometry. The loads of detected pharmaceuticals and their removal rates were studied in seven wastewater treatment plants (WWTPs) located in the main cities along the basin. Total loads ranged from 2 to 5 and from 0.5 to 1.5 g/d/1,000 inhabitants in influent and effluent wastewaters, respectively. High removal rates (60-90%) were achieved mainly for analgesics and anti-inflammatories. The other groups showed lower rates, ranging from 20 to 60%, and in most cases, the antiepileptic carbamazepine, macrolide antibiotics, and trimethoprim were not eliminated at all. Finally, the contribution of WWTP effluents to the presence of pharmaceuticals in receiving river waters was surveyed. In receiving surface water, the most ubiquitous compounds were the analgesics and anti-inflammatories ibuprofen, diclofenac, and naproxen; the lipid regulators bezafibrate and gemfibrozil; the antibiotics erythromycin, azithromycin, sulfamethoxazole, trimethoprim, and less frequently, ofloxacin; the antiepileptic carbamazepine; the antihistamine ranitidine; and the beta-blockers atenolol and sotalol. Although levels found in WWTP effluents ranged from low microg/L to high ng/L, pharmaceuticals in river waters occurred at levels at least one order of magnitude lower (low ng/L range) because of dilution effect. From the results obtained, it was proved that WWTP are hot spots of aquatic contamination concerning pharmaceuticals of human consumption.

Diclofenac/misoprostol: novel findings and their clinical potential.

PubMed

Shield, M J

1998-05-01

The new class of antiinflammatory and analgesic drugs, the selective cyclooxygenase (COX-2) inhibitors, which promise to be devoid of the types of toxicity associated with nonsteroidal antiinflammatory drugs (NSAID), especially adverse gastrointestinal effects, are under clinical trial but are not yet available for use. All NSAID, including those most recently introduced, exhibit nonselectivity of action, producing therapeutic blood levels that inhibit constitutive COX-1 and deplete tissue protective prostaglandins. Among NSAID, the diclofenac/misoprostol combination (Arthrotec) is unique in possessing an active component, misoprostol, to help prevent NSAID induced gastrointestinal damage. Ulcer damage and associated serious complications probably represent only the tip of the iceberg in relation to clinically significant side effects associated with the use of NSAID. In this context, metaanalysis of 8 large multicenter studies reported here has shown that patients taking NSAID show a mean decrease in hemoglobin over 4 - 12 weeks' assessment, with some 10-20% of patients exhibiting clinically significant decreases (> or = 1 g/dl) early in treatment. Patients taking diclofenac/misoprostol showed significantly less of a decline in hemoglobin and up to 50% fewer clinically significant decreases than patients receiving diclofenac alone. The misoprostol component of diclofenac/misoprostol may also help to restore homeostasis in tissues other than the gut. Inhibition of the activity or release of various tissue damaging agents and inflammatory cytokines, e.g., thromboxane and interleukin 1, are described, as are in vivo animal studies that have revealed synergistic or potentiating analgesic and antiinflammatory activities between misoprostol and NSAID, particularly diclofenac. Clinical studies in postsurgical dental pain in more than 500 patients have now shown enhanced analgesia, with greater relief over a longer period, for the diclofenac/misoprostol combination compared with diclofenac alone. The relevance of these findings to pain and inflammation control in arthritis is discussed. Enhanced control of morning stiffness provided by diclofenac/misoprostol, possibly also the result of misoprostol/diclofenac synergy, is also reported, and the development of an objective system that measures 24 hour ambulatory activity is described. Using this Numact recorder, improved mobility in patients receiving diclofenac 75 mg/misoprostol 200 microg was observed compared with patients treated with diclofenac 75 mg slow release. Further studies are being performed employing magnetic resonance imaging both to assess antiinflammatory effects in joint soft tissue architecture and to assess whether the synergistic stimulatory effects of diclofenac and misoprostol on human osteoarthritic cartilage that have been reported in vitro are clinically evident. A growing body of evidence supports the view that the diclofenac/misoprostol combination provides an improved therapeutic ratio over diclofenac alone, not only by improving gastrointestinal safety but also by enhancing analgesic/antiinflammatory effects.

Evaluation of fatty acid amides in the carrageenan-induced paw edema model

PubMed Central

Wise, Laura E.; Cannavacciulo, Roberta; Cravatt, Benjamin F.; Martin, Billy F.; Lichtman, Aron H.

2008-01-01

While it has long been recognized that Δ9-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis, and other cannabinoid receptor agonists possess anti-inflammatory properties, their well known CNS effects have dampened enthusiasm for therapeutic development. On the other hand, genetic deletion of fatty acid amide hydrolase (FAAH), the enzyme responsible for degradation of fatty acid amides, including endogenous cannabinoid N-arachidonoyl ethanolamine (anandamide; AEA), N-palmitoyl ethanolamine (PEA), N-oleoyl ethanolamine (OEA), and oleamide, also elicits anti-edema, but does not produce any apparent cannabinoid effects. The purpose of the present study was to investigate whether exogenous administration of FAAs would augment the anti-inflammatory phenotype of FAAH (-/-) mice in the carrageenan model. Thus, we evaluated the effects of the FAAs AEA, PEA, OEA, and oleamide in wild-type and FAAH (-/-) mice. For comparison, we evaluated the anti-edema effects of THC, dexamethasone (DEX), a synthetic glucocorticoid, diclofenac (DIC), a nonselective cyclooxygenase (COX) inhibitor, in both genotypes. A final study determined if tolerance to the anti-edema effects of PEA occurs after repeated dosing. PEA, THC, DEX, DIC elicited significant decreases in carrageenan-induced paw edema in wild type mice. In contrast OEA produced a less reliable anti-edema effect than these other drugs, and AEA and oleamide failed to produce any significant decreases in paw edema. Moreover, none of the agents evaluated augmented the anti-edema phenotype of FAAH (-/-) mice, suggesting that maximal anti-edema effects had already been established. PEA was the most effective FAA in preventing paw edema and its effects did not undergo tolerance. While the present findings do not support a role for AEA in preventing carrageenan-induced edema, PEA administration and FAAH blockade elicited anti-edema effects of an equivalent magnitude as produced by THC, DEX, and DIC in this assay. PMID:17675189

Investigation of nepetolide as a novel lead compound: Antioxidant, antimicrobial, cytotoxic, anticancer, anti-inflammatory, analgesic activities and molecular docking evaluation.

PubMed

Ur Rehman, Tanzeel; Khan, Arif-Ullah; Abbas, Azar; Hussain, Javid; Khan, Farman Ullah; Stieglitz, Kimberly; Ali, Shamsher

2018-03-01

In the present study, we describe various pharmacological effects and computational analysis of nepetolide, a tricyclic clerodane-type diterpene, isolated from Nepeta suavis . Nepetolide concentration-dependently (1.0-1000 µg/mL) exhibited 1,1-diphenyl,2-picrylhydrazyl free radical scavenging activity with maximum effect of 87.01 ± 1.85%, indicating its antioxidant potential, as shown by standard drug, ascorbic acid. It was moderately active against bacterial strain of Staphylococcus aureus . In brine shrimp's lethality model, nepetolide potently showed cytotoxic effect, with LC 50 value of 8.7 µg/mL. When evaluated for antitumor activity in potato disc tumor assay, nepetolide exerted tumor inhibitory effect of 56.5 ± 1.5% at maximum tested concentration of 1000 µg/mL. Nepetolide at 20 mg/kg reduced carrageenan-induced inflammation (P < .001 vs. saline group) in rat paw. Nepetolide dose-dependently (100-500 mg/kg) decreased acetic acid evoked writhes, as exhibited by diclofenac sodium. In-silico investigation of nepetolide was carried out against cyclooxygenase-2, epidermal growth factor receptor and lipoxygenase-2 targets. Virtual screening through Patchdock online docking server identified primarily hydrophobic interactions between ligand nepetolide and receptors proteins. Enhanced hydrogen bonding was predicted with Autodock showing 6-8 hydrogen bonds per target. These results indicate that nepetolide exhibits antioxidant, antibacterial, cytotoxic, anticancer, anti-inflammatory and analgesic activities and should be considered as a lead compound for developing drugs for the remedy of oxidative stress-induced disorders, microbial infections, cancers, inflammations and pain.

The role of nonsteroidal anti-inflammatory drugs intramuscular injection in the development and severity of deep soft tissue infection in mice.

PubMed

Ture, Zeynep; Demiraslan, Hayati; Kontas, Olgun; Alp, Emine; Doganay, Mehmet

2018-04-01

The aim of this study was to determine the role of nonsteroidal anti-inflammatory drugs (NSAID) injection on the severity of local infection and the effect on the progression of soft tissue infection (STI).The mouse model of STI with Group A streptococcus (GAS) was developed and treated with diclofenac sodium (DS) intramuscularly. Mice were divided into five groups: administered DS for 48 h before GAS (Group 1), GAS-DS and maintained DS for 48 h (Group 2), DS for 48 h (Group 3), GAS on zero time (Group 4), and control (Group 5). In vitro, a high concentration (40 mg/L) of DS inhibited GAS growth, whereas a lower concentration (0.4 mg/L) was not effective. Sepsis was observed in animals with DS and GAS inoculation (group 1 and 2). Group 4 had statistically significant higher bacterial load than groups 1 and 2. All groups had a higher inflammation rate than the control group. The median of TNF-alpha and mean IL-6 in the groups 1, 2, and 4 was significantly higher than those in the control group. Even if the animals that were treated with DS injection prior to the GAS inoculation had similar inflammation score, similar cytokine levels and low bacterial load in the tissue, they had a rather high rate of sepsis. In conclusion, DS injection prior to bacterial inoculation might predispose to bacteremia and sepsis. © 2017 Société Française de Pharmacologie et de Thérapeutique.

Underutilization of gastroprotective drugs in patients receiving non-steroidal anti-inflammatory drugs.

PubMed

Thiéfin, Gérard; Schwalm, Marie-Sophie

2011-03-01

To assess the prevalence of gastroprotective agent prescription in patients treated with non-steroidal anti-inflammatory drugs in France and to analyze the determinants of this prescription. A cross-sectional observational study was performed in 2576 patients treated with non-steroidal anti-inflammatory drugs recruited prospectively in the French primary care system. Thirty-nine percent of the patients (n=1002) received gastroprotective agents, mostly proton pump inhibitors (99.5%). In patients with a single risk factor, the gastroprotection rates were: 50% for age>65, 67% for concurrent use of corticosteroids or antithrombotics, and 87% and 100% for history of uncomplicated and complicated gastroduodenal ulcers. In patients without risk factors, gastroprotective agents were prescribed in 31.8%. Among them, two thirds had symptoms of gastro-oesophageal reflux or history of non-steroidal anti-inflammatory drug intolerance or dyspepsia. Conversely, 40% (n=256) of at-risk non-steroidal anti-inflammatory drug users did not receive gastroprotective agents. Gastroprotection was significantly associated with history of gastroduodenal ulcer (OR: 8.2; 95%CI: 4.3-15.6) or history of non-steroidal anti-inflammatory drug intolerance (OR: 6; 95%CI: 4.5-8.1), gastro-oesophageal reflux (OR: 6; 95%CI: 4.4-8.2), dyspepsia (OR: 5.2; 95%CI: 3.7-7.5), concurrent gastrotoxic treatment (OR: 3.3; 95%CI: 1.9-5.6) and age>65 (OR: 3; 95%CI: 2.3-4.1). Despite widespread recommendations, gastroprotection is still largely underprescribed in patients at risk of gastrointestinal non-steroidal anti-inflammatory drug complications in France. Only half of non-steroidal anti-inflammatory drug users above 65 years are prescribed gastroprotective agents. Copyright © 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Anti-inflammatory Agents: Present and Future

PubMed Central

Dinarello, Charles A.

2012-01-01

Inflammation involving the innate and adaptive immune systems is a normal response to infection. However, when allowed to continue unchecked, inflammation may result in autoimmune or autoinflammatory disorders, neurodegenerative disease, or cancer. A variety of safe and effective anti-inflammatory agents are available, including aspirin and other nonsteroidal anti-inflammatories, with many more drugs under development. In particular, the new era of anti-inflammatory agents includes “biologicals” such as anticytokine therapies and small molecules that block the activity of kinases. Other anti-inflammatories currently in use or under development include statins, histone deacetylase inhibitors, PPAR agonists, and small RNAs. This Review discusses the current status of anti-inflammatory drug research and the development of new anti-inflammatory therapeutics. PMID:20303881

Benign stricture of the oesophagus: role of non-steroidal anti-inflammatory drugs.

PubMed Central

Wilkins, W E; Ridley, M G; Pozniak, A L

1984-01-01

The medication history of patients presenting with benign oesophageal stricture is compared with an age and sex matched control population selected from the community. Fifty five out of 151 consecutive admissions to a dysphagia clinic were found to have benign oesophageal stricture. Twenty six out of 53 (49%) had been prescribed non-steroidal anti-inflammatory drugs in the year preceding their clinic appointment. Ten patients (19%) had been prescribed other drugs implicated in oesophageal disease over the same period. In the control population, 20 out of 165 (12%) had been prescribed non-steroidal anti-inflammatory drugs, and 31 out of 165 had been prescribed 'other' drugs in the preceding year. The difference between numbers on non-steroidal anti-inflammatory drugs in the patient and control groups was highly significant (X2 = 23.87, p less than 0.1%). This study has shown an association between the prescribing of non-steroidal anti-inflammatory drugs and benign stricture of the oesophagus. PMID:6714790

Ion-exchange selectivity of diclofenac, ibuprofen, ketoprofen, and naproxen in ureolyzed human urine.

PubMed

Landry, Kelly A; Sun, Peizhe; Huang, Ching-Hua; Boyer, Treavor H

2015-01-01

This research advances the knowledge of ion-exchange of four non-steroidal anti-inflammatory drugs (NSAIDs) - diclofenac (DCF), ibuprofen (IBP), ketoprofen (KTP), and naproxen (NPX) - and one analgesic drug-paracetamol (PCM) - by strong-base anion exchange resin (AER) in synthetic ureolyzed urine. Freundlich, Langmuir, Dubinin-Astakhov, and Dubinin-Radushkevich isotherm models were fit to experimental equilibrium data using nonlinear least squares method. Favorable ion-exchange was observed for DCF, KTP, and NPX, whereas unfavorable ion-exchange was observed for IBP and PCM. The ion-exchange selectivity of the AER was enhanced by van der Waals interactions between the pharmaceutical and AER as well as the hydrophobicity of the pharmaceutical. For instance, the high selectivity of the AER for DCF was due to the combination of Coulombic interactions between quaternary ammonium functional group of resin and carboxylate functional group of DCF, van der Waals interactions between polystyrene resin matrix and benzene rings of DCF, and possibly hydrogen bonding between dimethylethanol amine functional group side chain and carboxylate and amine functional groups of DCF. Based on analysis of covariance, the presence of multiple pharmaceuticals did not have a significant effect on ion-exchange removal when the NSAIDs were combined in solution. The AER reached saturation of the pharmaceuticals in a continuous-flow column at varying bed volumes following a decreasing order of DCF > NPX ≈ KTP > IBP. Complete regeneration of the column was achieved using a 5% (m/m) NaCl, equal-volume water-methanol solution. Results from multiple treatment and regeneration cycles provide insight into the practical application of pharmaceutical ion-exchange in ureolyzed urine using AER.

Pharmacy Use and Costs in Employer-Provided Health Plans. Insights for TRICARE Benefit Design from the Private Sector

DTIC Science & Technology

2005-01-01

non - steroidal anti - inflammatory drugs ( NSAIDs ), oral antihistamines, gastrointestinal agents, and oral...National Defense Authorization Act NSAID non - steroidal anti - inflammatory drug OLS ordinary least squares p-value probability value P&T Pharmacy...antihypertensives, non - steroidal anti - inflammatory drugs ( NSAIDs ), oral antihistamines, gastrointestinal agents, and oral hy-

Contrasting effects of cord injury on intravenous and oral pharmacokinetics of diclofenac: a drug with intermediate hepatic extraction.

PubMed

Cruz-Antonio, L; Arauz, J; Franco-Bourland, R E; Guízar-Sahagún, G; Castañeda-Hernández, G

2012-08-01

Laboratory investigation in rats submitted to experimental spinal cord injury (SCI). To determine the effect of acute SCI on the pharmacokinetics of diclofenac, a marker drug of intermediate hepatic extraction, administered by the intravenous and the oral routes. Female Wistar rats were submitted to complete section of the spinal cord at the T8 level. SCI and sham-injured rats received 3.2 mg kg(-1) of diclofenac sodium either intravenously or orally, diclofenac concentration was measured in whole blood samples and pharmacokinetic parameters were estimated. Diclofenac was not selected as test drug because of its therapeutic properties, but because to its biopharmaceutical properties, that is, intermediate hepatic extraction. Diclofenac bioavailability after intravenous administration was increased in injured rats compared with controls due to a reduced clearance. In contrast, oral diclofenac bioavailability was diminished in SCI animals due to a reduction in drug absorption, which overrides the effect on clearance. Acute SCI induces significant pharmacokinetic changes for diclofenac, a marker drug with intermediate hepatic extraction. SCI-induced pharmacokinetic changes are not only determined by injury characteristics, but also by the route of administration and the biopharmaceutical properties of the studied drug.

The analgesic, anti-inflammatory and calcium antagonist potential of Tanacetum artemisioides.

PubMed

Bukhari, Ishfaq Ali; Khan, Rafeeq Alam; Gilani, Anwar-ul Hassan; Shah, Abdul Jabbar; Hussain, Javid; Ahmad, Viqar Uddin

2007-03-01

Several species of the genus Tanacetum are traditionally used in a variety of health conditions including pain, inflammation, respiratory and gastrointestinal disorders. In the current investigation, we evaluated the plant extract of T. artemisioides and some of its pure compounds (flavonoids) for analgesic, anti-inflammatory and calcium antagonist effects in various in-vivo and in vitro studies. Using the actetic acid induced writhing test, intraperitoneal (i.p) administration of the plant extract (25-50 mg/kg) and its flavonoid compounds TA-1 and TA-2 (1-5 mg/kg ) exhibited significant analgesic actvity. The maximum analgesic effect observed with the crude extract of the plant was 71% at 50 mg/kg, while that of compounds TA-1 and TA-2 (5 mg/kg i.p) was 75 and 47%, respectively. The plant extract and its pure compounds caused inhbition of formalin induced paw licking in mice predominatly in the second phase of the test. Diclofenac sodium, a standard reference compound, showed a simlar effect in these chemical induced pain models. In the carrgeenan induced rat paw edema assay, the plant extract (50-200 mg/kg i.p) demonstrated significant (P< 0.01) anti-inflammatory activity which was comparable to that obtained with diclofenac sodium and indomethacin. In isolated rabbit jejunum preprations the plant extract showed an atropine sensitive dose-dependent (0.10-1.0 mg/mL) spasmogenic activity followed by a spasmolytic effect at the next higher doses (3-5 mg/mL). The crude extract of the plant also inhibited the high K+-induced contractions, indicating a calcium channel blocking (CCB) activity, which was further confirmed when the plant extract caused a rightward shift in the Ca++ concentration response curves in the isolated rabbit jejunum preparations, similar to that seen with verapamil. The flavonoid compounds isolated from the plant were devoid of any activity in the isolated tissue preparations. These results indicate that the plant extract of T. artemisioides possesses analgesic, anti-inflammatory and CCB activities. The flavonoid compounds of the plant may have a role in its observed analgesic and antiinflammatory activities, while the CCB activity of the plant may be attributed to some other chemical constituents present. Moreover the findings support the traditional reputation of the genus Tanacetum for its therapeutic benefits in pain and inflammatory conditions.

A new antibacterial silver(I) complex incorporating 2,5-dimethylpyrazine and the anti-inflammatory diclofenac.

PubMed

Hamamci Alisir, Sevim; Dege, Necmi

2016-12-01

Ag I -containing coordination complexes have attracted attention because of their photoluminescence properties and antimicrobial activities and, in principle, these properties depend on the nature of the structural topologies. A novel two-dimensional silver(I) complex with the anti-inflammatory diclofenac molecule, namely bis{μ-2-[2-(2,6-dichloroanilino)phenyl]acetato-κ 3 O,O':O}bis(μ-2,5-dimethylpyrazine-κ 2 N:N')silver(I), [Ag 2 (C 14 H 10 Cl 2 NO 2 ) 2 (C 6 H 8 N 2 )] n , (I), has been synthesized and characterized by single-crystal X-ray diffraction, revealing that the Ag I ions are chelated by the carboxylate groups of the anionic 2-[2-(2,6-dichloroanilino)phenyl]acetate (dicl) ligand in a μ 3 -η 1 :η 2 coordination mode. Each dicl ligand links three Ag I atoms to generate a one-dimensional infinite chain. Adjacent chains are connected through 2,5-dimethylpyrazine (dmpyz) ligands to form a two-dimensional layer structure parallel to the crystallographic bc plane. The layers are further connected by C-H...π interactions to generate a three-dimensional supramolecular structure. Additionally, the most striking feature is that the structure contains an intramolecular C-H ...Ag anagostic interaction. Furthermore, the title complex has been tested for its in vitro antibacterial activity and is determined to be highly effective on the studied microorganisms.

Therapeutic effect of irradiation of magnetic infrared laser on osteoarthritis rat model.

PubMed

Moon, Chul-Hwan; Kwon, Ogon; Woo, Chang-Hoon; Ahn, Hee-Duk; Kwon, Young-Sam; Park, Soo-Jin; Song, Chang-Hyun; Ku, Sae-Kwang

2014-01-01

Osteoarthritis (OA) is a degenerative joint disease caused by articular cartilage loss. Many complementary and alternative medicines for OA have been reported so far, but the effectiveness is controversial. Previously, we have shown anti-inflammatory effects of low level laser therapy with static magnetic field, magnetic infrared laser (MIL), in various animal models. Therefore, the beneficial effects were examined in OA rat model. Rats were divided by six groups; no treatment controls of sham and OA model, three MIL treatment groups of OA model at 6.65, 2.66 and 1.33 J cm(-2), and Diclofenac group of OA model with 2 mg kg(-1) diclofenac sodium. The OA control exhibited typical symptoms of OA, but 4-week MIL treatment improved the functional movement of knee joint with reduced edematous changes. In addition, cartilage GAGs were detected more in all MIL treatment groups than OA control. It suggests that 4-week MIL irradiation has dose-dependent anti-inflammatory and chondroprotective effects on OA. Histopathological analyses revealed that MIL treatment inhibits the cartilage degradation and enhances chondrocyte proliferation. The fact that MIL has an additional potential for the cartilage formation and no adverse effects can be regarded as great advantages for OA treatment. These suggest that MIL can be useful for OA treatment. © 2014 The American Society of Photobiology.

Seasonal occurrence, removal, mass loading and environmental risk assessment of 55 pharmaceuticals and personal care products in a municipal wastewater treatment plant in Central Greece.

PubMed

Papageorgiou, Myrsini; Kosma, Christina; Lambropoulou, Dimitra

2016-02-01

A comprehensive study, which contains the seasonal occurrence, removal, mass loading and environmental risk assessment of 55 multi-class pharmaceuticals and personal care products (PPCPs), took place in the wastewater treatment plant (WWTP) of Volos, Greece. A one year monitoring study was performed and the samples were collected from the influent and the effluent of the WWTP. Solid phase extraction was used for the pre-concentration of the samples followed by an LC-DAD-ESI/MS analysis. Positive samples were further confirmed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The maximum concentrations of the PPCPs varied between 21 ng/L and 15,320 ng/L in the influents and between 18 ng/L and 9965 ng/L in the effluents. The most commonly detected PPCPs were the diuretic furosemide, the beta-blockers atenolol and metoprolol, the analgesics paracetamol, nimesulide, salicylic acid and diclofenac and the psychomotor stimulant caffeine. The removal efficiencies ranged between negative and high removal rates, demonstrating that the WWTP is not able to efficiently remove the complex mixture of PPCPs. The estimated mass loads ranged between 5.1 and 3513 mg/day/1000 inhabitants for WWTP influent and between 4.1 to 2141 mg/day/1000 inhabitants for WWTP effluent. Finally, environmental risk assessment has been regarded a necessary part of the general research. According to the results produced from the calculation of the risk quotient on three trophic levels, the anti-inflammatory drug diclofenac and the antibiotics, trimethoprim and ciprofloxacin, identified to be of high potential environmental risk for acute toxicity, while diclofenac also for chronic toxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

A concise review on advances in development of small molecule anti-inflammatory therapeutics emphasising AMPK: An emerging target.

PubMed

Gejjalagere Honnappa, Chethan; Mazhuvancherry Kesavan, Unnikrishnan

2016-12-01

Inflammatory diseases are complex, multi-factorial outcomes of evolutionarily conserved tissue repair processes. For decades, non-steroidal anti-inflammatory drugs and cyclooxygenase inhibitors, the primary drugs of choice for the management of inflammatory diseases, addressed individual targets in the arachidonic acid pathway. Unsatisfactory safety and efficacy profiles of the above have necessitated the development of multi-target agents to treat complex inflammatory diseases. Current anti-inflammatory therapies still fall short of clinical needs and the clinical trial results of multi-target therapeutics are anticipated. Additionally, new drug targets are emerging with improved understanding of molecular mechanisms controlling the pathophysiology of inflammation. This review presents an outline of small molecules and drug targets in anti-inflammatory therapeutics with a summary of a newly identified target AMP-activated protein kinase, which constitutes a novel therapeutic pathway in inflammatory pathology. © The Author(s) 2016.

Chemical composition, in vitro antioxidant and anti-inflammatory properties of essential oils of four dietary and medicinal plants from Cameroon.

PubMed

Ndoye Foe, Florentine Marie-Chantal; Tchinang, Tatiana Flore Kemegni; Nyegue, Ascencion Maximilienne; Abdou, Jean-Pierre; Yaya, Abel Joel Gbaweng; Tchinda, Alembert Tiabou; Essame, Jean-Louis Oyono; Etoa, François-Xavier

2016-04-07

In the Cameroonian traditional medicine, plants of the Capparidaceae, Euphorbiaceae and Liliaceae families are used to treat several metabolic diseases. These plants are rich in various compounds belonging to the glucosinolates and thiosulfinates family. Till date, very little studies have been done aiming at assessing the antioxidant and inflammatory properties of the essential oils (EOs) of these plants. Essential oils are volatile extracts produced by secondary metabolism. They are usually constituted of terpens and may also contain specific non terpenic components such as glucosinolates and thiosulfinates for the species that are being considered in the present study. This study highlights and compares the chemical composition, antioxidant and anti-inflammatory properties of the essential oils of the stem barks of Drypetes gossweileri (Euphorbiaceae), roots of Pentadiplandra brazzeana (Capparidaceae), red bulbs of Allium cepa and Alium sativum (Liliaceae) collected in Cameroon (Central Africa). The essential oils were extracted by hydrodistillation and analyzed by gas chromatography (GC) and gas chromatography coupled to mass spectrometry (GC-MS). In vitro antioxidant activities were determined using the radical scavenging assay, total phenolic content, ferric reducing antioxidant power (FRAP) assay and determination of antioxidant activity index (AAI) according to the method described by Scherer and Godoy. The anti-inflammatory activities were evaluated using albumin denaturation method. Differences (p < 0.05) between the experimental and the control groups were evaluated using one way analysis of variance (ANOVA) followed by Tukey's test for multiple comparisons. The main components of Allium sativum essential oil were diallyl trisulfide (41.62 %), diallyl disulfide (19.74 %), allyl methyl trisulfide (12.95 %), diallyl sulfide (7.1 %) and diallyl tetrasulfide (4.22 %). Those of Allium cepa essential oil were diallyl trisulfide (22.17 %), dipropyl trisulfide (11.11 %), 2-methyl-3,4-dithiaheptane (9.88 %), methyl propyl trisulfide (8.14 %), dipropyl tetrasulfide (8.07 %) and 2-propenyl propyl disulfide (5.15 %). Drypetes gossweileri and Pentadiplandra brazzeana essential oils presented similar chemical compositions as compared with benzylisothiocyanate content (63.19 and 97.63 % respectively), but differed in benzylcyanide content (35.72 and 0.86 % respectively). The essential oils were rich in phenolic compounds in the following order Allium sativum < Allium cepa < D. gossweileiri < P. brazzeana. The essential oils exhibited high antioxidant and DPPH radical scavenging effect but low ferric reducing power activity. Moreover, the four essential oils showed anti-inflammatory activities (by heat denaturation of Bovine Serum Albumin). The anti-inflammatory activities of P. brazzeana and A. cepa essential oils were comparable but higher than those of D. gossweileri and sodium diclofenac used as a reference non-steroidal anti-inflammatory drug. The essential oils of the plants were rich in organosulfur compounds. These compounds were probably responsible for their appreciable antioxidant and anti-inflammatory activities. Due to their antioxidant and anti-inflammatory properties, the essential oils of some of these plants might be used as natural additives in the pharmaceutical, cosmetic and agro-industries.

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

PubMed

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

2016-06-01

Scientists have always been trying to use artificial zeolites to make modified-release drug delivery systems in the gastrointestinal tract. An ideal carrier should have the capability to release the drug in the intestine, which is the main area of absorption. Zeolites are mineral aluminosilicate compounds with regular structure and huge porosity, which are available in natural and artificial forms. In this study, soaking, filtration and solvent evaporation methods were used to load the drugs after activation of the zeolites. Weight measurement, spectroscopy FTIR, thermogravimetry and scanning electronic microscope were used to determine drug loading on the systems. Finally, consideration of drug release was made in a simulated gastric fluid and a simulated intestinal fluid for all matrixes (zeolites containing drugs) and drugs without zeolites. Diclofenac sodium (D) and piroxicam (P) were used as the drug models, and zeolites X and Y as the carriers. Drug loading percentage showed that over 90% of drugs were loaded on zeolites. Dissolution tests in stomach pH environment showed that the control samples (drug without zeolite) released considerable amount of drugs (about 90%) within first 15 min when it was about 10-20% for the matrixes. These results are favorable as NSAIDs irritate the stomach wall and it is ideal not to release much drugs in the stomach. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples in intestine pH environment. © 2016 John Wiley & Sons A/S.

Esophageal Cancer Prevention

MedlinePlus

... agents to try to reduce the risk of cancer. Nonsteroidal anti-inflammatory drugs (NSAIDs) include aspirin and other drugs ... agents to try to reduce the risk of cancer. Nonsteroidal anti-inflammatory drugs (NSAIDs) include aspirin and other drugs ...

Modeling Natural Anti-Inflammatory Compounds by Molecular Topology

PubMed Central

Galvez-Llompart, María; Zanni, Riccardo; García-Domenech, Ramón

2011-01-01

One of the main pharmacological problems today in the treatment of chronic inflammation diseases consists of the fact that anti-inflammatory drugs usually exhibit side effects. The natural products offer a great hope in the identification of bioactive lead compounds and their development into drugs for treating inflammatory diseases. Computer-aided drug design has proved to be a very useful tool for discovering new drugs and, specifically, Molecular Topology has become a good technique for such a goal. A topological-mathematical model, obtained by linear discriminant analysis, has been developed for the search of new anti-inflammatory natural compounds. An external validation obtained with the remaining compounds (those not used in building up the model), has been carried out. Finally, a virtual screening on natural products was performed and 74 compounds showed actual anti-inflammatory activity. From them, 54 had been previously described as anti-inflammatory in the literature. This can be seen as a plus in the model validation and as a reinforcement of the role of Molecular Topology as an efficient tool for the discovery of new anti-inflammatory natural compounds. PMID:22272145

Cyclodextrin Enhances Corneal Tolerability and Reduces Ocular Toxicity Caused by Diclofenac

PubMed Central

Abdelkader, Hamdy; Fathalla, Zeinab; Moharram, Hossam; Ali, Taha F. S.

2018-01-01

With advances in refractive surgery and demand for cataract removal and lens replacement, the ocular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has increased. One of the most commonly used NSAIDs is diclofenac (Diclo). In this study, cyclodextrins (CDs), α-, β-, γ-, and HP-β-CDs, were investigated with in vitro irritation and in vivo ulceration models in rabbits to reduce Diclo toxicity. Diclo-, α-, β-, γ-, and HP-β-CD inclusion complexes were prepared and characterized and Diclo-CD complexes were evaluated for corneal permeation, red blood cell (RBCs) haemolysis, corneal opacity/permeability, and toxicity. Guest- (Diclo-) host (CD) solid inclusion complexes were formed only with β-, γ-, and HP-β-CDs. Amphipathic properties for Diclo were recorded and this surfactant-like functionality might contribute to the unwanted effects of Diclo on the surface of the eye. Contact angle and spreading coefficients were used to assess Diclo-CDs in solution. Reduction of ocular toxicity 3-fold to16-fold and comparable corneal permeability to free Diclo were recorded only with Diclo-γ-CD and Diclo-HP-β-CD complexes. These two complexes showed faster healing rates without scar formation compared with exposure to the Diclo solution and to untreated groups. This study also highlighted that Diclo-γ-CD and Diclo-HP-β-CD demonstrated fast healing without scar formation. PMID:29636847

Synthesis of high surface area carbon adsorbents prepared from pine sawdust-Onopordum acanthium L. for nonsteroidal anti-inflammatory drugs adsorption.

PubMed

Álvarez-Torrellas, S; Muñoz, M; Zazo, J A; Casas, J A; García, J

2016-12-01

Chemically activated carbon materials prepared from pine sawdust-Onopordum acanthium L. were studied for the removal of diclofenac and naproxen from aqueous solution. Several carbons, using different proportions of precursors were obtained (carbon C1 to carbon C5) and the chemical modification by liquid acid and basic treatments of C1 were carried out. The textural properties of the carbons, evaluated by N2 adsorption-desorption isotherms, revealed that the treatments with nitric acid and potassium hydroxide dramatically reduced the specific surface area and the pore volume of the carbon samples. The surface chemistry characterization, made by thermal programmed decomposition studies, determination of isoelectric point and Boehm's titration, showed the major presence of lactone and phenol groups on the activated carbons surface, being higher the content when the acidic strength of the carbon increased. Diclofenac and naproxen kinetic data onto C1 carbon followed pseudo-second order model. The adsorption equilibrium isotherms of C1 and the modified carbons were well described by both Sips and GAB isotherm equations. The highest adsorption capacity was found for naproxen onto C1 activated carbon, 325 mg g(-1), since the liquid acid and basic functionalization of the carbon led to a severe decreasing in the adsorption removal of the target compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

"Old drugs" for the treatment of rheumatoid arthritis: will the cholinergic anti-inflammatory pathway and anti-nociceptive pathway work?

PubMed

Pan, Xiaohua; Yu, Xiaowei; Qin, Ling; Zhang, Peng

2010-12-01

Based on the newly discovered cholinergic anti-inflammatory pathway, on the anti-nociceptive pathway and on our preliminary research, we raise a new strategy for the treatment of rheumatoid arthritis (RA) which mainly focuses on the application of old drugs that can activate both of the above mentioned pathways. It has been reported that nicotinic receptor agonists used for the treatment of neurological diseases were expected to be applied to the therapy of inflammatory diseases (RA). Therefore, it is promising that old drugs available in clinics may exert new functions for the treatment of RA, which may greatly reduce the expense of such treatment, once applied. These currently-used old drugs should be considered as another new resource in exploring anti-rheumatic agents under the guidance of the newly discovered cholinergic anti-inflammatory pathway and the anti-nociceptive pathway.

Release of salicylic acid, diclofenac acid and diclofenac acid salts from isotropic and anisotropic nonionic surfactant systems across rat skin.

PubMed

Gabboun, N H; Najib, N M; Ibrahim, H G; Assaf, S

2001-01-05

Release of salicylic acid, diclofenac acid, diclofenac diethylamine and diclofenac sodium, from lyotropic structured systems, namely; neat and middle liquid crystalline phases, across mid-dorsal hairless rat skin into aqueous buffer were studied. Release results were compared with those from the isotropic systems. The donor systems composed of the surfactant polyoxyethylene (20) isohexadecyl ether, HCl buffer of pH 1 or distilled water and the specific drug. High performance liquid chromatography (HPLC) methods were used to monitor the transfer of the drugs across the skin barrier. Results indicated that the rate-determining step in the transport process was the release of the drug from the specified donor system. Further, apparent zero order release was demonstrated with all systems. Except for diclofenac sodium, drug fluxes decreased as the donor medium changed from isotropic to anisotropic. The decrease in fluxes was probably due to the added constrains on the movement of drug molecules. By changing the anisotropic donor medium from neat to middle phase, drug flux decreased in case of salicylic acid and diclofenac sodium. In the mean time, flux increased in case of the diethylamine salt and appeared nearly similar in case of diclofenac acid. Rates of drug transfer across the skin from the anisotropic donors seemed to be largely controlled by the entropy contribution to the transport process. The type and extent of drug-liquid crystal interactions probably influenced the latter.

Anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation: frequency and power dependence.

PubMed

Gapeyev, A B; Mikhailik, E N; Chemeris, N K

2008-04-01

Using a model of acute zymosan-induced footpad edema in NMRI mice, the frequency and power dependence of anti-inflammatory effect of low-intensity extremely high-frequency electromagnetic radiation (EHF EMR) was found. Single whole-body exposure of animals to EHF EMR at the intensity of 0.1 mW/cm(2) for 20 min at 1 h after zymosan injection reduced both the footpad edema and local hyperthermia on average by 20% at the frequencies of 42.2, 51.8, and 65 GHz. Some other frequencies from the frequency range of 37.5-70 GHz were less effective or not effective at all. At fixed frequency of 42.2 GHz and intensity of 0.1 mW/cm(2), the effect had bell-shaped dependence on exposure duration with a maximum at 20-40 min. Reduction of intensity to 0.01 mW/cm(2) resulted in a change of the effect dependence on exposure duration to a linear one. Combined action of cyclooxygenase inhibitor sodium diclofenac and EHF EMR exposure caused a partial additive effect of decrease in footpad edema. Combined action of antihistamine clemastine and EHF EMR exposure caused a dose-dependent abolishment of the anti-inflammatory effect of EHF EMR. The results obtained suggest that arachidonic acid metabolites and histamine are involved in realization of anti-inflammatory effects of low-intensity EHF EMR. (c) 2007 Wiley-Liss, Inc.

DNA binding, anti-inflammatory and analgesic evaluation of metal complexes of N/S/O donor ligands; Synthesis, spectral characterization

NASA Astrophysics Data System (ADS)

Kumar Naik, K. H.; Ashok, B.; Naik, Nagaraja; Mulla, Jameel Ahmed S.; Prakasha, Avinash

2015-04-01

Transition metal complexes containing tri-dentate NSN donor ligands i.e., 5-((1(aminomethyl)cyclohexyl)methyl)-1,3,4-thiadiazol-2-amine (AMTA) (2) and 5-(2-aminophenyl)-1,3,4-thiadiazol-2-amine (ATA) (4i-ii) have been synthesized. The newly synthesized ligands and their respective complexes were characterized by elemental analysis, molar conductance measurement and various spectral studies [infrared (IR), electronic, and NMR (for ligands only)]. Metal complexes are like [M(AMTA)2], [M(ATA)2] type, where M = Mn(II), Co(II) and Cu(II). The proposed geometries of the complexes are octahedral in nature. The synthesized ligands and their complexes were exhibits effective anti-inflammatory, analgesic and DNA binding activities. All the tested compounds exhibited significant analgesic activity, whereas the compound 4i, 4(ia) and 4(iib) is equipotent with Diclofenac sodium.

Comparison of the physicochemical properties of the N-(2-hydroxyethyl) pyrrolidine, diethylamine and sodium salt forms of diclofenac.

PubMed

O'Connor, K M; Corrigan, O I

2001-07-17

Non steroidal anti-inflammatory agents (NSAIDs) such as diclofenac have very low aqueous solubilities and consequently salt formation may be used to enhance solubility and dissolution rate. In this study, we examined the physicochemical properties of three diclofenac salts, diclofenac sodium (DNa), diclofenac N-(2-hydroxyethyl)pyrrolidine (DHEP) and diclofenac diethylamine (DDEA), and their different solid state forms to determine the influence of salt form on solubility, dissolution rate and membrane transport. The equilibrium solubility of DDEA at 25 degrees C was determined as 33 mM, lower than the solubilities of DHEP (273 mM) and DNa (66 mM) previously reported (Ledwidge and Corrigan, 1998). In addition to the dihydrate form of DHEP previously characterised, monohydrate forms of DHEP and DDEA were identified. Intrinsic dissolution rate studies were used to determine the solubility ratios of the hydrated and anhydrous forms. The monohydrate form of DHEP was found to be 1.8 times less soluble than the anhydrate, whereas DDEA anhydrate was approximately 1.7 times as soluble as the monohydrate form. On investigation of the pH-solubility profile (25 degrees C) of DDEA, appreciable supersaturation (76 mM) relative to the theoretical profile, was detected at the pH(max). This contrasts with values of >800 and 67 mM for DHEP and DNa, respectively. The transport of salt solutions through a porous membrane (Visking) was investigated. A linear relationship between concentration (mM) and rate of transport (mmol/h) was established for DNa and DHEP solutions. The mass transfer coefficient determined for DHEP was lower than that for the other two salts. Nevertheless, the maximum transport rate obtained for DHEP is almost six times higher than that obtained for DDEA.

Ultra-high-performance liquid chromatography-Time-of-flight high resolution mass spectrometry to quantify acidic drugs in wastewater.

PubMed

Becerra-Herrera, Mercedes; Honda, Luis; Richter, Pablo

2015-12-04

A novel analytical approach involving an improved rotating-disk sorptive extraction (RDSE) procedure and ultra-high-performance liquid chromatography (UHPLC) coupled to an ultraspray electrospray ionization source (UESI) and time-of-flight mass spectrometry (TOF/MS), in trap mode, was developed to identify and quantify four non-steroidal anti-inflammatory drugs (NSAIDs) (naproxen, ibuprofen, ketoprofen and diclofenac) and two anti-cholesterol drugs (ACDs) (clofibric acid and gemfibrozil) that are widely used and typically found in water samples. The method reduced the amount of both sample and reagents used and also the time required for the whole analysis, resulting in a reliable and green analytical strategy. The analytical eco-scale was calculated, showing that this methodology is an excellent green analysis, increasing its ecological worth. The detection limits (LOD) and precision (%RSD) were lower than 90ng/L and 10%, respectively. Matrix effects and recoveries were studied using samples from the influent of a wastewater treatment plant (WWTP). All the compounds exhibited suppression of their signals due to matrix effects, and the recoveries were approximately 100%. The applicability and reliability of this methodology were confirmed through the analysis of influent and effluent samples from a WWTP in Santiago, Chile, obtaining concentrations ranging from 1.1 to 20.5μg/L and from 0.5 to 8.6μg/L, respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

Polyphenols from Cymbopogon citratus leaves as topical anti-inflammatory agents.

PubMed

Costa, Gustavo; Ferreira, João Pinto; Vitorino, Carla; Pina, Maria Eugénia; Sousa, João José; Figueiredo, Isabel Vitória; Batista, Maria Teresa

2016-02-03

A variety of plant polyphenols have been reported to have anti-inflammatory, frequently associated with erythema, edema, hyperplasia, skin photoaging and photocarcinogenesis. Cymbopogon citratus (DC). Stapf (Poaceae) is a worldwide known medicinal plant, used in traditional medicine in inflammation-related conditions. In this work, the anti-inflammatory potential of C. citratus infusion (CcI) and its polyphenols as topical agents was evaluated in vivo. The plant extract was prepared and its fractioning led two polyphenol-rich fractions: flavonoids fraction (CcF) and tannins fraction (CcT). An oil/water emulsion was developed with each active (CcI, CcF+CcT and diclofenac), pH and texture having been evaluated. Release tests were further performed using static Franz diffusion cells and all collected samples were monitored by HPLC-PDA. In vivo topical anti-inflammatory activity evaluation was performed by the carrageenan-induced rat paw edema model. The texture analysis revealed statistically significant differences for all tested parameters to CcF+CcT, supporting its topical application. Release experiments lead to the detection of the phenolic compounds from each sample in the receptor medium and the six major flavonoids were quantified, by HPLC-PDA: carlinoside, isoorientin, cynaroside, luteolin 7-O-neohesperidoside, kurilesin A and cassiaoccidentalin B. The CcF+CcT formulation prompted to the higher release rate for all these flavonoids. CcI4%, CcI1% and CcF+CcT exhibited an edema reduction of 43.18, 29.55 and 59.09%, respectively. Our findings highlight that CcI, containing luteolin 7-O-neohesperidoside, cassiaoccidentalin B, carlinoside, cynaroside and tannins have a potential anti-inflammatory topical activity, suggesting their promising application in the treatment of skin inflammatory pathologies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Comparative cardiovascular safety of nonsteroidal anti-inflammatory drugs in patients with hypertension: a population-based cohort study.

PubMed

Dong, Yaa-Hui; Chang, Chia-Hsuin; Wu, Li-Chiu; Hwang, Jing-Shiang; Toh, Sengwee

2018-05-01

Previous studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with higher cardiovascular risks. However, few have been active comparison studies that directly assessed the potential differential cardiovascular risk between NSAID classes or across individual NSAIDs. We compared the risk of major cardiovascular events between cyclooxygenase 2 (COX-2)-selective and nonselective NSAIDs in patients with hypertension. We conducted a cohort study of patients with hypertension who initiated COX-2-selective or nonselective NSAIDs in a population-based Taiwanese database. The outcomes included hospitalization for the following major cardiovascular events: ischaemic stroke, acute myocardial infarction, congestive heart failure, transient ischaemic attack, unstable angina or coronary revascularization. We followed patients for up to 4 weeks, based on the as-treated principle. We used inverse probability weighting to control for baseline and time-varying covariates, and estimated the on-treatment hazard ratios (HRs) and 95% conservative confidence interval (CIs). We identified 2749 eligible COX-2-selective NSAID users and 52 880 eligible nonselective NSAID users. The HR of major cardiovascular events comparing COX-2-selective with nonselective NSAIDs after adjusting for baseline and time-varying covariates was 1.07 (95% CI 0.65, 1.74). We did not observe a differential risk when comparing celecoxib to diclofenac (HR 1.17; 95% CI 0.61, 2.25), ibuprofen (HR 1.36; 95% CI 0.58, 3.18) or naproxen (HR 0.75; 95% CI 0.23, 2.44). There was an increased risk with COX-2-selective NSAIDs, however, when comparing COX-2-selective NSAIDs with mefenamic acid (HR 2.11; 95% CI 1.09, 4.09). Our results provide important information about the comparative cardiovascular safety of NSAIDs in patients with hypertension. © 2018 The British Pharmacological Society.

Systematic review of the cost effectiveness of prophylactic treatments in the prevention of gastropathy in patients with rheumatoid arthritis or osteoarthritis taking non-steroidal anti-inflammatory drugs

PubMed Central

van Dieten, H. E M; Bos, I.; van Tulder, M. W; Lems, W.; Dijkmans, B.; Boers, M.

2000-01-01

A systematic review on the cost effectiveness of prophylactic treatments of non-steroidal anti-inflammatory drug (NSAID) induced gastropathy in patients with osteoarthritis or rheumatoid arthritis was conducted. Two reviewers conducted the literature search and the review. Both full and partial economic evaluations published in English, Dutch, or German were included. The criteria list published in the textbook of Drummond was used to determine the quality of the economic evaluations. The methodological quality of three randomised controlled trials (RCTs) in which the economic evaluations obtained probability estimates of NSAID induced gastropathy and adverse events was assessed by a list of internal validity criteria. The conclusions were based on a rating system consisting of four levels of evidence.
  Ten economic evaluations were included; three were based on RCTs. All evaluations studied misoprostol as prophylactic treatment: in one evaluation misoprostol was studied as a fixed component in a combination with diclofenac (Arthrotec). All economic evaluations comprised analytical studies containing a decision tree. The three trials were of high methodological quality. Nine economic evaluations were considered high quality and one economic evaluation was considered of low methodological quality. There is strong evidence (level "A") that the use of misoprostol for the prevention of NSAID induced gastropathy is cost effective, and limited evidence (level "C") that the use of Arthrotec is cost effective. Although the levels of evidence used in this review are arbitrary, it is believed that a qualitative analysis is useful: quantitative analyses in this field are hampered by the heterogeneity of economic evaluations. Existing criteria to evaluate the methodological quality of economic evaluations may need refinement for use in systematic reviews.

 PMID:11005773

Systematic review of the cost effectiveness of prophylactic treatments in the prevention of gastropathy in patients with rheumatoid arthritis or osteoarthritis taking non-steroidal anti-inflammatory drugs.

PubMed

van Dieten, H E; Korthals-de Bos, I B; van Tulder, M W; Lems, W F; Dijkmans, B A; Boers, M

2000-10-01

A systematic review on the cost effectiveness of prophylactic treatments of non-steroidal anti-inflammatory drug (NSAID) induced gastropathy in patients with osteoarthritis or rheumatoid arthritis was conducted. Two reviewers conducted the literature search and the review. Both full and partial economic evaluations published in English, Dutch, or German were included. The criteria list published in the textbook of Drummond was used to determine the quality of the economic evaluations. The methodological quality of three randomised controlled trials (RCTs) in which the economic evaluations obtained probability estimates of NSAID induced gastropathy and adverse events was assessed by a list of internal validity criteria. The conclusions were based on a rating system consisting of four levels of evidence. Ten economic evaluations were included; three were based on RCTs. All evaluations studied misoprostol as prophylactic treatment: in one evaluation misoprostol was studied as a fixed component in a combination with diclofenac (Arthrotec). All economic evaluations comprised analytical studies containing a decision tree. The three trials were of high methodological quality. Nine economic evaluations were considered high quality and one economic evaluation was considered of low methodological quality. There is strong evidence (level "A") that the use of misoprostol for the prevention of NSAID induced gastropathy is cost effective, and limited evidence (level "C") that the use of Arthrotec is cost effective. Although the levels of evidence used in this review are arbitrary, it is believed that a qualitative analysis is useful: quantitative analyses in this field are hampered by the heterogeneity of economic evaluations. Existing criteria to evaluate the methodological quality of economic evaluations may need refinement for use in systematic reviews.

Occurrence of non-steroidal anti-inflammatory drugs in Tehran source water, municipal and hospital wastewaters, and their ecotoxicological risk assessment.

PubMed

Eslami, Akbar; Amini, Mostafa M; Yazdanbakhsh, Ahmad Reza; Rastkari, Noushin; Mohseni-Bandpei, Anoushiravan; Nasseri, Simin; Piroti, Ehsan; Asadi, Anvar

2015-12-01

Pharmaceuticals are becoming widely distributed in waters and wastewaters and pose a serious threat to public health. The present study aimed to analyze non-steroidal anti-inflammatory drugs (NSAIDs) in surface waters, drinking water, and wastewater in Tehran, Iran. Thirty-six samples were collected from surface waters, tap water, and influent and effluent of municipal and hospital wastewater treatment plants (WWTP). A solid-phase extraction (SPE) followed by liquid chromatography-tandem mass spectrometry method was used for the determination of pharmaceuticals, namely ibuprofen (IBP), naproxen (NPX), diclofenac (DIC), and indomethacin (IDM). IBP was found in most of the samples and had the highest concentration. The highest concentrations of NSAIDs were found in the municipal WWTP influents and hospital WWTP effluents. In the municipal WWTP influent samples, the concentrations of IBP, NPX, DIC, and IDM were 1.05, 0.43, 0.23, and 0.11 μg/L, respectively. DIC was found only in one river sample. All NSAIDs were detected in tap water samples. However, their concentration was very low and the maximum values for IBP, NPX, DIC, and IDM were 47, 39, 24, and 37 ng/L, respectively, in tap water samples. Results showed that the measured pharmaceuticals were detected in all rivers with low concentrations in nanograms per liter range, except DIC which was found only in one river. Furthermore, this study showed that the aforementioned pharmaceuticals are not completely removed during their passage through WWTPs. A potential environmental risk of selected NSAIDs for the urban wastewater has been discussed. However, given their low measured concentrations, no ecotoxicological effect is suspected to occur.

Helicobacter pylori eradication prior to initiation of long-term non-steroidal anti-inflammatory drug therapy in Chinese patients-a cost-effectiveness analysis.

PubMed

You, J H S; Lau, W; Lee, I Y C; Yung, M; Ching, J Y L; Chan, F K L; Lee, K K C

2006-04-01

Recent randomized clinical trials suggested that eradication of Helicobacter pylori prior to initiation of non-steroidal anti-inflammatory drug (NSAID) therapy would reduce the rate of peptic ulcer disease (PUD). To analyze the cost-effectiveness of H. pylori eradication prior to initiation of long-term NSAID therapy for prevention of NSAID-induced PUD in a cohort of Chinese patients at high risk for PUD. Clinical and economic data of 100 participants from a previously reported clinical trial conducted in Hong Kong were analyzed. Patients with a history of peptic ulcers were randomized to 1-week omeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg twice daily (eradication group; n = 51) or 1-week omeprazole 20 mg twice daily (omeprazole group; n = 49) before initiation of diclofenac 100 mg daily for 6 months. The rates of PUD and healthcare utilization for routine follow-up as well as for management of symptomatic PUD of the 2 groups were retrieved from medical records. The rate of symptomatic ulcers in eradication group and omeprazole group were 3.9% and 18%, respectively. The mean direct medical cost of the eradication group was significantly lower than that of the omeprazole group by 30% (US dollar 797 (95% CI = 685 - 909) versus US dollar 1,128 (95% CI = 879 - 1,377)) (p = 0.018). The results were robust to variation of all the cost items. H. pylori eradication prior to initiation of NSAID therapy appeared to reduce the ulcer rate and mean direct medical cost when compared to no eradication for Chinese H. pylori-infected NSAID users at high risk for PUD.

Effect of the Association of Nonsteroidal Anti-inflammatory and Antibiotic Drugs on Antibiofilm Activity and pH of Calcium Hydroxide Pastes.

PubMed

de Freitas, Rafaela Pignatti; Greatti, Vanessa Raquel; Alcalde, Murilo Priori; Cavenago, Bruno Cavalini; Vivan, Rodrigo Ricci; Duarte, Marco Antonio Hungaro; Weckwerth, Ana Carolina Villas Bôas; Weckwerth, Paulo Henrique

2017-01-01

The objective of the present study was to evaluate the in vitro antibiofilm activity and pH of calcium hydroxide associated with different nonsteroidal anti-inflammatory drugs (NSAIDs). The groups analyzed were as follows: group 1, calcium hydroxide paste with propylene glycol; group 2, calcium hydroxide paste with propylene glycol + 5% diclofenac sodium; group 3, calcium hydroxide paste with propylene glycol + 5% ibuprofen; group 4, calcium hydroxide paste with propylene glycol + 5% ciprofloxacin; and group 6, positive control (without medication). For analysis of the pH, the pastes were inserted into tubes and immersed in flasks containing ultrapure water. At the time intervals of 3, 24, 72, and 168 hours, the pH was measured with a calibrated pH meter. For microbial analysis, biofilm was induced in 30 bovine dentin blocks for 21 days. Subsequently, the pastes were placed on the blocks with biofilm for 7 days. Afterward, the pastes were removed by irrigation with sterile water, and the specimens were analyzed with a laser scanning confocal microscope with the 50 μL Live/Dead BacLight Bacterial Viability solution L7012 Kit (Molecular Probes, Inc, Eugene, OR). Data were subjected to statistical analysis at a significance level of 5%. The highest pH values were found for calcium hydroxide associated with ciprofloxacin in all periods analyzed. With the exception of pure calcium hydroxide paste, the other groups showed statistically significant differences (P < .05) in comparison with the positive control. The association of NSAIDs or antibiotic did not interfere with the pH of calcium hydroxide paste and increased the antimicrobial action of calcium hydroxide paste against Enterococcus faecalis biofilm formation. Published by Elsevier Inc.

Preadmission use of nonaspirin nonsteroidal anti-inflammatory drugs and 30-day stroke mortality.

PubMed

Schmidt, Morten; Hováth-Puhó, Erzsébet; Christiansen, Christian Fynbo; Petersen, Karin L; Bøtker, Hans Erik; Sørensen, Henrik Toft

2014-11-25

To examine whether preadmission use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) influenced 30-day stroke mortality. We conducted a nationwide population-based cohort study. Using medical databases, we identified all first-time stroke hospitalizations in Denmark between 2004 and 2012 (n = 100,043) and subsequent mortality. We categorized NSAID use as current (prescription redemption within 60 days before hospital admission), former, and nonuse. Current use was further classified as new or long-term use. Cox regression was used to compute hazard ratios (HRs) of death within 30 days, controlling for potential confounding through multivariable adjustment and propensity score matching. The adjusted HR of death for ischemic stroke was 1.19 (95% confidence interval [CI]: 1.02-1.38) for current users of selective cyclooxygenase (COX)-2 inhibitors compared with nonusers, driven by the effect among new users (1.42, 95% CI: 1.14-1.77). Comparing the different COX-2 inhibitors, the HR was driven by new use of older traditional COX-2 inhibitors (1.42, 95% CI: 1.14-1.78) among which it was 1.53 (95% CI: 1.02-2.28) for etodolac and 1.28 (95% CI: 0.98-1.68) for diclofenac. The propensity score-matched analysis supported the association between older COX-2 inhibitors and ischemic stroke mortality. There was no association for former users. Mortality from intracerebral hemorrhage was not associated with use of nonselective NSAIDs or COX-2 inhibitors. Preadmission use of COX-2 inhibitors was associated with increased 30-day mortality after ischemic stroke, but not hemorrhagic stroke. Use of nonselective NSAIDs at time of admission was not associated with mortality from ischemic stroke or intracerebral hemorrhage. © 2014 American Academy of Neurology.

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

PubMed

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.

Removal of endocrine disruptors and non-steroidal anti-inflammatory drugs through wastewater chlorination: the effect of pH, total suspended solids and humic acids and identification of degradation by-products.

PubMed

Noutsopoulos, Constantinos; Koumaki, Elena; Mamais, Daniel; Nika, Maria-Christina; Bletsou, Anna A; Thomaidis, Nikolaos S

2015-01-01

Endocrine disrupting chemicals (EDCs) and non-steroidal anti-inflammatory drugs (NSAIDs) are two groups of emerging pollutants the significance of which rests on their persistent detection in the aquatic environment and their possible adverse effects. Wastewater treatment plants are one of the major ways for transporting such chemicals in the aquatic environment. Chlorination is usually the last stage of treatment before wastewater being disposed to the aquatic environment. This work focuses on the evaluation of the effect of chlorine dose and specific wastewater characteristics (pH, total suspended solids and humic acids) on the removal of target EDCs and NSAIDs through chlorination. Another objective of this study is the identification of chlorination by-products of specific EDCs and NSAIDs and their dependence on contact time. Based on the results it is concluded that the effect of chlorine dose and humic acids concentration on the degradation of target compounds during chlorination is minimal. On the contrary, pH is a critical parameter which highly affects process performance. Moreover, it is concluded that not only the free available chlorine species, but also the properties of EDCs and NSAIDs under different pH conditions can affect chlorination process performance. The effect of TSS on the degradation of the target compounds during chlorination is more profound for chemicals with high Kow values and therefore higher affinity to partition to the particulate phase (i.e. nonylphenols, triclosan). Several degradation by-products were identified through chlorination of nonylphenol, bisphenol A and diclofenac. The dependence of these by-products on chlorination contact time is also demonstrated. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of new polyherbal formulations DF1911, DF2112 and DF2813 on CFA induced inflammation in rat model.

PubMed

Nagarkar, Bhagyashri; Jagtap, Suresh

2017-04-04

Aim of the present study was to evaluate anti-inflammatory activity of newly developed polyherbal formulations DF1911, DF2112 and DF2813. These newly developed formulations are modifications of Dashamoola, a well known Ayurvedic formulation, along with addition of new plants. Complete Freund's adjuvant (CFA) induced inflammation in rat was used as an experimental model. Effects of the treatment in rats were monitored by physiological and biochemical parameters, histopathology and through gene expression studies. Diclofenac sodium showed maximum percentage inhibition (56.8 ± 3.5%) of paw edema followed by Dashamoola Kwatha (19.9 ± 1.8%). Among test formulations treated groups, DF1911 at 250 mg/kg bw (48.2 ± 5.4%, p < 0.001) and DF2112 at 250 mg/kg bw (49.9 ± 3.5%, p < 0.001) showed significant and maximum increase in percentage inhibition of paw edema as compared to Dashamoola Kwatha. Hematological alterations in CFA rats were normalized after treatment with test formulations. Results of serum markers and histopathological observations also supported the activity of formulations. Increased MDA levels in liver tissue of CFA injected animals significantly (p < 0.05) decreased by Diclofenac sodium and test formulation treated groups. DF1911, DF2112 and DF2813 showed down-regulation of IL1-β (~6.4-fold, ~5.2-fold and ~7.6-fold), IL-6 (~1.1-fold, ~1.6-fold and ~1.9-fold), TNF-α (~2.0-fold, ~4.6-fold and ~3.5-fold), and iNOS (~1.2-fold, ~1.8-fold and ~1.1-fold) in inflamed paw tissue compared to negative control group, respectively. The anti-inflammatory effects of DF1911 and DF2112 in rats were significantly higher than the Dashamoola Kwatha and are comparable to Diclofenac sodium.

Protective Effect of High Molecular Weight Protein Sub-fraction of Calotropis procera Latex in Monoarthritic Rats.

PubMed

Chaudhary, Priyanka; Ramos, Marcio V; Vasconcelos, Mirele da Silveira; Kumar, Vijay L

2016-05-01

Proteins present in the latex of Calotropis procera have been shown to produce anti-inflammatory effect and to afford protection in various disease models. To determine the efficacy of high molecular weight protein sub-fraction (LPPI) of latex of C. procera in ameliorating joint inflammation and hyperalgesia in a preclinical model of arthritis. Monoarthritis was induced in rats by intra-articular injection of Freund's complete adjuvant (FCA) and the effect of two doses of LPPI (5 and 25 mg/kg) and diclofenac (5 mg/kg) was evaluated on joint swelling, stair climbing ability, motility, and dorsal flexion pain on day 3. The rats were sacrificed on day 3 to measure tissue levels of reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS). Evaluation of joint histology was also made. Intra-articular injection of FCA produced joint swelling and difficulty in stair climbing ability, motility, and pain on flexion of the joint as revealed by scores obtained for these functional parameters. LPPI produced a dose-dependent decrease in joint swelling and improved joint functions. Arthritic rats also revealed altered oxidative homeostasis where joint tissue GSH levels were decreased and TBARS levels were increased as compared to normal rats. The levels of these oxidative stress markers were near normal in arthritic rats treated with LPPI. Moreover, treatment with LPPI also maintained the structural integrity of the joint. The protective effect of LPPI was comparable to the standard anti-inflammatory drug, diclofenac. The findings of the present study show that LPPI fraction comprising high molecular weight proteins could be used for the alleviation of arthritic symptoms. High molecular weight protein sub-fraction of latex of Calotropis procera (LPPI) reduced joint swelling and hyperalgesia in arthritic ratsLPPI produced a significant improvement in stair climbing ability and motility in arthritic ratsLPPI normalized the levels of oxidative stress markers in the arthritic jointsTreatment with LPPI reduced neutrophil influx and edema in the arthritic joints Abbreviations used: FCA: Freund's complete adjuvant, GSH: Glutathione, TBARS: Thiobarbituric acid reactive substances, TBA: Thiobarbituric acid, MDA: Malondialdehyde, LPPI: Latex protein fraction PI.

The structural and electronical factors that contribute affinity for the time-dependent inhibition of PGHS-1 by indomethacin, diclofenac and fenamates

NASA Astrophysics Data System (ADS)

Pouplana, R.; Pérez, C.; Sánchez, J.; Lozano, J. J.; Puig-Parellada, P.

1999-05-01

PGHS-1 and PGHS-2 are the targets of nonsteroidal anti- inflammatory drugs (NSAIDs). It appears that the high degree of selectivity for inhibition of PGHS-2 shown by certain compounds is the result of two mechanisms (time-dependent and time-independent inhibition), by which they interact with each isoform. The fenamic acids can be divided into competitive inhibitors of substrate binding and competitive inhibitors that cause time-dependent losses of cyclooxygenase activity. The cyclooxygenase activity was measured by oxygen consumption following preincubation of the enzyme and the inhibitor for increasing periods of time. The rate constants associated with binding inhibition kinetics and structure-activity relationships were calculated for a large number of fenamates, diclofenac and indomethacin. The KI* values are similar but the individual rate constants are markedly different: KI is two-fold lower, and k2 is six-fold slower for diclofenac than for indomethacin. All the active time-dependent compounds show MEPs with a negative conical surface, with their vertex on the minimum of the carboxyl group, which extends around the first aromatic ring to the central region. The conical surface keeps an open angle of 61° or larger, and a close contact surface with the residues Ala527, Ileu523, Val349, and Ser530, in the zones surrounding the bridging amino group and the chlorine atoms for meclofenamate and diclofenac, or in the region around the carbonyl group for indomethacin. The KI* and IC50 values indicate that the interactions that promote the slow binding kinetics must be examined in relation to the reaction energies of formation (ΔHr) of an ionic bond between the deprotonated carboxylic acid group of acid NSAIDs with the monocationic guanidinum group of Arg120, the free energies of solvation in aqueous solution, and the molecular volumes measured. Presumably indomethacin, diclofenac and meclofenamate cause the enzyme to undergo a subtle conformational change to a form that binds compounds even more tightly, with some slight structural changes confined to reorientations of the Arg277 and Gln358 side chains. These results show that the model has reliably chosen regions of biological significance consistent with both the X-ray crystallographic and kinetic results.

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

DTIC Science & Technology

2015-10-01

This proposal aims to identify topically applied anti-inflammatory drugs that will reduce recipient site inflammation and skin graft contraction. We...hypothesize that the elevated and prolonged inflammatory state of the recipient wound bed is a causative factor in the development of skin graft contraction...Using a porcine model of skin graft contraction, we will screen for anti-inflammatory agents (dose, schedule of administration, drug class

The Concomitant Consumption of Cod Liver Oil Causes a Reduction in the Daily Diclofenac Sodium Usage in Rheumatoid Arthritis Patients: A Pilot Study

PubMed Central

Gupta, Vinay Kumar; Khan, Z. Y. Zafer; Ahmad, Mushtaq

2013-01-01

Objective: To evaluate whether the concomitant consumption of Cod liver oil can reduce the daily dose of Diclofenac Sodium and probably the risk of the side effects which are associated with it in Rheumatoid Arthritis patients. Material and Methods: This longitudinal, prospective, open label study was conducted from April to September 2012 at Mahatma Gandhi Medical College and Hospital, Jaipur, India. 30 Rheumatoid Arthritis patients who were aged between 19 to 60 years, who fulfilled the inclusion criteria, were enrolled. Each patient was given five Cod liver oil capsules twice a day, for a period of 24 weeks. Each capsule which contained 300 mg of Cod liver oil had Eicosapentaenoic acid-20 mg and Docosahexaenoic acid-30 mg. The patients who took different Nonsteroidal anti-inflammatory drugs daily were switched over to Diclofenac Sodium 50 mg as a single dose, up to a maximum dose of 200 mg per day. The dose of Diclofenac Sodium which was consumed per day and the average daily requirement at different visits were recorded in each patient and they were compared. The patients were assessed for their pain scores by using the Visual Analogue Scale (VAS) at different weeks. In addition, the ‘Subjective Response’ to the pain was evaluated in each patient at the respective visits. The Student’s “t”-test was applied for the analysis of the VAS pain score and for the evaluation of the reduction in the mean daily dose of the Diclofenac Sodium consumption. A probability value of less than 0.05 (p< 0.05) was considered to be statistically significant. Moreover, the results of the ‘Subjective Response’ to the pain were expressed as percentage. Results: A significant decrease (p< 0.05) in the mean VAS pain score from 80.38 ± 6.4 at week 0 to 67.30 ± 5.3 at week 24 was noted in the patients. There was a significant reduction (p<0.05) in mean dose of Diclofenac Sodium consumed from 115.04 ± 24.56 at week 4 to 98.83 ± 22.32 at week 24. Moreover, the percentage of the patients who experienced a ‘Better’ Subjective Response increased from 15.38% at week 4 to 61.53% at week 24 of the treatment follow up. Conclusion: This study revealed that the concurrent use of Cod liver oil which contained n-3 Essential Fatty Acid in Rheumatoid Arthritis patients reduced the mean daily dose of Diclofenac Sodium consumed and probably the incidence of the side effects which were associated with it. PMID:23998063

Microwave-assisted activated carbon from cocoa shell as adsorbent for removal of sodium diclofenac and nimesulide from aqueous effluents.

PubMed

Saucier, Caroline; Adebayo, Matthew A; Lima, Eder C; Cataluña, Renato; Thue, Pascal S; Prola, Lizie D T; Puchana-Rosero, M J; Machado, Fernando M; Pavan, Flavio A; Dotto, G L

2015-05-30

Microwave-induced chemical activation process was used to prepare an activated carbon from cocoa shell for efficient removal of two anti-inflammatories, sodium diclofenac (DFC) and nimesulide (NM), from aqueous solutions. A paste was obtained from a mixture of cocoa shell and inorganic components; with a ratio of inorganic: organic of 1 (CSC-1.0). The mixture was pyrolyzed in a microwave oven in less than 10 min. The CSC-1.0 was acidified with a 6 mol L(-1) HCl under reflux to produce MWCS-1.0. The CSC-1.0 and MWCS-1.0 were characterized using FTIR, SEM, N2 adsorption/desorption curves, X-ray diffraction, and point of zero charge (pHpzc). Experimental variables such as initial pH of the adsorbate solutions and contact time were optimized for adsorptive characteristics of MWCS-1.0. The optimum pH for removal of anti-inflammatories ranged between 7.0 and 8.0. The kinetic of adsorption was investigated using general order, pseudo first-order and pseu do-second order kinetic models. The maximum amounts of DCF and NM adsorbed onto MWCS-1.0 at 25 °C are 63.47 and 74.81 mg g(-1), respectively. The adsorbent was tested on two simulated hospital effluents. MWCS-1.0 is capable of efficient removal of DCF and NM from a medium that contains high sugar and salt concentrations. Copyright © 2015 Elsevier B.V. All rights reserved.

Naturally derived anti-inflammatory compounds from Chinese medicinal plants.

PubMed

Wang, Qiuhong; Kuang, Haixue; Su, Yang; Sun, Yanping; Feng, Jian; Guo, Rui; Chan, Kelvin

2013-03-07

Though inflammatory response is beneficial to body damage repair, if it is out of control, it can produce adverse effects on the body. Although purely western anti-inflammatory drugs, orthodox medicines, can control inflammation occurrence and development, it is not enough. The clinical efficacy of anti-inflammation therapies is unsatisfactory, thus the search for new anti-inflammation continues. Chinese Material Medica (CMM) remains a promising source of new therapeutic agents. CMM and herbal formulae from Traditional Chinese Medicine (TCM), unorthodox medicines, play an improtant anti-inflammatory role in multi-targets, multi-levels, and multi-ways in treating inflammation diseases in a long history in China, based on their multi-active ingredient characteristics. Due to these reasons, recently, CMM has been commercialized as an anti-inflammation agent which has become increasingly popular in the world health drug markets. Major research contributions in ethnopharmacology have generated vast amount of data associated with CMM in anti-inflammtion aspect. Therefore, a systematic introduction of CMM anti-inflammatory research progress is of great importance and necessity. This paper strives to describe the progress of CMM in the treatment of inflammatory diseases from different aspects, and provide the essential theoretical support and scientific evidence for the further development and utilization of CMM resources as a potential anti-inflammation drug through a variety of databases. Literature survey was performed via electronic search (SciFinder®, Pubmed®, Google Scholar and Web of Science) on papers and patents and by systematic research in ethnopharmacological literature at various university libraries. This review mainly introduced the current research on the anti-inflammatory active ingredient, anti-inflammatory effects of CMM, their mechanism, anti-inflammatory drug development of CMM, and toxicological information. CMM is used clinically to treat inflammation symptoms in TCM, and its effect is mediated by multiple targets through multiple active ingredients. Although scholars around the world have made studies on the anti-inflammatory studies of CMM from different pathways and aspects and have made substantial progress, further studies are warranted to delineate the inflammation actions in more cogency models, establish the toxicological profiles and quality standards, assess the potentials of CMM in clinical applications, and make more convenient preparations easy to administrate for patients. Development of the clinically anti-inflammatory drugs are also warranted. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Urinary proteomic profiling reveals diclofenac-induced renal injury and hepatic regeneration in mice

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

Swelm, Rachel P.L. van; Laarakkers, Coby M.M.; Pertijs, Jeanne C.L.M.

Diclofenac (DF) is a widely used non-steroidal anti-inflammatory drug for the treatment of rheumatic disorders, but is often associated with liver injury. We applied urinary proteomic profiling using MALDI-TOF MS to identify biomarkers for DF-induced hepatotoxicity in mice. Female CH3/HeOUJIco mice were treated with 75 mg/kg bw DF by oral gavage and 24 h urine was collected. Proteins identified in urine of DF-treated mice included epidermal growth factor, transthyretin, kallikrein, clusterin, fatty acid binding protein 1 and urokinase, which are related to liver regeneration but also to kidney injury. Both organs showed enhanced levels of oxidative stress (TBARS, p

Occurrence and geodatabase mapping of three contaminants of emerging concern in receiving water and at effluent from waste water treatment plants - A first overview of the situation in the Republic of Ireland.

PubMed

Tahar, Alexandre; Tiedeken, Erin Jo; Rowan, Neil J

2018-03-01

This constitutes the first study to address occurrence and geodatabase mapping of the anti-inflammatory drug diclofenac (DCL) and the natural (17-beta-estradiol or E2) and synthetic (17-alpha-ethynylestradiol or EE2) estrogenic hormones in Republic of Ireland receiving waters over the period 1999 to 2015. Among these data, 317 samples came from concentration studies, while 205 were from effect-based studies. Monitoring data came from 16 waste water treatment plants (WWTPs), 23 water bodies (including rivers, lakes, marine and transitional waters) and 7 from domestic locations. Out of approximately 1000 WWPTs in the Republic of Ireland, only 16 have been monitored for at least one of these compounds of emerging concern (CECs). Diclofenac is found in treated effluents from 5 WWTPs at levels at least as high as other European WWPTs, and sometime higher. Measurements of E2 and EE2 in WWPT effluents were rare and effluents were more often evaluated for total estrogens; these CECs were generally not detected using conventional analytical methods because of limits of detection being too high compared to environmental concentrations and WFD environmental quality standards. There was good agreement between occurrence of these CEC and regional drug dispensing data in Ireland. Mapping the aforementioned data onto appropriate river basin catchment management tools will inform predictive and simulated risk determinations to inform investment in infrastructure that is necessary to protect rivers and beaches and economic activities that rely on clean water. There is a pressing commensurate need to refine/develop new analytical methods with low levels of detection for future CEC intervention. Copyright © 2017 Elsevier B.V. All rights reserved.

Temperature-responsive nanogel multilayers of poly(N-vinylcaprolactam) for topical drug delivery.

PubMed

Zavgorodnya, Oleksandra; Carmona-Moran, Carlos A; Kozlovskaya, Veronika; Liu, Fei; Wick, Timothy M; Kharlampieva, Eugenia

2017-11-15

We report nanothin temperature-responsive hydrogel films of poly(N-vinylcaprolactam) nanoparticles (νPVCL) with remarkably high loading capacity for topical drug delivery. Highly swollen (νPVCL) n multilayer hydrogels, where n denotes the number of nanoparticle layers, are produced by layer-by-layer hydrogen-bonded assembly of core-shell PVCL-co-acrylic acid nanoparticles with linear PVPON followed by cross-linking of the acrylic acid shell with either ethylene diamine (EDA) or adipic acid dihydrazide (AAD). We demonstrate that a (νPVCL) 5 film undergoes dramatic and reversible swelling up to 9 times its dry thickness at pH = 7.5, indicating 89v/v % of water inside the network. These hydrogels exhibit highly reversible ∼3-fold thickness changes with temperature variations from 25 to 50°C at pH = 5, the average pH of human skin. We also show that a (νPVCL) 30 hydrogel loaded with ∼120µgcm -2 sodium diclofenac, a non-steroidal anti-inflammatory drug used for osteoarthritis pain management, provides sustained permeation of this drug through an artificial skin membrane for up to 24h at 32°C (the average human skin surface temperature). The cumulative amount of diclofenac transported at 32°C from the (νPVCL) 30 hydrogel after 24h is 12 times higher than that from the (νPVCL) 30 hydrogel at 22°C. Finally, we demonstrate that the (νPVCL) hydrogels can be used for multiple drug delivery by inclusion of Nile red, fluorescein and DAPI dyes within the νPVCL nanoparticles prior to hydrogel assembly. Using confocal microscopy we observed the presence of separate dye-loaded νPVCL compartments within the hydrogel matrix with all three dyes confined to the nanogel particles without intermixing between the dyes. Our study provides opportunity for development of temperature-responsive multilayer hydrogel coatings made via the assembly of core-shell nanogel particles which can be used for skin-sensitive materials for topical drug delivery. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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.

Pharmacological Evaluation and Preparation of Nonsteroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit

PubMed Central

de Melo, Thais Regina Ferreira; Chelucci, Rafael Consolin; Pires, Maria Elisa Lopes; Dutra, Luiz Antonio; Barbieri, Karina Pereira; Bosquesi, Priscila Longhin; Trossini, Gustavo Henrique Goulart; Chung, Man Chin; dos Santos, Jean Leandro

2014-01-01

A series of anti-inflammatory derivatives containing an N-acyl hydrazone subunit (4a–e) were synthesized and characterized. Docking studies were performed that suggest that compounds 4a–e bind to cyclooxygenase (COX)-1 and COX-2 isoforms, but with higher affinity for COX-2. The compounds display similar anti-inflammatory activities in vivo, although compound 4c is the most effective compound for inhibiting rat paw edema, with a reduction in the extent of inflammation of 35.9% and 52.8% at 2 and 4 h, respectively. The anti-inflammatory activity of N-acyl hydrazone derivatives was inferior to their respective parent drugs, except for compound 4c after 5 h. Ulcerogenic studies revealed that compounds 4a–e are less gastrotoxic than the respective parent drug. Compounds 4b–e demonstrated mucosal damage comparable to celecoxib. The in vivo analgesic activities of the compounds are higher than the respective parent drug for compounds 4a–b and 4d–e. Compound 4a was more active than dipyrone in reducing acetic-acid-induced abdominal constrictions. Our results indicate that compounds 4a–e are anti-inflammatory and analgesic compounds with reduced gastrotoxicity compared to their respective parent non-steroidal anti-inflammatory drugs. PMID:24714090

Evaluation of Skin Penetration of Diclofenac from a Novel Topical Non Aqueous Solution: A Comparative Bioavailability Study

PubMed Central

Nivsarkar, Manish; Patel, Ketan R.; Patel, Dixit D.

2015-01-01

Introduction Different topical formulations of diclofenac have varying skin penetration profile. Recent advances in science and technology has led to the development of many new formulations of drugs for topical drug delivery. One such technological development has led to the innovation of Dynapar QPS, a novel, non-aqueous, quick penetrating solution (QPS) of diclofenac diethylamine. Aim This study was aimed to measure the total exposure from the drug penetrating the skin in healthy human subjects and comparing the relative systemic bioavailability of Dynapar QPS® with diclofenac emulgel. Materials and Methods A 200 mg of diclofenac from either Dynapar QPS® (5 ml) or emulgel (20 g) was applied on back of subject as per the randomisation schedule. Blood samples were collected up to 16 hours post drug application. Plasma concentration of diclofenac was measured by pre-validated HPLC method. Pharmacokinetic (PK) parameters like Cmax, Tmax, t1/2, AUC0-t, AUC0-∞, and Kel, of diclofenac were determined for both the formulations. Results Mean Cmax after administration of Dynapar QPS® and diclofenac emulgel were 175.93 and 40.04 ng/ml, respectively. Tmax of diclofenac was almost half with QPS compared to emulgel (5.24 hrs versus 9.53 hrs respectively). The mean AUC0–t and AUC0-∞ after administration of Dynapar QPS® was higher as compared to diclofenac emulgel (AUC0–t: 1224.19 versus 289.78 ng.h/ml, respectively; AUC0-∞: 1718.21 versus 513.83 ng.h/ml, respectively). None of the subject experienced any adverse event during the study. Conclusion The results indicate an enhanced penetration and subsequent absorption of diclofenac from Dynapar QPS® as compared to diclofenac emulgel. Higher penetration is likely to translate into better pain relief in patients. PMID:26816910

Evaluation of Skin Penetration of Diclofenac from a Novel Topical Non Aqueous Solution: A Comparative Bioavailability Study.

PubMed

Nivsarkar, Manish; Maroo, Sanjaykumar H; Patel, Ketan R; Patel, Dixit D

2015-12-01

Different topical formulations of diclofenac have varying skin penetration profile. Recent advances in science and technology has led to the development of many new formulations of drugs for topical drug delivery. One such technological development has led to the innovation of Dynapar QPS, a novel, non-aqueous, quick penetrating solution (QPS) of diclofenac diethylamine. This study was aimed to measure the total exposure from the drug penetrating the skin in healthy human subjects and comparing the relative systemic bioavailability of Dynapar QPS(®) with diclofenac emulgel. A 200 mg of diclofenac from either Dynapar QPS(®) (5 ml) or emulgel (20 g) was applied on back of subject as per the randomisation schedule. Blood samples were collected up to 16 hours post drug application. Plasma concentration of diclofenac was measured by pre-validated HPLC method. Pharmacokinetic (PK) parameters like Cmax, Tmax, t1/2, AUC0-t, AUC0-∞, and Kel, of diclofenac were determined for both the formulations. Mean Cmax after administration of Dynapar QPS(®) and diclofenac emulgel were 175.93 and 40.04 ng/ml, respectively. Tmax of diclofenac was almost half with QPS compared to emulgel (5.24 hrs versus 9.53 hrs respectively). The mean AUC0-t and AUC0-∞ after administration of Dynapar QPS(®) was higher as compared to diclofenac emulgel (AUC0-t: 1224.19 versus 289.78 ng.h/ml, respectively; AUC0-∞: 1718.21 versus 513.83 ng.h/ml, respectively). None of the subject experienced any adverse event during the study. The results indicate an enhanced penetration and subsequent absorption of diclofenac from Dynapar QPS(®) as compared to diclofenac emulgel. Higher penetration is likely to translate into better pain relief in patients.

Drug Targets for Cardiovascular-Safe Anti-Inflammatory: In Silico Rational Drug Studies

PubMed Central

Shahbazi, Sajad; Sahrawat, Tammanna R.; Ray, Monalisa; Dash, Swagatika; Kar, Dattatreya; Singh, Shikha

2016-01-01

Cyclooxygenase-2 (COX-2) plays an important role in memory consolidation and synaptic activity, the most fundamental functions of the brain. It converts arachidonic acid to prostaglandin endoperoxide H2. In contrast, if over-expressed, it causes inflammation in response to cytokine, pro-inflammatory molecule, and growth factor. Anti-inflammatory agents, by allosteric or competitive inhibition of COX-2, alleviate the symptoms of inflammation. Coxib family drugs, particularly celecoxib, are the most famous anti-inflammatory agents available in the market showing significant inhibitory effect on COX-2 activity. Due to high cardiovascular risk of this drug group, recent researches are focused on the investigation of new safer drugs for anti-inflammatory diseases. Natural compounds, particularly, phytochemicals are found to be good candidates for drug designing and discovery. In the present study, we performed in silico studies to quantitatively scrutinize the molecular interaction of curcumin and its structural analogs with COX-2, COX-1, FXa and integrin αIIbβIII to investigate their therapeutic potential as a cardiovascular-safe anti-inflammatory medicine (CVSAIM). The results of both ADMET and docking study indicated that out of all the 39 compounds studied, caffeic acid had remarkable interaction with proteins involved in inflammatory response. It was also found to inhibit the proteins that are involved in thrombosis, thereby, having the potential to be developed as therapeutic agent. PMID:27258084

Topical ketoprofen TDS patch versus diclofenac gel: efficacy and tolerability in benign sport related soft‐tissue injuries

PubMed Central

Esparza, Francisco; Cobián, César; Jiménez, José Fernando; García‐Cota, Juan José; Sánchez, Carlos; SETRADE, Antonio Maestro and the working group for the acute pain study of

2007-01-01

Objective To compare the ketoprofen TDS patch with diclofenac gel in the treatment of traumatic acute pain in benign sport‐related soft‐tissue injuries. Design 7–14 treatment days, prospective, randomised, open study. Patients Outpatients aged 18–70 years diagnosed for painful benign sport‐related soft‐tissue injury (sprains, strains and contusions within the prior 48 h), randomised to either ketoprofen patch 100 mg once daily (n = 114) or diclofenac gel 2–4 g three times daily (n = 109). Intervention 7–14 days of topical non‐steroidal anti‐inflammatory drugs treatment to assess the pain intensity changes (daily activities and spontaneous at rest) in a daily diary (100‐mm Visual Analogue Scale (VAS)). Main outcome measurement Pain intensity (VAS). Results The ketoprofen patch was not inferior to diclofenac gel in reducing the baseline pain during daily activities (difference of –1.17 mm in favour of ketoprofen patch, 95% CI (–5.86 to 3.52), reducing to the baseline VAS 79%. Ketoprofen patch presented also a higher cure rate (64%) than diclofenac gel (46%) at day 7 (p = 0.004). Patient opinions about the treatment comfort (pharmaceutical shape, application and dosage) were also statistically higher for the ketoprofen patch (>80% of the patients rated as good or excellent the patch removal and skin adherence). Conclusion Ketoprofen patches are effective and safe pain relievers for the treatment of sports injury pain with advantages compared with diclofenac gel. PMID:17138642

Piriformis Syndrome

MedlinePlus

... Treatment Generally, treatment for the disorder begins with stretching exercises and massage. Anti-inflammatory drugs may be ... Treatment Generally, treatment for the disorder begins with stretching exercises and massage. Anti-inflammatory drugs may be ...

Pharmacology and potential therapeutic applications of nitric oxide-releasing non-steroidal anti-inflammatory and related nitric oxide-donating drugs

PubMed Central

Keeble, J E; Moore, P K

2002-01-01

This review examines the biological significance, therapeutic potential and mechanism(s) of action of a range of nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAID) and related nitric oxide-releasing donating drugs (NODD). The slow release of nitric oxide (NO) from these compounds leads to subtle changes in the profile of pharmacological activity of the parent, non-steroidal anti-inflammatory drugs (NSAID). For example, compared with NSAID, NO-NSAID cause markedly diminished gastrointestinal toxicity and improved anti-inflammatory and anti-nociceptive efficacy. In addition, nitroparacetamol exhibits hepatoprotection as opposed to the hepatotoxic activity of paracetamol. The possibility that NO-NSAID or NODD may be of therapeutic benefit in a wide variety of disease states including pain and inflammation, thrombosis and restenosis, neurodegenerative diseases of the central nervous system, colitis, cancer, urinary incontinence, liver disease, impotence, bronchial asthma and osteoporosis is discussed. PMID:12237248

Evaluation of diclofenac prodrugs for enhancing transdermal delivery.

PubMed

Lobo, Shabbir; Li, Henan; Farhan, Nashid; Yan, Guang

2014-03-01

Abstract Objective: The purpose of this study was to evaluate the approach of using diclofenac acid (DA) prodrugs for enhancing transdermal delivery. Methanol diclofenac ester (MD), ethylene glycol diclofenac ester (ED), glycerol diclofenac ester (GD) and 1,3-propylene glycol diclofenac ester (PD) were synthesized and evaluated for their physicochemical properties such as solubilities, octanol/water partition coefficients, stratum corneum/water partition coefficients, hydrolysis rates and bioconversion rates. In vitro fluxes across human epidermal membrane (HEM) in the Franz diffusion cell were determined on DA-, MD-, ED-, GD- and PD-saturated aqueous solutions. The formation of GD and ED led to the prodrugs with higher aqueous solubilities and lower partition coefficients than those of the parent drug. Prodrugs with improved aqueous solubility showed better fluxes across HEM in aqueous solution than that of the parent drug, with GD showing the highest aqueous solubility and also the highest flux. There is a linear relationship between the aqueous solubility and flux for DA, ED and PD, but GD and MD deviated from the linear line. Diclofenac prodrugs with improved hydrophilicity than the parent drug could be utilized for enhancing transdermal diclofenac delivery.

Impact of traditional therapies and biologics on cardiovascular diseases in rheumatoid arthritis.

PubMed

Boyer, Jean-Frédéric; Cantagrel, Alain; Constantin, Arnaud

2008-07-01

In chronic inflammatory diseases such as rheumatoid arthritis (RA), systemic inflammation appears as an independent risk factor, contributing to increased cardiovascular mortality. This high cardiovascular mortality reveals the existence of accelerated atherosclerosis, the pathogenesis of which may be associated with traditional risk factors such as smoking, hypertension, dyslipidemia, deterioration of insulin sensitivity, and less traditional risk factors such as hyperhomocysteinemia, inflammatory conditions and endothelial dysfunction. Control of systemic inflammation theoretically provides a means of preventing this higher cardiovascular mortality among RA patients. In this review we address the question of the impact of anti-rheumatic drugs currently used in RA, such as non-steroidal anti-inflammatory drugs (e.g. non-selective or cyclooxygenase-2 selective inhibitors), steroidal anti-inflammatory drugs (glucocorticoids), traditional disease-modifying anti-rheumatic drugs (e.g. methotrexate) or biologics (e.g. anti-tumour necrosis factor alpha anti-tumour necrosis factor alpha) on cardiovascular diseases in RA patients. We also discuss the specific mechanisms involved in the differential cardiovascular effects of these therapeutic agents.

Targeted eco-pharmacovigilance for ketoprofen in the environment: Need, strategy and challenge.

PubMed

Wang, Jun; Zhao, Shu-Qi; Zhang, Meng-Ya; He, Bing-Shu

2018-03-01

Implementing "targeted" eco-pharmacovigilance(EPV) which focuses on individual or specific pharmaceuticals on a prioritised basis is a feasible, economical and customized approach to reduce the environmental concentrations and risks of pharmaceuticals. Non-steroidal anti-inflammatory drugs(NSAIDs) remaining in environment are a kind of priority hazard substances, due to a notable case that diclofenac residues caused the loss of more than 99% of vultures across the Indian sub-continent. Ketoprofen, as another widely used NSAID with comparable or even higher global consumption than diclofenac, in the environment has been shown to present a potential risk to non-target terrestrial and aquatic species. Based on the review of 85 articles reporting the analyses of ketoprofen residues in environment since 2010, we found that this NSAID frequently present in various environmental compartments around the world. Therefore, it is urgent to implement EPV targeting ketoprofen pollution. Here, we provide some recommendations for implementing the targeted EPV for ketoprofen, including: Closely monitoring ketoprofen in the natural environment; Reducing the residues of ketoprofen through source control; Encouraging urine source separation and treatment; Limiting the application of veterinary ketoprofen; Designing and constituting a framework system of targeted EPV. But some challenges, such as ambiguity in the accountability of the main bodies responsible for continued monitoring of ketoprofen residues, the lack of optimized urine source separation scenarios and procedure, the need for detailed design and application schemes of the framework system of targeted EPV, etc. should be addressed. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Adverse effects of non-steroidal anti-inflammatory drugs. A prevalence study in Austria].

PubMed

Kolarz, Gernot; Mayrhofer, Franz; Neumann, Kurt; Singer, Franz

2003-01-31

Gastrointestinal side effects are the limiting factor in the prescription of non-steroidal antirheumatic drugs (NSAID). However, there are no recent data from Austria. The aim of this prevalence study was therefore to assess the gastrointestinal risk from NSAID in Austria. A total of 1347 patients were observed in an outpatient setting between March 2000 and February 2001. Side effects from NSAID were documented by questionnaire at two time points with a mean interval of 31 days. Documented data were analysed descriptively using an explorative strategy. The prevalence of side effects was compared to data from literature. Side effects were reported by 18.1% of the patients, severe gastro-intestinal complications (ulcer, bleeding, perforation) were diagnosed in 0.7%. Prescription of effective GI-protection (proton pump inhibitors, misoprostole, famotidin in high dose) was seen in only one third of the patients at risk. The prevalence of severe gastrointestinal side effects by NSAIDs assessed in our study was clearly lower than the prevalence reported in the Anglo-American literature. This may be due to a different prescription behaviour: about 75% of the patients took Diclofenac, lbuprofen or Meloxicam, drugs which have a very low potential of gastrointestinal complications. However, more information for general practitioners is needed yet to sufficiently protect patients at gastrointestinal risk from NSAID.

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

PubMed Central

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

Novel enzyme formulations for improved pharmacokinetic properties and anti-inflammatory efficacies.

PubMed

Yang, Lan; Yan, Shenglei; Zhang, Yonghong; Hu, Xueyuan; Guo, Qi; Yuan, Yuming; Zhang, Jingqing

2018-02-15

Anti-inflammatory enzymes promote the dissolution and excretion of sticky phlegm, clean the wound surface and accelerate drug diffusion to the lesion. They play important roles in treating different types of inflammation and pain. Currently, various formulations of anti-inflammatory enzymes are successfully prepared to improve the enzymatic characteristics, pharmacokinetic properties and anti-inflammatory efficacies. The work was performed by systematically searching all available literature. An overall summary of current research about various anti-inflammatory enzymes and their novel formulations is presented. The original and improved enzymatic characteristics, pharmacokinetic properties, action mechanisms, clinical information, storage and shelf life, treatment efficacies of anti-inflammatory enzymes and their different formulations are summarized. The influencing factors such as enzyme type, source, excipient, pharmaceutical technique, administration route and dosage are analyzed. The combined application of enzymes and other drugs are included in this paper. Anti-inflammatory enzymes were widely applied in treating different types of inflammation and diseases with accompanying edema. Their novel formulations increased enzymatic stabilities, improved pharmacokinetic properties, provided different administration routes, and enhanced anti-inflammatory efficacies of anti-inflammatory enzymes but decreased side effects and toxicity. Novel enzyme formulations improve and expand the usage of anti-inflammatory enzymes. Copyright © 2017 Elsevier B.V. All rights reserved.

Intragastric acid control in non-steroidal anti-inflammatory drug users: comparison of esomeprazole, lansoprazole and pantoprazole.

PubMed

Goldstein, J L; Miner, P B; Schlesinger, P K; Liu, S; Silberg, D G

2006-04-15

Studies to date have not directly compared the pharmacodynamic efficacies of different proton pump inhibitors in controlling intragastric acidity in patients treated with non-steroidal anti-inflammatory drugs. To compare acid suppression with once-daily esomeprazole 40 mg, lansoprazole 30 mg and pantoprazole 40 mg in patients receiving non-selective or cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drug therapy. In this multicentre, open-label, comparative, three-way crossover study, adult patients (n = 90) receiving non-steroidal anti-inflammatory drugs were randomized to one of six treatment sequences. At the study site, patients were administered esomeprazole 40 mg, lansoprazole 30 mg and pantoprazole 40 mg for 5 days each, with a washout period of > or =10 days between each treatment. Twenty-four-hour pH testing was performed on day 5 of each dosing period. The mean percentage of time during the 24-h pH monitoring period that gastric pH was >4.0 was significantly greater with esomeprazole (74.2%) compared with lansoprazole (66.5%; P < 0.001) and pantoprazole (60.8%; P < 0.001), and significantly greater with esomeprazole (P < 0.05) than with the comparators regardless of whether using non-selective vs. cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drugs. At the doses studied, esomeprazole treatment provides significantly greater gastric acid suppression than lansoprazole or pantoprazole in patients receiving non-selective or cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drugs.

Peptic ulcer frequency differences related to h. Pylori or aines.

PubMed

Carli, Diego Michelon de; Pires, Rafael Cardoso; Rohde, Sofia Laura; Kavalco, Caroline Mayara; Fagundes, Renato Borges

2015-01-01

Peptic ulcer etiology has been changing because of H. pylori decline. To estimate peptic ulcer prevalence in 10 years-interval and compare the association with H. pylori and use of non-steroidal anti-inflammatory drugs. Methods Records assessment in two periods: A (1997-2000) and B (2007-2010), searching for peptic ulcer, H. pylori infection and non-steroidal anti-inflammatory drugs use. Peptic ulcer occurred in 30.35% in A and in 20.19% in B. H. pylori infection occurred in 73.3% cases in A and in 46.4% in B. Non-steroidal anti-inflammatory drugs use was 3.5% in A and 13.3% in B. Neither condition occurred in 10.4% and 20.5% in A and B respectively. Comparing both periods, we observed reduction of peptic ulcer associated to H. pylori (P=0.000), increase of peptic ulcer related to non-steroidal anti-inflammatory drugs (P=0.000) and idiopathic peptic ulcer (P=0.002). The concurrent association of H. pylori and non-steroidal anti-inflammatory drugs was also higher in B (P=0.002). Rates of gastric ulcer were higher and duodenal ulcer lower in the second period. After 10 years, the prevalence of peptic ulcer decreased, as well as ulcers related to H. pylori whereas ulcers associated to non-steroidal anti-inflammatory drugs increased. There was an inversion in the pattern of gastric and duodenal ulcer and a rise of idiopathic peptic ulcer.

Occurrence of pharmaceutical, recreational and psychotropic drug residues in surface water on the northern Antarctic Peninsula region.

PubMed

González-Alonso, Silvia; Merino, Luis Moreno; Esteban, Sara; López de Alda, Miren; Barceló, Damià; Durán, Juan José; López-Martínez, Jerónimo; Aceña, Jaume; Pérez, Sandra; Mastroianni, Nicola; Silva, Adrián; Catalá, Myriam; Valcárcel, Yolanda

2017-10-01

Human presence in the Antarctic is increasing due to research activities and the rise in tourism. These activities contribute a number of potentially hazardous substances. The aim of this study is to conduct the first characterisation of the pharmaceuticals and recreational drugs present in the northern Antarctic Peninsula region, and to assess the potential environmental risk they pose to the environment. The study consisted of a single sampling of ten water samples from different sources, including streams, ponds, glacier drains, and a wastewater discharge into the sea. Twenty-five selected pharmaceuticals and 21 recreational drugs were analysed. The highest concentrations were found for the analgesics acetaminophen (48.74 μg L -1 ), diclofenac (15.09 μg L -1 ) and ibuprofen (10.05 μg L -1 ), and for the stimulant caffeine (71.33 μg L -1 ). All these substances were detected in waters that were discharged directly into the ocean without any prior purification processes. The hazard quotient (HQ) values for ibuprofen, diclofenac and acetaminophen were far in excess of 10 at several sampling points. The concentrations of each substance measured and used as measured environmental concentration values for the HQ calculations are based on a one-time sampling. The Toxic Unit values indicate that analgesics and anti-inflammatories are the therapeutic group responsible for the highest toxic burden. This study is the first to analyse a wide range of substances and to determine the presence of pharmaceuticals and psychotropic drugs in the Antarctic Peninsula region. We believe it can serve as a starting point to focus attention on the need for continued environmental monitoring of these substances in the water cycle, especially in protected regions such as the Antarctic. This will determine whether pharmaceuticals and recreational drugs are hazardous to the environment and, if so, can be used as the basis for risk-assessment studies to prioritise the exposure to risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hydro-ethanolic leaf extract of Ziziphus abyssinica Hochst Ex A. Rich (Rhamnaceae) exhibits anti-nociceptive effects in murine models.

PubMed

Boakye-Gyasi, Eric; Henneh, Isaac Tabiri; Abotsi, Wonder Kofi Mensah; Ameyaw, Elvis Ofori; Woode, Eric

2017-04-26

Despite substantial advances in pain research and treatment, millions of people continue to suffer from pain and this has been attributed mainly to the unavailability of effective and safer analgesics. The use of plants as medicines is still widespread and plants constitute a large source of novel phytocompounds that might become leads for the discovery of newer, effective and safer alternatives. Various parts of Ziziphus abyssinica have been used in folk medicine in several African countries as painkillers. However, there is no report on the possible anti-nociceptive effects of this plant especially the leaves, hence the need for this current study. The possible anti-nociceptive activity of hydro-ethanolic leaf extract of Ziziphus abyssinica (EthE) was assessed in rodents using chemical (acetic acid, formalin and glutamate), thermal (tail-immersion test) and mechanical/inflammatory (carrageenan) models of nociception. EthE (30-300 mg/kg, p.o.) dose-dependently and significantly inhibited chemical-induced nociception with a maximum inhibition of 86.29 ± 2.27%, 76.34 ± 5.67%, 84.97 ± 5.35%, and 82.81 ± 5.97% respectively for acetic acid, formalin (phase 1), formalin (phase 2) and glutamate tests at its highest dose. EthE also dose-dependently and significantly increased reaction times in both tail-immersion and carrageenan-induced hypernociceptive tests. The activities of the extract in the various models were comparable with the effect of morphine hydrochloride and diclofenac sodium used as standard analgesic drugs. Oral administration of hydro-ethanolic leaf extract of Ziziphus abyssinica ameliorates nocifensive behaviours associated with chemical-, thermal- and mechanical/inflammatory - induced nociceptive pain.

Anti-inflammatory and anti-hyperlipidemic effect of Semecarpus anacardium in a high fat diet: STZ-induced type 2 diabetic rat model.

PubMed

Khan, Haseena Banu Hedayathullah; Vinayagam, Kaladevi Siddhi; Moorthy, Balaji T; Palanivelu, Shanthi; Panchanatham, Sachdanandam

2013-02-01

Semecarpus anacardium, known as marking nut, has been used in indigenous system of medicine against various ailments. To evaluate the antilipidemic and anti-inflammatory effect of S. anacardium Linn. nut milk extract (SA) in Type 2 diabetic rats. Diabetes was induced in rats by feeding them with a high fat diet followed by i.p. of 35 mg/kg body weight of streptozotocin. Diabetic rats were treated with the drugs, SA (200 mg/kg body weight) and metformin (500 mg/kg body weight) for 30 days. Antilipidemic effect of the drug was established by studying the lipoprotein alterations and also the alterations in the lipid profile and lipid metabolizing enzymes in the experimental group of rats. The effect of the drug on the expression of PPAR γ was also studied. To determine the anti-inflammatory effect of the drug, the levels of inflammatory cytokines, TNF-α and IL-6 and also C-reactive protein were determined. Semecarpus anacardium nut milk extract at a dosage of 200 mg/kg orally significantly (p < 0.05) reduced and normalized the alterations in the lipid metabolism in diabetic rats effectively than metformin. SA treatment significantly (p < 0.05) increased the mRNA expression of PPAR γ, thereby establishing the antilipidemic effect of the drug. The increase in the levels of inflammatory cytokines were significantly (p < 0.05) brought down to near normal levels on treatment with the drug SA. The present study thereby establishes the antilipidemic and anti-inflammatory effect of the drug. Thus, by decreasing the alterations in the lipid metabolism and inflammatory status, the drug can effectively improve the insulin sensitivity in rats and can serve as an excellent drug in the treatment of Type 2 diabetes mellitus.

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

PubMed

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.

Optimization and Pharmacological Validation of a Leukocyte Migration Assay in Zebrafish Larvae for the Rapid In Vivo Bioactivity Analysis of Anti-Inflammatory Secondary Metabolites

PubMed Central

Vicet-Muro, Liliana; Wilches-Arizábala, Isabel María; Esguerra, Camila V.; de Witte, Peter A. M.; Crawford, Alexander D.

2013-01-01

Over the past decade, zebrafish (Danio rerio) have emerged as an attractive model for in vivo drug discovery. In this study, we explore the suitability of zebrafish larvae to rapidly evaluate the anti-inflammatory activity of natural products (NPs) and medicinal plants used in traditional medicine for the treatment of inflammatory disorders. First, we optimized a zebrafish assay for leukocyte migration. Inflammation was induced in four days post-fertilization (dpf) zebrafish larvae by tail transection and co-incubation with bacterial lipopolysaccharides (LPS), resulting in a robust recruitment of leukocytes to the zone of injury. Migrating zebrafish leukocytes were detected in situ by myeloperoxidase (MPO) staining, and anti-inflammatory activity was semi-quantitatively scored using a standardized scale of relative leukocyte migration (RLM). Pharmacological validation of this optimized assay was performed with a panel of anti-inflammatory drugs, demonstrating a concentration-responsive inhibition of leukocyte migration for both steroidal and non-steroidal anti-inflammatory drugs (SAIDs and NSAIDs). Subsequently, we evaluated the bioactivity of structurally diverse NPs with well-documented anti-inflammatory properties. Finally, we further used this zebrafish-based assay to quantify the anti-inflammatory activity in the aqueous and methanolic extracts of several medicinal plants. Our results indicate the suitability of this LPS-enhanced leukocyte migration assay in zebrafish larvae as a front-line screening platform in NP discovery, including for the bioassay-guided isolation of anti-inflammatory secondary metabolites from complex NP extracts. PMID:24124487

Antioxidant, Anti-inflammatory, Analgesic Properties, and Phytochemical Characterization of Stem Bark Extract and Fractions of Anthocleista nobilis

PubMed Central

Ngwoke, Kenneth Gerald; Akwagbulam, Amaka Godsaveus; Erhirhie, Ernest Oghenesuvwe; Ajaghaku, Daniel Lotanna; Okoye, Festus Basden Chiedu; Esimone, Charles Okechukwu

2018-01-01

Background: Anthocleista nobilis (Loganiaceae) is used by Mbano people of Imo State, Nigeria, for the treatment of various ailments Objective: The aim of this study is to evaluate the antioxidant, anti-inflammatory, and analgesic properties of the methanol extract, fractions, and subfractions of A. nobilis. Materials and Methods: The powdered stem bark was extracted with methanol and sequentially fractionated into n-hexane, ethyl acetate, and butanol fractions. The constituents of the fractions were analyzed using high-pressure liquid chromatography (HPLC), and the components were identified by dereplication. Antioxidant potential of the extracts and fractions was investigated using 2,2-diphenyl-1-picrylhydrazyl free-radical scavenging method. Anti-inflammatory and analgesic activities of the extract and fractions were also investigated using xylene-induced inflammation and acetic acid-induced writhing models, respectively. Results: A total of five compounds isovitexin (Rt = 18.77 min), isovitexin-2''-O-xyl (Rt = 19.68 min), p-Hydroxybenzoic acid (Rt = 11.88 min), Sarasinoside L (Rt = 19.64 min), isovitexin (Rt = 18.77), and apigenin monoglycoside (Rt = 19.64 min) were identified by HPLC analysis and dereplication. The ethyl acetate fraction and subfraction elicited the best anti-inflammatory activity. The ethyl acetate subfraction also inhibited acetic acid-induced pain by 79% and 85.0% at the doses of 100 mg/kg and 200 mg/kg, respectively, which was better than 71.1% and 81.3% observed for diclofenac at similar doses. Conclusion: A. nobilis could be a potential source of anti-inflammatory and analgesic lead compounds. SUMMARY The extract, fractions and subfractions of Anthocleista nobilis were screened or antioxidant, anti-inflammatory and Analgesic properties in vitro and in mice models. Some of the components were identified by dereplication after HPLC analysis. The results demonstrated potent anti-inflammatory and analgesic property of the extracts and fractions. The dereplication analysis also identified vitexin and related compounds. Abbreviation used: HPLC: High performance Liquid Chromatography; VLC: Vacuum Liquid Chromatography; DPPH: 2,2-Diphenyl-1-pycrylhydrazine; SPSS: Statistical Package for the Social Sciences; ROS: Reactive Oxygen Species PMID:29568192

Antioxidant, Anti-inflammatory, Analgesic Properties, and Phytochemical Characterization of Stem Bark Extract and Fractions of Anthocleista nobilis.

PubMed

Ngwoke, Kenneth Gerald; Akwagbulam, Amaka Godsaveus; Erhirhie, Ernest Oghenesuvwe; Ajaghaku, Daniel Lotanna; Okoye, Festus Basden Chiedu; Esimone, Charles Okechukwu

2018-01-01

Anthocleista nobilis ( Loganiaceae ) is used by Mbano people of Imo State, Nigeria, for the treatment of various ailments. The aim of this study is to evaluate the antioxidant, anti-inflammatory, and analgesic properties of the methanol extract, fractions, and subfractions of A. nobilis . The powdered stem bark was extracted with methanol and sequentially fractionated into n-hexane, ethyl acetate, and butanol fractions. The constituents of the fractions were analyzed using high-pressure liquid chromatography (HPLC), and the components were identified by dereplication. Antioxidant potential of the extracts and fractions was investigated using 2,2-diphenyl-1-picrylhydrazyl free-radical scavenging method. Anti-inflammatory and analgesic activities of the extract and fractions were also investigated using xylene-induced inflammation and acetic acid-induced writhing models, respectively. A total of five compounds isovitexin ( R t = 18.77 min), isovitexin-2''-O-xyl ( R t = 19.68 min), p-Hydroxybenzoic acid ( R t = 11.88 min), Sarasinoside L ( R t = 19.64 min), isovitexin ( R t = 18.77), and apigenin monoglycoside ( R t = 19.64 min) were identified by HPLC analysis and dereplication. The ethyl acetate fraction and subfraction elicited the best anti-inflammatory activity. The ethyl acetate subfraction also inhibited acetic acid-induced pain by 79% and 85.0% at the doses of 100 mg/kg and 200 mg/kg, respectively, which was better than 71.1% and 81.3% observed for diclofenac at similar doses. A. nobilis could be a potential source of anti-inflammatory and analgesic lead compounds. The extract, fractions and subfractions of Anthocleista nobilis were screened or antioxidant, anti-inflammatory and Analgesic properties in vitro and in mice models. Some of the components were identified by dereplication after HPLC analysis. The results demonstrated potent anti-inflammatory and analgesic property of the extracts and fractions. The dereplication analysis also identified vitexin and related compounds. Abbreviation used: HPLC: High performance Liquid Chromatography; VLC: Vacuum Liquid Chromatography; DPPH: 2,2-Diphenyl-1-pycrylhydrazine; SPSS: Statistical Package for the Social Sciences; ROS: Reactive Oxygen Species.

Targeting the Hemoglobin Scavenger receptor CD163 in Macrophages Highly Increases the Anti-inflammatory Potency of Dexamethasone

PubMed Central

Graversen, Jonas H; Svendsen, Pia; Dagnæs-Hansen, Frederik; Dal, Jakob; Anton, Gabriele; Etzerodt, Anders; Petersen, Mikkel D; Christensen, Peter A; Møller, Holger J; Moestrup, Søren K

2012-01-01

Synthetic glucocorticoids are potent anti-inflammatory drugs but serious side effects such as bone mobilization, muscle mass loss, immunosuppression, and metabolic alterations make glucocorticoid therapy a difficult balance. The therapeutic anti-inflammatory effect of glucocorticoids relies largely on the suppressed release of tumor-necrosis factor-α and other cytokines by macrophages at the sites of inflammation. We have now developed a new biodegradable anti-CD163 antibody-drug conjugate that specifically targets the glucocorticoid, dexamethasone to the hemoglobin scavenger receptor CD163 in macrophages. The conjugate, that in average contains four dexamethasone molecules per antibody, exhibits retained high functional affinity for CD163. In vitro studies in rat macrophages and in vivo studies of Lewis rats showed a strong anti-inflammatory effect of the conjugate measured as reduced lipopolysaccharide-induced secretion of tumor-necrosis factor-α. The in vivo potency of conjugated dexamethasone was about 50-fold that of nonconjugated dexamethasone. In contrast to a strong systemic effect of nonconjugated dexamethasone, the equipotent dose of the conjugate had no such effect, measured as thymus lymphocytes apoptosis, body weight loss, and suppression of endogenous cortisol levels. In conclusion, the study shows antibody-drug conjugates as a future approach in anti-inflammatory macrophage-directed therapy. Furthermore, the data demonstrate CD163 as an excellent macrophage target for anti-inflammatory drug delivery. PMID:22643864

Home pharmacies in Serbia: an insight into self-medication practice.

PubMed

Kusturica, Milica Paut; Tomic, Zdenko; Bukumiric, Zoran; Ninkovic, Ljiljana; Tomas, Ana; Stilinovic, Nebojsa; Sabo, Ana

2015-04-01

Worldwide data indicate that self-medication is frequently used inappropriately. Although self-medication is encouraged in most of the countries by introducing over-the-counter drugs, it bears the risk of misuse of drugs issued on prescription due to low observance of legislation of medicines requiring prescription by some pharmacies. The objective of this study was to explore the self-medication practice, with an emphasis on self-medication with prescription-only medications. Households in Novi Sad city, Serbia. The study was conducted over 8 month period (December 2011-July 2012) and involved a random sample of households. The questionnaire-based study and personal insight into household drug supplies was performed by a trained interviewer. Main outcome measure Number of drugs obtained without prescription or without consulting a physician in surveyed households. The total number of drug items present in the 383 households was 4,384 with a median of 11 drugs per household. More than a half of drugs in households were prescription-only medication (58.5 %). Approximately one third of prescription-only medications were obtained without prescription. The most common drugs obtained without prescription were anti-inflammatory and antirheumatic products and antibacterials for systemic use. Ibuprofen and diclofenac were the most common self-medicated drugs. Number of prescription-only medications bought with ought prescription was significantly higher in households with children under 12 years of age compared to other types of households. Our survey indicated that self-medication with prescription drugs appeared to be a rather common practice, which is far away from the concept of "responsible self-medication", especially regarding antibiotics.

Reversible ovulatory failure associated with the development of luteinized unruptured follicles in women with inflammatory arthritis taking non-steroidal anti-inflammatory drugs.

PubMed

Smith, G; Roberts, R; Hall, C; Nuki, G

1996-05-01

The case histories of three young women with ankylosing spondylitis, rheumatoid arthritis and a seronegative inflammatory polyarthritis undergoing investigations for infertility are presented. In each, non-steroidal anti-inflammatory drug (NSAID) therapy was associated with the recurrent development of luteinized unruptured ovarian follicles and normal ovulation following drug withdrawal. It is suggested that NSAID therapy may be an important and frequently overlooked cause of anovulation and infertility.

Diclofenac degradation by heterogeneous photocatalysis with Fe3O4/Ti x O y /activated carbon fiber composite synthesized by ultrasound irradiation

NASA Astrophysics Data System (ADS)

Moreno-Valencia, E. I.; Paredes-Carrera, S. P.; Sánchez-Ochoa, J. C.; Flores-Valle, S. O.; Avendaño-Gómez, J. R.

2017-11-01

In this work, a photocatalytic system to degrade diclofenac was developed using a composite Fe3O4/Ti x O y on an activated carbon fiber. Diclofenac is widely used as an anti-inflammatory compound worldwide and it is constantly being added as waste in the environment (Heberer 2002 J. Hydrol. 266 175-89), exceeding the permissible maximum concentration in the wastewater (GEO-3 2002 Programa de las Naciones Unidas para el Medio Ambiente; Golet et al 2003 Environ. Sci. Technol. 37 3243-9 Oviedo et al 2010 Environ. Toxicol. Pharmacol. 29 9-43 Le-Minh et al 2010 Water Res. 44 4295-323 Legrini et al 1993 Chem. Rev. 1093 671-98). The composite was synthesized by sol-gel technique with and without ultrasound irradiation (Singh and Nakate 2014 J. Nanopart. 2014 326747). The solids were deposited by ultrasound irradiation on active carbon fiber in order to optimize the diclofenac degradation. The solids were characterized by x-ray diffraction (XRD), nitrogen physisorption (BET), and scanning electron microscopy with EDS microanalysis (SEM-EDS). The crystal size was calculated with the Debye-Scherrer equation, and the band gap values by the diffuse reflectance method. The evaluation process was studied by UV-vis spectroscopy (Rizzoa et al 2009 Water Res. 43 979-88). It was found that in this synthesis method (ultrasound), textural properties such as porosity, specific surface area and morphology depend on the ultrasound irradiation. The proposed system, Fe3O4/titanium oxide hydrate showed better degradation profile than TiO2 anatase phase; the increase of diclofenac degradation was attributed to the textural properties of the composite, it avoids the filtering process since the separation can be achieved by magnetizing and/or decantation.

[Allergic and non-allergic hypersensitivity to non-opioid analgesics, antipyretics and nonsteroidal anti-inflammatory drugs in children: epidemiology, clinical aspects, pathophysiology, diagnosis and prevention].

PubMed

Ponvert, C

2012-05-01

Non-opioid analgesics, antipyretics and nonsteroidal anti-inflammatory drugs are widely used, but suspected allergic reactions to these drugs are rare, especially in children. Most frequent reactions are cutaneous (urticaria, angioedema) and respiratory (rhinitis, asthma). Other reactions (anaphylaxis, potentially harmful toxidermias) are rare. In a few patients, reactions may result from a specific (allergic) hypersensitivity, with positive responses in prick and intradermal tests (anaphylaxis, immediate urticaria and/or angioedema) and in intradermal and patch tests (non-immediate reactions). However, most reactions result from a non-specific (non-allergic) hypersensitivity (intolerance), with a frequent cross-reactivity between the various families of analgesics, antipyretics and nonsteroidal anti-inflammatory drugs, including paracetamol. Based on a convincing clinical history and/or positive responses in challenge tests, intolerance to non-opioid analgesics, antipyretics and nonsteroidal anti-inflammatory drugs has been diagnosed in 13 to 50% of the patients with allergic-like reactions to these drugs. Risk factors are a personal atopy and age. Prevention is based on administration of other (families of) analgesics, antipyretics and nonsteroidal anti-inflammatory drugs in patients with allergic hypersensitivity to these drugs. In patients with non-allergic hypersensitivity, prevention is based on administration of drugs with a low cyclo-oxygenase-1 inhibitory activity (if tolerated). Desensitization is efficient in patients with respiratory reactions, but does not work in patients with mucocutaneous reactions and anaphylaxis. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Interventions for postoperative pain in children: An overview of systematic reviews.

PubMed

Boric, Krste; Dosenovic, Svjetlana; Jelicic Kadic, Antonia; Batinic, Marijan; Cavar, Marija; Urlic, Marjan; Markovina, Nikolina; Puljak, Livia

2017-09-01

The aim of this study was to conduct an overview of systematic reviews that summarizes the results about efficacy and safety from randomized controlled trials involving the various strategies used for postoperative pain management in children. We searched the Cochrane Database of Systematic Reviews, CINAHL, Database of Reviews of Effect, Embase, MEDLINE, and PsycINFO from the earliest date to January 24, 2016. This overview included 45 systematic reviews that evaluated interventions for postoperative pain in children. Out of 45 systematic reviews that investigated various interventions for postoperative pain in children, 19 systematic reviews (42%) presented conclusive evidence of efficacy. Positive conclusive evidence was reported in 18 systematic reviews (40%) for the efficacy of diclofenac, ketamine, caudal analgesia, dexmedetomidine, music therapy, corticosteroid, epidural analgesia, paracetamol, and/or nonsteroidal anti-inflammatory drugs and transversus abdominis plane block. Only one systematic review reported conclusive evidence of equal efficacy that involved a comparison of dexmedetomidine vs morphine and fentanyl. Safety of interventions was reported as conclusive in 14 systematic reviews (31%), with positive conclusive evidence for dexmedetomidine, corticosteroid, epidural analgesia, transversus abdominis plane block, and clonidine. Seven systematic reviews reported equal conclusive safety for epidural infusion, diclofenac intravenous vs ketamine added to opioid analgesia, bupivacaine, ketamine, paracetamol, and dexmedetomidine vs intravenous infusions of various opioid analgesics, oral suspension and suppository of diclofenac, only opioid, normal saline, no treatment, placebo, and midazolam. Negative conclusive statement for safety was reported in one systematic review for caudal analgesia vs noncaudal regional analgesia. More than half of systematic reviews included in this overview were rated as having medium methodological quality. Of 45 included systematic reviews, 10 were Cochrane reviews and they had higher methodological quality than non-Cochrane reviews. As evidence concerning efficacy and safety is inconclusive for most of the analyzed interventions, our review points out the need for more rigorous trials concerning pain management in children. © 2017 John Wiley & Sons Ltd.

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

PubMed

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.

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

PubMed Central

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. PMID:27621596

Virgin coconut oil supplementation ameliorates cyclophosphamide-induced systemic toxicity in mice.

PubMed

Nair, S S; Manalil, J J; Ramavarma, S K; Suseela, I M; Thekkepatt, A; Raghavamenon, A C

2016-02-01

Virgin coconut oil (VCO) is an unrefined kernal oil, prepared from Cocos nucifera L., having substantial nutritional and medicinal value. Experimental studies have suggested its antioxidant, anti-inflammatory, immunostimulatory and hypolipidemic effects. The present study assesses its effect on formalin-induced chronic inflammation and cyclophosphamide (CTX)-induced systemic toxicity in murine models. Oral administration of VCO effectively reduced formalin-induced paw oedema in mice with more or less similar efficacy as that of diclofenac. The CTX-induced hike in blood urea, creatinine, thiobarbituric acid reactive substances (TBARS) and liver marker enzymes in mice was marginally decreased by VCO (8 g/kg body weight) ingestion orally. The liver and kidney catalase, superoxide dismutase and glutathione peroxidase activities, together with cellular glutathione and TBARS levels, were found to be improved in these animals. Overall the study reveals the protective efficacy of VCO against secondary toxicity induced by CTX possibly through its antioxidant and anti-inflammatory properties. © The Author(s) 2015.

Therapeutic effects of lornoxicam-loaded nanomicellar formula in experimental models of rheumatoid arthritis.

PubMed

Helmy, Hebatullah Samy; El-Sahar, Ayman E; Sayed, Rabab H; Shamma, Rehab Nabil; Salama, Alaa Hamed; Elbaz, Eman Maher

2017-01-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease treated by nonsteroidal anti-inflammatory drugs (NSAIDs) including lornoxicam (LX). Nanocarriers have been used to increase the efficacy and reduce the side effects of various drugs. The objective of the present study was to compare the therapeutic efficacy of systemic administration of lornoxicam-loaded nanomicellar formula (LX-NM) with that of free LX. The LX-loaded mixed polymeric nanomicellar formula was prepared by direct equilibrium technique. Two rat models were used in the study: carrageenan-induced acute edema and Freund's complete adjuvant (FCA)-induced chronic arthritis. The inhibitory effect of LX-NM on carrageenan-induced edema was higher than free LX for the same dose (1.3 mg/kg, i.p.). LX-NM (0.325 mg/kg, i.p.) produced effects comparable to that of diclofenac, which served as a standard. In the FCA model, daily treatment with LX-NM (0.325 mg/kg, i.p.) starting on day 14 significantly reduced the percentage of edema and increased weight growth. However, the same dose of LX failed to confer any significant change. Additionally, LX-NM significantly attenuated the rise of tumor necrosis factor-α (TNF-α), interleukin-1β, prostaglandin E2, nuclear factor-κβ, malondialdehyde and nitric oxide serum levels. In contrast, LX failed to show any significant reduction in elevated serum biomarkers except for TNF-α. LX-NM is an alternative delivery system that is simply prepared at low costs. It showed a superior therapeutic efficacy against RA compared to free LX. Thus, LX-NM can be considered as a promising candidate for treatment of RA and similar inflammatory disorders.

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

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-2-0153 TITLE: Decreasing Skin Graft Contraction through Topical Wound Bed Preparation with Anti - Inflammatory Agents...Sep 2015 4. TITLE AND SUBTITLE Decreasing Skin Graft Contraction Through Topical Wound Bed Preparation with Anti - Inflammatory Agents 5a. CONTRACT...applied anti - inflammatory drugs that will reduce recipient site inflammation and skin graft contraction. 15. SUBJECT TERMS Graft contraction, anti

Variable Effects of Non-steroidal Anti-inflammatory Drugs (NSAIDs) on Selected Biochemical Processes Mediated by Soil Microorganisms

PubMed Central

Cycoń, Mariusz; Borymski, Sławomir; Żołnierczyk, Bartłomiej; Piotrowska-Seget, Zofia

2016-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently used group of pharmaceuticals. The high consumption and the uncontrolled disposal of unused drugs into municipal waste or their deposit in landfills can result in an increased concentration of these compounds in soils. Moreover, these drugs can affect the microbial activity. However, there is a lack of knowledge about these effects or it is very limited. Therefore, the objective of this study was to compare the impact of selected commercially available NSAIDs, i.e., diclofenac (DCF), naproxen (NPX), ibuprofen (IBF) and ketoprofen (KTP), applied at concentrations of 1 and 10 mg/kg soil, on the activity of soil microorganisms during the 90-day experiment. To ascertain this impact, substrate-induced respiration (SIR), soil enzyme activities, i.e., dehydrogenase (DHA), acid and alkaline phosphatases (PHOS-H and PHOS-OH) and urease (URE) as well as changes in the rates of nitrification and ammonification processes were determined. In addition, the number of culturable bacteria and fungi were enumerated. In general, the obtained data showed a significant stimulatory effect of NSAIDs on the microbial activity. Higher concentrations of NSAIDs caused a greater effect, which was observed for SIR, PHOS-H, PHOS-OH, URE, N-NO3- and N-NH4+, even during the whole incubation period. Moreover, the number of heterotrophic bacteria and fungi increased significantly during the experiment, which was probably a consequence of the evolution of specific microorganisms that were capable of degrading NSAIDs and used them as an additional source of carbon and energy. However, an inhibitory effect of NPX, IBF or KTP for SIR, DHA, on both phosphatases and culturable bacteria and fungi was observed at the beginning of the experiment. At lower concentrations of NSAIDs, in turn, the effects were negligible or transient. In conclusion, the application of NSAIDs altered the biochemical and microbial activity of soil what may cause the disturbance in soil functioning. It is reasonable to assume that some components of the NSAID formulations could stimulate soil microorganisms, thus resulting in an increase in biochemical activities of the soil. PMID:28018307

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

PubMed

Klein, Mads

2012-03-01

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 to achieve this, the following studies were performed. Study I was a retrospective, case-control study in 75 patients undergoing laparoscopic colorectal resection for colorectal cancer. 33 of these patients received the NSAID diclofenac in the postoperative period; the remaining 42 did not receive any NSAID. There were significantly more ALs among the patients receiving diclofenac (7/33 vs. 1/42, p=0.018). In uni- and multivariate logistic regression analyses, diclofenac was the only factor associated with increased AL rate. This study functioned as a hypothesis generating study and laid the ground for the subsequent studies. Study II was an experimental, randomized, case-control study in 32 Wistar rats. The rats had a colonic anastomosis performed and were randomized to diclofenac or placebo treatment. After three days, the rats were sacrificed and the anastomoses were harvested. First, the anastomotic strengths were tested by longitudinal; subsequently, the levels of the enzyme cyclooxygenase-2 (COX-2) in the anastomotic tissues were measured. There was no difference among the groups with regard to anastomotic strength, but the animals treated with diclofenac had significantly lower COX-2 levels (median (range) 1.30 (0.42-3.31) ng/mg vs. 2.44 (0.88 - 18.94) ng/mg, p<0.001). This study showed that the used dose of diclofenac was sufficient and relevant, but did not show a direct damaging effect on the anastomoses due to NSAID treatment. Study III was also an experimental, randomized, case-control study. This time round, 60 Wistar rats were included. Again, colonic anastomoses were performed and the rats were randomized to diclofenac or placebo. Also, expanded polytetrafluoruethylene (ePTFE) tubes were placed under the skin of the rats. In this material, substituents of connective tissue accumulate and the amount of accumulation can be measured. After 7 days, the rats were sacrificed and, again, anastomotic strengths were measured along with collagen content in the ePTFE tubes. Anastomotic strength was similar in the two groups while collagen accumulation was significantly decreased among the rats treated with diclofenac (median (i.q.r.) 0.29 (0.13-0.47) vs. 0.47 (0.28-0.62) mcg/mg, p = 0.03). This study for the first time showed that NSAID inhibit subcutaneous collagen formation and that this formation is reversely correlated to anastomotic strength. This information can be used in further studies in this subject. Study IV was the final experimental case-control study in 40 Wistar rats. This time, in order to more easily extrapolate experimental results to daily clinical life, the colonic anastomoses were sutured with the same type of suture material as used in the clinical setting. Thus, half the anastomoses was performed with resorbable suture; the other half with non-resorbable suture. None of the rats received NSAID. The breaking strength was compared and found similar in the two groups. This study showed that experimental studies can be optimized in order to make comparisons and extrapolations to the clinical setting easier. Study V was a database study based on data from the Danish Colorectal Cancer Group's (DCCG) prospective database and electronically registered medical records. From the database information on demographic, surgical and postoperative variables (including AL) were provided. Information on NSAID consumption was retrieved by individual searches in the patients' medical records. Based on these data, uni- and multivariate logistic regression analyses were performed. These analyses identified NSAID treatment in the postoperative period as an individual risk factor for AL. Other risk factors identified were consistent with the available literature. The detrimental effect of the NSAIDs are possibly due to an effect on collagen metabolism leading to weakened tissue around the anastomosis and/or on the risk of thrombosis formation leading to more thromboses in the vessels supplying the anastomosis, thereby limiting anastomotic blood flow. In conclusion, the studies included in this thesis have elucidated some of the physiological and pathophysiological mechanisms involved in anastomotic healing and leakage, and furthermore have shown that the use of NSAIDs in the postoperative period increase the risk of AL in patients undergoing colorectal surgery with primary anastomosis. Based on the findings in these studies, and based on existing knowledge, it is recommended that NSAIDs be abandoned after colorectal resection with primary anastomosis. It should be investigated whether the NSAIDs are also harmful to other types of anastomoses and after other surgical procedures where early tissue healing is crucial.

The Effect of COX-2 Inhibitors on the Aromatase Gene (CYP19) Expression in Human Breast Cancer

DTIC Science & Technology

2006-12-01

drug is it is associated with less side effects than non - steroidal inflammatory drugs ( NSAIDs ), particularly gastroduodenal ulcers. Randomized...Nested case-control study of effects of non - steroidal anti - inflammatory drugs on breast cancer risk and stage. B J Cancer 2000;83:112-120. 18...another non - steroidal anti - inflammatory ; 1 was determined to need neoadjuvant chemotherapy; 1 had a benign core biopsy, and 2

Drugs for Autoimmune Inflammatory Diseases: From Small Molecule Compounds to Anti-TNF Biologics

PubMed Central

Li, Ping; Zheng, Ying; Chen, Xin

2017-01-01

Although initially described as an anti-tumor mediator, tumor necrosis factor-alpha (TNF) is generally considered as the master pro-inflammatory cytokine. It plays a crucial role in the pathogenesis of inflammatory diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease, ankylosing spondylitis (AS), and psoriasis. Consequently, anti-TNF therapy has become mainstay treatment for autoimmune diseases. Historically, anti-inflammatory agents were developed before the identification of TNF. Salicylates, the active components of Willow spp., were identified in the mid-19th century for the alleviation of pain, fever, and inflammatory responses. Study of this naturally occurring compound led to the discovery of aspirin, which was followed by the development of non-steroidal anti-inflammatory drugs (NSAIDs) due to the chemical advances in the 19th–20th centuries. Initially, the most of NSAIDs were organic acid, but the non-acidic compounds were also identified as NSAIDs. Although effective in the treatment of inflammatory diseases, NSAIDs have some undesirable and adverse effect, such as ulcers, kidney injury, and bleeding in the gastrointestinal tract. In the past two decades, anti-TNF biologics were developed. Drugs belong to this class include soluble TNF receptor 2 fusion protein and anti-TNF antibodies. The introduction of anti-TNF therapeutics has revolutionized the management of autoimmune diseases, such as RA, psoriatic arthritis (PsA), plaque psoriasis (PP), AS, CD and ulcerative colitis (UC). Nevertheless, up to 40% of patients have no response to anti-TNF treatment. Furthermore, this treatment is associated with some adverse effects such as increased risk of infection, and even triggered the de novo development of autoimmune diseases. Such harmful effect of anti-TNF treatment is likely caused by the global inhibition of TNF biological functions. Therefore, specific inhibition of TNF receptor (TNFR1 or TNFR2) may represent a safer and more effective treatment, as proposed by some recent studies. In this review article, the historical development of anti-inflammatory drugs after World War II as briefly described above will be reviewed and analyzed. The future trend in the development of novel TNF receptor-targeting therapeutics will be discussed in the context of latest progress in the research of TNF biology. PMID:28785220

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.

PubMed

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-aspirin antiplatelet agents. H. pylori-positive patients on combined antiplatelet therapy carry the highest risk for peptic ulcer bleeding. © 2018 John Wiley & Sons Ltd.

Nonsteroidal anti-inflammatory drug activated gene-1 (NAG-1) modulators from natural products as anti-cancer agents

USDA-ARS?s Scientific Manuscript database

Natural products are rich source of gene modulators for prevention and treatment of cancer. In recent days, nonsteroidal anti-inflammatory drug (NSAID) activated gene-1 (NAG-1) has been focused as a new target of diverse cancers like colorectal, pancreatic, prostate, and breast. A variety of natural...

The hepatic safety and tolerability of the cyclooxygenase-2 selective NSAID celecoxib: pooled analysis of 41 randomized controlled trials.

PubMed

Soni, Paresh; Shell, Briton; Cawkwell, Gail; Li, Chunming; Ma, Hong

2009-08-01

To assess the hepatic safety and tolerability of celecoxib versus placebo and three commonly prescribed nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). This was a retrospective, pooled analysis of a 41-study dataset involving patients with osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, chronic low back pain, and Alzheimer's disease. Criteria for selection of studies were: (1) Randomized, parallel-group design and planned treatment duration of > or =2 weeks (2) > or =1 placebo or NSAID comparator (3) > or =1 arm with celecoxib at total daily dose of > or =200 mg (4) Data available as of October 31, 2004 Data were pooled by treatment and subject from the safety analysis population of included studies. Treatment-emergent hepatobiliary adverse events (AEs) were compared for celecoxib <200 mg/day (943 patients), 200 mg/day (12 008 patients), 400 mg/day (7380 patients), and 800 mg/day (4602 patients); placebo (4057 patients); diclofenac 100-150 mg/day (7639 patients); naproxen 1000 mg/day (2953 patients); and ibuprofen 2400 mg/day (2484 patients). Hepatobiliary laboratory abnormalities were also analyzed. There were no cases of liver failure, treatment-related liver transplant, or treatment-related hepatobiliary death. Incidence of serious hepatic AEs was low, with 13 (0.05%) serious hepatic AEs among 24 933 celecoxib-treated patients, and 16 (0.21%) among 7639 diclofenac-treated patients. No patients receiving celecoxib or any nonselective NSAID met criteria for Hy's rule (alanine aminotransferase [ALT] > or =3 x upper limit of normal [ULN] with bilirubin > or =2 x ULN). The incidence of notable (> or =5 x ULN) and severe (> or =10 x ULN) ALT elevations was similar for all treatment groups except diclofenac. Significantly fewer hepatobiliary AEs were reported for celecoxib (any dose; 1.11%) than for diclofenac (vs. 4.24%, p < 0.0001); for ibuprofen (vs. 1.53%, p = 0.06) and placebo (vs. 0.89%, p = 0.21) the incidence of AEs was comparable to celecoxib. A number of limitations should be considered when evaluating the results: findings were limited by the quality and reporting of the studies selected; difficulty in estimating the incidence of AEs due to the low frequency of events; acetaminophen not included as an active comparator. In this pooled analysis, the incidence of hepatic AEs in patients treated with celecoxib was similar to that for both placebo-treated patients and patients treated with ibuprofen or naproxen, but lower than for diclofenac.

Progress with anti-tumor necrosis factor therapeutics for the treatment of inflammatory bowel disease.

PubMed

Fernandes, Carlos; Allocca, Mariangela; Danese, Silvio; Fiorino, Gionata

2015-01-01

Anti-tumor necrosis factor (TNF) therapy is a valid, effective and increasingly used option in inflammatory bowel disease management. Nevertheless, further knowledge and therapeutic indications regarding these drugs are still evolving. Anti-TNF therapy may be essential to achieve recently proposed end points, namely mucosal healing, prevention of bowel damage and prevention of patient's disability. Anti-TNF drugs are also suggested to be more effective in early disease, particularly in early Crohn's disease. Moreover, its efficacy for prevention of postoperative recurrence in Crohn's disease is still debated. Costs and adverse effects, the relevance of drug monitoring and the possibility of anti-TNF therapy withdrawal in selected patients are still debated issues. This review aimed to describe and discuss the most relevant data about the progress with anti-TNF therapy for the management of inflammatory bowel disease.

Effectiveness and tolerance of anti-inflammatory drugs' add-on therapy in major mental disorders: a systematic qualitative review.

PubMed

Fond, G; Hamdani, N; Kapczinski, F; Boukouaci, W; Drancourt, N; Dargel, A; Oliveira, J; Le Guen, E; Marlinge, E; Tamouza, R; Leboyer, M

2014-03-01

To provide a systematic review of the literature regarding the efficacy of anti-inflammatory drugs in three major mental disorders [major depressive disorder (MDD), schizophrenia and bipolar disorders]. Four databases were explored, without any year or language restrictions. The baseline search paradigm was limited to open-labelled clinical and randomized controlled trials (RCTs). Four major classes of anti-inflammatory drugs were identified, namely polyunsaturated fatty acids (PUFAs), cyclooxygenase (COX) inhibitors, anti-TNFalpha and minocycline. Effectiveness and benefit/risk ratio of each class in MDD, bipolar disorders and schizophrenia was detailed when data were available. Several meta-analyses indicated effectiveness of PUFAs in MDD with a good tolerance profile. One meta-analysis indicated that COX-2 specific inhibitors showed effectiveness in schizophrenia. Anti-TNFalpha showed important effectiveness in resistant MDD with blood inflammatory abnormalities. Minocycline showed effectiveness in schizophrenia. Polyunsaturated fatty acids seem to have the best benefit/risk ratio profile but proved their effectiveness only in MDD. A number of anti-inflammatory drugs are available as adjunct treatment for treatment-resistant patients with MDD, schizophrenia and bipolar disorder. If used with caution regarding their possible side-effects, they may be reasonable therapeutic alternatives for resistant symptomatology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Stability Indicating HPLC Method for Simultaneous Determination of Mephenesin and Diclofenac Diethylamine

PubMed Central

Mulgund, S. V.; Phoujdar, M. S.; Londhe, S. V.; Mallade, P. S.; Kulkarni, T. S.; Deshpande, A. S.; Jain, K. S.

2009-01-01

A simple, specific, accurate and stability-indicating reversed phase high performance liquid chromatographic method was developed for the simultaneous determination of mephenesin and diclofenac diethylamine, using a Spheri-5-RP-18 column and a mobile phase composed of methanol: water (70:30, v/v), pH 3.0 adjusted with o-phosphoric acid. The retention times of mephenesin and diclofenac diethylamine were found to be 3.9 min and 14.5 min, respectively. Linearity was established for mephenesin and diclofenac diethylamine in the range of 50-300 μg/ml and 10-60 μg/ml, respectively. The percentage recoveries of mephenesin and diclofenac diethylamine were found to be in the range of 99.06-100.60% and 98.95-99.98%, respectively. Both the drugs were subjected to acid, alkali and neutral hydrolysis, oxidation, dry heat, photolytic and UV degradation. The degradation studies indicated, mephenesin to be susceptible to neutral hydrolysis, while diclofenac diethylamine showed degradation in acid, H2O2, photolytic and in presence of UV radiation. The degradation products of diclofenac diethylamine in acidic and photolytic conditions were well resolved from the pure drug with significant differences in their retention time values. This method can be successfully employed for simultaneous quantitative analysis of mephenesin and diclofenac diethylamine in bulk drugs and formulations. PMID:20177453

Stability indicating HPLC method for simultaneous determination of mephenesin and diclofenac diethylamine.

PubMed

Mulgund, S V; Phoujdar, M S; Londhe, S V; Mallade, P S; Kulkarni, T S; Deshpande, A S; Jain, K S

2009-01-01

A simple, specific, accurate and stability-indicating reversed phase high performance liquid chromatographic method was developed for the simultaneous determination of mephenesin and diclofenac diethylamine, using a Spheri-5-RP-18 column and a mobile phase composed of methanol: water (70:30, v/v), pH 3.0 adjusted with o-phosphoric acid. The retention times of mephenesin and diclofenac diethylamine were found to be 3.9 min and 14.5 min, respectively. Linearity was established for mephenesin and diclofenac diethylamine in the range of 50-300 mug/ml and 10-60 mug/ml, respectively. The percentage recoveries of mephenesin and diclofenac diethylamine were found to be in the range of 99.06-100.60% and 98.95-99.98%, respectively. Both the drugs were subjected to acid, alkali and neutral hydrolysis, oxidation, dry heat, photolytic and UV degradation. The degradation studies indicated, mephenesin to be susceptible to neutral hydrolysis, while diclofenac diethylamine showed degradation in acid, H(2)O(2), photolytic and in presence of UV radiation. The degradation products of diclofenac diethylamine in acidic and photolytic conditions were well resolved from the pure drug with significant differences in their retention time values. This method can be successfully employed for simultaneous quantitative analysis of mephenesin and diclofenac diethylamine in bulk drugs and formulations.

In-line carbon nanofiber reinforced hollow fiber-mediated liquid phase microextraction using a 3D printed extraction platform as a front end to liquid chromatography for automatic sample preparation and analysis: A proof of concept study.

PubMed

Worawit, Chanatda; Cocovi-Solberg, David J; Varanusupakul, Pakorn; Miró, Manuel

2018-08-01

A novel concept for automation of nanostructured hollow-fiber supported microextraction, combining the principles of liquid-phase microextraction (LPME) and sorbent microextraction synergically, using mesofluidic platforms is proposed herein for the first time, and demonstrated with the determination of acidic drugs (namely, ketoprofen, ibuprofen, diclofenac and naproxen) in urine as a proof-of-concept applicability. Dispersed carbon nanofibers (CNF) are immobilized in the pores of a single-stranded polypropylene hollow fiber (CNF@HF) membrane, which is thereafter accommodated in a stereolithographic 3D-printed extraction chamber without glued components for ease of assembly. The analytical method involves continuous-flow extraction of the acidic drugs from a flowing stream donor (pH 1.7) into an alkaline stagnant acceptor (20 mmol L -1 NaOH) containing 10% MeOH (v/v) across a dihexyl ether impregnated CNF@HF membrane. The flow setup features entire automation of the microextraction process including regeneration of the organic film and on-line injection of the analyte-laden acceptor phase after downstream neutralization into a liquid chromatograph (LC) for reversed-phase core-shell column-based separation. Using a 12-cm long CNF@HF and a sample volume of 6.4 mL, linear dynamic ranges of ketoprofen, naproxen, diclofenac and ibuprofen, taken as models of non-steroidal anti-inflammatory drugs, spanned from ca. 5-15 µg L -1 to 500 µg L -1 with enhancement factors of 43-97 (against a direct injection of 10 µL standards into LC), and limits of detection from 1.6 to 4.3 µg L -1 . Relative recoveries in real urine samples ranged from 97% to 105%, thus demonstrating the reliability of the automatic CNF@HF-LPME method for in-line matrix clean-up and determination of drugs in urine at therapeutically relevant concentrations. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of the effect of physical variables on in vitro release of diclofenac pellets using Box-Behnken design

PubMed Central

Enayatifard, Reza; Mahjoob, Aiding; Ebrahimi, Pouneh; Ebrahimnejad, Pedram

2015-01-01

Objective(s): A Box-Behnken design was used for evaluation of Eudragit coated diclofenac pellets. The purpose of this work was to optimize diclofenac pellets to improve the physicochemical properties using experimental design. Materials and Methods: Diclofenac was loaded onto the non-pareil beads using conventional coating pan. Film coating of pellets was done at the same pan. The effect of plasticizer level, curing temperature and curing time was determined on the release of diclofenac from pellets coated with polymethacrylates. Results: Increasing the plasticizer in the coating formula led to decrease in drug release and increasing the curing temperature and time resulted in higher drug release. The optimization process generated an optimum of 35% drug release at 3 hr. The level of plasticizer concentration, curing temperature and time were 20% w/w, 55 °C and 24 hr, respectively. Conclusion: This study showed that by controllinig the physical variables optimum drug release were obtained. PMID:26351563

The Use of Nonsteroidal Anti-Inflammatory Drugs in Sports.

ERIC Educational Resources Information Center

Calabrese, Leonard H.; Rooney, Theodore W.

1986-01-01

Recent advances in the understanding of the mechanism of action and clinical pharmacology of the new nonsteroidal anti-inflammatory drugs (NSAIDs) can help practitioners decide which to use and how to administer them. Indications for and effects of NSAIDs are described. (MT)

Non-Steroid Anti-Infflamatory Drugs in Municipal Wastewater and Surface Waters/ Niesteroidowe Leki Przeciwzaplane W Ściekach Mieskich I Wodach Powierzchniowych

NASA Astrophysics Data System (ADS)

Płuciennik-Koropczuk, Ewelina

2014-09-01

Increased production and consumption of drugs influences the pollution pharmaceuticals. Recent years have seen a significant increase in the consumption of non-prescription medicines, among which, are a large group of non-steroidal anti-inflammatory drugs (NSAIDs). Research conducted in Poland and abroad showed the presence of NSAIDs, both in treated wastewater in surface waters and drinking waters. One of the most frequently detected drugs in the environment is diclofenac, belongs to NSAID. Its concentration in surface waters range from 9 to 3363 ng/L. Traditional wastewater treatment plants are not specialized enough in removing the pharmaceuticals and their metabolites, and with purified wastewater are introduced into surface waters. Diclofenac concentrations in treated wastewater range from 0.29 to 2.5 μg/L, the average removal efficiency is about 40%. Wzrost produkcji i spożycia leków wpływa na zanieczyszczenie środowiska farmaceutykami. W ostatnich latach zaobserwowano zdecydowany wzrost spożycia leków dostępnych bez recepty, wśród których znaczną grupę stanowią niesteroidowe leki przeciwzapalne (NLPZ). Badania prowadzone na świecie i w Polsce wykazały obecność niesteroidowych leków przeciwzapalnych zarówno w ściekach oczyszczonych, w wodach powierzchniowych oraz w wodach pitnych. Jednym z najczęściej wykrywanych leków w środowisku jest diklofenak należący NLPZ. Jego stężenia w wodach powierzchniowych wynoszą od 9 do 3633 ng/dm3. Tradycyjne układy technologiczne oczyszczania nie eliminują zupełnie farmaceutyków i ich metabolitów i wraz ze ściekami oczyszczonymi są one wprowadzane do wód powierzchniowych. Stężenia diklofenaku w ściekach oczyszczonych wynoszą od 0,29 do 2,5 μg/dm3, a średnia skuteczność usuwania jest na poziomie ok 40%. Należy zaznaczyć, że dane te nie odzwierciedlają stanu rzeczywistego, gdyż badania są prowadzone wyrywkowo. W 2013 r. Komisja Europejska w dyrektywie Parlamentu Europejskiego i Rady (2013/39/EU) w zakresie substancji priorytetowych w dziedzinie polityki wodnej, umieściła na liście obserwacyjnej trzy substancje farmaceutyczne, wśród których wymieniany jest diklofenak. Ciągle jednak nie ustalono limitów dotyczących wprowadzania substancji farmaceutycznych do środowiska.

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

PubMed Central

Mahdizadeh, Shahla; Khaleghi Ghadiri, Maryam; Gorji, Ali

2015-01-01

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. PMID:26101752

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

PubMed Central

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 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 towards a long-term cure for type I diabetes. PMID:23660251

Medicinal Chemistry Approaches of Controlling Gastrointestinal Side Effects of Non-Steroidal Anti-Inflammatory Drugs. Endogenous Protective Mechanisms and Drug Design.

PubMed

Tziona, Paraskevi; Theodosis-Nobelos, Panagiotis; Rekka, Eleni A

2017-01-01

Non-steroidal anti-inflammatory drugs are the oldest and most widely used medicines. However, their untoward effects, especially gastrointestinal toxicity, remain the main obstacle to their application. Because of their mechanism of action, cycloxygenase (COX) inhibition, in combination with the weekly acidic character of most of them, major protective mechanisms of the gastrointestinal system are suppressed and deregulated. In this review, several compounds designed to retain anti-inflammatory activity, but devoid of gastrointestinal side effects, are presented. Thus, gastro-protective drugs, selective COX-2 inhibitors, nitric monoxide- and hydrogen sulphide-releasing agents, prodrugs, lipoxygenase (LOX) inhibitors and dual COX/LOX inhibitors are presented. Their mechanism of action, as well as their advantages and disadvantages are discussed. Efforts, aiming to the development of safe non-steroidal anti-inflammatory agents, are evolving, however there are still several problems concerning gastro-protection to be efficiently solved, thus, design of effective and safe agents for the treatment of inflammatory conditions still remains a major challenge. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Marine algal natural products with anti-oxidative, anti-inflammatory, and anti-cancer properties

PubMed Central

2013-01-01

For their various bioactivities, biomaterials derived from marine algae are important ingredients in many products, such as cosmetics and drugs for treating cancer and other diseases. This mini-review comprehensively compares the bioactivities and biological functions of biomaterials from red, green, brown, and blue-green algae. The anti-oxidative effects and bioactivities of several different crude extracts of algae have been evaluated both in vitro and in vivo. Natural products derived from marine algae protect cells by modulating the effects of oxidative stress. Because oxidative stress plays important roles in inflammatory reactions and in carcinogenesis, marine algal natural products have potential for use in anti-cancer and anti-inflammatory drugs. PMID:23724847

Preventing Post-ERCP Pancreatitis: The Role of Prophylactic Pancreatic Duct Stenting in the Rectal NSAID Era

PubMed Central

Bekkali, Noor-L-Houda; Thomas, Tom; Keane, Margaret Geraldine; Murray, Sam; Joshi, Deepak; Elsayed, Ghassan; Johnson, Gavin James; Chapman, Michael Huw; Pereira, Stephen Paul; Webster, George John Mitchell

2018-01-01

Background Rectal non-steroidal anti-inflammatory drug at endoscopic retrograde cholangiopancreatography is now the standard of care to reduce the risk of post-ERCP pancreatitis. Pancreatic duct stenting also reduces the risk of post- ERCP pancreatitis in high-risk patients, but failed pancreatic duct stenting carries an increased PEP rate (up to 35%). Study Aim To assess the impact on post-ERCP pancreatitis of successful and unsuccessful pancreatic duct stent placement in the setting of universal rectal non-steroidal anti-inflammatory drug use. Methods Between 2013–2015, all patients undergoing endoscopic retrograde cholangiopancreatographys in our tertiary referral centre (where rectal non-steroidal anti-inflammatory drugs are used routinely) were included. The electronic patient’s records were reviewed and the following parameters were analysed: indication for pancreatic duct stenting; deployment success; and adverse events. Results A total of 1633 endoscopic retrograde cholangiopancreatographys were performed, and pancreatic duct stenting was attempted in 324 cases (20%), with successful placement in 307 patients (95%). Contra-indications to non-steroidal anti-inflammatory drugs were found in 106 (6.5%) patients. Prophylactic stenting failed in 12 of 213 patients; of whom one patient developed post-ERCP pancreatitis (8%). Eighteen (9%) patients with prophylactic pancreatic duct stents developed post-ERCP pancreatitis compared to 1.4% without prophylactic stents (RR 8.4, p=0.04). Conclusion A lack of difference in post-ERCP pancreatitis in those who underwent successful, and unsuccessful, pancreatic duct stent placement may reflect the protective effect of non-steroidal anti-inflammatory drugs. This data adds to evidence suggesting that pancreatic duct stenting may be less important, even in high-risk patients, with the widespread use of non-steroidal anti-inflammatory drugs. PMID:29731700

Comparative studies on osmosis based encapsulation of sodium diclofenac in porcine and outdated human erythrocyte ghosts.

PubMed

Bukara, Katarina; Drvenica, Ivana; Ilić, Vesna; Stančić, Ana; Mišić, Danijela; Vasić, Borislav; Gajić, Radoš; Vučetić, Dušan; Kiekens, Filip; Bugarski, Branko

2016-12-20

The objective of our study was to develop controlled drug delivery system based on erythrocyte ghosts for amphiphilic compound sodium diclofenac considering the differences between erythrocytes derived from two readily available materials - porcine slaughterhouse and outdated transfusion human blood. Starting erythrocytes, empty erythrocyte ghosts and diclofenac loaded ghosts were compared in terms of the encapsulation efficiency, drug releasing profiles, size distribution, surface charge, conductivity, surface roughness and morphology. The encapsulation of sodium diclofenac was performed by an osmosis based process - gradual hemolysis. During this process sodium diclofenac exerted mild and delayed antihemolytic effect and increased potassium efflux in porcine but not in outdated human erythrocytes. FTIR spectra revealed lack of any membrane lipid disorder and chemical reaction with sodium diclofenac in encapsulated ghosts. Outdated human erythrocyte ghosts with detected nanoscale damages and reduced ability to shrink had encapsulation efficiency of only 8%. On the other hand, porcine erythrocyte ghosts had encapsulation efficiency of 37% and relatively slow drug release rate. More preserved structure and functional properties of porcine erythrocytes related to their superior encapsulation and release performances, define them as more appropriate for the usage in sodium diclofenac encapsulation process. Copyright © 2016 Elsevier B.V. All rights reserved.

[U.S. Food and Drug Administration (FDA) strengthens warning that non-aspirin non steroidal anti-inflammatory drugs (NSAIDs) can cause myocardial infarctions or strokes: the dentist's perspective].

PubMed

Rosen, E; Tsesis, I; Vered, M

2015-10-01

This short communication is aimed to update dental practitioners regarding the recently published warning of the U.S. Food and Drug Administration (FDA) regarding the risk for severe cardiovascular complications such as myocardial infarction or stroke following the use of non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs).

Expression of pleiotrophin, an important regulator of cell migration, is inhibited in intestinal epithelial cells by treatment with non-steroidal anti-inflammatory drugs

USDA-ARS?s Scientific Manuscript database

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs for the suppression of inflammation and pain. However, the analgesic properties of NSAIDs are also associated with significant negative side effects, most notably in the gastrointestinal (GI) tract. Increasingly, evi...

HPLC detection of plasma concentrations of diclofenac in human volunteers administered with povidone-ethylcellulose-based experimental transdermal matrix-type patches.

PubMed

Mukherjee, B; Mahapatra, S; Das, S; Roy, G; Dey, S

2006-06-01

By developing a high-performance liquid chromatography (HPLC) method, we estimated the blood concentrations of diclofenac in human volunteers administered with the transdermal patches prepared with povidone-ethylcellulose and oral diclofenac tablets. Drug-excipient interaction studies were done using the FTIR technique. The external morphology of the prepared patch before and after application to human skin was analyzed with scanning electron microscopy. FTIR studies revealed that there was no predominant interaction between the drug and polymers. In vivo studies revealed that the average concentrations of drug in plasma were 376, 1562, 2953, 2902, 2864, and 2948 ng/ml after 2, 4, 8, 24, 30, and 48 h from patches each containing 50 mg of diclofenac diethylamine, respectively, and the mean concentrations of drug in plasma after the oral administration of marketed tablet containing 50 mg diclofenac sodium were 383.7, 2569, 3693.5, 162.5, and 55.3 ng/ml at 2, 4, 8, 24, and 30 h after oral administration. Values of Cmax were 3693.5 after oral administration and 2953.8 ng/ml in the case of transdermal application. From this study, we have achieved the sustained blood level of diclofenac from the experimental patches along with an analytical method based on HPLC to determine the diclofenac blood level. Copyright 2006 Prous Science.

Endotoxin molecule lipopolysaccharide-induced zebrafish inflammation model: a novel screening method for anti-inflammatory drugs.

PubMed

Yang, Li-Ling; Wang, Guo-Quan; Yang, Li-Mei; Huang, Zhi-Bing; Zhang, Wen-Qing; Yu, Lin-Zhong

2014-02-21

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

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

PubMed Central

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. PMID:23589694

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

PubMed

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.

Formulation and pharmacokinetics of diclofenac lipid nanoemulsions for parenteral application.

PubMed

Ramreddy, Srividya; Kandadi, Prabhakar; Veerabrahma, Kishan

2012-01-01

The objective of the present study was to formulate and determine the pharmacokinetics of stable o/w parenteral lipid nanoemulsions (LNEs) of diclofenac acid used to treat arthritic conditions. The LNEs of diclofenac acid with a mean size ranging from 200 to 240 nm and a zeta potential of -29.4 ± 1.04 mV (negatively charged LNEs) and 62.1 ± 3.5 (positively charged LNEs) emulsions were prepared by hot homogenization and ultrasonication process. The influence of formulation variables, such as the change in proportion of cholesterol, was studied, and optimized formulations were developed. The optimized formulations were relatively stable during centrifugal stress, dilution stress, and storage. The drug content and entrapment efficiency were determined using high-performance liquid chromatography. The in vitro drug release was carried out in phosphate-buffered saline pH 7.4 and cumulative amount of drug released was estimated using a UV-visible spectro-photometer. During in vivo pharmacokinetic studies in male Wistar rats, diclofenac serum concentration from LNEs was higher than that of Voveran injection and was detectable up to 12 h. Diclofenac in LNEs showed improved pharmacokinetic profile with increase in area under the curve, elimination half-life and mean residence time in comparison to Voveran. Our aim was to prepare and determine the pharmacokinetics of injectable lipid nanoemulsions of diclofenac acid for treating arthritic conditions by reducing the frequency of dosing and pain at site of injection. The nanoemulsions of diclofenac acid were prepared by homogenization and ultrasonication process. The sizes and charges of oil globules were determined. The effect of cholesterol on stability of emulsion was studied, and an optimized preparation was developed. The optimized formulations were stable during centrifugation, dilution, and storage. The total amount of drug in emulsion and percentage amount of drug present in emulsion globules were determined using high-performance liquid chromatography. The drug release from preparation was carried out in phosphate-buffered saline pH 7.4. The cumulative amount of drug released was estimated using a spectrophotometer. The time course of the released drug in rat serum was determined. Diclofenac concentrations from lipid nanoemulsions were higher than that of Voveran injection (solution form) in serum.

The anti-arthritic, anti-inflammatory, antioxidant activity and relationships with total phenolics and total flavonoids of nine South African plants used traditionally to treat arthritis.

PubMed

Elisha, Ishaku Leo; Dzoyem, Jean-Paul; McGaw, Lyndy Joy; Botha, Francien S; Eloff, Jacobus Nicolaas

2016-08-23

Oxidative stress predisposes the human and animal body to diseases like cancer, diabetes, arthritis, rheumatoid arthritis, atherosclerosis and chronic inflammatory disorders. Hence, this study seeks to determine the antioxidant, anti-inflammatory and anti-arthritic activities of acetone leaf extracts of nine South African medicinal plants that have been used traditionally to treat arthritis and inflammation. The anti-inflammatory activity of the extracts was determined by investigating inhibition of nitric oxide production in lipopolysaccharide activated RAW 264.7 macrophages as well as 15-lipoxygenase enzyme inhibition. An anti-protein denaturation assay was used to determine the anti-arthritic properties of the extracts. The antioxidant activity was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethyl-benzthiazoline-6-sulfonic acid) (ABTS) radical scavenging assays and ferric reducing antioxidant power (FRAP). The total phenolic and total flavonoid concentration of extracts were determined by using standard methods. All extracts inhibited nitric oxide production in a dose-dependent manner in the LPS-stimulated RAW 264.7 macrophages. Extracts of Maesa lanceolata and Heteromorpha arborescens inhibited NO production by 99.16 % and 89.48 % at a concentration of 30 μg/ml respectively. Elaeodendron croceum and Calpurnia aurea extracts had strong activity against 15-lipoxygenase activity with IC50 values of 26.23 and 34.70 μg/ml respectively. Morus mesozygia and Heteromorpha arborescens extracts had good in vitro anti-arthritic activity with IC50 values of 11.89 and 53.78 μg/ml, the positive control diclofenac sodium had IC50 value of 32.37 μg/ml. The free radical scavenging activity of the extracts in DPPH assays ranged between 7.72 and 154.77 μg/ml. Trolox equivalent antioxidant capacity (TEAC) and FRAP values ranged from 0.06 to 1.32 and 0.06 to 0.99 respectively. Results from this study support the traditional use of the selected medicinal plants in the management of arthritis and other inflammatory conditions. The free radical scavenging capacity of the extracts may be related to an immune boosting potential.

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

PubMed

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.

Central nervous system toxicity of mefenamic acid overdose compared with other NSAIDs: an analysis of cases reported to the United Kingdom National Poisons Information Service.

PubMed

Kamour, Ashraf; Crichton, Siobhan; Cooper, Gill; Lupton, David J; Eddleston, Michael; Vale, J Allister; Thompson, John P; Thomas, Simon H L

2017-04-01

Case reports and small case series suggest increased central nervous system (CNS) toxicity, especially convulsions, after overdose of mefenamic acid, compared with other nonsteroidal anti-inflammatory drugs (NSAIDs), although comparative epidemiological studies have not been conducted. The current study compared rates of CNS toxicity after overdose between mefenamic acid, ibuprofen, diclofenac and naproxen, as reported in telephone enquiries to the UK National Poisons Information Service (NPIS). NPIS telephone enquiries related to the four NSAIDs, received between January 2007 and December 2013, were analysed, comparing the frequency of reported CNS toxicity (convulsions, altered conscious level, agitation or aggression, confusion or disorientation) using multivariable logistic regression. Of 22 937 patient-specific telephone enquiries, 10 398 did not involve co-ingestion of other substances (mefenamic acid 461, ibuprofen 8090, diclofenac 1300, naproxen 547). Patients taking mefenamic acid were younger and more commonly female than those using other NSAIDs. Those ingesting mefenamic acid were more likely to experience CNS toxicity than those ingesting the other NSAIDs combined [adjusted odds ratio (OR) 7.77, 95% confidence interval (CI) 5.68, 10.62], especially convulsions (adjusted OR 81.5, 95% CI 27.8, 238.8). Predictors of CNS toxicity included reported dose and age, but not gender. Mefenamic acid overdose is associated with a much larger and dose-related risk of CNS toxicity, especially convulsions, compared with overdose of other NSAIDs. The benefit-risk profile of mefenamic acid should now be re-evaluated in light of effective and less toxic alternatives. © 2016 The British Pharmacological Society.

In Vivo Anti-Inflammatory, Anti-Bacterial and Anti-Diarrhoeal Activity of Ziziphus Jujuba Fruit Extract.

PubMed

Mesaik, Ahmed M; Poh, Hiap Wei; Bin, Ooi Yan; Elawad, Izzaddinn; Alsayed, Badr

2018-05-20

Ziziphus jujuba belongs to family Rhamnaceae widely distributed in subtropical and tropical countries. It is used traditionally for several pharmacological purposes including anti-inflammation, antidiarrhoeal and antibacterial, as well as tonic and sometimes as hypnotic (sedative). To determine the in vivo antidiarrhoeal, antibacterial and anti-inflammatory activities of Z. jujuba fruit ethanolic extract. The fruit was macerated and extracted by 95% (v/v) ethanol. The antidiarrhoeal activity was evaluated using castor oil and Escherichia coli induced diarrhoea mouse model. The antidiarrhoeal and antibacterial activity was investigated at graded doses (400-1200 mg/kg). The anti-inflammatory effects were tested using the carrageenan-induced paw oedema in female Wistar rats. Rat's treatment groups received tragacanth, 100 mg/kg diclofenac sodium, 800 mg/kg, 1200 mg/kg or 1600 mg/kg of an ethanolic extract of Z. jujuba (EEZJ). All treatment groups were fed with the compounds one hour before carrageenan injection at of rat's paw. Also, the EEZJ was further analysed by HPLC-PDA system for identification of the presence of betulinic acid and quercetin. EEZJ different doses did not show inhibitory activity against castor oil induced diarrhoea except for the higher (1200 mg/kg) dose. However, the frequency of defecation of stools and watery stool were reduced significantly when compared to control group (P ≤ 0.05 and P ≤ 0.01 respectively), resulted in overall 67% inhibition of diarrhoea. Our anti-inflammatory results demonstrated that EEZJ was able to inhibit the carrageenan-induced paw oedema in rats to a significant degree (p ≤ 0.05) and the paw volume and thickness of both left and right paw were affected compared to the negative control group. EEZJ possesses antidiarrhoeal and antibacterial activity in a dose depending manner and may provide a pharmacological basis for its clinical use in diarrheal diseases. The activity may partially be due to the presence of betulinic acid and quercetin.

Is the risk of cardiovascular disease altered with anti-inflammatory therapies? Insights from rheumatoid arthritis

PubMed Central

Kraakman, Michael J; Dragoljevic, Dragana; Kammoun, Helene L; Murphy, Andrew J

2016-01-01

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide. Atherosclerosis is the most common form of CVD, which is complex and multifactorial with an elevated risk observed in people with either metabolic or inflammatory diseases. Accumulating evidence now links obesity with a state of chronic low-grade inflammation and has renewed our understanding of this condition and its associated comorbidities. An emerging theme linking disease states with atherosclerosis is the increased production of myeloid cells, which can initiate and exacerbate atherogenesis. Although anti-inflammatory drug treatments exist and have been successfully used to treat inflammatory conditions such as rheumatoid arthritis (RA), a commonly observed side effect is dyslipidemia, inadvertently, a major risk factor for the development of atherosclerosis. The mechanisms leading to dyslipidemia associated with anti-inflammatory drug use and whether CVD risk is actually increased by this dyslipidemia are of great therapeutic importance and currently remain poorly understood. Here we review recent data providing links between inflammation, hematopoiesis, dyslipidemia and CVD risk in the context of anti-inflammatory drug use. PMID:27350883

Layered gadolinium hydroxides for simultaneous drug delivery and imaging.

PubMed

Xu, Yadong; Goyanes, Alvaro; Wang, Yuwei; Weston, Andrew J; So, Po-Wah; Geraldes, Carlos F G C; Fogg, Andrew M; Basit, Abdul W; Williams, Gareth R

2018-02-27

The potential of the layered gadolinium hydroxide (LGdH) [Gd 2 (OH) 5 ]Cl·yH 2 O (LGdH-Cl) for simultaneous drug delivery and magnetic resonance imaging was explored in this work. Three non-steroidal anti-inflammatory drugs (diclofenac [dic], ibuprofen [ibu], and naproxen [nap]) were intercalated into LGdH-Cl for the first time, using three different routes (ion exchange intercalation, coprecipitation, and exfoliation-self-assembly). X-ray diffraction, elemental microanalysis and IR spectroscopy confirmed successful incorporation of the drug into the interlayer spaces of the LGdH in all cases. From a comparison of the guest anion sizes and interlayer spacings, the active ingredients are believed to adopt intertwined bilayer configurations between the LGdH layers. The materials prepared by coprecipitation in general have noticeably higher drug loadings than those produced by ion exchange or self-assembly, as a result of the incorporation of some neutral drug into the composites. The LGdH-drug intercalates are stable at neutral pH, but rapidly degrade in acidic conditions to free Gd 3+ into solution. While LGdH-nap releases its drug loading into solution very rapidly (within ca. 1.5 h) at pH 7.4, LGdH-dic shows sustained release over 4 h, and LGdH-ibu extends this to 24 h. The latter composites therefore can be incorporated into enteric-coated tablets to provide sustained release in the small intestine. The drug intercalates are highly biocompatible and retain the proton relaxivity properties of the parent LGdH-Cl, with the materials most promising for use as negative contrast agents in MRI. Overall, the LGdH-drug intercalation compounds appear to have great potential for use in theranostic applications.

Celecoxib enhances the anti-inflammatory effects of farnesylthiosalicylic acid on T cells independent of prostaglandin E(2) production.

PubMed

Mor, Adam; Aizman, Elizabeta; Kloog, Yoel

2012-10-01

Celecoxib (Celebrex(®)), a non-steroidal anti-inflammatory drug and selective cyclooxygenase-2 inhibitor, is widely used to treat arthritis and other inflammatory disorders. Awareness of its anti-proliferative properties has prompted another indication for its use, in preventing colon polyps in high-risk populations. Farnesylthiosalicylic acid (FTS; Salirasib(®)), designed to inhibit oncogenic Ras and currently under evaluation in phase I/II and II clinical trials, was recently shown by our group to exert anti-inflammatory effects on both lymphocytes and mast cells. Here we examined whether celecoxib combined with FTS would enhance this anti-inflammatory activity. While each drug separately inhibited Ras activation in these cells, their combination yielded more marked inhibition as well as further inhibition of ERK phosphorylation, lymphocyte adhesion, and interleukin-2 secretion. The inhibitory effects, moreover, were independent of prostaglandin E(2) secretion. These data point to the promising potential of combined treatment with celecoxib and FTS for inflammatory disorders involving lymphocytes.

Mechanisms of Analgesic and Anti-Inflammatory Properties of Annona muricata Linn. (Annonaceae) Fruit Extract in Rodents

PubMed Central

Ishola, Ismail O.; Olusayero, Abayomi Micheal; Ochieng, Charles O.

2014-01-01

Abstract Unripe fruit of Annona muricata Linn. (Annonaceae) (soursop) is used in traditional African medicine for the treatment of neuralgia, rheumatism, and arthritic pain. This study sought to investigate the analgesic and anti-inflammatory effects of lyophilized fruit extract of Annona muricata (AM) in rodents. The analgesic activity was evaluated using the mouse writhing, formalin, and hot-plate tests while the anti-inflammatory action was investigated using the carrageenan-induced rat paw edema and xylene-induced ear edema tests. Pretreatment with AM (50, 100, and 200 mg/kg, p.o.) produced dose-dependent (P<.001) inhibition of writhes and formalin-induced pain in the late phase. AM and morphine produced time-course increase in pain threshold in hot-plate test. However, the analgesic effect elicited by AM was reversed (P<.05) by naloxone pretreatment. Similarly, the time-dependent increase in paw circumference induced by carrageenan was inhibited by AM treatment with peak effect (0.23±0.10 cm; P<.001, 200 mg/kg; 6 h), which was comparatively similar to that of diclofenac treated. Further, the xylene-induced ear edema was significantly reduced by AM (50 or 100 mg/kg) pretreatment; however, the anti-inflammatory effect elicited by AM was prevented by pretreatment of mice with NG-nitro-l-arginine (20 mg/kg, i.p., nitric-oxide synthase inhibitor) 15 min before AM (200 mg/kg, p.o.). The in vitro cyclooxygenase assay also showed that AM produced concentration-dependent inhibition of both cyclooxygenase (COX)-1 and COX-2 activity by 39.44%±0.05% and 55.71%±0.12%, respectively, at 100 μg/mL. In conclusion, A. muricata possesses analgesic effect through interaction with opioidergic pathway and anti-inflammatory property through inhibition of chemical mediators of inflammation. PMID:25133801

Anti-inflammatory and immunosuppressive drugs and reproduction.

PubMed

Østensen, Monika; Khamashta, Munther; Lockshin, Michael; Parke, Ann; Brucato, Antonio; Carp, Howard; Doria, Andrea; Rai, Raj; Meroni, Pierluigi; Cetin, Irene; Derksen, Ronald; Branch, Ware; Motta, Mario; Gordon, Caroline; Ruiz-Irastorza, Guillermo; Spinillo, Arsenio; Friedman, Deborah; Cimaz, Rolando; Czeizel, Andrew; Piette, Jean Charles; Cervera, Ricard; Levy, Roger A; Clementi, Maurizio; De Carolis, Sara; Petri, Michelle; Shoenfeld, Yehuda; Faden, David; Valesini, Guido; Tincani, Angela

2006-01-01

Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given.

Analgesic and anti-inflammatory controlled-released injectable microemulsion: Pseudo-ternary phase diagrams, in vitro, ex vivo and in vivo evaluation.

PubMed

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.

Characterization of the anti-inflammatory properties of NCX 429, a dual-acting compound releasing nitric oxide and naproxen.

PubMed

Amoruso, Angela; Fresu, Luigia Grazia; Dalli, Jesmond; Miglietta, Daniela; Bardelli, Claudio; Federici Canova, Donata; Perretti, Mauro; Brunelleschi, Sandra

2015-04-01

Cyclooxygenase (COX)-inhibiting nitric oxide donors (CINODs) are a new class of drugs that structurally combine a COX inhibitor with a nitric oxide (NO) donating moiety. This combination reduces potential toxicity of the non-steroidal anti-inflammatory drugs (NSAIDs) whilst maintaining the analgesic and anti-inflammatory effects. The present study was undertaken to investigate the anti-inflammatory effects of NCX 429, a naproxen-based CINOD, and to assess the additional properties of NO donation beyond those related to naproxen. We evaluated the in vitro effects of NCX 429 on oxy-radical production, phagocytosis, cytokine release, MMP-9, PPARγ expression and NF-κB activation in human monocytes/MDM and compared to naproxen. Moreover, we compared the in vivo efficacy of NCX 429 and naproxen in a murine model of peritonitis. In all the experiments performed in vitro, NCX 429 reduced the inflammatory responses with equal or higher efficacy compared to naproxen. Moreover, in in vivo experiments, NCX 429, at the lowest dose tested, was able to significantly inhibit cell influx in response to IL-1β administration although naproxen was found to be more potent than NCX 429 at reducing PGE2 in inflammatory exudates. These results demonstrate that both in vitro and in vivo--in a murine model of peritonitis--NCX 429 elicits significant anti-inflammatory activity, beyond the simple COX inhibition or pure NO release. Therefore, NO donation along with COX inhibition may represent a strategy for investigating inflammatory diseases in which pain and function are not fully resolved by analgesics/anti-inflammatory drugs. © 2015.

Comparing the Efficacy of Ophthalmic NSAIDs in Common Indications: A Literature Review to Support Cost-effective Prescribing.

PubMed

Wilson, Daniel J; Schutte, Scott M; Abel, Steven R

2015-06-01

To review the commercially available ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs), identify opportunities for therapeutic substitutions within and outside of their Food and Drug Administration (FDA)-approved indications, and identify clinically superior drugs within the class for specific indications. A PubMed search (1992 through January 2014) was performed on the terms diclofenac, ketorolac, flurbiprofen, bromfenac, and nepafenac. Clinical trials, meta-analyses, and review articles were evaluated if they were written in English and pertained to human subjects. Studies were excluded if they were in vitro studies, solely evaluated pharmacokinetic or pharmacodynamic properties, did not relate to the topical ophthalmic route, did not evaluate the FDA-approved indications of any available ophthalmic NSAID, or compared a reviewed drug with a nonreviewed drug (without placebo comparison). A total of 67 articles met the criteria for evaluation. Article quality, study design, and dosing of the medications were assessed to determine the clinical applicability of the results. The quality of the article was determined using the Oxford Centre for Evidence-based Medicine Levels of Evidence 1. Many formulations of the 5 reviewed NSAIDs have been studied across the 4 primary indications. These indications are (1) pain and inflammation associated with cataract surgery, (2) pain associated with corneal refractive surgery, (3) inhibition of intraoperative miosis, and (4) seasonal allergic conjunctivitis. Several studies have directly compared drugs within this class and have identified instances in which certain selections are therapeutically superior or equivalent to another. This information provides practitioners with guidance in selecting an optimal medication. © The Author(s) 2015.

Physicochemical characterization and in vivo evaluation of thermosensitive diclofenac liquid suppository.

PubMed

Yong, Chul Soon; Choi, Young-Kwon; Kim, Yong-Il; Park, Byung-Joo; Quan, Qi-Zhe; Rhee, Jong-Dal; Kim, Chong-Kook; Choi, Han-Gon

2003-02-01

Liquid suppository systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and mucoadhesive to the rectal tissues without leakage after the dose. However, a liquid suppository containing diclofenac sodium could not be developed using bioadhesive polymers, since the drug was precipitated in this preparation. To develop a liquid suppository system using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers and sodium chloride were investigated. Furthermore, the pharmacokinetic study of diclofenac sodium delivered by the liquid suppository was performed. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. The liquid suppositories with less than 1.0% of sodium chloride, in which the drug was not precipitated, were inserted into the rectum without difficulty and leakage. Furthermore, liquid suppository gave significantly higher initial plasma concentrations and faster Tmax of diclofenac sodium than did solid suppository, indicating that drug from liquid suppository could be absorbed faster than that from solid one in rats. Our results suggested that a thermosensitive liquid suppository system with sodium chloride and poloxamers was a more physically stable, convenient and effective rectal dosage form for diclofenac sodium.

Carvedilol alleviates adjuvant-induced arthritis and subcutaneous air pouch edema: Modulation of oxidative stress and inflammatory mediators

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

Arab, Hany H., E-mail: hany_h_arab@yahoo.com; Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo; El-Sawalhi, Maha M.

Rheumatoid arthritis (RA) is a systemic inflammatory disease with cardiovascular complications as the leading cause of morbidity. Carvedilol is an adrenergic antagonist which has been safely used in treatment of several cardiovascular disorders. Given that carvedilol has powerful antioxidant/anti-inflammatory properties, we aimed to investigate its protective potential against arthritis that may add further benefits for its clinical usefulness especially in RA patients with concomitant cardiovascular disorders. Two models were studied in the same rat; adjuvant arthritis and subcutaneous air pouch edema. Carvedilol (10 mg/kg/day p.o. for 21 days) effectively suppressed inflammation in both models with comparable efficacy to the standardmore » anti-inflammatory diclofenac (5 mg/kg/day p.o.). Notably, carvedilol inhibited paw edema and abrogated the leukocyte invasion to air pouch exudates. The latter observation was confirmed by the histopathological assessment of the pouch lining that revealed mitigation of immuno-inflammatory cell influx. Carvedilol reduced/normalized oxidative stress markers (lipid peroxides, nitric oxide and protein thiols) and lowered the release of inflammatory cytokines (TNF-α and IL-6), and eicosanoids (PGE{sub 2} and LTB{sub 4}) in sera and exudates of arthritic rats. Interestingly, carvedilol, per se, didn't present any effect on assessed biochemical parameters in normal rats. Together, the current study highlights evidences for the promising anti-arthritic effects of carvedilol that could be mediated through attenuation of leukocyte migration, alleviation of oxidative stress and suppression of proinflammatory cytokines and eicosanoids. - Highlights: ► Carvedilol possesses promising anti-arthritic properties. ► It markedly suppressed inflammation in adjuvant arthritis and air pouch edema. ► It abrogated the leukocyte invasion to air pouch exudates and linings. ► It reduced/normalized oxidative stress markers in sera and exudates of arthritic rats. ► It also mitigated the release of proinflammatory cytokines and eicosanoids.« less

The use of Brazilian propolis for discovery and development of novel anti-inflammatory drugs.

PubMed

Franchin, Marcelo; Freires, Irlan Almeida; Lazarini, Josy Goldoni; Nani, Bruno Dias; da Cunha, Marcos Guilherme; Colón, David Fernando; de Alencar, Severino Matias; Rosalen, Pedro Luiz

2018-06-10

Anti-Inflammatory drugs have been routinely used in the management of acute and chronic inflammatory conditions. Nevertheless, their undesirable side and adverse effects have encouraged the development of more selective, tolerable and efficacious drugs able to modulate the inflammatory process through distinct mechanisms than those of drugs currently available in the market, for instance, inhibition of leukocyte recruitment (chemotaxis, rolling, adhesion and transmigration). Natural products, including Brazilian propolis, have been considered a rich source of anti-inflammatory molecules due to a very complex phytochemical diversity. Brazil has at least thirteen distinct types of propolis and many bioactive compounds have been isolated therefrom, such as apigenin, artepillin C, vestitol, neovestitol, among others. These molecules were proven to play a significant immunomodulatory role through (i) inhibition of inflammatory cytokines (e.g. TNF-α) and chemokines (CXCL1/KC and CXCL2/MIP2); (ii) inhibition of IκBα, ERK1/2, JNK and p38MAPK phosphorylation; (iii) inhibition of NF-κB activation; and (iv) inhibition of neutrophil adhesion and transmigration (ICAM-1, VCAM-1 and E-selectin expression). In this review, we shed light on the new advances in the research of compounds isolated from Brazilian propolis from Apis mellifera bees as potentially novel anti-inflammatory drugs. The compilation of data and insights presented herein may open further avenues for the pharmacological management of oral and systemic inflammatory conditions. Further research should focus on clinical and acute/chronic toxicological validation of the most promising compounds described in this review. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

PubMed

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.

Study of pharmaceuticals in surface and wastewater from Cuernavaca, Morelos, Mexico: Occurrence and environmental risk assessment.

PubMed

Rivera-Jaimes, José Abraham; Postigo, Cristina; Melgoza-Alemán, Rosa María; Aceña, Jaume; Barceló, Damia; López de Alda, Miren

2018-02-01

The present work describes the first known study to date on the occurrence of pharmaceuticals in surface water and wastewater of Cuernavaca, the capital of the state of Morelos (México). Selected pharmaceuticals (a total of 35) were extracted from the collected water samples with a generic solid phase extraction (SPE) protocol and determined in the sample extracts by means of high-performance liquid chromatography coupled to electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS). A screening level risk assessment combining the measured environmental concentrations (MECs) with dose-response data based on predicted no-effect concentrations (PNECs) was also applied to estimate Hazard Quotients (HQs) for the pharmaceuticals detected in the investigated area. A total of twelve pharmaceuticals were found in the water samples analyzed, with detection frequencies above 78% and in most cases of 100%. Overall, the most abundant pharmaceuticals in surface water were the analgesic and anti-inflammatory drugs naproxen (732-4880ng/L), acetaminophen (354-4460ng/L), and diclofenac (258-1398ng/L), and the lipid regulator bezafibrate (286-2100ng/L). On the contrary, other compounds like the β-blocker atenolol and the psychiatric drug carbamazepine were found at only a few ng or tens of ng per liter in the Apatlaco River. Despite the fact that some of the most abundant compounds showed good removal (>97%) during wastewater treatment, concentrations downstream the WWTP were only slightly lower than upstream. This indicates the existence of additional inputs of untreated wastewater into the river. Based on the obtained HQ-values, the concentrations of ibuprofen, sulfamethoxazole, diclofenac and naproxen present in the river could pose a high toxicity risk for the aquatic ecosystem. These findings highlight these pharmaceuticals as relevant organic contaminants in the area of study and the need to further monitor them in order to adopt appropriate measures to safeguard the ecosystem, and eventually human health. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

Lu, Pinyi; Hontecillas, Raquel; Horne, William T; Carbo, Adria; Viladomiu, Monica; Pedragosa, Mireia; Bevan, David R; Lewis, Stephanie N; Bassaganya-Riera, Josep

2012-01-01

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

Computational Modeling-Based Discovery of Novel Classes of Anti-Inflammatory Drugs That Target Lanthionine Synthetase C-Like Protein 2

PubMed Central

Lu, Pinyi; Hontecillas, Raquel; Horne, William T.; Carbo, Adria; Viladomiu, Monica; Pedragosa, Mireia; Bevan, David R.; Lewis, Stephanie N.; Bassaganya-Riera, Josep

2012-01-01

Background Lanthionine synthetase component C-like protein 2 (LANCL2) is a member of the eukaryotic lanthionine synthetase component C-Like protein family involved in signal transduction and insulin sensitization. Recently, LANCL2 is a target for the binding and signaling of abscisic acid (ABA), a plant hormone with anti-diabetic and anti-inflammatory effects. Methodology/Principal Findings The goal of this study was to determine the role of LANCL2 as a potential therapeutic target for developing novel drugs and nutraceuticals against inflammatory diseases. Previously, we performed homology modeling to construct a three-dimensional structure of LANCL2 using the crystal structure of lanthionine synthetase component C-like protein 1 (LANCL1) as a template. Using this model, structure-based virtual screening was performed using compounds from NCI (National Cancer Institute) Diversity Set II, ChemBridge, ZINC natural products, and FDA-approved drugs databases. Several potential ligands were identified using molecular docking. In order to validate the anti-inflammatory efficacy of the top ranked compound (NSC61610) in the NCI Diversity Set II, a series of in vitro and pre-clinical efficacy studies were performed using a mouse model of dextran sodium sulfate (DSS)-induced colitis. Our findings showed that the lead compound, NSC61610, activated peroxisome proliferator-activated receptor gamma in a LANCL2- and adenylate cyclase/cAMP dependent manner in vitro and ameliorated experimental colitis by down-modulating colonic inflammatory gene expression and favoring regulatory T cell responses. Conclusions/Significance LANCL2 is a novel therapeutic target for inflammatory diseases. High-throughput, structure-based virtual screening is an effective computational-based drug design method for discovering anti-inflammatory LANCL2-based drug candidates. PMID:22509338

Acetaminophen and non-steroidal anti-inflammatory drugs interact with morphine and tramadol analgesia for the treatment of neuropathic pain in rats.

PubMed

Shinozaki, Tomonari; Yamada, Toshihiko; Nonaka, Takahiro; Yamamoto, Tatsuo

2015-06-01

Although non-steroidal anti-inflammatory drugs and acetaminophen have no proven efficacy against neuropathic pain, they are frequently prescribed for neuropathic pain patients. We examined whether the combination of opioids (tramadol and morphine) with indomethacin or acetaminophen produce favorable effects on neuropathic pain and compared the efficacy for neuropathic pain with that for inflammatory pain. The carrageenan model was used as the inflammatory pain model while the tibial neuroma transposition (TNT) model was used as the neuropathic pain model. The tibial nerve is transected in the TNT model, with the tibial nerve stump then transpositioned to the lateral aspect of the hindlimb. Neuropathic pain (mechanical allodynia and neuroma pain) is observed after TNT injury. Drugs were administered orally. In the carrageenan model, all drugs produced anti-allodynic effects and all drug combinations, but not tramadol + indomethacin combination, produced synergistic anti-allodynic effects. In the TNT model, tramadol and morphine, but not acetaminophen and indomethacin, produced anti-neuropathic pain effects. In the combination, with the exception of morphine + acetaminophen combination, both acetaminophen and indomethacin reduced the 50% effective dose (ED50) of tramadol and morphine as compared with the ED50s for the single drug study in the TNT model. The ED50s of tramadol and morphine in the carrageenan combination test were not statistically significantly different from the ED50s in the TNT model combination study. The combination of opioids with indomethacin or acetaminophen produced a synergistic analgesic effect both in inflammatory and neuropathic pain with some exceptions. The efficacy of these combinations for neuropathic pain was not different from that for inflammatory pain.

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

PubMed

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

2016-08-01

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

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

PubMed

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

1998-10-01

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

Current perspectives in NSAID-induced gastropathy.

PubMed

Sinha, Mau; Gautam, Lovely; Shukla, Prakash Kumar; Kaur, Punit; Sharma, Sujata; Singh, Tej P

2013-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most highly prescribed drugs in the world. Their analgesic, anti-inflammatory, and antipyretic actions may be beneficial; however, they are associated with severe side effects including gastrointestinal injury and peptic ulceration. Though several approaches for limiting these side effects have been adopted, like the use of COX-2 specific drugs, comedication of acid suppressants like proton pump inhibitors and prostaglandin analogs, these alternatives have limitations in terms of efficacy and side effects. In this paper, the mechanism of action of NSAIDs and their critical gastrointestinal complications have been reviewed. This paper also provides the information on different preventive measures prescribed to minimize such adverse effects and analyses the new suggested strategies for development of novel drugs to maintain the anti-inflammatory functions of NSAIDs along with effective gastrointestinal protection.

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

PubMed Central

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

Integrated Assessment of Diclofenac Biotransformation, Pharmacokinetics, and Omics-Based Toxicity in a Three-Dimensional Human Liver-Immunocompetent Coculture System

PubMed Central

Ravindra, Kodihalli C.; Large, Emma; Young, Carissa L.; Rivera-Burgos, Dinelia; Yu, Jiajie; Cirit, Murat; Hughes, David J.; Wishnok, John S.; Lauffenburger, Douglas A.; Griffith, Linda G.

2017-01-01

In vitro hepatocyte culture systems have inherent limitations in capturing known human drug toxicities that arise from complex immune responses. Therefore, we established and characterized a liver immunocompetent coculture model and evaluated diclofenac (DCF) metabolic profiles, in vitro–in vivo clearance correlations, toxicological responses, and acute phase responses using liquid chromatography–tandem mass spectrometry. DCF biotransformation was assessed after 48 hours of culture, and the major phase I and II metabolites were similar to the in vivo DCF metabolism profile in humans. Further characterization of secreted bile acids in the medium revealed that a glycine-conjugated bile acid was a sensitive marker of dose-dependent toxicity in this three-dimensional liver microphysiological system. Protein markers were significantly elevated in the culture medium at high micromolar doses of DCF, which were also observed previously for acute drug-induced toxicity in humans. In this immunocompetent model, lipopolysaccharide treatment evoked an inflammatory response that resulted in a marked increase in the overall number of acute phase proteins. Kupffer cell–mediated cytokine release recapitulated an in vivo proinflammatory response exemplified by a cohort of 11 cytokines that were differentially regulated after lipopolysaccharide induction, including interleukin (IL)-1β, IL-1Ra, IL-6, IL-8, IP-10, tumor necrosis factor-α, RANTES (regulated on activation normal T cell expressed and secreted), granulocyte colony-stimulating factor, macrophage colony-stimulating factor, macrophage inflammatory protein-1β, and IL-5. In summary, our findings indicate that three-dimensional liver microphysiological systems may serve as preclinical investigational platforms from the perspective of the discovery of a set of clinically relevant biomarkers including potential reactive metabolites, endogenous bile acids, excreted proteins, and cytokines to predict early drug-induced liver toxicity in humans. PMID:28450578

Hypersensitivity reactions to non-steroidal anti-inflammatory drugs.

PubMed

Cornejo-Garcia, José Antonio; Blanca-López, Natalia; Doña, Inmaculada; Andreu, Inmaculada; Agúndez, José A G; Carballo, Miguel; Blanca, Miguel; Canto, María Gabriela

2009-11-01

NSAIDs are the most important group of drugs involved in hypersensitivity drug reactions, and include heterogeneous compounds with very different chemical structures. These reactions can be IgE dependent (immediate reactions), T cell-mediated (non-immediate), or induced by a non-specific immunological mechanism related with the blocking of the COX-1 enzyme and the shunting to the lipooxygenase pathway (cross-intolerant reactions). Cutaneous symptoms are the most frequent, with ibuprofen, naproxen and diclofenac being common culprit drugs worldwide, although others can be involved because patterns of consumption and exposure rates vary between countries. A very important proportion of immunological reactions are immediate, with urticaria and anaphylaxis being the typical clinical manifestations. Non-immediate reactions comprise a number of heterogeneous entities ranging from mild exanthema to severe TEN or DRESS syndrome, as well as organ-specific reactions such as hepatitis or pneumonitis. Cross-intolerant reactions appear to non-chemically related drugs, and involve respiratory airways, skin or both. In vivo diagnostic tests are based on the capacity of the skin to respond to the culprit drug, but their sensitivity is in many instances rather low. The approach for in vitro testing consists of either detecting specific IgE antibodies or studying the proliferation of T lymphocytes toward the eliciting drug. No appropriate tests are yet available for the in vitro validation of cross-intolerance reactions, although techniques based on the stimulation of basophils have been proposed. Based on these findings, the diagnostic approach is often based on the controlled administration of the drug to assess tolerance. In this work we review current knowledge on hypersensitivity reactions to NSAIDs, including diagnostic approach and genetic studies.

Amides of non-steroidal anti-inflammatory drugs with thiomorpholine can yield hypolipidemic agents with improved anti-inflammatory activity.

PubMed

Theodosis-Nobelos, Panagiotis; Kourti, Malamati; Gavalas, Antonios; Rekka, Eleni A

2016-02-01

Novel amides of non steroidal anti-inflammatory drugs (NSAIDs), α-lipoic acid and indole-3-acetic acid with thiomorpholine were synthesised by a simple method and at high yields (60-92%). All the NSAID derivatives highly decreased lipidemic indices in the plasma of Triton treated hyperlipidemic rats. The most potent compound was the indomethacin derivative, which decreased total cholesterol, triglycerides and LDL cholesterol by 73%, 80% and 83%, respectively. They reduced acute inflammation equally or more than most parent acids. Hence, it could be concluded that amides of common NSAIDs with thiomorpholine acquire considerable hypolipidemic potency, while they preserve or augment their anti-inflammatory activity, thus addressing significant risk factors for atherogenesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Novel Pleiotropic Anti-Inflammatory Drug to Reduce ARDS Incidence

DTIC Science & Technology

2017-07-01

12 and decided the optimal strategy would be to modify the route of drug delivery from gavage to intravenous (IV). We tested several vehicles and...the most likely reason for these negative results was either our injury model is too severe causing the animals to be moribund or the mode of drug ...Page 1 AWARD NUMBER: W81XWH-16-1-0288 TITLE: A Novel Pleiotropic Anti-Inflammatory Drug to Reduce ARDS Incidence PRINCIPAL INVESTIGATOR: Gary

Nonsteroidal anti-inflammatory drugs-induced failure of lower esophageal and pyloric sphincter and counteraction of sphincters failure with stable gatric pentadecapeptide BPC 157 in rats.

PubMed

Vitaic, S; Stupnisek, M; Drmic, D; Bauk, L; Kokot, A; Klicek, R; Vcev, A; Luetic, K; Seiwerth, S; Sikiric, P

2017-04-01

The sphincters failure is a part of NSAIDs-toxicity that can be accordingly counteracted. We used a safe stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419), LD1 not achieved, since successful in inflammatory bowel disease trials, and counteracts esophagitis, sphincters failure, gastrointestinal ulcer and skin ulcer, external and internal fistulas in rats, and particularly counteracts all NSAIDs-lesions. We assessed lower esophageal sphincter and pyloric sphincter pressure (cmH 2 O) in rats treated with various NSAIDs regimens, at corresponding time points, known to produce stomach, small intestine lesions, hepatotoxicity and encephalopathy. Assessment was after diclofenac (12.5 mg/kg, 40 mg/kg intraperitoneal challenge), ibuprofen (400 mg/day/kg intraperitoneally for 4 weeks), paracetamol (5.0 g/kg intraperitoneal challenge), aspirin (400 mg/kg intraperitoneally or intragastrically), celecoxib (0.5 mg/kg, 1.0 mg/kg intraperitoneally). BPC 157 (10 μg/kg, 10 ng/kg) was given immediately after NSAIDs (intraperitoneally or intragastrically) or given in drinking water. Regularly, in all control NSAIDs fall of pressure occurred in both sphincters rapidly and then persisted. By contrast, in all NSAIDs-rats that received BPC 157, initial fall of pressure was minimized and pressure values restored to normal values. All tested NSAIDs decrease pressure in both sphincters, whilst BPC 157 counteracts their effects and restored both sphincters function.

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

PubMed

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.

Anti-inflammatory and immunosuppressive drugs and reproduction

PubMed Central

Østensen, Monika; Khamashta, Munther; Lockshin, Michael; Parke, Ann; Brucato, Antonio; Carp, Howard; Doria, Andrea; Rai, Raj; Meroni, Pierluigi; Cetin, Irene; Derksen, Ronald; Branch, Ware; Motta, Mario; Gordon, Caroline; Ruiz-Irastorza, Guillermo; Spinillo, Arsenio; Friedman, Deborah; Cimaz, Rolando; Czeizel, Andrew; Piette, Jean Charles; Cervera, Ricard; Levy, Roger A; Clementi, Maurizio; De Carolis, Sara; Petri, Michelle; Shoenfeld, Yehuda; Faden, David; Valesini, Guido; Tincani, Angela

2006-01-01

Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given. PMID:16712713

Montmorillonite-Alginate Composites as a Drug delivery System: Intercalation and In vitro Release of Diclofenac sodium

PubMed Central

Kevadiya, B. D.; Patel, H. A.; Joshi, G. V.; Abdi, S. H. R.; Bajaj, H. C.

2010-01-01

Diclofenac sodium and alginate was intercalated into montmorillonite to form uniform sized beads by gelation method. The structure and surface morphology of the synthesized composite beads were characterized by powdered X-ray diffraction, Fourier transform infrared spectroscopy, thermo gravimetric analysis and scanning electron microscopy. Diclofenac release kinetics of the composite in simulated intestinal fluid medium (pH 7.4) and effect of montmorillonite content on the in vitro release of diclofenac from diclofenac-montmorillonite-alginate composites bead was investigated by UV/Vis spectrophotometer. Diclofenac encapsulation efficiency in the montmorillonite-alginate composites bead increases with an increase in the montmorillonite content. The control release of diclofenac from diclofenac-montmorillonite-alginate composites beads was observed to be better as compared to diclofenac-alginate beads. PMID:21969745

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

PubMed

Fajardo, Alexandra M; Piazza, Gary A

2015-07-15

Colorectal cancer (CRC) is one of the most common human malignancies and a leading cause of cancer-related deaths in developed countries. Identifying effective preventive strategies aimed at inhibiting the development and progression of CRC is critical for reducing the incidence and mortality of this malignancy. The prevention of carcinogenesis by anti-inflammatory agents including nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, and natural products is an area of considerable interest and research. Numerous anti-inflammatory agents have been identified as potential CRC chemopreventive agents but vary in their mechanism of action. This review will discuss the molecular mechanisms being studied for the CRC chemopreventive activity of NSAIDs (i.e., aspirin, sulindac, and ibuprofen), COX-2 inhibitors (i.e., celecoxib), natural products (i.e., curcumin, resveratrol, EGCG, genistein, and baicalein), and metformin. A deeper understanding of how these anti-inflammatory agents inhibit CRC will provide insight into the development of potentially safer and more effective chemopreventive drugs. Copyright © 2015 the American Physiological Society.

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

PubMed Central

Piazza, Gary A.

2015-01-01

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

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

PubMed

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.

The anti-seizure drugs vinpocetine and carbamazepine, but not valproic acid, reduce inflammatory IL-1β and TNF-α expression in rat hippocampus.

PubMed

Gómez, Carlos D; Buijs, Rudolf M; Sitges, María

2014-09-01

In the present study, the effects of the two classical anti-epileptic drugs, carbamazepine and valproic acid, and the non-classical anti-seizure drug vinpocetine were investigated on the expression of the pro-inflammatory cytokines IL-1β and TNF-α in the hippocampus of rats by PCR or western blot after the administration of one or seven doses. Next, the effects of the anti-seizure drugs were investigated on the rise in cytokine expression induced by lipopolysaccharides (LPS) inoculation in vivo. To validate our methods, the changes induced by the pro-convulsive agents 4-aminopyridine, pentylenetetrazole and pilocarpine were also tested. Finally, the effect of the anti-seizure drugs on seizures and on the concomitant rise in pro-inflammatory cytokine expression induced by 4-aminopyridine was explored. Results show that vinpocetine and carbamazepine reduced the expression of IL-1β and TNF-α from basal conditions, and the increase in both pro-inflammatory cytokines induced by LPS. In contrast, valproic acid failed to reduce both the expression of the cytokines from basal conditions and the rise in IL-1β and TNF-α expression induced by LPS. Tonic-clonic seizures induced either by 4-aminopyridine, pentylenetetrazole or pilocarpine increased the expression of IL-1β and TNF-α markedly. 4-aminopyridine-induced changes were reduced by all the tested anti-seizure drugs, although valproic acid was less effective. We conclude that the anti-seizure drugs, vinpocetine and carbamazepine, whose mechanisms of action involve a decrease in ion channels permeability, also reduce cerebral inflammation. The mechanism of action of anti-seizure drugs like vinpocetine and carbamazepine involves a decrease in Na(+) channels permeability. We here propose that this mechanism of action also involves a decrease in cerebral inflammation. © 2014 International Society for Neurochemistry.

Synergistic interaction between metformin and sulfonylureas on diclofenac-induced antinociception measured using the formalin test in rats

PubMed Central

Ortiz, Mario I

2013-01-01

BACKGROUND There is evidence that biguanides and sulfonylureas block diclofenac-induced antinociception (DIA) in rat models. However, little is known about the interaction between these hypoglycemics with respect to DIA. OBJECTIVE: To determine whether metformin-sulfonylurea combinations affect DIA during the formalin test. METHODS: Rats received the appropriate vehicle or diclofenac before 1% formaldehyde was injected into the paw. Rats were also pretreated with vehicle, glibenclamide, glipizide, metformin or glibenclamide/metformin and glipizide/metformin combinations before the diclofenac and formaldehyde injections, and the effect on antinociception was assessed. Isobolograms of the combinations were constructed to test for a synergistic interaction. RESULTS: Systemic injection of diclofenac resulted in antinociception during the second phase of the test. Systemic pretreatment with the combinations of glibenclamide (0.56 mg/kg to 10 mg/kg)/metformin (10 mg/kg to 180 mg/kg) and glipizide (0.56 mg/kg to10 mg/kg)/metformin (10 mg/kg to 180 mg/kg) blocked DIA. The derived theoretical effective doses for 50% of subjects (ED50) for the glibenclamide/metformin and glipizide/metformin combinations were 32.52 mg/kg and 32.42 mg/kg, respectively, and were significantly higher than the actual observed experimental ED50 values (7.57 mg/kg and 8.43 mg/kg, respectively). CONCLUSION: Pretreatment with glibenclamide, glipizide or metformin blocked DIA in a dose-dependent manner, and combining either sulfonylurea with metformin produced even greater effects. The observed ED50s for the combinations were approximately fourfold lower than the calculated additive effects. These data indicate that sulfonylureas interact to produce antagonism of DIA. Combination therapy is a common second-line treatment for patients with diabetes and metabolic syndrome, a group that experiences pain from multiple sources. The results suggest that at least some anti-inflammatory agents may not be effective in this group. PMID:23985578

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

PubMed

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.

Rescue strategies against non-steroidal anti-inflammatory drug-induced gastroduodenal damage.

PubMed

Lim, Yun Jeong; Lee, Jeong Sang; Ku, Yang Suh; Hahm, Ki-Baik

2009-07-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed drugs worldwide, which attests to their efficacy as analgesic, antipyretic and anti-inflammatory agents as well as anticancer drugs. However, NSAID use also carries a risk of major gastroduodenal events, including symptomatic ulcers and their serious complications that can lead to fatal outcomes. The development of "coxibs" (selective cyclooxygenase-2 [COX-2] inhibitors) offered similar efficacy with reduced toxicity, but this promise of gastroduodenal safety has only partially been fulfilled, and is now dented with associated risks of cardiovascular or intestinal complications. Recent advances in basic science and biotechnology have given insights into molecular mechanisms of NSAID-induced gastroduodenal damage beyond COX-2 inhibition. The emergence of newer kinds of NSAIDs should alleviate gastroduodenal toxicity without compromising innate drug efficacy. In this review, novel strategies for avoiding NSAID-associated gastroduodenal damage will be described.

Chitosan nanoparticles as a modified diclofenac drug release system

NASA Astrophysics Data System (ADS)

Duarte Junior, Anivaldo Pereira; Tavares, Eraldo José Madureira; Alves, Taís Vanessa Gabbay; de Moura, Márcia Regina; da Costa, Carlos Emmerson Ferreira; Silva Júnior, José Otávio Carréra; Ribeiro Costa, Roseane Maria

2017-08-01

This study evaluated a modified nanostructured release system employing diclofenac as a drug model. Biodegradable chitosan nanoparticles were prepared with chitosan concentrations between 0.5 and 0.8% ( w/ v) by template polymerization method using methacrylic acid in aqueous solution. Chitosan-poly(methacrylic acid) (CS-PMAA) nanoparticles showed uniform size around 50-100 nm, homogeneous morphology, and spherical shape. Raw material and chitosan nanoparticles were characterized by thermal analysis, Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM), confirming the interaction between chitosan and methacrylic acid during nanoparticles preparation. Diclofenac sorption on the chitosan nanoparticles surface was achieved by incubation in water/ethanol (1:1) drug solution in concentrations of 0.5 and 0.8 mg/mL. The diclofenac amount sorbed per gram of CS-PMAA nanoparticles, when in a 0.5 mg/mL sodium diclofenac solution, was as follows: 12.93, 15, 20.87, and 29.63 mg/g for CS-PMAA nanoparticles 0.5, 0.6, 0.7, and 0.8% ( w/ v), respectively. When a 0.8 mg/mL sodium diclofenac solution was used, higher sorption efficiencies were obtained: For CS-PMAA nanoparticles with chitosan concentrations of 0.5, 0.6, 0.7, and 0.8% ( w/ v), the sorption efficiencies were 33.39, 49.58, 55.23, and 67.2 mg/g, respectively. Diclofenac sorption kinetics followed a second-order kinetics. Drug release from nanoparticles occurred in a period of up to 48 h and obeyed Korsmeyer-Peppas model, which was characterized mainly by Fickian diffusion transport. [Figure not available: see fulltext.

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

PubMed Central

Condorelli, Rosita A.

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. PMID:28164122

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

PubMed

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.

Molecular insights into microbial β-glucuronidase inhibition to abrogate CPT-11 toxicity.

PubMed

Roberts, Adam B; Wallace, Bret D; Venkatesh, Madhu Kumar; Mani, Sridhar; Redinbo, Matthew R

2013-08-01

Bacterial β-glucuronidases expressed by the symbiotic intestinal microbiota appear to play important roles in drug-induced epithelial cell toxicity in the gastrointestinal (GI) tract. For the anticancer drug CPT-11 (irinotecan) and the nonsteroidal anti-inflammatory drug diclofenac, it has been shown that removal of the glucuronide moieties from drug metabolites by bacterial β-glucuronidases in the GI lumen can significantly damage the intestinal epithelium. Furthermore, selective disruption of bacterial β-glucuronidases by small molecule inhibitors alleviates these side effects, which, for CPT-11 {7-ethyl-10-[4-(1-piperidino)-1-piperidino]}, can be dose limiting. Here we characterize novel microbial β-glucuronidase inhibitors that inhibit Escherichia coli β-glucuronidase in vitro with Ki values between 180 nM and 2 μM, and disrupt the enzyme in E. coli cells, with EC50 values as low as 300 nM. All compounds are selective for E. coli β-glucuronidase without inhibiting purified mammalian β-glucuronidase, and they do not impact the survival of either bacterial or mammalian cells. The 2.8 Å resolution crystal structure of one inhibitor bound to E. coli β-glucuronidase demonstrates that it contacts and orders only a portion of the "bacterial loop" present in microbial, but not mammalian, β-glucuronidases. The most potent compound examined in this group was found to protect mice against CPT-11-induced diarrhea. Taken together, these data advance our understanding of the chemical and structural basis of selective microbial β-glucuronidase inhibition, which may improve human drug efficacy and toxicity.

Molecular Insights into Microbial β-Glucuronidase Inhibition to Abrogate CPT-11 Toxicity

PubMed Central

Roberts, Adam B.; Wallace, Bret D.; Venkatesh, Madhu Kumar; Mani, Sridhar

2013-01-01

Bacterial β-glucuronidases expressed by the symbiotic intestinal microbiota appear to play important roles in drug-induced epithelial cell toxicity in the gastrointestinal (GI) tract. For the anticancer drug CPT-11 (irinotecan) and the nonsteroidal anti-inflammatory drug diclofenac, it has been shown that removal of the glucuronide moieties from drug metabolites by bacterial β-glucuronidases in the GI lumen can significantly damage the intestinal epithelium. Furthermore, selective disruption of bacterial β-glucuronidases by small molecule inhibitors alleviates these side effects, which, for CPT-11 {7-ethyl-10-[4-(1-piperidino)-1-piperidino]}, can be dose limiting. Here we characterize novel microbial β-glucuronidase inhibitors that inhibit Escherichia coli β-glucuronidase in vitro with Ki values between 180 nM and 2 μM, and disrupt the enzyme in E. coli cells, with EC50 values as low as 300 nM. All compounds are selective for E. coli β-glucuronidase without inhibiting purified mammalian β-glucuronidase, and they do not impact the survival of either bacterial or mammalian cells. The 2.8 Å resolution crystal structure of one inhibitor bound to E. coli β-glucuronidase demonstrates that it contacts and orders only a portion of the “bacterial loop” present in microbial, but not mammalian, β-glucuronidases. The most potent compound examined in this group was found to protect mice against CPT-11–induced diarrhea. Taken together, these data advance our understanding of the chemical and structural basis of selective microbial β-glucuronidase inhibition, which may improve human drug efficacy and toxicity. PMID:23690068

Development and evaluation of natural gum-based extended release matrix tablets of two model drugs of different water solubilities by direct compression.

PubMed

Ofori-Kwakye, Kwabena; Mfoafo, Kwadwo Amanor; Kipo, Samuel Lugrie; Kuntworbe, Noble; Boakye-Gyasi, Mariam El

2016-01-01

The study was aimed at developing extended release matrix tablets of poorly water-soluble diclofenac sodium and highly water-soluble metformin hydrochloride by direct compression using cashew gum, xanthan gum and hydroxypropylmethylcellulose (HPMC) as release retardants. The suitability of light grade cashew gum as a direct compression excipient was studied using the SeDeM Diagram Expert System. Thirteen tablet formulations of diclofenac sodium (∼100 mg) and metformin hydrochloride (∼200 mg) were prepared with varying amounts of cashew gum, xanthan gum and HPMC by direct compression. The flow properties of blended powders and the uniformity of weight, crushing strength, friability, swelling index and drug content of compressed tablets were determined. In vitro drug release studies of the matrix tablets were conducted in phosphate buffer (diclofenac: pH 7.4; metformin: pH 6.8) and the kinetics of drug release was determined by fitting the release data to five kinetic models. Cashew gum was found to be suitable for direct compression, having a good compressibility index (ICG) value of 5.173. The diclofenac and metformin matrix tablets produced generally possessed fairly good physical properties. Tablet swelling and drug release in aqueous medium were dependent on the type and amount of release retarding polymer and the solubility of drug used. Extended release of diclofenac (∼24 h) and metformin (∼8-12 h) from the matrix tablets in aqueous medium was achieved using various blends of the polymers. Drug release from diclofenac tablets fitted zero order, first order or Higuchi model while release from metformin tablets followed Higuchi or Hixson-Crowell model. The mechanism of release of the two drugs was mostly through Fickian diffusion and anomalous non-Fickian diffusion. The study has demonstrated the potential of blended hydrophilic polymers in the design and optimization of extended release matrix tablets for soluble and poorly soluble drugs by direct compression.

Physicochemical characterization of diclofenac sodium-loaded poloxamer gel as a rectal delivery system with fast absorption.

PubMed

Yong, Chul Soon; Sah, Hongkee; Jahng, Yurngdong; Chang, Hyeun Wook; Son, Jong-Keun; Lee, Seung Ho; Jeong, Tae Cheon; Rhee, Jong-Dal; Baek, Suk Hwan; Kim, Chong-Kook; Choi, Han-Gon

2003-05-01

Rectal poloxamer gel systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and were mucoadhesive to the rectal tissues without leakage after the dose. However, a poloxamer gel containing diclofenac sodium could not be developed using bioadhesive polymers, since the drug was precipitated in this preparation. To develop a poloxamer gel using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength, and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers, and sodium chloride were investigated. Furthermore, the pharmacokinetic study of diclofenac sodium delivered by the poloxamer gel was performed. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. The poloxamer gels with less than 1.0% sodium chloride, in which the drug was not precipitated, were inserted into the rectum without difficulty and leakage, and were retained in the rectum of rats for at least 6 hr. Furthermore, poloxamer gel gave significantly higher initial plasma concentrations and faster Tmax of diclofenac sodium than did solid suppository, indicating that drug from poloxamer gel could be absorbed faster than that from the solid one in rats. Our results suggested that a rectal poloxamer gel system with sodium chloride and poloxamers was a more physically stable, convenient, and effective rectal dosage form for diclofenac sodium.

Occurrence and removal of pharmaceuticals in wastewater treatment plants at the Spanish Mediterranean area of Valencia.

PubMed

Gracia-Lor, Emma; Sancho, Juan V; Serrano, Roque; Hernández, Félix

2012-04-01

A survey on the presence of pharmaceuticals in urban wastewater of a Spanish Mediterranean area (Castellon province) was carried out. The scope of the study included a wide variety of pharmaceuticals belonging to different therapeutical classes. For this purpose, 112 samples, including influent and effluent wastewater, from different conventional wastewater treatment plants were collected. Two monitoring programmes were carried out along several seasons. The first was in June 2008 and January 2009, and the second in April and October 2009. During the first monitoring, the occurrence of 20 analytes in 84 urban wastewater samples (influent and effluent) was studied. The selection of these pharmaceuticals was mainly based on consumption. From these, 17 compounds were detected in the samples, with analgesics and anti-inflammatories, cholesterol lowering statin drugs and lipid regulators being the most frequently detected groups. 4-Aminoantipyrine, bezafibrate, diclofenac, gemfibrozil, ketoprofen, naproxen and venlafaxine were the compounds most frequently found. In the highlight of these results, the number of analytes was increased up to around 50. A lot of antibiotic compounds were added to the target list as they were considered "priority pharmaceuticals" due to their more potential hazardous effects in the aquatic environment. Data obtained during the second monitoring programme (spring and autumn) corroborated the results from the first one (summer and winter). Analgesics and anti-inflammatories, lipid regulators together with quinolone and macrolide antibiotics were the most abundant pharmaceuticals. Similar median concentrations were found over the year and seasonal variation was not clearly observed. The removal efficiency of pharmaceuticals in the wastewater treatment plants was roughly evaluated. Our results indicated that elimination of most of the selected compounds occurred during the treatment process of influent wastewater, although it was incomplete. Copyright © 2011 Elsevier Ltd. All rights reserved.

Optimization of naltrexone diclofenac codrugs for sustained drug delivery across microneedle-treated skin.

PubMed

Ghosh, Priyanka; Lee, DoMin; Kim, Kyung Bo; Stinchcomb, Audra L

2014-01-01

The purpose of this work was to optimize the structure of codrugs for extended delivery across microneedle treated skin. Naltrexone, the model compound was linked with diclofenac, a nonspecific cyclooxygenase inhibitor to enhance the pore lifetime following microneedle treatment and develop a 7 day transdermal system for naltrexone. Four different codrugs of naltrexone and diclofenac were compared in terms of stability and solubility. Transdermal flux, permeability and skin concentration of both parent drugs and codrugs were quantified to form a structure permeability relationship. The results indicated that all codrugs bioconverted in the skin. The degree of conversion was dependent on the structure, phenol linked codrugs were less stable compared to the secondary alcohol linked structures. The flux of naltrexone across microneedle treated skin and the skin concentration of diclofenac were higher for the phenol linked codrugs. The polyethylene glycol link enhanced solubility of the codrugs, which translated into flux enhancement. The current studies indicated that formulation stability of codrugs and the flux of naltrexone can be enhanced via structure design optimization. The polyethylene glycol linked naltrexone diclofenac codrug is better suited for a 7 day drug delivery system both in terms of stability and drug delivery.

Systems Pharmacology Dissection of the Anti-Inflammatory Mechanism for the Medicinal Herb Folium Eriobotryae

PubMed Central

Zhang, Jingxiao; Li, Yan; Chen, Su-Shing; Zhang, Lilei; Wang, Jinghui; Yang, Yinfeng; Zhang, Shuwei; Pan, Yanqiu; Wang, Yonghua; Yang, Ling

2015-01-01

Inflammation is a hallmark of many diseases like diabetes, cancers, atherosclerosis and arthritis. Thus, lots of concerns have been raised toward developing novel anti-inflammatory agents. Many alternative herbal medicines possess excellent anti-inflammatory properties, yet their precise mechanisms of action are yet to be elucidated. Here, a novel systems pharmacology approach based on a large number of chemical, biological and pharmacological data was developed and exemplified by a probe herb Folium Eriobotryae, a widely used clinical anti-inflammatory botanic drug. The results show that 11 ingredients of this herb with favorable pharmacokinetic properties are predicted as active compounds for anti-inflammatory treatment. In addition, via systematic network analyses, their targets are identified to be 43 inflammation-associated proteins including especially COX2, ALOX5, PPARG, TNF and RELA that are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway, the rheumatoid arthritis pathway and NF-κB signaling pathway. All these demonstrate that the integrated systems pharmacology method provides not only an effective tool to illustrate the anti-inflammatory mechanisms of herbs, but also a new systems-based approach for drug discovery from, but not limited to, herbs, especially when combined with further experimental validations. PMID:25636035

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

PubMed

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.

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

PubMed Central

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

2006-01-01

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 treating asthma may be enhanced through the use of this novel drug delivery system. PMID:16930490

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

PubMed

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 system.

Current Perspectives in NSAID-Induced Gastropathy

PubMed Central

Sinha, Mau; Gautam, Lovely; Shukla, Prakash Kumar; Kaur, Punit; Sharma, Sujata; Singh, Tej P.

2013-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most highly prescribed drugs in the world. Their analgesic, anti-inflammatory, and antipyretic actions may be beneficial; however, they are associated with severe side effects including gastrointestinal injury and peptic ulceration. Though several approaches for limiting these side effects have been adopted, like the use of COX-2 specific drugs, comedication of acid suppressants like proton pump inhibitors and prostaglandin analogs, these alternatives have limitations in terms of efficacy and side effects. In this paper, the mechanism of action of NSAIDs and their critical gastrointestinal complications have been reviewed. This paper also provides the information on different preventive measures prescribed to minimize such adverse effects and analyses the new suggested strategies for development of novel drugs to maintain the anti-inflammatory functions of NSAIDs along with effective gastrointestinal protection. PMID:23576851

Analysis and quantification of self-medication patterns of customers in community pharmacies in southern Chile.

PubMed

Fuentes Albarrán, Katherine; Villa Zapata, Lorenzo

2008-12-01

Self-medication refers to using drugs which have not been prescribed, recommended or controlled by a licensed health care specialist. Marketing, in Chile only admitted for over-the-counter medications, influences the practice of self-medication and extends it to prescription drugs. Thus, a complex self-medication process is started, due to reuse of a previous prescription, using drugs purchased directly at the pharmacy or drugs coming from family first-aid kits. The purpose of this study is to determine the frequency of self-medication, the type of medications involved, the dosages used, and the reasons for this practice. An observation-based cross-sectional study was carried out at three pharmacies belonging to a pharmacy chain in the city of Valdivia (southern Chile). In addition, a previously validated form was used. Customers who requested over-the-counter medications were surveyed to identify the patterns that foster the self-medication practice. Of 909 surveyed customers, 75% self-medicate. Of these, 31% stated that they commonly self-medicate due to suffering from light symptoms, such as headaches (19%), the common cold (8.8%), sore muscles (6.7%), and bone pains (5.3%). The group of medications most requested in this study was nonsteroidal anti-inflammatory drugs (NSAIDs) (33%), with diclofenac sodium being the most used (14%). Influence from other people did not exceed 20% and reusing prior prescriptions reached 46%. There were significant differences when assessing consumer knowledge, reading of information leaflets, and opinions about self-medication at each surveyed pharmacy (P < 0.001). Most consumers at the surveyed pharmacies use medications without proper knowledge of their benefits, treatment method, and duration. Drug dispensing at community pharmacies should include active pharmacist involvement to divulge the sensible use of drugs.

Diclofenac Salts, VIII. Effect of the Counterions on the Permeation through Porcine Membrane from Aqueous Saturated Solutions.

PubMed

Fini, Adamo; Bassini, Glenda; Monastero, Annamaria; Cavallari, Cristina

2012-09-12

The following bases: monoethylamine (EtA), diethylamine (DEtA), triethylamine (TEtA), monoethanolamine (MEA), diethanolamine (DEA), triethanolamine (TEA), pyrrolidine (Py), piperidine (Pp), morpholine (M), piperazine (Pz) and their N-2-hydroxyethyl (HE) analogs were employed to prepare 14 diclofenac salts. The salts were re-crystallized from water in order to obtain forms that are stable in the presence of water. Vertical Franz-type cells with a diffusional surface area of 9.62 cm2 were used to study the permeation of these diclofenac salts from their saturated solutions through an internal pig ear membrane. The receptor compartments of the cells contained 100 mL of phosphate buffer (pH 7.4); a saturated solution (5 mL) of each salt was placed in the donor compartment, thermostated at 37 °C. Aliquots were withdrawn at predetermined time intervals over 8 h and then immediately analyzed by HPLC. Fluxes were determined by plotting the permeated amount, normalized for the membrane surface area versus time. Permeation coefficients were obtained dividing the flux values J by the concentration of the releasing phase-that is, water solubility of each salt. Experimental results show that fluxes could be measured when diclofenac salts with aliphatic amines are released from a saturated aqueous solution. Different chemical species (acid, anion, ion pairs) contribute to permeation of the anti-inflammatory agent even though ion-pairs could be hypothesized to operate to a greater extent. Permeation coefficients were found higher when the counterion contains a ring; while hydroxy groups alone do not appear to play an important role, the ring could sustain permeation, disrupting the organized domains of the membrane.

Diclofenac Salts, VIII. Effect of the Counterions on the Permeation through Porcine Membrane from Aqueous Saturated Solutions

PubMed Central

Fini, Adamo; Bassini, Glenda; Monastero, Annamaria; Cavallari, Cristina

2012-01-01

The following bases: monoethylamine (EtA), diethylamine (DEtA), triethylamine (TEtA), monoethanolamine (MEA), diethanolamine (DEA), triethanolamine (TEA), pyrrolidine (Py), piperidine (Pp), morpholine (M), piperazine (Pz) and their N-2-hydroxyethyl (HE) analogs were employed to prepare 14 diclofenac salts. The salts were re-crystallized from water in order to obtain forms that are stable in the presence of water. Vertical Franz-type cells with a diffusional surface area of 9.62 cm2 were used to study the permeation of these diclofenac salts from their saturated solutions through an internal pig ear membrane. The receptor compartments of the cells contained 100 mL of phosphate buffer (pH 7.4); a saturated solution (5 mL) of each salt was placed in the donor compartment, thermostated at 37 °C. Aliquots were withdrawn at predetermined time intervals over 8 h and then immediately analyzed by HPLC. Fluxes were determined by plotting the permeated amount, normalized for the membrane surface area versus time. Permeation coefficients were obtained dividing the flux values J by the concentration of the releasing phase—that is, water solubility of each salt. Experimental results show that fluxes could be measured when diclofenac salts with aliphatic amines are released from a saturated aqueous solution. Different chemical species (acid, anion, ion pairs) contribute to permeation of the anti-inflammatory agent even though ion-pairs could be hypothesized to operate to a greater extent. Permeation coefficients were found higher when the counterion contains a ring; while hydroxy groups alone do not appear to play an important role, the ring could sustain permeation, disrupting the organized domains of the membrane. PMID:24300300

Insulin Resistance, IGFs and Energy Balance on the Risk of Breast Cancer

DTIC Science & Technology

2005-09-01

50 epidemiologic studies have evaluated Nonsteroidal anti - inflammatory drugs the relationship between OC use and breast cancer risk. Combined OCs...contain ethyl estradiol and a pro- Nonsteroidal anti - inflammatory drugs ( NSAIDs ) gestin. The role of contraceptives in breast cancer risk are among the...arthritis. The term " NSAIDs " ap- Ultraviolet-A (UV-A) radiation from sunlight can plies to all "aspirin-like" drugs that are used clinically suppress

Anti-inflammatory and immunomodulatory properties of Carica papaya.

PubMed

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

2016-07-01

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

Anti-inflammatory effect of Naravelia zeylanica DC via suppression of inflammatory mediators in carrageenan-induced abdominal oedema in zebrafish model.

PubMed

Ekambaram, Sanmuga Priya; Perumal, Senthamil Selvan; Pavadai, Selvaranjani

2017-02-01

The traditional herbal medicines are receiving great importance in the health care sector, especially in Indian system of medicine, i.e, Ayurveda. The present study focused on the standardization of Naravelia zeylanica (L.) DC in terms of its active phytochemicals and to evaluate the anti-inflammatory activity of ethanol extract of N. zeylanica (ENZ). An analytical method was developed by high-performance liquid chromatography for simultaneous determination of β-sitosterol, lupeol and oleanolic acid in ENZ. The cell viability of ENZ was investigated using MTT assay. IC 50 value of ENZ on cell viability was found to be 653.01 µg/mL. To determine the anti-inflammatory activity of ENZ by in vitro method, LPS was added to the macrophage cells to induce activation and ENZ was further added to observe the recovery of inflamed cells. These cells when treated with ENZ, the percentage of viable cells were considerably increased to 74.68%. Loss of mitochondrial membrane potential on treatment with LPS and its recovery by ENZ was studied and found that the number of cells that were damaged on treatment with ENZ + LPS was comparatively lesser than treatment with LPS only. An in vivo anti-inflammatory study was carried out in carrageenan-induced abdominal oedema method in adult zebrafish which revealed the percentage inhibition of inflammation at graded dose levels of ENZ as 23.5% at 100 mg/kg, 62.4% at 200 mg/kg and 87.05% at 350 mg/kg when compared with standard of diclofenac which showed 85% inhibition at 100 mg/kg. The PCR amplification of DNA extracted from adult zebrafish showed that increased concentration of ENZ considerably downregulates the expression of TNF-α and iNOS, the mediators of inflammation.

Anti-inflammatory effects of nitric oxide-releasing hydrocortisone NCX 1022, in a murine model of contact dermatitis

PubMed Central

Hyun, Eric; Bolla, Manlio; Steinhoff, Martin; Wallace, John L; Soldato, Piero del; Vergnolle, Nathalie

2004-01-01

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. 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. 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. 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. 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. PMID:15313880

Anti-inflammatory effects of nitric oxide-releasing hydrocortisone NCX 1022, in a murine model of contact dermatitis.

PubMed

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.

Can Inhibitors of Snake Venom Phospholipases A₂ Lead to New Insights into Anti-Inflammatory Therapy in Humans? A Theoretical Study.

PubMed

Sales, Thaís A; Marcussi, Silvana; da Cunha, Elaine F F; Kuca, Kamil; Ramalho, Teodorico C

2017-10-25

Human phospholipase A₂ ( h PLA₂) of the IIA group (HGIIA) catalyzes the hydrolysis of membrane phospholipids, producing arachidonic acid and originating potent inflammatory mediators. Therefore, molecules that can inhibit this enzyme are a source of potential anti-inflammatory drugs, with different action mechanisms of known anti-inflammatory agents. For the study and development of new anti-inflammatory drugs with this action mechanism, snake venom PLA₂ ( sv PLA₂) can be employed, since the sv PLA₂ has high similarity with the human PLA₂ HGIIA. Despite the high similarity between these secretory PLA₂s , it is still not clear if these toxins can really be employed as an experimental model to predict the interactions that occur with the human PLA₂ HGIIA and its inhibitors. Thus, the present study aims to compare and evaluate, by means of theoretical calculations, docking and molecular dynamics simulations, as well as experimental studies, the interactions of human PLA₂ HGIIA and two sv PLA₂s , Bothrops toxin II and Crotoxin B (BthTX-II and CB, respectively). Our theoretical findings corroborate experimental data and point out that the human PLA₂ HGIIA and sv PLA₂ BthTX-II lead to similar interactions with the studied compounds. From our results, the sv PLA₂ BthTX-II can be used as an experimental model for the development of anti-inflammatory drugs for therapy in humans.

Diclofenac enhances proinflammatory cytokine-induced nitric oxide production through NF-{kappa}B signaling in cultured astrocytes

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

Kakita, Hiroki; Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601; Department of Neonatology, Aichi Human Service Center Central Hospital, 713-8 Kamiya-Cho, Kasugai 480-0392

2009-07-01

Recently, the number of reports of encephalitis/encephalopathy associated with influenza virus has increased. In addition, the use of a non-steroidal anti-inflammatory drug, diclofenac sodium (DCF), is associated with a significant increase in the mortality rate of influenza-associated encephalopathy. Activated astrocytes are a source of nitric oxide (NO), which is largely produced by inducible NO synthase (iNOS) in response to proinflammatory cytokines. Therefore, we investigated whether DCF enhances nitric oxide production in astrocytes stimulated with proinflammatory cytokines. We stimulated cultured rat astrocytes with three cytokines, interleukin-1{beta}, tumor necrosis factor-{alpha} and interferon-{gamma}, and then treated the astrocytes with DCF or acetaminophen (N-acetyl-p-aminophenol:more » APAP). iNOS and NO production in astrocyte cultures were induced by proinflammatory cytokines. The addition of DCF augmented NO production, but the addition of APAP did not. NF-{kappa}B inhibitors SN50 and MG132 inhibited iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. Similarly, NF-{kappa}B p65 Stealth small interfering RNA suppressed iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. LDH activity and DAPI staining showed that DCF induces cell damage in cytokine-stimulated astrocytes. An iNOS inhibitor, L-NMMA, inhibited the cytokine- and DCF-induced cell damage. In conclusion, this study demonstrates that iNOS and NO are induced in astrocyte cultures by proinflammatory cytokines. Addition of DCF further augments NO production. This effect is mediated via NF-{kappa}B signaling and leads to cell damage. The enhancement of DCF on NO production may explain the significant increase in the mortality rate of influenza-associated encephalopathy in patients treated with DCF.« less

The effectiveness of cyclooxygenase-2 inhibitors and evaluation of angiogenesis in the model of experimental colorectal cancer.

PubMed

Gungor, Hilal; Ilhan, Nevin; Eroksuz, Hatice

2018-06-01

Colorectal cancer (CRC) is an important cause of cancer-related deaths worldwide. Early diagnosis and treatment of CRCs are of importance for improving the survival. In the present study, we studied the effects of nonsteroidal anti-inflammatory drugs (NSAIDs)-induced chemopreventive effects on tumor development incidence and angiogenesis in experimental CRC rats. 1,2-Dimethylhydrazine dihydrochloride (DMH) was used as cancer-inducing agent and two NSAIDs (celecoxib and diclofenac) were given orally as chemopreventive agents. Histopathological and immuno histochemical evaluations were performed in colorectal tissue samples, whereas angiogenesis parameters were studied in blood samples. Histopathological examination showed that adenocarcinoma (62.5%), dysplastic changes (31.25%) and inflammattory changes (6.25%) were detected in DMH group, whereas no pathological change was observed in control rats. In treatment groups, there was marked decrease in adenocarcinoma rate (30% and 10%, respectively). A significant increase was detected in MMP-2, MMP-9 levels and MMP-2/TIMP-2 ratio in DMH group as compared with controls and treatment groups. In immunohistochemical evaluations, there was an increase in intensity and extent of staining of MMP-2 and MMP-9 in DMH group as compared to controls and treatment groups. The decrease in celecoxib group was more prominent. Overall, it was concluded that NSAIDs, particularly cyclooxygenase-2 (COX-2) inhibitors, might have a protective effect on CRC development and slow down progression of tumor in a DMH-induced experimental cancer model. One of the possible mechanisms in the chemoprevention of colon cancer seems to be inhibition of angiogenesis by diclofenac and celecoxib. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Diclofenac in municipal wastewater treatment plant: quantification using laser diode thermal desorption--atmospheric pressure chemical ionization--tandem mass spectrometry approach in comparison with an established liquid chromatography-electrospray ionization-tandem mass spectrometry method.

PubMed

Lonappan, Linson; Pulicharla, Rama; Rouissi, Tarek; Brar, Satinder K; Verma, Mausam; Surampalli, Rao Y; Valero, José R

2016-02-12

Diclofenac (DCF), a prevalent non-steroidal anti-inflammatory drug (NSAID) is often detected in wastewater and surface water. Analysis of the pharmaceuticals in complex matrices is often laden with challenges. In this study a reliable, rapid and sensitive method based on laser diode thermal desorption/atmospheric pressure chemical ionization (LDTD/APCI) coupled with tandem mass spectrometry (MS/MS) has been developed for the quantification of DCF in wastewater and wastewater sludge. An established conventional LC-ESI-MS/MS (liquid chromatography-electrospray ionization-tandem mass spectrometry) method was compared with LDTD-APCI-MS/MS approach. The newly developed LDTD-APCI-MS/MS method reduced the analysis time to 12s in lieu of 12 min for LC-ESI-MS/MS method. The method detection limits for LDTD-APCI-MS/MS method were found to be 270 ng L(-1) (LOD) and 1000 ng L(-1) (LOQ). Furthermore, two extraction procedures, ultrasonic assisted extraction (USE) and accelerated solvent extraction (ASE) for the extraction of DCF from wastewater sludge were compared and ASE with 95.6 ± 7% recovery was effective over USE with 86 ± 4% recovery. The fate and partitioning of DCF in wastewater (WW) and wastewater sludge (WWS) in wastewater treatment plant was also monitored at various stages of treatment in Quebec Urban community wastewater treatment plant. DCF exhibited affinity towards WW than WWS with a presence about 60% of DCF in WW in contrary with theoretical prediction (LogKow=4.51). Copyright © 2016 Elsevier B.V. All rights reserved.

Ultrasonic degradation, mineralization and detoxification of diclofenac in water: optimization of operating parameters.

PubMed

Naddeo, V; Belgiorno, V; Kassinos, D; Mantzavinos, D; Meric, S

2010-01-01

The 20 kHz ultrasound-induced degradation of non-steroidal, anti-inflammatory drug diclofenac (DCF) was investigated. Several operating conditions, such as power density (25-100 W/L), substrate concentration (2.5-80 mg/L), initial solution pH (3.5-11), liquid bulk temperature and the type of sparging gas (air, oxygen, argon), were tested concerning their effect on DCF degradation (as assessed measuring absorbance at 276 nm) and hydroxyl radicals generation (as assessed measuring H(2)O(2) concentration). Sample mineralization (in terms of TOC and COD removal), aerobic biodegradability (as assessed by the BOD(5)/COD ratio) and ecotoxicity to Daphnia magna and Artemia salina were followed too. DCF conversion is enhanced at increased applied power densities and liquid bulk temperatures, acidic conditions and in the presence of dissolved air or oxygen. The reaction rate increases with increasing DCF concentration in the range 2.5-5mg/L but it remains constant in the range 40-80 mg/L, indicating different kinetic regimes (i.e. first and zero order, respectively). H(2)O(2) production rates in pure water are higher than those in DCF solutions, implying that decomposition basically proceeds through hydroxyl radical reactions. Mineralization is a slow process as reaction by-products are more stable than DCF to total oxidation; nonetheless, they are also more readily biodegradable. Toxicity to D. magna increases during the early stages of the reaction and then decreases progressively upon degradation of reaction by-products; nevertheless, complete toxicity elimination cannot be achieved at the conditions in question. Neither the original nor the treated DCF samples are toxic to A. salina.

Analysis of analgesic, antipyretic, and nonsteroidal anti-inflammatory drug use in pediatric prescriptions.

PubMed

Ferreira, Tânia R; Lopes, Luciane C

2016-01-01

Data on clinical practice in pediatrics on the use of analgesic, antipyretic, and nonsteroidal anti-inflammatory drugs considering the best available evidence and regulatory-agency approved use are uncertain. This study aimed to determine the frequency of prescription of these drugs according to the best scientific evidence and use approved by regulatory agencies. This was a cross-sectional study of 150 pediatric prescriptions containing analgesic, antipyretic, and nonsteroidal anti-inflammatory drugs, followed by interview with caregivers at 18 locations (nine private drugstores and nine Basic Health Units of the Brazilian Unified Health System). The assessed outcomes included recommended use or use with no contraindication, indications with benefit evidence, and health surveillance agency-approved use. Data were analyzed in electronic databases and the variables were summarized by simple frequency. A total of 164 analgesic, antipyretic, and nonsteroidal anti-inflammatory drugs were prescribed to 150 children aged 1-4 years (38.6%). Dipyrone was included in 82 (54.6%) and ibuprofen in 40 (26.6%) prescriptions. Non-recommended uses were identified in 15% of prescriptions and contraindicated uses were observed in 13.3%. Nimesulide (1.5%) is still prescribed to children younger than 12 years. The dose was incorrect in 74.3% of prescriptions containing dipyrone. Of the 211 reported clinical indications, 56 (26.5%) had no evidence of benefit according to the best available scientific evidence and 66 (31.3%) had indications not approved by the regulatory agencies. There are significant discrepancies between clinical practice and recommended use of analgesic, antipyretic, and nonsteroidal anti-inflammatory drugs in pediatrics. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

The role of anti-inflammatory agents in age-related macular degeneration (AMD) treatment

PubMed Central

Wang, Y; Wang, V M; Chan, C-C

2011-01-01

Although age-related macular degeneration (AMD) is not a classic inflammatory disease like uveitis, inflammation has been found to have an important role in disease pathogenesis and progression. Innate immunity and autoimmune components, such as complement factors, chemokines, cytokines, macrophages, and ocular microglia, are believed to be heavily involved in AMD development. Targeting these specific inflammatory molecules has recently been explored in an attempt to better understand and treat AMD. Although antivascular endothelial growth factor therapy is the first line of defence against neovascular AMD, anti-inflammatory agents such as corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), immunosuppressive agents (eg, methotrexate and rapamycin), and biologics (eg, infliximab, daclizumab, and complement inhibitors) may provide an adjunct or alternative mechanism to suppress the inflammatory processes driving AMD progression. Further investigation is required to evaluate the long-term safety and efficacy of these drugs for both neovascular and non-neovascular AMD. PMID:21183941

Some Novel Mannich Bases of 5-(3,4-Dichlorophenyl)-1,3,4-oxadiazole-2(3H)-one and Their Anti-Inflammatory Activity.

PubMed

Koksal, Meric; Ozkan-Dagliyan, Irem; Ozyazici, Tugce; Kadioglu, Beril; Sipahi, Hande; Bozkurt, Ayhan; Bilge, Suleyman S

2017-09-01

Non-steroidal anti-inflammatory drugs (NSAIDs), which are widely used for the treatment of rheumatic arthritis, pain, and many different types of inflammatory disorders, cause serious gastrointestinal (GI) side effects. The free carboxylic acid group existing on their chemical structure is correlated with GI toxicity related with all routine NSAIDs. Replacing this functional group with the 1,3,4-oxadiazole bioisostere is a generally used strategy to obtain an anti-inflammatory agent devoid of GI side effects. In the present work, a novel group of 5-(3,4-dichlorophenyl)-1,3,4-oxadiazole-2(3H)-one Mannich bases were synthesized and characterized on the basis of IR, 1 H NMR, and elemental analysis results. The target compounds were first tested for cytotoxicity to determine a non-toxic concentration for anti-inflammatory screening. Anti-inflammatory effects of the compounds were evaluated by in vitro lipopolysaccharide (LPS)-induced NO production and in vivo carrageenan footpad edema with ulcerogenic profile. In LPS-induced RAW 264.7 macrophages, most of the compounds showed inhibitory activity on nitrite production while compounds 5a, 5h, and 5j exhibited the best profiles by suppressing the NO production. To evaluate the in vivo anti-inflammatory potency of the compounds, the inflammatory response was quantified by increment in paw size in the carrageenan footpad edema assay. The anti-inflammatory data scoring showed that compounds 5a-d, 5g, and 5j, at the dose of 100 mg/kg, exhibited anti-inflammatory activity, which for compound 5g was comparable to that of the reference drug indomethacin with 53.9% and 55.5% inhibition in 60 and 120 min, respectively. © 2017 Deutsche Pharmazeutische Gesellschaft.

Aerosolized Surfactants, Anti-Inflammatory Drugs, and Analgesics.

PubMed

Willson, Douglas F

2015-06-01

Drug delivery by aerosol may have several advantages over other modes, particularly if the lung is the target organ. Aerosol delivery may allow achievement of higher concentrations while minimizing systemic effects and offers convenience, rapid onset of action, and avoidance of the needles and sterile technique necessary with intravenous drug administration. Aerosol delivery may change the pharmacokinetics of many drugs, however, and an awareness of the caveats of aerosolized drug delivery is mandatory to ensure both safety and adequate drug delivery. This paper discusses the administration of surfactants, anti-inflammatory agents, and analgesics by the aerosol route. Copyright © 2015 by Daedalus Enterprises.

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

PubMed

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.

Analytical strategy for the determination of non-steroidal anti-inflammatory drugs in plasma and improved analytical strategy for the determination of authorized and non-authorized non-steroidal anti-inflammatory drugs in milk by LC-MS/MS.

PubMed

Dowling, Geraldine; Malone, Edward; Harbison, Tom; Martin, Sheila

2010-07-01

A sensitive and selective method for the determination of six non-steroidal anti-inflammatory drugs (NSAIDs) in bovine plasma was developed. An improved method for the determination of authorized and non-authorized residues of 10 non-steroidal anti-inflammatory drugs in milk was developed. Analytes were separated and acquired by high performance liquid chromatography coupled with an electrospray ionisation tandem mass spectrometer (ESI-MS/MS). Target compounds were acidified in plasma, and plasma and milk samples were extracted with acetonitrile and both extracts were purified on an improved solid phase extraction procedure utilising Evolute ABN cartridges. The accuracy of the methods for milk and plasma was between 73 and 109%. The precision of the method for authorized and non-authorized NSAIDs in milk and plasma expressed as % RSD, for the within lab reproducibility was less than 16%. The % RSD for authorized NSAIDs at their associated MRL(s) in milk was less than 10% for meloxicam, flunixin and tolfenamic acid and was less than 25% for hydroxy flunixin. The methods were validated according to Commission Decision 2002/657/EC.

The safety of treatment options available for gout.

PubMed

Schlesinger, Naomi

2017-04-01

Gout is the most common inflammatory arthritis in humans. Gout treatment includes rapid initiation of anti-inflammatory medications for acute attacks and chronically treating with urate lowering drugs as well as chronic anti-inflammatory prophylaxis. Areas covered: This review aims to provide an overview and discussion of the safety concerns of current treatment options available for gout. Expert opinion: Gout is a curable disease with appropriate treatment. The advent of new therapies provides encouraging opportunities to improve gout management. However, clinicians should be aware of some of the safety concerns of medications used to treat acute and chronic gout. When prescribing medications for gout one has to be mindful of the presence of comorbidities commonly affecting gout patients that may affect drug safety and efficacy, especially in the elderly and in patients treated with multiple drugs. The benefits of gout drugs, usually, outweigh their safety concerns. Studies are needed in gout patients with chronic kidney disease and/or cardiovascular disease, so that escalation of dosing /combination of anti-inflammatory drugs needed to suppress gouty inflammation as well as escalation of dosing/combination of urate lowering drugs needed to achieve target serum urate level will lead to better understanding of gout treatment safety issues.

Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis

PubMed Central

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 <6 mo in 1940 to >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

Discovery of Indeno[1,2-c]quinoline Derivatives as Potent Dual Antituberculosis and Anti-Inflammatory Agents.

PubMed

Tseng, Chih-Hua; Tung, Chun-Wei; Wu, Chen-Hsin; Tzeng, Cherng-Chyi; Chen, Yen-Hsu; Hwang, Tsong-Long; Chen, Yeh-Long

2017-06-16

A series of indeno[1,2- c ]quinoline derivatives were designed, synthesized and evaluated for their anti-tuberculosis (anti-TB) and anti-inflammatory activities. The minimum inhibitory concentration (MIC) of the newly synthesized compound was tested against Mycobacterium tuberculosis H 37 R V . Among the tested compounds, ( E )- N '-[6-(4-hydroxypiperidin-1-yl)-11 H -indeno[1,2- c ]quinolin-11-ylidene]isonicotino-hydrazide ( 12 ), exhibited significant activities against the growth of M. tuberculosis (MIC values of 0.96 μg/mL) with a potency approximately equal to that of isoniazid (INH), an anti-TB drug. Important structure features were analyzed by quantitative structure-activity relationship (QSAR) analysis to give better insights into the structure determinants for predicting the anti-TB activity. The anti-inflammatory activity was induced by superoxide anion generation and neutrophil elastase (NE) release using the formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLF)-activated human neutrophils method. Results indicated that compound 12 demonstrated a potent dual inhibitory effect on NE release and superoxide anion generation with IC 50 values of 1.76 and 1.72 μM, respectively. Our results indicated that compound 12 is a potential lead compound for the discovery of dual anti-TB and anti-inflammatory drug candidates. In addition, 6-[3-(hydroxymethyl)piperidin-1-yl]-9-methoxy-11 H -indeno[1,2- c ]quinolin-11-one ( 4g ) showed a potent dual inhibitory effect on NE release and superoxide anion generation with IC 50 values of 0.46 and 0.68 μM, respectively, and is a potential lead compound for the discovery of anti-inflammatory drug candidates.

Dissolution stability studies of suspensions of prolonged-release diclofenac microcapsules prepared by the Wurster process: I. Eudragit-based formulation and possible drug-excipient interaction.

PubMed

Adeyeye, M C; Mwangi, E; Katondo, B; Jain, A; Ichikawa, H; Fukumori, Y

2005-06-01

The aim was to evaluate possible interaction in solid and liquid state of the drug with formulation excipients consequent to very fast drug release of diclofenac-Eudragit prolonged release microcapsules. The microcapsules were prepared by drug layering on calcium carbonate cores and coated with Eudragit RS 30D and L30D-55 as previously reported. Suspension of the microcapsules was prepared using microcrystalline cellulose/sodium carboxymethyl cellulose (Avicel CL-611) as medium. In vitro dissolution testing of the suspension was done, and, based on the dissolution results, possible interaction between diclofenac and Eudragit and Avicel in the medium was studied. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) analyses were performed using 1:1 binary, 1:1:1 ternary mixtures and a ratio equivalent to that in the formulation. The mixtures were prepared by mixing the dispersions--Eudragit RS 30D or L30D-55 with the drug or other components, followed by drying at 60 degrees C for 48 h. Dry mixing was done using the powder equivalents of the polymers, Eudragit RS PO and L100-55, Avicel and calcium carbonate. In vitro dissolution of the suspended microcapsules showed a very fast release after 48 h (T50 = <1 h) compared to the solid microcapsules (T50 = 6 h). DSC curves of the formulation components or microcapsules did not show the characteristic endothermic peak of diclofenac at 287 degrees C. Powder X-ray diffraction of the binary or ternary mixtures of diclofenac and Eudragit polymers indicated reduction, shift or modification of the crystalline peaks of the drug or excipients at 2theta of 12 degrees and 18 degrees , suggestive of interaction. Some changes in drug peak characteristics at 18 degrees and 23 degrees were observed for Avicel/drug mixture, though not significant. The DSC curves of the binary mixture of diclofenac co-dried with liquid forms of Eudragit (i.e. RS 30D or L30D-55) revealed greater interaction compared to the curves of drug and powdered forms of Eudragit (RS PO or L100-55). This was depicted by greater shift in fusion points of the mixtures relative to the drug. However, comparing the RS and L-type Eudragit, the latter generally showed greater interaction with the drug. Interaction between diclofenac and L-type Eudragit polymers can occur in liquid formulations.

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

PubMed

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.

Antibacterial, anti-inflammatory, and bone-regenerative dual-drug-loaded calcium phosphate nanocarriers-in vitro and in vivo studies.

PubMed

Madhumathi, K; Rubaiya, Y; Doble, Mukesh; Venkateswari, R; Sampath Kumar, T S

2018-05-01

A dual local drug delivery system (DDS) composed of calcium phosphate bioceramic nanocarriers aimed at treating the antibacterial, anti-inflammatory, and bone-regenerative aspects of periodontitis has been developed. Calcium-deficient hydroxyapatite (CDHA, Ca/P = 1.61) and tricalcium phosphate (β-TCP) were prepared by microwave-accelerated wet chemical synthesis method. The phase purity of the nanocarriers was confirmed by x-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR), while the transmission electron microscopy (TEM) confirmed their nanosized morphology. CDHA was selected as carrier for the antibiotic (tetracycline) while TCP was chosen as the anti-inflammatory drug (ibuprofen) carrier. Combined drug release profile was studied in vitro from CDHA/TCP (CTP) system and compared with a HA/TCP (BCP) biphasic system. The tetracycline and ibuprofen release rate was 71 and 23% from CTP system as compared to 63 and 20% from BCP system. CTP system also showed a more controlled drug release profile compared to BCP system. Modeling of drug release kinetics from CTP system indicated that the release follows Higuchi model with a non-typical Fickian diffusion profile. In vitro biological studies showed the CTP system to be biocompatible with significant antibacterial and anti-inflammatory activity. In vivo implantation studies on rat cranial defects showed greater bone healing and new bone formation in the drug-loaded CTP system compared to control (no carrier) at the end of 12 weeks. The in vitro and in vivo results suggest that the combined drug delivery platform can provide a comprehensive management for all bone infections requiring multi-drug therapy.

Anti-inflammatory activity of the essential oil obtained from Ocimum basilicum complexed with β-cyclodextrin (β-CD) in mice.

PubMed

Rodrigues, Lindaiane Bezerra; Martins, Anita Oliveira Brito Pereira Bezerra; Ribeiro-Filho, Jaime; Cesário, Francisco Rafael Alves Santana; E Castro, Fyama Ferreira; de Albuquerque, Thaís Rodrigues; Fernandes, Maria Neyze Martins; da Silva, Bruno Anderson Fernandes; Quintans Júnior, Lucindo José; Araújo, Adriano Antunes de Sousa; Menezes, Paula Dos Passos; Nunes, Paula Santos; Matos, Isabella Gonçalves; Coutinho, Henrique Douglas Melo; Goncalves Wanderley, Almir; de Menezes, Irwin Rose Alencar

2017-11-01

Cyclodextrins (CDs) are cyclic oligosaccharides can enhance the bioavailability of drugs. Ocimum basilicum is an aromatic plant found in Brazil used in culinary. The essential oil of this plant presents anti-edematogenic and anti-inflammatory activities in acute and chronic inflammation. The aim of this study was to investigate the anti-inflammatory effects of the essential oil obtained from O. basilicum complexed with β - cyclodextrin (OBEO/β-CD) in mice. The complexation with β-cyclodextrin (β-CD) was performed by different methods and analyzed by differential scanning calorimetry (DSC), thermogravimetry (TG) and scanning electron microscopy (SEM). The anti-inflammatory activity was evaluated using mice models of paw edema induced by carrageenan, dextran, histamine and arachidonic acid (AA); vascular permeability and peritonitis induced by carrageenan and granuloma induced by cotton block introduction. The DSC, TG and SEM analysis indicated that the OBEO was successfully complexed with β-CD. The oral administration of OEOB/β-CD prevented paw edema formation by decreasing vascular permeability in vivo, inhibited leukocyte recruitment to the peritoneal cavity, and inhibited granuloma formation in mice. Our results indicate that conjugation with β-CD improves the anti-inflammatory effects of OBEO in mice models of acute and chronic inflammation, indicating that this complex can be used in anti-inflammatory drug development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pharmacological therapy of spondyloarthritis.

PubMed

Palazzi, Carlo; D'Angelo, Salvatore; Gilio, Michele; Leccese, Pietro; Padula, Angela; Olivieri, Ignazio

2015-01-01

The current pharmacological therapy of spondyloarthritis (SpA) includes several drugs: Non-steroidal anti-inflammatory drugs, corticosteroids, traditional disease-modifying antirheumatic drugs and biologic drugs. A systematic literature search was completed using the largest electronic databases (Medline, Embase and Cochrane), starting from 1995, with the aim to review data on traditional and biologic agents commercialised for SpA treatment. Randomised controlled trials and large observational studies were considered. In addition, studies performed in SpA patients treated with other, still unapproved, drugs (rituximab, anti-IL6 agents, apremilast, IL17 inhibitors and anakinra) were also taken into account. Biologic agents, especially anti-TNF drugs, have resulted in significant progress in improving clinical symptoms and signs, reducing inflammatory features in laboratory tests and imaging findings, and recovering all functional indexes. Anti-TNF drugs have radically changed the evolution of radiographic progression in peripheral joints; the first disappointing data concerning their efficacy on new bone formation of axial SpA has been recently challenged by studies enrolling patients who have been earlier diagnosed and treated. The opportunity to extend the interval of administration or to reduce the doses of anti-TNF agents can favourably influence the costs. Ustekinumab, the first non-anti-TNF biologic drug commercialised for psoriatic arthritis, offers new chances to patients that are unresponsive to anti-TNF.

Ethnopharmacological in vitro studies on Austria's folk medicine—An unexplored lore in vitro anti-inflammatory activities of 71 Austrian traditional herbal drugs☆

PubMed Central

Vogl, Sylvia; Picker, Paolo; Mihaly-Bison, Judit; Fakhrudin, Nanang; Atanasov, Atanas G.; Heiss, Elke H.; Wawrosch, Christoph; Reznicek, Gottfried; Dirsch, Verena M.; Saukel, Johannes; Kopp, Brigitte

2013-01-01

Ethnopharmacological relevance In Austria, like in most Western countries, knowledge about traditional medicinal plants is becoming scarce. Searching the literature concerning Austria's ethnomedicine reveals its scant scientific exploration. Aiming to substantiate the potential of medicinal plants traditionally used in Austria, 63 plant species or genera with claimed anti-inflammatory properties listed in the VOLKSMED database were assessed for their in vitro anti-inflammatory activity. Material and methods 71 herbal drugs from 63 plant species or genera were extracted using solvents of varying polarities and subsequently depleted from the bulk constituents, chlorophylls and tannins to avoid possible interferences with the assays. The obtained 257 extracts were assessed for their in vitro anti-inflammatory activity. The expression of the inflammatory mediators E-selectin and interleukin-8 (IL-8), induced by the inflammatory stimuli tumor necrosis factor alpha (TNF-α) and the bacterial product lipopolysaccharide (LPS) was measured in endothelial cells. The potential of the extracts to activate the nuclear factors PPARα and PPARγ and to inhibit TNF-α-induced activation of the nuclear factor-kappa B (NF-κB) in HEK293 cells was determined by luciferase reporter gene assays. Results In total, extracts from 67 of the 71 assessed herbal drugs revealed anti-inflammatory activity in the applied in vitro test systems. Thereby, 30 could downregulate E-selectin or IL-8 gene expression, 28 were strong activators of PPARα or PPARγ (inducing activation of more than 2-fold at a concentration of 10 µg/mL) and 21 evoked a strong inhibition of NF-κB (inhibition of more than 80% at 10 µg/mL). Conclusion Our research supports the efficacy of herbal drugs reported in Austrian folk medicine used for ailments associated with inflammatory processes. Hence, an ethnopharmacological screening approach is a useful tool for the discovery of new drug leads. PMID:23770053

Recent Advances in Nanoparticle-Mediated Delivery of Anti-Inflammatory Phytocompounds

PubMed Central

Conte, Raffaele; Marturano, Valentina; Peluso, Gianfranco; Calarco, Anna; Cerruti, Pierfrancesco

2017-01-01

Phytocompounds have been used in medicine for decades owing to their potential in anti-inflammatory applications. However, major difficulties in achieving sustained delivery of phyto-based drugs are related to their low solubility and cell penetration, and high instability. To overcome these disadvantages, nanosized delivery technologies are currently in use for sustained and enhanced delivery of phyto-derived bioactive compounds in the pharmaceutical sector. This review focuses on the recent advances in nanocarrier-mediated drug delivery of bioactive molecules of plant origin in the field of anti-inflammatory research. In particular, special attention is paid to the relationship between structure and properties of the nanocarrier and phytodrug release behavior. PMID:28350317

The laser desorption/laser ionization mass spectra of some anti-inflammatory drugs

NASA Astrophysics Data System (ADS)

Milnes, John; Rogers, Kevin; Jones, Sian; Gormally, John

1994-03-01

The IR laser desorption/ultraviolet laser ionization time-of-flight mass spectra are reported for the anti-inflammatory drugs indomethacin, acemetacin, ibuprofen, flurbiprofen, diflunisal and mefenamic acid. It is found that the six compounds can be readily ionized by two photon absorption at a fixed wavelength of 266 nm. Mass spectra have been obtained under conditions of high ionizing irradiance and the observed fragmentation behaviour is discussed.

Anti-inflammatory and anti-oxidant properties of Curcuma longa (turmeric) versus Zingiber officinale (ginger) rhizomes in rat adjuvant-induced arthritis.

PubMed

Ramadan, Gamal; Al-Kahtani, Mohammed Ali; El-Sayed, Wael Mohamed

2011-08-01

Turmeric (rich in curcuminoids) and ginger (rich in gingerols and shogaols) rhizomes have been widely used as dietary spices and to treat different diseases in Ayurveda/Chinese medicine since antiquity. Here, we compared the anti-inflammatory/anti-oxidant activity of these two plants in rat adjuvant-induced arthritis (AIA). Both plants (at dose 200 mg/kg body weight) significantly suppressed (but with different degrees) the incidence and severity of arthritis by increasing/decreasing the production of anti-inflammatory/pro-inflammatory cytokines, respectively, and activating the anti-oxidant defence system. The anti-arthritic activity of turmeric exceeded that of ginger and indomethacin (a non-steroidal anti-inflammatory drug), especially when the treatment started from the day of arthritis induction. The percentage of disease recovery was 4.6-8.3% and 10.2% more in turmeric compared with ginger and indomethacin (P < 0.05), respectively. The present study proves the anti-inflammatory/anti-oxidant activity of turmeric over ginger and indomethacin, which may have beneficial effects against rheumatoid arthritis onset/progression as shown in AIA rat model.

Ontology-based systematic representation and analysis of traditional Chinese drugs against rheumatism.

PubMed

Liu, Qingping; Wang, Jiahao; Zhu, Yan; He, Yongqun

2017-12-21

Rheumatism represents any disease condition marked with inflammation and pain in the joints, muscles, or connective tissues. Many traditional Chinese drugs have been used for a long time to treat rheumatism. However, a comprehensive information source for these drugs is still missing, and their anti-rheumatism mechanisms remain unclear. An ontology for anti-rheumatism traditional Chinese drugs would strongly support the representation, analysis, and understanding of these drugs. In this study, we first systematically collected reported information about 26 traditional Chinese decoction pieces drugs, including their chemical ingredients and adverse events (AEs). By mostly reusing terms from existing ontologies (e.g., TCMDPO for traditional Chinese medicines, NCBITaxon for taxonomy, ChEBI for chemical elements, and OAE for adverse events) and making semantic axioms linking different entities, we developed the Ontology of Chinese Medicine for Rheumatism (OCMR) that includes over 3000 class terms. Our OCMR analysis found that these 26 traditional Chinese decoction pieces are made from anatomic entities (e.g., root and stem) from 3 Bilateria animals and 23 Mesangiospermae plants. Anti-inflammatory and antineoplastic roles are important for anti-rheumatism drugs. Using the total of 555 unique ChEBI chemical entities identified from these drugs, our ChEBI-based classification analysis identified 18 anti-inflammatory, 33 antineoplastic chemicals, and 9 chemicals (including 3 diterpenoids and 3 triterpenoids) having both anti-inflammatory and antineoplastic roles. Furthermore, our study detected 22 diterpenoids and 23 triterpenoids, including 16 pentacyclic triterpenoids that are likely bioactive against rheumatism. Six drugs were found to be associated with 184 unique AEs, including three AEs (i.e., dizziness, nausea and vomiting, and anorexia) each associated with 5 drugs. Several chemical entities are classified as neurotoxins (e.g., diethyl phthalate) and allergens (e.g., eugenol), which may explain the formation of some TCD AEs. The OCMR could be efficiently queried for useful information using SPARQL scripts. The OCMR ontology was developed to systematically represent 26 traditional anti-rheumatism Chinese drugs and their related information. The OCMR analysis identified possible anti-rheumatism and AE mechanisms of these drugs. Our novel ontology-based approach can also be applied to systematic representation and analysis of other traditional Chinese drugs.

The Role of Th17 in Neuroimmune Disorders: A Target for CAM Therapy. Part III.

PubMed

Vojdani, Aristo; Lambert, Jama; Kellermann, Gottfried

2011-01-01

Abundant research has mapped the inflammatory pathways leading to autoimmunity and neuroinflammatory disorders. The latest T helper to be identified, Th17, through its proinflammatory cytokine IL-17, plays a pathogenic role in many inflammatory conditions. Today, healthcare providers have a wealth of anti-inflammatory agents from which to choose. On one hand, pharmaceutical companies market brand-name drugs direct to the public and physicians. Medical botanical knowledge, on the other hand, has been passed down from generation to generation. The demands for natural healing therapies have brought corresponding clinical and laboratory research studies to elucidate the medicinal properties of alternative practices. With a variety of options, it can be difficult to pinpoint the proper anti-inflammatory agent for each case presented. In this review, the authors highlight a vast array of anti-inflammatory medicaments ranging from drugs to vitamins and from botanicals to innate molecules. This compilation may serve as a guide for complimentary and alternative healthcare providers who need to target neuroinflammation driven by Th17 and its inflammatory cytokine IL-17. By understanding the mechanisms of anti-inflammatory agents, CAM practitioners can tailor therapeutic interventions to fit the needs of the patient, thereby providing faster relief from inflammatory complaints.

Immunomodulatory therapies for acute pancreatitis

PubMed Central

Li, Jing; Yang, Wen-Juan; Huang, Lu-Ming; Tang, Cheng-Wei

2014-01-01

It is currently difficult for conventional treatments of acute pancreatitis (AP), which primarily consist of anti-inflammatory therapies, to prevent the progression of AP or to improve its outcome. This may be because the occurrence and progression of AP, which involves various inflammatory cells and cytokines, includes a series of complex immune events. Considering the complex immune system alterations during the course of AP, it is necessary to monitor the indicators related to immune cells and inflammatory mediators and to develop more individualized interventions for AP patients using immunomodulatory therapy. This review discusses the recent advances in immunomodulatory therapies. It has been suggested that overactive inflammatory responses should be inhibited and excessive immunosuppression should be avoided in the early stages of AP. The optimal duration of anti-inflammatory therapy may be shorter than previously expected (< 24 h), and appropriate immunostimulatory therapies should be administered during the period from the 3rd d to the 14th d in the course of AP. A combination therapy of anti-inflammatory and immune-stimulating drugs would hopefully constitute an alternative to anti-inflammatory drug monotherapy. Additionally, the detection of the genotypes of critical inflammatory mediators may be useful for screening populations of AP patients at high risk of severe infections to enable the administration of early interventions to improve their prognosis. PMID:25493006

Natural product HTP screening for attenuation of cytokine-induced neutrophil chemo attractants (CINCs) and NO2- in LPS/IFNγ activated glioma cells.

PubMed

Mazzio, Elizabeth A; Bauer, David; Mendonca, Patricia; Taka, Equar; Soliman, Karam F A

2017-01-15

Chronic and acute central nervous system (CNS) inflammation are contributors toward neurological injury associated with head trauma, stroke, infection, Parkinsons or Alzheimers disease. CNS inflammatory illnesses can also contribute toward risk of developing glioblastoma multiforme (GBM). With growing public interest in complementary and alternative medicines (CAMs), we conduct a high throughput (HTP) screening of >1400 natural herbs, plants and over the counter (OTC) products for anti-inflammatory effects on lipopolysaccharide (LPS)/interferon gamma (IFNγ) activated C6 glioma cells. Validation studies were performed showing a pro-inflammatory profile of [LPS 3 µg/ml/ IFNγ 3 ng/ml] consistent with greater release [>8.5 fold] of MCP-1, NO2-, cytokine-induced neutrophil chemo-attractants (CINC) 1, CINC 2a and CINC3. The data show no changes to the following, IL-13, TNF-a, fracktaline, leptin, LIX, GM-CSF, ICAM1, L-Selectin, activin A, agrin, IL-1α, MIP-3a, B72/CD86, NGF, IL-1b, MMP-8, IL-1 R6, PDGF-AA, IL-2, IL-4, prolactin R, RAGE, IL-6, Thymus Chemokine-1, CNTF,IL-10 or TIMP-1. A HTP screening was conducted, where we employ an in vitro efficacy index (iEI) defined as the ratio of toxicity (LC 50 )/anti-inflammatory potency (IC 50 ). The iEI was precautionary to ensure biological effects were occurring in fully viable cells (ratio > 3.8) independent of toxicity. Using NO2- as a guideline molecule, the data show that 1.77% (25 of 1410 tested) had anti-inflammatory effects with iEI ratios >3.8 and IC 50 s <250µg/ml. These include reference drugs (hydrocortisone, dexamethasone N6-(1-iminoethyl)-l-lysine and NSAIDS: diclofenac, tolfenamic acid), a histone deacetylase inhibitor (apicidin) and the following natural products; Ashwaganda (Withania somnifera), Elecampagne Root (Inula helenium), Feverfew (Tanacetum parthenium), Green Tea (Camellia sinensis), Turmeric Root (Curcuma longa) Ganthoda (Valeriana wallichii), Tansy (Tanacetum vulgare), Maddar Root (Rubia tinctoria), Red Sandle wood (Pterocarpus santalinus), Bay Leaf (Laurus nobilis, Lauraceae), quercetin, cardamonin, fisetin, EGCG, biochanin A, galangin, apigenin and curcumin. The herb with the largest iEI was Ashwaganda where the IC 50 /LC 50 was 11.1/>1750.0μg/ml, and the compound with the greatest iEI was quercetin where the IC 50 /LC 50 was 10.0/>363.6μg/ml. These substances also downregulate the production of iNOS expression and attenuate CINC-3 release. In summary, this HTP screening provides guideline information about the efficacy of natural products that could prevent inflammatory processes associated with neurodegenerative disease and aggressive glioma tumor growth. Copyright © 2016 Elsevier B.V. All rights reserved.

A Comprehensive Review of Non-Steroidal Anti-Inflammatory Drug Use in The Elderly

PubMed Central

Wongrakpanich, Supakanya; Wongrakpanich, Amaraporn; Melhado, Katie; Rangaswami, Janani

2018-01-01

NSAIDs, non-steroidal anti-inflammatory drugs, are one of the most commonly prescribed pain medications. It is a highly effective drug class for pain and inflammation; however, NSAIDs are known for multiple adverse effects, including gastrointestinal bleeding, cardiovascular side effects, and NSAID induced nephrotoxicity. As our society ages, it is crucial to have comprehensive knowledge of this class of medication in the elderly population. Therefore, we reviewed the pharmacodynamics and pharmacokinetics, current guidelines for NSAIDs use, adverse effect profile, and drug interaction of NSAIDs and commonly used medications in the elderly. PMID:29392089

In-vitro assessment and pharmacodynamics of nimesulide incorporated Aloe vera transemulgel.

PubMed

Vandana, K R; Yalavarthi, Prasanna R; Sundaresan, C R; Sriramaneni, Raghava N; Vadlamudi, Harini C

2014-06-01

The aim of the investigation was to prepare nimesulide emulsion for incorporation in Aloe vera gel base to formulate 'nimesulide - Aloe vera transemulgel' (NAE) and to carryout in-vitro assessment and in-vivo anti-inflammatory studies of the product. Although the use of nimesulide is banned for oral administration, due to its potential for inducing hepatotoxicity and thrombocytopenia, the use of nimesulide for topical delivery is prominent in the treatment of many inflammatory conditions including rheumatoid arthritis. The drug loading capacity of transdermal gels is low for hydrophobic drugs such as nimesulide. Nimesulide can be effectively incorporated into emulgels (a combination of emulsion and gel). Aloe vera has a mild anti-inflammatory effect and in the present study Aloe vera gel was formulated and used as a gel base to prepare NAE. The emulgels thus prepared were evaluated for viscosity, pH, in-vitro permeation, stability and skin irritation test. In-vivo anti-inflammatory studies were performed using carrageenan induced hind paw edema method in Wistar rats. The results were compared with that of commercial nimesulide gel (CNG). From the in-vitro studies, effective permeation of nimesulide from NAE (53.04 %) was observed compared to CNG (44.72 %) at 30 min indicating better drug release from NAE. Topical application of the emulgel found no skin irritation. Stability studies proved the integrity of the formulation. The percentage of inhibition of edema was highest for the prepared NAE (67.4 % inhibition after 240 min) compared to CNG (59.6 %). From our results, it was concluded that the Aloe vera gel acts as an effective gel base to prepare nimesulide emulgel with high drug loading capacity (86.4 % drug content) compared to CNG (70.5 % drug content) with significant anti-inflammatory effect.

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

PubMed

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.

In vitro analysis of metabolic predisposition to drug hypersensitivity reactions.

PubMed Central

Riley, R J; Leeder, J S

1995-01-01

Idiosyncratic hypersensitivity reactions may account for up to 25% of all adverse reactions, and pose a constant problem to physicians because of their unpredictable nature, potentially fatal outcome and resemblance to other disease processes. Current understanding of how drug allergy arises is based largely on the hapten hypothesis: since most drugs are not chemically reactive per se, they must be activated metabolically to reactive species which may become immunogenic through interactions with cellular macromolecules. The role of drug metabolism is thus pivotal to the hapten hypothesis both in activation of the parent compound and detoxification of the reactive species. Although conjugation reactions may occasionally produce potential immunogens (for example, the generation of acylglucuronides from non-steroidal anti-inflammatory drugs such as diclofenac), bioactivation is catalysed most frequently by cytochrome P450 (P450) enzymes. The multifactorial nature of hypersensitivity reactions, particularly the role of often unidentified, reactive drug metabolites in antigen generation, has hampered the routine diagnosis of these disorders by classical immunological methods designed to detect circulating antibodies or sensitized T cells. Similarly, species differences in drug metabolism and immune system regulation have largely precluded the establishment of appropriate animal models with which to examine the immunopathological mechanisms of these toxicities. However, the combined use of in vitro toxicity assays incorporating human tissues and in vivo phenotyping (or, ultimately, in vitro genotyping) methods for drug detoxification pathways may provide the metabolic basis for hypersensitivity reactions to several drugs. This brief review highlights recent efforts to unravel the bases for hypersensitivity reactions to these therapeutic agents (which include anticonvulsants and sulphonamides) using drug metabolism and immunochemical approaches. In particular, examples are provided which illustrate breakthroughs in the identification of the chemical nature of the reactive metabolites which become bound to cellular macromolecules, the enzyme systems responsible for their generation and (possibly) detoxification, and the target proteins implicated in the subsequent immune response. PMID:7813099

Synthesis, analgesic, anti-inflammatory and anti-ulcerogenic activities of certain novel Schiff's bases as fenamate isosteres.

PubMed

Alafeefy, Ahmed M; Bakht, Mohammed A; Ganaie, Majid A; Ansarie, Mohd N; El-Sayed, Nahed N; Awaad, Amani S

2015-01-15

A series of certain novel Schiff bases as fenamate isosteres (VI:a-k) were synthesized to locate analgesic, anti-inflammatory agent with minimal ulcerogenic potential. The structures of the newly synthesized compounds were elucidated on the basis of their elemental analysis as well as IR, and NMR and mass spectroscopic data. All the compounds were evaluated for their anti-inflammatory activity by carrageenan induced paw oedema method. The compounds possessing good anti-inflammatory activity were further tested for analgesic, ulcerogenic, lipid peroxidation potentials and liver toxicity. Compounds (VI-c), (VI-f), (VI-h) and (VI-i) showed the best anti-inflammatory and significant analgesic activities at doses comparable to that of the standard drug Indomethacin. However, compounds (VI-c) and (VI-f) could be considered the most potent anti-inflammatory and analgesic molecules with maximum reduction in gastro-intestinal ulceration with no hepatocyte necrosis or liver degeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

IL-6 inhibitors for treatment of rheumatoid arthritis: past, present, and future.

PubMed

Kim, Go Woon; Lee, Na Ra; Pi, Ryo Han; Lim, Yee Seul; Lee, Yu Mi; Lee, Jong Min; Jeong, Hye Seung; Chung, Sung Hyun

2015-01-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by polyarthritis. Numerous agents with varying mechanisms are used in the treatment of RA, including non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, and some biological agents. Studies to uncover the cause of RA have recently ended up scrutinizing the importance of pro-inflammatory cytokine such as tumor necrosis factor α (TNF-α) and interleukin (IL)-6 in the pathogenesis of RA. TNF-α inhibitors are increasingly used to treat RA patients who are non-responsive to conventional anti-arthritis drugs. Despite its effectiveness in a large patient population, up to two thirds of RA patients are found to be partially responsive to anti-TNF therapy. Therefore, agents targeting IL-6 such as tocilizumab (TCZ) attracted significant attention as a promising agent in RA treatment. In this article, we review the mechanism of anti-IL-6 in the treatment of RA, provide the key efficacy and safety data from clinical trials of approved anti-IL-6, TCZ, as well as six candidate IL-6 blockers including sarilumab, ALX-0061, sirukumab, MEDI5117, clazakizumab, and olokizumab, and their future perspectives in the treatment of RA.

Encouraging physician appropriate prescribing of non-steroidal anti-inflammatory therapies: protocol of a randomized controlled trial [ISRCTN43532635

PubMed Central

Doupe, Malcolm; Katz, Alan; Kvern, Brent; Manness, Lori-Jean; Metge, Colleen; Thomson, Glen TD; Morrison, Laura; Rother, Kat

2004-01-01

Background Traditional non-steroidal anti-inflammatory drugs (NSAIDs) are a widely used class of therapy in the treatment of chronic pain and inflammation. The drugs are effective and can be relatively inexpensive thanks to available generic versions. Unfortunately the traditional NSAIDs are associated with gastrointestinal complications in a small proportion of patients, requiring costly co-therapy with gastro-protective agents. Recently, a new class of non-steroidal anti-inflammatory agents known as coxibs has become available, fashioned to be safer than the traditional NSAIDs but priced considerably higher than the traditional generics. To help physicians choose appropriately and cost-effectively from the expanded number of anti-inflammatory therapies, scientific bodies have issued clinical practice guidelines and third party payers have published restricted reimbursement policies. The objective of this study is to determine whether an educational intervention can prompt physicians to adjust their prescribing in accordance with these expert recommendations. Methods This is an ongoing, randomized controlled trial. All primary care physicians in Manitoba, Canada have been randomly assigned to a control group or an intervention study group. The educational intervention being evaluated consists of an audit and feedback mechanism combined with optional participation in a Continuing Medical Education interactive workshop. The primary outcome of the study is the change, from pre-to post-intervention, in physicians' appropriate prescribing of non-steroidal anti-inflammatory therapies for patients requiring chronic treatment. Three classes of non-steroidal anti-inflammatory therapies have been identified: coxib therapy, traditional NSAID monotherapy, and traditional NSAID therapy combined with gastro-protective agents. Appropriate prescribing is defined based on international clinical practice guidelines and the provincial drug reimbursement policy in Manitoba. PMID:15327694

Assessment of the Presence of Pharmaceutical Compounds in Seawater Samples from Coastal Area of Gran Canaria Island (Spain)

PubMed Central

Afonso-Olivares, Cristina; Torres-Padrón, Mª Esther; Sosa-Ferrera, Zoraida; Santana-Rodríguez, José Juan

2013-01-01

This study presents the evaluation of seven pharmaceutical compounds belonging to different commonly used therapeutic classes in seawater samples from coastal areas of Gran Canaria Island. The target compounds include atenolol (antihypertensive), acetaminophen (analgesic), norfloxacin and ciprofloxacin (antibiotics), carbamazepine (antiepileptic) and ketoprofen and diclofenac (anti-inflammatory). Solid phase extraction (SPE) was used for the extraction and preconcentration of the samples, and liquid chromatography tandem mass spectrometry (LC-MS/MS) was used for the determination of the compounds. Under optimal conditions, the recoveries obtained were in the range of 78.3% to 98.2%, and the relative standard deviations were less than 11.8%. The detection and quantification limits of the method were in the ranges of 0.1–2.8 and 0.3–9.3 ng·L−1, respectively. The developed method was applied to evaluate the presence of these pharmaceutical compounds in seawater from four outfalls in Gran Canaria Island (Spain) during one year. Ciprofloxacin and norfloxacin were found in a large number of samples in a concentration range of 9.0–3551.7 ng·L−1. Low levels of diclofenac, acetaminophen and ketoprofen were found sporadically. PMID:27029304

Effect of Nonsteroidal Anti-inflammatory Drug as an Oral Premedication on the Anesthetic Success of Inferior Alveolar Nerve Block in Treatment of Irreversible Pulpitis: A Systematic Review with Meta-analysis and Trial Sequential Analysis.

PubMed

Nagendrababu, Venkateshbabu; Pulikkotil, Shaju Jacob; Veettil, Sajesh K; Teerawattanapong, Nattawat; Setzer, Frank C

2018-06-01

Successful anesthesia with an inferior alveolar nerve block (IANB) is imperative for treating patients with irreversible pulpitis in mandibular teeth. This systematic review assessed the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) as oral premedications on the success of IANBs in irreversible pulpitis. Three databases were searched to identify randomized clinical trials (RCTs) published up until September 2017. Retrieved RCTs were evaluated using the revised Cochrane Risk of Bias Tool. The primary efficacy outcome of interest was the success rate of IANB anesthesia. Meta-analytic estimates (risk ratio [RR] with 95% confidence intervals [CIs]) performed using a random effects model and publication bias determined using funnel plot analysis were assessed. Random errors were evaluated with trial sequential analyses, and the quality of evidence was appraised using a Grading of Recommendations, Assessment, Development and Evaluation approach. Thirteen RCTs (N = 1034) were included. Eight studies had low risk of bias. Statistical analysis of good-quality RCTs showed a significant beneficial effect of any NSAID in increasing the anesthetic success of IANBs compared with placebo (RR = 1.92; 95% CI, 1.55-2.38). Subgroup analyses showed a similar beneficial effect for ibuprofen, diclofenac, and ketorolac (RR = 1.83 [95% CI, 1.43-2.35], RR = 2.56 [95% CI, 1.46-4.50], and RR = 2.07 [95% CI, 1.47-2.90], respectively). Dose-dependent ibuprofen >400 mg/d (RR = 1.85; 95% CI, 1.39-2.45) was shown to be effective; however, ibuprofen ≤400 mg/d showed no association (RR = 1.78; 95% CI, 0.90-3.55). TSA confirmed conclusive evidence for a beneficial effect of NSAIDs for IANB premedication. The Grading of Recommendations, Assessment, Development and Evaluation approach did not reveal any concerns regarding the quality of the results. Oral premedication with NSAIDs and ibuprofen (>400 mg/d) increased the anesthetic success of IANBs in patients with irreversible pulpitis. Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Safety and efficacy of long-term esomeprazole 20 mg in Japanese patients with a history of peptic ulcer receiving daily non-steroidal anti-inflammatory drugs.

PubMed

Sugano, Kentaro; Kinoshita, Yoshikazu; Miwa, Hiroto; Takeuchi, Tsutomu

2013-03-26

Non-steroidal anti-inflammatory drugs (NSAIDs) are an effective and common treatment for chronic pain disorders, but long-term use is associated with risk of potentially life-threatening gastrointestinal adverse events (AEs). The proton pump inhibitor esomeprazole has been found to be effective for gastroprotection in NSAID users, but few long-term studies have been conducted in Japan. This was an open-label, multicentre, single-arm, prospective 1-year study of treatment with esomeprazole (20 mg once daily) in Japanese patients (aged ≥20 years) with endoscopic evidence of previous peptic ulcer and receiving daily oral NSAID therapy (at a stable dose) for a chronic condition. Eligibility was not dictated by type of oral NSAID. The primary objective was to determine long-term safety and tolerability of esomeprazole. Efficacy for prevention of peptic ulcers was also determined (Kaplan-Meier method). All statistical analyses were descriptive. A total of 130 patients (73.1% women, mean age 62.1 years, 43.8% Helicobacter pylori-positive) received treatment with esomeprazole in addition to long-term NSAID therapy (most commonly for rheumatoid arthritis [n=42] and osteoarthritis [n=34]). Loxoprofen, meloxicam and diclofenac were the most commonly used NSAIDs; cyclo-oxygenase (COX)-2 selective agents were used by 16.2% of patients (n=21). Long-term compliance with esomeprazole (capsule counts) was >75% for the majority of patients. Although 16.9% of patients (n=22) experienced AEs judged to be possibly related to treatment with esomeprazole, they were mostly mild and transient. The most commonly reported possibly treatment-related AEs were abnormal hepatic function, headache, increased γ-glutamyltransferase levels and muscle spasms (2 patients each). Overall, 95.9% (95% confidence interval: 92.3, 99.4) of patients remained ulcer free at 1 year. Long-term treatment with esomeprazole (20 mg once daily) is well tolerated and efficacious for preventing ulcer recurrence in Japanese NSAID users with a history of peptic ulcer. ClinicalTrials.gov identifier NCT00595517.

Safety and efficacy of long-term esomeprazole 20 mg in Japanese patients with a history of peptic ulcer receiving daily non-steroidal anti-inflammatory drugs

PubMed Central

2013-01-01

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are an effective and common treatment for chronic pain disorders, but long-term use is associated with risk of potentially life-threatening gastrointestinal adverse events (AEs). The proton pump inhibitor esomeprazole has been found to be effective for gastroprotection in NSAID users, but few long-term studies have been conducted in Japan. Methods This was an open-label, multicentre, single-arm, prospective 1-year study of treatment with esomeprazole (20 mg once daily) in Japanese patients (aged ≥20 years) with endoscopic evidence of previous peptic ulcer and receiving daily oral NSAID therapy (at a stable dose) for a chronic condition. Eligibility was not dictated by type of oral NSAID. The primary objective was to determine long-term safety and tolerability of esomeprazole. Efficacy for prevention of peptic ulcers was also determined (Kaplan-Meier method). All statistical analyses were descriptive. Results A total of 130 patients (73.1% women, mean age 62.1 years, 43.8% Helicobacter pylori-positive) received treatment with esomeprazole in addition to long-term NSAID therapy (most commonly for rheumatoid arthritis [n=42] and osteoarthritis [n=34]). Loxoprofen, meloxicam and diclofenac were the most commonly used NSAIDs; cyclo-oxygenase (COX)-2 selective agents were used by 16.2% of patients (n=21). Long-term compliance with esomeprazole (capsule counts) was >75% for the majority of patients. Although 16.9% of patients (n=22) experienced AEs judged to be possibly related to treatment with esomeprazole, they were mostly mild and transient. The most commonly reported possibly treatment-related AEs were abnormal hepatic function, headache, increased γ-glutamyltransferase levels and muscle spasms (2 patients each). Overall, 95.9% (95% confidence interval: 92.3, 99.4) of patients remained ulcer free at 1 year. Conclusion Long-term treatment with esomeprazole (20 mg once daily) is well tolerated and efficacious for preventing ulcer recurrence in Japanese NSAID users with a history of peptic ulcer. Trial registration ClinicalTrials.gov identifier NCT00595517. PMID:23530709

Insight in modulation of inflammation in response to diclofenac intervention: a human intervention study

USDA-ARS?s Scientific Manuscript database

Background. Chronic systemic low-grade inflammation in obese subjects is associated with health complications including cardiovascular diseases, insulin resistance and diabetes. Reducing inflammatory responses may reduce these risks. However, available markers of inflammatory status inadequately des...

Non-steroidal anti-inflammatory drugs. Current status and rational therapeutic use.

PubMed

Hart, F D; Huskisson, E C

1984-03-01

Aspirin (acetylsalicylic acid), the first of the NSAIDs (introduced in 1899), was initially never referred to as an anti-inflammatory agent. It was the advent of cortisone in 1949 that demonstrated dramatically that corticosteroids had anti-inflammatory properties and the term 'non-steroidal anti-inflammatory drug' was first used when phenylbutazone was introduced 3 years later. Since then, the NSAIDs have proliferated. There is to date no good evidence that they halt progression of rheumatoid disease, but by easing pain and diminishing swelling they make life much easier in osteoarthrosis, rheumatoid arthritis and many other types of arthritis, and are the drugs of first choice in acute gout. Their mode (or modes) of action are obscure and though inhibition of cyclo-oxygenase (prostaglandin synthetase) is clearly important, other mechanisms are also involved. The assessment of the anti-inflammatory action of these agents has received considerable attention in clinical trials because, whatever their action may be in experimental animal models, their action in inflamed joints in human patients must be ascertained, since there may be little parallel between the two. Different experimental animal models give different results with various agents and often bear little relation to their therapeutic action in man. No attempt has been made here to review in depth all the NSAIDs that have appeared since 1952. All have anti-inflammatory and analgesic activity and all can cause gastrointestinal side effects, though effectiveness and toxicity vary from drug to drug and patient to patient, there being very great interpatient variability. Non-reactors, patients who apparently fail to respond to certain agents, need further study, for it seems that these subjects may metabolise these agents differently from others. Considerable ingenuity has been shown not only in evolving new NSAIDs but in finding new ways of administering them. The number and variety of NSAIDs in their various forms varies greatly from country to country, depending largely on the regulatory bodies of those countries. In the meantime, the search for a better, less toxic compound continues with the hope that one may be found which has a deeper and more basic action on the underlying disease process.

Optimization of diclofenac sodium profile from halloysite nanotubules.

PubMed

Krejčová, Kateřina; Deasy, Patrick B; Rabišková, Miloslava

2013-04-01

Halloysite, aluminosilicate clay with the particle shape of multilayered hollow nanotubes, used in various non-medical applications, e.g. in ceramic industry, was discovered for pharmaceutical purposes in recent years. Several drugs of hydrophilic and lipophilic nature have been successfully encapsulated into halloysite tubules in order to modify their dissolution profile. The main goal of this experiment was to optimize the dissolution profile of diclofenac sodium - a drug with problematic solubility - from halloysite tubules using various polymers. Loading of the drug together with povidone or Eudragit® RS did not lead to drug burst effect reduction and its slower dissolution. In the case of povidone, drug improved wettability and solubilization rather than viscosity increasing expectations were observed. Eudragit® RS formed a solid dispersion with diclofenac sodium and thus the solvent/drug solution penetration through the polymer and not the drug solubility was the dissolution rate limiting factor. Reduction of the burst effect and further prolongation of drug release was achieved by coating the drug-loaded halloysite with chitosan. This formulation exhibited a diffusion-controlled prolonged release following Higuchi kinetic model.

Synthesis and pharmacological evaluation of polyfunctional benzimidazole-NSAID chimeric molecules combining anti-inflammatory, immunomodulatory and antioxidant activities.

PubMed

Bansal, Yogita; Silakari, Om

2014-11-01

Polyfunctional compounds comprise a novel class of therapeutic agents for treatment of multifactorial diseases. The present study reports a series of benzimidazole-non-steroidal anti-inflammatory drugs (NSAIDs) conjugates (1-10) as novel polyfunctional compounds synthesized in the presence of orthophosphoric acid. The compounds were evaluated for anti-inflammatory (carageenan-induced paw edema model), immunomodulatory (direct haemagglutination test and carbon clearance index models), antioxidant (in vitro and in vivo) and for ulcerogenic effects. Each of the compound has retained the anti-inflammatory activity of the corresponding parent NSAID while exhibiting significantly reduced gastric ulcers. Additionally, the compounds are found to possess potent immunostimulatory and antioxidant activities. The compound 8 was maximally potent (antibody titre value 358.4 ± 140.21, carbon clearance index 0.053 ± 0.002 and antioxidant EC50 value 0.03 ± 0.006). These compounds, exhibiting such multiple pharmacological activities, can be taken as lead for the development of potent drugs for the treatment of chronic multifactorial diseases involving inflammation, immune system modulation and oxidative stress such as cancers. The Lipinski's parameters suggested the compounds to be bear drug like properties.

High-Throughput Screening Platform for the Discovery of New Immunomodulator Molecules from Natural Product Extract Libraries.

PubMed

Pérez Del Palacio, José; Díaz, Caridad; de la Cruz, Mercedes; Annang, Frederick; Martín, Jesús; Pérez-Victoria, Ignacio; González-Menéndez, Víctor; de Pedro, Nuria; Tormo, José R; Algieri, Francesca; Rodriguez-Nogales, Alba; Rodríguez-Cabezas, M Elena; Reyes, Fernando; Genilloud, Olga; Vicente, Francisca; Gálvez, Julio

2016-07-01

It is widely accepted that central nervous system inflammation and systemic inflammation play a significant role in the progression of chronic neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, neurotropic viral infections, stroke, paraneoplastic disorders, traumatic brain injury, and multiple sclerosis. Therefore, it seems reasonable to propose that the use of anti-inflammatory drugs might diminish the cumulative effects of inflammation. Indeed, some epidemiological studies suggest that sustained use of anti-inflammatory drugs may prevent or slow down the progression of neurodegenerative diseases. However, the anti-inflammatory drugs and biologics used clinically have the disadvantage of causing side effects and a high cost of treatment. Alternatively, natural products offer great potential for the identification and development of bioactive lead compounds into drugs for treating inflammatory diseases with an improved safety profile. In this work, we present a validated high-throughput screening approach in 96-well plate format for the discovery of new molecules with anti-inflammatory/immunomodulatory activity. The in vitro models are based on the quantitation of nitrite levels in RAW264.7 murine macrophages and interleukin-8 in Caco-2 cells. We have used this platform in a pilot project to screen a subset of 5976 noncytotoxic crude microbial extracts from the MEDINA microbial natural product collection. To our knowledge, this is the first report on an high-throughput screening of microbial natural product extracts for the discovery of immunomodulators. © 2016 Society for Laboratory Automation and Screening.

Prevention and management of non-steroidal anti-inflammatory drugs-induced small intestinal injury

PubMed Central

Park, Sung Chul; Chun, Hoon Jai; Kang, Chang Don; Sul, Donggeun

2011-01-01

Non-steroidal anti-inflammatory drug (NSAID)-induced small bowel injury is a topic that deserves attention since the advent of capsule endoscopy and balloon enteroscopy. NSAID enteropathy is common and is mostly asymptomatic. However, massive bleeding, stricture, or perforation may occur. The pathogenesis of small intestine injury by NSAIDs is complex and different from that of the upper gastrointestinal tract. No drug has yet been developed that can completely prevent or treat NSAID enteropathy. Therefore, a long-term randomized study in chronic NSAID users is needed. PMID:22180706

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

PubMed

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.