WorldWideScience

Sample records for antiinflammatory drug chemistry

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

    Science.gov (United States)

    Cossermelli, W; Pastor, E H

    1995-01-01

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

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

    NARCIS (Netherlands)

    Vonkeman, Harald Erwin; van de Laar, Mart A F J

    2010-01-01

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

  3. Non-steroidal Anti-inflammatory Drugs Are Caspase Inhibitors.

    Science.gov (United States)

    Smith, Christina E; Soti, Subada; Jones, Torey A; Nakagawa, Akihisa; Xue, Ding; Yin, Hang

    2017-03-16

    Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in the world. While the role of NSAIDs as cyclooxygenase (COX) inhibitors is well established, other targets may contribute to anti-inflammation. Here we report caspases as a new pharmacological target for NSAID family drugs such as ibuprofen, naproxen, and ketorolac at physiologic concentrations both in vitro and in vivo. We characterize caspase activity in both in vitro and in cell culture, and combine computational modeling and biophysical analysis to determine the mechanism of action. We observe that inhibition of caspase catalysis reduces cell death and the generation of pro-inflammatory cytokines. Further, NSAID inhibition of caspases is COX independent, representing a new anti-inflammatory mechanism. This finding expands upon existing NSAID anti-inflammatory behaviors, with implications for patient safety and next-generation drug design. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. [A novel class of anti-inflammatory and analgesic drugs--NO-donating NSAIDs].

    Science.gov (United States)

    Zhang, Yi-hua; Ji, Hui; Peng, Si-xun

    2007-04-01

    Traditional non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 selective inhibitors are among the most widely used drugs. However, their significant side effects in gastrointestinal and cardiovascular systems limited the use of these drugs. Recently, research and development of NO-donating NSAIDs (NO-NSAIDs) have become one of the most important strategies to reduce these side effects. NO-NSAIDs may exert a broad range of positive effects in terms of NO-mediated gastrointestinal and cardiovascular safety as well as comparable or increased anti-inflammatory, analgesic properties relative to NSAIDs. This review briefly deals with chemistry of NO-NSAIDs, more details are focused on biological significance, mechanism of action, and therapeutic potential of this novel class of drugs.

  5. Can Patients with Cardiovascular Disease Take Nonsteroidal Antiinflammatory Drugs?

    Science.gov (United States)

    ... Antiinflammatory Drugs? Kathryn A. Taubert Download PDF https://doi.org/10.1161/CIRCULATIONAHA.107.749135 Circulation. 2008; 117: ... e322-e324 , originally published April 28, 2008 https://doi.org/10.1161/CIRCULATIONAHA.107.749135 Citation Manager Formats ...

  6. Non-steroidal antiinflammatory drugs fail to enhance healing of ...

    African Journals Online (AJOL)

    The effects of two non-steroidal anti-inflammatory drugs (NSAIDs), meclofenamate and diclofenac, in combination with physiotherapy modalities on the rate of healing of acute hamstring muscle tears were studied in a doubleblind, placebo-controlled trial. Forty-four of the 75 patients with this injury recruited were assessed ...

  7. Mechanisms of nonsteroidal anti-inflammatory drugs in cancer prevention.

    Science.gov (United States)

    Umar, Asad; Steele, Vernon E; Menter, David G; Hawk, Ernest T

    2016-02-01

    Various clinical and epidemiologic studies show that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and cyclooxygenase inhibitors (COXIBs) help prevent cancer. Since eicosanoid metabolism is the main inhibitory targets of these drugs the resulting molecular and biological impact is generally accepted. As our knowledge base and technology progress we are learning that additional targets may be involved. This review attempts to summarize these new developments in the field. Published by Elsevier Inc.

  8. Anti-inflammatory drugs and psychosis

    NARCIS (Netherlands)

    Laan, W.

    2008-01-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  11. Nonsteroidal Anti-Inflammatory Drugs and Prostatic Diseases

    Directory of Open Access Journals (Sweden)

    Hitoshi Ishiguro

    2014-01-01

    Full Text Available Prostatic diseases are characterized by increased activity of cytokines, growth factors, and cyclooxygenases- (COX- 1 and 2. Activation of COX-1 and COX-2 results in increased levels of prostaglandins and the induction of angiogenic, antiapoptotic and inflammatory processes. Inhibition of COX enzymes by members of the widely used nonsteroidal anti-inflammatory drug (NSAID class of drugs decreases prostaglandin production, and exerts a variety of anti-inflammatory, antipyretic, and antinociceptive effects. While numerous in vitro, in vivo, and clinical studies have shown that NSAIDs inhibit the risk and progression of prostatic diseases, the relationship between NSAIDs and such diseases remains controversial. Here we review the literature in this area, critically analyzing the benefits and caveats associated with the use of NSAIDs in the treatment of prostatic diseases.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Guillermo de Anda-Jáuregui

    2018-03-01

    Full Text Available 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

  14. Topical Nonsteroidal Anti-Inflammatory Drugs for Macular Edema

    Directory of Open Access Journals (Sweden)

    Andrea Russo

    2013-01-01

    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are nowadays widely used in ophthalmology to reduce eye inflammation, pain, and cystoid macular edema associated with cataract surgery. Recently, new topical NSAIDs have been approved for topical ophthalmic use, allowing for greater drug penetration into the vitreous. Hence, new therapeutic effects can be achieved, such as reduction of exudation secondary to age-related macular degeneration or diabetic maculopathy. We provide an updated review on the clinical use of NSAIDs for retinal diseases, with a focus on the potential future applications.

  15. Topical nonsteroidal anti-inflammatory drugs for macular edema.

    Science.gov (United States)

    Russo, Andrea; Costagliola, Ciro; Delcassi, Luisa; Parmeggiani, Francesco; Romano, Mario R; Dell'Omo, Roberto; Semeraro, Francesco

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are nowadays widely used in ophthalmology to reduce eye inflammation, pain, and cystoid macular edema associated with cataract surgery. Recently, new topical NSAIDs have been approved for topical ophthalmic use, allowing for greater drug penetration into the vitreous. Hence, new therapeutic effects can be achieved, such as reduction of exudation secondary to age-related macular degeneration or diabetic maculopathy. We provide an updated review on the clinical use of NSAIDs for retinal diseases, with a focus on the potential future applications.

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

    OpenAIRE

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

    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, affectin...

  17. Utilization of non-steroidal anti-inflammatory drugs in patients ...

    African Journals Online (AJOL)

    Non-steroidal anti-inflammatory drugs are widely prescribed worldwide. In Nigeria there is unrestricted access to these useful, yet potentially harmful drugs. We set out to assess the utilization of non-steroidal anti-inflammatory drugs in outpatients attending clinics in a Teaching Hospital in Nigeria. Consecutive patients were ...

  18. Nonsteroidal antiinflammatory drugs are associated with increased aortic stiffness

    Directory of Open Access Journals (Sweden)

    Martin Claridge

    2005-07-01

    Full Text Available Martin Claridge1, Simon Hobbs1, Clive Quick2, Nick Day3, Andrew Bradbury1, Teun Wilmink11Department of Vascular Surgery, University of Birmingham, Birmingham Heartlands Hospital Birmingham, UK; 2Department of Surgery, Hinchingbrooke Hospital, Huntingdon, UK; 3Department of Epidemiology and Biostatistics, University of Cambridge, Cambridge, UKObjectives: Nonsteroidal antiinflammatory drugs (NSAIDS have been shown to retard aneurysm growth in animal models. In vitro studies have shown an inhibitory effect of NSAIDS on matrix metalloproteinase-9, interleukin-1β, and IL-6 mediated arterial wall elastolysis. The aim of this study was to investigate the effects of NSAIDs on arterial stiffness, a surrogate marker of elastolysis.Methods: 447 subjects enrolled in a community-based abdominal aortic aneurysm (AAA screening program were assessed for age, blood pressure, smoking status, and drug history. Aortic diameter and stiffness were measured by M-Mode ultrasound. The concentration of the amino-terminal propeptide of type III procollagen was used as a proxy measurement of type III collagen turnover.Results: NSAID ingestion was significantly (p = 0.006 associated with increased aortic wall stiffness after adjusting for age, aortic diameter, blood pressure, and smoking status. No such effect was seen for β-blockers, calcium channel antagonists, nitrates, angiotensin-converting enzyme inhibitors, diuretics, or antiplatelet agents.Discussion: These novel data show that NSAIDS are associated with increased aortic stiffness, possibly through the effects of cytokine mediated elastolysis. This in turn may prevent aortic expansion and the development of AAA.Keywords: nonsteroidal antiinflammatory drugs, abdominal aortic aneurysm, aortic stiffness, elastolysis

  19. Fluridone as a new anti-inflammatory drug.

    Science.gov (United States)

    Magnone, Mirko; Scarfì, Sonia; Sturla, Laura; Guida, Lucrezia; Cuzzocrea, Salvatore; Di Paola, Rosanna; Bruzzone, Santina; Salis, Annalisa; De Flora, Antonio; Zocchi, Elena

    2013-11-15

    Fluridone is a herbicide extensively utilized in agriculture for its documented safety in animals. Fluridone contains a 4(1H)-pyridone and a trifluoromethyl-benzene moiety, which are also present in molecules with analgesic and anti-inflammatory properties. The established absence of adverse effects of Fluridone on animals prompted us to investigate whether it could represent a new anti-inflammatory compound targeting human cells. In stimulated human monocytes, micromolar Fluridone inhibited cyclooxygenase-2 expression and the release of monocyte chemoattractant protein-1 and prostaglandin-E2, to a similar extent as Acetylsalicylic acid. Fluridone also inhibited the proliferation of aortic smooth muscle cells and reduced proliferation and cytokine release by human activated lymphocytes. The mechanism of Fluridone seems to rely on the dose-dependent inhibition of the nuclear translocation of nuclear factor-κB, a transcription factor playing a pivotal role in inflammation. Fluridone also inhibited the release from stimulated human monocytes of abscisic acid, a plant stress hormone recently discovered also in mammalian cells, where it stimulates pro-inflammatory responses. Interestingly, the mechanism of Fluridone's toxicity in plants relies on the inhibition of the enzyme phytoene desaturase, involved in the biosynthetic pathway of ß-carotene, the precursor of absciscic acid in plants. Finally, administration of Fluridone reduced peritoneal inflammation in Zymosan-treated mice. These results suggest that Fluridone could represent a new prototype of anti-inflammatory drug, also active on abscisic acid pro-inflammatory pathway. © 2013 Elsevier B.V. All rights reserved.

  20. Anti-inflammatory drugs in the 21st century.

    Science.gov (United States)

    Rainsford, K D

    2007-01-01

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

  1. Drug Targets for Cardiovascular-Safe Anti-Inflammatory: In Silico Rational Drug Studies.

    Directory of Open Access Journals (Sweden)

    Sajad Shahbazi

    Full Text Available 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.

  2. Nonsteroidal anti-inflammatory drugs in clinical and experimental epilepsy.

    Science.gov (United States)

    Radu, Beatrice Mihaela; Epureanu, Florin Bogdan; Radu, Mihai; Fabene, Paolo Francesco; Bertini, Giuseppe

    2017-03-01

    Current antiepileptic drugs have limited efficacy and provide little or no benefits in 30% of the patients. Given that a role for brain inflammation in epilepsy has been repeatedly reported in recent years, the potential of anti-inflammatory drugs should be explored in depth, as they may provide new therapeutical approaches in preventing or reducing epileptogenesis. Here, we review preclinical (both in vivo and in vitro) and clinical epilepsy studies in which nonsteroidal antiinflammatory drugs (NSAIDs), i.e. cyclooxygenase-2 (COX-2) selective inhibitors (COXIBs) and nonselective NSAIDs, were used for seizure control. The effects of NSAIDs are reviewed in animal models of both chemical (pilocarpine, kainic acid, pentylenetetrazol, or carbachol administration) and electrical (tetanic hippocampal stimulation, electroshock) seizure induction. In the pilocarpine model, NSAIDs are neuroprotective, reduce mossy fiber sprouting or diminish P-glycoprotein upregulation, but only rarely protect against seizures. While neuroprotective effects have also been observed in the kainic acid model, NSAIDs tend in general to worsen seizure activity. Effects of COXIB administration in the pentylenetetrazol-induced seizures model are variable, alternating from protection against seizures to null effects or even increased incidence of convulsions. Moreover, NSAIDs tested in the tetanic hippocampal stimulation model diminished the seizure-associated P-glycoprotein upregulation, but were not very effective in seizure control. NSAIDs efficacy in experimental in vivo epilepsy studies may be influenced by multiple factors, including the timing of administration (before or after status epilepticus induction), the animal model of epilepsy or some of the signaling pathways involved in cyclooxygenase induction (e.g. prostaglandins and their receptors). On the other hand, the few clinical studies on the use of NSAIDs in neurological pathologies accompanied/characterized by seizures indicate that

  3. Anti-inflammatory drugs and uterine cervical cancer cells: Antineoplastic effect of meclofenamic acid

    OpenAIRE

    SORIANO-HERNANDEZ, ALEJANDRO D.; MADRIGAL-PÉREZ, DANIELA; GALVAN-SALAZAR, HECTOR R.; MARTINEZ-FIERRO, MARGARITA L.; VALDEZ-VELAZQUEZ, LAURA L.; ESPINOZA-GÓMEZ, FRANCISCO; VAZQUEZ-VUELVAS, OSCAR F.; OLMEDO-BUENROSTRO, BERTHA A.; GUZMAN-ESQUIVEL, JOSE; RODRIGUEZ-SANCHEZ, IRAM P.; LARA-ESQUEDA, AGUSTIN; MONTES-GALINDO, DANIEL A.; DELGADO-ENCISO, IVAN

    2015-01-01

    Uterine cervical cancer (UCC) is one of the main causes of cancer-associated mortality in women. Inflammation has been identified as an important component of this neoplasia; in this context, anti-inflammatory drugs represent possible prophylactic and/or therapeutic alternatives that require further investigation. Anti-inflammatory drugs are common and each one may exhibit a different antineoplastic effect. As a result, the present study investigated different anti-inflammatory models of UCC ...

  4. Cause-specific cardiovascular risk associated with nonsteroidal antiinflammatory drugs among healthy individuals

    DEFF Research Database (Denmark)

    Fosbøl, Emil Loldrup; Folke, Fredrik; Jacobsen, Søren

    2010-01-01

    Studies have raised concern on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). We studied safety of NSAID therapy in a nationwide cohort of healthy individuals.......Studies have raised concern on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). We studied safety of NSAID therapy in a nationwide cohort of healthy individuals....

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

    Czech Academy of Sciences Publication Activity Database

    Čapka, Lukáš; Lacina, P.; Vávrová, M.

    2012-01-01

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

  6. Virtual drug discovery: beyond computational chemistry?

    Science.gov (United States)

    Gilardoni, Francois; Arvanites, Anthony C

    2010-02-01

    This editorial looks at how a fully integrated structure that performs all aspects in the drug discovery process, under one company, is slowly disappearing. The steps in the drug discovery paradigm have been slowly increasing toward virtuality or outsourcing at various phases of product development in a company's candidate pipeline. Each step in the process, such as target identification and validation and medicinal chemistry, can be managed by scientific teams within a 'virtual' company. Pharmaceutical companies to biotechnology start-ups have been quick in adopting this new research and development business strategy in order to gain flexibility, access the best technologies and technical expertise, and decrease product developmental costs. In today's financial climate, the term virtual drug discovery has an organizational meaning. It represents the next evolutionary step in outsourcing drug development.

  7. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Induced Dyspepsia.

    Science.gov (United States)

    Yap, Paul Ray-Yee; Goh, Khean-Lee

    2015-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed group of drugs in the world. They are used primarily for pain relief in chronic inflammatory joint disease and act by inhibiting enzymes COX1 and COX2 and ultimately preventing the production of active prostanoids which are required for the innate inflammatory pathway. The use of NSAIDs have been associated with the development of gastrointestinal (GI) symptoms ranging from simple dyspepsia to life threatening GI bleeds and perforations. The definition of dyspepsia has evolved over the years and this has hampered accurate studies on the prevalence of dyspepsia as different studies used varying criteria to define dyspepsia. It is now known that NSAIDs significantly increase the risk of dyspepsia.The risk of developing peptic ulcer disease vary with specific NSAIDs and dosages but there is no correlation between the symptoms of dyspepsia and underlying peptic ulcers. The pathogenesis of dyspepsia with NSAIDs is not completely understood. Peptic ulceration alone is not able to account for the majority of dyspepsia symptoms encountered by NSAIDs users. Erosive oesophagitis secondary to NSAIDs may be contributing factor to the prevalence of dyspepsia in NSAIDs users. Altered gut permeability and changes in gastric mechanosensory function due to NSAIDs may also be a contributory factor. Management of NSAID induced dyspepsia is involves a multipronged approach. Drug avoidance if possible would be ideal. Other options include using the lowest effective dose, changing to an NSAIDs with a safer GI risk profile, avoiding concurrent use with other NSAIDs or if the patient has a previous history of peptic ulcer disease, and co-prescribing with anti-secretory medications such as proton pump inhibitors. Eradication of Helicobacter pylori has a protective role against developing peptic ulcers and may also improve symptoms of NSAIDs induced dyspepsia.

  8. Non-steroidal Anti-inflammatory Drugs in Raptors

    Science.gov (United States)

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

    2012-01-01

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

  9. Nonsteroidal Anti-Inflammatory Drugs and Risk of Melanoma

    Directory of Open Access Journals (Sweden)

    Joanne M. Jeter

    2011-01-01

    Full Text Available Because nonsteroidal anti-inflammatory drugs (NSAIDs inhibit tumor growth in vitro, we investigated the association between NSAIDs and melanoma to determine if there was epidemiologic evidence of a chemopreventive effect from these medications. Three hundred twenty-seven subjects with incident melanoma and 119 melanoma-free controls completed a structured interview assessing melanoma risk factors. The unadjusted odds ratio (OR for use of nonaspirin NSAIDs was 0.58 (95% CI 0.31–1.11, in a comparison of subjects with melanoma to controls. After adjustment for melanoma risk factors, the OR was 0.71 (95% CI 0.23–2.02. Aspirin users had an unadjusted OR of 0.85 (95% CI 0.45–1.69 and an adjusted OR of 1.45 (95% CI 0.44–4.74. In this pilot study, we found no evidence of a significant association between analgesic use and melanoma risk when potential confounders are assessed. Based on conflicting reports in the literature, meta-analysis may be appropriate.

  10. Pharmacoeconomics of nonsteroidal anti-inflammatory drugs (NSAIDs).

    Science.gov (United States)

    Wynne, H A; Campbell, M

    1993-02-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the relief of the symptoms of osteoarthritis (OA), rheumatoid arthritis (RA), sprains and strains, sports injuries and menstrual disorders, and have a small role in the management of patent ductus arteriosus in the neonate. In patients with RA, symptom relief through use of NSAIDs is firmly established, although it remains unclear whether they influence the course and outcome of the disease. For the average patient with RA taking NSAIDs, the attributable risk of hospitalisation with gastrointestinal problems related to NSAIDs is 1.3 to 1.6% annually and risk of death is 0.15%. Associations of therapy with risk are greatest with age, corticosteroid use and previous NSAID-related gastrointestinal adverse effects, and less marked with disability and high NSAID dose. These are important data in attempting to balance risk of therapy with clinical efficacy in an individual patient, and assessing the cost-effectiveness of prophylaxis. Although half of all NSAID consumption is for control of pain associated with degenerative conditions, their superiority over simple analgesics in osteoarthritis is poorly documented. This finding supports the use of the simple analgesic paracetamol (acetaminophen) as the preferred therapy of osteoarthritis, especially when its lower cost and low incidence of adverse effects are taken into consideration. Consistent differences in clinical effectiveness of individual NSAIDs have not been demonstrated, although unpredictable interpatient variation in response to individual agents is of considerable clinical importance, and a more expensive NSAID may prove cost effective for some patients. Cost effectiveness can be improved by a self-adjusted dosage regime which also leads to lower overall drug consumption. The adverse gastrointestinal effects of these drugs account for about 30% of the overall cost of arthritis treatment, and although studies to date have been too limited to

  11. Aspirin and its related non-steroidal anti-inflammatory drugs

    African Journals Online (AJOL)

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

  12. Oral nonsteroidal anti-inflammatory drugs for fibromyalgia in adults.

    Science.gov (United States)

    Derry, Sheena; Wiffen, Philip J; Häuser, Winfried; Mücke, Martin; Tölle, Thomas Rudolf; Bell, Rae F; Moore, R Andrew

    2017-03-27

    Oral nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of pain in fibromyalgia, despite being considered not to be effective. To assess the analgesic efficacy, tolerability (drop-out due to adverse events), and safety (serious adverse events) of oral nonsteroidal anti-inflammatory drugs for fibromyalgia in adults. We searched CENTRAL, MEDLINE, and Embase for randomised controlled trials from inception to January 2017. We also searched the reference lists of retrieved studies and reviews, and online clinical trial registries. We included randomised, double-blind trials of two weeks' duration or longer, comparing any oral NSAID with placebo or another active treatment for relief of pain in fibromyalgia, with subjective pain assessment by the participant. Two review authors independently extracted data and assessed trial quality and potential bias. Primary outcomes were participants with substantial pain relief (at least 50% pain relief over baseline or very much improved on Patient Global Impression of Change scale (PGIC)) or moderate pain relief (at least 30% pain relief over baseline or much or very much improved on PGIC), serious adverse events, and withdrawals due to adverse events; secondary outcomes were adverse events, withdrawals due to lack of efficacy, and outcomes relating to sleep, fatigue, and quality of life. Where pooled analysis was possible, we used dichotomous data to calculate risk difference (RD) and number needed to treat for an additional beneficial outcome (NNT), using standard methods. We assessed the quality of the evidence using GRADE and created a 'Summary of findings' table. Our searches identified six randomised, double-blind studies involving 292 participants in suitably characterised fibromyalgia. The mean age of participants was between 39 and 50 years, and 89% to 100% were women. The initial pain intensity was around 7/10 on a 0 to 10 pain scale, indicating severe pain. NSAIDs tested were etoricoxib 90 mg

  13. The Epidemiology of Nonsteroidal Anti-Inflammatory Drugs

    Directory of Open Access Journals (Sweden)

    Jerry Tenenbaum

    1999-01-01

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

  14. A Novel Pleiotropic Anti-Inflammatory Drug to Reduce ARDS Incidence

    Science.gov (United States)

    2017-07-01

    Page 1 AWARD NUMBER: W81XWH-16-1-0288 TITLE: A Novel Pleiotropic Anti-Inflammatory Drug to Reduce ARDS Incidence PRINCIPAL INVESTIGATOR: Gary...Pleiotropic Anti-Inflammatory Drug to Reduce ARDS Incidence 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Gary...N0224 is effective for trauma and/or sepsis. 15. SUBJECT TERMS Hemorrhagic shock, acute respiratory distress syndrome (ARDS), TRB-N0224 to prevent ARDS

  15. Immortal time bias in drug safety cohort studies: spontaneous abortion following nonsteroidal antiinflammatory drug exposure.

    Science.gov (United States)

    Daniel, Sharon; Koren, Gideon; Lunenfeld, Eitan; Levy, Amalia

    2015-03-01

    Experimental research of drug safety in pregnancy is generally not feasible because of ethical issues. Therefore, most of the information about drug safety in general and teratogenicity in particular is obtained through observational studies, which require careful methodologic design to obtain unbiased results. Immortal time bias occurs when some cases do not "survive" sufficient time in the study, and as such, they have reduced chances of being defined as "exposed" simply because the durations of their follow-ups were shorter. For example, studies that examine the risk for spontaneous abortions in women exposed to a drug during pregnancy are susceptible to immortal time bias because the chance of drug exposure increases the longer a pregnancy lasts. Therefore, the drug tested may falsely be found protective against the outcome tested. The objective of the current study was to illustrate the extent of immortal time bias using a cohort study of pregnancies assessing the risk for spontaneous abortions following nonsteroidal antiinflammatory drug exposure. We assembled 3 databases containing data on spontaneous abortions, births and drug dispensions to create the present study's cohort. The risk for spontaneous abortion was assessed using 2 statistical analysis methods that were compared for 2 definitions of exposure (dichotomous, exposed vs unexposed, regular Cox regression vs Cox regression with time-varying exposure). Significant differences were found in the risk for spontaneous abortions between the 2 statistical methods, both for groups and for most specific nonsteroidal antiinflammatory drugs (nonselective Cox inhibitors - hazard ratio, 0.70; 95% confidence interval, 0.61-0.94 vs hazard ratio, 1.10; 95% confidence interval, 0.99-1.22 for dichotomous vs time-varying exposure analyses, respectively). Furthermore, a significant correlation was found between the median misclassified immortal time for each drug and the extent of the bias. Immortal time bias can

  16. Repurposing drugs for treatment of tuberculosis: a role for non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    Maitra, Arundhati; Bates, Sadé; Shaik, Monisha; Evangelopoulos, Dimitrios; Abubakar, Ibrahim; McHugh, Timothy D; Lipman, Marc; Bhakta, Sanjib

    2016-06-01

    The number of cases of drug-resistant Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), has risen rapidly in recent years. This has led to the resurgence in repurposing existing drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs), for anti-TB treatment. Evidence from novel drug screening in vitro, in vivo, pharmacokinetic/pharmacodynamics analyses and clinical trials has been used for the preparation of this systematic review of the potential of NSAIDs for use as an adjunct in new TB chemotherapies. Certain NSAIDs have demonstrated inhibitory properties towards actively replicating, dormant and drug-resistant clinical isolates of M. tuberculosis cells. NSAIDs are a diverse class of drugs, which have reported off-target activities, and their endogenous antimicrobial mechanism(s) of action is still unclear. It is essential that clinical trials of NSAIDs continue, in order to assess their suitability for addition to the current TB treatment regimen. Repurposing molecules such as NSAIDs is a vital, low-risk strategy to combat the trend of rapidly increasing antibiotic resistance. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Non-steroidal anti-inflammatory drugs for sciatica.

    Science.gov (United States)

    Rasmussen-Barr, Eva; Held, Ulrike; Grooten, Wilhelmus Ja; Roelofs, Pepijn Ddm; Koes, Bart W; van Tulder, Maurits W; Wertli, Maria M

    2016-10-15

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently prescribed drugs for the treatment of sciatica. A previous Cochrane review on the efficacy of NSAIDs summarised findings for acute and chronic low back pain (LBP) and sciatica. This is an update of the original review (2008) focusing on people suffering from sciatica. To determine the efficacy of NSAIDs in pain reduction, overall improvement, and reported side effects in people with sciatica. We performed electronic searches up to 24 June 2015 in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PubMed, and two trials registers. We searched reference lists of included studies and relevant reviews on the topics for additional trials. We included randomised controlled trials (double-blind, single-blind, and open-label) that assessed the efficacy of NSAIDs in sciatica. We included all trials that compared NSAIDs to placebo, to other NSAIDs, or to other medication. Additional interventions were allowed if there was a clear contrast for the treatment with NSAIDs in the trial. Three review authors independently assessed the risk of bias and extracted the data. Where feasible we calculated pooled results using Review Manager 5.3. We reported pain relief outcomes using mean difference (MD) with 95% confidence intervals (95% CI). We used risk ratios (RR) with 95% CI to report global improvement of treatment, adverse effects, and additional medication. We performed a meta-analysis if possible. We assessed level of evidence using the GRADE approach. We used standard methodological procedures recommended by The Cochrane Collaboration. We included 10 trials reported in 9 publications (N = 1651). Only one trial out of 10 was assessed at low risk of bias. Five trials used the currently recommended daily dose for the drug, and two trials used lower daily doses available over the counter. Three trials investigated NSAIDs no longer approved for human use. The follow-up duration

  18. Suppression of Tumor Angiogenesis by Nonsteroidal Anti-Inflammatory Drugs: A New Function for Old Drugs

    Directory of Open Access Journals (Sweden)

    Curzio Raegg

    2001-01-01

    Full Text Available There is solid epidemiological evidence demonstrating that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs reduces the risk of developing colorectal cancer, and to a lesser extent gastric and esophageal cancers[1]. Importantly, NSAIDs suppress colon polyp formation and progression in patients diagnosed with familial adenomatous polyposis coli (APC[2]. In many animal studies, NSAIDs have been shown to prevent tumor formation and slow tumor progression, thus confirming and extending the clinical observations[3,4,5]. Recent findings have demonstrated that NSAIDs inhibit angiogenesis, suggesting that the tumor suppressive activity of these drugs may be due, at least in part, to their ability to inhibit tumor angiogenesis[6]. The study of the mechanism by which NSAIDs suppress tumor angiogenesis, is matter of intense research.

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

    Directory of Open Access Journals (Sweden)

    Christopher J. Hall

    2014-09-01

    Full Text Available 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.

  20. [Clinical relevance of drug interactions between nonsteroidal antiinflammatory drugs (NSAIDs) and antihypertensives].

    Science.gov (United States)

    Villa, Juan; Cano, Alejandra; Franco, David; Monsalve, Mauricio; Hincapié, Jaime; Amariles, Pedro

    2014-11-01

    To establish the clinical relevance of drug interactions between nonsteroidal antiinflammatory drugs (NSAIDs) and antihypertensives, based on the interaction severity and probability of occurrence. Systematic review. A PubMed/Medline search was made using the MeSH terms: NSAIDs, Antihypertensive drugs, and Drug interactions. Articles between 2002 and 2012, human studies, in Spanish and English and full text access were included. Found articles were included and some of the references used in this works. Studies with in vitro methods, effects on ocular hypertension and those who do not consider the interaction NSAIDs, antihypertensives were excluded. For the selection of the papers included three independent reviewers were involved. We used a tool for data extraction and for assess of the interaction clinical relevance. Nineteen of 50 papers found were included. There were identified 21 interactions with pharmacodynamic mechanism, classified by their clinical relevance in level-2 high risk (76.2%) and level-3 medium risk (23.8%). In addition, evidence of 16 combinations of no interaction were found. Some NSAIDs may attenuate the effectiveness of antihypertensive drugs when used concurrently, especially with angiotensin converting enzyme inhibitors, diuretics, beta blockers and angiotensin receptorsii blockers. There was no evidence of effect modification of calcium channel antagonists, especially dihydropyridine, by concurrent use of NSAIDs. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

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

    DEFF Research Database (Denmark)

    Aalykke, C; Lauritsen, Jens; Hallas, J

    1999-01-01

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

  2. Organic carbamates in drug design and medicinal chemistry.

    Science.gov (United States)

    Ghosh, Arun K; Brindisi, Margherita

    2015-04-09

    The carbamate group is a key structural motif in many approved drugs and prodrugs. There is an increasing use of carbamates in medicinal chemistry and many derivatives are specifically designed to make drug-target interactions through their carbamate moiety. In this Perspective, we present properties and stabilities of carbamates, reagents and chemical methodologies for the synthesis of carbamates, and recent applications of carbamates in drug design and medicinal chemistry.

  3. [A short history of anti-rheumatic therapy. III. Non steroidal anti-inflammatory drugs].

    Science.gov (United States)

    Pasero, G; Marson, P

    2010-01-01

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

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

    Science.gov (United States)

    Barkin, Robert L

    2015-01-01

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

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

    Science.gov (United States)

    Knowles, Richard Graham

    2014-01-01

    The research and development process for novel drugs to treat inflammatory diseases is described, and several current issues and debates relevant to this are raised: the decline in productivity, attrition, challenges and trends in developing anti-inflammatory drugs, the poor clinical predictivity of experimental models of inflammatory diseases, heterogeneity within inflammatory diseases, 'improving on the Beatles' in treating inflammation, and the relationships between big pharma and biotechs. The pharmaceutical research and development community is responding to these challenges in multiple ways which it is hoped will lead to the discovery and development of a new generation of anti-inflammatory medicines. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    G.V. Dzyak

    2013-02-01

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

  7. The patterns of toxicity and management of acute nonsteroidal anti-inflammatory drug (NSAID overdose

    Directory of Open Access Journals (Sweden)

    Hunter L

    2011-07-01

    Full Text Available Laura J Hunter, David M Wood, Paul I DarganClinical Toxicology, Guy’s and St Thomas’ NHS Foundation Trust, London, UKAbstract: The nonsteroidal anti-inflammatory drugs (NSAIDs are widely used for their analgesic, anti-inflammatory and antipyretic actions. They are commonly taken in overdose in many areas of the world. The majority of patients with acute NSAID overdose will remain asymptomatic or develop minor self-limiting gastrointestinal symptoms. However, serious clinical sequelae have been reported in patients with acute NSAID overdose and these include convulsions, metabolic acidosis, coma and acute renal failure. There appear to be some differences between the NSAIDs in terms of the relative risk of these complications; in particular mefenamic acid is most commonly associated with convulsions. The management of these serious clinical features is largely supportive and there are no specific antidotes for acute NSAID toxicity.Keywords: nonsteroidal anti-inflammatory drugs (NSAID, ibuprofen, toxicity, poisoning, overdose, management

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

    Science.gov (United States)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

    Klein, Mads; Gögenur, Ismail; Rosenberg, Jacob

    2012-01-01

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

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  14. Antimicrobial activity of non-steroidal anti-inflammatory drugs with ...

    African Journals Online (AJOL)

    The non-steroidal anti-inflammatory drugs (NSAIDs) as the name implies are compounds of nonsteroidal origin, with the capability of inhibiting/reducing inflammatory response associated with tissue injury which could be as a result of physical trauma, noxious chemicals or microorganisms. There is however reason to ...

  15. Review of the safety of nonsteroidal anti-inflammatory drugs and ...

    African Journals Online (AJOL)

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most common classes of medication used worldwide, and as the ageing population increases, the prevalence of painful arthritic conditions parallels this, resulting in the increased use of NSAIDs. Selective and nonselective cyclo-oxygenase inhibitors should be ...

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

    DEFF Research Database (Denmark)

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

    1995-01-01

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

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

    Science.gov (United States)

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

    2007-04-01

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

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

    NARCIS (Netherlands)

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

    2004-01-01

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

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  20. The role of nonsteroidal anti-inflammatory drugs in colorectal cancer prevention

    NARCIS (Netherlands)

    Giardiello, F. M.; Offerhaus, G. J.; DuBois, R. N.

    1995-01-01

    Colorectal cancer is the second leading cause of cancer death in the U.S.A. Recent research suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in the prevention of colorectal neoplasia. This review summarises the results of research in animals and humans of these compounds in

  1. [The possible suppression of Alzheimer's disease by nonsteroidal anti-inflammatory drugs

    NARCIS (Netherlands)

    Jong, D. de; Jansen, R.W.M.M.; Verbeek, M.M.; Kremer, H.P.H.

    2002-01-01

    Ever since inflammatory mediators were detected in and around amyloid plaques in the brain of patients with Alzheimer's disease, there has been great interest in the inflammatory hypothesis and the possibility of treating Alzheimer's disease with anti-inflammatory drugs. Various epidemiological

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

    Directory of Open Access Journals (Sweden)

    Stanos SP

    2013-04-01

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

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

    Directory of Open Access Journals (Sweden)

    M S Eliseev

    2008-01-01

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

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

    Science.gov (United States)

    Smith, Lucille L.; And Others

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

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

    African Journals Online (AJOL)

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

  6. Action of β-endorphin and nonsteroidal anti-inflammatory drugs, and the possible effects of nonsteroidal anti-inflammatory drugs on β-endorphin.

    Science.gov (United States)

    Luan, Yuan-Hang; Wang, Di; Yu, Qi; Chai, Xiao-Qing

    2017-02-01

    This study aimed to review research on the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on β-endorphin. NSAIDs are commonly used as anti-inflammatory and analgesic drugs. They are well known for inducing peripheral analgesia by inhibiting cyclooxygenase (COX). However, an increasing number of studies have shown that NSAIDs have an analgesic effect not only in the periphery but also at the center. It means that a central analgesic mechanism of the action of NSAIDs exists besides the peripheral mechanism, and the central mechanism likely involves β-endorphin. β-Endorphin is one of the most prominent endogenous peptides, existing in the hypophysis cerebri and hypothalamus. It plays an irreplaceable role in the central and peripheral analgesia in the human body mainly through three mechanisms including three parts, the spinal cord, the supraspinal cord, and peripheries. β-Endorphin plays an important role in the development of hyperalgesia. However, the specific signal transduction pathways between prostaglandin E 2 or NSAIDs and β-endorphin are still not quite clear. Whether NSAIDs can lead to the increased content of β-endorphin in all patients after any operation needs further investigation. Further studies should determine the optimal dose when NSAIDs and opioid drugs are used together, and also explore the existence of one NSAID that has the potential to replace the traditional opioid drugs and can achieve adequate analgesia. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Nonsteroidal anti-inflammatory drugs as the first step in treating musculoskeletal pain

    Directory of Open Access Journals (Sweden)

    Andrei Evgenyevich Karateev

    2015-01-01

    Full Text Available Pain control is a fundamental task in the management of patients with locomotor diseases. Analgesic therapy holds the most important position in treating common diseases, such as osteoarthritis, nonspecific spinal pain, and rheumatic diseases of juxtaarticular soft tissues. Pain development and chronization in these conditions are determined by a uniform pathogenetic mechanism, the key component of which should be considered to be inflammation. This necessitates the use of antiinflammatory drugs, first of all, nonsteroidal antiinflammatory drugs (NSAIDs. When the latter are used, the risk of their adverse reactions should be necessarily taken into account and the choice of a specific drug should be based on an efficacy-safety ratio. Aceclofenac may be legally regarded as one of the most balanced NSAIDs in this respect. The paper reviews the data available in the literature on the use of this drug, including the largest clinical and epidemiological studies.

  8. "Drug" Discovery with the Help of Organic Chemistry.

    Science.gov (United States)

    Itoh, Yukihiro; Suzuki, Takayoshi

    2017-01-01

    The first step in "drug" discovery is to find compounds binding to a potential drug target. In modern medicinal chemistry, the screening of a chemical library, structure-based drug design, and ligand-based drug design, or a combination of these methods, are generally used for identifying the desired compounds. However, they do not necessarily lead to success and there is no infallible method for drug discovery. Therefore, it is important to explore medicinal chemistry based on not only the conventional methods but also new ideas. So far, we have found various compounds as drug candidates. In these studies, some strategies based on organic chemistry have allowed us to find drug candidates, through 1) construction of a focused library using organic reactions and 2) rational design of enzyme inhibitors based on chemical reactions catalyzed by the target enzyme. Medicinal chemistry based on organic chemical reactions could be expected to supplement the conventional methods. In this review, we present drug discovery with the help of organic chemistry showing examples of our explorative studies on histone deacetylase inhibitors and lysine-specific demethylase 1 inhibitors.

  9. Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain

    NARCIS (Netherlands)

    Ong, Cliff K. S.; Seymour, Robin A.; Lirk, Phillip; Merry, Alan F.

    2010-01-01

    BACKGROUND: There has been a trend over recent years for combining a nonsteroidal antiinflammatory drug (NSAID) with paracetamol (acetaminophen) for pain management. However, therapeutic superiority of the combination of paracetamol and an NSAID over either drug alone remains controversial. We

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

    Science.gov (United States)

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

    2014-04-01

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

  11. Do anti-inflammatory drugs worsen odontogenic cervico-facial cellulitis?

    Science.gov (United States)

    Nicot, R; Hippy, C; Hochart, C; Wiss, A; Brygo, A; Gautier, S; Caron, J; Ferri, J; Raoul, G

    2014-11-01

    The aim of this prospective study was to determine the influence of anti-inflammatory drugs on the severity of odontogenic cellulitis in patients admitted to our hospital emergency unit. The study was made from April 30 to October 31 2006. The clinical and pharmacological data was prospectively collected at admission, during hospitalization, and during systematic follow-up. We first studied the whole population and then compared the 2 groups: patients having received anti-inflammatory drugs before admission or not. Two hundred and sixty-seven patients were included. The only severity criterion significantly different between the 2 groups was spreading of cervical lymphangitis (P=0.028). None of the 4 studied parameters was identified as a risk factor for spreading of cervical lymphangitis in multivariate analysis: anti-inflammatory use (OR=5.99, 95%CI [0.71-50.88]), alcohol abuse (OR=4.00, 95%CI [0.66-24.12]), dental hygiene (OR=1.53, 95%CI [0.36-6.56]), and tobacco use (OR=0.27, 95%CI [0.57-1.28]). The use of anti-inflammatory drugs during the initial phase of an odontogenic infection was not related to the severity of infection. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. Chemistry and pharmacology of anticancer drugs

    National Research Council Canada - National Science Library

    Thurston, David E

    2007-01-01

    ... in the development of novel drugs and therapies has occurred within the last 60 years and, thanks to the discovery of drugs such as cisplatin, the taxanes, and the nitrogen mustards in the last century, trea...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    OBJECTIVE: Safety data regarding the use of etoricoxib and other nonsteroidal antiinflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather limited. Our objective was to estimate and compare rates of gastrointestinal, renovascular, and cardio......OBJECTIVE: Safety data regarding the use of etoricoxib and other nonsteroidal antiinflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather limited. Our objective was to estimate and compare rates of gastrointestinal, renovascular...... exposure was assessed time dependently based on the prescription drug register from 2006-2009, adjusting for sociodemographics and comorbidities derived from national population-based registers. RESULTS: Exposure to etoricoxib, celecoxib, and nonselective NSAIDs was 7.6%, 3.9%, and 71.2%, respectively...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

    Ahlehoff, O; Skov, L; Gislason, Gunnar

    2015-01-01

    .34-0.83) was associated with reduced risk of the composite endpoint and a comparable but non-significant protective effect was observed with biological drugs (HR 0.58; CI 0.30-1.10), whereas no protective effect was apparent with cyclosporine (HR 1.06; CI 0.26-4.27) and retinoids (HR 1.80; CI 1.03-2.96). Tumour necrosis......BACKGROUND: Psoriasis is a common disease and is associated with cardiovascular diseases. Systemic anti-inflammatory drugs may reduce risk of cardiovascular events. We therefore examined the rate of cardiovascular events, i.e. cardiovascular death, myocardial infarction and stroke, in patients...... with severe psoriasis treated with systemic anti-inflammatory drugs. METHODS: Individual-level linkage of administrative registries was used to perform a longitudinal nationwide cohort study. Time-dependent multivariable adjusted Cox regression was used to estimate hazard ratios (HRs) with 95% confidence...

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

    Science.gov (United States)

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

    2011-01-11

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

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

    Directory of Open Access Journals (Sweden)

    P. Marson

    2011-06-01

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

  18. [Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs): short update].

    Science.gov (United States)

    Bumbăcea, Roxana Silvia; Olariu, Sandra; Bumbăcea, Dragoş; Strâmbu, Irina

    2014-01-01

    Hypersensitivity reactions to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are a challenge to the clinicians, due to their severity. In susceptible individuals, NSAIDs induce a wide spectrum of reactions with various timing and organ manifestations, involving immunological and non-immunological mechanisms. Diagnosis of hypersensitivity to NSAID is based on characteristic symptoms precipitated with ASA/NSAIDs. Oral challenge with NSAID is the "gold standard" for the diagnosis and can be performed in order to confirm hypersensitivity to the culprit drug or to confirm or exclude tolerance to an alternative drug. Diagnosis process includes understanding of the underlying mechanism, and is mandatory for prevention of future events.

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

    Science.gov (United States)

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

    2016-01-01

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

  20. The Effect of Opioids, Alcohol, and Nonsteroidal Anti-inflammatory Drugs on Fracture Union.

    Science.gov (United States)

    Richards, Christopher J; Graf, Kenneth W; Mashru, Rakesh P

    2017-10-01

    The estimated rate of fracture nonunion is between 5% and 10%, adding significant cost to the health care system. The cause of fracture nonunion is multifactorial, including the severity of the injury, patient factors resulting in aberrancies in the biology of fracture, and the side effects of pain control modalities. Minimizing surgeon-controlled factors causing nonunion is important to reduce the cost of health care and improve patient outcomes. Opioids, alcohol, and nonsteroidal anti-inflammatory drugs have been implicated as risk factors for fracture nonunion. Current literature was reviewed to examine the effects of opioids, alcohol, and nonsteroidal anti-inflammatory drugs on fracture union. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

    Ahlehoff, O; Skov, L; Gislason, G

    2013-01-01

    OBJECTIVES: Psoriasis is a chronic inflammatory disorder associated with cardiovascular morbidity and mortality. Systemic anti-inflammatory drugs, including biological agents, are widely used in the treatment of patients with moderate to severe psoriasis and may attenuate the risk of cardiovascular...... disease events. We therefore examined the rate of cardiovascular disease events in patients with severe psoriasis treated with systemic anti-inflammatory drugs. DESIGN, SETTING AND PARTICIPANTS: Individual-level linkage of nationwide administrative databases was used to assess the event rates associated...... with biological agents and 799 treated with methotrexate, were identified. Incidence rates per 1000 patient-years and 95% confidence intervals (CIs) for the composite endpoint were 6.0 (95% CI 2.7-13.4), 17.3 (95% CI 12.3-24.3) and 44.5 (95% CI 34.6-57.0) for patients treated with biological agents, methotrexate...

  2. Synthesis, anti-inflammatory, bactericidal activities and docking studies of novel 1,2,3-triazoles derived from ibuprofen using click chemistry.

    Science.gov (United States)

    Angajala, Kishore Kumar; Vianala, Sunitha; Macha, Ramesh; Raghavender, M; Thupurani, Murali Krishna; Pathi, P J

    2016-01-01

    Nonsteroidal anti-inflammatory drugs are of vast therapeutic benefit in the treatment of different types of inflammatory conditions. 1,2,3-Triazoles and their derivatives have a wide range of applications as anti-bacterial, anti-fungal, anti-tubercular, cytostatic, anti-HIV, anti-allergic, anti-neoplastic and anti-inflammatory (AI) agents. Considering the individual biological and medicinal importance of ibuprofen and 1,2,3-triazoles, we wanted to explore novel chemical entities based on ibuprofen and triazole moieties towards their biological significance. Click chemistry has utilized as an ideal strategy to prepare novel ibuprofen-based 1,4-disubstituted 1,2,3-triazole containing molecules. These compounds were screened for their in vivo AI activity, among all the synthesized analogues 13o was shown potent effect than the reference AI drug ibuprofen at the same concentration (10 mg/kg body weight). Compounds 13l, 13g, 13c, 13k, 13i, 13n, 13m and 13j were shown significant AI activity. These triazole analogues were also screened for their bactericidal profile. Compounds 13c, 13i, 13l and 13o exhibited considerable bactericidal activity against gram positive and gram negative strains. In addition to this, molecular docking studies were also carried out into cyclooxygenase-2 active site to predict the affinity and orientation of these novel compounds (13a-q). In summary, we have designed and synthesized 1,2,3-triazole analogues of ibuprofen in good yields using Click chemistry approach. AI and bactericidal activities of these compounds were evaluated and shown remarkable results.

  3. [Pharmaceutical chemistry of drug-initiated photosensitivity].

    Science.gov (United States)

    Rácz, Ákos; Tóth, Lívia

    2015-01-01

    The photosensitivity originated from drugs is a common problem in medical and pharmaceutical practice. It is of prominent importance in drug development and in regulatory issues. The photosensitizer effect of drug substances is determined by their chemical structures, and it mainly originates from aromatic chromophore systems and photo-dissociable bonds forming free radicals. The photodegradation may happen in many different types of chemical reaction pathways. Our aim is to demonstrate in this review the interrelations between structure and photodegradation. We show examples for the different reaction types, with drugs from different pharmacologic therapeutic classes. The in vivo chemical reactivity of photodegradates of pharmaceutical substances, the in vitro methods of investigation for testing photoreactivity and phototoxicity, and briefly the clinical tests for photosensitivity disorders are also discussed.

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

    Directory of Open Access Journals (Sweden)

    Viktoriya Georgievna Barskova

    2011-01-01

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

  5. Non-Steroidal Anti-Inflammatory Drugs: An Overview of Cardiovascular Risks

    Directory of Open Access Journals (Sweden)

    Mart A.F.J. van de Laar

    2010-07-01

    Full Text Available While aspirin may offer protection, other non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs can cause serious cardiovascular side effects and complications. This has led to a general "black box" warning for cardiovascular adverse events for NSAIDs. This review explores the different mechanisms underlying the protective effects of aspirin, the NSAID associated renovascular effects causing hypertension, edema and heart failure, the cardiovascular effects causing myocardial infarction and stroke, and the possible deleterious interaction between NSAIDs and aspirin.

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

    OpenAIRE

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

    2013-01-01

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

  7. Calotropis procera Latex-Induced Inflammatory Hyperalgesia—Effect of Antiinflammatory Drugs

    Directory of Open Access Journals (Sweden)

    Raman Sehgal

    2005-01-01

    Full Text Available The milky white latex of plant Calotropis procera produces inflammation of the skin and mucous membranes on accidental exposure. It produces edema on local administration due to the release of histamine and prostaglandins and is associated with hyperalgesia. In the present study we have evaluated the antiedematous and analgesic activity of antiinflammatory drugs against inflammatory response induced by dried latex (DL of C procera in rat paw edema model. An aqueous extract of DL of C procera was injected into the subplantar surface of the rat paw and the paw volume was measured by a plethysmometer at 0, 1, 2, 6, 12, and 24 hours. Concomitantly the hyperalgesic response was also evaluated by motility test, stair climbing ability test, dorsal flexion pain test, compression test, and observing the grooming behavior. The inhibitory effect of diclofenac and rofecoxib on edema formation and hyperalgesic response was compared with cyproheptadine (CPH. DL-induced edema formation was maximum at 2 hours that was associated with decreased pain threshold, functional impairment, and grooming. Treatment with antiinflammatory drugs and CPH significantly attenuated the edematous response and grooming, increased the pain threshold, and improved functional parameters. Both antiinflammatory and antiserotonergic drugs significantly inhibited the hyperalgesia associated with DL-induced paw edema. Rofecoxib was found to be superior than diclofenac and was as effective as CPH in ameliorating the hyperalgesia. However, it was found to be less effective than CPH in attenuating edema formation.

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

    Directory of Open Access Journals (Sweden)

    Santosh Thapa

    2016-01-01

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

  9. Pharmacology of Acetaminophen, Nonsteroidal Antiinflammatory Drugs, and Steroid Medications: Implications for Anesthesia or Unique Associated Risks.

    Science.gov (United States)

    Candido, Kenneth D; Perozo, Oscar J; Knezevic, Nebojsa Nick

    2017-06-01

    Acetaminophen, nonsteroidal antiinflammatory drugs (NSAIDs), and corticosteroids, historically used in perioperative management, are potent analgesic medications. They primarily inhibit the cyclooxygenase (COX) enzyme, decreasing the synthesis of prostaglandins, and modulating pain and temperature. Acetaminophen does not inhibit this synthesis at the inflammatory site. The primary mechanism of action of corticosteroids involves regulation of nuclear expression of genes involved in inflammatory pathways and other systemic effects. Metaanalyses have added purposeful perioperative indications, clarified misconceptions, and established protocols for administering these drugs. Some indications, doses, clinical considerations, and adverse effects need to be further studied. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND: Regular aspirin use is associated with reduced risk of several malignancies. Epidemiologic studies analyzing aspirin, nonaspirin nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen use and ovarian cancer risk have been inconclusive. METHODS: We analyzed pooled data from 12 ...

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

    Science.gov (United States)

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

    2014-05-15

    Iontophoresis is an important approach to improve transdermal drug delivery. However, The transdermal enhancement mechanism of iontophoresis was not well known. The relationship between the physicochemical properties of drugs and the transdermal enhancement effect of iontophoresis was revealed in this study. Non-steroidal anti-inflammatory drugs (NSAIDs) were used as the models, including aspirin, ibuprofen and indomethacin. Their oil-water partition coefficients were measured. The carbomer-based hydrogels of them were prepared. Iontophoresis significantly enhanced in vitro transdermal delivery across the rat skins. Strong lipophilicity could lead to high permeation of drugs. However, the dissociation extent (indicated as pKa) of drugs was the key factor to determine the transdermal enhancement effect of iontophoresis. The more dissociation the drugs were, the higher the transdermal enhancement effect of iontophoresis. The drug-loaded hydrogels combined with iontophoresis improved the treatment of rat raw's inflammatory syndrome. Iontophoresis significantly improved the drugs penetrating into the hypodermis, dermis and epidermis, more deeply than the application of drugs alone according to the experimental result of 5-carboxylfluorescein hydrogels. Iontophoresis led to the unordered arrangement of skin intercellular lipids, the significantly increased flowability and loose stratum corneum structure. Iontophoresis is a promising approach to improve transdermal drug delivery with safety and high efficiency. Copyright © 2014. Published by Elsevier B.V.

  12. Cause-Specific Cardiovascular Risk Associated with Nonsteroidal Anti-Inflammatory Drugs among Myocardial Infarction Patients - A Nationwide Study

    DEFF Research Database (Denmark)

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

    2013-01-01

    Non steroidal anti-inflammatory drugs (NSAIDs) increase mortality and morbidity after myocardial infarction (MI). We examined cause-specific mortality and morbidity associated with NSAIDs in a nationwide cohort of MI patients.......Non steroidal anti-inflammatory drugs (NSAIDs) increase mortality and morbidity after myocardial infarction (MI). We examined cause-specific mortality and morbidity associated with NSAIDs in a nationwide cohort of MI patients....

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

    DEFF Research Database (Denmark)

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

    1996-01-01

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

  14. The Critical Role of Organic Chemistry in Drug Discovery.

    Science.gov (United States)

    Rotella, David P

    2016-10-19

    Small molecules remain the backbone for modern drug discovery. They are conceived and synthesized by medicinal chemists, many of whom were originally trained as organic chemists. Support from government and industry to provide training and personnel for continued development of this critical skill set has been declining for many years. This Viewpoint highlights the value of organic chemistry and organic medicinal chemists in the complex journey of drug discovery as a reminder that basic science support must be restored.

  15. Editorial: in silico drug design and medicinal chemistry).

    Science.gov (United States)

    Singla, Rajeev K

    2015-01-01

    Medicinal chemistry is not limited to molecules, their structures and design but also highly cohesive to pharmacological activities. The potency of a molecule varies by its structure. Hence structural activity relationship is the sub-branch which deals with the estimation of ability of a molecule in depicting any pharmacological activity. In silico drug design is a novel technique which is employed in designing a molecule by using computer aided software’s and bringing a superior and potent molecule. In recent years, in silico drug design has been merged with medicinal chemistry especially by the techniques like ligand based strategy to isolate the required structures. By such strategic techniques, there are high chances of delivering high throughput screening which involves of screening large number of molecules in a very less time. Involvement of such techniques would be a boon for development of new drug entity as it can aid in development of newer, safe, effective and potent drug molecules. Hence, the present issue is aimed to emphasize the cohesion between in silico drug design and it significance in medicinal chemistry. The articles which would be published will mainly focus on the role of in silico drug design techniques in the development of molecules to target various disease and disorders. Molecules can from natural/ synthetic/semi synthetic origin. Articles will be a treasure box consisting of employment of computational methods for unprecedented molecules. The issue will be sure an endorsement for international readership and researchers.

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

    Science.gov (United States)

    Rattner, Barnett A; Whitehead, Maria A; Gasper, Grace; Meteyer, Carol U; Link, William A; Taggart, Mark A; Meharg, Andrew A; Pattee, Oliver H; Pain, Deborah J

    2008-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Miyatake S

    2016-08-01

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

  19. The use of Brazilian propolis for discovery and development of novel anti-inflammatory drugs.

    Science.gov (United States)

    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

    2017-06-27

    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.

  20. Molecular basis for nonspecificity of nonsteroidal anti-inflammatory drugs (NSAIDs).

    Science.gov (United States)

    Dwivedi, Avaneesh K; Gurjar, Vaishali; Kumar, Sanjit; Singh, Nagendra

    2015-07-01

    Inhibition of the production of inflammatory mediators by the action of nonsteroidal anti-inflammatory drugs (NSAIDs) is highly accredited to their recognition of cyclooxygenase enzymes. Along with inflammation relief, however, NSAIDs also cause adverse effects. Although NSAIDs strongly inhibit enzymes of the prostaglandin synthesis pathways, several other proteins also serve as fairly potent targets for these drugs. Based on their recognition pattern, these receptors are categorised as enzymes modifying NSAIDs, noncatalytic proteins binding to NSAIDs and enzymes with catalytic functions that are inhibited by NSAIDs. The extensive binding of NSAIDs is responsible for their limited in vivo efficacy as well as the large spectrum of their effects. The biochemical nature of drugs binding to multiple protein targets and its implications on physiology are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Evolution of nonsteroidal anti-inflammatory drugs (NSAIDs): cyclooxygenase (COX) inhibition and beyond.

    Science.gov (United States)

    Rao, Praveen; Knaus, Edward E

    2008-09-20

    NSAIDs constitute an important class of drugs with therapeutic applications that have spanned several centuries. Treatment of inflammatory conditions such as rheumatoid arthritis (RA) and osteoarthritis (OA) starting from the classic drug aspirin to the recent rise and fall of selective COX-2 inhibitors has provided an enthralling evolution. Efforts to discover an ultimate magic bullet to treat inflammation continues to be an important drug design challenge. This review traces the origins of NSAIDs, their mechanism of action at the molecular level such as cyclooxygenase (COX) inhibition, development of selective COX-2 inhibitors, their adverse cardiovascular effects, and some recent developments targeted to the design of effective anti-inflammatory agents with reduced side effects. Literature data is presented describing important discoveries pertaining to the sequential development of classical NSAIDs and then selective COX-2 inhibitors, their mechanism of action, the structural basis for COX inhibition, and recent discoveries. A brief history of the development of NSAIDs and the market withdrawal of selective COX-2 inhibitors is explained, followed by the description of prostaglandin biosynthesis, COX isoforms, structure and function. The structural basis for COX-1 and COX-2 inhibition is described along with methods used to evaluate COX-1/COX-2 inhibition. This is followed by a section that encompasses the major chemical classes of selective COX-2 inhibitors. The final section describes briefly some of the recent advances toward developing effective anti-inflammatory agents such as nitric oxide donor NO-NSAIDs, dual COX/LOX inhibitors and anti-TNF therapy. A great deal of progress has been made toward developing novel anti-inflammatory agents. In spite of the tremendous advances in the last decade, the design and development of a safe, effective and economical therapy for treating inflammatory conditions still presents a major challenge.

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

    Science.gov (United States)

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

    2014-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Wawryk-Gawda Ewelina

    2014-09-01

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

  4. [Appropriate prescription, adherence and safety of non-steroidal anti-inflammatory drugs].

    Science.gov (United States)

    Sostres, Carlos; Lanas, Ángel

    2016-03-18

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the most numerous category of drugs sharing the same mechanism of action and therapeutic activities (anti-inflammatory, analgesic and anti-pyretic). Despite having similar efficacy for pain relieve, the different available NSAIDs show variability in its safety profile. The risk of gastrointestinal and cardiovascular complications varies depending on the dose of NSAID and also the presence of different risk factors. It is necessary, therefore, an individualized case assessment before establishing the indication of the best NSAID for each patient, taking account of the best gastroprotection strategy. Improved prescription and enhanced treatment adherence are central objectives to reduce NSAID-related complications. A recent consensus of the Spanish Association of Gastroenterology and the Spanish societies of Cardiology and Rheumatology intends to promote the rational use of NSAIDs according to new recent studies. This review provides additional aspects to facilitate the optimal decision-making process in the routine use of these drugs in clinical practice. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

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

    Science.gov (United States)

    Qandil, Amjad M.

    2012-01-01

    The design and the synthesis of prodrugs for nonsteroidal anti-inflammatory drugs (NSAIDs) have been given much attention by medicinal chemists, especially in the last decade. As a therapeutic group, NSAIDs are among the most widely used prescribed and over the counter (OTC) medications. The rich literature about potential NSAID prodrugs clearly shows a shift from alkyl, aryalkyl or aryl esters with the sole role of masking the carboxylic acid group, to more elaborate conjugates that contain carefully chosen groups to serve specific purposes, such as enhancement of water solubility and dissolution, nitric oxide release, hydrogen sulfide release, antioxidant activity, anticholinergic and acetylcholinesterase inhibitory (AChEI) activity and site-specific targeting and delivery. This review will focus on NSAID prodrugs that have been designed or were, later, found to possess intrinsic pharmacological activity as an intact chemical entity. Such intrinsic activity might augment the anti-inflammatory activity of the NSAID, reduce its side effects or transform the potential therapeutic use from classical anti-inflammatory action to something else. Reports discussed in this review will be those of NO-NSAIDs, anticholinergic and AChEI-NSAIDs, Phospho-NSAIDs and some miscellaneous agents. In most cases, this review will cover literature dealing with these NSAID prodrugs from the year 2006 and later. Older literature will be used when necessary, e.g., to explain the chemical and biological mechanisms of action. PMID:23247285

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with severe renal complications, including acute renal failure, reduced glomerular filtration rate and interstitial nephritis. Caution against NSAIDs is therefore recommended in advanced chronic kidney disease. In this study...... prescribed NSAID in the 3¿years before the start of RRT. These patients were older (mean age = 63.0 vs 61.4¿years) and had a significantly higher degree of comorbidity (Charlson score = 2.85 vs 2.61, p¿...

  7. Pain Relief for Acute Urolithiasis: The Case for Non-Steroidal Anti-Inflammatory Drugs.

    Science.gov (United States)

    Steinberg, Peter L; Chang, Steven L

    2016-07-01

    Pain from renal colic is often severe and incapacitating. Many patients require emergent hospitalization and aggressive analgesia to relieve such discomfort. For many years, the optimal analgesic strategy has been sought to manage such severe pain. One of the mainstays of therapy for acute renal colic is with non-steroidal anti-inflammatory drugs (NSAIDs). This paper reviews the mechanism by which NSAIDs allow pain relief in renal colic, the evidence for their use in this condition, and the use of NSAIDs combined with other agents in renal colic.

  8. Role of Non-Steroidal Anti-Inflammatory Drugs in Gynecology

    Directory of Open Access Journals (Sweden)

    Anna Livshits

    2010-07-01

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

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

    Directory of Open Access Journals (Sweden)

    John S. Witte

    2010-10-01

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

  10. Nonsteroidal anti-inflammatory drugs may affect cytokine response and benefit healing of combat-related extremity wounds.

    Science.gov (United States)

    Lisboa, Felipe A; Bradley, Matthew J; Hueman, Matthew T; Schobel, Seth A; Gaucher, Beverly J; Styrmisdottir, Edda L; Potter, Benjamin K; Forsberg, Jonathan A; Elster, Eric A

    2017-04-01

    After adequate operative debridement and antimicrobial therapies, combat-related extremity wounds that either heal or fail are both associated with a distinct inflammatory response. Short-term use of nonsteroidal anti-inflammatory drugs in postoperative pain management may affect this response and, by consequence, the healing potential of these wounds. We investigated whether patients treated with nonsteroidal anti-inflammatory drugs had a distinct inflammatory response; different rates of critical colonization, defined as >10 5 colony forming units on quantitative bacteriology; and healing potential. We retrospectively reviewed the records of 73 patients with combat-related extremity wounds. Patients were separated into 2 groups: those who received nonsteroidal anti-inflammatory drugs during the debridement period (nonsteroidal anti-inflammatory drugs group, N = 17) and those who did not (control group; N = 56). Serum and wound tissue samples collected during each operative debridement were measured for 32 known cytokines and tested for quantitative bacteriology, respectively. We compared cytokine concentrations between groups and then designed a logistic regression model to identify variables associated with successful wound healing, while controlling for known confounders. Despite similar demographics and wound characteristics, the nonsteroidal anti-inflammatory drugs group had significant lesser concentrations of inflammatory cytokines, interleukin-2, interleukin-6, interleukin-8, and monocyte chemoattractant protein-1. On multivariate analysis, nonsteroidal anti-inflammatory drug treatment emerged as a predictor of successful wound healing after controlling for known confounders such as wound size, tobacco use, Acute Physiology and Chronic Health Evaluation II score, and critical colonization. Treatment with nonsteroidal anti-inflammatory drugs for postoperative pain management after major combat-related extremity trauma is associated with lesser

  11. Isotope chemistry; a useful tool in the drug discovery arsenal.

    Science.gov (United States)

    Elmore, Charles S; Bragg, Ryan A

    2015-01-15

    As Medicinal Chemists are responsible for the synthesis and optimization of compounds, they often provide intermediates for use by isotope chemistry. Nevertheless, there is generally an incomplete understanding of the critical factors involved in the labeling of compounds. The remit of an Isotope Chemistry group varies from company to company, but often includes the synthesis of compounds labeled with radioisotopes, especially H-3 and C-14 and occasionally I-125, and stable isotopes, especially H-2, C-13, and N-15. Often the remit will also include the synthesis of drug metabolites. The methods used to prepare radiolabeled compounds by Isotope Chemists have been reviewed relatively recently. However, the organization and utilization of Isotope Chemistry has not been discussed recently and will be reviewed herein. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Click Chemistry in Peptide-Based Drug Design

    Directory of Open Access Journals (Sweden)

    Irwin Chaiken

    2013-08-01

    Full Text Available Click chemistry is an efficient and chemoselective synthetic method for coupling molecular fragments under mild reaction conditions. Since the advent in 2001 of methods to improve stereochemical conservation, the click chemistry approach has been broadly used to construct diverse chemotypes in both chemical and biological fields. In this review, we discuss the application of click chemistry in peptide-based drug design. We highlight how triazoles formed by click reactions have been used for mimicking peptide and disulfide bonds, building secondary structural components of peptides, linking functional groups together, and bioconjugation. The progress made in this field opens the way for synthetic approaches to convert peptides with promising functional leads into structure-minimized and more stable forms.

  13. Helicobacter pylori associated chronic gastritis and peptic ulceration in patients taking non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    Shallcross, T M; Rathbone, B J; Wyatt, J I; Heatley, R V

    1990-10-01

    Helicobacter pylori is now recognized as a frequent cause of histological chronic gastritis, and this has radically changed our understanding of this common condition. In the light of these developments, the traditional view that non-steroidal anti-inflammatory drugs are one of the common 'environmental' causes of chronic gastritis has been re-examined. Gastric mucosal biopsies have been studied from 430 patients undergoing routine upper gastrointestinal endoscopy, 99 of whom had recently been taking non-steroidal anti-inflammatory drugs. No significant association was found between the use of these drugs and either the presence of chronic gastritis or the frequency of colonization with H. pylori, although there was a strong association (P less than 0.0001) between H. pylori and gastritis. Non-steroidal anti-inflammatory drugs appear, however, to modify the inflammatory process in the gastric body, leading to a lower frequency of atrophic gastritis (P less than 0.05). The majority of peptic ulcers were associated with H. pylori irrespective of non-steroidal anti-inflammatory drug use, but there was a higher frequency of H. pylori negative ulceration in the patients who had used these agents (P less than 0.04). Peptic ulceration was uncommon in the absence of either H. pylori or recent non-steroidal anti-inflammatory drug use.

  14. Nonsteroidal antiinflammatory drugs and dyspepsia in general practice – a prospective, controlled study

    Directory of Open Access Journals (Sweden)

    Marija Skok

    2005-01-01

    Full Text Available Background: Treatment of dyspeptic patients is a diagnostic and therapeutic problem frequently encountered by general and family practitioners, by internists and gastroenterologists.Aims: In our study we attempted to assess the prevalence of dyspeptic symptoms in patients over 60 who are regular users of nonsteroidal antiinflammatory drugs.Patients and methods: This is a prospective cohort study based on an interview during examination in the OPC, the results obtained by the diagnostic procedures and follow-up. It was carried out between 1999 and 2003 at a family practitioner’s and a gastroenterologic OPC. In patients who were regular users of nonsteroidal antiinflammatory drugs, we established the prevalence of dyspeptic symptoms, the most often used drugs and the type of diagnostic procedure applied to define the cause of dyspepsia. The control group was composed of patients over 60 who were also exhibiting dyspeptic symptoms but not using any NSAID.Results: The study comprised 50 patients, 27 women and 23 men, the mean age was 67.3 years, the range 60–80 years. The control group comprised 50 patients, 28 women and 22 men, the mean age was 66.6 years, the range 61–80 years. All patients of the study group had used NSAR or preparations of acetylsalicylic acid during the past 3 months. There were no statistically significant differences between the patients of both groups as regards the number and use of other drugs, p = 0.65. The average score of dyspeptic complaints in our study group was 3.02, SD ± 0.6, and 70% of patients wished to use H2 antagonists or proton pump inhibitors for these complaints. In patients of the control group, the average score of complaints was 2.72, SD ± 0.7, and they also took drugs for the alleviation of their complaints more rarely.Conclusions: Nonsteroidal antiinflammatory drugs belong among the important causes of dyspepsia in the elderly. When making decisions about the various diagnostic procedures for

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-12-31

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

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  17. Industrial natural product chemistry for drug discovery and development.

    Science.gov (United States)

    Bauer, Armin; Brönstrup, Mark

    2014-01-01

    Covering: up to March 2013. In addition to their prominent role in basic biological and chemical research, natural products are a rich source of commercial products for the pharmaceutical and other industries. Industrial natural product chemistry is of fundamental importance for successful product development, as the vast majority (ca. 80%) of commercial drugs derived from natural products require synthetic efforts, either to enable economical access to bulk material, and/or to optimize drug properties through structural modifications. This review aims to illustrate issues on the pathway from lead to product, and how they have been successfully addressed by modern natural product chemistry. It is focused on natural products of current relevance that are, or are intended to be, used as pharmaceuticals.

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    DEFF Research Database (Denmark)

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

    1999-01-01

    Nabumetone, a newer non-steroidal anti-inflammatory drug (NSAID) which preferentially blocks cyclo-oxygenase-2 activity, may be less nephrotoxic than indomethacin. This study tested whether nabumetone has effects different from those of indomethacin on exercise-induced changes in renal function...... and the renin-aldosterone system. In a randomized fashion, ten subjects were studied after indomethacin (100 mg), nabumetone (1 g) or no medication (control) administered orally at 22.00 hours on the day before each study day, and again at 8.00 hours upon arrival at the laboratory. Renal function was studied...... decreased the plasma renin concentration. Thus, during exercise, nabumetone may decrease the excretion of 6-oxo-PGF(1alpha) by inhibition of cyclo-oxygenase-1 or by inhibition of specific exercise-induced activation of cyclo-oxygenase-2, or both. None of the drugs changed the renal response to exercise...

  1. Anti-tumor activity of non-steroidal anti-inflammatory drugs: Cyclooxygenase-independent targets

    Science.gov (United States)

    Liggett, Jason L.; Zhang, Xiaobo; Eling, Thomas E.; Baek, Seung Joon

    2014-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are used extensively for analgesic and antipyretic treatments. In addition, NSAIDs reduce the risk and mortality to several cancers. Their mechanisms in anti-tumorigenesis are not fully understood, but both cyclooxygenase (COX)-dependent and -independent pathways play a role. We and others have been interested in elucidating molecular targets of NSAID-induced apoptosis. In this review, we summarize updated literature regarding cellular and molecular targets modulated by NSAIDs. Among those NSAIDs, sulindac sulfide and tolfenamic acid are emphasized in this review because these two drugs have been well investigated for their anti-tumorigenic activity in many different types of cancer. PMID:24486220

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

    International Nuclear Information System (INIS)

    Ekinci, Neslihan; Kavaz, Esra; Özdemir, Yüksel

    2014-01-01

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

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

    Science.gov (United States)

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

    2018-04-14

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

  4. Effect of lipid molecule headgroup mismatch on non steroidal anti-inflammatory drugs induced membrane fusion.

    Science.gov (United States)

    Mondal Roy, Sutapa; Sarkar, Munna

    2011-12-20

    Membrane fusion is an essential process guiding many important biological events, which most commonly requires the aid of proteins and peptides as fusogenic agents. Small drug induced fusion at low drug concentration is a rare event. Only three drugs, namely, meloxicam (Mx), piroxicam (Px), and tenoxicam (Tx), belonging to the oxicam group of non steroidal anti-inflammatory drugs (NSAIDs) have been shown by us to induce membrane fusion successfully at low drug concentration. A better elucidation of the mechanism and the effect of different parameters in modulating the fusion process will allow the use of these common drugs to induce and control membrane fusion in various biochemical processes. In this study, we monitor the effect of lipid headgroup size mismatch in the bilayer on oxicam NSAIDs induced membrane fusion, by introducing dimyristoylphosphatidylethanolamine (DMPE) in dimyristoylphosphatidylcholine (DMPC) small unilamellar vesicles (SUVs). Such headgroup mismatch affects various lipid parameters which includes inhibition of trans-bilayer motion, domain formation, decrease in curvature, etc. Changes in various lipidic parameters introduce defects in the membrane bilayer and thereby modulate membrane fusion. SUVs formed by DMPC with increasing DMPE content (10, 20, and 30 mol %) were used as simple model membranes. Transmission electron microscopy (TEM) and differential scanning calorimetry (DSC) were used to characterize the DMPC-DMPE mixed vesicles. Fluorescence assays were used to probe the time dependence of lipid mixing, content mixing, and leakage and also used to determine the partitioning of the drugs in the membrane bilayer. How the inhibition of trans-bilayer motion, heterogeneous distribution of lipids, decrease in vesicle curvature, etc., arising due to headgroup mismatch affect the fusion process has been isolated and identified here. Mx amplifies these effects maximally followed by Px and Tx. This has been correlated to the enhanced

  5. Nonsteroidal Anti-inflammatory Drug-related Gastrointestinal Bleeding in the Elderly

    Directory of Open Access Journals (Sweden)

    Shou-Chuan Shih

    2007-03-01

    Full Text Available Nonsteroidal anti-inflammatory drug (NSAID could induce gastrointestinal (GI injury by way of topical (mucus, gastric acid and drug interaction and systemic mechanism (decreased prostaglandin synthesis. Compared with non-NSAID users, elderly taking NSAID or aspirin have a higher chance than younger people of developing GI bleeding (5.5-fold vs. 1.65-fold. Endoscopy is the best tool to identify the source and severity of ulcer with bleeding. The use of NSAID or aspirin should be weighed carefully in elderly who have a history of peptic ulcer. If necessary, it is better to choose cyclooxygenase-2 inhibitor since it has been reported that the drug has less than half the risk of non-selective NSAID to ignite GI complications. Eradication of Helicobacter pylori might reduce ulcer risk in new NSAID users, but not in patients with long-term therapy. Proton pump inhibitor is the drug of choice that is effective for both treatment and prevention (taken together with NSAID of NSAID-related GI bleeding.

  6. Effect of nonsteroidal anti-inflammatory drug Rofecoxib (Vioxx™ on the bone repair

    Directory of Open Access Journals (Sweden)

    Luiz Alberto Milanezi

    2008-01-01

    Full Text Available Objective: To evaluate the effect of the nonsteroidal anti-inflammatory drug Rofecoxib (Vioxx™ on the bone repair process in the tibiae of stressed rats. Methods: In this study, use was made of 48 young male (Albinus Wistar rats weighing between 150 and 200 grams, divided into three groups of 16 animals each. The following procedures were performed: Group I was used as the control group, and in it, only the bone defect was performed; in Group II the animals received stressor stimulus in the three pre-operative days and three post- operative days after the defect was performed, up to the time of sacrifice; in Group III the animals received the administration of nonsteroidal anti-inflammatory medication (pre-operatively, stressor stimulus one hour after drug administration, in the pre-operative period, bone defect and stress in the post-operative period, up to the time of sacrifice. In groups of four, the animals were sacrificed at 7, 14, 30 and 60 post-operative days, by means of cervical column dislocation. After being sacrificed, the right and left tibiae were removed, fixed in formalin, decalcified in ethylenodiaminatetracetic acid (Na.2H2.2H2O and included in paraffin. Cuts of 6 micrometers thickness were stained with hematoxylin and eosin for microscopic analysis. Results: The results obtained were described as a function of the post-operative time of the histomorphologic occurrences observed in the different experimental groups. Conclusion: The results allowed one to conclude that: 1 repair of the bone defect caused in the rats of Group II were shown to be more delayed than those in Group I; 2 repair of the bone defect caused in the rats of Group III were shown to be less delayed than those in Group II; 3 the prescription of the anti-inflammatory drug Rofecoxib can be indicated in the case of experiments with stressed animals, because it diminished the effect of stress on bone repair, in the case of defects caused in the tibia of rats.

  7. Development of novel transdermal self-adhesive films for tenoxicam, an anti-inflammatory drug.

    Science.gov (United States)

    Nesseem, Demiana I; Eid, S F; El-Houseny, S S

    2011-09-26

    The purpose of this study was to develop transdermal films (TFs) with the addition of different polymer ratios that incorporated 0.5% tenoxicam in order to ensure maximum controlled and sustained drug release capacity. Tenoxicam is a non-steroidal anti-inflammatory drug (NSAID) widely used in the treatment of rheumatic diseases and characterized by its efficacy and reduced side effects in comparison to other NSAIDs. Transdermal films of tenoxicam were designed with the Eudragit L30D-55copolymer with permeation enhancers like polyethylene glycol (PEG) and propylene glycol (PG) incorporated at different concentrations using the casting evaporation technique. Evaluations of these formulae were performed through mechanical characterizations and Fourier Transform Infrared Spectroscopy [FTIR]. In-vitro release studies were performed during 24h using diffusion cells. The film formulations with optimum in vitro-release rate have been taken up for testing of the anti-inflammatory effects and the sustaining action of tenoxicam. The in-vivo studies performed included carrageenan-induced hind paw edema and skin biopsies in Wistar rats. Formulation (F7) had the best effective combination [glycerol (0.25g), PEG200 (0.5g), PEG400 (1g) and PG (10%) and 0.5% dispersed drug] among all of the tenoxicam TF formulations studied. Also, this formula had the highest release value than formula 1 (F1) that contains [glycerol (2.5g), PEG200 (0.5g), PEG400 (0.5g) and 0.5% dissolved drug] or a commercially available gel after 24h. FTIR revealed that there was an interaction between the polymer and the drug. The drug-polymer interaction occurring between tenoxicam and Eudragit L30D-55 seems to cause a drag effect, leading to a delay of the tenoxicam release from the Eudragit L film. When the films were applied half an hour before the subplantar injection of carrageenan in the hind paw of Wistar rats, it was observed that formula F7 provided maximum inhibition of paw edema in rats over 24h in

  8. Overview of the prescribing patterns of non-steroidal anti-inflammatory drugs : 2004-2006 / Magdalena Adriana Harmzen

    OpenAIRE

    Harmzen, Magdalena Adriana

    2008-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for systemic control of acute and chronic pain and inflammation (Lin et ah, 2000:1129), but usage problems and side-effects that occur during the post-marketing phase of these drugs are well documented (Thiefin & Beaugerie, 2005:287). Following the demonstration of the value of anti-inflammatory therapy in diseases like rheumatoid arthritis (Boardman & Dudley Hart, 1967:268), new NSAIDs appeared on the market (Dieppe et al., 2004:...

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  10. Non-steroidal anti-inflammatory drugs in sports medicine: guidelines for practical but sensible use.

    Science.gov (United States)

    Paoloni, J A; Milne, C; Orchard, J; Hamilton, B

    2009-10-01

    Non-steroidal anti-inflammatory drugs (NSAID) are commonly used in sports medicine. NSAID have known anti-inflammatory, analgesic, antipyretic and antithrombotic effects, although their in-vivo effects in treating musculoskeletal injuries in humans remain largely unknown. NSAID analgesic action is not significantly greater than paracetamol for musculoskeletal injury but they have a higher risk profile, with side-effects including asthma exacerbation, gastrointestinal and renal side-effects, hypertension and other cardiovascular diseases. The authors recommend an approach to NSAID use in sports medicine whereby simple analgesia is preferentially used when analgesia is the primary desired outcome. However, based both on the current pathophysiological understanding of most injury presentations and the frequency that inflammation may actually be a component of the injury complex, it is premature to suppose that NSAID are not useful to the physician managing sports injuries. The prescribing of NSAID should be cautious and both situation and pathology specific. Both dose and duration minimisation should be prioritized and combined with simple principles of protection, rest, ice, compression, elevation (PRICE), which should allow NSAID-sparing. NSAID use should always be coupled with appropriate physical rehabilitation. NSAID are probably most useful for treating nerve and soft-tissue impingements, inflammatory arthropathies and tenosynovitis. They are not generally indicated for isolated chronic tendinopathy, or for fractures. The use of NSAID in treating muscle injury is controversial. Conditions in which NSAID use requires more careful assessment include ligament injury, joint injury, osteoarthritis, haematoma and postoperatively.

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

    Directory of Open Access Journals (Sweden)

    Mohamed Nadjib Boukhatem

    2014-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-12-01

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

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

    International Nuclear Information System (INIS)

    Al-Rajab, Abdul Jabbar; Sabourin, Lyne; Lapen, David R.; Topp, Edward

    2010-01-01

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

  14. [Present status of gastrointestinal damage due to non-steroidal anti-inflammatory drugs (NSAIDs)].

    Science.gov (United States)

    Inaba, Tomoki; Ishikawa, Shigenao; Miyoshi, Masatsugu; Kurahara, Koichi

    2013-06-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are roughly divided into a low-dose aspirin group used for primary and secondary prevention of cardiovascular events and non-aspirin NSAIDs used for treatment of bone and joint diseases. Both cause gastrointestinal damage directly or indirectly. In the present study, we reviewed gastrointestinal damage due to non-aspirin NSAIDs with respect to the esophagus, stomach/duodenum, small intestine and colon. Damage due to NSAIDs occurs in all digestive tracts and since the analgesic effect of NSIADs hides subjective symptoms, the symptoms are often not treated until they are advanced to a serious state. Further, patients receiving NSAIDs are mostly elderly and have complications so that the onset of the conditions is serious and prevention is important. It is necessary to investigate a method that is effective for preventing damage for all digestive tracts and the mechanisms of damage must be understood for this reason.

  15. DNA replication is the target for the antibacterial effects of nonsteroidal anti-inflammatory drugs.

    Science.gov (United States)

    Yin, Zhou; Wang, Yao; Whittell, Louise R; Jergic, Slobodan; Liu, Michael; Harry, Elizabeth; Dixon, Nicholas E; Kelso, Michael J; Beck, Jennifer L; Oakley, Aaron J

    2014-04-24

    Evidence suggests that some nonsteroidal anti-inflammatory drugs (NSAIDs) possess antibacterial properties with an unknown mechanism. We describe the in vitro antibacterial properties of the NSAIDs carprofen, bromfenac, and vedaprofen, and show that these NSAIDs inhibit the Escherichia coli DNA polymerase III β subunit, an essential interaction hub that acts as a mobile tether on DNA for many essential partner proteins in DNA replication and repair. Crystal structures show that the three NSAIDs bind to the sliding clamp at a common binding site required for partner binding. Inhibition of interaction of the clamp loader and/or the replicative polymerase α subunit with the sliding clamp is demonstrated using an in vitro DNA replication assay. NSAIDs thus present promising lead scaffolds for novel antibacterial agents targeting the sliding clamp. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Do non-steroidal anti-inflammatory drugs or smoking predispose to Helicobacter pylori infection?

    Science.gov (United States)

    Maxton, D G; Srivastava, E D; Whorwell, P J; Jones, D M

    1990-09-01

    Susceptibility to Helicobacter pylori infection is a poorly understood phenomenon. This study was undertaken to establish whether either smoking or chronic non-steroidal anti-inflammatory drug (NSAID) consumption might in some way predispose to H. pylori infection and hence lead to peptic ulceration. Serological evidence of H. pylori infection was assessed in 100 consecutive subjects receiving NSAIDs without any evidence of gastrointestinal upset and 100 matched controls. All subjects had a full assessment of their smoking habits. Sixty-three per cent of patients taking NSAIDs compared to 51% of controls had evidence of H. pylori infection (NS). Smoking habit also had no effect on H. pylori colonization. The ulcerogenic potential of NSAIDs and smoking does not appear to be mediated via a prediposition to H. pylori infection.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

    Klein, Mads; Gögenur, Ismail; Rosenberg, Jacob

    2012-01-01

    ) 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......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...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    Epidemiologic studies investigating the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on breast cancer have yielded conflicting results. We examined the association between use of aspirin and nonaspirin NSAIDs and breast cancer risk among 28 695 women in the Danish Diet, Cancer...... was unrelated to breast cancer incidence. The increased breast cancer incidence among NSAID users may reflect a noncausal association, but our study provides no evidence of a chemopreventive effect of NSAIDs against breast cancer over the durations studied. Udgivelsesdato: 2008-Apr...... and Health cohort. Information on NSAID and paracetamol use was obtained from a self-administered questionnaire completed at baseline (1993-1997) and updated through 2003 using a nationwide prescription database. Detailed information on breast cancer incidence and tumour characteristics was obtained from...

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

    DEFF Research Database (Denmark)

    Brøns, Nanna; Baandrup, Louise; Dehlendorff, Christian

    2015-01-01

    -matched female controls were randomly selected by risk-set sampling. Information on NSAID use was collected from the Prescription Registry and classified according to duration and intensity. Conditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs), adjusting......PURPOSE: We examined the association between use of low-dose aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) and endometrial cancer risk in a nationwide case-control study. METHODS: Cases were all women in Denmark diagnosed with endometrial cancer during 2000-2009. Age...... with use of low-dose aspirin (OR 0.97, 95 % CI 0.89-1.05) or non-aspirin NSAIDs (OR 0.96, 95 % CI 0.91-1.02) compared with nonuse. The ORs did not vary with increasing duration or intensity of NSAID use or with type of endometrial cancer. Interaction analyses showed reduced endometrial cancer risk...

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

    DEFF Research Database (Denmark)

    Skriver, Charlotte; Dehlendorff, Christian; Borre, Michael

    2016-01-01

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

  2. The Use of Stilbene Scaffold in Medicinal Chemistry and Multi- Target Drug Design.

    Science.gov (United States)

    Giacomini, Elisa; Rupiani, Sebastiano; Guidotti, Laura; Recanatini, Maurizio; Roberti, Marinella

    2016-01-01

    The stilbene scaffold is a basic element for a number of biologically active natural and synthetic compounds, and it is considered as a privileged structure. Stilbenes exemplified by resveratrol, combretastatin A-4 and pterostilbene are of significant interest for drug research and development because of their potential in therapeutic and preventive application. Resveratrol, present in grapes and other food products, plays a role in the prevention of several human pathological processes and has been suggested as an anticancer agent. Moreover, recent evidence has revealed its potential effect on the aging process, diabetes and neurological dysfunction. Combretastatin A-4, from the bark of South African bush willow Combretum caffrum, also shows significant antitumor activity. Pterostilbene is closely related to resveratrol, sharing the same unique therapeutic potential as anti-inflammatory, antineoplastic and antioxidant agent. Therefore, research and development of stilbene-based medicinal chemistry have become rapidly evolving and increasingly active topics covering almost the whole range of therapeutic fields. In the present review, we provide an overview of the role of stilbenes in medicinal chemistry. In this context, we highlight the chemical methodologies adopted for the synthesis of stilbene derivatives, and outline the successful design of novel stilbene based hybrids in the field of cancer, Alzheimer's and other relevant diseases. This information may be useful in further design of stilbene-based molecules as new leads for the development of novel agents with clinical potential or as effective chemical probes to dissect biological processes.

  3. No Impact of Preadmission Anti-Inflammatory Drug Use on Risk of Depression and Anxiety After Critical Illness.

    Science.gov (United States)

    Medici, Clara R; Gradus, Jaimie L; Pedersen, Lars; Sørensen, Henrik T; Østergaard, Søren D; Christiansen, Christian F

    2017-10-01

    Risk of depression and anxiety is elevated after intensive care. Drugs with anti-inflammatory properties may have antidepressant and anxiolytic effects. The aim of this study was to investigate the association between preadmission use of drugs with anti-inflammatory effects and risk of new-onset depression and anxiety among adult patients admitted to an ICU. Propensity score-matched, population-based cohort study. All ICUs in Denmark from 2005 to 2013. Adults receiving mechanical ventilation in an ICU. None. A total of 48,207 ICU patients were included. Exposures were preadmission single-agent or combined use of statins, nonsteroidal anti-inflammatory drugs, or glucocorticoids. Outcomes were cumulative incidence (risk) and risk ratio of new-onset psychiatrist-diagnosed depression or anxiety or prescriptions for antidepressants or anxiolytics. Propensity score matching yielded 6,088 statin user pairs, 2,886 nonsteroidal anti-inflammatory drug user pairs, 1,440 glucocorticoid user pairs, and 1,743 combination drug user pairs. The cumulative incidence of anxiety and depression during the 3 years following intensive care was 18.0% (95% CI, 17.0-19.0%) for statin users, 21.3% (95% CI, 19.8-22.9%) for nonsteroidal anti-inflammatory drug users, 17.4% (95% CI, 15.4-19.5%) for glucocorticoid users, and 19.0% (95% CI, 16.3-20.2%) for combination users. The cumulative incidence was similar in nonusers compared with users in all drug groups. The risk ratio of depression and anxiety 3 years after admission to ICU was 1.04 (95% CI, 0.96-1.13) for statin users, 1.00 (95% CI, 0.90-1.11) for nonsteroidal anti-inflammatory drug users, 0.97 (95% CI, 0.82-1.14) for glucocorticoid users, and 1.05 (95% CI, 0.90-1.21) for combination users, compared with nonusers. Results were consistent across subgroups (gender, age, preadmission diseases, type of admission) and sensitivity analyses (depression and anxiety separately). Preadmission use of statins, nonsteroidal anti-inflammatory drugs

  4. Prevention of Renal Complications Induced by Non- Steroidal Anti-Inflammatory Drugs.

    Science.gov (United States)

    Ković, Sonja Vuč; Vujović, Katarina Savić; Srebro, Dragana; Medić, Branislava; Ilic-Mostic, Tatjana

    2016-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for the treatment of pain, inflamation and fever. They are usually well tolerated in healthy persons, but in patients with risk factors (advanced age, renal impairment, heart failure, liver disease, concurrent medications with antihypertensive drugs), NSAIDs can induce serious renal adverse effects. They include sodium and water retention with edema, worsening of heart failure, hypertension, hyponatremia, hyperkalemia, acute kidney injury, chronic kidney disease, renal papillary necrosis and acute interstitial nephritis. The majority of these adverse effects are due to the inhibition of prostaglandins synthesis and they are dose and duration-dependent. Acute forms of kidney injuries are transient and often reversible upon drug withdrawal. Chronic use of NSAIDs in some patients may result in chronic kidney disease. It is recommended that patients at risk should have preventative strategies in place, including the use of the "lowest effective dose" of NSAID for the "shortest possible time" and monitoring renal function, fluid retention and electrolyte abnormalities. Patients who are taking antihypertensive medications should be monitored for high blood pressure and the doses of antihypertensive medications should be adjusted if needed. In general, the combination of NSAIDs and angiotensin inhibitors should be avoided. Some other preventive measures are dietary salt restriction, use of topical NSAIDs/non-pharmacological therapies and use of calcium channel blockers for treating hypertension.

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

    Science.gov (United States)

    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.

  6. Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy

    Science.gov (United States)

    Wallace, John L

    2013-01-01

    This article reviews the latest developments in understanding the pathogenesis, detection and treatment of small intestinal damage and bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs). With improvements in the detection of NSAID-induced damage in the small intestine, it is now clear that this injury and the associated bleeding occurs more frequently than that occurring in the stomach and duodenum, and can also be regarded as more dangerous. However, there are no proven-effective therapies for NSAID-enteropathy, and detection remains a challenge, particularly because of the poor correlation between tissue injury and symptoms. Moreover, recent studies suggest that commonly used drugs for protecting the upper gastrointestinal tract (i.e., proton pump inhibitors) can significantly worsen NSAID-induced damage in the small intestine. The pathogenesis of NSAID-enteropathy is complex, but studies in animal models are shedding light on the key factors that contribute to ulceration and bleeding, and are providing clues to the development of effective therapies and prevention strategies. Novel NSAIDs that do not cause small intestinal damage in animal models offer hope for a solution to this serious adverse effect of one of the most widely used classes of drugs. PMID:23569332

  7. Extractive spectrophotometric determination of some nonsteroidal anti-inflammatory drugs using methylene blue.

    Science.gov (United States)

    El-Kommos, Michael E; Mohamed, Niveen A; Hakiem, Ahmed F Abdel

    2013-01-01

    A simple, rapid, sensitive, and accurate extractive spectrophotometric method has been developed for the determination of seven nonsteroidal anti-inflammatory drugs (NSAIDs)--namely diclofenac sodium, ibuprofen, indomethacin, ketoprofen, ketorolac tromethamine, mefenamic acid, and naproxen-in pure forms as well as their pharmaceutical dosage forms (tablets, capsules, effervescent granules, syrups, oral drops, ampules, eye drops, gels, and suppositories). The method depends on the formation of an intensely colored ion-pair complex between the acidic drug and methylene blue in alkaline medium. The complex is stable and extractable into methylene chloride. All parameters were optimized. Beer-Lambert's law was obeyed in concentrations ranging from 0.04 to 9 microg/mL. Statistical analysis of the calibration data was carried out, and correlation coefficients were in the range from 0.9996 to 0.9998. The developed method was fully validated according to International Conference on Harmonization guidelines, and complied with U.S. Pharmacopeia guidelines. The proposed method was applied to the analysis of the investigated drugs in their pharmaceutical formulations, and good recoveries were obtained. The results obtained were compared with those of reported and official methods, and no significant differences were found with t- and F-tests. Interference effects of some compounds usually present in combination with NSAIDs were studied, and the tolerance limits of these compounds were determined.

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

    Science.gov (United States)

    Nechipadappu, Sunil Kumar; Trivedi, Darshak R.

    2017-08-01

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

  9. Differential impairment of aspirin-dependent platelet cyclooxygenase acetylation by nonsteroidal antiinflammatory drugs

    Science.gov (United States)

    Li, Xuanwen; Fries, Susanne; Li, Ruizhi; Lawson, John A.; Propert, Kathleen J.; Diamond, Scott L.; Blair, Ian A.; FitzGerald, Garret A.; Grosser, Tilo

    2014-01-01

    The cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs) may be influenced by interactions with antiplatelet doses of aspirin. We sought to quantitate precisely the propensity of commonly consumed NSAIDs—ibuprofen, naproxen, and celecoxib—to cause a drug–drug interaction with aspirin in vivo by measuring the target engagement of aspirin directly by MS. We developed a novel assay of cyclooxygenase-1 (COX-1) acetylation in platelets isolated from volunteers who were administered aspirin and used conventional and microfluidic assays to evaluate platelet function. Although ibuprofen, naproxen, and celecoxib all had the potential to compete with the access of aspirin to the substrate binding channel of COX-1 in vitro, exposure of volunteers to a single therapeutic dose of each NSAID followed by 325 mg aspirin revealed a potent drug–drug interaction between ibuprofen and aspirin and between naproxen and aspirin but not between celecoxib and aspirin. The imprecision of estimates of aspirin consumption and the differential impact on the ability of aspirin to inactivate platelet COX-1 will confound head-to-head comparisons of distinct NSAIDs in ongoing clinical studies designed to measure their cardiovascular risk. PMID:25385584

  10. Experimental evidence of MAP kinase gene expression on the response of intestinal anti-inflammatory drugs.

    Science.gov (United States)

    Quaglio, Ana Elisa Valencise; Castilho, Anthony Cesar Souza; Di Stasi, Luiz Claudio

    2015-09-01

    The etiopathogenesis of inflammatory bowel disease (IBD) is unclear and further understanding of the mechanisms that regulate intestinal barrier integrity and function could give insight into its pathophysiology and mode of action of current drugs used to treat human IBD. Therefore, we investigated how intestinal inflammation affects Map kinase gene expression in rats, and if current intestinal anti-inflammatory drugs (sulphasalazine, prednisolone and azathioprine) act on these expressions. Macroscopic parameters of lesion, biochemical markers (myeloperoxidase, alkaline phosphatase and glutathione), gene expression of 13Map kinases, and histologic evaluations (optic, electronic scanning and transmission microscopy) were performed in rats with colonic inflammation induced by trinitrobenzenesulphonic (TNBS) acid. The colonic inflammation was characterized by a significant increase in the expression of Mapk1, Mapk3 and Mapk9 accompanied by a significant reduction in the expression ofMapk6. Alterations inMapk expression induced by TNBS were differentially counteracted after treatment with sulphasalazine, prednisolone and azathioprine. Protective effects were also related to the significant reduction of oxidative stress, which was related to increase Mapk1/3 expressions, which were reduced after pharmacological treatment. Mapk1, Mapk3,Mapk6 and Mapk9 gene expressionswere affected by colonic inflammation induced by TNBS in rats and counteracted by sulphasalazine, prednisolone and azathioprine treatments, suggesting that these genes participate in the pharmacological response produced for these drugs.

  11. Radioiodination and bio-evaluation of some anti-inflammatory drugs

    International Nuclear Information System (INIS)

    Mohamed, H.H.

    2009-01-01

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

  12. Pharmacology of nonsteroidal anti-inflammatory drugs. Practical review for clinicians.

    Science.gov (United States)

    O'Brien, W M

    1983-10-31

    Aspirin and the newer nonsteroidal anti-inflammatory drugs are the mainstay of basic therapy in rheumatoid arthritis and the other rheumatic diseases. Despite its many years of clinical use, the pharmacologic actions of aspirin are still not fully understood; those of many of the newer nonsteroidals may offer significant advantages in terms of long-term safety. Studies in animals and normal human volunteers, as well as clinical trials, provide useful information about the absorption, metabolism, excretion, efficacy, appropriate dosage, and safety of a given nonsteroidal agent. Because all of the newer agents have been developed using the same basic animal tests of efficacy, they all closely resemble indomethacin. Differences in half-life, however, may be important in determining the relative safety of a nonsteroidal, especially in older patients. Most of the nonsteroidals bind only to albumin, and therefore have a kind of built-in safety mechanism: once the albumin binding sites are saturated, free drug is rapidly excreted by the kidney and drug accumulation is prevented. Despite this fact, the clinician must be concerned about two frequent sorts of problems that may arise from the prostaglandin-inhibiting effects of the nonsteroidals. Gastrointestinal side effects may include minor symptoms; diffuse gastritis; small erosions of the gastric mucosa, visible only by endoscope; and frank ulceration, which may rarely be life-threatening. Animal studies, various tests in normal volunteers, and pre-marketing clinical studies may all shed light on the relative ulcerogenicity of a given nonsteroidal agent. Long-term clinical experience especially helps indicate which agents appear to be more ulcerogenic than average and which appear to be less than average. Renal effects of the nonsteroidals are also related to their inhibition of prostaglandin synthesis. The most serious of these--a characteristic kind of interstitial nephritis, renal papillary necrosis, and hyperkalemia

  13. Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes–2

    Directory of Open Access Journals (Sweden)

    Diego Muñoz-Torrero

    2017-12-01

    Full Text Available Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials, which are published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules [...

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

    International Nuclear Information System (INIS)

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

    1996-01-01

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    OpenAIRE

    Guslandi, Mario

    2006-01-01

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

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

    DEFF Research Database (Denmark)

    Kjær, Birgitte; Struve, Casper; Friis, Tina

    2010-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit tumor growth and angiogenesis. Covalent linkage of naproxen to human serum albumin (HSA) has been shown to target it efficiently to the liver and this may potentially be exploited for liver-selective inhibition of angiogenesis. With the aim...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    NARCIS (Netherlands)

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

    1998-01-01

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

  20. Bladder Pain Syndrome Treated with Triple Therapy with Gabapentin, Amitriptyline, and a Nonsteroidal Anti-Inflammatory Drug

    OpenAIRE

    Lee, Jea Whan; Han, Dong Youp; Jeong, Hee Jong

    2010-01-01

    Purpose Bladder pain syndrome is a chronic disease that manifests as bladder pain, frequency, nocturia, and urgency. Gabapentin, amitriptyline, and nonsteroidal anti-inflammatory drugs are efficacious treatments for bladder pain syndrome. Here, we assessed the effect of triple therapy with these drugs in women with bladder pain syndrome. Methods Between May 2007 and May 2010, we conducted a prospective nonrandomized study on 74 patients with bladder pain syndrome. Of these patients, 38 (11 me...

  1. Click chemistry with polymers, dendrimers, and hydrogels for drug delivery.

    Science.gov (United States)

    Lallana, Enrique; Fernandez-Trillo, Francisco; Sousa-Herves, Ana; Riguera, Ricardo; Fernandez-Megia, Eduardo

    2012-04-01

    During the last decades, great efforts have been devoted to design polymers for reducing the toxicity, increasing the absorption, and improving the release profile of drugs. Advantage has been also taken from the inherent multivalency of polymers and dendrimers for the incorporation of diverse functional molecules of interest in targeting and diagnosis. In addition, polymeric hydrogels with the ability to encapsulate drugs and cells have been developed for drug delivery and tissue engineering applications. In the long road to this successful story, pharmaceutical sciences have been accompanied by parallel advances in synthetic methodologies allowing the preparation of precise polymeric materials with enhanced properties. In this context, the introduction of the click concept by Sharpless and coworkers in 2001 focusing the attention on modularity and orthogonality has greatly benefited polymer synthesis, an area where reaction efficiency and product purity are significantly challenged. The purpose of this Expert Review is to discuss the impact of click chemistry in the preparation and functionalization of polymers, dendrimers, and hydrogels of interest in drug delivery.

  2. Modern advances in heterocyclic chemistry in drug discovery.

    Science.gov (United States)

    Taylor, Alexandria P; Robinson, Ralph P; Fobian, Yvette M; Blakemore, David C; Jones, Lyn H; Fadeyi, Olugbeminiyi

    2016-07-12

    New advances in synthetic methodologies that allow rapid access to a wide variety of functionalized heterocyclic compounds are of critical importance to the medicinal chemist as it provides the ability to expand the available drug-like chemical space and drive more efficient delivery of drug discovery programs. Furthermore, the development of robust synthetic routes that can readily generate bulk quantities of a desired compound help to accelerate the drug development process. While established synthetic methodologies are commonly utilized during the course of a drug discovery program, the development of innovative heterocyclic syntheses that allow for different bond forming strategies are having a significant impact in the pharmaceutical industry. This review will focus on recent applications of new methodologies in C-H activation, photoredox chemistry, borrowing hydrogen catalysis, multicomponent reactions, regio- and stereoselective syntheses, as well as other new, innovative general syntheses for the formation and functionalization of heterocycles that have helped drive project delivery. Additionally, the importance and value of collaborations between industry and academia in shaping the development of innovative synthetic approaches to functionalized heterocycles that are of greatest interest to the pharmaceutical industry will be highlighted.

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

    Directory of Open Access Journals (Sweden)

    Alireza Rouhani

    2013-09-01

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

  4. Mechanisms of peroxisome proliferator activated receptor γ regulation by non-steroidal anti-inflammatory drugs

    Science.gov (United States)

    Puhl, Ana C.; Milton, Flora A.; Cvoro, Aleksandra; Sieglaff, Douglas H.; Campos, Jéssica C.L.; Bernardes, Amanda; Filgueira, Carly S.; Lindemann, Jan Lammel; Deng, Tuo; Neves, Francisco A.R.; Polikarpov, Igor; Webb, Paul

    2015-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) display anti-inflammatory, antipyretic and analgesic properties by inhibiting cyclooxygenases and blocking prostaglandin production. Previous studies, however, suggested that some NSAIDs also modulate peroxisome proliferator activated receptors (PPARs), raising the possibility that such off target effects contribute to the spectrum of clinically relevant NSAID actions. In this study, we set out to understand how peroxisome proliferator activated receptor-γ (PPARγ/PPARG) interacts with NSAIDs using X-ray crystallography and to relate ligand binding modes to effects on receptor activity. We find that several NSAIDs (sulindac sulfide, diclofenac, indomethacin and ibuprofen) bind PPARγ and modulate PPARγ activity at pharmacologically relevant concentrations. Diclofenac acts as a partial agonist and binds to the PPARγ ligand binding pocket (LBP) in typical partial agonist mode, near the β-sheets and helix 3. By contrast, two copies of indomethacin and sulindac sulfide bind the LBP and, in aggregate, these ligands engage in LBP contacts that resemble agonists. Accordingly, both compounds, and ibuprofen, act as strong partial agonists. Assessment of NSAID activities in PPARγ-dependent 3T3-L1 cells reveals that NSAIDs display adipogenic activities and exclusively regulate PPARγ-dependent target genes in a manner that is consistent with their observed binding modes. Further, PPARγ knockdown eliminates indomethacin activities at selected endogenous genes, confirming receptor-dependence of observed effects. We propose that it is important to consider how individual NSAIDs interact with PPARγ to understand their activities, and that it will be interesting to determine whether high dose NSAID therapies result in PPAR activation. PMID:26445566

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

    Science.gov (United States)

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

    2015-11-01

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

  6. Non-steroidal anti-inflammatory drugs, antiplatelet medications and spinal axis anesthesia.

    Science.gov (United States)

    Broadman, Lynn M

    2005-03-01

    Many individuals use cyclo-oxygenase inhibitors (COX-1 and COX-2 non-steroidal anti-inflammatory drugs) and antiplatelet medications on a regular basis. This is particularly true of the elderly, who are more prone to having osteoarthritis, rheumatoid arthritis, and cardiac disease. Some of these agents alter platelet function and may increase the risk of spinal/epidural hematoma formation if spinal axis anesthesia is utilized without following proper precautions. All anesthesiologists should be familiar with these agents and how they work. More importantly, they should be familiar with the established guidelines set forth by the American Society of Regional Anesthesia (ASRA) [Regional anesthesia in the anticoagulated patient-defining the risk (2002); Reg. Anes. Pain Med. 28 (2003)172], the German Society of Anesthesiology and Intensive Care Medicine (DGAI) [Anaesthesiol. Intensivmed. 38 (1997) 623], and the Spanish Consensus Forum [Rev. Esp. Anesthesiol. Reanim. 48 (2001) 270]. This article explains the mechanism of action of each of the medications which alter platelet function, defines the risks of hematoma formation should the medication be inadvertently continued into the perioperative period, and provides guidelines and recommendations on how to manage each class of drug prior to the placement of spinal/epidural blocks.

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

    Directory of Open Access Journals (Sweden)

    Elena Rusu

    2014-12-01

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

  8. Use of a /sup 51/Cr technique to detect gastrointestinal microbleeding associated with nonsteroidal antiinflammatory drugs

    Energy Technology Data Exchange (ETDEWEB)

    Lussier, A.; Arsenault, A.; Varady, J.; de Medicis, R.; Lussier, Y.; LeBel, E.

    1987-02-01

    Of techniques used to evaluate gastrointestinal (GI) bleeding, use of radiochromium (/sup 51/Cr)-tagged erythrocytes is the most quantitative and scientifically acceptable method. The value of this technique as well as systematic errors possible with its use are discussed. The medical literature concerning /sup 51/Cr evaluation of GI microbleeding with naproxen therapy is critically reviewed. We suggest that future studies using this technique be parallel, randomized, double-blind, and include a 1-week placebo baseline phase for all subjects. Treatment with nonsteroidal antiinflammatory drugs (NSAIDs) should last 3 to 4 weeks. A parallel group of subjects should receive placebo throughout the study. For valid statistical analyses, randomization must achieve baseline comparability of weight, height, age, and sex in the treatment groups. Data transformations may be necessary to satisfy the assumptions of the statistical model. Following these guidelines will enable investigators to better evaluate GI microbleeding during treatment with naproxen or other NSAIDs, and, hopefully, to establish the safety profiles of these drugs.37 references.

  9. Eco-pharmacovigilance of non-steroidal anti-inflammatory drugs: Necessity and opportunities.

    Science.gov (United States)

    He, Bing-Shu; Wang, Jun; Liu, Juan; Hu, Xia-Min

    2017-08-01

    Eco-pharmacovigilance (EPV) is a practical and powerful approach to minimize the potential risks posed by pharmaceutical residues in environment. However, it is impracticable to practise rigorous and unitary EPV process for all the existing and new pharmaceuticals. Here, we focused on non-steroidal anti-inflammatory drugs (NSAIDs), and discussed the necessity and potential opportunities of practising EPV of NSAIDs. We found that the consumption of NSAIDs is huge and ubiquitous across the globe. NSAIDs were worldwidely reported as one of the most dominant and frequently detected groups in environmental matrices including wastewater, surface water, suspended solids, sediments, groundwater, even drinking water. Besides, there is definitive evidence for the adverse impacts of NSAID residues on scavenging birds and aquatic species. These data suggested the necessity of implementing EPV of NSAIDs. From the perspective of drug administration, we identified some things that can be done as management practice options for EPV implementation on NSAIDs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Prohypertensive effects of non-steroidal anti-inflammatory drugs are mostly due to vasoconstriction.

    Science.gov (United States)

    Pavlicević, Ivancica; Glavaski, Milan; Rumboldt, Mirjana; Rumboldt, Zvonko

    2011-09-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have prohypertensive effects and blunt the effects of many antihypertensives. The mechanism of this interaction is still not understood enough. The objective of this investigation was to determine the level of prohypertensive effects of two NSAIDs (ibuprofen, piroxicam) and paracetamol, co-prescribed with two antihypertensive drugs (lisinopril + hydrochlorothiazide, amlodipine), and to improve the understanding of this interaction. A prospective clinical trial, conducted in a Croatian family practice, included 110 already treated hypertensive patients, aged 56-85 years; 50 control patients and 60 patients who were also taking NSAIDs for osteoarthritis treatment. The antihypertensive regimens remained the same during this study, while NSAIDs and paracetamol were crossed-over in three monthly periods. Blood pressure, body weight, serum creatinine, potassium, sodium, diuresis and 24 h urinary sodium excretion were followed-up. In the lisinopril/hydrochlorothiazide subgroup, both ibuprofen and piroxicam elevated mean arterial pressure by 8.9-9.5% (p NSAID's prohypertensive effects seem to be mostly due to vasoconstriction and, to a minor degree, to volume expansion, since no marked changes in body weight, urinary output, serum creatinine or serum/urinary electrolyte profile were observed.

  11. Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement.

    Science.gov (United States)

    Cuzick, Jack; Otto, Florian; Baron, John A; Brown, Powel H; Burn, John; Greenwald, Peter; Jankowski, Janusz; La Vecchia, Carlo; Meyskens, Frank; Senn, Hans Jörg; Thun, Michael

    2009-05-01

    Evidence clearly shows a chemopreventive effect for aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) on colorectal cancer and probably other cancer types; however, data on the risk-benefit profile for cancer prevention are insufficient and no definitive recommendations can be made. Aspirin has emerged as the most likely NSAID for use in chemoprevention because of its known cardiovascular benefit and available safety and efficacy data. Other traditional NSAIDs, particularly sulindac, and selective COX-2 inhibitors are now given to patients at high risk of colorectal cancer, although these drugs do not provide cardioprotection. More studies of aspirin and cancer prevention are needed to define the lowest effective dose, the age at which to initiate therapy, the optimum treatment duration, and the subpopulations for which the benefits of chemoprevention outweigh the risks of adverse side-effects. Although it might be possible to answer some of these questions with longer follow-up of existing clinical trials, randomised controlled trials with new study designs will be needed. Future projects should investigate the effects of aspirin treatment on multiple organ systems. Cancers of interest are colorectal, breast, prostate, lung, stomach, and oesophageal. The main side-effect of aspirin is peptic ulcers; therefore coadministration of aspirin with a proton-pump inhibitor is an attractive option and is under investigation in the AspECT trial.

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

    LENUS (Irish Health Repository)

    Kitchen, J

    2012-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Hongsik Cho

    2015-01-01

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

  14. Non-steroidal Anti-inflammatory Drug Induced Injury to the Small Intestine

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    Ilja Tachecí

    2010-01-01

    Full Text Available Non-steroidal anti-inflammatory drug (NSAIDs induced enteropathy represents an important complication of one of the most commonly used drugs worldwide. Due to previous diagnostics difficulties the real prevalence of this disease was underestimated for a long time. The pathogenesis of NSAID-enteropathy is more multifactorial and complex than formerly assumed but has still not been fully uncovered. A combination of the local and systemic effect plays an important role in pathogenesis. Thanks to novel enteroscopy methods (wireless capsule endoscopy, double balloon enteroscopy, small bowel lesions are described in a substantial section of NSAID users although most are clinically asymptomatic. The other non-invasive tests (small bowel permeability, faecal calprotectin, scintigraphy using faecal excretion of 111-indium-labelled leukocytes etc. proposed for diagnostics are not generally used in clinical practice, mainly because of their non-specificity. Despite intensive research into possible treatment, the main measure for patients with NSAID-enteropathy is still withdrawal of NSAIDs. Double balloon enteroscopy plays an important role in the treatment of complications (bleeding, strictures.

  15. Variability of the drug response to nonsteroidal anti-inflammatory drugs according to cyclooxygenase-2 genetic polymorphism

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    Lee SJ

    2017-09-01

    Full Text Available Sook Joung Lee,1,* Min Kyu Park,2,* Dong-Seong Shin,3 Min Ho Chun4 1Department of Physical Medicine and Rehabilitation, Dong-A University College of Medicine, Dong-A University Hospital, 2Department of Pharmacology and Clinical Pharmacology, Dong-A University College of Medicine, Dong-A University Hospital, Busan, 3Clinical Trials Center, Gachon University Gil Medical Center, Incheon, 4Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea *These authors contributed equally to this work Purpose: Cyclooxygenase (COX is the main pharmacodynamic target of nonsteroidal anti-inflammatory drugs (NSAIDs. We investigated the inhibitory effects on COX-2 after NSAIDs administration using a lipopolysaccharide (LPS-derived COX-2 induction model in whole blood, according to the genotypes of COX-2 single-nucleotide polymorphisms (SNPs. Patients and methods: Seven genotypes of COX-2 SNPs were selected from public databases and analyzed in 324 healthy subjects. Two genotypes showing a high percentage of variability were selected. A clinical trial examining pharmacodynamics according to the genotype of two SNPs (rs5275 and rs689466 was conducted. Twenty subjects were administered a single oral dose of 200 mg of celecoxib, and pharmacokinetic and pharmacodynamic analyses were performed. Results: In the analysis of the pharmacokinetic parameters, significant differences in drug exposure were not investigated for each SNP genotype. The pharmacodynamic analysis revealed that the maximum effect of COX-2 inhibition was achieved at 2.0 hours for all genotypes of COX-2 SNPs after a single oral administration of 200 mg celecoxib. The inhibitory effects according to the genotype of COX-2 SNPs were investigated, and the area under the effect curve of the rs689466 GG genotype was significantly lower than that for the AA or AG genotype. Conclusion: Our results demonstrated that inhibitory effects of

  16. A química medicinal de N-acilidrazonas: novos compostos-protótipos de fármacos analgésicos, antiinflamatórios e anti-trombóticos Medicinal chemistry of N-acylhydrazones: novel lead-compounds of analgesic, antiinflammatory and antithrombotic drugs

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    Eliezer J. Barreiro

    2002-02-01

    Full Text Available In this article are described new bioactive N-acylhydrazone (NAH derivatives, structurally designed as optimization of aryl hydrazones precursors planned by molecular hybridization of two 5-lipoxigenase inhibitors, e.g. CBS-1108 and BW-755c. The analgesic, antiedematogenic and anti-platelet aggregating profile of several isosteric compounds was investigated by using classic pharmacological assays in vivo and ex-vivo, allowing to identify new potent peripheric analgesic lead, a new anti-inflammatory and an antithrombotic agent. During this study was discovered dozen of active NAH compounds clarifying the structure-activity relationship for this series of NAH derivatives, indicating the pharmacophore character of the N-acylhydrazone functionality.

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

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    Erica Hoffer

    2002-01-01

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

  18. Effect of nonsteroidal anti-inflammatory drugs on colorectal distension-induced visceral pain

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    Baskın, Veysel; Bilge, S. Sırrı; Bozkurt, Ayhan; Akyüz, Bahar; Ağrı, Arzu Erdal; Güzel, Hasan; İlkaya, Fatih

    2016-01-01

    Objectives: To investigate nonsteroidal anti-inflammatory drugs effectiveness in colorectal distension (CRD)-induced visceral pain model. Materials and Methods: Male Sprague–Dawley (250–300 g) rats were anesthetized with ketamine (50 mg/kg, intraperitoneally [i.p.]) and chlorpromazine (25 mg/kg, i.p.). Two bipolar Teflon-coated Ni/Cr wire electrodes (80-M diameter) were placed in the abdominal external oblique muscle for the recording of electromyography. Jugular vein catheter was placed for the administration of drugs. CRD method was applied to evaluate of visceral pain. All drugs (paracetamol, meloxicam, metamizole, and dexketoprofen) administered intravenously. Results: Paracetamol 200, 400, and 600 mg/kg did not change the visceromotor response (VMR) when compare with the control group. Meloxicam 2 and 4 mg/kg showed no effect but at doses of 6 mg/kg meloxicam significantly ([51.9 ± 6.4%] [P Dexketoprofen 2 and 4 mg/kg did not cause a change in VMR but 6 mg/kg dose significantly reduced response compared with the control group ([43.9 ± 3.9%, 36.8 ± 2.8%, 34.8 ± 2.5%, 42.1 ± 4.8%, 40.7 ± 3.5%, 36.4 ± 2.7%, and 26.1 ± 2.2%]; from 10 min to 70 min, respectively, [P dexketoprofen and meloxicam show antinociceptive effect with different duration of action on CRD-induced visceral pain model. This condition can be explained due to different chemical structures and different mechanisms which play a role in modulation of pain. PMID:27114637

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

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

    2012-10-01

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

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

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    Daniele A. Cardinale

    2017-12-01

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

  1. Anti-Inflammatory Drugs and Herbs with Special Emphasis on Herbal Medicines for Countering Inflammatory Diseases and Disorders - A Review.

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    Yatoo, Mohd Iqbal; Gopalakrishnan, Arumugam; Saxena, Archana; Parray, Oveas Rafiq; Tufani, Noore Alam; Chakraborty, Sandip; Tiwari, Ruchi; Dhama, Kuldeep; Iqbal, Hafiz M N

    2018-01-15

    Diseases with inflammatory etiopathology have increased in incidence in recent times. Drugs used for therapeutic management of such inflammatory diseases are relieving the ailment but at the same time also countering serious life-threatening consequences. Moreover, they are costly and rarely available at all places. In this context, research and development on medicinal herbs have opened a new era in the prophylactic and therapeutic management of inflammatory diseases. To highlight the importance of anti-inflammatory medicine-synthetic drugs and natural herbs, their constituents, mechanism of action, benefits, side effects and future prospects. The overall aim is to provide better health services to patiens regardless of their background on equality basis. Anti-inflammatory herbs have proven beneficial by combating inflammatory responses that lead to severe abnormality in body systems. Inflammation though a protective response to infection or injury and may result in pathological outcome when aggravated or of severe degree thus needs an early intervention for proper resolution. Medicinal plants or their constituents are considered beneficial due to the properties i.e., satisfactory potency, ease of availability, cheapness, less or no side effects, safer and efficient as compared to the synthetic counterparts. These medicinal herbs contain phytoconstituents that can prevent undesirable inflammatory processes and also posses anti-inflammatory activity. Steroids, glycosides, phenolics, flavonoids, alkaloids, polysaccharides, terpenoids, cannabinoids, fatty acids are common phytoconstituents present in these plants. Different mechanisms have been explored for the anti-inflammatory action of these active ingredients. They may synergize the anti-inflammatory pathway enzymes, factors, proteins or interfere with these in the inflammatory pathway like lipooxygenases, cyclooxygenases, tumor necrosis factors, interleukins, prostaglandin, nitric oxide, mitogen

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

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

    1982-08-01

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

  3. Mechanisms of action of non-steroidal anti-inflammatory drugs (NSAIDs) and mesalazine in the chemoprevention of colorectal cancer.

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    Stolfi, Carmine; De Simone, Veronica; Pallone, Francesco; Monteleone, Giovanni

    2013-09-03

    Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide. Although conclusive evidence is still lacking, epidemiologic studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) has chemopreventive properties against CRC. Similarly, regular consumption of mesalazine, a drug structurally related to NSAIDs, seems to reduce the risk of CRC in patients with ulcerative colitis. These observations are supported by a large body of experimental data showing the ability of such drugs to inhibit multiple pathways that sustain colon carcinogenesis. This review summarizes the current information on the molecular mechanisms by which NSAIDs and mesalazine could interfere with CRC cell growth and survival.

  4. Mechanisms of Action of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Mesalazine in the Chemoprevention of Colorectal Cancer

    Science.gov (United States)

    Stolfi, Carmine; De Simone, Veronica; Pallone, Francesco; Monteleone, Giovanni

    2013-01-01

    Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide. Although conclusive evidence is still lacking, epidemiologic studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) has chemopreventive properties against CRC. Similarly, regular consumption of mesalazine, a drug structurally related to NSAIDs, seems to reduce the risk of CRC in patients with ulcerative colitis. These observations are supported by a large body of experimental data showing the ability of such drugs to inhibit multiple pathways that sustain colon carcinogenesis. This review summarizes the current information on the molecular mechanisms by which NSAIDs and mesalazine could interfere with CRC cell growth and survival. PMID:24005861

  5. Development of non-steroidal anti-inflammatory drug intolerance over a 3 year period

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    Toshihiro Shirai

    2004-01-01

    Full Text Available We report the detailed clinical course of a 47-year-old woman with aspirin-induced asthma in which non-steroidal anti-inflammatory drug (NSAID intolerance developed over a 3 year period. The patient had mild asthma and was admitted with a femoral fracture in August 1996. Although she was given NSAIDs, including rectal diclofenac and oral loxoprofen, there was no worsening of asthma. After discharge, she was followed as having NSAID-tolerant asthma. When she developed perennial rhinitis and anosmia subsequent to an upper respiratory tract infection, asthma control was well maintained. Later, she experienced three episodes of severe asthmatic attacks after intake of aspirin or ketoprofen. Thus, we investigated her NSAID tolerability in September 1999. Sodium tolmetin inhalation challenge demonstrated a positive reaction, leading to the diagnosis of aspirin-induced asthma. Open challenges with loxoprofen and diclofenac also provoked positive reactions. The present case illustrates the potential variability of aspirin-induced asthma. Aspirin or NSAIDs challenge tests should be performed when nasal symptoms, particularly anosmia, develop or worsen.

  6. Characteristics of hemorrhagic peptic ulcers in patients receiving antithrombotic/nonsteroidal antiinflammatory drug therapy.

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    Nakamura, Kazuhiko; Akahoshi, Kazuya; Ochiai, Toshiaki; Komori, Keishi; Haraguchi, Kazuhiro; Tanaka, Munehiro; Nakamura, Norimoto; Tanaka, Yoshimasa; Kakigao, Kana; Ogino, Haruei; Ihara, Eikichi; Akiho, Hirotada; Motomura, Yasuaki; Kabemura, Teppei; Harada, Naohiko; Chijiiwa, Yoshiharu; Ito, Tetsuhide; Takayanagi, Ryoichi

    2012-10-01

    Antithrombotic/nonsteroidal antiinflammatory drug (NSAID) therapies increase the incidence of upper gastrointestinal bleeding. The features of hemorrhagic peptic ulcer disease in patients receiving antithrombotic/NSAID therapies were investigated. We investigated the medical records of 485 consecutive patients who underwent esophagogastroduodenoscopy and were diagnosed with hemorrhagic gastroduodenal ulcers. The patients treated with antithrombotic agents/NSAIDs were categorized as the antithrombotic therapy (AT) group (n=213). The patients who were not treated with antithrombotics/NSAIDs were categorized as the control (C) group (n=263). The clinical characteristics were compared between the groups. The patients in the AT group were significantly older than those in the C group (p<0.0001). The hemoglobin levels before/without transfusion were significantly lower in the AT group (8.24±2.41 g/dL) than in the C group (9.44±2.95 g/dL) (p<0.0001). After adjusting for age, the difference in the hemoglobin levels between the two groups remained significant (p=0.0334). The transfusion rates were significantly higher in the AT group than in the C group (p=0.0002). However, the outcome of endoscopic hemostasis was similar in the AT and C groups. Patients with hemorrhagic peptic ulcers receiving antithrombotic/NSAID therapies were exposed to a greater risk of severe bleeding that required transfusion but were still treatable by endoscopy.

  7. Cardiovascular safety of non-steroidal anti-inflammatory drugs revisited.

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    Walker, Chris; Biasucci, Luigi M

    2018-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used to treat inflammatory pain for decades. More recently, newer NSAIDs were developed to target the inducible isoform of cyclooxygenase (COX), COX-2, with the aim of reducing gastrointestinal toxicity. While the COX-2 selective inhibitors were effective in reducing pain and gastrointestinal harm, they soon were associated with an increased risk of adverse cardiovascular events. Initially, the view emerged that selective inhibition of COX-2, and sparing of COX-1, was responsible for the increased cardiovascular harm observed. However, as more data from different human populations has become available this view has begun to be challenged. This review examines the current understanding of the role of prostaglandins and COX-1 and COX-2, particularly in platelets, the vasculature, and the kidney together with an overview of the cardiovascular and renal safety of both traditional NSAIDs and COX-2 selective inhibitors. Available data from active comparator randomized controlled trials, including the data from the PRECISION trial investigating the long term cardiovascular safety of patients exclusively with elevated baseline cardiovascular risk, are presented. The data, when considered holistically, support the idea that all NSAIDs carry some level of cardiovascular risk, be they traditional NSAIDs or COX-2 selective agents. There is also some evidence of heterogeneity of effect with NSAIDs particularly in relation to effects on blood pressure, with no clear demarcation based on the degree of COX-2 selectivity.

  8. Non-steroidal anti-inflammatory drug indometacin enhances endogenous remyelination.

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    Preisner, Anna; Albrecht, Stefanie; Cui, Qiao-Ling; Hucke, Stephanie; Ghelman, Julia; Hartmann, Christine; Taketo, Makoto Mark; Antel, Jack; Klotz, Luisa; Kuhlmann, Tanja

    2015-08-01

    Multiple sclerosis is the most frequent demyelinating disease in the CNS that is characterized by inflammatory demyelinating lesions and axonal loss, the morphological correlate of permanent clinical disability. Remyelination does occur, but is limited especially in chronic disease stages. Despite effective immunomodulatory therapies that reduce the number of relapses the progressive disease phase cannot be prevented. Therefore, promotion of neuroprotective and repair mechanisms, such as remyelination, represents an attractive additional treatment strategy. A number of pathways have been identified that may contribute to impaired remyelination in MS lesions, among them the Wnt/β-catenin pathway. Here, we demonstrate that indometacin, a non-steroidal anti-inflammatory drug (NSAID) that has been also shown to modulate the Wnt/β-catenin pathway in colorectal cancer cells promotes differentiation of primary human and murine oligodendrocytes, myelination of cerebellar slice cultures and remyelination in cuprizone-induced demyelination. Our in vitro experiments using GSK3β inhibitors, luciferase reporter assays and oligodendrocytes expressing a mutant, dominant stable β-catenin indicate that the mechanism of action of indometacin depends on GSK3β activity and β-catenin phosphorylation. Indometacin might represent a promising treatment option to enhance endogenous remyelination in MS patients.

  9. Do Nonsteroidal Anti-Inflammatory Drugs Affect Bone Healing? A Critical Analysis

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    Ippokratis Pountos

    2012-01-01

    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs play an essential part in our approach to control pain in the posttraumatic setting. Over the last decades, several studies suggested that NSAIDs interfere with bone healing while others contradict these findings. Although their analgesic potency is well proven, clinicians remain puzzled over the potential safety issues. We have systematically reviewed the available literature, analyzing and presenting the available in vitro animal and clinical studies on this field. Our comprehensive review reveals the great diversity of the presented data in all groups of studies. Animal and in vitro studies present so conflicting data that even studies with identical parameters have opposing results. Basic science research defining the exact mechanism with which NSAIDs could interfere with bone cells and also the conduction of well-randomized prospective clinical trials are warranted. In the absence of robust clinical or scientific evidence, clinicians should treat NSAIDs as a risk factor for bone healing impairment, and their administration should be avoided in high-risk patients.

  10. An update on the efficacy of non-steroidal anti-inflammatory drugs in Alzheimer's disease.

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    Imbimbo, Bruno P

    2009-08-01

    Several epidemiological studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer's disease (AD), especially for patients carrying one or more epsilon4 allele of the apolipoprotein E. The biological mechanism of this protection is not completely understood and may involve inhibition of COX activity, inhibition of beta-amyloid(1-42) (Abeta42) production and aggregation, inhibition of beta-secretase activity, activation of PPAR-gamma or stimulation of neurotrophin synthesis. Unfortunately, long-term, placebo-controlled clinical trials with both non-selective and COX-2 selective NSAIDs in AD patients produced negative results. A secondary prevention study with rofecoxib in patients with mild cognitive impairment and a primary prevention study with naproxen and celecoxib in elderly subjects with a family history of AD were also negative. All these failures have diminished the hope that NSAIDs could be beneficial in the treatment of AD. It is hypothesized that the chronic use of NSAIDs may be beneficial only in the normal brain by inhibiting the production of Abeta42. Once the Abeta deposition process has started, NSAIDs are no longer effective and may even be detrimental because of their inhibiting activity on activated microglia of the AD brain, which mediates Abeta clearance and activates compensatory hippocampal neurogenesis.

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

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

    2007-01-01

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

  12. Innovative sampling and extraction methods for the determination of nonsteroidal anti-inflammatory drugs in water.

    Science.gov (United States)

    Tanwar, Shivani; Di Carro, Marina; Magi, Emanuele

    2015-03-15

    Two different innovative approaches were used for the determination of nonsteroidal anti-inflammatory drugs (NSAIDs) in water: stir bar sorptive extraction (SBSE) and passive sampling, followed by electrospray ionization liquid chromatography-tandem mass spectrometry. SBSE was developed by comparing EG-Silicone and PDMS stir bars and optimizing main parameters to attain high preconcentration. Quantitative analysis was carried out by mass spectrometry in negative ionization mode and multiple reaction monitoring. The SBSE-LC-MS/MS method provided satisfactory figures of merit with LOD (7.5-71 ng L(-1)) and LOQ (22.5-213 ng L(-1)). The developed method was successfully applied to real samples collected from river water and wastewater effluents. The obtained results showed the presence of all analytes at trace levels, in a wide range of concentrations. The passive sampling approach was carried out by using Polar Organic Chemical Integrative Sampler (POCIS); samplers were deployed for 15 days in river and tap water, allowing to detect analytes at ultra-trace levels. Time-Weighted Average concentration of NSAIDs in river water was estimated in the range 0.33-0.46 ng L(-1), using the sampling rates previously obtained by means of a simple calibration system. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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    Pajaree Sriuttha

    2018-01-01

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

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

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    Ingela Wiklund

    1999-01-01

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

  15. Nonsteroidal Anti-inflammatory Drugs for Sciatica: An Updated Cochrane Review.

    Science.gov (United States)

    Rasmussen-Barr, Eva; Held, Ulrike; Grooten, Wilhelmus J A; Roelofs, Pepijn D D M; Koes, Bart W; van Tulder, Maurits W; Wertli, Maria M

    2017-04-15

    Systematic review and meta-analysis. To determine the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) on pain reduction, overall improvement, and reported adverse effects in people with sciatica. NSAIDs are one of the most frequently prescribed drugs for sciatica. We updated a 2008 Cochrane Review through June 2015. Randomized controlled trials that compared NSAIDs with placebo, with other NSAIDs, or with other medication were included. Outcomes included pain using mean difference (MD, 95% confidence intervals [95% CI]). For global improvement and adverse effects risk ratios (RR, 95% CI) were used. We assessed level of evidence using the Grades of Recommendation, Assessment, Development and Evaluation approach. Ten trials were included (N = 1651). Nine out of 10 trials were assessed at high risk of bias. For pain reduction (visual analog scale, 0 to 100) NSAIDs were no more effective than placebo (MD -4.56, 95% CI -11.11 to 1.99, quality of evidence: very low). For global improvement NSAIDs were more effective than placebo (RR 1.14 [95% CI 1.03 to 1.27], low quality of evidence). One trial reported the effect of NSAIDs on disability with very low-quality evidence that NSAIDs are no more effective than placebo. There was low-quality evidence that the risk for adverse effects is higher for NSAID than placebo (RR 1.40, 95% CI 1.02 to 1.93). Our findings show very low-quality evidence that the efficacy of NSAIDs for pain reduction is comparable with that of placebo, low-quality evidence that NSAIDs is better than placebo for global improvement and low-quality evidence for higher risk of adverse effects using NSAIDs compared with placebo. The findings must be interpreted with caution, due to small study samples, inconsistent results, and a high risk of bias in the included trials. 1.

  16. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs do not influence the urinary testosterone/epitestosterone glucuronide ratio

    Directory of Open Access Journals (Sweden)

    Jonas eLundmark

    2013-05-01

    Full Text Available The UDP Glucuronosyl Transferase (UGT enzymes are important in the pharmacokinetics, and conjugation, of a variety of drugs including nonsteroidal anti-inflammatory drugs (NSAIDs as well as anabolic androgenic steroids (AAS. Testosterone glucuronidation capacity is strongly associated with a deletion polymorphism in the UGT2B17 gene. As the use of high doses of NSAIDs has been observed in athletes there is a risk for a drug-drug interaction that may influence the doping tests for AAS. In-vitro studies show inhibitory potential on UGT2B7, 2B15 and 2B17 enzymes by NSAIDs. The aim of this study was to investigate if concomitant use of NSAIDs and a single dose of testosterone enanthate would affect the excretion rate of testosterone and epitestosterone glucuronide (TG and EG as well as the T/E ratio, thereby affecting the outcome of the testosterone doping test.The study was designed as an open, randomized, cross-over study with subjects being their own control. The 23 healthy male volunteers, with either two, one or no allele (ins/ins, ins/del or del/del of the UGT2B17 gene, received the maximum recommended dose of NSAID (Ibuprofen or Diclofenac for six days. On day three, 500 mg of testosterone enanthate was administered. Spot urine samples were collected for 17 days. After a wash out period of four months the volunteers received 500 mg testosterone enanthate only, with subsequent spot urine collection for 14 days. The glucuronides of testosterone and epitestosterone were quantified. NSAIDs did not affect the excretion of TG or EG before the administration of testosterone. The concomitant use of NSAIDs and testosterone slightly increased the TG excretion while the EG excretion was less suppressed compared to testosterone use only. The effects of the NSAIDs on the TG and EG excretion did not differ between the UGT2B17 genotype groups. In conclusion, the outcome of testosterone doping tests does not seem to be affected by the use of NSAIDs.

  17. Conformational Analysis of Drug Molecules: A Practical Exercise in the Medicinal Chemistry Course

    Science.gov (United States)

    Yuriev, Elizabeth; Chalmers, David; Capuano, Ben

    2009-01-01

    Medicinal chemistry is a specialized, scientific discipline. Computational chemistry and structure-based drug design constitute important themes in the education of medicinal chemists. This problem-based task is associated with structure-based drug design lectures. It requires students to use computational techniques to investigate conformational…

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    OBJECTIVE: To examine the risk of major cardiovascular disease associated with non-steroidal anti-inflammatory drugs (NSAIDs) in a large 'real-world' contemporary rheumatoid arthritis (RA) cohort. METHODS: A longitudinal cohort study was conducted with use of Danish nationwide individual-level re......OBJECTIVE: To examine the risk of major cardiovascular disease associated with non-steroidal anti-inflammatory drugs (NSAIDs) in a large 'real-world' contemporary rheumatoid arthritis (RA) cohort. METHODS: A longitudinal cohort study was conducted with use of Danish nationwide individual......-level registry data on inpatient and outpatient health care provision, pharmacotherapy and income during 1997-2009. 17 320 RA patients were identified and matched with 69 280 controls (4 : 1) by age and sex. NSAID-associated risk of major cardiovascular disease defined as the combined endpoint of myocardial...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    INTRODUCTION: Helicobacter pylori (HP) infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs)/acetyl salicylic acid (ASA) are risk factors for bleeding peptic ulcer. HP eradication reduces the risk of rebleeding. Antibiotics, proton pump inhibitors (PPI) and presence of blood in the s......INTRODUCTION: Helicobacter pylori (HP) infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs)/acetyl salicylic acid (ASA) are risk factors for bleeding peptic ulcer. HP eradication reduces the risk of rebleeding. Antibiotics, proton pump inhibitors (PPI) and presence of blood...... in the stomach can affect the HP test. The objectives of this study were to determine the HP prevalence and NSAID/ASA use in patients with bleeding ulcer in a low-prevalence HP area, to determine the proportion of idiopathic ulcers and to estimate the proportion of initially false negative HP tests. In addition...

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

    DEFF Research Database (Denmark)

    Nørgård, Bente Mertz

    2011-01-01

    The clinical epidemiological studies included in this thesis fall into three parts. The first part includes studies on birth outcome in women with ulcerative colitis. The second part includes pharmacoepidemiological studies on birth outcome after anti-inflammatory drug therapy in pregnancy......, including patients with ulcerative colitis and Crohn's disease. The third part (and the latest publications) includes birth outcome in women with Crohn's disease; and the methods of cohort establishment in these studies are developed and improved due to the knowledge gathered from conducting the earlier...... in children born by women with ulcerative colitis. The pharmacoepidemiological studies on birth outcomes after use of anti-inflammatory drug therapy in pregnancy, including women with ulcerative colitis and Crohn's disease, are based on data from the Hungarian case-control data set, a countywide Danish...

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

    Science.gov (United States)

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

    2017-09-01

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

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

    OpenAIRE

    Lionberger, David

    2010-01-01

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

  3. Microwave-assisted formulation of solid lipid nanoparticles loaded with non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    Shah, Rohan M; Eldridge, Daniel S; Palombo, Enzo A; Harding, Ian H

    2016-12-30

    Stearic acid-based solid lipid nanoparticles (SLNs) were prepared using the microwave assisted one-pot microemulsions procedure pioneered by our group. In this study, non-steroidal anti-inflammatory drugs (NSAIDs) including indomethacin, ketoprofen and nimesulide were selected as ideal "test" drugs, based on their poor water solubility. The model drugs were incorporated within the SLNs by the microwave-assisted procedure at the time of SLN production. The microwave-produced drug-loaded SLNs were evaluated in terms of their physicochemical characteristics, drug release behavior and their uptake into against A549 cell line (human lung epithelial cells). The microwave-produced drug-loaded SLNs had a small particle size distribution, negative zeta potential and high encapsulation efficiency. The drug release studies were consistent with a core-shell structure of SLNs (probably a drug-loaded shell) which results in biphasic drug release from the SLNs. The drug release kinetics suggested a good fit of the release data to the Makoid-Banakar model and was governed by Fickian diffusion. The drug-loaded SLNs showed concentration-dependent cytotoxicity and reduced IL-6 and IL-8 secretion in lipopolysaccharide-induced cells. All of the above findings suggest that the microwave-produced SLNs could be promising drug carriers of NSAIDs and will further facilitate their development for topical, oral and/or nasal administration. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Pharmacokinetics and Efficacy of Topically Applied Nonsteroidal Anti-Inflammatory Drugs in Retinochoroidal Tissues in Rabbits

    Science.gov (United States)

    Kida, Tetsuo; Kozai, Seiko; Takahashi, Hiroaki; Isaka, Mitsuyoshi; Tokushige, Hideki; Sakamoto, Taiji

    2014-01-01

    Purpose To evaluate the pharmacokinetics and efficacy of topically applied nonsteroidal anti-inflammatory drugs (NSAIDs) in the retinochoroidal tissues of rabbits. Methods The cyclooxygenase (COX) inhibitory activity of diclofenac, bromfenac, and amfenac, an active metabolite of nepafenac, were determined using human-derived COX-1 and COX-2. Each of the three NSAIDs was applied topically to rabbits, and after 0.5 to 8 hrs, the concentration of each drug in the aqueous humor and the retinochoroidal tissues was measured by liquid chromatography-tandem mass spectrometry. The pharmacokinetics of the drugs in the tissues after repeated doses as is done on patients was calculated by a simulation software. The inhibitory effect of each NSAID on the breakdown of the blood-retinal barrier was assessed by the vitreous protein concentration on concanavalin A-induced retinochoroidal inflammation in rabbits. Results The half-maximal inhibitory concentration (IC50) of diclofenac, bromfenac, and amfenac was 55.5, 5.56, and 15.3 nM for human COX-1, and 30.7, 7.45, and 20.4 nM for human COX-2, respectively. The three NSAIDs were detected in the aqueous humor and the retinochoroidal tissue at all-time points. Simulated pharmacokinetics showed that the levels of the three NSAIDs were continuously higher than the IC50 of COX-2, as an index of efficacy, in the aqueous humor, whereas only the bromfenac concentration was continuously higher than the IC50 at its trough level in the retinochoroidal tissues. The intravitreous concentration of proteins was significantly reduced in rabbits that received topical bromfenac (P = 0.026) but not the other two NSAIDs. Conclusions Topical bromfenac can penetrate into the retinochoroidal tissues in high enough concentrations to inhibit COX-2 and exerts its inhibitory effect on the blood-retinal barrier breakdown in an experimental retinochoroidal inflammation in rabbits. Topical bromfenac may have a better therapeutic benefit than diclofenac and

  5. Pharmacokinetics and efficacy of topically applied nonsteroidal anti-inflammatory drugs in retinochoroidal tissues in rabbits.

    Directory of Open Access Journals (Sweden)

    Tetsuo Kida

    Full Text Available PURPOSE: To evaluate the pharmacokinetics and efficacy of topically applied nonsteroidal anti-inflammatory drugs (NSAIDs in the retinochoroidal tissues of rabbits. METHODS: The cyclooxygenase (COX inhibitory activity of diclofenac, bromfenac, and amfenac, an active metabolite of nepafenac, were determined using human-derived COX-1 and COX-2. Each of the three NSAIDs was applied topically to rabbits, and after 0.5 to 8 hrs, the concentration of each drug in the aqueous humor and the retinochoroidal tissues was measured by liquid chromatography-tandem mass spectrometry. The pharmacokinetics of the drugs in the tissues after repeated doses as is done on patients was calculated by a simulation software. The inhibitory effect of each NSAID on the breakdown of the blood-retinal barrier was assessed by the vitreous protein concentration on concanavalin A-induced retinochoroidal inflammation in rabbits. RESULTS: The half-maximal inhibitory concentration (IC50 of diclofenac, bromfenac, and amfenac was 55.5, 5.56, and 15.3 nM for human COX-1, and 30.7, 7.45, and 20.4 nM for human COX-2, respectively. The three NSAIDs were detected in the aqueous humor and the retinochoroidal tissue at all-time points. Simulated pharmacokinetics showed that the levels of the three NSAIDs were continuously higher than the IC50 of COX-2, as an index of efficacy, in the aqueous humor, whereas only the bromfenac concentration was continuously higher than the IC50 at its trough level in the retinochoroidal tissues. The intravitreous concentration of proteins was significantly reduced in rabbits that received topical bromfenac (P = 0.026 but not the other two NSAIDs. CONCLUSIONS: Topical bromfenac can penetrate into the retinochoroidal tissues in high enough concentrations to inhibit COX-2 and exerts its inhibitory effect on the blood-retinal barrier breakdown in an experimental retinochoroidal inflammation in rabbits. Topical bromfenac may have a better therapeutic benefit

  6. Basophil activation after nonsteroidal anti-inflammatory drugs stimulation in patients with immediate hypersensitivity reactions to these drugs.

    Science.gov (United States)

    Ariza, Adriana; Fernandez, Tahia D; Doña, Inmaculada; Aranda, Ana; Blanca-Lopez, Natalia; Melendez, Lidia; Canto, Gabriela; Blanca, Miguel; Torres, Maria J; Mayorga, Cristobalina

    2014-05-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in allergic reactions of which two main types exist: IgE-mediated and crossintolerance. The diagnosis of crossintolerance reactions is often based on the drug provocation test. The potential value of the basophil activation test (BAT) was evaluated using different basophil markers in the diagnosis of patients with crossintolerance to NSAIDs and cutaneous symptoms. We studied 46 patients with crossintolerance to NSAIDs and 45 tolerant controls. BAT was performed with acetyl salicylic acid, paracetamol, diclofenac, dipyrone, naproxen, and ibuprofen at four different concentrations using CD193 and CD203c as basophil markers and CD63 as activation marker. We compared BAT results using CD193⁺ or CD193⁺ CD203c⁺ for basophil selection and found a significant increase in the stimulation index when using CD193⁺ CD203c⁺ in both patients and controls (P = 0.004 and P = 0.017, respectively). Selection of living cells only produced an increase in basophil stimulation in patients for both CD193⁺ and CD193⁺ CD203c⁺ (P < 0.001 for both), whereas in controls there was no change with CD193⁺ and a decrease with CD193⁺ CD203c⁺ (P = 0.001). We found that CD193⁺ CD203c⁺ increased the percentage of positive cases in patients and controls when compared with CD193⁺. When excluding dead cells, there was an increase of 21.7% in patients and 10% in controls. These results indicate that using CD193⁺ CD203⁺, excluding dead cells, is the best approach for BAT although this test is not recommended for the diagnosis of patients with crossintolerance to NSAIDs owing to its low sensitivity and specificity. © 2014 International Society for Advancement of Cytometry.

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

    Science.gov (United States)

    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.

  8. Regulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) by non-steroidal anti-inflammatory drugs (NSAIDs).

    Science.gov (United States)

    Tai, Hsin-Hsiung; Chi, Xiuling; Tong, Min

    2011-11-01

    NSAIDs are known to be inhibitors of cyclooxygenase-2 (COX-2) accounting for their anti-inflammatory and anti-tumor activities. However, the anti-tumor activity cannot be totally attributed to their COX-2 inhibitory activity as these drugs can also inhibit the growth and tumor formation of COX-2-null cell lines. Several potential targets aside from COX-2 for NSAIDs have been proposed. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH), a key prostaglandin catabolic enzyme, was recently shown to be a tumor suppressor. Effects of NSAIDs on 15-PGDH expression were therefore studied. Flurbiprofen, indomethacin and other NSAIDs stimulated 15-PGDH activity in colon cancer HT29 cells as well as in lung cancer A549 cells and glioblastoma T98G cells. (R)-flurbiprofen and sulindac sulfone, COX-2 inactive analogs, also stimulated 15-PGDH activity indicating induction of 15-PGDH is independent of COX-2 inhibition. Stimulation of 15-PGDH expression and activity by NSAIDs was examined in detail in colon cancer HT29 cells using flurbiprofen as a stimulant. Flurbiprofen stimulated 15-PGDH expression and activity by increasing transcription and translation and by decreasing the turnover of 15-PGDH. Mechanism of stimulation of 15-PGDH expression is not clear. Protease(s) involved in the turnover of 15-PGDH remains to be identified. However, flurbiprofen down-regulated matrix metalloproteinase-9 (MMP-9) which was shown to degrade 15-PGDH, but up-regulated tissue inhibitor of metalloproteinase-1 (TIMP-1), an inhibitor of MMP-9 contributing further to a slower turnover of 15-PGDH. Taken together, NSAIDs may up-regulate 15-PGDH by increasing the protein expression as well as decreasing the turnover of 15-PGDH in cancer cells. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Should nonsteroidal anti-inflammatory drugs (NSAIDs) be prescribed to the older adult?

    Science.gov (United States)

    Barkin, Robert L; Beckerman, Mihail; Blum, Steven L; Clark, Frank M; Koh, Eun-Kyu; Wu, Dickson S

    2010-10-01

    The prevalence of chronic pain increases with age, exceeding 50% in individuals aged ≥65 years. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a mainstay of chronic pain management but carry significant dose-related risks of cardiovascular, renal, haematological and other systemic adverse events (AEs). Older patients have an increased risk of these AEs and are more likely to take multiple medications that can potentially interact with NSAIDs. In particular, older patients are more likely to have cardiovascular disease and a natural age-related decline in renal function, increasing the risks of cardiovascular, haematological and renal AEs. Given these risks, recent guidelines for the management of chronic pain in the elderly recommend using NSAIDs rarely and only in carefully selected patients. NSAIDs currently available in the US fall into three categories: nonselective NSAIDs that act via inhibition of cyclo-oxygenase (COX)-1 and COX-2; celecoxib, a selective inhibitor of COX-2; and topical NSAIDs that inhibit both COX-1 and COX-2 but result in much less systemic NSAID exposure than oral formulations. Topical NSAIDs have demonstrated efficacy similar to oral NSAIDs, with an incidence of AEs similar to placebo; however, these agents are an option only in patients with localized pain in superficial joints. Safe pain management in older patients therefore requires cautious choice of selective and nonselective oral NSAIDs, topical NSAIDs or non-NSAID analgesics. This article discusses the risks and benefits of NSAID therapy, reviews its mechanism of action as the source of adverse effects and provides recommendations for maximizing NSAID safety, particularly in older patients. Articles cited in this review were identified via a search of PubMed (January 2005 to November 2009) and a manual search of reference lists from the articles identified in that search. Priority was given to articles discussing NSAID use in older populations, clinical trials of high quality

  10. Degradation of the anti-inflammatory drug ibuprofen by electro-peroxone process.

    Science.gov (United States)

    Li, Xiang; Wang, Yujue; Yuan, Shi; Li, Zhaoxin; Wang, Bin; Huang, Jun; Deng, Shubo; Yu, Gang

    2014-10-15

    Electro-peroxone (E-peroxone) treatment of the anti-inflammatory drug ibuprofen aqueous solution was investigated in this study. The E-peroxone process combined conventional ozonation with electrolysis processes, and used a carbon-polytetrafluorethylene cathode to electrochemically generate H2O2 from O2 in the sparged ozone generator effluent (O2 and O3 mixture). The in-situ generated H2O2 then reacted with the sparged O3 to produce aqueous •OH, which can in turn oxidize pollutants effectively in the bulk solution. The E-peroxone process overcomes several intrinsic limitations of conventional ozonation and electrolysis processes for pollutant degradation such as the selective oxidation with O3 and mass transfer limitations of pollutants to the electrodes, and thus significantly enhanced both ibuprofen degradation and total organic carbon (TOC) mineralization. Results show that ibuprofen could be completely degraded much more rapidly in the E-peroxone process (e.g., 5-15 min under all tested reaction conditions) than in ozonation (≥30 min) and electrolysis (several hours) processes. In addition, thanks to the powerful and non-selective oxidation capacity of •OH, toxic intermediates formed during ibuprofen degradation could be completely mineralized in the E-peroxone process. The E-peroxone effluent (2 h) thus exhibited much lower toxicity (5% inhibition of bioluminescence of Vibrio fisheri) than the ozonation and electrolysis effluents (22% and 88% inhibition, respectively). The results of this study indicate that the E-peroxone process may provide a promising technology for pharmaceutical wastewater treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Choice of a nonsteroidal anti-inflammatory drug in ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Rimma Mikhailovna Balabanova

    2014-01-01

    Full Text Available Ankylosing spondylitis (AS is a chronic systemic disease with predominant axial skeleton injury, peripheral articular and entheseal involvements, and extra-skeletal manifestations. 8–10 years elapse since the first manifestations of AC to its diagnosis, leading to delays in adequate therapy, to the progression of structural and functional impairments in the axial skeleton and peripheral joints and to the development of complications. According to the international and Russia's Association of Rheumatologists guidelines, nonsteroidal anti-inflammatory drugs (NSAIDs are an important component of AS therapy. It is necessary to carefully choose the safest NSAID for these patients, by taking into consideration that AS therapy should be long-term and continuous.The trial previously performed by the authors evaluated comorbidity in 220 AS patients long receiving nimesulide. Its long-term administration was shown to cause no increase in the level of liver enzymes. Esophagogastroduodenoscopy revealed antral gastritis in 23.6% of the patients, gastric mucosal erosions in 13, and gastric ulcer disease without an exacerbation in 3.6%. It was noted that the physicians had not prescribed gastroprotectors to the patients. Nimesulide caused no blood pressure (BP elevation even in patients who had baseline hypertension. Elevated BP occurred in 2.5% of the patients. There was no clear association of higher BP with nimesulide intake since the patients had previously used other NSAIDs, mainly diclofenac, to treat severe pain syndrome. These findings suggest that in addition to its analgesic activity, nimesulide shows good tolerability in patients with AS, which permits its long-term use, but in this case the gastrointestinal tract and BD should be carefully monitored, which will be able to prevent the possible adverse events characteristic of the entire group of NSAIDs.

  12. Nonsteroidal Anti-Inflammatory Drug Use is Not Associated With Reduced Risk of Barrett's Esophagus

    Science.gov (United States)

    Thrift, Aaron P.; Anderson, Lesley A.; Murray, Liam J.; Cook, Michael B.; Shaheen, Nicholas J.; Rubenstein, Joel H.; El-Serag, Hashem B.; Vaughan, Thomas L.; Schneider, Jennifer L.; Whiteman, David C.; Corley, Douglas A.

    2016-01-01

    OBJECTIVES Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced risk of esophageal adenocarcinoma. Epidemiological studies examining the association between NSAID use and the risk of the precursor lesion, Barrett's esophagus, have been inconclusive. METHODS We analyzed pooled individual-level participant data from six case-control studies of Barrett's esophagus in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). We compared medication use from 1474 patients with Barrett's esophagus separately with two control groups: 2256 population-based controls and 2018 gastroesophageal reflux disease (GERD) controls. Study-specific odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression models and were combined using a random effects meta-analytic model. RESULTS Regular (at least once weekly) use of any NSAIDs was not associated with the risk of Barrett's esophagus (vs. population-based controls, adjusted OR = 1.00, 95% CI = 0.76–1.32; I2=61%; vs. GERD controls, adjusted OR = 0.99, 95% CI = 0.82–1.19; I2=19%). Similar null findings were observed among individuals who took aspirin or non-aspirin NSAIDs. We also found no association with highest levels of frequency (at least daily use) and duration (≥5 years) of NSAID use. There was evidence of moderate between-study heterogeneity; however, associations with NSAID use remained non-significant in “leave-one-out” sensitivity analyses. CONCLUSIONS Use of NSAIDs was not associated with the risk of Barrett's esophagus. The previously reported inverse association between NSAID use and esophageal adenocarcinoma may be through reducing the risk of neoplastic progression in patients with Barrett's esophagus. PMID:27575711

  13. Differential Risk of Peptic Ulcer Among Users of Antidepressants Combined With Nonsteroidal Anti-inflammatory Drugs.

    Science.gov (United States)

    Shin, Ju-Young; Song, Inmyung; Lee, Jin-Ho; Yoon, Jong Lull; Kwon, Jun Soo; Park, Byung-Joo

    2017-04-01

    Selective serotonin reuptake inhibitors (SSRIs) have been reported to have an increased risk of gastrointestinal adverse events, and the risk may be further increased by combined use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, little has been known about the risk of peptic ulcer associated with other classes of antidepressants or individual antidepressants combined with NSAIDs. We conducted a retrospective cohort study to define the risk of peptic ulcer associated with combined use of antidepressants and NSAIDs, as compared with use of antidepressants alone. Using the Korean Health Insurance Review and Assessment Service database, we identified a total of 1,127,622 patients who began receiving antidepressants between 2009 and 2012. Propensity-based matching and Cox proportional hazards models were used to compare the risk of peptic ulcer between antidepressant users with NSAIDs and those without NSAIDs matched in a 1:1 ratio, for a total of 768,850 patients. The risk of peptic ulcer did not increase with combined use of overall antidepressants and NSAIDs, as compared with antidepressant use alone (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.99-1.06). A slightly increased risk was observed for combined use of NSAIDs with tricyclic antidepressants (HR, 1.15; 95% CI, 1.09-1.21) and with SSRIs (HR, 1.08; 95% CI, 1.01-1.16). We found that although concomitant use of NSAIDs and antidepressants was not associated with an increased risk of peptic ulcer for antidepressants in general, it was so for some specific classes including tricyclic antidepressants and SSRIs. However, we cannot rule out the possibility that the increased risk was solely due to NSAID use.

  14. Perioperative Topical Nonsteroidal Anti-inflammatory Drugs for Macular Edema Prophylaxis Following Cataract Surgery.

    Science.gov (United States)

    Modjtahedi, Bobeck S; Paschal, John F; Batech, Michael; Luong, Tiffany Q; Fong, Donald S

    2017-04-01

    To describe the effect of routine use of topical nonsteroidal anti-inflammatory drugs (NSAIDs) on the incidence of postoperative macular edema (PME) after cataract surgery. The role of diabetic retinopathy on the relationship between NSAID use and PME was further analyzed. Retrospective matched cohort study. Patients undergoing cataract surgery between January 2007 and June 2014 were included in this study. A total of 108 093 Kaiser Permanente Southern California patients underwent cataract surgery and 89 731 met inclusion criteria. Cataract surgery patients who had a perioperative prescription of topical NSAIDs filled in addition to topical steroids were compared to those taking topical steroids only. The main outcome measure was the diagnosis of macular edema within 90 days of cataract surgery. A prescription for an NSAID was filled by 56.4% of patients. The prevalence of PME was 1.3% among those prescribed and 1.7% among those not prescribed NSAIDs. The number needed to treat was 320 patients to prevent 1 case of PME. A matched cohort analysis was performed to account for confounders. NSAID use was associated with a lower incidence of PME in patients without diabetes [relative risk (RR) 0.68, 95% confidence interval (CI) 0.58-0.72] and diabetics without retinopathy (RR 0.51, 95% CI 0.32-0.82). NSAID use was not associated with a change in the incidence of PME among patients with diabetic retinopathy (RR 1.06, 95% 0.81-1.38). Topical NSAIDs were associated with a modest reduction of PME incidence in patients undergoing cataract surgery; however, this relationship was not seen among those with diabetic retinopathy. The risk for PME is low and the number of patients benefiting from treatment is small. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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    R Lad

    1999-01-01

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

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

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    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.

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

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

    2011-01-01

    AIM: To establish the prevalence of Helicobacter pylori (H. pylori) infection in patients with a bleeding peptic ulcer after consumption of non-steroidal antiinflammatory drugs (NSAIDs). METHODS: A very early upper endoscopy was performed to find the source of upper gastrointestinal bleeding and to take biopsy specimens for analysis of H. pylori infection by the rapid urease (CLO) test, histological examination, and bacterial culture. IgG anti-CagA were also sought. The gold standard for identifying H. pylori infection was positive culture of biopsy specimens or contemporary positivity of the CLO test and the presence of H. pylori on tissue sections. RESULTS: Eighty patients, 61 males (76.3%), mean age 61.2 ± 15.9 years, were consecutively enrolled. Forty-seven (58.8%) patients occasionally consumed NSAIDs, while 33 (41.3%) were on chronic treatment with low-dose aspirin (LD ASA). Forty-four (55.0%) patients were considered infected by H. pylori. The infection rate was not different between patients who occasionally or chronically consumed NSAIDs. The culture of biopsy specimens had a sensitivity of 86.4% and a specificity of 100%; corresponding figures for histological analysis were 65.9% and 77.8%, for the CLO test were 68.2% and 75%, for the combined use of histology and the CLO test were 56.8% and 100%, and for IgG anti-CagA were 90% and 98%. The highest accuracy (92.5%) was obtained with the culture of biopsy specimens. CONCLUSION: Patients with a bleeding peptic ulcer after NSAID/LD ASA consumption frequently have H. pylori infection. Biopsy specimen culture after an early upper gastrointestinal tract endoscopy seems the most efficient test to detect this infection. PMID:22110282

  18. The effect of non-steroidal anti-inflammatory drugs on risk of benign prostatic hyperplasia.

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    Nygård, Lotta H; Talala, Kirsi; Taari, Kimmo; Tammela, Teuvo L J; Auvinen, Anssi; Murtola, Teemu J

    2017-06-01

    Inflammation may play a role in pathogenesis of benign prostatic hyperplasia (BPH). However, the role of non-steroidal anti-inflammatory drugs (NSAIDs) as BPH risk factor is unclear. The objective of this study was to examine risk of BPH by NSAID use in a population-based cohort. A total of 74 754 Finnish men without previous BPH at baseline in 1996-1999 were linked to national medication reimbursement database for information on physician-prescribed NSAID purchases during 1995-2009. Information on BPH procedures and diagnoses was obtained from national Care Register for Health Care. Cox regression with adjustment for age and use of cholesterol-lowering, antidiabetic and antihypertensive medication, with NSAID use as time-dependent variable was used to analyse the risk of BPH surgery, medication use, and recorded diagnosis. Of the subjects 57 707 men (77.2%) used prescription NSAIDs. The risk of BPH was elevated among NSAID users compared to non-users: HR 2.04, 95% CI 1.97-2.10 for BPH medication use, HR 1.59, 95% CI 1.47-1.71 for recorded diagnosis and HR 1.61, 95% CI 1.49-1.74 for surgery. The risk increase correlated with duration of NSAID usage, less with annual dosage. Nevertheless, the risk increase was observed already at short-term and low-dosage use. NSAID use is associated with an increased risk of BPH. The association is affected by systematic differences by NSAID use as the risk increase was observed already at short-term use. Nevertheless, the association correlated with duration of use, suggesting that NSAID usage or the conditions indicating it may increase BPH risk. © 2017 Wiley Periodicals, Inc.

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

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

    2017-12-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are the cornerstone of pain management. There are no detailed data on NSAIDs use in Poland, especially in patients with chronic kidney disease (CKD). The aim of this study was to evaluate the frequency, circumstances, and causes of NSAIDs use as well as knowledge of their side-effects in patients with CKD. This cross-sectional study was conducted in 972 individuals with CKD, enrolled in a written survey originally developed by the authors. There were 574 patients with CKD stage I-IV, 414 patients after renal transplantation stage II-IV (CKDT) and 84 dialyzed patients (44 peritoneal, 40 hemodialysis). Among the entire study group, 16.9 % of patients used NSAIDs every day, or several times a week. The average number of tablets taken within a month was 21.8. Subgroup analysis revealed that NSAIDs were taken most often by patients on hemodialysis: 35 % of them used NSAIDs every day or several times a week (43.15 pills per month). The most common reason for using NSAIDs were bone-joint pain (29.3 %) and headache (26.2 %). Side effects of painkillers such as renal function deterioration and the possible promotion of stomach ulcers were experienced by 43.6 and 37.6 % of respondents, respectively. Patients with CKD often take NSAIDs. This applies especially to the group of people undergoing hemodialysis, which is mainly associated with chronic osteo-articular pain. The results also show a low awareness of painkillers' adverse effects.

  20. Perioperative use of non-steroidal anti-inflammatory drugs might impair dental implant osseointegration.

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    Winnett, Brent; Tenenbaum, Howard C; Ganss, Ben; Jokstad, Asbjørn

    2016-02-01

    To appraise whether adverse biological events following oral implant placement may be associated with perioperative use of non-steroidal anti-inflammatory drugs (NSAIDs). All patients treated in a university faculty postgraduate dental clinic between 1979 and 2012 that had experienced a failing and surgically removed dental implant (292 implants in 168 patients) were contacted to solicit additional information about their present dental and medical status and frequency of current and past use of NSAIDs. Potential associations between perioperative NSAIDs use and the occurrence of adverse biological events were explored by the use of 2 × 2 tables and two-tailed Fisher's exact tests. One hundred and four patients with initially 468 implants had experienced 238 implant failures, of which 197 were due to failing osseointegration (42%). Sixty of the participants, initially with 273 implants, had used NSAIDs perioperatively and experienced 44% implant failures, versus 38% in the non-NSAID cohort. The NSAID cohort experienced 3.2 times more cases of radiographic bone loss greater than 30% of the vertical height of their remaining implants and 1.9 times more cases of cluster failures, defined as failure of 50% or more of the implant(s) placed. Notwithstanding that a retrospective study design is open to potential bias, the current data indicate that dental implant osseointegration may be affected negatively by an inhibitory effect of NSAIDs on bone healing in vulnerable patients. Future and better clinical studies than the current should be designed to appraise more precisely the potential effects of NSAIDs on implant osseointegration in study populations that are not limited by stringent medical inclusion and exclusion criteria. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Analgesic efficacy and safety of nonsteroidal anti-inflammatory drugs after transurethral resection of prostate

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    Cengiz Kara

    2010-02-01

    Full Text Available OBJECTIVES: The aim of this study was to assess the analgesic efficacy and safety of nonsteroidal anti-inflammatory drugs (NSAIDs, administered as intramuscular diclofenac in comparison with intravenous paracetamol after transurethral resection of the prostate (TURP. MATERIALS AND METHODS: Fifty men, aged 55 to 75 years, undergoing TURP at our hospital were included in this study. Patients were divided randomly and prospectively into two groups (25 patients in each group. Group I (NSAID received 75 mg of diclofenac i.m. at the end of the operation followed by 75 mg of diclofenac i.m. for 24 hours (75 mg x 2 once a day = 150 mg/24 h postoperatively. The other group (Group II consisted of patients who received 1g/100 mL i.v. paracetamol 15 minutes twice daily as postoperative analgesia. Postoperative pain scores were evaluated at 30 minutes, 1, 2, 4 and 6 hours after administration of each analgesic, using a visual analogue scale (VAS. Furthermore, preoperative and postoperative hemoglobin (Hb levels and hemostatic variables (bleeding time, prothrombine time and the international normalized ratio?, i.e. the ratio of a patient's prothrombin time to a normal [control] sample were recorded in all patients. RESULTS: The pain score changes during a 4 hour period between the two groups was similar (p = 0.162. Thirty minutes after surgery, pain scores were high (> 3 cm in both groups and without differences between groups (p = 0.11 but 6 hours after surgery, pain scores were significantly higher with paracetamol compared to diclofenac (p < 0.05. No significant difference was observed between the groups regarding the amount of resected tissue, operating time, preoperative-postoperative Hb levels and hemostatic variables. In the both groups, no patient required blood transfusion postoperatively. CONCLUSIONS: NSAIDs are not a contraindication to TURP and should be used for the control of postoperative pain if indicated.

  2. Determination of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs in Milk and Fresh Cheese Based on the Inhibition of Cyclooxygenase

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    Giulia Di Persio

    2009-01-01

    Full Text Available A biosensor for rapid determination of nonsteroidal anti-inflammatory drugs (NSAIDs is described based on the inhibition of cyclooxygenase enzyme (both isoforms by NSAIDs. The results show the full validity of the method, which has also been optimized by comparing the inhibition of two enzyme isoforms, COX-1 and COX-2, in the presence of different tested pharmaceutical drugs (diclofenac, naproxen, ibuprofen, tolmetin. Also, recovery trials were performed in milk and fresh cheese adulterated with known quantities of NSAIDs, always obtaining recovery values >88 %.

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

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    Brune K

    2015-02-01

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

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

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    Ashraf Z

    2016-07-01

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

  5. Computational Drug Repositioning for Peripheral Arterial Disease: Prediction of anti-inflammatory and pro-angiogenic therapeutics

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    Liang-Hui eChu

    2015-08-01

    Full Text Available Peripheral arterial disease (PAD results from atherosclerosis that leads to blocked arteries and reduced blood flow, most commonly in the arteries of the legs. PAD clinical trials to induce angiogenesis to improve blood flow conducted in the last decade have not succeeded. We have recently constructed PADPIN, protein-protein interaction network (PIN of PAD, and here we combine it with the drug-target relations to identify potential drug targets for PAD. Specifically, the proteins in the PADPIN were classified as belonging to the angiome, immunome, and arteriome, characterizing the processes of angiogenesis, immune response/inflammation, and arteriogenesis, respectively. Using the network-based approach we predict the candidate drugs for repositioning that have potential applications to PAD. By compiling the drug information in two drug databases DrugBank and PharmGKB, we predict FDA-approved drugs whose targets are the proteins annotated as anti-angiogenic and pro-inflammatory, respectively. Examples of pro-angiogenic drugs are carvedilol and urokinase. Examples of anti-inflammatory drugs are ACE inhibitors and maraviroc. This is the first computational drug repositioning study for PAD.

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

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    Zi Gu

    2014-05-01

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

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

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    Przemysław Dyrla

    2016-03-01

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

  8. Recent advances in medicinal chemistry of sulfonamides. Rational design as anti-tumoral, anti-bacterial and anti-inflammatory agents.

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    Shah, Syed Shoaib Ahmad; Rivera, Gildardo; Ashfaq, Muhammad

    2013-01-01

    Now-a-days, cancer is becoming one of the major problems of public health in the world. Pharmacology treatment is a way to increase quality and long life. Predominantly, in last decade sulfonamide derivatives have been described as potential carbonic anhydrase inhibitors. In the present work, we describe recent advances during the last decade in medicinal chemistry of sulfonamides derivatives with some examples of rational design as anti-tumoral, antibacterial and anti-inflammatory agents. We show strategy design, structure-activity relationship, biological activity and advances of new sulfonamide compounds that have more health significance than some clinically used sulfonamides.

  9. Non steroidal anti-inflammatory drugs in the prevention of cystoid macular edema after uneventful cataract surgery

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    Quintana NE

    2014-06-01

    Full Text Available Nicolás E Quintana,* Alejandro R Allocco,* Julia A Ponce,* Mauricio GB Magurno Instituto Santa Lucía, Paraná, Argentina *These authors contributed equally to this work Background: Cystoid macular edema (CME remains an important complication after cataract surgery. There is no consensus about how to prevent this frequent complication. The purpose of this study was to conceive an effective anti-inflammatory strategy using nonsteroidal anti-inflammatory drugs (NSAIDs together with regular treatment with corticosteroids to prevent CME and improve visual acuity after cataract surgery in patients without risk factors. Materials and methods: We searched the PubMed, Cochrane, and Google Scholar databases focused on prospective, controlled, randomized, double-blind clinical trials published in the last 10 years, with a minimum follow-up of 4 weeks. Results: A total of nine clinical trials, one systematic review, and two reviews satisfied our search criteria. Most studies highlighted that NSAIDs are as powerful as corticosteroids to diminish postoperative inflammation, and demonstrated an additional benefit when used in combination with standard corticosteroid postsurgical therapy. In addition, the use of NSAIDs in the perioperative period seems to significantly improve the outcome after surgery and helps prevent CME in low-risk patients. Conclusion: The prophylactic use of NSAIDs in combination with the standard postoperative steroid scheme appears to be a positive course of action for preventing CME after cataract surgery. We suggest a therapeutic scheme based on the administration of one drop four times a day, beginning the day before surgery and for 4 weeks after the procedure. It is also advisable to administer one drop every 15 minutes in the hour prior to surgery in order to obtain better anti-inflammatory efficacy. Keywords: cystoid macular edema, non-steroidal anti-inflammatory drugs, cataract surgery, NSAIDs, CME

  10. Use of Aspirin or Nonsteroidal Anti-inflammatory Drugs Increases Risk for Diverticulitis and Diverticular Bleeding

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    Strate, Lisa L.; Liu, Yan L.; Huang, Edward S.; Giovannucci, Edward L.; Chan, Andrew T.

    2011-01-01

    BACKGROUND & AIMS Nonsteroidal Anti-inflammatory Drugs (NSAIDs), including aspirin, have been implicated in diverticular complications. We examined the influence of aspirin and NSAID use on risk of diverticulitis and diverticular bleeding in a large prospective cohort. METHODS We studied 47,210 US men in the Health Professionals Follow-up Study cohort who were 40–75 years old at baseline, in 1986. We assessed use of aspirin, non-aspirin NSAIDs, and other risk factors biennially. We identified men with diverticulitis or diverticular bleeding based on responses to biennial and supplemental questionnaires. RESULTS We documented 939 cases of diverticulitis and 256 cases of diverticular bleeding during a 22-year period of follow-up. After adjustment for risk factors, men who used aspirin regularly (≥2 times per week) had a multivariable relative risk (RR) of 1.25 (95% confidence interval [CI], 1.05–1.47) for diverticulitis and RR of 1.70 (95% CI, 1.21–2.39) for diverticular bleeding, compared with non-users of aspirin and NSAIDs. Use of aspirin at intermediate doses (2–5.9 standard, 325 mg, tablets per week) and frequency (4–6 days per week) were associated with the highest risk of bleeding (multivariable RR=2.32; 95% CI, 1.34–4.02, and multivariable RR=3.13; 95% CI, 1.82–5.38, respectively). Regular users of non-aspirin NSAIDs also had an increased risk of diverticulitis (multivariable RR=1.72; 95% CI, 1.40–2.11) and diverticular bleeding (multivariable RR=1.74; 95% CI, 1.15–2.64), compared with men who denied use of these medications. CONCLUSIONS Regular use of aspirin or NSAIDs is associated with an increased risk for diverticulitis and diverticular bleeding. Patients at risk of diverticular complications should carefully consider the potential risks and benefits of using these medications. PMID:21320500

  11. Nonsteroidal anti-inflammatory drugs and the risk of Barrett's esophagus.

    Science.gov (United States)

    Khalaf, Natalia; Nguyen, Theresa; Ramsey, David; El-Serag, Hashem B

    2014-11-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have been suggested to protect against esophageal adenocarcinoma (EAC). This study examined the effect of NSAIDs on the risk of developing Barrett's esophagus (BE), the precursor lesion to EAC. We conducted a case-control study among eligible patients scheduled for either elective esophagogastroduodenoscopy (EGD) or recruited from primary care clinics to undergo a study EGD. We compared 323 patients with BE (296 nondysplastic and 27 dysplastic) with 2 separate control groups: 1347 patients from the elective EGD group (endoscopy controls) and 502 patients from the primary care group (primary care controls) with no endoscopic or histopathologic BE. Use of aspirin products and 23 nonaspirin NSAIDs was ascertained from detailed, self-reported questionnaires. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression models. There were no significant differences in self-reported NSAID use between all BE cases and all controls (58.2% vs 54.6%; P = .33); this was seen for aspirin products (43.0% vs 37.4%; P = .08) and nonaspirin NSAIDs (7.7% vs 8.9%; P = .46). These findings persisted in the multivariable model for any NSAIDs (adjusted OR, 0.89; 95% CI, 0.75-1.28), aspirin (adjusted OR, 1.16; 95% CI, 0.90-1.51), and nonaspirin NSAIDs (adjusted OR, 0.88; 95% CI, 0.55-1.39). Use of a combination of aspirin and nonaspirin NSAIDs was reported in 7.4% of cases and 8.3% of controls, and a nonsignificant inverse association with BE was seen (adjusted OR, 0.70; 95% CI, 0.44-1.11). There was no significant association between BE and daily NSAID use (adjusted OR, 1.03; 95% CI, 0.78-1.37). Similar findings were observed for comparisons involving nondysplastic or dysplastic BE cases, and endoscopy or primary care control groups separately or combined. The use of NSAIDs was not associated with a reduced risk of BE. It is likely that the protective mechanism of NSAIDs on EAC occurs subsequent

  12. 2-hydroxy arachidonic acid: a new non-steroidal anti-inflammatory drug.

    Directory of Open Access Journals (Sweden)

    Daniel H Lopez

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

  13. Using Free Computational Resources to Illustrate the Drug Design Process in an Undergraduate Medicinal Chemistry Course

    Science.gov (United States)

    Rodrigues, Ricardo P.; Andrade, Saulo F.; Mantoani, Susimaire P.; Eifler-Lima, Vera L.; Silva, Vinicius B.; Kawano, Daniel F.

    2015-01-01

    Advances in, and dissemination of, computer technologies in the field of drug research now enable the use of molecular modeling tools to teach important concepts of drug design to chemistry and pharmacy students. A series of computer laboratories is described to introduce undergraduate students to commonly adopted "in silico" drug design…

  14. Oral nonsteroidal anti-inflammatory drugs (NSAIDs) for cancer pain in adults.

    Science.gov (United States)

    Derry, Sheena; Wiffen, Philip J; Moore, R Andrew; McNicol, Ewan D; Bell, Rae F; Carr, Daniel B; McIntyre, Mairead; Wee, Bee

    2017-07-12

    Pain is a common symptom with cancer, and 30% to 50% of all people with cancer will experience moderate to severe pain that can have a major negative impact on their quality of life. Non-opioid drugs are commonly used to treat cancer pain, and are recommended for this purpose in the World Health Organization (WHO) cancer pain treatment ladder, either alone or in combination with opioids.A previous Cochrane review that examined the evidence for nonsteroidal anti-inflammatory drugs (NSAIDs) or paracetamol, alone or combined with opioids, for cancer pain was withdrawn in 2015 because it was out of date; the date of the last search was 2005. This review, and another on paracetamol, updates the evidence. To assess the efficacy of oral NSAIDs for cancer pain in adults, and the adverse events reported during their use in clinical trials. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to April 2017, together with reference lists of retrieved papers and reviews, and two online study registries. We included randomised, double-blind, single-blind, or open-label studies of five days' duration or longer, comparing any oral NSAID alone with placebo or another NSAID, or a combination of NSAID plus opioid with the same dose of the opioid alone, for cancer pain of any pain intensity. The minimum study size was 25 participants per treatment arm at the initial randomisation. Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE and created a 'Summary of findings' table. Eleven studies satisfied inclusion criteria, lasting one week or longer; 949 participants with mostly moderate or severe pain were randomised initially, but fewer completed treatment or had results of treatment. Eight studies were double-blind, two single-blind, and

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

    Science.gov (United States)

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

    2016-01-18

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

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

    Science.gov (United States)

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

    1990-10-01

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

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

    NARCIS (Netherlands)

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

    2000-01-01

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

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

    Science.gov (United States)

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

    2010-03-18

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

  19. Interaction of nonsteroidal anti-inflammatory drugs with membranes: in vitro assessment and relevance for their biological actions.

    Science.gov (United States)

    Pereira-Leite, Catarina; Nunes, Cláudia; Reis, Salette

    2013-10-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in the world due to their anti-inflammatory, analgesic and antipyretic properties. Nevertheless, the consumption of these drugs is still associated with the occurrence of a wide spectrum of adverse effects. Regarding the major role of membranes in cellular events, the hypothesis that the biological actions of NSAIDs may be related to their effect at the membrane level has triggered the in vitro assessment of NSAIDs-membrane interactions. The use of membrane mimetic models, cell cultures, a wide range of experimental techniques and molecular dynamics simulations has been providing significant information about drugs partition and location within membranes and also about their effect on diverse membrane properties. These studies have indeed been providing evidences that the effect of NSAIDs at membrane level may be an additional mechanism of action and toxicity of NSAIDs. In fact, the pharmacokinetic properties of NSAIDs are closely related to the ability of these drugs to interact and overcome biological membranes. Moreover, the therapeutic actions of NSAIDs may also result from the indirect inhibition of cyclooxygenase due to the disturbing effect of NSAIDs on membrane properties. Furthermore, increasing evidences suggest that the disordering effects of these drugs on membranes may be in the basis of the NSAIDs-induced toxicity in diverse organ systems. Overall, the study of NSAIDs-membrane interactions has proved to be not only important for the better understanding of their pharmacological actions, but also for the rational development of new approaches to overcome NSAIDs adverse effects. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Impact of non-steroidal anti-inflammatory drugs on gastrointestinal cancers: current state-of-the science.

    Science.gov (United States)

    Sahin, Ibrahim Halil; Hassan, Manal M; Garrett, Christopher R

    2014-04-10

    Growing evidence from epidemiologic and preclinical studies suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of gastrointestinal (GI) cancers, including esophageal, gastric, pancreatic, colorectal cancer, and hepatocellular carcinoma. However, there is also evidence indicating the absence of this benefit. The exact mechanism of NSAIDs' action on GI tumors is not known. Although some studies have suggested inhibition of carcinogenesis by NSAIDs through suppression effect on inflammation-associated cyclooxygenase-2 (COX-2) expression, other studies have suggested COX-2-independent mechanisms. Herein, we summarize the current state of-the-science regarding NSAID benefit for patients with GI cancers. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

    Honoré, B; Brodersen, R

    1984-01-01

    Binding equilibria of 12 nonsteroidal, anti-inflammatory substances, salicylic acid, diflunisal, phenylbutazone, azapropazone, fenbufen, biphenylacetic acid, naproxen, flurbiprofen, ibuprofin, diclofenac, indomethacin, and benoxaprofen, to defatted human serum albumin has been investigated at 37...... degrees, pH 7.4, in a sodium phosphate buffer, 66 mM, by means of equilibrium dialysis and, in case of salicylic acid, by dialysis rate determinations. Cobinding of each of these drugs with monoacetyl-4,4'-diaminodiphenyl sulfone, warfarin, and diazepam has been studied by measuring dialysis rates...

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    BACKGROUND: Selective cyclooxygenase-2 inhibitors and conventional non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) have been associated with adverse cardiovascular (CV) effects. We compared the CV safety of switching to celecoxib vs. continuing nsNSAID therapy in a European setting...... infarction or other biomarker positive acute coronary syndrome, non-fatal stroke or CV death analysed using a Cox model with a pre-specified non-inferiority limit of 1.4 for the hazard ratio (HR). RESULTS: In total, 7297 participants were randomized. During a median 3-year follow-up, fewer subjects than...

  3. Influence of non-steroidal anti-inflammatory drugs on organic anion transporting polypeptide (OATP) 1B1- and OATP1B3-mediated drug transport.

    Science.gov (United States)

    Kindla, Juergen; Müller, Fabian; Mieth, Maren; Fromm, Martin F; König, Jörg

    2011-06-01

    The transporter-mediated uptake of drugs from blood into hepatocytes is a prerequisite for intrahepatic drug action or intracellular drug metabolism before excretion. Therefore, uptake transporters, e.g., members of the organic anion transporting polypeptide (OATP) family are important determinants of drug pharmacokinetics. Highly and almost exclusively expressed in hepatocytes are the OATP family members OATP1B1 (SLCO1B1) and OATP1B3 (SLCO1B3). Drug substrates of OATP1B1 and OATP1B3 include antibiotics and HMG-CoA reductase inhibitors (statins). It has been demonstrated that administration of two or more drugs that are substrates for these hepatic uptake transporters may lead to transporter-mediated drug-drug interactions, resulting in altered transport kinetics for drug substrates. In this study we investigated whether non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol interact with OATP1B1 and OATP1B3 using the standard substrate BSP and the drug substrate pravastatin. Using human embryonic kidney cells stably expressing OATP1B1 or OATP1B3, we demonstrated that bromosulfophthalein uptake was inhibited by diclofenac, ibuprofen. and lumiracoxib. Of interest, pravastatin uptake was stimulated by these NSAIDs, and for ibuprofen we determined activation constants (EC₅₀ values) of 64.0 and 93.1 μM for OATP1B1- and OATP1B3-mediated uptake, respectively. Furthermore, we investigated whether NSAIDs were also substrates for OATP1B1 and OATP1B3 and demonstrated that only diclofenac was significantly transported by OATP1B3, whereas all other NSAIDs investigated were not substrates for these uptake transporters. These results demonstrated that drugs may interact with transport proteins by allosteric mechanisms without being substrates and, therefore, not only uptake inhibition but also allosteric-induced modulation of transport function may be an important mechanism in transporter-mediated drug-drug interactions.

  4. Non-steroidal anti-inflammatory drugs versus corticosteroids for controlling inflammation after uncomplicated cataract surgery.

    Science.gov (United States)

    Juthani, Viral V; Clearfield, Elizabeth; Chuck, Roy S

    2017-07-03

    Cataract is a leading cause of blindness worldwide. Cataract surgery is commonly performed but can result in postoperative inflammation of the eye. Inadequately controlled inflammation increases the risk of complications. Non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are used to prevent and reduce inflammation following cataract surgery, but these two drug classes work by different mechanisms. Corticosteroids are effective, but NSAIDs may provide an additional benefit to reduce inflammation when given in combination with corticosteroids. A comparison of NSAIDs to corticosteroids alone or combination therapy with these two anti-inflammatory agents will help to determine the role of NSAIDs in controlling inflammation after routine cataract surgery. To evaluate the comparative effectiveness of topical NSAIDs (alone or in combination with topical corticosteroids) versus topical corticosteroids alone in controlling intraocular inflammation after uncomplicated phacoemulsification. To assess postoperative best-corrected visual acuity (BCVA), patient-reported discomfort, symptoms, or complications (such as elevation of IOP), and cost-effectiveness with the use of postoperative NSAIDs or corticosteroids. To identify studies relevant to this review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register (2016, Issue 12), MEDLINE Ovid (1946 to December 2016), Embase Ovid (1947 to 16 December 2016), PubMed (1948 to December 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 16 December 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com; last searched 17 June 2013), ClinicalTrials.gov (www.clinicaltrials.gov; searched December 2016), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en; searched December 2016). We included randomized controlled trials (RCTs) in which

  5. Gene expression profile of coronary artery cells treated with nonsteroidal anti-inflammatory drugs reveals off-target effects.

    Science.gov (United States)

    Palayoor, Sanjeewani T; J-Aryankalayil, Molykutty; Makinde, Adeola Y; Cerna, David; Falduto, Michael T; Magnuson, Scott R; Coleman, C Norman

    2012-06-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have come under scrutiny because of the gastrointestinal, renal, and cardiovascular toxicity associated with prolonged use of these drugs. The purpose of this study was to identify molecular targets for NSAIDs related to cellular toxicity with a view to optimize drug efficacy in the clinic. Coronary artery smooth muscle cells and endothelial cells were treated with low (clinically achievable) and high (typically used in preclinical studies) concentrations of celecoxib, NS398, and ibuprofen for 24 hours. NSAIDs-induced gene expression changes were evaluated by microarray analysis and validated by real-time reverse-transcription polymerase chain reaction and western blotting. The functional significance of differentially expressed genes was evaluated by Ingenuity Pathway Analysis. At high concentrations, NSAIDs altered the expression of genes regulating cell proliferation and cell death. NSAIDs also altered genes associated with cardiovascular functions including inflammation, thrombosis, fibrinolysis, coronary artery disease, and hypertension. The gene expression was most impacted by ibuprofen, celecoxib, and NS398, in that order. This study revealed that NSAIDs altered expression of an array of genes associated with cardiovascular events and emphasizes the potential for fingerprinting drugs in preclinical studies to assess the potential drug toxicity and to optimize the drug efficacy in clinical settings.

  6. Drug interactions between antihypertensive drugs and non-steroidal anti-inflammatory agents: a descriptive study using the French Pharmacovigilance database.

    Science.gov (United States)

    Fournier, Jean-Pascal; Sommet, Agnès; Durrieu, Geneviève; Poutrain, Jean-Christophe; Lapeyre-Mestre, Maryse; Montastruc, Jean-Louis

    2014-04-01

    Drug-drug interactions (DDIs) between antihypertensive drugs and non-steroidal anti-inflammatory drugs (NSAIDs) can lead to adverse drug reactions (ADRs). Guidelines are available to help prescribers deal with these drug associations, but their implementation is not well evaluated. The aims of this study were to assess the prevalence of NSAIDs exposure in patients treated with antihypertensive drugs, using the French Pharmacovigilance database, and explore the ADRs related to DDIs between antihypertensive drugs and NSAIDs. Over the 11, 442 notifications of ADRs recorded in this database in patients treated with oral antihypertensive drugs between 2008 and 2010, 517 (4.5 and 95% CI: 4.1-4.9) also included exposure to NSAIDs. These subjects were more frequently women, took more drugs in general, and were younger and less frequently treated with antiplatelet drugs. In 24.2% of them (125 patients), a DDI between NSAIDs and antihypertensive drugs was potentially the cause of the reported ADR. Acute renal failure caused by DDIs between NSAIDs and angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), or diuretics was the most frequently reported ADR (20.7%). Finally, in the French Pharmacovigilance database, around one-fourth of associations NSAIDs  +  antihypertensive drugs are associated with a 'serious' ADR (mainly acute renal failure), suggesting that this well-known DDI is not enough taken into account by prescribers. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.

  7. Prehospital use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of trauma-induced coagulopathy.

    Science.gov (United States)

    Neal, Matthew D; Brown, Joshua B; Moore, Ernest E; Cuschieri, Joseph; Maier, Ronald V; Minei, Joseph P; Billiar, Timothy R; Peitzman, Andrew B; Cohen, Mitchell J; Sperry, Jason L

    2014-08-01

    To determine whether prehospital nonsteroidal anti-inflammatory drug (NSAID) use may lead to a reduced incidence of trauma-induced coagulopathy (TIC) in severely injured patients. TIC is present in up to a quarter of severely injured trauma patients and is linked to worse outcomes after injury. Evidence linking TIC to inflammation has emerged; however, the mechanism behind this association is still under investigation. NSAIDs are commonly used anti-inflammatory drugs, but their effects on TIC and outcomes after injury are largely unexplored. We performed a secondary analysis of the Inflammation and the Host Response to Injury Large Scale Collaborative Program (Glue Grant) data set. Prehospital medications and comorbidities were analyzed by logistic regression analysis for association with TIC as defined by laboratory (international normalized ratio >1.5) or clinical (transfusion >2 units of fresh frozen plasma or >1 pack of platelets in 6 hours) parameters. Prehospital NSIAD use was independently associated with a 72% lower risk of TIC and was the only medication among 15 analyzed to retain significance in the model. Stepwise logistic regression also demonstrated that preadmission use of NSAIDs was independently associated with a 66% lower risk of clinically significant coagulopathy. These findings were independent of comorbid conditions linked to NSAID use. NSAID use before admission for severe injury is associated with a reduced incidence of TIC. These findings provide further evidence to a potential leak between TIC and inflammation.

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

    Science.gov (United States)

    Utzeri, Erika; Usai, Paolo

    2017-06-14

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

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

    Directory of Open Access Journals (Sweden)

    Vera M. Kroesen

    2017-06-01

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

  10. Topical non-steroidal anti-inflammatory drugs for analgesia in traumatic corneal abrasions.

    Science.gov (United States)

    Wakai, Abel; Lawrenson, John G; Lawrenson, Annali L; Wang, Yongjun; Brown, Michael D; Quirke, Michael; Ghandour, Omar; McCormick, Ryan; Walsh, Cathal D; Amayem, Ahmed; Lang, Eddy; Harrison, Nick

    2017-05-18

    Traumatic corneal abrasions are relatively common and there is a lack of consensus about analgesia in their management. It is therefore important to document the clinical efficacy and safety profile of topical ophthalmic non-steroidal anti-inflammatory drugs (NSAIDs) in the management of traumatic corneal abrasions. To identify and evaluate all randomised controlled trials (RCTs) comparing the use of topical NSAIDs with placebo or any alternative analgesic interventions in adults with traumatic corneal abrasions (including corneal abrasions arising from foreign body removal), to reduce pain, and its effects on healing time. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 2), MEDLINE Ovid (1946 to 30 March 2017), Embase Ovid (1947 to 30 March 2017), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 30 March 2017), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/); searched 30 March 2017, ZETOC (1993 to 30 March 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 30 March 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 30 March 2017 and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 30 March 2017. We did not use any date or language restrictions in the electronic searches for trials.We checked the reference lists of identified trials to search for further potentially relevant studies. RCTs comparing topical NSAIDs to placebo or any alternative analgesic interventions in adults with traumatic corneal abrasions. Two review authors independently performed data extraction and assessed risks of bias in the included studies. We rated the certainty of the evidence using GRADE. We included nine studies that met the inclusion criteria, reporting data on 637 participants.The studies took place in the UK, USA, Israel, Italy

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-06-01

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

  12. Recent Advances in chemistry and pharmacology of 2-methoxyestradiol: An anticancer investigational drug.

    Science.gov (United States)

    Kumar, B Sathish; Raghuvanshi, Dushyant Singh; Hasanain, Mohammad; Alam, Sarfaraz; Sarkar, Jayanta; Mitra, Kalyan; Khan, Feroz; Negi, Arvind S

    2016-06-01

    2-Methoxyestradiol (2ME2), an estrogen hormone metabolite is a potential cancer chemotherapeutic agent. Presently, it is an investigational drug under various phases of clinical trials alone or in combination therapy. Its anticancer activity has been attributed to its antitubulin, antiangiogenic, pro-apoptotic and ROS induction properties. This anticancer drug candidate has been explored extensively in last twenty years for its detailed chemistry and pharmacology. Present review is an update of its chemistry and biological activity. It also extends an assessment of potential of 2ME2 and its analogues as possible anticancer drug in future. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Chiral Drug Analysis in Forensic Chemistry: An Overview

    OpenAIRE

    Cláudia Ribeiro; Cristiana Santos; Valter Gonçalves; Ana Ramos; Carlos Afonso; Maria Elizabeth Tiritan

    2018-01-01

    Many substances of forensic interest are chiral and available either as racemates or pure enantiomers. Application of chiral analysis in biological samples can be useful for the determination of legal or illicit drugs consumption or interpretation of unexpected toxicological effects. Chiral substances can also be found in environmental samples and revealed to be useful for determination of community drug usage (sewage epidemiology), identification of illicit drug manufacturing locations, ille...

  14. Non-steroidal anti-inflammatory drugs (NSAIDs) for treating lateral elbow pain in adults.

    Science.gov (United States)

    Pattanittum, Porjai; Turner, Tari; Green, Sally; Buchbinder, Rachelle

    2013-05-31

    Lateral elbow pain, or tennis elbow, is a common condition that causes pain in the elbow and forearm. Although self-limiting, it can be associated with significant disability and often results in work absence. It is often treated with topical and oral non-steroidal anti-inflammatory drugs (NSAIDs). This is an update of a review first published in 2002 (search date October 11, 2012). To assess the benefits and harms of topical and oral NSAIDs for treating people with lateral elbow pain. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL, EMBASE and SciSearch up to October 11, 2012. No language restriction was applied. Studies were included if they were randomised or quasi-randomised controlled trials (RCTs or CCTs) that compared topical or oral NSAIDs with placebo or another intervention, or compared two NSAIDs in adults with lateral elbow pain. Outcomes of interest were pain, function, quality of life, pain-free grip strength, overall treatment success, work loss and adverse effects. Two review authors independently selected the studies for inclusion, extracted the data, and performed a risk of bias assessment. Fifteen trials, involving 759 participants and reporting 17 comparisons, were included in the review. Four new trials identified from the updated search were included, along with 11 of 14 trials included in the original review (three trials included in the previous review were found not to meet inclusion criteria). Of eight trials that studied topical NSAIDs (301 participants), five compared topical NSAIDs with placebo, one compared manipulative therapy and topical NSAIDs with manipulative therapy alone, one compared leech therapy with topical NSAIDs and one compared two different topical NSAIDs. Of seven trials that investigated oral NSAIDs (437 participants), two compared oral NSAIDs with placebo, one compared oral NSAIDs and bandaging with bandaging alone, three compared oral NSAIDs with glucocorticoid injection, one compared

  15. Postoperative non-steroidal anti-inflammatory drugs and colorectal anastomotic leakage. NSAIDs and anastomotic leakage.

    Science.gov (United States)

    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, pNSAID treatment. Study III was also an experimental, randomized, case-control study. This time round, 60 Wistar

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

    Directory of Open Access Journals (Sweden)

    Sophie Seehase

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

  17. Nonsteroidal anti-inflammatory drugs (NSAIDs) and non-opioids for acute renal colic.

    Science.gov (United States)

    Afshar, Kourosh; Jafari, Siavash; Marks, Andrew J; Eftekhari, Arash; MacNeily, Andrew E

    2015-06-29

    Renal colic is acute pain caused by urinary stones. The prevalence of urinary stones is between 10% and 15% in the United States, making renal colic one of the common reasons for urgent urological care. The pain is usually severe and the first step in the management is adequate analgesia. Many different classes of medications have been used in this regard including non-steroidal anti-inflammatory drugs and narcotics. The aim of this review was to assess benefits and harms of different NSAIDs and non-opioids in the treatment of adult patients with acute renal colic and if possible to determine which medication (or class of medications) are more appropriate for this purpose. Clinically relevant outcomes such as efficacy of pain relief, time to pain relief, recurrence of pain, need for rescue medication and side effects were explored. We searched the Cochrane Renal Group's Specialised Register (to 27 November 2014) through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Only randomised or quasi randomised studies were included. Other inclusion criteria included adult patients with a clinical diagnosis of renal colic due to urolithiasis, at least one treatment arm included a non-narcotic analgesic compared to placebo or another non-narcotic drug, and reporting of pain outcome or medication adverse effect. Patient-rated pain by a validated tool, time to relief, need for rescue medication and pain recurrence constituted the outcomes of interest. Any adverse effects (minor or major) reported in the studies were included. Abstracts were reviewed by at least two authors independently. Papers meeting the inclusion criteria were fully reviewed and relevant data were recorded in a standardized Cochrane Renal Group data collection form. For dichotomous outcomes relative risks and 95% confidence intervals were calculated. For continuous outcomes the weighted mean difference was estimated. Both fixed and random models were used for meta

  18. Gene Expression Profile of Coronary Artery cells Treated with Non-steroidal Anti-inflammatory Drugs Reveals Off-target Effects

    OpenAIRE

    Palayoor, Sanjeewani T.; J-Aryankalayil, Molykutty; Makinde, Adeola. Y.; Cerna, David; Falduto, Michael T.; Magnuson, Scott. R.; Coleman, C. Norman

    2012-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have come under scrutiny because of the gastrointestinal, renal and cardiovascular toxicity associated with prolonged use of these drugs. The purpose of this study was to identify molecular targets for NSAIDs related to cellular toxicity with a view to optimize drug efficacy in clinic. Coronary artery smooth muscle cells (CASMC) and endothelial cells (HCAEC) were treated with low (clinically achievable) and high (typically used in preclinical stu...

  19. Integrating medicinal chemistry, organic/combinatorial chemistry, and computational chemistry for the discovery of selective estrogen receptor modulators with Forecaster, a novel platform for drug discovery.

    Science.gov (United States)

    Therrien, Eric; Englebienne, Pablo; Arrowsmith, Andrew G; Mendoza-Sanchez, Rodrigo; Corbeil, Christopher R; Weill, Nathanael; Campagna-Slater, Valérie; Moitessier, Nicolas

    2012-01-23

    As part of a large medicinal chemistry program, we wish to develop novel selective estrogen receptor modulators (SERMs) as potential breast cancer treatments using a combination of experimental and computational approaches. However, one of the remaining difficulties nowadays is to fully integrate computational (i.e., virtual, theoretical) and medicinal (i.e., experimental, intuitive) chemistry to take advantage of the full potential of both. For this purpose, we have developed a Web-based platform, Forecaster, and a number of programs (e.g., Prepare, React, Select) with the aim of combining computational chemistry and medicinal chemistry expertise to facilitate drug discovery and development and more specifically to integrate synthesis into computer-aided drug design. In our quest for potent SERMs, this platform was used to build virtual combinatorial libraries, filter and extract a highly diverse library from the NCI database, and dock them to the estrogen receptor (ER), with all of these steps being fully automated by computational chemists for use by medicinal chemists. As a result, virtual screening of a diverse library seeded with active compounds followed by a search for analogs yielded an enrichment factor of 129, with 98% of the seeded active compounds recovered, while the screening of a designed virtual combinatorial library including known actives yielded an area under the receiver operating characteristic (AU-ROC) of 0.78. The lead optimization proved less successful, further demonstrating the challenge to simulate structure activity relationship studies.

  20. Non-steroidal anti-inflammatory drugs (NSAIDs) and hypertension treatment intensification: a population-based cohort study.

    Science.gov (United States)

    Fournier, Jean-Pascal; Sommet, Agnès; Bourrel, Robert; Oustric, Stéphane; Pathak, Atul; Lapeyre-Mestre, Maryse; Montastruc, Jean-Louis

    2012-11-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are known to antagonize the effects of antihypertensive drugs, and these associations can lead to an increase in arterial blood pressure. However, the impact of NSAIDs on hypertension treatment management in large-scale populations remains poorly evaluated. We examined whether the introduction of NSAID into the treatment regimen would induce an intensification of hypertension treatment (defined as the introduction of a new antihypertensive drug). We conducted a cohort study involving 5,710 hypertensive subjects included in the French health insurance system database who had been treated and stabilized with their antihypertensive therapy and not exposed to any NSAID between 1 April 2005 and 1 April 2006. The maximum follow-up duration was 4 years. Adjusted hazard ratios (HR) for hypertension treatment intensification were 1.34 [95 % confidence interval (CI) 1.05-1.71] for NSAIDs in general, 1.79 (95 % CI 1.15-2.78) for diclofenac and 2.02 (95 % CI:1.09-3.77) for piroxicam. There were significant interactions between NSAIDs and angiotensin converting enzyme inhibitors (ACEIs; HR 4.09, 95 % CI 2.02-8.27) or angiotensin receptor blockers (ARBs; HR 3.62, 95 % CI 1.80-7.31), but not with other antihypertensive drugs. Exposure to NSAIDs leads to an intensification of hypertension treatment, especially in patients treated with ACEIs or ARBs. Renin-angiotensin system blockers should be avoided whenever NSAIDs are prescribed.

  1. [Direction of strategic use: a new classification of non-steroidal anti-inflammatory drugs based on reactivity with peroxidase].

    Science.gov (United States)

    Miura, Toshiaki

    2013-01-01

      The pharmaceutical effects of non-steroidal anti-inflammatory drugs (NSAIDs) occur through the inhibition of prostaglandin H synthase (PGHS). Prostaglandin H2 is produced from arachidonic acid via peroxidase and cyclooxygenase cycles in PGHS. NSAIDs exhibit different levels of reactivity in these reaction cycles. To prevent the development of side effect while maintaining the beneficial effects of drugs, a therapeutic strategy should be used. A new classification of NSAIDs has been proposed based on reactivity to peroxidase. Class 1 includes the majority of NSAIDs, which react with horseradish peroxidase (HRP) compounds I and II. Also, their drugs exhibit spectral changes induced by PGHS peroxidase and diminished ESR signals of the tyrosyl radical of metmyoglobin. They reduce compounds I and II of HRP and scavenge tyrosyl radicals. The branched chain mechanism by which the porphyrin radical is transferred to the tyrosine residue of the protein might be blocked by these NSAIDs. Class 2 includes salicylic acid derivatives that react only with the porphyrin radical and do not react with HRP compound II (oxoferryl species). Class 3 includes aspirin, nimesulide, tolmetin, and arylpropionic acid derivatives, including ibuprofen and the coxibs such as celecoxib and rofecoxib, which are not substrates for HRP or PGHS peroxidase. It seems that the selectivity of NSAIDs to PGHS1 and PGHS2 depends on their reactivity with cyclooxygenase rather than with the peroxidase of PGHS. The best drug for each inflammatory disease should therefore be selected for therapy.

  2. NO-NSAIDs. Part 3: nitric oxide-releasing prodrugs of non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    Borhade, Namdev; Pathan, Asif Rahimkhan; Halder, Somnath; Karwa, Manoj; Dhiman, Mini; Pamidiboina, Venu; Gund, Machhindra; Deshattiwar, Jagannath Janardhan; Mali, Sunil Vasantrao; Deshmukh, Nitin Janardanrao; Senthilkumar, Subrayan Palanisamy; Gaikwad, Parikshit; Tipparam, Santhosh Goud; Mudgal, Jayesh; Dutta, Milan Chandra; Burhan, Aslam Usmangani; Thakre, Gajanan; Sharma, Ankur; Deshpande, Shubhada; Desai, Dattatraya Chandrakant; Dubash, Nauzer Pervez; Jain, Arun Kumar; Sharma, Somesh; Nemmani, Kumar Venkata Subrahmanya; Satyam, Apparao

    2012-01-01

    In continuation of our efforts to discover novel nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) as potentially "Safe NSAIDs," we report herein the design, synthesis and evaluation of 21 new NO-NSAIDs of commonly used NSAIDs such as aspirin, diclofenac, naproxen, flurbiprofen, ketoprofen, sulindac, ibuprofen and indomethacin. These prodrugs have NO-releasing disulfide linker attached to a parent NSAID via linkages such as an ester (compounds 9-16), a double ester (compounds 17-24), an imide (compounds 25-30) or an amide (compounds 31-33). Among these NO-NSAIDs, the ester-containing NO-aspirin (9), NO-diclofenac (10), NO-naproxen (11), and the imide-containing NO-aspirin (25), NO-flurbiprofen (27) and NO-ketoprofen (28) have shown promising oral absorption, anti-inflammatory activity and NO-releasing property, and also protected rats from NSAID-induced gastric damage. NO-aspirin compound 25, on further co-evaluation with aspirin at equimolar doses, exhibited comparable dose-dependent pharmacokinetics, inhibition of gastric mucosal prostaglandin E(2) (PGE(2)) synthesis and analgesic properties to those of aspirin, but retained its gastric-sparing properties even after doubling its oral dose. These promising NO-NSAIDs could therefore represent a new class of potentially "Safe NSAIDs" for the treatment of arthritic pain and inflammation.

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

    Science.gov (United States)

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

    2016-03-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are emerging as novel chemopreventive agents against a variety of cancers owing to their capability in blocking the tumor development by cellular proliferation and by promoting apoptosis. Inflammation is principal cause of colon carcinogenesis. A missing link between inflammation and cancer could be the activation of NF-κB, which is a hallmark of inflammatory response, and is commonly detected in malignant tumors. Therefore, targeting pro-inflammatory cyclooxygenase enzymes and transcription factors will be profitable as a mechanism to inhibit tumor growth. In the present study, we have studied the role of various pro-inflammatory enzymes and transcription factors in the development of the 1,2-dimethylhydrazine dihydrochloride (DMH)-induced colorectal cancer and also observed the role of three NSAIDs, viz., Celecoxib, Etoricoxib and Diclofenac. Carcinogenic changes were observed in morphological and histopathological studies, whereas protein regulations of various biomolecules were identified by immunofluorescence analysis. Apoptotic studies was done by TUNEL assay and Hoechst/PI co-staining of the isolated colonocytes. It was found that DMH-treated animals were having an over-expression of pro-inflammatory enzymes, aberrant nuclear localization of activated cell survival transcription factor, NF-κB and suppression of anti-inflammatory transcription factor PPAR-γ, thereby suggesting a marked role of inflammation in the tumor progression. However, co-administration of NSAIDs has significantly reduced the inflammatory potential of the growing neoplasm. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

    Lehrer, Steven; Rheinstein, Peter H

    2015-05-01

    The Alzheimer's Association recently reported that a woman's estimated lifetime risk of developing Alzheimer's at age 65 is 1 in 6, compared to nearly 1 in 11 for a man (ie, female to male ratio 1.8). Based on female to male ratio, Alzheimer's disease could well be an autoimmune disorder. Like Alzheimer's, multiple sclerosis, an autoimmune inflammation of the central nervous system, has a female to male ratio of 2.3. Also based on female to male ratio, Alzheimer's resembles the autoimmune inflammatory disease rheumatoid arthritis, which has a female to male ratio of 2.7. The reasons for the female preponderance in autoimmune disease are unclear, but nonsteroidal anti-inflammatory drugs (NSAIDs) are widely and successfully employed to treat autoimmune anti-inflammatory disease and dramatically relieve symptoms. Moreover, oral NSAIDs consistently reduce the risk of Alzheimer's disease, although they have been totally ineffective as a treatment in multiple failed clinical trials. A basis for this failure might well be that the brain dose after oral administration is too small and not sufficiently early in the pathogenesis of the disorder. But NSAID brain dose could be significantly increased by delivering the NSAIDs intranasally. © The Author(s) 2014.

  5. Self-Nanoemulsifying Drug Delivery Systems Containing Plantago lanceolata—An Assessment of Their Antioxidant and Antiinflammatory Effects

    Directory of Open Access Journals (Sweden)

    Azin Kalantari

    2017-10-01

    Full Text Available The most important components of Plantago lanceolata L. leaves are catalpol, aucubin, and acteoside (=verbascoside. These bioactive compounds possess different pharmacological effects: anti-inflammatory, antioxidant, antineoplastic, and hepatoprotective. The aim of this study was to protect Plantago lanceolata extract from hydrolysis and to improve its antioxidant effect using self-nano-emulsifying drug delivery systems (SNEDDS. Eight SNEDDS compositions were prepared, and their physical properties, in vitro cytotoxicity, and in vivo AST/ALT values were investigated. MTT cell viability assay was performed on Caco-2 cells. The well-diluted samples (200 to 1000-fold dilutions proved to be non-cytotoxic. The acute administration of PL-SNEDDS compositions resulted in minor changes in hepatic markers (AST, ALT, except for compositions 4 and 8 due to their high Transcutol contents (80%. The non-toxic compositions showed a significant increase in free radical scavenger activity measured by the DPPH test compared to the blank SNEDDS. An indirect dissolution test was performed, based on the result of the DPPH antioxidant assay; the dissolution profiles of Plantago lancolata extract were statistically different from each SNEDDS. The anti-inflammatory effect of PL-SNEDDS compositions was confirmed by the ear inflammation test. For the complete examination period, all compositions decreased ear edema as compared to the positive (untreated control. It can be concluded that PL-SNEDDS compositions could be used to deliver active natural compounds in a stable, efficient, and safe manner.

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

    Science.gov (United States)

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

    2015-11-01

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

  7. Drug repurposing: translational pharmacology, chemistry, computers and the clinic.

    Science.gov (United States)

    Issa, Naiem T; Byers, Stephen W; Dakshanamurthy, Sivanesan

    2013-01-01

    The process of discovering a pharmacological compound that elicits a desired clinical effect with minimal side effects is a challenge. Prior to the advent of high-performance computing and large-scale screening technologies, drug discovery was largely a serendipitous endeavor, as in the case of thalidomide for erythema nodosum leprosum or cancer drugs in general derived from flora located in far-reaching geographic locations. More recently, de novo drug discovery has become a more rationalized process where drug-target-effect hypotheses are formulated on the basis of already known compounds/protein targets and their structures. Although this approach is hypothesis-driven, the actual success has been very low, contributing to the soaring costs of research and development as well as the diminished pharmaceutical pipeline in the United States. In this review, we discuss the evolution in computational pharmacology as the next generation of successful drug discovery and implementation in the clinic where high-performance computing (HPC) is used to generate and validate drug-target-effect hypotheses completely in silico. The use of HPC would decrease development time and errors while increasing productivity prior to in vitro, animal and human testing. We highlight approaches in chemoinformatics, bioinformatics as well as network biopharmacology to illustrate potential avenues from which to design clinically efficacious drugs. We further discuss the implications of combining these approaches into an integrative methodology for high-accuracy computational predictions within the context of drug repositioning for the efficient streamlining of currently approved drugs back into clinical trials for possible new indications.

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

    Science.gov (United States)

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

    2016-10-01

    Drug release from inorganic supports is a challenge for the scientific community for various reasons, related to the low costs of the systems and the possibility of easily regulating the drug release. In the present work, surface-modified zeolite particles are used as carriers for non steroidal antiflammatory drugs (NSAIDs). The release of the drug has been studied in a solution that simulates the intestinal fluid as well as in a gel-like system, based on a surfactant and a binding salt. In the solution case, the quantity of drug released has been tracked via spectrophotometric assay. Release in the gel has been monitored by rheological methods. The molecular conformation of the NSAIDs is fundamental for the interaction with the zeolite surface, whose modified surface has a strong binding energy. It has been proven that the main mechanism for the drug release is anion exchange. It has been found that the NSAIDs, used in their sodic form, can act as binding salts by themselves in the gel-like system, thus changing the viscoelastic response of the overall solution. Drug release kinetics in the solution compare quantitatively well with the released drug in the gel-like fluid, as measured by rheometry. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Review of the safety of nonsteroidal anti-inflammatory drugs and ...

    African Journals Online (AJOL)

    A systemic review found that NSAIDs were one of four drugs associated with the highest number of drug-related hospital admissions. The others were diuretics, anticoagulants and antiplatelet agents.1 A wide range of adverse events are caused by both selective and nonselective cyclo-oxygenase. (COX) inhibitors.

  10. Histometric study of alveolar bone healing in rats treated with the nonsteroidal anti-inflammatory drug nimesulide.

    Science.gov (United States)

    Teófilo, Juliana Mazzonetto; Giovanini, Gabriela Salgueiro; Fracon, Ricardo Nogueira; Lamano, Teresa

    2011-04-01

    There is extensive experimental and clinical evidence in the orthopedic area that prolonged use of nonselective (inhibitor of both cyclooxygenases 1 and 2) nonsteroidal anti-inflammatory drugs can hinder long bone fracture healing, spinal fusion rate, and new bone formation around implants. The purpose of the present study was to investigate whether nimesulide (Nimesulida, Medley S.A., Campinas, SP, Brazil), a preferential cyclooxygenase-2 inhibitor, can hinder alveolar bone healing, in rats. Treated rats received oral doses (5 mg/kg/rat/day) of nimesulide from the day of tooth extraction until euthanasia 2 weeks later and control rats received tap water (n = 5 per group). The volume of neoformed bone inside the alveolar socket was estimated in semiserial longitudinal histological sections by a differential point-counting method, and the significance of the difference between groups was analyzed by Student t test (P alveolar bone healing in rats.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    INTRODUCTION: Helicobacter pylori (HP) infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs)/acetyl salicylic acid (ASA) are risk factors for bleeding peptic ulcer. HP eradication reduces the risk of rebleeding. Antibiotics, proton pump inhibitors (PPI) and presence of blood...... years. The HP-prevalence was 34%, and 81% had used NSAID/ASA, as compared with 55% in 1990-1992. The proportion of idiopathic peptic ulcer disease was 6.6%. At admission, 19% and 17% of the patients were in treatment with PPI and antibiotics, respectively. Thirteen percent of the initially HP...... in the stomach can affect the HP test. The objectives of this study were to determine the HP prevalence and NSAID/ASA use in patients with bleeding ulcer in a low-prevalence HP area, to determine the proportion of idiopathic ulcers and to estimate the proportion of initially false negative HP tests. In addition...

  12. Leclercia adecarboxylata bacteremia in a patient with long-term use of nonsteroidal anti-inflammatory drugs.

    Science.gov (United States)

    Jean, Shio-Shin; Lee, Wen-Sen; Bai, Kuan-Jen; Lam, Carlos; Hsu, Chin-Wang; Chen, Ray-Jade; Hsueh, Po-Ren

    2016-06-01

    Leclercia adecarboxylata, a ubiquitous Gram-negative bacillus, is generally viewed as an opportunistic pathogen because it is rarely cultured from clinical samples. Although rare, bacteremia due to L. adecarboxylata tends to occur in immunocompromised hosts and patients with systemic comorbidities. Only one case of bacteremia due to L. adecarboxylata has been reported in a previously healthy patient. We describe a male patient with an active peptic ulcer who developed L. adecarboxylata bacteremia after a long-term use of nonsteroidal anti-inflammatory drugs. The abdomen is believed to have been the most probable portal of entry. After appropriate medical management, the patient recovered without sequela. Copyright © 2013. Published by Elsevier B.V.

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

    Science.gov (United States)

    Gil, Michał; Douhal, Abderrazzak

    2008-06-01

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

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

    DEFF Research Database (Denmark)

    Nørgård, Bente Mertz

    2011-01-01

    increased risk of preterm birth when women give birth 0-6 months after establishment of the diagnosis. It is considered whether the increased risk may be influenced by disease activity around the time of establishing the diagnosis. 2) No increased risk of giving birth to children with low birth weight...... in children of women with ulcerative colitis, ii) pharmacoepidemiological studies on the risk of adverse birth outcome after maternal azathioprine/6-mercaptopurine exposure in pregnancy, and the risk of congenital abnormalities in children fathered by men treated with azathioprine/6-mercaptopurine before......The clinical epidemiological studies included in this thesis fall into three parts. The first part includes studies on birth outcome in women with ulcerative colitis. The second part includes pharmacoepidemiological studies on birth outcome after anti-inflammatory drug therapy in pregnancy...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  16. Necrotizing Sialometaplasia of the Hard Palate in a Patient Treated with Topical Nonsteroidal Anti-Inflammatory Drug

    Directory of Open Access Journals (Sweden)

    Alessandro Gatti

    2016-01-01

    Full Text Available Necrotizing sialometaplasia is a rare, benign, self-limiting, necrotizing process involving the minor salivary glands, mainly the mucoserous glands of the hard palate. It is thought to be the result of an ischemic event of the vasculature supplying the salivary gland lobules. Some predisposing factors such as smoking, use of alcohol, denture wearing, recent surgery, traumatic injuries, respiratory infections, systemic diseases bulimia, and anorexia have been described. Herein we present a case of necrotizing sialometaplasia of the hard palate in a patient without known predisposing factors, in our opinion, resulting from the use of topical anti-inflammatory drug. After diagnosis, the patient underwent treatment with chlorhexidine gluconate and a full palatal acrylic guard to protect the exposed bone from food residues during meals. After the sixth week the lesion regressed.

  17. Non-Steroidal Anti-Inflammatory Drugs in Alzheimer's Disease and Parkinson's Disease: Reconsidering the Role of Neuroinflammation.

    Science.gov (United States)

    Moore, Amy H; Bigbee, Matthew J; Boynton, Grace E; Wakeham, Colin M; Rosenheim, Hilary M; Staral, Christopher J; Morrissey, James L; Hund, Amanda K

    2010-06-02

    Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases with age as the greatest risk factor. As the general population experiences extended life span, preparation for the prevention and treatment of these and other age-associated neurological diseases are warranted. Since epidemiological studies suggested that non-steroidal anti-inflammatory drug (NSAID) use decreased risk for AD and PD, increasing attention has been devoted to understanding the costs and benefits of the innate neuroinflammatory response to functional recovery following pathology onset. This review will provide a general overview on the role of neuroinflammation in these neurodegenerative diseases and an update on NSAID treatment in recent experimental animal models, epidemiological analyses, and clinical trials.

  18. Non-Steroidal Anti-Inflammatory Drugs in Alzheimer's Disease and Parkinson's Disease: Reconsidering the Role of Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Amy H. Moore

    2010-06-01

    Full Text Available Alzheimer's disease (AD and Parkinson's disease (PD are the most common neurodegenerative diseases with age as the greatest risk factor. As the general population experiences extended life span, preparation for the prevention and treatment of these and other age-associated neurological diseases are warranted. Since epidemiological studies suggested that non-steroidal anti-inflammatory drug (NSAID use decreased risk for AD and PD, increasing attention has been devoted to understanding the costs and benefits of the innate neuroinflammatory response to functional recovery following pathology onset. This review will provide a general overview on the role of neuroinflammation in these neurodegenerative diseases and an update on NSAID treatment in recent experimental animal models, epidemiological analyses, and clinical trials.

  19. Efficacy of nonsteroidal anti-inflammatory drugs in the treatment of acute renal colic. A meta-analysis.

    Science.gov (United States)

    Labrecque, M; Dostaler, L P; Rousselle, R; Nguyen, T; Poirier, S

    1994-06-27

    To evaluate the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) compared with placebo or analgesic agents in the treatment of acute renal colic. The MEDLINE and EMBASE databases were searched using the following terms: anti-inflammatory agent, colic, kidney diseases, and ureteral diseases. The Family Medicine Library Index, references of retrieved articles, and documentation centers of pharmaceutical companies were also consulted. Among 60 retrieved articles, 19 were selected by consensus of a group of four physicians, based on the following criteria: randomized controlled trials, NSAID compared with placebo or analgesic agent in the treatment of acute renal colic, and articles written in either French or English. Independent data extraction by four evaluators using a 20-item checklist. Final assessment was by group consensus. The 19 articles presented 20 studies, most comparing parenteral diclofenac or indomethacin (18 of 20) with placebo (n = 4) or analgesic agents (n = 16), most of which were narcotic agents. The results of pain relief 20 to 30 minutes after drug administration were pooled using the Mantel-Haenszel method for three distinct groups of studies: (1) NSAIDs vs placebo (n = 4): relative risk (RR), 2.34 (95% confidence interval [CI], 1.79 to 3.07); (2) NSAIDs vs analgesic agents, partial pain relief (n = 9): RR, 1.07 (95% CI, 1.02 to 1.12); and (3) NSAIDs vs analgesic agents, complete pain relief (n = 9): RR, 1.19 (95% CI, 1.03 to 1.37). Parenteral NSAIDs are more effective than placebo and as effective as analgesic agents in the treatment of acute renal colic.

  20. High doses of anti-inflammatory drugs compromise muscle strength and hypertrophic adaptations to resistance training in young adults.

    Science.gov (United States)

    Lilja, M; Mandić, M; Apró, W; Melin, M; Olsson, K; Rosenborg, S; Gustafsson, T; Lundberg, T R

    2018-02-01

    This study tested the hypothesis that high doses of anti-inflammatory drugs would attenuate the adaptive response to resistance training compared with low doses. Healthy men and women (aged 18-35 years) were randomly assigned to daily consumption of ibuprofen (IBU; 1200 mg; n = 15) or acetylsalicylic acid (ASA; 75 mg; n = 16) for 8 weeks. During this period, subjects completed supervised knee-extensor resistance training where one leg was subjected to training with maximal volitional effort in each repetition using a flywheel ergometer (FW), while the other leg performed conventional (work-matched across groups) weight-stack training (WS). Before and after training, muscle volume (MRI) and strength were assessed, and muscle biopsies were analysed for gene and protein expression of muscle growth regulators. The increase in m. quadriceps volume was similar between FW and WS, yet was (averaged across legs) greater in ASA (7.5%) compared with IBU (3.7%, group difference 34 cm 3 ; P = 0.029). In the WS leg, muscle strength improved similarly (11-20%) across groups. In the FW leg, increases (10-23%) in muscle strength were evident in both groups yet they were generally greater (interaction effects P training effects, the only group interaction (P strength and muscle hypertrophic adaptations to 8 weeks of resistance training in young adults. Thus, young individuals using resistance training to maximize muscle growth or strength should avoid excessive intake of anti-inflammatory drugs. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  1. Selective modulation of Abeta42 production in Alzheimer's disease: non-steroidal anti-inflammatory drugs and beyond.

    Science.gov (United States)

    Leuchtenberger, Stefanie; Beher, Dirk; Weggen, Sascha

    2006-01-01

    The amyloid-beta (Abeta) peptides and in particular the longer, highly amyloidogenic isoform Abeta42 are believed by many to be the central disease-causing agents in Alzheimer's disease (AD). Consequently, academic and pharmaceutical laboratories have focused on elucidating the mechanisms of Abeta production and developing strategies to diminish Abeta formation for treatment or prevention of AD. The most substantial advances have been made with respect to inhibitors of the gamma-secretase enzyme, which catalyzes the final step in the generation of Abeta from the amyloid precursor protein (APP). Highly potent gamma-secretase inhibitors which suppress production of all Abeta peptides are available today. However, due to the promiscuous substrate specificity of gamma-secretase and its essential role in the NOTCH signaling pathway overt mechanism-based toxicity has been observed in preclinical studies of gamma-secretase inhibitors. For that reason, specific blockage of Abeta42 production might be preferable over non-discriminatory gamma-secretase inhibition but small molecule inhibitors of Abeta42 production have remained elusive until recently. This has changed with the discovery that certain non-steroidal anti-inflammatory drugs (NSAIDs) including ibuprofen possess preferential Abeta42-lowering activity. These compounds seem to offer a window of modulation where Abeta42 production is potently inhibited whereas processing of the NOTCH receptor and other gamma-secretase substrates remains unaffected. The Abeta42-lowering activity of NSAIDs is not related to inhibition of cyclooxygenases and can be dissociated from the anti-inflammatory properties of this class of drugs. Ongoing efforts concentrate on uncovering the mechanism of action and improving potency and brain permeability of Abeta42-lowering compounds. Hopes are high that in the near future this will lead to the development of clinically viable compounds which selectively target Abeta42 as a key molecule in the

  2. The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs

    Science.gov (United States)

    Reid, Glen; Wielinga, Peter; Zelcer, Noam; van der Heijden, Ingrid; Kuil, Annemieke; de Haas, Marcel; Wijnholds, Jan; Borst, Piet

    2003-01-01

    Prostaglandins are involved in a wide variety of physiological and pathophysiological processes, but the mechanism of prostaglandin release from cells is not completely understood. Although poorly membrane permeable, prostaglandins are believed to exit cells by passive diffusion. We have investigated the interaction between prostaglandins and members of the ATP-binding cassette (ABC) transporter ABCC [multidrug resistance protein (MRP)] family of membrane export pumps. In inside-out membrane vesicles derived from insect cells or HEK293 cells, MRP4 catalyzed the time- and ATP-dependent uptake of prostaglandin E1 (PGE1) and PGE2. In contrast, MRP1, MRP2, MRP3, and MRP5 did not transport PGE1 or PGE2. The MRP4-mediated transport of PGE1 and PGE2 displayed saturation kinetics, with Km values of 2.1 and 3.4 μM, respectively. Further studies showed that PGF1α, PGF2α, PGA1, and thromboxane B2 were high-affinity inhibitors (and therefore presumably substrates) of MRP4. Furthermore, several nonsteroidal antiinflammatory drugs were potent inhibitors of MRP4 at concentrations that did not inhibit MRP1. In cells expressing the prostaglandin transporter PGT, the steady-state accumulation of PGE1 and PGE2 was reduced proportional to MRP4 expression. Inhibition of MRP4 by an MRP4-specific RNA interference construct or by indomethacin reversed this accumulation deficit. Together, these data suggest that MRP4 can release prostaglandins from cells, and that, in addition to inhibiting prostaglandin synthesis, some nonsteroidal antiinflammatory drugs might also act by inhibiting this release. PMID:12835412

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

    Directory of Open Access Journals (Sweden)

    Irene eRamos

    2015-07-01

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

  4. Efficacy and safety of rabeprazole in non-steroidal anti-inflammatory drug-induced ulcer in Japan.

    Science.gov (United States)

    Mizokami, Yuji

    2009-10-28

    To investigate the efficacy and safety of rabeprazole under continuous non-steroidal anti-inflammatory drug (NSAID) administration for NSAID-induced ulcer in Japan. Subjects comprised patients undergoing NSAID treatment in whom upper gastrointestinal endoscopy revealed an ulcerous lesion (open ulcer) with diameter > or = 3 mm, who required continuous NSAID treatment. Endoscopies were performed at the start of treatment, during the treatment period, and at the conclusion (or discontinuation) of treatment. Findings were evaluated as size (maximum diameter) and stage based on the Sakita-Miwa classification. An ulcer was regarded as cured when the "white coating" was seen to have disappeared under endoscopy. As criteria for evaluating safety, all medically untoward symptoms and signs (adverse events, laboratory abnormalities, accidental symptoms, etc.) occurring after the start of rabeprazole treatment were handled as adverse events. Endoscopic cure rate in 38 patients in the efficacy analysis (endoscopic evaluation) was 71.1% (27/38). Among those 38 patients, 35 had gastric ulcer with a cure rate of 71.4% (25/35), and 3 had duodenal ulcer with a cure rate of 66.7% (2/3). Three adverse drug reactions were reported from 64 patients in the safety analysis (interstitial pneumonia, low white blood cell count and pruritus); thus, the incidence rate for adverse drug reactions was 4.7% (3/64). The treatment efficacy of rabeprazole for NSAID-induced ulcer under continuous NSAID administration was confirmed.

  5. Levetiracetam+nonsteroidal anti-inflammatory drug binary systems: A contribution to the development of new solid dosage forms.

    Science.gov (United States)

    Machado, Sara M T; Castro, Ricardo A E; Maria, Teresa M R; Canotilho, João; Eusébio, M Ermelinda S

    2017-11-25

    A study has been carried out of binary solid systems made up of the antiepileptic drug levetiracetam, LEV, and a nonsteroidal anti-inflammatory drug, NSAID, capable of managing the inflammation that accompanies epileptic activity. One aim of this research was to identify eutectic mixtures and co-crystals, which are able to impact positively on their biopharmaceutical properties. The NSAIDs studied are (S)- and (R,S)-ibuprofen, (S)- and (R,S)-naproxen, (R,S)-ketoprofen and (R,S)-flurbiprofen, all class II in the Biopharmaceutical Classification System. A green mechanochemical methodology has been used to prepare binary mixtures with different molar ratios, and the binary solid-liquid phase diagrams established. For LEV+(S)-ibuprofen, formation of a single (1:1) co-crystal was confirmed; this was found to melt incongruently. The co-crystal was found to be stable in accelerated stability tests. For the other systems, interesting eutectic mixtures were identified, which showed enhanced dissolution rates of the NSAID relative to the pure drug. For LEV+(R,S)-ibuprofen, LEV+(S)-naproxen and LEV+(R,S)-naproxen, the eutectic mixture compositions have the effective doses of both components. All the NSAIDs investigated are chiral, and their racemates are racemic compounds. Levetiracetam, the (S)-enantiomer of etiracetam, was not efficient in enantiomer discrimination, as all the racemic compound structures are present as the prepared solid mixtures. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Shunji Fujimori

    2010-04-01

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

  7. Mannich bases in medicinal chemistry and drug design.

    Science.gov (United States)

    Roman, Gheorghe

    2015-01-07

    The biological activity of Mannich bases, a structurally heterogeneous class of chemical compounds that are generated from various substrates through the introduction of an aminomethyl function by means of the Mannich reaction, is surveyed, with emphasis on the relationship between structure and biological activity. The review covers extensively the literature reports that have disclosed Mannich bases as anticancer and cytotoxic agents, or compounds with potential antibacterial and antifungal activity in the last decade. The most relevant studies on the activity of Mannich bases as antimycobacterial agents, antimalarials, or antiviral candidates have been included as well. The review contains also a thorough coverage of anticonvulsant, anti-inflammatory, analgesic and antioxidant activities of Mannich bases. In addition, several minor biological activities of Mannich bases, such as their ability to regulate blood pressure or inhibit platelet aggregation, their antiparasitic and anti-ulcer effects, as well as their use as agents for the treatment of mental disorders have been presented. The review gives in the end a brief overview of the potential of Mannich bases as inhibitors of various enzymes or ligands for several receptors. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  8. Chiral Drug Analysis in Forensic Chemistry: An Overview

    Directory of Open Access Journals (Sweden)

    Cláudia Ribeiro

    2018-01-01

    Full Text Available Many substances of forensic interest are chiral and available either as racemates or pure enantiomers. Application of chiral analysis in biological samples can be useful for the determination of legal or illicit drugs consumption or interpretation of unexpected toxicological effects. Chiral substances can also be found in environmental samples and revealed to be useful for determination of community drug usage (sewage epidemiology, identification of illicit drug manufacturing locations, illegal discharge of sewage and in environmental risk assessment. Thus, the purpose of this paper is to provide an overview of the application of chiral analysis in biological and environmental samples and their relevance in the forensic field. Most frequently analytical methods used to quantify the enantiomers are liquid and gas chromatography using both indirect, with enantiomerically pure derivatizing reagents, and direct methods recurring to chiral stationary phases.

  9. [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].

    Science.gov (United States)

    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).

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2007-01-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  13. The smallest worthwhile effect of nonsteroidal anti-inflammatory drugs and physiotherapy for chronic low back pain: a benefit harm trade-off study

    NARCIS (Netherlands)

    Ferreira, M.L.; Herbert, R.D.; Ferreira, P.H.; Latimer, J.; Ostelo, R.W.J.G.; Grotle, M.; Barrett, B.

    2013-01-01

    Objective The aim of this study was to determine the smallest worthwhile effects of two treatments for nonspecific low back pain (LBP). Study Design and Setting The benefit-harm trade-off method was used to estimate the smallest worthwhile effect of nonsteroidal anti-inflammatory drugs (NSAIDs) and

  14. Effects of paracetamol, non-steroidal anti-inflammatory drugs, acetylsalicylic acid, and opioids on bone mineral density and risk of fracture

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  15. Exposure to non-steroidal anti-inflammatory drugs during pregnancy and the risk of selected birth defects: a prospective cohort study

    NARCIS (Netherlands)

    Gelder, M.M.H.J. van; Roeleveld, N.; Nordeng, H.

    2011-01-01

    BACKGROUND: Since use of non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy is common, small increases in the risk of birth defects may have significant implications for public health. Results of human studies on the teratogenic risks of NSAIDs are inconsistent. Therefore, we evaluated

  16. Early drug discovery and the rise of pharmaceutical chemistry.

    Science.gov (United States)

    Jones, Alan Wayne

    2011-06-01

    Studies in the field of forensic pharmacology and toxicology would not be complete without some knowledge of the history of drug discovery, the various personalities involved, and the events leading to the development and introduction of new therapeutic agents. The first medicinal drugs came from natural sources and existed in the form of herbs, plants, roots, vines and fungi. Until the mid-nineteenth century nature's pharmaceuticals were all that were available to relieve man's pain and suffering. The first synthetic drug, chloral hydrate, was discovered in 1869 and introduced as a sedative-hypnotic; it is still available today in some countries. The first pharmaceutical companies were spin-offs from the textiles and synthetic dye industry and owe much to the rich source of organic chemicals derived from the distillation of coal (coal-tar). The first analgesics and antipyretics, exemplified by phenacetin and acetanilide, were simple chemical derivatives of aniline and p-nitrophenol, both of which were byproducts from coal-tar. An extract from the bark of the white willow tree had been used for centuries to treat various fevers and inflammation. The active principle in white willow, salicin or salicylic acid, had a bitter taste and irritated the gastric mucosa, but a simple chemical modification was much more palatable. This was acetylsalicylic acid, better known as Aspirin®, the first blockbuster drug. At the start of the twentieth century, the first of the barbiturate family of drugs entered the pharmacopoeia and the rest, as they say, is history. Copyright © 2011 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

    Nørgård, Bente Mertz

    2011-12-01

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

  18. Clinical guidelines «Rational use of nonsteroidal anti-inflammatory drugs (NSAIDs in clinical practice»

    Directory of Open Access Journals (Sweden)

    A. E. Karateev

    2015-01-01

    Full Text Available The paper presents the new version of the clinical guidelines «Rational use of nonsteroidal anti-inflammatory drugs (NSAIDs in clinical practice » prepared by the Association of Rheumatologists of Russia, the Russian Pain Society, the Russian Gastroenterological Association, the Russian Society of Cardiology, the Association of Traumatologists and Orthopedists of Russia, the Association of Interdisciplinary Medicine, and the Russian Association of Palliative Medicine.In our country, NSAIDs are the most important and most popular class of analgesics. Unlike global practice, Russian physicians rather rarely recommend paracetamol as a first-line drug to relieve moderate or severe pain, by giving preference to NSAIDs; the use of opioid analgesics for noncancers is minimized because of tight legal restrictions.NSAIDs are effective and easy-to-use; however, they are far from safe; the administration of these medications may lead to serious gastrointestinal, cardiovascular, renal, and other complications in a number of cases. So the use of NSAIDs should be compulsorily monitored for adverse reactions and the choice of a specific drug for each clinical case should be based on the objective estimation of a ratio of its efficacy to safety.In recent years, there have been fresh data on the use of NSAIDs for different diseases and a few novel representatives of this drug group have appeared on the Russian pharmacological market.This all has necessitated a new version of the guidelines on the rational use of NSAIDs. These are based on the provisions that have high validity and have been confirmed by the results of well-organized clinical and large-scale population-based studies, as well as by their meta-analysis.The guidelines are intended for physicians of all specialties. 

  19. In Silico Screening of Nonsteroidal Anti-Inflammatory Drugs and Their Combined Action on Prostaglandin H Synthase-1

    Directory of Open Access Journals (Sweden)

    Alexey Goltsov

    2010-07-01

    Full Text Available The detailed kinetic model of Prostaglandin H Synthase-1 (PGHS-1 was applied to in silico screening of dose-dependencies for the different types of nonsteroidal anti-inflammatory drugs (NSAIDs, such as: reversible/irreversible, nonselective/selective to PGHS-1/PGHS-2 and time dependent/independent inhibitors (aspirin, ibuprofen, celecoxib, etc. The computational screening has shown a significant variability in the IC50s of the same drug, depending on different in vitro and in vivo experimental conditions. To study this high heterogeneity in the inhibitory effects of NSAIDs, we have developed an in silico approach to evaluate NSAID action on targets under different PGHS-1 microenvironmental conditions, such as arachidonic acid, reducing cofactor, and peroxide concentrations. The designed technique permits translating the drug IC50, obtained in one experimental setting to another, and predicts in vivo inhibitory effects based on the relevant in vitro data. For the aspirin case, we elucidated the mechanism underlying the enhancement and reduction (aspirin resistance of its efficacy, depending on PGHS-1 microenvironment in in vitro/in vivo experimental settings. We also present the results of the in silico screening of the combined action of sets of two NSAIDs (aspirin with ibuprofen, aspirin with celecoxib, and study the mechanism of the experimentally observed effect of the suppression of aspirin-mediated PGHS-1 inhibition by selective and nonselective NSAIDs. Furthermore, we discuss the applications of the obtained results to the problems of standardization of NSAID test assay, dependence of the NSAID efficacy on cellular environment of PGHS-1, drug resistance, and NSAID combination therapy.

  20. Transcriptional and cellular effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in experimentally exposed mussels, Mytilus galloprovincialis.

    Science.gov (United States)

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

    2016-11-01

    The aim of the present investigation was to provide new insights on accumulation and possible adverse effects of various non-steroidal anti-inflammatory drugs (NSAIDs) in mussels, Mytilus galloprovincialis, exposed to an environmentally realistic concentration (0.5μg/L) of individual compounds, Acetaminophen (AMP), Diclofenac (DIC), Ibuprofen (IBU), Ketoprofen (KET) or Nimesulide (NIM). The measurement of drugs in mussel tissues was integrated with both functional alterations at cellular level and transcriptomic responses. Results indicated the capability of mussels to accumulate DIC and NIM, while AMP, IBU and KET were always below detection limit. A large panel of ecotoxicological biomarkers revealed the early onset of alterations induced by tested NSAIDs on immunological responses, lipid metabolism and DNA integrity. The gene transcription analysis through DNA microarrays, supported cellular biomarker results, with clear modulation of a large number of genes involved in the arachidonic acid and lipid metabolism, immune responses, cell cycle and DNA repair. The overall results indicated an ecotoxicological concern for pharmaceuticals in M. galloprovincialis, with transcriptional responses appearing as sensitive exposure biomarkers at low levels of exposure: such changes, however, are not always paralleled by corresponding functional effects, suggesting caution when interpreting observed effects in terms of perturbed cellular pathways. Fascinating similarities can also be proposed in the mode of action of NSAIDs between bivalves and vertebrate species. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Cheng, Huiwen; Mollica, Molly Y; Lee, Shin Hee; Wang, Lei; Velázquez-Martínez, Carlos A; Wu, Shiyong

    2012-10-15

    A new class of nitric oxide (NO•)-releasing nonsteroidal anti-inflammatory drugs (NONO-NSAIDs) were developed in recent years and have shown promising potential as NSAID substitutes due to their gentle nature on cardiovascular and gastrointestinal systems. Since nitric oxide plays a role in regulation of cell adhesion, we assessed the potential use of NONO-NSAIDs as anti-metastasis drugs. In this regard, we compared the effects of NONO-aspirin and a novel NONO-naproxen to those exerted by their respective parent NSAIDs on avidities of human melanoma M624 cells. Both NONO-NSAIDs, but not the corresponding parent NSAIDs, reduced M624 adhesion on vascular cellular adhesion molecule-1 (VCAM-1) by 20-30% and fibronectin by 25-44% under fluid flow conditions and static conditions, respectively. Only NONO-naproxen reduced (~56%) the activity of β1 integrin, which binds to α4 integrin to form very late antigen-4 (VLA-4), the ligand of VCAM-1. These results indicate that the diazeniumdiolate (NO•)-donor moiety is critical for reducing the adhesion between VLA-4 and its ligands, while the NSAID moiety can impact the regulation mechanism of melanoma cell adhesion. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Genetic variants of the arachidonic acid pathway in non-steroidal anti-inflammatory drug-induced acute urticaria.

    Science.gov (United States)

    Cornejo-García, J A; Jagemann, L R; Blanca-López, N; Doña, I; Flores, C; Guéant-Rodríguez, R M; Torres, M J; Fernández, J; Laguna, J J; Rosado, A; Agúndez, J A G; García-Martín, E; Canto, G; Guéant, J-L; Blanca, M

    2012-12-01

    To date, genetic studies of hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) have been carried out mainly in aspirin-induced asthma and to a lesser extent in chronic urticaria, with no studies in patients with acute urticaria (AU), the most common entity induced by these drugs. In this work, we analysed the association of common variants of 15 relevant genes encoding both enzymes and receptors from the arachidonic acid (AA) pathway with NSAID-induced AU. Patients were recruited in several Allergy Services that are integrated into the Spanish network RIRAAF, and diagnosed of AU induced by cross-intolerance (CRI) to NSAIDs. Genotyping was carried out by TaqMan allelic discrimination assays. A total of 486 patients with AU induced by CRI to NSAIDs and 536 unrelated controls were included in this large Spanish case-control study. Seven variants from 31 tested in six genes were associated in a discovery study population from Malaga (0.0003 ≤ p-value ≤ 0.041). A follow-up analysis in an independent sample from Madrid replicated three of the SNPs from the ALOX15 (rs7220870), PTGDR (rs8004654) and CYSLTR1 (rs320095) genes (1.055x10(-6) ≤meta-analysis p-value ≤ 0.003). Genetic variants of the AA pathway may play an important role in NSAID-induced AU. These data may help understand the mechanism underlying this disease. © 2012 Blackwell Publishing Ltd.

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-11-15

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

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

    Science.gov (United States)

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

    2017-05-01

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

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

    Science.gov (United States)

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

    2017-04-01

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

  7. Inhibition of angiogenesis by nonsteroidal anti-inflammatory drugs: insight into mechanisms and implications for cancer growth and ulcer healing.

    Science.gov (United States)

    Jones, M K; Wang, H; Peskar, B M; Levin, E; Itani, R M; Sarfeh, I J; Tarnawski, A S

    1999-12-01

    Angiogenesis, the formation of new capillary blood vessels, is essential not only for the growth and metastasis of solid tumors, but also for wound and ulcer healing, because without the restoration of blood flow, oxygen and nutrients cannot be delivered to the healing site. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, indomethacin and ibuprofen are the most widely used drugs for pain, arthritis, cardiovascular diseases and, more recently, the prevention of colon cancer and Alzheimer disease. However, NSAIDs produce gastroduodenal ulcers in about 25% of users (often with bleeding and/or perforations) and delay ulcer healing, presumably by blocking prostaglandin synthesis from cyclooxygenase (COX)-1 and COX-2 (ref. 10). The hypothesis that the gastrointestinal side effects of NSAIDs result from inhibition of COX-1, but not COX-2 (ref. 11), prompted the development of NSAIDs that selectively inhibit only COX-2 (such as celecoxib and rofecoxib). Our study demonstrates that both selective and nonselective NSAIDs inhibit angiogenesis through direct effects on endothelial cells. We also show that this action involves inhibition of mitogen-activated protein (MAP) kinase (ERK2) activity, interference with ERK nuclear translocation, is independent of protein kinase C and has prostaglandin-dependent and prostaglandin-independent components. Finally, we show that both COX-1 and COX-2 are important for the regulation of angiogenesis. These findings challenge the premise that selective COX-2 inhibitors will not affect the gastrointestinal tract and ulcer/wound healing.

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

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Huiwen [Edison Biotechnology Institute, Ohio University, Athens, OH 45701 (United States); Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701 (United States); Mollica, Molly Y.; Lee, Shin Hee [Edison Biotechnology Institute, Ohio University, Athens, OH 45701 (United States); Wang, Lei [Edison Biotechnology Institute, Ohio University, Athens, OH 45701 (United States); Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701 (United States); Velázquez-Martínez, Carlos A., E-mail: velazque@ualberta.ca [Chemistry Section, Laboratory of Comparative Carcinogenesis and Basic Research Program, SAIC-Frederick Inc., National Cancer Institute at Frederick, Frederick, MD 21702 (United States); Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton Alberta, Canada T6G 2N8 (Canada); Wu, Shiyong, E-mail: wus1@ohio.edu [Edison Biotechnology Institute, Ohio University, Athens, OH 45701 (United States); Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701 (United States)

    2012-10-15

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

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

    Directory of Open Access Journals (Sweden)

    Jean-Pascal Fournier

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

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

    Science.gov (United States)

    Cooper, Tess E; Heathcote, Lauren C; Anderson, Brian; Grégoire, Marie-Claude; Ljungman, Gustaf; Eccleston, Christopher

    2017-07-24

    Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization (WHO) guidelines for pharmacological treatments for persisting pain in children acknowledge that pain in children is a major public health concern of high significance in most parts of the world. Views on children's pain have changed over time and relief of pain is now seen as important. In the past, pain was largely dismissed and was frequently left untreated, and it was assumed that children quickly forgot about painful experiences.We designed a suite of seven reviews in chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol as priority areas) to review the evidence for children's pain using pharmacological interventions.As one of the leading causes of mortality and morbidity for children and adolescents in the world today, childhood cancer (and its associated pain) is a major health concern. Specific mortality and morbidity data relating to children are not currently identified. All childhood cancer rates are on the rise; for example, in the USA approximately 10,380 children aged under 15 years were expected to be diagnosed with cancer by the end of 2016. However, with survival rates also increasing, over 80% of paediatric cancer patients are expected to survive for five years or more, thus identifying the need to address pain management in this population.Cancer pain in infants, children, and adolescents is primarily nociceptive pain with negative long term effects. Cancer-related pain is generally caused directly by the tumour itself such as compressing on the nerve or inflammation of the organs. Cancer-related pain generally occurs as a result of perioperative procedures, nerve damage caused by radiation or chemotherapy treatments, or mucositis. However, this review focused on pain caused directly by the tumour

  11. Analgesic-antiinflammatory drugs inhibit orbicularis oculi reflexes in humans via a central mode of action.

    Science.gov (United States)

    Ferracuti, S; Leardi, M G; Cruccu, G; Fabbri, A; Itil, T M

    1994-01-01

    1. A cross-over single blind study examined the possible central effects of non-opioid analgesic drugs on the trigeminal reflexes. 2. The corneal reflex and blink reflex (R1, R2) were recorded electromyographically and response areas measured in healthy volunteers before and after intramuscular injection of piroxicam (40 mg); and after intravenous injection of lysine acetylsalicylate (500 mg). After the last drug recording the subjects received intravenous naloxone (2 mg) followed 5 minutes later by further reflex testing. Saline was used as a placebo in control experiments. 3. Both analgesics reduced the corneal reflex: piroxicam induced a 27% and lysine acetylsalicylate a 21% a reduction that naloxone did not reverse. Neither drug reduced the early or the late component of the blink reflex. 4. The marked inhibitory changes that the two non-narcotic analgesics produced on the corneal reflex--a nociceptive response--indicate a centrally-mediated action. 5. Naloxone's failure to reverse the induced analgesia argues against opiate receptor mediation.

  12. [Analysis of 76 patients with urticaria and angioedema induced by non-steroidal anti-inflammatory drugs (NSAIDs) in Japan].

    Science.gov (United States)

    Moriya, Maki; Aihara, Michiko; Hirota, Rie; Hirata, Yuko; Ikinaga, Naoko; Takamura, Naoko; Kunimi, Yuko; Uchida, Takahisa; Ikezawa, Zenro

    2011-06-01

    The pathogenesis of urticaria and angioedema induced by non-steroidal anti-inflammatory drugs (NSAIDs) is still obscure. We analyzed the clinical characteristics of patients with NSAIDs-induced urticaria and angioedema without asthma in Japan. We retrospectively collected the cases of NSAIDs-induced urticaria and angioedema from Japanese medical journals in 2000-2009. Seventy-six patients were analyzed. The male/female ratio was 1:2.5 and the mean age was 38.1 years. Urticaria was most frequent clinical manifestation in 3 groups; urticaria alone, urticaria and angioedema, and angioedema alone. Time interval from drug administration to onset was 5 minutes to 48 hours by aspirin at a dose of 25-1000 mg. Skin prick test was performed with aspirin in 33 patients, and the results were negative in all patients. Meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor, and celecoxib, a new selective COX-2 inhibitor, were administered safely in 4 of 6 patients and in 2 of 3 patients with NSAIDs-induced urticaria, respectively. These drugs were administered safely in all administered patients with NSAIDs-induced angioedema. Tiaramidehydrochroride (a basic COX-1 inhibitor) was safely used in 23 administered patients with NSAIDs-induced angioedema. Leukotriene receptor antagonists were effective in 2 of 5 patients administered, but aggravated symptoms in the others. Diversity of NSAIDs-induced urticaria and angioedema was shown in this study. Pathogenesis of NSAIDs-induced urticaria and angioedema without asthma seems to be different from that of NSAIDs-induced asthma.

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

    Science.gov (United States)

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

    2012-01-01

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

  14. Medicinal chemistry of antischistosomal drugs: Praziquantel and oxamniquine.

    Science.gov (United States)

    da Silva, Vinícius Barros Ribeiro; Campos, Bruna Rafaella Koresch Leiva; de Oliveira, Jamerson Ferreira; Decout, Jean-Luc; do Carmo Alves de Lima, Maria

    2017-07-01

    Neglected tropical diseases (NTDs) are a group of diseases that, besides prevailing in poverty conditions, contribute to the maintenance of social inequality, being a strong barrier to a country development. Schistosomiasis, a NTD, is a tropical and subtropical disease caused by the trematode Schistosoma mansoni (Africa, Middle East, Caribbean, Brazil, Venezuela, Suriname), japonicum (China, Indonesia, the Philippines), mekongi (several districts of Cambodia and the Lao People's Democratic Republic), intercalatum and guianensis (areas of tropical rainforests in Central Africa) and hematobium (Middle East Africa, Corsica, France) whose adult forms inhabit the mesenteric vessels of the host, while the intermediate forms are found in the aquatic gastropod snails of the genus Biomphalaria. Currently, praziquantel (PZQ) is the first line drug chosen for the treatment of schistosomiasis according to the World Health Organization (WHO) Model List of Essential Medicines, 2015. PZQ chemotherapy is considered to be the most important development for decades in the treatment of schistosomiasis. Beside the PZQ, oxamniquine (OXA) has been first described in 1969 and launched in Brazil by Pfizer under the name of Mansil® for oral administration. It has a lower cost when compared to PZQ, being active in the intestinal and hepatosplenic infections caused exclusively by S. mansoni, single species in Brazil. Both PZQ and OXA have limitations, as low efficacy in the treatment of acute schistosomiasis, low activity against S. mansoni in immature stages and resistance or tolerance, which is the reason why further research are still necessary for the development of a second generation of antischistosomal drugs. For the development of new PZQ analogs, three main strategies can be adopted: (a) synthesis and evaluation of PZQ analogues; (b) rational design of new pharmacophores; (c) discovery of new active compounds from screening programs on a large scale. Such (b) approach is difficult

  15. Medicinal chemistry in drug discovery in big pharma: past, present and future.

    Science.gov (United States)

    Campbell, Ian B; Macdonald, Simon J F; Procopiou, Panayiotis A

    2018-02-01

    The changes in synthetic and medicinal chemistry and related drug discovery science as practiced in big pharma over the past few decades are described. These have been predominantly driven by wider changes in society namely the computer, internet and globalisation. Thoughts about the future of medicinal chemistry are also discussed including sharing the risks and costs of drug discovery and the future of outsourcing. The continuing impact of access to substantial computing power and big data, the use of algorithms in data analysis and drug design are also presented. The next generation of medicinal chemists will communicate in ways that reflect social media and the results of constantly being connected to each other and data. Copyright © 2017. Published by Elsevier Ltd.

  16. A review of drug delivery systems based on nanotechnology and green chemistry: green nanomedicine

    Directory of Open Access Journals (Sweden)

    Jahangirian H

    2017-04-01

    Full Text Available Hossein Jahangirian,1 Ensieh Ghasemian Lemraski,2 Thomas J Webster,1 Roshanak Rafiee-Moghaddam,3 Yadollah Abdollahi4 1Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 2Department of Chemistry, Faculty of Science, Ilam University, Ilam, Iran; 3School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Selangor, 4Department of Electrical Engineering, Faculty of Engineering, University of Malaysia, Kuala Lumpur, Malaysia Abstract: This review discusses the impact of green and environmentally safe chemistry on the field of nanotechnology-driven drug delivery in a new field termed “green nanomedicine”. Studies have shown that among many examples of green nanotechnology-driven drug delivery systems, those receiving the greatest amount of attention include nanometal particles, polymers, and biological materials. Furthermore, green nanodrug delivery systems based on environmentally safe chemical reactions or using natural biomaterials (such as plant extracts and microorganisms are now producing innovative materials revolutionizing the field. In this review, the use of green chemistry design, synthesis, and application principles and eco-friendly synthesis techniques with low side effects are discussed. The review ends with a description of key future efforts that must ensue for this field to continue to grow. Keywords: green chemistry, cancer, drug delivery, nanoparticle

  17. Home Manufacture of Drugs: An Online Investigation and a Toxicological Reality Check of Online Discussions on Drug Chemistry.

    Science.gov (United States)

    Hearne, Evelyn; Alves, Emanuele Amorim; Van Hout, Marie Claire; Grund, Jean-Paul C

    2017-01-01

    Emerging trends in market dynamics and the use of new psychoactive substances are both a public health concern and a complex regulatory issue. One novel area of investigation is the availability of homemade opioids, amphetamines and dissociatives, and the potential fueling of interest in clandestine home manufacture of drugs via the Internet. We illustrate here how online communal folk pharmacology of homemade drugs on drug website forums may actually inform home manufacture practices or contribute to the reduction of harms associated with this practice. Discrepancies between online information around purification and making homemade drugs safer, and the synthesis of the same substances in a proper laboratory environment, exist. Moderation and shutdown of synthesis queries and discussions online are grounded in drug websites adhering to harm-reduction principles by facilitating discussions around purification of homemade drugs only. Drug discussion forums should consider reevaluating their policies on chemistry discussions in aiming to reach people who cannot or will not refrain from cooking their own drugs with credible information that may contribute to reductions in the harms associated with this practice.

  18. Chemistry

    International Nuclear Information System (INIS)

    Gomez G, H.

    1989-01-01

    A brief description about the development and activities executed in chemistry, in the Instituto de Asuntos Nucleares, during the last years is presented. The plans and feasibility of nuclear techniques in Colombia are also described

  19. The Analytical Chemistry of Drug Monitoring in Athletes

    Science.gov (United States)

    Bowers, Larry D.

    2009-07-01

    The detection and deterrence of the abuse of performance-enhancing drugs in sport are important to maintaining a level playing field among athletes and to decreasing the risk to athletes’ health. The World Anti-Doping Program consists of six documents, three of which play a role in analytical development: The World Anti-Doping Code, The List of Prohibited Substances and Methods, and The International Standard for Laboratories. Among the classes of prohibited substances, three have given rise to the most recent analytical developments in the field: anabolic agents; peptide and protein hormones; and methods to increase oxygen delivery to the tissues, including recombinant erythropoietin. Methods for anabolic agents, including designer steroids, have been enhanced through the use of liquid chromatography/tandem mass spectrometry and gas chromatography/combustion/isotope-ratio mass spectrometry. Protein and peptide identification and quantification have benefited from advances in liquid chromatography/tandem mass spectrometry. Incorporation of techniques such as flow cytometry and isoelectric focusing have supported the detection of blood doping.

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

    Science.gov (United States)

    Chang, Young Woon

    2016-06-25

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

  1. Effects on growth of human osteoblast-like cells of three nonsteroidal anti-inflammatory drugs: metamizole, dexketoprofen, and ketorolac.

    Science.gov (United States)

    De Luna-Bertos, Elvira; Ramos-Torrecillas, Javier; Manzano-Moreno, Francisco Javier; García-Martínez, Olga; Ruiz, Concepción

    2015-01-01

    Some nonsteroidal anti-inflammatory drugs (NSAIDs) have adverse effects on bone tissue. The objective of this study was to determine the effect of different doses of dexketoprofen, ketorolac, and metamizole on growth of the osteoblast MG63 cell line. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide spectrophotometry results showed that MG63 cell growth was significantly inhibited after 24 hr of culture with doses of 10, 20, 100, or 1,000 µM of each NSAID and with doses of 0.1, 1, or 5 µM of dexketoprofen and ketorolac but not metamizole. Cell-cycle studies revealed that dexketoprofen and ketorolac treatments significantly arrested the cell cycle in phase G0/G1, increasing the percentage of cells in this phase. Apoptosis/necrosis studies showed significant changes versus control cells, with an increased percentage of cells in apoptosis after treatment with 10, 100, or 1,000 µM of metamizole and after treatment with 1, 10, 100, or 1,000 µM of dexketoprofen or ketorolac. In conclusion, treatment of osteoblast-like cells with high doses of the NSAIDs tested increased not only the percentage of cells in apoptosis but also the percentage of necrotic cells. © The Author(s) 2014.

  2. Double-contrast barium enteroclysis as a patency tool for nonsteroidal anti-inflammatory drug-induced enteropathy.

    Science.gov (United States)

    Matsumoto, Takayuki; Esaki, Motohiro; Kurahara, Koichi; Hirai, Fumihito; Fuchigami, Tadahiko; Matsui, Toshiyuki; Iida, Mitsuo

    2011-11-01

    Evaluating small bowel patency is recommended for capsule endoscopy in patients suspected of nonsteroidal anti-inflammatory drug-induced (NSAID) enteropathy. The aim of this investigation was to examine whether radiography is a candidate of patency tool in NSAID enteropathy. We reviewed double-contrast barium enteroclysis in 21 patients with NSAID enteropathy diagnosed either by capsule endoscopy or balloon-assisted endoscopy. The endoscopic findings were classified into circular ulcers, linear ulcers and small mucosal defects. The radiographic signs of the corresponding endoscopic findings were retrieved and the depiction rate was calculated. Of the 21 patients, endoscopy detected circular ulcers, linear ulcers, and small ulcers in 12, 3 and 12 patients, respectively. Small bowel radiography depicted circular narrowing as pseudo-folds in 10 patients (83%) and linear ulcers as eccentric rigidity in 2 patients (67%). However, radiography was able to depict small mucosal defects in only 3 patients (17%). Two of 5 patients with pseudo-folds experienced retention of the capsule. "Pseudo-folds" is a sign corresponding to circular ulcer in NSAID enteropathy, which may be predictive of capsule retention.

  3. [Effect of nonsteroidal anti-inflammatory drugs and paracetamol on hemodynamic changes during postoperative analgesia in children].

    Science.gov (United States)

    Leont'ev, D V; Babaev, B D; Shishkov, M V; Ostreĭkov, I F

    2005-01-01

    The purpose of the present study was to comparatively assess the adequacy of postoperative analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol in children undergone "minor" surgical interventions. For postoperative analgesia in children, the authors used paracetamol in a single dose of 25-30 mg/kg, diclofenac in a dose of 1.5-2.0 mg/kg, which were rectally administered as suppositories, as well as diclofenac in the same dose as intramuscular injections (Group 1). A comparison was made with postoperative analgesia using analgin and promedole (Group 2 (control)). Group 1 comprised 63 patients and Group 2 included 26 patients with identical diseases (inguinal hernias, varicocele, phimosis). Functional parameters were recorded in patients in the lying position before, 30 min, 1, 2, and 3 hours after surgery. The efficiency of postoperative analgesia was evaluated, by using central hemodynamic parameters that many investigators consider to be one of the major criteria for the adequacy of anesthesia. Comparison of postoperative data has revealed a difference between the groups, which suggests that the use of NSAIDs and paracetamol for preventive and postoperative analgesia in children substantially improves the postoperative period and promotes a rapid rehabilitation in patients. Comparative analysis of the efficiency of postoperative analgesia of the above agents has indicated that diclofenac and paracetamol have a sufficient analgesic activity and at the same time do not show the adverse reactions unique to narcotic analgesics.

  4. The effect of non-steroidal anti-inflammatory drugs on severity of acute pancreatitis and pancreatic necrosis.

    Science.gov (United States)

    Baxter, K A; Pucher, P H; Berry, D P; Elberm, H; Abu-Hilal, M; Marangoni, G; Hamady, Zzr

    2018-03-01

    Introduction Acute pancreatitis (AP) is a common emergency presentation and can be disabling. There is significant morbidity and mortality associated with AP, and it places a considerable burden on the healthcare system. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to have a protective effect in some elective contexts. This retrospective study aimed to evaluate the effect of NSAIDs on the course of AP and the severity of the disease. Methods A retrospective analysis was carried out of 324 patients admitted as an emergency with a diagnosis of AP to two UK hospitals. Patients were divided into two groups: those already taking NSAIDs for other co-morbidities and those not taking NSAIDs. Variables compared included: admission to a high dependency or intensive care unit; pancreatic necrosis; pseudocyst development; need for surgery; serum inflammatory markers; modified early warning scores on days 1, 3 and 5; length of stay; and mortality. Results Patients not taking NSAIDs were more likely to have a C-reactive protein level of ≥150mg/l (p=0.007). Patients in the NSAID group experienced less pancreatic necrosis (p=0.019) and lower rates of pseudocyst formation (p=0.010). Other variables showed no difference between the two groups, specifically length of stay and mortality. Conclusions Routine NSAID use may exert a protective effect on the development of AP, its severity, and complications. Therapeutic use of NSAIDs in acute presentations with pancreatitis should be further evaluated.

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

    International Nuclear Information System (INIS)

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

    1991-01-01

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

  6. NON-STEROIDAL ANTI-INFLAMMATORY DRUGS'S ANTINOCICEPTION MEDIATED BY THE OPIOID MECHANISM IN THE NUCLEUS RAPHE MAGNUS.

    Science.gov (United States)

    Gorgiladze, T; Nozadze, I; Abzianidze, E; Tsagareli, M

    2017-04-01

    It has been established that the midbrain periaqueductal gray matter (PAG) and rostral ventro-medial medulla (RVM) are involved in the descending pain control system. The latter involves the midline nucleus raphe magnus (NRM) and adjacent reticular formation. These brain structures are is one of important parts of CNS circuit that controls nociceptive transmission at the level of spinal cord. Here we report that microinjection of commonly used non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac, ketorolac, metamizol, and xefocam into the NRM produces strong antinociception which is mediated by the opioid mechanism. The experiments were carried out on experimental and control (saline) white albino male rats. Animals were implanted with a guide cannula in the NRM and tested for antinociception following microinjection of NSAIDs into the NRM in the tail flick (TF) and hot plate (HP) tests. The analysis of variance (ANOVA) with post-hoc Tukey-Kramer multiple comparison tests were used for statistical evaluation. The obtained data show that microinjection of these NSAIDs into the NRM produced antinociception as revealed by a latency increase in the tail-flick (TF) and hot plate (HP) latencies compared to the saline control microinjected into the same nucleus. Furthermore, we definitely showed that pre-treatment with opioid antagonist naloxone in the NRM diminishes NSAID-induced antinociception expressing in significant decrease in TF and HP latencies (PNSAIDs are mediated via an endogenous opioid system possibly involving the descending pain modulatory circuit.

  7. Effect of N-Phenylanthranilic Acid Scaffold Nonsteroidal Anti-inflammatory Drugs on the Mitochondrial Permeability Transition.

    Science.gov (United States)

    Tatematsu, Yohei; Hayashi, Hiroki; Taguchi, Ryo; Fujita, Haruhi; Yamamoto, Atsushi; Ohkura, Kazuto

    2016-01-01

    Hepatotoxicity is a known side effect of nonsteroidal anti-inflammatory drugs (NSAIDs). In the present study, the effects of N-phenylanthranilic acid (NPA) scaffold NSAIDs on rat liver mitochondria were examined. Mefenamic acid (MEF, 200 µM) induced mitochondrial swelling, which was inorganic phosphate (Pi)-dependent and suppressed by cyclosporin A (CsA, 2.5 µM), similar to calcium-induced swelling. Mitochondrial swelling was also observed following the addition of 200 µM flufenamic acid (FLU), meclofenamic acid (MCL), and tolfenamic acid (TOL). Less swelling was observed with the addition of 200 µM diclofenac (DIC) or NPA. Diphenylamine (DPA)-induced swelling occurred in a Pi-independent manner and was not sensitive to CsA. The mechanism by which DPA interacted with the mitochondrial inner membrane differed from those of the other NPA scaffold NSAIDs. The addition of 50 µM MEF, MCL, TOL, and FLU had uncoupling effects in mitochondrial inner membrane. These NSAIDs dose-dependently obstructed electron transport in the respiratory chain. NSAIDs are known to have various dynamic structures, and the solvation free energies (dGWs: an index of stereo-hydrophobicity) of the conformers obtained were determined using a molecular orbital analysis. The relationship between the dynamic structures and swelling induced by NPA scaffold NSAIDs was also examined.

  8. [Clinical features and diagnosis of non-steroidal anti-inflammatory drugs induced ulcers of the stomach].

    Science.gov (United States)

    Watari, Jiro; Kim, Yongmin; Yokoyama, Satoko; Hori, Kazutoshi; Miwa, Hiroto

    2011-06-01

    Helicobacter pylori (H. pylori) infection and non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin induce serious gastrointestinal ulcer and bleeding. Also both H. pylori infection and NSAIDs or aspirin use independently and significantly increase the risk of peptic ulcer and its complications. Interestingly, it has been reported that no evidence exists that reducing the dose or using modified release formulations such as enteric-coated of aspirin would reduce the incidence of ulcer bleeding. Selective COX-2 inhibitors use shows a low relative risk of ulcer bleeding than NSAIDs. However, when combined with aspirin, the differences between selective COX-2 inhibitors and NSAIDs tend to disappear. NSAIDs/aspirin dominantly develops multiple ulcers from the angulus to the antrum regardless of H. pylori infection. In contrast, the irregular shape of ulcer is more frequently detected in patients taking NSAIDs in comparison with H. pylori-associated ulcer, but the association was not seen in cases taking aspirin. This result indicates that the mechanism of ulcer formation may be different between NSAIDs and aspirin.

  9. Effects of non-steroidal anti-inflammatory drugs on Abeta deposition in Abeta(1-42) transgenic C. elegans.

    Science.gov (United States)

    Morita, Masahiko; Osoda, Kazuhiko; Yamazaki, Mayako; Shirai, Fumiyuki; Matsuoka, Nobuya; Arakawa, Hiroyuki; Nishimura, Shintaro

    2009-10-27

    Although epidemiological studies have shown that long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer's disease (AD), the mechanism(s) by which NSAIDs reduce the risk of AD remain to be determined. As C. elegans possess neither inflammatory cells nor the arachidonate cascade, we could evaluate the effects of NSAIDs on amyloid beta (Abeta) deposition in the absence of immune cells using Abeta-transgenic C. elegans. For this purpose, we established a strain of Abeta-transgenic C. elegans in which thioflavin S-reactive deposits are reproducibly detectable by confocal microscopy. Among the NSAIDs examined, ibuprofen and naproxen reduced the number of thioflavin S-reactive deposits. Furthermore, ibuprofen and naproxen neither affect the thioflavin S binding to Abeta nor Abeta expression in transgenic C. elegans. These data suggest that ibuprofen and naproxen, the most frequently used NSAIDs for the treatment of AD, have an inhibitory effect on Abeta deposition that is independent of the arachidonate cascade and cellular immune systems.

  10. The nature of hydrogen-bonding interactions in nonsteroidal anti-inflammatory drugs revealed by polarized IR spectroscopy

    Science.gov (United States)

    Hachuła, Barbara

    2018-01-01

    The influence of hydrogen-bonding interactions in the solid phase on the IR spectroscopic pattern of the νOsbnd H band of nonsteroidal anti-inflammatory drugs (NSAIDs) was studied experimentally by IR spectroscopy with the use of polarized light at two temperatures (293 K and 77 K) and in isotopic dilution. The neat and deuterated crystals of (S)-naproxen ((S)-NPX), (R)-flurbiprofen ((R)-FBP), (RS)-flurbiprofen ((RS)-FBP) and (RS)-ketoprofen ((RS)-KTP) were obtained by melt crystallization between the two squeezed CaF2 plates. The vibrational spectra of selected α-aryl propionic acid derivatives (2APAs) reflected the characteristics of their hydrogen-bond networks, i.e., 2APAs were characterized by the chain ((S)-NPX, (R)-FBP) and by dimeric ((RS)-FBP, (RS)-KTP) arrangement of hydrogen bonds in the crystal lattice. Spectroscopic results showed that the interchain (through-space) exciton coupling, between two laterally-spaced hydrogen bonds, dominates in the crystals of four NSAIDs. The same exciton coupled hydrogen bonds were also responsible for the H/D isotopic recognition mechanism in the crystalline spectra of deuterated 2APAs. The presented spectral results may help to predict the hydrogen bond motifs in the crystalline NSAIDs, which structures are not yet known, based on their IR spectra of hydrogen bond in the crystals.

  11. Effect of temperature on volumetric and viscometric properties of some non-steroidal anti-inflammatory drugs in aprotic solvents

    Energy Technology Data Exchange (ETDEWEB)

    Iqbal, Muhammad Javed, E-mail: mjiqauchem@yahoo.co [Department of Chemistry, Quaid-i-Azam University, Islamabad 45320 (Pakistan); Chaudhry, Mansoora Ahmed [Department of Chemistry, Quaid-i-Azam University, Islamabad 45320 (Pakistan)

    2010-08-15

    Densities and viscosities of salicyl amide, salicylic acid, and acetyl salicylic acid (non-steroidal anti-inflammatory drugs) in two aprotic solvents namely, dimethyl sulfoxide and acetonitrile at T = (293.15, 298.15, 303.15, 308.15, 310.15, and 313.15) K have been determined in a molality range of (9.7 . 10{sup -3} to 33.3 . 10{sup -3}) mol . kg{sup -1}. The data have been used to calculate apparent molar volumes (V{sub {phi}}), and viscosity B-coefficients. The partial molar volumes and hydration numbers have been determined at different temperatures. The effect of temperature on the thermodynamic properties has been studied by determining partial molar expansibilities ({partial_derivative}V{sub m}{sup 0}/{partial_derivative}T) and Hepler's constant ({partial_derivative}{sup 2}V{sub m}{sup 0}/{partial_derivative}T{sup 2}). Free energies of activation for viscous flow of the solution were obtained by application of the transition state theory of solutions to the B-coefficient data and the corresponding activation enthalpies are reported.

  12. Piroxicam, a traditional non-steroidal anti-inflammatory drug (NSAID) causes apoptosis by ROS mediated Akt activation.

    Science.gov (United States)

    Rai, Neha; Sarkar, Munna; Raha, Sanghamitra

    2015-12-01

    Piroxicam (Px) belongs to the oxicam group of the non-steroidal anti-inflammatory drugs (NSAIDs) and have been shown to exert chemopreventive and chemotherapeutic effects in animal models and cultured animal cells. However, little is known about the mode of action of Px and its cellular targets. We explored the role of Px, in triggering apoptosis and examined the involvement of upstream cellular mechanisms in apoptosis induction by Px. Our studies with human breast cancer cells MCF-7 show that Px induces reactive oxygen species (ROS) generation along with apoptotic cell death. ROS release lead to Akt activation. On evaluation it became evident that ROS mediated apoptosis induction was due to Akt activation (hyper phosphorylation). Silencing the expression of Akt using siRNA and a specific Akt inhibitor, triciribine further confirmed the findings. However Px failed to cause ROS generation, cell death or Akt phosphorylation in another human breast cancer cells MDA-MB-231 which is estrogen receptor negative and more aggressive compared to MCF-7 cells. This suggests that Px has cell type specific effects. Thus we revealed for the first time that Px can induce apoptosis by ROS mediated Akt hyperphosphorylation/activation. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  13. Evaluation of various ways to deliver information concerning non-steroidal anti-inflammatory drugs to osteoarthritis patients.

    Science.gov (United States)

    Gremeaux, V; Durand, S; Benaïm, C; Hérisson, C; Monleaud, J; Hansel, S; Coudeyre, E

    2013-02-01

    It is essential to provide complete information to patients using non-steroidal anti-inflammatory drugs (NSAIDs) because of the risk of side effects. Today, most healthcare professionals recommend and privilege oral information regarding NSAIDs. Evaluate the impact of three standardized NSAIDs information-delivery modalities on knowledge, anxiety and satisfaction of patients hospitalized in a Physical Medicine and Rehabilitation unit for debilitating and degenerative locomotor diseases. Randomized prospective study with an alternate month design. Two control groups were provided with only one type of information modality: written (information sheet) or oral (presentation). The intervention group received both modalities of information. The information included: the definition of NSAIDs, advantages and side effects, and practical advice regarding proper use. The main evaluation criterion was knowledge progression assessed by a specific questionnaire. Secondary criteria were anxiety evolution (STAI-Y questionnaire) and satisfaction related to the information delivered. One hundred and forty patients were included. Knowledge was improved in the three groups, with a greater score improvement in the group that received both modalities (P=0.05). No intergroup difference was noted on anxiety or satisfaction. Associating both information-delivery modalities (written+oral) contributes to improving knowledge but does not seem to have an impact on the anxiety of patients treated with NSAIDs for their degenerative locomotor disease. Using standardized information sheets with a validated content could help pharmacists in their role as healthcare education provider and effectively complement the information delivered orally. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2002-01-01

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

  16. Non steroidal anti-inflammatory drugs for preventing cystoid macular edema after cataract surgeries:a Meta-analysis

    Directory of Open Access Journals (Sweden)

    Xue-Jiao Xu

    2015-12-01

    Full Text Available AIM:To systematic evaluate the preventive effect of non-steroidal anti-inflammatory drugs(NSAIDson the cystoid macular edema(CMEafter the cataract surgery. METHODS:Searching literature which were published by March 2015 and which were the random control test(RCTon the preventive effect of NSAIDs on CME after the cataract surgery in PubMed, EMbase, Cochrane Library, MEDLINE, CNKI, Wanfang Data, Chongqing Weipu and Chinese biomedical literature database and through Internet with computer. Meanwhile, relevant articles, journals, conference papers and their reference were manually retrieved. According to inclusion and exclusion criteria,the study objects were limited.Revman5.0 software provided by the Cochrane Collaboration was used to analysis the incidence of CME after cataract surgeries.RESULTS:A total of 7 RCT were included in the study(1422 cases, 712 cases in the trial group, 710 cases in the control group. Using NSAIDs before and after cataract surgeries could significantly reduce the post-operative incidence of CME(OR=0.31, 95%CI:0.18~0.52, PCONCLUSION:Using NSAIDs before and after cataract surgeries can significantly reduce the incidence of postoperative CME. Due to the small sample size and the medium methodological quality, the conclusion is not powerful enough. More high-quality RCTs with larger sample size are needed to make the evaluation more objective, accurate and comprehensive.

  17. Role of dietary fiber in formation and prevention of small intestinal ulcers induced by nonsteroidal anti-inflammatory drug.

    Science.gov (United States)

    Satoh, Hiroshi

    2010-01-01

    Recent advances in endoscopic techniques such as capsule endoscopy have revealed that nonsteroidal anti-inflammatory drugs (NSAIDs) often cause ulcers in the small intestine in humans, but there are few effective agents for treatment of small intestinal ulcers. Although the pathogenesis of NSAID-induced intestinal ulcer has been widely studied, dietary factors have seldom been considered. In the present review, the role of dietary fiber (DF) in the formation of NSAID-induced intestinal ulcers is discussed. In previous studies, small intestinal lesions were not observed when NSAIDs were administered to fasted rats, dogs, and cats, but were observed in conventionally-fed animals, suggesting the importance of feeding in the formation of intestinal lesions induced by NSAIDs. However, in animals fed diets containing low or no DF, indomethacin (IND) did not produce lesions in the small intestine, but did produce lesions in animals fed diets supplemented with insoluble dietary fiber (IDF, cellulose). The results suggest that IDF in the diet plays an important role in the formation of NSAID-induced intestinal lesions. On the other hand, addition of soluble dietary fibers (SDFs) such as pectin or mucin to regular diet markedly decreased NSAID-induced intestinal lesions. Thus, IDF and SDF have opposing effects on IND-induced intestinal lesions, i.e., IDF is harmful while SDF is protective. SDFs potentially represent a novel and safe means for protecting the small intestine against NSAID-induced intestinal lesions.

  18. Life cycle assessment and costing of urine source separation: Focus on nonsteroidal anti-inflammatory drug removal.

    Science.gov (United States)

    Landry, Kelly A; Boyer, Treavor H

    2016-11-15

    Urine source separation has the potential to reduce pharmaceutical loading to the environment, while enhancing nutrient recovery. The focus of this life cycle assessment (LCA) was to evaluate the environmental impacts and economic costs to manage nonsteroidal anti-inflammatory drugs (NSAIDs) (i.e., diclofenac, ibuprofen, ketoprofen and naproxen) and nutrients in human urine. Urine source separation was compared with centralized wastewater treatment (WWT) (biological or upgraded with ozonation). The current treatment method (i.e., centralized biological WWT) was compared with hypothetical treatment scenarios (i.e., centralized biological WWT upgraded with ozonation, and urine source separation). Alternative urine source separation scenarios included varying collection and handling methods (i.e., collection by vacuum truck, vacuum sewer, or decentralized treatment), pharmaceuticals removal by ion-exchange, and struvite precipitation. Urine source separation scenarios had 90% lower environmental impact (based on the TRACI impact assessment method) compared with the centralized wastewater scenarios due to reduced potable water production for flush water, reduced electricity use at the wastewater treatment plant, and nutrient offsets from struvite precipitation. Despite the greatest reduction of pharmaceutical toxicity, centralized treatment upgraded with ozone had the greatest ecotoxicity impacts due to ozonation operation and infrastructure. Among urine source separation scenarios, decentralized treatment of urine and centralized treatment of urine collected by vacuum truck had negligible cost differences compared with centralized wastewater treatment. Centralized treatment of urine collected by vacuum sewer and centralized treatment with ozone cost 30% more compared with conventional wastewater treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Influence of non-steroidal anti-inflammatory drugs (NSAIDs) on osseointegration of dental implants in rabbit calvaria.

    Science.gov (United States)

    Cai, Wei Xin; Ma, Li; Zheng, Li Wu; Kruse-Gujer, Astrid; Stübinger, Stefan; Lang, Niklaus P; Zwahlen, Roger A

    2015-04-01

    Until recently, adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) on osseointegration of dental implants were unknown. Hence, this study investigated the short- and long-term effects of a 7-day regimen of parecoxib and diclofenac sodium on osseointegration of dental implants in calvarial bone. Eighteen New Zealand White rabbits were randomly allocated into three groups (each n = 6): Control group with no postoperative pain killers (Group A), diclofenac group (Group B) and parecoxib group (Group C). In each animal, one dental implant was placed into the calvarial bone (total n = 18). Three rabbits from each group were sacrificed in Week 4. The other three rabbits from each group were sacrificed in Week 12 postoperatively. The implant together with the calvarial bone and dura mater was harvested and subjected to micro-computed tomography (micro-CT) and histomorphometric analysis. Quantitative analysis of micro-CT data and histomorphometric data neither revealed any statistically significant (P ≤ 0.05) differences between the three different groups related to osseointegration nor between different time points of observation. In rabbits, a 7-day regimen of appropriate doses of diclofenac sodium and parecoxib did not adversely affect osseointegration of dental implants and bone healing in calvaria, neither short nor long term (12 weeks). © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Xiao-Xing Li

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

  2. Persistent nonmalignant pain management using nonsteroidal anti-inflammatory drugs in older patients and use of inappropriate adjuvant medications

    Directory of Open Access Journals (Sweden)

    Rianon N

    2015-01-01

    Full Text Available Nahid Rianon,1 Maureen E Knell,2 Walter Agbor-Bawa,3 Joan Thelen,4 Crystal Burkhardt,3 Rafia S Rasu3 1Division of Geriatric and Palliative Medicine, Department of Internal Medicine, University of Texas Medical School at Houston, Houston, TX, USA; 2Department of Pharmacy Practice and Administration, University of Missouri-Kansas City School of Pharmacy, Kansas City, MO, USA; 3Department of Pharmacy Practice, University of Kansas School of Pharmacy, Lawrence, KS, USA; 4Department of Psychology, University of Missouri-Kansas City, Kansas City, MO, USA Objective: Due to the high risk of life-threatening side effects, nonsteroidal anti-inflammatory drugs (NSAIDs are not favored for treating persistent nonmalignant pain in the elderly. We report national prescription trends with determinants of NSAIDs prescription for persistent nonmalignant pain among older patients (age 65 and over in the US outpatient setting. Methods: A cross-sectional analysis was performed using National Ambulatory Medical Care Survey data. Prescriptions for NSAIDs, opioids, and adjuvant agents were identified using five-digit National Ambulatory Medical Care Survey drug codes. Results: About 89% of the 206,879,848 weighted visits in the US from 2000 to 2007 recorded NSAIDs prescriptions in patients (mean age =75.4 years. Most NSAIDs users had Medicare (75%, and about 25% were prescribed with adjuvant medications considered inappropriate for their age. Compared to men, women were 1.79 times more likely to be prescribed NSAIDs. Conclusion: The high percentage of NSAIDs prescription in older patients is alarming. We recommend investigating the appropriateness of the high prevalence of NSAIDs use among older patients reported in our study. Keywords: pain management, NSAIDs, inappropriate adjuvant, AGS guideline, NAMCS

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

    Science.gov (United States)

    Lionberger, David R; Brennan, Michael J

    2010-11-10

    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.

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

    Directory of Open Access Journals (Sweden)

    David R Lionberger

    2010-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Anne-Marie Schjerning Olsen

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

  6. Comparative effects of non-steroidal anti-inflammatory drugs (NSAIDs) on blood pressure in patients with hypertension.

    Science.gov (United States)

    Aljadhey, Hisham; Tu, Wanzhu; Hansen, Richard A; Blalock, Susan J; Brater, D Craig; Murray, Michael D

    2012-10-24

    Nonsteroidal anti-inflammatory drugs (NSAIDs) may disrupt control of blood pressure in hypertensive patients and increase their risk of morbidity, mortality, and the costs of care. The objective of this study was to examine the association between incident use of NSAIDs and blood pressure in patients with hypertension. We conducted a retrospective cohort study of adult hypertensive patients to determine the effects of their first prescription for NSAID on systolic blood pressure and antihypertensive drug intensification. Data were collected from an electronic medical record serving an academic general medicine practice in Indianapolis, Indiana, USA. Using propensity scores to minimize bias, we matched a cohort of 1,340 users of NSAIDs with 1,340 users of acetaminophen. Propensity score models included covariates likely to affect blood pressure or the use of NSAIDs. The study outcomes were the mean systolic blood pressure measurement after starting NSAIDs and changes in antihypertensive therapy. Compared to patients using acetaminophen, NSAID users had a 2 mmHg increase in systolic blood pressure (95% CI, 0.7 to 3.3). Ibuprofen was associated with a 3 mmHg increase in systolic blood pressure compared to naproxen (95% CI, 0.5 to 4.6), and a 5 mmHg increase compared to celecoxib (95% CI, 0.4 to 10). The systolic blood pressure increase was 3 mmHg in a subgroup of patients concomitantly prescribed angiotensin converting enzyme inhibitors or calcium channel blockers and 6 mmHg among those prescribed a beta-adrenergic blocker. Blood pressure changes in patients prescribed diuretics or multiple antihypertensives were not statistically significant. Compared to acetaminophen, incident use of NSAIDs, particularly ibuprofen, is associated with a small increase in systolic blood pressure in hypertensive patients. Effects in patients prescribed diuretics or multiple antihypertensives are negligible.

  7. Non-Steroidal Anti-Inflammatory Drugs and Aspirin Therapy for the Treatment of Acute and Recurrent Idiopathic Pericarditis

    Directory of Open Access Journals (Sweden)

    Nicholas Schwier

    2016-03-01

    Full Text Available Aspirin (ASA and non-steroidal anti-inflammatory drugs (NSAIDs are a mainstay of therapy for the treatment of idiopathic pericarditis (IP. A comprehensive review consisting of pertinent clinical literature, pharmacokinetic, and pharmacodynamic considerations, has not been released in recent years. This review will facilitate the clinician’s understanding of pharmacotherapeutic considerations for using ASA/NSAIDs to treat IP. Data were compiled using clinical literature consisting of case reports, cohort data, retrospective and prospective studies, and manufacturer package inserts. ASA, ibuprofen, indometacin, and ketorolac relatively have the most evidence in the treatment of IP, provide symptomatic relief of IP, and should be tapered accordingly. ASA is the drug of choice in patients with coronary artery disease (CAD, heart failure (HF, or renal disease, but should be avoided in patients with asthma and nasal polyps, who are naïve to ASA therapy. Ibuprofen is an inexpensive and relatively accessible option in patients who do not have concomitant CAD, HF, or renal disease. Indometacin is not available over-the-counter in the USA, and has a relatively higher incidence of central nervous system (CNS adverse effects. Ketorolac is an intravenous option; however, clinicians must be mindful of the maximum dose that can be administered. While ASA/NSAIDs do not ameliorate the disease process of IP, they are part of first-line therapy (along with colchicine, for preventing recurrence of IP. ASA/NSAID choice should be dictated by comorbid conditions, tolerability, and adverse effects. Additionally, the clinician should be mindful of considerations such as tapering, high-sensitivity CRP monitoring, bleeding risk, and contraindications to ASA/NSAID therapy.

  8. Carboxylesterases 1 and 2 Hydrolyze Phospho-Nonsteroidal Anti-Inflammatory Drugs: Relevance to Their Pharmacological Activity

    Science.gov (United States)

    Wong, Chi C.; Cheng, Ka-Wing; Xie, Gang; Zhou, Dingying; Zhu, Cai-Hua; Constantinides, Panayiotis P.

    2012-01-01

    Phospho-nonsteroidal anti-inflammatory drugs (phospho-NSAIDs) are novel NSAID derivatives with improved anticancer activity and reduced side effects in preclinical models. Here, we studied the metabolism of phospho-NSAIDs by carboxylesterases and assessed the impact of carboxylesterases on the anticancer activity of phospho-NSAIDs in vitro and in vivo. The expression of human liver carboxylesterase (CES1) and intestinal carboxylesterase (CES2) in human embryonic kidney 293 cells resulted in the rapid intracellular hydrolysis of phospho-NSAIDs. Kinetic analysis revealed that CES1 is more active in the hydrolysis of phospho-sulindac, phospho-ibuprofen, phospho-naproxen, phospho-indomethacin, and phospho-tyrosol-indomethacin that possessed a bulky acyl moiety, whereas the phospho-aspirins are preferentially hydrolyzed by CES2. Carboxylesterase expression leads to a significant attenuation of the in vitro cytotoxicity of phospho-NSAIDs, suggesting that the integrity of the drug is critical for anticancer activity. Benzil and bis-p-nitrophenyl phosphate (BNPP), two carboxylesterase inhibitors, abrogated the effect of carboxylesterases and resensitized carboxylesterase-expressing cells to the potent cytotoxic effects of phospho-NSAIDs. In mice, coadministration of phospho-sulindac and BNPP partially protected the former from esterase-mediated hydrolysis, and this combination more effectively inhibited the growth of AGS human gastric xenografts in nude mice (57%) compared with phospho-sulindac alone (28%) (p = 0.037). Our results show that carboxylesterase mediates that metabolic inactivation of phospho-NSAIDs, and the inhibition of carboxylesterases improves the efficacy of phospho-NSAIDs in vitro and in vivo. PMID:22085648

  9. Patterns of use and public perception of over-the-counter pain relievers: focus on nonsteroidal antiinflammatory drugs.

    Science.gov (United States)

    Wilcox, C Mel; Cryer, Byron; Triadafilopoulos, George

    2005-11-01

    To assess the frequency and indications for over-the-counter (OTC) nonsteroidal antiinflammatory drug (NSAID) use and to what degree the public is aware of their side effects. Two surveys totaling 9062 respondents were performed of the American public. The Roper survey, conducted in 1997, and the National Consumers League (NCL) survey, conducted in December 2002, were intended primarily to assess the public's use of and attitudes toward NSAID and OTC analgesics. Ibuprofen based drugs were the most frequently used OTC in both surveys (57% Roper, 33% NCL). In the Roper survey, 17% of respondents used NSAID, with 38% using both prescription and OTC. Forty-six percent of exclusive OTC users believed OTC were safer, while 56% of exclusive users of prescription NSAID believed they were safer. Sixty percent and 29% of exclusive OTC users were neither aware of nor believed they were at risk for side effects from NSAID, respectively. Twenty-six percent of respondents used more than the recommended dose on the label, while 22% believed warning symptoms would always precede any NSAID induced complications. In the NCL survey, 83% had used an OTC agent in the last year, with 15% reporting daily use, and 49% were not concerned about potential side effects. In this survey, 30% believed there was less risk with OTC analgesics, and 44% consumed more than the recommended dosage on the label. OTC analgesics including NSAID are widely used, are frequently taken inappropriately and potentially dangerously, and users are generally unaware of the potential for adverse side effects. Educational intervention directed toward both patients and physicians appears warranted.

  10. Non-Steroidal Anti-Inflammatory Drugs and Aspirin Therapy for the Treatment of Acute and Recurrent Idiopathic Pericarditis

    Science.gov (United States)

    Schwier, Nicholas; Tran, Nicole

    2016-01-01

    Aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) are a mainstay of therapy for the treatment of idiopathic pericarditis (IP). A comprehensive review consisting of pertinent clinical literature, pharmacokinetic, and pharmacodynamic considerations, has not been released in recent years. This review will facilitate the clinician’s understanding of pharmacotherapeutic considerations for using ASA/NSAIDs to treat IP. Data were compiled using clinical literature consisting of case reports, cohort data, retrospective and prospective studies, and manufacturer package inserts. ASA, ibuprofen, indometacin, and ketorolac relatively have the most evidence in the treatment of IP, provide symptomatic relief of IP, and should be tapered accordingly. ASA is the drug of choice in patients with coronary artery disease (CAD), heart failure (HF), or renal disease, but should be avoided in patients with asthma and nasal polyps, who are naïve to ASA therapy. Ibuprofen is an inexpensive and relatively accessible option in patients who do not have concomitant CAD, HF, or renal disease. Indometacin is not available over-the-counter in the USA, and has a relatively higher incidence of central nervous system (CNS) adverse effects. Ketorolac is an intravenous option; however, clinicians must be mindful of the maximum dose that can be administered. While ASA/NSAIDs do not ameliorate the disease process of IP, they are part of first-line therapy (along with colchicine), for preventing recurrence of IP. ASA/NSAID choice should be dictated by comorbid conditions, tolerability, and adverse effects. Additionally, the clinician should be mindful of considerations such as tapering, high-sensitivity CRP monitoring, bleeding risk, and contraindications to ASA/NSAID therapy. PMID:27023565

  11. Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) and cardiovascular risk.

    Science.gov (United States)

    Fanelli, Andrea; Romualdi, Patrizia; Vigano', Roberto; Lora Aprile, Pierangelo; Gensini, Gianfranco; Fanelli, Guido

    2013-06-01

    NSAIDs are largely used for the treatment of a huge variety of clinical conditions in order to relieve symptoms related to inflammation.The use of NSAIDs is associated with a potential increased risk of gastrointestinal and cardiovascular complications.The cardiovascular risk related to NSAIDs administration is often underestimated and it is frequently believed to be less important than the gastrointestinal risk. Adverse effects of NSAIDs are specifically related to their underlying mechanisms of action.The most plausible mechanism underlying the cardiovascular risk of NSAIDs has been identified in the profound inhibition of COX-2-dependent PGI2 in the presence of incomplete and intermittent inhibition of platelet COX-1. Nevertheless, the cardiovascular risk related to the use of NSAIDs is not only due to the COX-2 selectivity. An important determinant of the clinical effects of NSAIDs depends on the pharmacokinetic features of the different drugs such as half-life, and type of formulations, which can influence the extent and duration of patient exposure to COXisozyme inhibition. The aim of this review is to analyse the mechanisms behind the cardiovascular risk of different NSAIDs.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  14. Safety of 5-Aminosalicylic Acid Derivatives in Patients with Sensitivity to Acetylsalicylic Acid and Nonsteroidal Anti-inflammatory Drugs.

    Science.gov (United States)

    Poh, Jennifer; Knowles, Sandra

    2014-01-01

    One of the cornerstones of the management of inflammatory bowel disease is the use of 5-aminosalicylic acid (5-ASA) compounds for treatment of flares and as maintenance therapy during remission. There are concerns about using 5-ASA in patients with a history of hypersensitivity to acetylsalicylic acid (ASA). To assess the literature with respect to the safety of 5-ASA compounds in patients with documented sensitivity to ASA or nonsteroidal anti-inflammatory drugs (NSAIDs). A literature search was conducted in the MEDLINE and Embase databases, using various search terms, including "aminosalicylic acids", "non-steroidal anti-inflammatory agents," "hypersensitivity", and "allergy". The search was limited to articles (of any study design) published in English. Abstracts, full articles, and reference lists from retrieved articles were assessed to identify further relevant literature. Of 485 citations identified in the initial search, 4 case reports were relevant to the study objective and were analyzed in detail. Three of the case reports described the successful use of 5-ASA compounds in patients with prior sensitivity to ASA or an NSAID. The fourth report described a reaction to 5-ASA in a patient who had previously tolerated ASA. All of the reports were limited by lack of investigation into the validity of the reported sensitivity to ASA or 5-ASA. There is a dearth of evidence demonstrating cross-reactivity between ASA or NSAID and 5-ASA. This lack of information may relate to the mechanism of action of 5-ASA. This agent controls inflammation by inhibiting prostaglandin E2 and leukotrienes. In contrast, ASA-induced or NSAID-induced reactions are due to inhibition of the cycloxygenase-1 enzyme and subsequent release of histamine and synthesis of leukotrienes. Further reports describing the safety of 5-ASA use in patients with sensitivity to ASA or NSAIDs are needed before safety in this situation can be definitively determined. In patients with sensitivity to ASA or

  15. Full factorial design optimization of anti-inflammatory drug release by PCL–PEG–PCL microspheres

    Energy Technology Data Exchange (ETDEWEB)

    Azouz, L' Hachemi, E-mail: azouz.chimie@gmail.com [Laboratoire des Matériaux Organiques (LMO), Faculté des Sciences Exactes, Département de Chimie, Université de Bejaia, 06000 Bejaia Algérie (Algeria); Dahmoune, Farid, E-mail: farid.dahmoune@yahoo.fr [Laboratoire de Biomathématiques, Biophysique, Biochimie et Scientométrie (L3BS-Bejaia), Faculté des Sciences de la Nature et de la Vie et des Sciences de la Terre, Université de Bouira 10000 Bouira (Algeria); Rezgui, Farouk, E-mail: rezgui-farouk@netcourrier.com [Laboratoire des Matériaux Organiques (LMO), Faculté de Technologie, Département de Génie des Procédés, Université de Bejaia, 06000 Bejaia (Algeria); G' Sell, Christian, E-mail: gsell.christian@univ-lorraine.fr [Université de Lorraine, Pôle scientifique M4, Institut Jean Lamour - UMR CNRS-UL 7198, Département SI2M, 54000 Nancy (France)

    2016-01-01

    A biodegradable triblock poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) copolymer was successfully synthesized by ring-opening polymerization of ε-caprolactone, and was characterized by intrinsic viscosimetry, {sup 1}H nuclear magnetic resonance, infrared spectroscopy and X-ray diffraction. Copolymer microparticles loaded with ibuprofen were prepared by an oil-in-water (o/w) emulsion solvent evaporation process. They were carefully weighted and characterized through their zeta potential. In this work, 4 selected process parameters (shaking speed X{sub 1}, time of contact X{sub 2}, poly(vinyl alcohol) concentration X{sub 3}, and ibuprofen concentration X{sub 4}) were adjusted at 2 different values. For each of the 16 experimental conditions, repeated twice, the drug encapsulation efficiency of the microspheres was determined, according to the following definition: EE (X{sub 1}, X{sub 2}, X{sub 3}, X{sub 4}) = mass of encapsulated ibuprofen / total weight of ibuprofen. A “full factorial design method” was applied to analyze the results statistically according to a polynomial fit and to determine the optimal conditions for the microencapsulation of the ibuprofen through an accurate statistical protocol. The microparticles obtained exhibit a spherical shape as shown by electron microscopy. - Highlights: • PCEC copolymer was synthesized by ring-opening polymerization of ε-caprolactone. • 2{sup 4} experimental design was used to optimize the IBF encapsulation efficiency (EE). • 88.86% of ibuprofen (IBF) was encapsulated in PCEC microspheres. • EE significantly decreases with increasing shaking speed (antagonist effect). • EE significantly increases with increasing IBF concentration (synergetic effect).

  16. Full factorial design optimization of anti-inflammatory drug release by PCL–PEG–PCL microspheres

    International Nuclear Information System (INIS)

    Azouz, L'Hachemi; Dahmoune, Farid; Rezgui, Farouk; G'Sell, Christian

    2016-01-01

    A biodegradable triblock poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) copolymer was successfully synthesized by ring-opening polymerization of ε-caprolactone, and was characterized by intrinsic viscosimetry, 1 H nuclear magnetic resonance, infrared spectroscopy and X-ray diffraction. Copolymer microparticles loaded with ibuprofen were prepared by an oil-in-water (o/w) emulsion solvent evaporation process. They were carefully weighted and characterized through their zeta potential. In this work, 4 selected process parameters (shaking speed X 1 , time of contact X 2 , poly(vinyl alcohol) concentration X 3 , and ibuprofen concentration X 4 ) were adjusted at 2 different values. For each of the 16 experimental conditions, repeated twice, the drug encapsulation efficiency of the microspheres was determined, according to the following definition: EE (X 1 , X 2 , X 3 , X 4 ) = mass of encapsulated ibuprofen / total weight of ibuprofen. A “full factorial design method” was applied to analyze the results statistically according to a polynomial fit and to determine the optimal conditions for the microencapsulation of the ibuprofen through an accurate statistical protocol. The microparticles obtained exhibit a spherical shape as shown by electron microscopy. - Highlights: • PCEC copolymer was synthesized by ring-opening polymerization of ε-caprolactone. • 2 4 experimental design was used to optimize the IBF encapsulation efficiency (EE). • 88.86% of ibuprofen (IBF) was encapsulated in PCEC microspheres. • EE significantly decreases with increasing shaking speed (antagonist effect). • EE significantly increases with increasing IBF concentration (synergetic effect).

  17. Recent advances in the chemistry and biology of anti-inflammatory and specialized pro-resolving mediators biosynthesized from n-3 docosapentaenoic acid.

    Science.gov (United States)

    Vik, Anders; Dalli, Jesmond; Hansen, Trond Vidar

    2017-06-01

    Several novel oxygenated polyunsaturated lipid mediators biosynthesized from n-3 docosapentaenoic acid were recently isolated from murine inflammatory exudates and human primary cells. These compounds belong to a distinct family of specialized pro-resolving mediators, and display potent in vivo anti-inflammatory and pro-resolution effects. The endogenously formed specialized pro-resolving mediators have attracted a great interest as lead compounds in drug discovery programs towards the development of new classes of drugs that dampen inflammation without interfering with the immune response. Detailed information on the chemical structures, cellular functions and distinct biosynthetic pathways of specialized pro-resolving lipid mediators is a central aspect of these biological actions. Herein, the isolation, structural elucidation, biosynthetic pathways, total synthesis and bioactions of the n-3 docosapentaenoic acid derived mediators PD1 n-3 DPA and MaR1 n-3 DPA are discussed. In addition, a brief discussion of a novel family of mediators derived from n-3 docosapentaenoic acid, termed 13-series resolvins is included. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Nonsteroidal anti-inflammatory drug choice and adverse outcomes in clopidogrel users: A retrospective cohort study.

    Science.gov (United States)

    Nam, Young Hee; Brensinger, Colleen M; Bilker, Warren B; Leonard, Charles E; Kasner, Scott E; Grosser, Tilo; Li, Xuanwen; Hennessy, Sean

    2018-01-01

    To examine the comparative safety of individual NSAIDs when given concomitantly with clopidogrel. We conducted a retrospective cohort study using Medicaid claims from five US states during 1999-2010, supplemented with Medicare claims for dual-enrollees. The exposure of interest was the first concomitant use of clopidogrel and one of the 10 selected NSAIDs after a 1-year baseline period. The outcomes were: all-cause mortality; acute myocardial infarction (AMI)/ischemic stroke; and gastrointestinal bleeding (GIB)/intracranial hemorrhage (ICH). We calculated the hazard ratio of each NSAID for each outcome, with ibuprofen as the reference drug, using high-dimensional propensity score-adjusted proportional-hazards regression models. Of 1,060,412 clopidogrel users, 268,114 concomitant NSAID users met inclusion/exclusion criteria, contributing 48,483 person-years. We observed 2,463 deaths, 2,822 AMI/ischemic stroke outcomes, and 2,620 GIB/ICH outcomes, for unadjusted incidence rates of 50.8, 58.6, and 54.3 per 1,000 person-years, respectively. Compared with ibuprofen and controlling for potential confounders, rofecoxib (hazard ratio [HR] = 1.22; 95% confidence interval [CI]: 1.04, 1.43) and valdecoxib (HR = 0.66; 95% CI: 0.48, 0.92) showed higher and lower hazards of mortality, respectively. Indomethacin showed an increased AMI/ischemic stroke hazard (HR = 1.38; 95% CI: 1.09, 1.74). For GIB/ICH, indomethacin (HR = 2.18; 95% CI: 1.74, 2.73), diclofenac (HR = 1.65; 95% CI: 1.39, 1.97), naproxen (HR = 1.47; 95% CI: 1.28, 1.70), and rofecoxib (HR = 1.26; 95% CI: 1.08, 1.48) showed higher hazards, and valdecoxib (HR = 0.73; 95% CI: 0.55, 0.98) showed a lower hazard. The bleeding risks of individual NSAIDs varied more markedly than thrombotic risks when used concomitantly with clopidogrel. Moreover, bleeding risk and thrombotic risk among individual NSAIDs did not appear to be inversely related to each other in the presence of clopidogrel. Further studies are needed to

  19. A review of drug delivery systems based on nanotechnology and green chemistry: green nanomedicine.

    Science.gov (United States)

    Jahangirian, Hossein; Lemraski, Ensieh Ghasemian; Webster, Thomas J; Rafiee-Moghaddam, Roshanak; Abdollahi, Yadollah

    2017-01-01

    This review discusses the impact of green and environmentally safe chemistry on the field of nanotechnology-driven drug delivery in a new field termed "green nanomedicine". Studies have shown that among many examples of green nanotechnology-driven drug delivery systems, those receiving the greatest amount of attention include nanometal particles, polymers, and biological materials. Furthermore, green nanodrug delivery systems based on environmentally safe chemical reactions or using natural biomaterials (such as plant extracts and microorganisms) are now producing innovative materials revolutionizing the field. In this review, the use of green chemistry design, synthesis, and application principles and eco-friendly synthesis techniques with low side effects are discussed. The review ends with a description of key future efforts that must ensue for this field to continue to grow.

  20. Risk of intracranial haemorrhage in antidepressant users with concurrent use of non-steroidal anti-inflammatory drugs: nationwide propensity score matched study

    OpenAIRE

    Shin, Ju-Young; Park, Mi-Ju; Lee, Shin Haeng; Choi, So-Hyun; Kim, Mi-Hee; Choi, Nam-Kyong; Lee, Joongyub; Park, Byung-Joo

    2015-01-01

    Objective To define the risk of intracranial haemorrhage among patients treated with antidepressants and non-steroid anti-inflammatory drugs (NSAIDs), compared with the risk among those treated with antidepressants without NSAIDs. Design Retrospective nationwide propensity score matched cohort study. Setting Korean nationwide health insurance database between 1 January 2009 and 31 December 2013. Participants Patients who began receiving antidepressants for the first time (index date) without ...

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

    NARCIS (Netherlands)

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

    1995-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Keping Xu

    2011-02-01

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

  3. BLEEDING PEPTIC ULCER, NONSTEROIDAL ANTIINFLAMMATORY DRUGS AND HELICOBACTER PYLORI INFECTION – A PROSPECTIVE, CONTROLLED, RANDOMIZED STUDY

    Directory of Open Access Journals (Sweden)

    Pavel Skok

    2002-06-01

    Full Text Available Background. The explanation of peptic ulcer etiology has changed significantly in the past decade after the clarification of the significance of Helicobacter pylori infection.Aim. To evaluate the effectiveness of Helicobacter pylori eradication in patients with hemorrhaging peptic ulcer and patients with peptic ulcer without complications.Study ethics. The study was approved in 1998 by the Medical Ethics Committee of the Republic of Slovenia (No. 90/09/98.Type of study. Prospective, controlled and randomized study, carried out between 1998–2000.Patients and methods. The study included 80 patients (50 male and 30 female, av.age 57.5 years, SD ± 17.1, range 22– 80 in which endoscopy confirmed hemorrhage from peptic ulcer of stomach or duodenum and Helicobacter pylori infection. In all cases endoscopic hemostasis was performed: injection sclerotherapy with diluted adrenalin 1:10,000 and 1% polidocanol or argon plasma coagulation. The control group was made up of 80 patients (50 male and 30 female, av.age 56.8 years, SD ± 16.8, range 19–80 with peptic ulcer of stomach or duodenum and Helicobacter pylori infection. Infection was confirmed by a rapid urease test and histologic investigation of the gastric mucosa. In all cases the recommended drug combinations were used in the treatment of the infection: a proton pump inhibitor, omeprazol (4 weeks, and combination of antibiotics, claritromycin and metronidazole or with regard to the antibiogram (1 week. The therapeutic success was ascertained endoscopically four weeks after inclusion in the study. Infection eradication was confirmed by the rapid urease test and histologic investigation of the gastric mucosa.Results. Four weeks after inclusion in the study the success of infection eradication was 92.5% in the study group, in the control group it was 91.3% (p > 0.05. In 6 patients (7.5%, 6/ 80 from the study group and in 7 (8.8%, 7/80 from the control group we introduced a replacement treatment

  4. The chemistry-biology-medicine continuum and the drug discovery and development process in academia.

    Science.gov (United States)

    Nicolaou, K C

    2014-09-18

    Admirable as it is, the drug discovery and development process is continuously undergoing changes and adjustments in search of further improvements in efficiency, productivity, and profitability. Recent trends in academic-industrial partnerships promise to provide new opportunities for advancements of this process through transdisciplinary collaborations along the entire spectrum of activities involved in this complex process. This perspective discusses ways to promote the emerging academic paradigm of the chemistry-biology-medicine continuum as a means to advance the drug discovery and development process. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. [Bioanalytics in medicinal chemistry: from assay development to evolutive drug design].

    Science.gov (United States)

    Jose, J

    2009-11-01

    During the last decade, the focus of bioanalytics shifted from the mere analysis of biomacromolecules to the application of proteins and nucleic acids for analytical purposes, e.g. accessing the biological role of cellular constituents, target identification and validation, quantification of receptor-ligand interactions and others. The increasing impact of combining biomacromolecules with standard analytic devices can be exemplified by the central role of DNA and protein micro-arrays in the fields of genomics, proteomics, transcriptomics or pharmacogenomics. Medicinal chemistry is considered as the scientific discipline concerned with the discovery, design, identification, and preparation of biologically active compounds and the interpretation of their mode of action at the molecular level and their metabolites. From this definition it is evident that bioanalytical tools put into service of medicinal chemistry needs can contribute substantially to progress in drug discovery, design and identification, especially in cases when these tools are well-adapted for miniaturisation and automation to enable high throughput screening. Many successful examples of combining biomacromolecules with standard instrumental analytics indicate that the former role of biochemical testing in medicinal chemistry is more and more replaced by what we call molecular bioanalytics. In recent research, we showed how molecular biology methods and whole cell approaches can be integrated into new bioanalytical tools of complex assembly and how these tools are applicable for drug discovery, drug synthesis and high throughput screening. This is exemplified by the evolutive development of enzyme inhibitors for targets in chronic inflammatory diseases (cathepsin G) or cancer (CK2, hyaluronidase).

  6. Chemistry

    International Nuclear Information System (INIS)

    Ferris, L.M.

    1975-01-01

    The chemical research and development efforts related to the design and ultimate operation of molten-salt breeder reactor systems are concentrated on fuel- and coolant-salt chemistry, including the development of analytical methods for use in these systems. The chemistry of tellurium in fuel salt is being studied to help elucidate the role of this element in the intergranular cracking of Hastelloy N. Studies were continued of the effect of oxygen-containing species on the equilibrium between dissolved UF 3 and dissolved UF 4 , and, in some cases, between the dissolved uranium fluorides and graphite, and the UC 2 . Several aspects of coolant-salt chemistry are under investigation. Hydroxy and oxy compounds that could be formed in molten NaBF 4 are being synthesized and characterized. Studies of the chemistry of chromium (III) compounds in fluoroborate melts were continued as part of a systematic investigation of the corrosion of structural alloys by coolant salt. An in-line voltammetric method for determining U 4+ /U 3+ ratios in fuel salt was tested in a forced-convection loop over a six-month period. (LK)

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

    Directory of Open Access Journals (Sweden)

    Patricia McGettigan

    2011-09-01

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

  8. The value of the clinical history for the diagnosis of immediate nonsteroidal anti-inflammatory drug hypersensitivity and safe alternative drugs in children.

    Science.gov (United States)

    Topal, Erdem; Celiksoy, Mehmet Halil; Catal, Ferhat; Gamze Sayan, Yekbun; Sancak, Recep

    2016-01-01

    Diagnosing hypersensitivity reactions that develop as a result of nonsteroidal anti-inflammatory drugs (NSAID) with a history is mostly misleading, and skin tests and/or provocation tests are needed for a definitive diagnosis. To determine the frequency of actual NSAID hypersensitivity and whether there are any parameters in the history to predict NSAID hypersensitivity. In addition, to determine safe alternative drugs for children who are diagnosed with actual NSAID hypersensitivity. Children with a history of NSAID hypersensitivity were evaluated by an allergist. Safe alternatives in children with a confirmed NSAID hypersensitivity were found by oral provocation tests. Sixty-four patients who were admitted with a suspicion of immediate-type reaction to NSAIDs were included in the study. The median age of the patients was 6 years old (range, 1-17 years), and 37 of the patients (57.8%) were boys. We performed skin tests for suspected NSAID in 35 patients (54.7%). Of these, two had positive results. Provocation tests were performed with 62 patients whose skin test results were negative or for whom skin tests were not available. During the provocation tests, 16 patients (25.8%) developed reactions. Low- and high-dose acetaminophen, nimesulide, and tolmetin sodium were used to find safe alternative drugs. Two patients developed reactions to high-dose acetaminophen but no reaction to nimesulide and tolmetin sodium. When statistically significant parameters were analyzed in a logistic regression model, the presence of multiple NSAIDs hypersensitivity in the patient history (odds ratio 26.6 [95% confidence interval, 1.47-481.63]; p = 0.026) and the emergence of a reaction within an hour (odds ratio 26.4 [95% confidence interval, 1.73-403.11]; p = 0.019) were found as the independent factors to predicted actual NSAID hypersensitivity. The emergence of a reaction within an hour of taking the drug and the presence of multiple NSAIDs hypersensitivity history increased the

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

    Science.gov (United States)

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

    2017-08-02

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

  10. Use of non-steroidal anti-inflammatory drugs in US adults: changes over time and by demographic.

    Science.gov (United States)

    Davis, Jennifer S; Lee, Hwa Young; Kim, Jihye; Advani, Shailesh M; Peng, Ho-Lan; Banfield, Emilyn; Hawk, Ernest T; Chang, Shine; Frazier-Wood, Alexis C

    2017-01-01

    Aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) are preventive against cardiovascular disease (CVD) and several cancer types, but long-term use has been associated with significant health risks, resulting in conflicting recommendations on NSAID use for prevention of CVD and cancer. Previous research indicates that aspirin use increases with age and CVD risk factors and that a large percentage of the US population regularly use analgesics, including NSAIDs, but there has not been a recent, in-depth assessment of NSAID use prevalence, changes in use over time or predictors of NSAID use in the USA. We used the cross-sectional, National Health And Nutrition Examination Survey (NHANES) from 1988 to 1994 and three continuous cycles (1999-2004) to assess regular NSAID use prevalence, changes over time and predictors of regular NSAID use. Overall, regular NSAID use increased over time and varied by demographic features. Participants over 60 years of age, women, participants with high body mass index, increased waist circumference or heart disease were significantly more likely to be regular NSAID users. By contrast, non-Hispanic African American and Mexican American participants were significantly less likely to regularly use NSAIDs. This study uses a nationally representative data set (NHANES) to provide an exploration of regular NSAID use patterns over time, highlighting several demographic, lifestyle and clinical conditions associated with regular NSAID use. Understanding who is likely to regularly use NSAIDs enables more targeted messaging both for increasing the preventive benefits and for limiting the toxicities associated with regular use of NSAIDs.

  11. Randomised clinical trial: esomeprazole for the prevention of nonsteroidal anti-inflammatory drug-related peptic ulcers in Japanese patients.

    Science.gov (United States)

    Sugano, K; Kinoshita, Y; Miwa, H; Takeuchi, T

    2012-07-01

    The use of proton pump inhibitors for prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal adverse events is well documented. However, data regarding the efficacy and safety of this approach in Japan are scarce. To evaluate the efficacy and tolerability of esomeprazole in preventing NSAID-induced peptic ulcers in Japanese at-risk patients. Male and female Japanese adult patients (aged ≥ 20 years) with endoscopically confirmed history of peptic ulcers who required long-term oral NSAID therapy for a chronic inflammatory condition were randomised to 24 weeks' treatment with esomeprazole 20 mg once daily or matching placebo. The primary end point was the Kaplan-Meier estimated proportion of ulcer-free patients. Overall, 343 patients were randomised to treatment (esomeprazole, n = 175; placebo, n = 168). The Kaplan-Meier estimated ulcer-free rate over the 24-week treatment period was significantly higher (log-rank P < 0.001) in esomeprazole-treated patients (96.0%; 95% CI 92.8, 99.1) than in placebo recipients (64.4%; 95% CI 56.8, 71.9). Esomeprazole was effective at preventing peptic ulcers in both Helicobacter pylori-positive and -negative patients (96.3% vs. 95.5% of patients ulcer-free, respectively); however, in the placebo group, the proportion of ulcer-free patients at 24 weeks was markedly lower among H. pylori-positive than -negative patients (59.7% vs. 69.9%). The NSAID type did not seem to affect the estimated ulcer-free rate with esomeprazole. Treatment with esomeprazole was well tolerated. Esomeprazole 20 mg once daily is effective and safe in preventing ulcer recurrence in Japanese patients with a definite history of peptic ulcers who were taking an NSAID (ClinicalTrials.gov identifier: NCT00542789). © 2012 Blackwell Publishing Ltd.

  12. Nonsteroidal anti-inflammatory drugs and glioma in the NIH-AARP Diet and Health Study cohort.

    Science.gov (United States)

    Daugherty, Sarah E; Moore, Steven C; Pfeiffer, Ruth M; Inskip, Peter D; Park, Yikyung; Hollenbeck, Albert; Rajaraman, Preetha

    2011-12-01

    Several case-control studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce risk for glioblastoma, an aggressive form of brain cancer. Prospective investigations have not observed such an association, but these studies lacked adequate brain cancer case numbers and did not stratify by histologic subtype. We prospectively investigated the association between NSAID use and risk of all glioma as well as the risk of glioblastoma subtype in the National Institutes of Health (NIH)-AARP Diet and Health Study. The frequency of aspirin and nonaspirin NSAID use 1 year prior to baseline was ascertained using a self-administered questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox regression models with age as the underlying time metric, adjusted for sex, race, and history of heart disease. The analysis included 302,767 individuals, with 341 incident glioma cases (264 glioblastoma). No association was observed between regular use (>2 times/wk) of aspirin and risk of glioma (HR = 1.16; 95% CI, 0.87-1.56) or glioblastoma (HR = 1.17; 95% CI, 0.83-1.64) as compared with no use. Null associations were also observed for nonaspirin NSAID use (HR for glioma = 0.90; 95% CI, 0.65-1.25 and HR for glioblastoma = 0.83; 95% CI, 0.56-1.20) as compared with no use. Our findings from this large prospective study do not support an inverse association between NSAIDs and risk of all glioma or glioblastoma. 2011 AACR

  13. Socio-demographic differences in risk information seeking sources for non-steroidal anti-inflammatory drugs (NSAIDS).

    Science.gov (United States)

    Houser, Shannon H; Au, David W; Miller, Michael J; Chen, Lang; Outman, Ryan C; Ray, Midge N; Saag, Kenneth G; Weech-Maldonado, Robert

    2016-10-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for musculoskeletal pain and inflammatory conditions. A better understanding of patient information seeking behavior can help bridge the gap between patient knowledge and health care resources. This study examines the primary sources of NSAID risk information and the associations with patient socio-demographic factors. A cross-sectional survey analysis of patients on prescription NSAIDs (n=220) seen by primary care physicians in Alabama. Bivariate and multivariable, multinomial logistic regression analyses were conducted to evaluate the associations among primary NSAID risk information sources used with patient socio-demographic factors. The primary patient source of information on NSAID risks was physician (57.3%), followed by internet (16.8%), pharmacist (16.4%), and other sources, such as nurses and family/friends (9.6%). Compared to people who use the internet as a primary source of NSAID risk information, patients who were Black/African-American (p=0.002) and 65 years of age or older (p=0.009) were more likely to use a physician. Older patients were also more likely to use a pharmacist (p=0.008) than the internet. In contrast, females (p=0.032) were less likely to use the pharmacist compared to the internet (p=0.032). Patients obtain information from a variety of sources, but primarily from health care providers. While the internet is a fast growing source of health information, socio-demographic disparities in internet use for seeking information exist. Health care providers should be aware of their patient preferences for information sources on medication risks to meet the age, race, and gender need differences of all patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Non-steroidal anti-inflammatory drugs (NSAIDs) for treating acute ankle sprains in adults: benefits outweigh adverse events.

    Science.gov (United States)

    van den Bekerom, Michel P J; Sjer, Arnout; Somford, Matthijs P; Bulstra, Gythe H; Struijs, Peter A A; Kerkhoffs, Gino M M J

    2015-08-01

    In the recent clinical guideline for acute lateral ankle sprain, the current best evidence for diagnosis, treatment and prevention strategies was evaluated. Key findings for treatment included the use of ice and compression in the initial phase of treatment, in combination with rest and elevation. A short period of taking non-steroidal anti-inflammatory drugs (NSAIDs) may facilitate a rapid decrease in pain and swelling can also be helpful in the acute phase. The objective was to assess the effectiveness and safety of oral and topical NSAID in the treatment for acute ankle sprains. Randomised controlled trials comparing oral or topic NSAID treatment with placebo or each other were included. Primary outcome measures were pain at rest or at mobilisation and adverse events. Trials were assessed using the Cochrane risk of bias tool. Twenty-eight studies were included, and 22 were available for meta-analysis. Superior results were reported for oral NSAIDs when compared with placebo, concerning pain on weight bearing on short term, pain at rest on the short term, and less swelling on short- and intermediate term. For topical NSAIDs, superior results compared with placebo were found for pain at rest (short term), persistent pain (intermediate term), pain on weight bearing (short- and intermediate term) and for swelling (short and intermediate term). No trials were included comparing oral with topic NSAIDs, so conclusions regarding this comparison are not realistic. The current evidence is limited due to the low number of studies, lack of methodological quality of the included studies as well as the small sample size of the included studies. Nevertheless, the findings from this review support the use of NSAIDs for the initial treatment for acute ankle sprains. Meta-analysis of RCTs, Level I.

  15. Layered double hydroxides based ion exchange extraction for high sensitive analysis of non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    Zhou, Wei; Wang, Chenlu; Liu, Yikun; Zhang, Wenpeng; Chen, Zilin

    2017-09-15

    Layered double hydroxides (LDHs) are ideal sorbents for solid phase extraction (SPE) because of the excellent ion exchange capacity and high specific surface area. However, difficult elution of the analytes from the LDHs is a problem due to the strong ionic interaction between anions and LDHs. High concentrated NaOH solution is employed to elute the sample, but it not suitable for analyzing by HPLC. To solve this problem, a simple acid-base neutralization method was proposed after elution, and then the neutral samples were directly injected to HPLC for analysis. Nickel-aluminum layered double hydroxides (NiAl-LDHs) were synthesized by co-precipitation method and packed into a micro pipette tip for the extraction of three non-steroidal anti-inflammatory drugs (NSAIDs) including ketoprofen, naproxen and flurbiprofen from aqueous samples. After optimization of the experimental parameters such as the concentration of the NaOH, sample pH, sampling rate and sample volume, excellent extraction efficiency towards three NSAIDs was obtained with high enrichment factors of 28-32. A NiAl-LDHs based SPE-HPLC method was developed for quantitative analysis of NSAIDs, and the method showed low limits of detection (0.002-0.1ng/mL), good linearity (R 2 ≥0.9995) and good reproducibility (intraday RSD≤4.37%). The developed method was also applied to the analysis of three NSAIDs in spiked human plasma and rat plasma after oral administration, which demonstrated the practicality of the proposed method. Copyright © 2017. Published by Elsevier B.V.

  16. Inactivation of cholinesterase induced by non-steroidal anti-inflammatory drugs with horseradish peroxidase: implication for Alzheimer's disease.

    Science.gov (United States)

    Muraoka, Sanae; Miura, Toshiaki

    2009-02-27

    To clarify the mechanism of the protective effect of non-steroidal anti-inflammatory drugs (NSAIDs) on Alzheimer's disease, inactivation of cholinesterase (ChE) induced by NSAIDs was examined. Equine ChE and rat brain homogenate were incubated with NSAIDs and horseradish peroxidase (HRP) and H(2)O(2) (HRP-H(2)O(2)). ChE activity was measured by using 5,5'-dithiobis(nitrobenzoic acid). By using electron spin resonance, NSAID radicals induced by reaction with HRP-H(2)O(2) were detected in the presence of spin trap agents. Equine ChE was inactivated by mefenamic acid with HRP-H(2)O(2). ChE activity in rat brain homogenate decreased dependent on the concentration of mefenamic acid in the presence of HRP-H(2)O(2). NSAIDs diclofenac, indomethacin, phenylbutazone, piroxicam and salicylic acid inactivated ChE. Oxygen radical scavengers did not prevent inactivation of ChE induced by mefenamic acid with HRP-H(2)O(2). However, spin trap agents 5,5-dimethyl-1-pyrroline-l-oxide and N-methyl-nitrosopropane, reduced glutathione and ascorbic acid strongly inhibited inactivation of ChE, indicating participation of mefenamic acid radicals. Fluorescent emission of ChE peaked at 400 nm, and the Vmax value of ChE changed during interaction of mefenamic acid with HRP-H(2)O(2), indicating that ChE may be inactivated through modification of tyrosine residues by mefenamic radicals. The protective effect of NSAIDs on Alzheimer's disease seems to occur through inactivation of ChE induced by NSAIDs radicals.

  17. Gastroduodenal toxicity of low-dose acetylsalicylic acid: a comparison with non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    Yeomans, Neville D; Hawkey, Christopher J; Brailsford, Wayne; Naesdal, Jørgen

    2009-11-01

    Low-dose acetylsalicylic acid (ASA; aspirin; 75-325 mg/day) is effective for the prevention of cardiovascular events, and its use in this indication is rapidly increasing. However, the use of ASA and, indeed, other non-steroidal anti-inflammatory drugs (NSAIDs) is limited by the incidence of adverse gastroduodenal events. OBJECTIVES AND SCOPE: To review the clinical evidence for, and the pharmacodynamic basis of, ASA-induced gastroduodenal toxicity in comparison with NSAIDs, and address the question of whether low-dose ASA is 'safe' from a gastroduodenal perspective. This was a narrative, descriptive review, rather than a formal systematic review. Adverse gastroduodenal effects, which are well known to occur with NSAIDs, are also prevalent in patients receiving low-dose ASA for cardiovascular protection even at doses as low as 75 mg/day. The risk of gastroduodenal toxicity is particularly high among 'at-risk' low-dose ASA patients (aged >70 years, previous ulcer or upper gastrointestinal bleeding and users of antiplatelets or NSAIDs). There are important differences in the mechanism of ASA-induced gastroduodenal toxicity, relative to NSAIDs. These differences include the effects on the cyclooxygenase (COX)-1 isoenzyme, local effects on the gastroduodenal mucosa specific to ASA and a reduction in platelet aggregation. Data suggest that ASA causes significant gastroduodenal damage even at the low doses used for cardiovascular protection. These effects (both systemic and possibly local) may be pharmacodynamically distinct from the gastroduodenal toxicity seen with NSAIDs. Studies are required to establish strategies for improving the tolerability of low-dose ASA, allowing patients to continue to benefit from the cardiovascular protection associated with such therapy.

  18. Non-steroidal anti-inflammatory drugs, acetaminophen, and risk of skin cancer in the Nurses' Health Study.

    Science.gov (United States)

    Jeter, J M; Han, J; Martinez, M E; Alberts, D S; Qureshi, A A; Feskanich, D

    2012-09-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with lower risk of certain cancers, but data on the effect on skin cancer risk have been limited and contradictory. We prospectively examined whether use of NSAIDS or acetaminophen was associated with a lower risk of skin cancer in women. The 92,125 Caucasian women in the Nurses' Health Study provided information on aspirin use in 1980. Other NSAIDs and acetaminophen were added in 1990. Medication use, frequency, and quantity were reassessed on biennial questionnaires. Through 2008, we confirmed 658 melanoma cases, 1,337 squamous cell carcinoma (SCC) cases, and had 15,079 self-reports of basal cell carcinoma (BCC). We used COX proportional hazards models to compute relative risks (RR) adjusted for known skin cancer risk factors. Neither aspirin nor non-aspirin NSAID use was associated with a lower risk of melanoma, SCC, or BCC, even for women with high quantity, frequency, or duration of use. Instead, we observed an increased risk of melanoma among current aspirin users (RR = 1.32, 95 % CI 1.03-1.70), though an increase of similar magnitude among past users and lack of a dose-response effect did not support a pharmacologic mechanism. We observed a mild reduction in SCC risk in current acetaminophen users (RR = 0.88, 95 % CI 0.75-1.02), with a linear decrease in risk with greater frequency of use (p = 0.04). Aspirin and other NSAIDs were not associated with a lower risk of melanoma, SCC, or BCC in women. Our large, prospective study does not support a chemoprotective effect of NSAIDs against skin cancers.

  19. Chemopreventive effects of non-steroidal anti-inflammatory drugs in early neoplasm of experimental colorectal cancer: an apoptosome study.

    Science.gov (United States)

    Vaish, Vivek; Tanwar, Lalita; Kaur, Jasmeet; Sanyal, Sankar Nath

    2011-12-01

    Apoptosis is a highly regulated mechanism of cell death where pro-apoptotic proteins and caspases play an important role. Activation of pro-caspases at a definite time is essential to control the whole caspase cascade. Mitochondrion contains some pro-apoptotic proteins, which need to come out in cytoplasm for apoptotic function such as Cytochrome c (Cyt c), while the Bcl-2 protein family works as the guard of mitochondrial membrane and prevents the escape of Cyt c. Once Cyt c is out in cytoplasm, it binds with Apaf-1 (another pro-apoptotic protein also essential for proper cell differentiation) and pro-caspase-9, forming the Apoptosome complex. In this study, the role of two non-steroidal anti-inflammatory drugs (NSAIDs), Diclofenac and Celecoxib, in experimentally induced early neoplasm of colon via apoptosome mechanism had been studied. It has been recognized that the prolonged use of NSAIDs has its effect on reducing the risk of colorectal cancer through apoptotic pathways. However, the role of NSAIDs in respect of apoptosome is not clear. Western blotting and immunohistochemistry were performed, along with morphological and histological analysis. According to the expression levels of Cytochrome c, Apaf-1, Caspases, and Bcl-2, it was observed that NSAIDs do follow the mitochondrial or intrinsic pathway of apoptosis. The effects of Diclofenac and Celecoxib on the expression of pro- and anti-apoptotic proteins have been observed, which may constitute the mechanism by which the NSAIDs are efficient in controlling the proliferation of neoplasm in the colon.

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

    Directory of Open Access Journals (Sweden)

    Yong Zhou

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Haifeng Zhang

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

  2. Soluble dietary fiber protects against nonsteroidal anti-inflammatory drug-induced damage to the small intestine in cats.

    Science.gov (United States)

    Satoh, Hiroshi; Hara, Toshiko; Murakawa, Daisuke; Matsuura, Masashi; Takata, Kenji

    2010-05-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) often cause ulcers in the small intestine in humans, but there are few effective agents for treatment of small intestinal ulcers. We found that soluble dietary fibers (SDFs), such as pectin, could prevent the formation of small intestinal lesions induced by indomethacin (IND) in cats. To elucidate the mechanism of protection by SDFs, we examined the viscosities of SDFs and the effects of pectin on gastrointestinal absorption of IND and intestinal hypermotility induced by IND. Cats were given regular dry food (RFD-Dry) or RFD-Dry supplemented with pectin, guar gum, polydextrose, or mucin twice daily. IND was administered orally once daily for 3 days. Mucosal lesions in the small intestine were examined 24 h after the final dosing of IND. Plasma concentrations of IND were measured by HPLC. GI motilities were measured using a telemetry system in conscious cats implanted with force transducers. Viscosities of the SDFs were measured using a viscosimeter. In cats given RFD-Dry, IND (3 mg/kg) increased motility and produced many lesions in the lower half of the small intestine; the total lesion area (TLA) was 7.5 +/- 2.6 cm(2) (n = 4). Lesions induced by IND were markedly decreased in cats given RFD-Dry supplemented with 3% pectin, guar gum, polydextrose or mucin; TLAs were 0.6 +/- 0.3, 0.0 +/- 0.0, 1.3 +/- 0.8 and 1.6 +/- 0.5 cm(2) (n = 4) (P 1,200, 1 and 4, respectively. Pectin did not affect the absorption of IND nor did it inhibit IND-induced intestinal hypermotility. SDFs protect the small intestine against NSAID-induced damage, probably by compensating a barrier function of the mucin decreased by IND. Viscosities of the SDFs play a role, at least in part, in the protective effects of the SDFs on the small intestine.

  3. [Profile of prescription and adequacy of treatment with non-steroidal anti-inflammatory drugs in diabetic patients].

    Science.gov (United States)

    Navarro-Martínez, A; Vidal-Martínez, M; García-Rosa, I; Lázaro-Gómez, M J; Brotons-Román, J

    2015-01-01

    The aim of this study was to quantify and describe the prescription profile, as well as to assess the adequacy of treatment with non-steroidal anti-inflammatory drugs (NSAIDs) in the diabetic population of a health district. This is a descriptive, cross-sectional study aimed at a target population of 2,795 diabetic patients. Data were collected from the computerised clinical records of a sample of 380 individuals. The adequacy of treatment was assessed using the recommendations proposed by the Spanish societies of Rheumatology, Cardiology and Gastroenterology. More than one-quarter (28%) of the diabetic patients received treatment with NSAIDs. The most commonly used ones were ibuprofen, naproxen, and dexketoprofen, with a defined daily dose per 1,000 inhabitants per day of 35.3, 17.2, and 13.2, respectively. In patients with a history of chronic kidney disease and cardiovascular high risk, fewer NSAIDs were prescribed, while they were used most frequently in patients with a risk for gastrointestinal adverse events. The prescription was considered adequate in 46.5% of diabetic patients. The main causes of inappropriate use were the inadequate prescription of NSAIDs (25.2%), and the use of any NSAID other than naproxen (20.6%). The most prescribed NSAIDs were those showing a low cardiovascular risk profile. Treatment with NSAIDs was inadequate in more than half of the patients. Risk factors for cardiovascular, and especially gastrointestinal, events must be considered in order to avoid its use when not indicated, as well as the use of any NSAIDs other than naproxen. Copyright © 2015 SECA. Published by Elsevier Espana. All rights reserved.

  4. Gastrointestinal events during treatment with nonsteroidal anti-inflammatory drugs (according to the data of the CONDOR study

    Directory of Open Access Journals (Sweden)

    Valeriy Vladimirovich Alekseev

    2010-01-01

    Full Text Available The paper presents the results of a randomized double-blind study of the impact of therapy with celecoxib and a combination of diclofenac and omeprazole in patients with osteoarthrosis and rheumatoid arthritis on a risk for developing gastrointestinal diseases. The study was conducted at health care facilities in 196 centers of 32 countries and covered 18-to-60-year-old patients who belonged to an increased gastrointestinal risk group and had a history of gastroduodenal ulcers and a negative Helicobacter pylori test at screening. The included patients were randomized by a computer program in a 1: 1 ratio to treatment groups receiving celecoxib in a dose of 200 mg twice daily or sustained-release diclofenac 75 mg twice daily + omeprazole 20 mg once daily. The primary efficacy criterion was assessed as the development of clinically relevant changes in the upper or lower gastrointestinal tract (GIT. 4484 patients were randomized to treatment groups (2238 took celecoxib; 2246 received diclofenac + omeprazole. Twenty (0.9% patients who took celecoxib and 81 (3.8% who used diclofenac + omeprazole achieved the primary assessment criterion (p<0.0001. One hundred and fourteen (6% patients who received celecoxib and 167 (8% who took diclofenac + omeprazole were withdrawn from the study prematurely because of adverse reactions in the GIT (p = 0.0006. The risk of clinically relevant GIT changes was lower in the patients treated with celecoxib, that is a selective cyclooxygenase 2 (COX-2 inhibitor, than in the patients who received diclofenac, a nonselective COX inhibitor, and omeprazole, the proton pump inhibitor. The findings should contribute to the revision of approaches to reducing the gastrointestinal risk in nonsteroidal anti-inflammatory drugs treatment.

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

    Science.gov (United States)

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

    2016-04-01

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

  6. The Efficacy and Safety of Treatments for Acute Gout: Results from a Series of Systematic Literature Reviews Including Cochrane Reviews on Intraarticular Glucocorticoids, Colchicine, Nonsteroidal Antiinflammatory Drugs, and Interleukin-1 Inhibitors

    NARCIS (Netherlands)

    Wechalekar, Mihir D.; Vinik, Ophir; Moi, John H. Y.; Sivera, Francisca; van Echteld, Irene A. A. M.; van Durme, Caroline; Falzon, Louise; Bombardier, Claire; Carmona, Loreto; Aletaha, Daniel; Landewé, Robert B.; van der Heijde, Désirée M. F. M.; Buchbinder, Rachelle

    2014-01-01

    Objective. To determine the efficacy and safety of glucocorticoids (GC), colchicine, nonsteroidal antiinflammatory drugs (NSAID), interleukin-1 (IL-1) inhibitors, and paracetamol to treat acute gout. Methods. We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to

  7. Photoactive platinum(II) complexes of nonsteroidal anti-inflammatory drug naproxen: Interaction with biological targets, antioxidant activity and cytotoxicity.

    Science.gov (United States)

    Srivastava, Payal; Singh, Khushbu; Verma, Madhu; Sivakumar, Sri; Patra, Ashis K

    2018-01-20

    The effect on the therapeutic efficacy of Pt(II) complexes on combining non-steroidal anti-inflammatory drugs (NSAIDs) is an attractive strategy to circumvent chronic inflammation mediated by cancer and metastasis. Two square-planar platinum(II) complexes: [Pt(dach)(nap)Cl] (1) and [Pt(dach)(nap) 2 ] (2), where dach = (1R,2R)-dichloro(cyclohexane-1,2-diamine) and NSAID drug naproxen (nap), have been designed for studying their biological activity. The naproxen bound to the Pt(II) centre get released upon photoirradiation with low-power UV-A light as confirmed by the significant enhancement in emission intensities of the complexes. The compounds were evaluated for their photophysical properties, photostability, reactivity with 5'-guanosine monophophosphate (5'-GMP), interactions with CT-DNA and BSA, antioxidant activity and reactive oxygen species mediated photo-induced DNA damage properties. ESI-MS studies demonstrated the formation of bis-adduct with 5'-GMP and the formation of Pt II -DNA crosslinks by gel electrophoretic mobility shift assay and ITC studies. The interaction of the complexes 1 and 2 with the CT-DNA exhibits potential binding affinity (K b  ∼ 10 4  M -1 , K app ∼ 10 5  M -1 ), implying intercalation to CT-DNA through planar naphthyl ring of the complexes. Both the complexes also exhibit strong binding affinity towards BSA (K BSA ∼ 10 5  M -1 ). The complexes exhibit efficient DNA damage activity on irradiation at 365 nm via formation of singlet oxygen ( 1 O 2 ) and hydroxyl radical ( • OH) under physiological conditions. Both the complexes were cytotoxic in dark and exhibit significant enhancement of cytotoxicity upon photo-exposure against HeLa and HepG2 cancer cells giving IC 50 values ranging from 8 to 12 μM for 1 and 2. The cellular internalization data showed cytosolic and nuclear localization of the complexes in the HeLa cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. Non-steroidal anti-inflammatory drugs for spinal pain: a systematic review and meta-analysis.

    Science.gov (United States)

    Machado, Gustavo C; Maher, Chris G; Ferreira, Paulo H; Day, Richard O; Pinheiro, Marina B; Ferreira, Manuela L

    2017-07-01

    While it is now clear that paracetamol is ineffective for spinal pain, there is not consensus on the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) for this condition. We performed a systematic review with meta-analysis to determine the efficacy and safety of NSAIDs for spinal pain. We searched MEDLINE, EMBASE, CINAHL, CENTRAL and LILACS for randomised controlled trials comparing the efficacy and safety of NSAIDs with placebo for spinal pain. Reviewers extracted data, assessed risk of bias and evaluated the quality of evidence using the Grade of Recommendations Assessment, Development and Evaluation approach. A between-group difference of 10 points (on a 0-100 scale) was used for pain and disability as the smallest worthwhile effect, as well as to calculate numbers needed to treat. Random-effects models were used to calculate mean differences or risk ratios with 95% CIs. We included 35 randomised placebo-controlled trials. NSAIDs reduced pain and disability, but provided clinically unimportant effects over placebo. Six participants (95% CI 4 to 10) needed to be treated with NSAIDs, rather than placebo, for one additional participant to achieve clinically important pain reduction. When looking at different types of spinal pain, outcomes or time points, in only 3 of the 14 analyses were the pooled treatment effects marginally above our threshold for clinical importance. NSAIDs increased the risk of gastrointestinal reactions by 2.5 times (95% CI 1.2 to 5.2), although the median duration of included trials was 7 days. NSAIDs are effective for spinal pain, but the magnitude of the difference in outcomes between the intervention and placebo groups is not clinically important. At present, there are no simple analgesics that provide clinically important effects for spinal pain over placebo. There is an urgent need to develop new drug therapies for this condition. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted

  9. The Effect of Limited Perioperative Nonsteroidal Anti-inflammatory Drugs on Patients Undergoing Anterior Cruciate Ligament Reconstruction.

    Science.gov (United States)

    Soreide, Endre; Granan, Lars-Petter; Hjorthaug, Geir A; Espehaug, Birgitte; Dimmen, Sigbjørn; Nordsletten, Lars

    2016-12-01

    The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) to patients undergoing anterior cruciate ligament reconstruction (ACLR) is controversial because it may impair tissue healing and clinical outcomes. To assess the effect of NSAID administration on patients undergoing ACLR. Cohort study; Level of evidence, 3. Included patients were aged >15 years and were registered in the Norwegian Knee Ligament Registry from 2008 until 2013 after the primary ACLR. Patients with insufficient data regarding administration of NSAIDs and those with associated knee ligament injuries requiring surgical treatment were excluded from this study. Graft survival was estimated using Kaplan-Meier survival curves, and hazard ratios (HRs) for revision were evaluated using Cox regression analysis. Logistic regression analysis was used to calculate the odds ratio (OR) for a Knee Injury and Osteoarthritis Outcome Score (KOOS)-quality of life (QOL) subscale score <44 at 2-year follow-up. A total of 7822 patients were included in the analysis for graft survival and assessment for risk of revision. Of these, 4144 patients were administered NSAIDs postoperatively. The mean duration of follow-up was 2.8 years (range, 0-5.9 years). Administration of NSAIDs did not influence graft survival (P = .568). Adjusted Cox regression analyses demonstrated the same finding regarding risk of revision (HR, 1.0; 95% CI, 0.8-1.3). ACLR using a bone-patellar tendon-bone autograft showed a reduced risk of revision (HR, 0.3; 95% CI, 0.1-0.8) among patients administered NSAIDs. In subgroup analyses of 3144 patients, administration of NSAIDs demonstrated a beneficial effect on the risk of a KOOS-QOL score <44 at 2-year follow-up (OR, 0.8; 95% CI, 0.6-0.9). Administration of NSAIDs to patients after ACLR does not have a negative effect on graft survival, risk of revision, or risk of a KOOS-QOL score <44 at 2-year follow-up. We emphasize using caution when administering NSAIDs by keeping the duration and

  10. Recent advances in medicinal chemistry and pharmaceutical technology--strategies for drug delivery to the brain.

    Science.gov (United States)

    Denora, Nunzio; Trapani, Adriana; Laquintana, Valentino; Lopedota, Angela; Trapani, Giuseppe

    2009-01-01

    This paper provides a mini-review of some recent approaches for the treatment of brain pathologies examining both medicinal chemistry and pharmaceutical technology contributions. Medicinal chemistry-based strategies are essentially aimed at the chemical modification of low molecular weight drugs in order to increase their lipophilicity or the design of appropriate prodrugs, although this review will focus primarily on the use of prodrugs and not analog development. Recently, interest has been focused on the design and evaluation of prodrugs that are capable of exploiting one or more of the various endogenous transport systems at the level of the blood brain barrier (BBB). The technological strategies are essentially non-invasive methods of drug delivery to malignancies of the central nervous system (CNS) and are based on the use of nanosystems (colloidal carriers) such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, polymeric micelles and dendrimers. The biodistribution of these nanocarriers can be manipulated by modifying their surface physico-chemical properties or by coating them with surfactants and polyethylene-glycols (PEGs). Liposomes, surfactant coated polymeric nanoparticles, and solid lipid nanoparticles are promising systems for delivery of drugs to tumors of the CNS. This mini-review discusses issues concerning the scope and limitations of both the medicinal chemistry and technological approaches. Based on the current findings, it can be concluded that crossing of the BBB and drug delivery to CNS is extremely complex and requires a multidisciplinary approach such as a close collaboration and common efforts among researchers of several scientific areas, particularly medicinal chemists, biologists and pharmaceutical technologists.

  11. Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) - classification, diagnosis and management: review of the EAACI/ENDA(#) and GA2LEN/HANNA*.

    Science.gov (United States)

    Kowalski, Marek L; Makowska, J S; Blanca, M; Bavbek, S; Bochenek, G; Bousquet, J; Bousquet, P; Celik, G; Demoly, P; Gomes, E R; Niżankowska-Mogilnicka, E; Romano, A; Sanchez-Borges, M; Sanz, M; Torres, M J; De Weck, A; Szczeklik, A; Brockow, K

    2011-07-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are responsible for 21-25% of reported adverse drug events which include immunological and nonimmunological hypersensitivity reactions. This study presents up-to-date information on pathomechanisms, clinical spectrum, diagnostic tools and management of hypersensitivity reactions to NSAIDs. Clinically, NSAID hypersensitivity is particularly manifested by bronchial asthma, rhinosinusitis, anaphylaxis or urticaria and variety of late cutaneous and organ-specific reactions. Diagnosis of hypersensitivity to a NSAID includes understanding of the underlying mechanism and is necessary for prevention and management. A stepwise approach to the diagnosis of hypersensitivity to NSAIDs is proposed, including clinical history, in vitro testing and/or provocation test with a culprit or alternative drug depending on the type of the reaction. The diagnostic process should result in providing the patient with written information both on forbidden and on alternative drugs. © 2011 John Wiley & Sons A/S.

  12. Nonallergic hypersensitivity to nonsteroidal antiinflammatory drugs, angiotensin-converting enzyme inhibitors, radiocontrast media, local anesthetics, volume substitutes and medications used in general anesthesia.

    Science.gov (United States)

    Jurakić Toncić, Ruzica; Marinović, Branka; Lipozencić, Jasna

    2009-01-01

    Urticaria and angioedema are common allergic manifestations and medications are one of common triggering factors. The most severe immediate drug reaction is anaphylaxis. Apart from the well established IgE-mediated immediate type hypersensitivity reactions, the pathogenesis of drug-induced urticaria, angioedema and anaphylaxis often remains obscure. In this article, emphasis is put on nonallergic reactions to the most commonly used drug groups of nonsteroidal antiinflammatory drugs, angiotensin-converting enzyme inhibitors, radiocontrast media, volume expanders and drugs used in general anesthesia. Urticaria is the second most common drug eruption after maculopapular exanthema. The mechanisms of acute urticarial reactions are multiple, mostly IgE mediated, but some drugs can induce immune complex reactions and activate complement cascade, while others can induce direct activation of mast cells and degranulation or activation of complement by non-immune mechanisms. With different types of medications different pathomechanisms are involved. Non-steroid anti-inflammatory drugs are thought to cause reaction due to cyclooxygenase-1 inhibition and overproduction of leukotrienes, blamed for cutaneous and respiratory symptoms. Angiotensin-converting enzyme inhibitors can cause fatal angioedema, which is partially explained with bradykinin excess and impairment of aminopeptidase P and dipeptidyl peptidase IV that are involved in the metabolism of substance P and bradykinin. It remains unknown what additional mechanisms are involved. Radiocontrast media and local anesthetics mostly cause nonallergic hypersensitivity reaction, but in rare cases true allergic reaction can occur. Dextran is known to cause IgG mediated, immune complex anaphylaxis and it is recommended to use human serum albumin as the safest colloid.

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

    Science.gov (United States)

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

    2017-12-01

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

  14. The novel phospho-non-steroidal anti-inflammatory drugs, OXT-328, MDC-22 and MDC-917, inhibit adjuvant-induced arthritis in rats.

    Science.gov (United States)

    Huang, L; Mackenzie, Gg; Ouyang, N; Sun, Y; Xie, G; Johnson, F; Komninou, D; Rigas, B

    2011-04-01

    The use of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis (RA) is limited by their toxicity. We evaluated the anti-inflammatory efficacy and safety of three novel modified NSAIDs, phospho-aspirin, phospho-ibuprofen and phospho-sulindac. We determined the anti-inflammatory effects and gastrointestinal safety of the phospho-NSAIDs in the rat adjuvant arthritis model and studied their mechanism of action in cultured cells, Cytokines were measured with elisa and activation of nuclear factor-κB (NF-κB) by immunohistochemistry. All three phospho-NSAIDs showed less gastrointestinal toxicity than their parent compounds and demonstrated strong anti-inflammatory effects, essentially reversing joint inflammation and oedema. They have a broad but not uniform effect on the expression of relevant cytokines, in general decreasing IL-6 and IL-1β and increasing IL-10 levels in rat plasma and cultured cells. Phospho-sulindac and phospho-ibuprofen but not phospho-aspirin suppressed PGE(2) production in vitro, whereas phospho-aspirin (in contrast to aspirin) showed the same effect in vivo. In joint tissues, phospho-aspirin inhibited NF-κB activation, and suppressed inflammation and bone resorption. Phospho-aspirin also inhibited Jurkat T cell proliferation. In general, phospho-aspirin had greater efficacy but different effects upon inflammatory mediators compared with aspirin. The chemical modification of the parent NSAIDs seems crucial for their safety and efficacy. Phospho-aspirin, phospho-ibuprofen and phospho-sulindac were safer than their parent NSAIDs, were highly effective in rat adjuvant arthritis and inhibited many key mediators in the pathophysiology of RA. These novel compounds are promising candidate drugs for the treatment of RA and merit further evaluation. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

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

    Science.gov (United States)

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

    2015-08-01

    Nonsteroidal anti-inflammatory drug (NSAID)-induced urticarial and angioedema reactions are among the most commonly encountered drug hypersensitivity reactions in clinical practice. Three major clinical phenotypes of NSAID-induced acute skin reactions manifesting with angioedema, urticaria, or both have been distinguished: NSAID-exacerbated cutaneous disease, nonsteroidal anti-inflammatory drug-induced urticaria/angioedema (NIUA), and single NSAID-induced urticaria and angioedema. In some patients clinical history alone might be sufficient to establish the diagnosis of a specific type of NSAID hypersensitivity, whereas in other cases oral provocation challenges are necessary to confirm the diagnosis. Moreover, classification of the type of cutaneous reaction is critical for proper management. For example, in patients with single NSAID-induced reactions, chemically nonrelated COX-1 inhibitors can be safely used. However, there is cross-reactivity between the NSAIDs in patients with NSAID-exacerbated cutaneous disease and NIUA, and thus only use of selective COX-2 inhibitors can replace the culprit drug if the chronic treatment is necessary, although aspirin desensitization will allow for chronic treatment with NSAIDs in some patients with NIUA. In this review we present a practical clinical approach to the patient with NSAID-induced urticaria and angioedema. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Optimized methods for in vitro and in vivo anti-inflammatory assays and its applications in herbal and synthetic drug analysis.

    Science.gov (United States)

    Nile, Shivraj Hariram; Park, Se Won

    2013-01-01

    Inflammatory diseases including, different types of rheumatic diseases are the major problems associated with the presently available non-steroidal anti-inflammatory agents. The numbers of plant derived drugs have been screened for their anti-inflammatory and anti-arthritic activity. Drug development in the recent times often relies on use of natural and synthetic drugs, which are promising candidates as therapeutic agents for prevention of diseases and disorders. These drugs possess different chemical structures, with wide range of therapeutic activities. The mechanism of Inflammation mainly involve in development of serious diseases, such as cancer, rheumatoid arthritis, sprains, bronchitis, muscle pains, chronic inflammatory bowel disease, persistent asthma, and liver fibrosis. Development of inflammatory events basically related to various chemicals, such as glucocorticoids (GCs) and mometasone furoate (MF); endogenous factors such as tumor necrosis factor alpha (TNF-α); enzymes and proteins such as copper and zinc-superoxide dismutase (SOD), proinflammatory peptide substance (PPS), RGD peptides, interleukin-4 (IL-4), IL-10, interferon-γ (IFN-γ), COX, LOX, cytokines such as interleukin-1 (IL-1); reactive oxygen species (ROS), nitric oxide (NO) and prostaglandin E2; as well as pro-inflammatory cells such as T and NK cells are well known to have an important role. Based on these correlations, numerous assays were used for inflammatory mechanism research, which was described in this paper.

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

    Directory of Open Access Journals (Sweden)

    Umesh B Mahajan

    2017-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

    To assess the cost-effectiveness of celecoxib and non-selective non-steroidal anti-inflammatory drugs for the treatment of osteoarthritis in clinical practice in Spain. A decision-tree model using distribution, doses, treatment duration and incidence of GI and CV events observed in the pragmatic PROBE-designed «GI-Reasons» trial was used for cost-effectiveness. Effectiveness was expressed in terms of event averted and quality-adjusted life-years (QALY) gained. QALY were calculated based on utility decrement in case of any adverse events reported in GI-Reasons trial. The National Health System perspective in Spain was applied; cost calculations included current prices of drugs plus cost of adverse events occurred. The analysis was expressed as an incremental cost-effectiveness ratio per QALY gained and per event averted. One-way and probabilistic analyses were performed. Compared with non-selective non-steroidal anti-inflammatory drugs, at current prices, celecoxib treatment had higher overall treatment costs €201 and €157, respectively. However, celecoxib was associated with a slight increase in QALY gain and significantly lower incidence of gastrointestinal events (p<.001), with mean incremental cost-effectiveness ratio of €13,286 per QALY gained and €4,471 per event averted. Sensitivity analyses were robust, and confirmed the results of the base case. Celecoxib at current price may be considered as a cost-effective alternative vs. non-selective non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis in daily practice in the Spanish NHS. Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Kuang-Ting Yeh

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

  20. Diclofenac 1,3,4-Oxadiazole Derivatives; Biology-Oriented Drug Synthesis (BIODS) in Search of Better Non-Steroidal, Non-Acid Antiinflammatory Agents.

    Science.gov (United States)

    Shah, Shazia; Arshia; Kazmi, Nida Siraj; Jabeen, Almas; Faheem, Aisha; Dastagir, Nida; Ahmed, Tariq; Khan, Khalid Mohammed; Ahmed, Shakil; Raza, Abeer; Perveen, Shahnaz

    2018-03-21

    Inflammation is defined as the response of immune system cells to damaged or injured tissues The major symptoms of inflammation include increased blood flow, cellular influx, edema, elevated cellular metabolism, reactive oxygen species (ROS) nitric oxide (NO) and vasodilation. This normally protective mechanism against harmful agents when this normal mechanism becomes dysregulated that can cause serious illnesses including ulcerative colitis, Crohn's disease, rheumatoid arthritis, osteoarthritis, sepsis, and chronic pulmonary inflammation . In this study synthetic transformations on diclofenac were carried out in search of better non-steroidal antiinflammatory drugs (NSAIDs), non-acidic, antiinflammatory agents. For this purpose diclofenac derivatives (2-20) were synthesized from diclofenac (1). All derivatives (2-20) and parent diclofenac (1) were evaluated for their antiinflammatory effect using different parameters including suppression of intracellular reactive oxygen species (ROS), produced by whole blood phagocytes, produced by neutrophils, and inhibition of nitric oxide (NO) production from J774.2 macrophages. Most active compound also evaluated for cytotoxicity activity. Diclofenac (1) inhibited the ROS with an IC50 of 3.9 ± 2.8, 1.2 ± 0.0 μg/mL respectively and inhibited NO with an IC50 of 30.01 ± 0.01 μg/mL. Among its derivatives 4, 5, 11, 16, and 20, showed better antiinflammatory potential. The compound 5 was found to be the most potent inhibitor of intracellular ROS as well as NO with an IC50 values of 1.9 ± 0.9, 1.7 ± 0.4 μg/mL respectively and 7.13 ± 1.0 μg/mL, respectively, and showed good inhibitory activity than parent diclofenac. The most active compounds were tested for their toxic effect on NIH-3T3 cells where all compounds were found to be non-toxic compared to the standard cytotoxic drug cyclohexamide. Five derivatives were found to be active. Compound 5 was found to be the most potent inhibitor of ROS and NO compared to parent

  1. Correlations between electrochemical behaviors and DNA photooxidative properties of non-steroïdal anti-inflammatory drugs and their photoproducts.

    Science.gov (United States)

    Michaud, Sandra; Hajj, Viviane; Latapie, Laure; Noirot, Arielle; Sartor, Valérie; Fabre, Paul-Louis; Chouini-Lalanne, Nadia

    2012-05-02

    Alkali-labile lesion to DNA photosensitized, via an electron transfer mechanism, by three non-steroidal anti-inflammatory drugs (NSAIDs), ketoprofen, tiaprofenic acid and naproxen and their photoproducts during drug photolysis, was investigated using (32)P-end labelled synthetic oligonucleotide. These photooxidative damages were correlated with the photophysical and electrochemical properties of drugs, appearing as the photosensitizer PS. Photophysical studies provided the excited state energies of the photosensitizer while their redox potentials and the relative stabilities of the PS(-) radical-anions were determined by cyclic voltammetry. On the basis of these data, we have calculated the Gibbs energy of photoinduced electron-transfer and evaluated the exergonicity of the oxidative photodamage. Moreover, kinetic control may be invoked according to the stabilities of PS(-). Applied to this NSAIDs family, the photoxidative damages through electron transfer mechanism were analyzed and a good correlation with photoredox and photobiological properties was established. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    1983-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1983-09-01

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

  4. Comparative efficacy and safety of the non-steroidal anti-inflammatory drugs nimesulide and diclofenac in patients with acute subdeltoid bursitis and bicipital tendinitis.

    Science.gov (United States)

    Wober, W; Rahlfs, V W; Büchl, N; Grässle, A; Macciocchi, A

    1998-01-01

    The efficacy and tolerability of nimesulide, a non-steroidal anti-inflammatory drug (NSAID) 100 mg twice daily were compared with diclofenac 75 mg b.i.d. in short term treatment of acute shoulder (acute subdeltoid bursitis and bicipital tendinitis) in adult patients. In this double-blind (double-dummy), randomised, parallel group study over two weeks, 122 patients were included. The Mann-Whitney statistics revealed therapeutic equivalence of both treatments with a slight superiority for nimesulide. The tolerability of nimesulide, judged by investigators and patients and analysed statistically, was superior to that of diclofenac. Thus, the benefit-risk relationship was better for the test drug than for the reference drug.

  5. Beyond relief : biomarkers of the anti-inflammatory effect and dose selection of COX inhibitors in early drug development

    NARCIS (Netherlands)

    Huntjens, Dymphy Regien Hans

    2008-01-01

    The main objective of the research described in this thesis is to demonstrate the relevance of biomarkers on the selection of the dose range of COX inhibitors for effective analgesic and anti-inflammatory response, as opposed to the focus on behavioural measures of pain and inflammation advocated by

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

    Directory of Open Access Journals (Sweden)

    Michael E. El-Kommos

    2013-02-01

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

  7. Inquiry-based Laboratory Activities on Drugs Analysis for High School Chemistry Learning

    Science.gov (United States)

    Rahmawati, I.; Sholichin, H.; Arifin, M.

    2017-09-01

    Laboratory activity is an important part of chemistry learning, but cookbook instructions is still commonly used. However, the activity with that way do not improve students thinking skill, especially students creativity. This study aims to improve high school students creativity through inquiry-based laboratory on drugs analysis activity. Acid-base titration is used to be method for drugs analysis involving a color changing indicator. The following tools were used to assess the activity achievement: creative thinking test on acid base titration, creative attitude and action observation sheets, questionnaire of inquiry-based lab activities, and interviews. The results showed that the inquiry-based laboratory activity improving students creative thinking, creative attitude and creative action. The students reacted positively to this teaching strategy as demonstrated by results from questionnaire responses and interviews. This result is expected to help teachers to overcome the shortcomings in other laboratory learning.

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

    Directory of Open Access Journals (Sweden)

    Mirela-Anca STOIA

    2015-12-01

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

  9. Effects of non-steroidal anti-inflammatory drugs on rat gastric mucosal leukotriene C4 and prostanoid release: relation to ethanol-induced injury.

    OpenAIRE

    Peskar, B. M.; Hoppe, U.; Lange, K.; Peskar, B. A.

    1988-01-01

    1. The effects of oral and subcutaneous administration of the non-steroidal anti-inflammatory drugs sodium salicylate, aspirin and indomethacin on ex vivo gastric mucosal release of leukotriene C4 (LTC4) prostaglandin E2 (PGE2), 6-oxo-PGF1 alpha and thromboxane B2 (TXB2) were investigated in rats under basal conditions as well as after challenge with ethanol. 2. Basal release of PGE2, 6-oxo-PGF1 alpha and TXB2 was inhibited by oral administration of aspirin (0.6-400 mgkg-1) and indomethacin (...

  10. A Randomized Trial Among Compression Plus Nonsteroidal Antiinflammatory Drugs, Aspiration, and Aspiration With Steroid Injection for Nonseptic Olecranon Bursitis.

    Science.gov (United States)

    Kim, Joon Yub; Chung, Seok Won; Kim, Joo Hak; Jung, Jae Hong; Sung, Gwang Young; Oh, Kyung-Soo; Lee, Jong Soo

    2016-03-01

    Olecranon bursitis might be a minor problem in the outpatient clinic but relatively be common to occur. However, there are few well-designed studies comparing approaches to treatment. (1) Which treatment (compression bandaging with nonsteroidal antiinflammatory drugs [NSAIDs], aspiration, or aspiration with steroid injections) is associated with the highest likelihood of resolution of nonseptic olecranon bursitis? (2) Which treatment is associated with earliest resolution of symptoms? (3) What factors are associated with treatment failure by 4 weeks? We enrolled 133 patients from two centers; after applying prespecified exclusions (septic bursitis or concomitant inflammatory arthritis, intraarticular elbow pathology, recent aspiration or steroid injection done elsewhere, and refusal to participate), 90 patients were randomly allocated to receive compression bandaging with NSAIDs (C), aspiration (A), or aspiration with steroid injection (AS) groups (30 patients in each). The groups were similar at baseline in terms of age and gender. Seven patients (four from Group A and three from Group AS) were lost to followup. All patients were followed up weekly for 4 weeks, and the same treatment procedure was repeated if the bursitis recurred with any substantial fluid collection. At 4 weeks, the state of resolution and pain visual analog scale (VAS) were evaluated. Failed resolution was defined as presence of persistent olecranon bursal fluid collection at Week 4 after the initiation of the treatment; on the contrary, if bursal fluid collection was clinically reduced or completely disappeared by the end of Week 4, the treatment was considered successful. We compared the proportion of resolution by Week 4 and the median times to resolution among the treatment groups. In addition, we evaluated whether the resolution affected pain VAS and what factors were associated with the resolution. There were no differences in the proportion of patients whose bursitis resolved by Week 4

  11. Non-steroidal anti-inflammatory drug related upper gastrointestinal bleeding: types of drug use and patient profiles in real clinical practice.

    Science.gov (United States)

    Sostres, Carlos; Carrera-Lasfuentes, Patrica; Lanas, Angel

    2017-10-01

    The best available evidence regarding non-steroidal anti-inflammatory drug (NSAID)-related gastrointestinal (GI) bleeding comes from randomized controlled trials including patients who use NSAIDs to manage chronic rheumatic diseases; however, patients with varying background profiles commonly take NSAIDs for many other reasons, often without prescription, and such usage has not been well studied. To define the characteristics of patients hospitalized for upper GI bleeding in clinical practice, we conducted a case-control study among patients with endoscopy-proven major upper GI bleeding due to gastroduodenal peptic lesions and control subjects. We used adjusted logistic regression models to estimate bleeding risks. Data analysis was performed using SPSS 22.0. Our analysis included 3785 cases and 6540 controls, including 1270 cases (33.55%) and 834 controls (12.75%) reporting recent use (NSAIDs including high-dose acetylsalicylic acid (ASA). NSAID use was associated with increased risk of upper GI bleeding, with an adjusted relative risk of 4.86 (95% CI, 4.32-5.46). Acute musculoskeletal pain (36.1%), chronic osteoarthritis (13.5%), and headache (13.6%) were the most common reasons for NSAID use. Among cases, only 17.31% took NSAIDs and 6.38% took high dose ASA due to chronic osteoarthritis. Demographic characteristics significantly differed between subjects with chronic vs. acute musculoskeletal pain. Proton pump inhibitor use was significantly higher in patients who used NSAIDs due to chronic osteoarthritis compared to patients with acute musculoskeletal pain. NSAID (65.15%) or high-dose ASA use (65.83%) preceding upper GI bleeding was most often short-term. In over half of cases (63.62%), the upper GI bleeding event was not preceded by dyspeptic warning symptoms. The majority of patients hospitalized due to NSAID-related upper GI bleeding reported short-term NSAID use for reasons other than chronic rheumatic disease. These findings suggest that current prevention

  12. Gene Expression Profile of Coronary Artery cells Treated with Non-steroidal Anti-inflammatory Drugs Reveals Off-target Effects

    Science.gov (United States)

    Palayoor, Sanjeewani T.; J-Aryankalayil, Molykutty; Makinde, Adeola. Y.; Cerna, David; Falduto, Michael T.; Magnuson, Scott. R.; Coleman, C. Norman

    2012-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have come under scrutiny because of the gastrointestinal, renal and cardiovascular toxicity associated with prolonged use of these drugs. The purpose of this study was to identify molecular targets for NSAIDs related to cellular toxicity with a view to optimize drug efficacy in clinic. Coronary artery smooth muscle cells (CASMC) and endothelial cells (HCAEC) were treated with low (clinically achievable) and high (typically used in preclinical studies) concentrations of celecoxib (CXB), NS398 (NS) and ibuprofen (IBU) for 24h. NSAIDs-induced gene expression changes were evaluated by microarray analysis and validated by real-time RT-PCR and western blotting. The functional significance of differentially expressed genes was evaluated by Ingenuity Pathway Analysis (IPA). At high concentrations, NSAIDs altered the expression of genes regulating cell proliferation and cell death. NSAIDs also altered genes associated with cardiovascular functions including inflammation, thrombosis, fibrinolysis, coronary artery disease and hypertension. The gene expression was most impacted by IBU, CXB and NS, in that order. This study revealed that NSAIDs altered expression of an array of genes associated with cardiovascular events and emphasizes the potential for fingerprinting drugs in preclinical studies to assess the potential drug toxicity and to optimize the drug efficacy in clinical settings. PMID:22668799

  13. Effects of non-steroidal anti-inflammatory drug treatments on cognitive decline vary by phase of pre-clinical Alzheimer disease: findings from the randomized controlled Alzheimer's Disease Anti-inflammatory Prevention Trial.

    Science.gov (United States)

    Leoutsakos, Jeannie-Marie S; Muthen, Bengt O; Breitner, John C S; Lyketsos, Constantine G

    2012-04-01

    We examined the effects of non-steroidal anti-inflammatory drugs on cognitive decline as a function of phase of pre-clinical Alzheimer disease. Given recent findings that cognitive decline accelerates as clinical diagnosis is approached, we used rate of decline as a proxy for phase of pre-clinical Alzheimer disease. We fit growth mixture models of Modified Mini-Mental State (3MS) Examination trajectories with data from 2388 participants in the Alzheimer's Disease Anti-inflammatory Prevention Trial and included class-specific effects of naproxen and celecoxib. We identified three classes: "no decline", "slow decline", and "fast decline", and examined the effects of celecoxib and naproxen on linear slope and rate of change by class. Inclusion of quadratic terms improved fit of the model (-2 log likelihood difference: 369.23; p < 0.001) but resulted in reversal of effects over time. Over 4 years, participants in the slow-decline class on placebo typically lost 6.6 3MS points, whereas those on naproxen lost 3.1 points (p-value for difference: 0.19). Participants in the fast-decline class on placebo typically lost 11.2 points, but those on celecoxib first declined and then gained points (p-value for difference from placebo: 0.04), whereas those on naproxen showed a typical decline of 24.9 points (p-value for difference from placebo: <0.0001). Our results appeared statistically robust but provided some unexpected contrasts in effects of different treatments at different times. Naproxen may attenuate cognitive decline in slow decliners while accelerating decline in fast decliners. Celecoxib appeared to have similar effects at first but then attenuated change in fast decliners. Copyright © 2011 John Wiley & Sons, Ltd.

  14. Using UV-VIS spectrophotometry for determining ecotoxicity of selected non-steroidal anti-inflammatory drugs

    Czech Academy of Sciences Publication Activity Database

    Čapka, Lukáš; Zlámalová Gargošová, H.; Vávrová, M.

    2015-01-01

    Roč. 24, 12C (2015), s. 4758-4762 ISSN 1018-4619 Institutional support: RVO:68081715 Keywords : ecotoxicity * NSAIDs * UV-VIS spectrophotometry Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 0.372, year: 2015

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

    Science.gov (United States)

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

    1984-01-01

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

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

    Science.gov (United States)

    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.

  17. [An anti-RNP antibody-positive case of aseptic meningitis induced by non-steroidal anti-inflammatory drugs in a young woman].

    Science.gov (United States)

    Matsui, Taro; Nakagawa, Keiichi; Yamazaki, Keishi; Wada, Taishi; Kadoya, Masato; Kaida, Kenichi

    2018-01-26

    A 19-year-old woman developed high fever, headache, and nausea after taking Loxoprofen for pharyngitis, followed by disturbed consciousness and nuchal stiffness. The patient and her mother had a history of Raynaud's phenomenon. Cerebrospinal fluid (CSF) examination indicated a diagnosis of aseptic meningitis and revealed high levels of Q albumin and IgG index. Anti-RNP antibodies were positive in serum and CSF. Her symptoms disappeared immediately after cessation of Loxoprofen and a drug lymphocyte stimulation test was negative, confirming a diagnosis of non-steroidal anti-inflammatory drugs (NSAIDs)-induced aseptic meningitis. It should be kept in mind that an immune abnormality such as serum and CSF anti-RNP antibodies may play a role in development of NSAIDs-induced aseptic meningitis. A history of usage of NSAIDs and a thorough examination of collagen diseases are useful for identification of the origin of aseptic meningitis in a young woman.

  18. Experimental evidence of heparanase, Hsp70 and NF-κB gene expression on the response of anti-inflammatory drugs in TNBS-induced colonic inflammation.

    Science.gov (United States)

    Quaglio, Ana E V; Castilho, Anthony C S; Di Stasi, Luiz C

    2015-11-15

    Etiopathogenesis of inflammatory bowel disease is unclear and results from a complex interplay of genetic, microbial, environmental and immune factors. Elucidating the mechanisms that drive IBD depends on the detailed characterization of human inflammatory mediators in animal models. Therefore, we studied how intestinal inflammation affects heparanase, NF-κB and Hsp70 gene expression in rats, and if current intestinal anti-inflammatory drugs (sulphasalazine, prednisolone and azathioprine) act on these expressions. Moreover, we investigated the relationships among these genes with colonic cytokines levels (IL-1β, TNF-α, IL-6, INF-γ and IL-10) and oxidative stress that have fundamental role in IBD. Macroscopic parameters (diarrhea, extension of lesion, colonic weight/length ratio and damage score), biochemical markers (myeloperoxidase and alkaline phosphatase activities, and glutathione, IL-1β, TNF-α, IL-6, INF-γ and IL-10 levels), gene expressions (heparanase, NF-κB and Hsp70), and microscopic evaluations (optic, electronic scanning and transmission microscopic) were performed in rats. Expression of heparanase, Hsp70 and NF-κB and oxidative stress were increased by inflammatory process and differentially modulated by sulphasalazine, prednisolone and azathioprine treatments. Protective effects of drugs were also related to differential modulation of cytokine changes induced by inflammatory process, showing different mechanisms to control inflammation. Heparanase, NF-κB and Hsp70 gene expression participate in the inflammatory response induced by TNBS and represent pharmacological targets of the intestinal anti-inflammatory drugs. In addition, current drugs used to treat IBD (sulphasalazine, prednisolone and azathioprine) differentially modulate heparanase, NF-κB and Hsp70 gene expression, cytokine production and oxidative stress.

  19. Combinatorial chemistry

    DEFF Research Database (Denmark)

    Nielsen, John

    1994-01-01

    An overview of combinatorial chemistry is presented. Combinatorial chemistry, sometimes referred to as `irrational drug design,' involves the generation of molecular diversity. The resulting chemical library is then screened for biologically active compounds.......An overview of combinatorial chemistry is presented. Combinatorial chemistry, sometimes referred to as `irrational drug design,' involves the generation of molecular diversity. The resulting chemical library is then screened for biologically active compounds....

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

    Science.gov (United States)

    2017-01-01

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

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

    Science.gov (United States)

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

    2015-07-17

    Axial spondyloarthritis (axSpA) comprises ankylosing spondylitis (radiographic axSpA) and non-radiographic (nr-)axSpA and is associated with psoriasis, uveitis and inflammatory bowel disease. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line drug treatment. To determine the benefits and harms of NSAIDs in axSpA. We searched CENTRAL, MEDLINE and EMBASE to 18 June 2014. Randomised controlled trials (RCTs) or quasi-RCTs of NSAIDs versus placebo or any comparator in adults with axSpA and observational cohort studies studying the long term effect (≥ six months) of NSAIDs on radiographic progression or adverse events (AEs). The main comparions were traditional or COX-2 NSAIDs versus placebo. The major outcomes were pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), radiographic progression, number of withdrawals due to AEs and number of serious AEs Two review authors independently selected trials for inclusion, assessed the risk of bias, extracted data and assessed the quality of evidence for major outcomes using GRADE. We included 39 studies (35 RCTs, two quasi-RCTs and two cohort studies); and 29 RCTs and two quasi-RCTs (n = 4356) in quantitative analyses for the comparisons: traditional NSAIDs versus placebo, cyclo-oxygenase-2 (COX-2) versus placebo, COX-2 versus traditional NSAIDs, NSAIDs versus NSAIDs, naproxen versus other NSAIDs, low versus high dose. Most trials were at unclear risk of selection bias (n = 29), although blinding of participants and personnel was adequate in 24 trials. Twenty-five trials had low risk of attrition bias and 29 trials had low risk of reporting bias. Risk of bias in both cohort studies was high for study participation, and low or unclear for all other criteria. No trials in the meta-analyses assessed patients with nr-axSpA.Traditional NSAIDs were more beneficial than placebo at six

  2. The influence of non-steroidal anti-inflammatory drugs and paracetamol used for pain control of orthodontic tooth movement: a systematic review.

    Science.gov (United States)

    Corrêa, Adriano S; Almeida, Vinícius L DE; Lopes, Beatriz M V; Franco, Ademir; Matos, Felipe R DE; Quintans-Júnior, Lucindo J; Rode, Sigmar M; Paranhos, Luiz R

    2017-01-01

    The present study aimed to perform a systematic literature review to determine if there is a non-steroidal anti-inflammatory drug (NSAID) that interferes less within tooth movement. This research was performed according to the PRISMA statement. Articles were searched in eight electronic databases (PubMed, Scopus, Embase, Web of Science, LILACS, SciELO, Google Scholar, and Open Grey). Only experimental studies on male Wistar rats were selected, which included experiments related to the influence of NSAIDs on orthodontic movement. Studies in animals with pathological conditions, literature review articles, letters to the editor and/or editorials, case reports, abstracts, books, and book chapters were excluded. Each of the steps of this systematic literature review was performed by two examiners independently. the total sample consisted of 505 articles, from which 6 studies were eligible after a qualitative analysis. From the drugs assessed, paracetamol was unanimous for not interfering within orthodontic movement when compared to the control group. However, drugs such as aspirin, ibuprofen, sodium diclofenac, and selective cyclooxygenase-2 inhibitors caused a reduction in tooth movement when compared to the control group. paracetamol could be considered the drug of choice for pain relief because it interferes less within tooth movement.

  3. The influence of non-steroidal anti-inflammatory drugs and paracetamol used for pain control of orthodontic tooth movement: a systematic review

    Directory of Open Access Journals (Sweden)

    ADRIANO S. CORRÊA

    2017-08-01

    Full Text Available ABSTRACT The present study aimed to perform a systematic literature review to determine if there is a non-steroidal anti-inflammatory drug (NSAID that interferes less within tooth movement. This research was performed according to the PRISMA statement. Articles were searched in eight electronic databases (PubMed, Scopus, Embase, Web of Science, LILACS, SciELO, Google Scholar, and Open Grey. Only experimental studies on male Wistar rats were selected, which included experiments related to the influence of NSAIDs on orthodontic movement. Studies in animals with pathological conditions, literature review articles, letters to the editor and/or editorials, case reports, abstracts, books, and book chapters were excluded. Each of the steps of this systematic literature review was performed by two examiners independently. Results: the total sample consisted of 505 articles, from which 6 studies were eligible after a qualitative analysis. From the drugs assessed, paracetamol was unanimous for not interfering within orthodontic movement when compared to the control group. However, drugs such as aspirin, ibuprofen, sodium diclofenac, and selective cyclooxygenase-2 inhibitors caused a reduction in tooth movement when compared to the control group. Conclusion: paracetamol could be considered the drug of choice for pain relief because it interferes less within tooth movement.

  4. Medicinal Chemistry and Molecular Modeling: An Integration to Teach Drug Structure-Activity Relationship and the Molecular Basis of Drug Action

    Science.gov (United States)

    Carvalho, Ivone; Borges, Aurea D. L.; Bernardes, Lilian S. C.

    2005-01-01

    The use of computational chemistry and the protein data bank (PDB) to understand and predict the chemical and molecular basis involved in the drug-receptor interactions is discussed. A geometrical and chemical overview of the great structural similarity in the substrate and inhibitor is provided.

  5. The role of mitochondria-derived reactive oxygen species in the pathogenesis of non-steroidal anti-inflammatory drug-induced small intestinal injury.

    Science.gov (United States)

    Handa, O; Majima, A; Onozawa, Y; Horie, H; Uehara, Y; Fukui, A; Omatsu, T; Naito, Y; Yoshikawa, T

    2014-09-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been implemented in clinical settings for a long time for their anti-inflammatory effects. With the number of NSAID users increasing, gastroenterological physicians and researchers have worked hard to prevent and treat NSAID-induced gastric mucosal injury, an effort that has for the large part being successful. However, the struggle against NSAID-induced mucosal damage has taken on a new urgency due to the discovery of NSAID-induced small intestinal mucosal injury. Although the main mechanism by which NSAIDs induce small intestinal mucosal injury has been thought to depend on the inhibitory effect of NSAIDs on cyclooxygenase (COX) activity, recent studies have revealed the importance of mitochondria-derived reactive oxygen species (ROS) production, which occurs independently of COX-inhibition. ROS production is an especially important factor in the increase of small intestinal epithelial cell permeability, an early stage in the process of small intestinal mucosal injury. By clarifying the precise mechanism, together with its clinical features using novel endoscopy, effective strategies for preventing NSAID-induced small intestinal damage, especially targeting mitochondria-derived ROS production, may be developed.

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

    Directory of Open Access Journals (Sweden)

    Rafael Perini

    2004-01-01

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

  7. 2013 Philip S. Portoghese Medicinal Chemistry Lectureship: Drug Discovery Targeting Allosteric Sites†

    Science.gov (United States)

    2015-01-01

    The identification of sites on receptors topographically distinct from the orthosteric sites, so-called allosteric sites, has heralded novel approaches and modes of pharmacology for target modulation. Over the past 20 years, our understanding of allosteric modulation has grown significantly, and numerous advantages, as well as caveats (e.g., flat structure–activity relationships, species differences, “molecular switches”), have been identified. For multiple receptors and proteins, numerous examples have been described where unprecedented levels of selectivity are achieved along with improved physiochemical properties. While not a panacea, these novel approaches represent exciting opportunities for tool compound development to probe the pharmacology and therapeutic potential of discrete molecular targets, as well as new medicines. In this Perspective, in commemoration of the 2013 Philip S. Portoghese Medicinal Chemistry Lectureship (LindsleyC. W.Adventures in allosteric drug discovery. Presented at the 246th National Meeting of the American Chemical Society, Indianapolis, IN, September 10, 2013; The 2013 Portoghese Lectureship), several vignettes of drug discovery campaigns targeting novel allosteric mechanisms will be recounted, along with lessons learned and guidelines that have emerged for successful lead optimization. PMID:25180768

  8. Drug Synthesis and Analysis on a Dime: A Capstone Medicinal Chemistry Experience for the Undergraduate Biochemistry Laboratory

    Science.gov (United States)

    Streu, Craig N.; Reif, Randall D.; Neiles, Kelly Y.; Schech, Amanda J.; Mertz, Pamela S.

    2016-01-01

    Integrative, research-based experiences have shown tremendous potential as effective pedagogical approaches. Pharmaceutical development is an exciting field that draws heavily on organic chemistry and biochemistry techniques. A capstone drug synthesis/analysis laboratory is described where biochemistry students synthesize azo-stilbenoid compounds…

  9. Early-life experience decreases drug-induced reinstatement of morphine CPP in adulthood via microglial-specific epigenetic programming of anti-inflammatory IL-10 expression.

    Science.gov (United States)

    Schwarz, Jaclyn M; Hutchinson, Mark R; Bilbo, Staci D

    2011-12-07

    A critical component of drug addiction research involves identifying novel biological mechanisms and environmental predictors of risk or resilience to drug addiction and associated relapse. Increasing evidence suggests microglia and astrocytes can profoundly affect the physiological and addictive properties of drugs of abuse, including morphine. We report that glia within the rat nucleus accumbens (NAcc) respond to morphine with an increase in cytokine/chemokine expression, which predicts future reinstatement of morphine conditioned place preference (CPP) following a priming dose of morphine. This glial response to morphine is influenced by early-life experience. A neonatal handling paradigm that increases the quantity and quality of maternal care significantly increases baseline expression of the anti-inflammatory cytokine IL-10 within the NAcc, attenuates morphine-induced glial activation, and prevents the subsequent reinstatement of morphine CPP in adulthood. IL-10 expression within the NAcc and reinstatement of CPP are negatively correlated, suggesting a protective role for this specific cytokine against morphine-induced glial reactivity and drug-induced reinstatement of morphine CPP. Neonatal handling programs the expression of IL-10 within the NAcc early in development, and this is maintained into adulthood via decreased methylation of the IL-10 gene specifically within microglia. The effect of neonatal handling is mimicked by pharmacological modulation of glia in adulthood with ibudilast, which increases IL-10 expression, inhibits morphine-induced glial activation within the NAcc, and prevents reinstatement of morphine CPP. Taken together, we have identified a novel gene × early-life environment interaction on morphine-induced glial activation and a specific role for glial activation in drug-induced reinstatement of drug-seeking behavior.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    BACKGROUND: Little is known about the relation between regular use of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of asthma at the population level. The aim of this study was to examine a possible association between intake of NSAIDs and risk of adult-onset asthma. METHODS: Using...... compared with non-users (7.7% vs 4.3%), OR = 1.87 (1.25-2.81), P = 0.002. The result remained significant after adjusting for sex, age, smoking, BMI, hay fever, eczema and intake of medications other than NSAIDs, OR = 1.90 (1.26-2.85), P = 0.002. CONCLUSIONS: Regular use of NSAIDs other than aspirin may...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  12. The Inhibitory Effect of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs on the Monophenolase and Diphenolase Activities of Mushroom Tyrosinase

    Directory of Open Access Journals (Sweden)

    Kazuomi Sato

    2011-06-01

    Full Text Available In the present work, we investigated the effect of non-steroidal anti-inflammatory drugs (NSAIDs on the monophenolase and diphenolase activity of mushroom tyrosinase. The results showed that diflunisal and indomethacin inhibited both monophenolase and diphenolase activity. For monophenolase activity, the lag time was extended in the presence of diflunisal. In the presence of indomethacin, the lag time did not change. IC50 values of monophenolase activity were estimated to be 0.112 mM (diflunisal and 1.78 mM (indomethacin. Kinetic studies of monophenolase activity revealed that both diflunisal and indomethacin were non-competitive inhibitors. For diphenolase activity, IC50 values were estimated to be 0.197 mM (diflunisal and 0.509 mM (indomethacin. Diflunisal and indomethacin were also found to be non-competitive diphenolase inhibitors.

  13. The inhibitory effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the monophenolase and diphenolase activities of mushroom tyrosinase.

    Science.gov (United States)

    Sato, Kazuomi; Toriyama, Masaru

    2011-01-01

    In the present work, we investigated the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the monophenolase and diphenolase activity of mushroom tyrosinase. The results showed that diflunisal and indomethacin inhibited both monophenolase and diphenolase activity. For monophenolase activity, the lag time was extended in the presence of diflunisal. In the presence of indomethacin, the lag time did not change. IC(50) values of monophenolase activity were estimated to be 0.112 mM (diflunisal) and 1.78 mM (indomethacin). Kinetic studies of monophenolase activity revealed that both diflunisal and indomethacin were non-competitive inhibitors. For diphenolase activity, IC(50) values were estimated to be 0.197 mM (diflunisal) and 0.509 mM (indomethacin). Diflunisal and indomethacin were also found to be non-competitive diphenolase inhibitors.

  14. Simultaneous determination of non-steroidal anti-inflammatory drugs in pharmaceutical formulations and human serum by reversed phase high performance liquid chromatography

    Directory of Open Access Journals (Sweden)

    Muhammad Nawaz

    2012-01-01

    Full Text Available A rapid and sensitive method using high performance liquid chromatography has been developed and validated for the simultaneous determination of non-steroidal anti-inflammatory drugs (NSAIDs in pharmaceutical formulations and human serum. Six NSAIDs including: naproxen sodium, diclofenac sodium, meloxicam, flurbiprofen, tiaprofenic and mefenamic acid were analyzed simultaneously in presence of ibuprofen as internal standard on Mediterranea C18 (5 µm, 250 x 0.46 mm column. Mobile phase comprised of methanol: acetonitrile: H2O (60:20:20, v/v; pH 3.35 and pumped at a flow rate of 1 mL min-1 using 265 nm UV detection. The method was linear over a concentration range of 0.25-50 µg mL-1 (r² = 0.9999.

  15. Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics

    DEFF Research Database (Denmark)

    Schjerning Olsen, Anne-Marie; Lindhardsen, Jesper; Gislason, Gunnar H

    2015-01-01

    STUDY QUESTION: What is the effect of proton pump inhibitors (PPIs) on the risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with non-steroidal anti-inflammatory drugs (NSAIDs)? METHODS: This was a nationwide cohort study based on linked...... plus antithrombotic therapy was estimated using adjusted time dependent Cox regression models. STUDY ANSWER AND LIMITATIONS: The use of PPIs was independently associated with decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated...... gastrointestinal bleeds occurred. The crude incidence rates of bleeding (events/100 person years) on NSAID plus antithrombotic therapy were 1.8 for patients taking PPIs and 2.1 for those not taking PPIs. The adjusted risk of bleeding was lower with PPI use (hazard ratio 0.72, 95% confidence interval 0.54 to 0...

  16. Resveratrol in medicinal chemistry: a critical review of its pharmacokinetics, drug-delivery, and membrane interactions.

    Science.gov (United States)

    Neves, A R; Lucio, M; Lima, J L C; Reis, S

    2012-01-01

    Resveratrol is a polyphenol that among other sources occurs in grapes and for this reason, red wines also contain considerable amounts of this compound. Resveratrol is thought to be responsible for the "French Paradox" which associates red wine consumption to the low incidence of cardiovascular diseases. The interest in resveratrol has increased due to its pharmacological effects that include cardio and neuroprotection and several other benefic actions (e.g. antioxidant, anti-inflammatory, anti-carcinogenic and anti-aging). Despite the therapeutic effects of resveratrol, its pharmacokinetic properties are not favorable since this compound has poor bioavailability being rapidly and extensively metabolized and excreted. To overcome this problem, drug delivery systems have been developed to protect and stabilize resveratrol and to enhance its bioavailability. Herein is presented an up-to-date revision covering the literature reported for nano and microformulations for resveratrol encapsulation that include liposomes, polymeric nanoparticles, solid lipid nanoparticles, lipospheres, cyclodextrins, polymeric microspheres, yeast cells carriers and calcium or zinc pectinate beads. Regarding the interaction of resveratrol with cell membranes, only few studies have been published so far. However, it is believed that this interaction can be implied in the biological activities of resveratrol since transmembranar proteins are one of its cellular targets. Indeed, resveratrol presents the capacity to modulate the membrane organization which may consequently affect the protein functionality. Therefore, the intracellular effects of resveratrol and the effects of this compound at the membrane level were also revised since their knowledge is essential for understanding the pharmacological and therapeutic activities of this bioactive compound.

  17. A multicenter prospective study on the prevalence of Helicobacter pylori-negative and nonsteroidal anti-inflammatory drugs-negative idiopathic peptic ulcers in Japan.

    Science.gov (United States)

    Kanno, Takeshi; Iijima, Katsunori; Abe, Yasuhiko; Yagi, Makoto; Asonuma, Sho; Ohyauchi, Motoki; Ito, Hirotaka; Koike, Tomoyuki; Shimosegawa, Tooru

    2015-05-01

    The prevalence of Helicobacter pylori-negative and nonsteroidal anti-inflammatory drug-negative peptic ulcers, commonly known as idiopathic peptic ulcers (IPUs), has been reported to be very low (0.9-2.6%) in Japan based on data from the 1990s. However, recent trends have yet to be been reported. Herein, we present a multicenter prospective analysis between 2012 and 2013 investigating current trends in the prevalence and characteristics of IPUs in Japan. Clinical data of all peptic ulcer subjects detected via endoscopy at four participating hospitals were prospectively collected between April 2012 and March 2013. Enrolled subjects were classified according to H. pylori infection status and intake of nonsteroidal anti-inflammatory drugs. Multiple logistic regression analyses were used to determine the risk factors for IPUs. Of 382 enrolled patients with peptic ulcers, 46 (12%) were judged to have IPUs. Compared with those with simple H. pylori-positive ulcers, patients with IPUs were significantly older (P < 0.02) and more often had underlying comorbidities such as hypertension (P < 0.02) and hyperlipidemia (P < 0.05). Multivariate regression analysis indicated that the presence of multiple underlying diseases was the only significant risk factor for IPUs, with an odds ratio of 3.8 (95% confidence interval, 1.3-11.1). This study revealed that the prevalence of IPUs in patients with peptic ulcers in Japan is 12%, much higher than previously reported. Presence of multiple underlying comorbid diseases, rather than aging itself, is an important risk factor for IPUs. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  18. Risk of incident active tuberculosis disease in patients treated with non-steroidal anti-inflammatory drugs: a population-based study.

    Science.gov (United States)

    Wu, Chun-Wei; Wu, Jiunn-Yih; Lee, Meng-Tse Gabriel; Lai, Chih-Cheng; Wu, I-Lin; Tsai, Yi-Wen; Chang, Shy-Shin; Lee, Chien-Chang

    2017-05-04

    Mycobacterium tuberculosis (TB) is one of the world's most devastating public health threats. Our goal is to evaluate whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) affect the risk of new incident active TB disease. We conducted a nested case-control analysis by using a 1 million longitudinally followed cohort, from Taiwan's national health insurance research database. Effects of NSAIDs on active TB were estimated by conditional logistic regression and adjusted using a TB-specific disease risk score (DRS). NSAIDs exposures were defined as having a prescription record of NSAIDs ≧ 7 days that ended between 31 and 90 days prior to the index date. A total of 123,419 users of traditional NSAIDs, 16,392 users of cyclooxygenase-2 selective inhibitor (Coxibs), and 4706 incident cases of active TB were identified. Compared with nonusers, use of traditional NSAIDs was associated with an increased risk of TB in the unadjusted analysis ([RR], 1.39; 95% [CI], 1.24 - 1.57 and DRS adjusted analysis ([ARR], 1.30; 95% [CI], 1.15- 1.47). However, use of Coxibs was not associated with a significant increase in the risk of TB after DRS adjustment ([ARR], 1.23; 95% [CI], 0.89 - 1.70). In this large population-based study, we found that subjects using traditional NSAIDs were associated with increased risk for active TB. We did not find evidence for a causative mechanism between traditional NSAIDs and TB, and more research is required to verify whether the association between traditional NSAIDs and TB is causal, or simply reflects an increased use of anti-inflammatory drugs in the early phases of TB onset.

  19. Susceptibility to excitotoxicity in aged hippocampal cultures and neuroprotection by non-steroidal anti-inflammatory drugs: role of mitochondrial calcium.

    Science.gov (United States)

    Calvo, María; Sanz-Blasco, Sara; Caballero, Erica; Villalobos, Carlos; Núñez, Lucía

    2015-02-01

    Brain damage after insult and cognitive decline are related to excitotoxicity and strongly influenced by aging, yet mechanisms of aging-dependent susceptibility to excitotoxicity are poorly known. Several non-steroidal anti-inflammatory drugs (NSAIDs) may prevent excitotoxicity and cognitive decline in the elderly by an unknown mechanism. Interestingly, after several weeks in vitro, hippocampal neurons display important hallmarks of neuronal aging in vivo. Accordingly, rat hippocampal neurons cultured for several weeks were used to investigate mechanisms of aging-related susceptibility to excitotoxicity and neuroprotection by NSAIDs. We found that NMDA increased cytosolic Ca(2+) concentration in young, mature and aged neurons but only promoted apoptosis in aged neurons. Resting Ca(2+) levels and responses to NMDA increased with time in culture which correlated with changes in expression of NMDA receptor subunits. In addition, NMDA promoted mitochondrial Ca(2+) uptake only in aged cultures. Consistently, specific inhibition of mitochondrial Ca(2+) uptake decreased apoptosis. Finally, we found that a series of NSAIDs depolarized mitochondria and inhibited mitochondrial Ca(2+) overload, thus preventing NMDA-induced apoptosis in aged cultures. We conclude that mitochondrial Ca(2+) uptake is critical for age-related susceptibility to excitotoxicity and neuroprotection by NSAIDs. Rat hippocampal neurons aged in culture were used to investigate mechanisms of age-related susceptibility to excitotoxicity and neuroprotection by non-steroidal anti-inflammatory drugs (NSAIDs). Old neurons display enhanced resting calcium and responses to NMDA along with increased expression of NMDA receptor subunits NR1 and NR2A altogether favoring mitochondrial calcium overload. NSAIDs protect neurons against excitotoxicity acting on mitochondrial calcium uptake. NMDA, N methyl d-aspartate. © 2014 International Society for Neurochemistry.

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  1. Use of Fixed Dose Combination (FDC) Drugs in India: Central Regulatory Approval and Sales of FDCs Containing Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), Metformin, or Psychotropic Drugs.

    Science.gov (United States)

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

    2015-05-01

    In 2012, an Indian parliamentary committee reported that manufacturing licenses for large numbers of fixed dose combination (FDC) drugs had been issued by state authorities without prior approval of the Central Drugs Standard Control Organization (CDSCO) in violation of rules, and considered that some ambiguity until 1 May 2002 about states' powers might have contributed. To our knowledge, no systematic enquiry has been undertaken to determine if evidence existed to support these findings. We investigated CDSCO approvals for and availability of oral FDC drugs in four therapeutic areas: analgesia (non-steroidal anti-inflammatory drugs [NSAIDs]), diabetes (metformin), depression/anxiety (anti-depressants/benzodiazepines), and psychosis (anti-psychotics). This was an ecologic study with a time-trend analysis of FDC sales volumes (2007-2012) and a cross-sectional examination of 2011-2012 data to establish the numbers of formulations on the market with and without a record of CDSCO approval ("approved" and "unapproved"), their branded products, and sales volumes. Data from the CDSCO on approved FDC formulations were compared with sales data from PharmaTrac, a database of national drug sales. We determined the proportions of FDC sales volumes (2011-2012) arising from centrally approved and unapproved formulations and from formulations including drugs banned/restricted internationally. We also determined the proportions of centrally approved and unapproved formulations marketed before and after 1 May 2002, when amendments were made to the drug rules. FDC approvals in India, the United Kingdom (UK), and United States of America (US) were compared. For NSAID FDCs, 124 formulations were marketed, of which 34 (27%) were centrally approved and 90 (73%) were unapproved; metformin: 25 formulations, 20 (80%) approved, five (20%) unapproved; anti-depressants/benzodiazepines: 16 formulations, three (19%) approved, 13 (81%) unapproved; anti-psychotics: ten formulations, three (30

  2. Use of Fixed Dose Combination (FDC Drugs in India: Central Regulatory Approval and Sales of FDCs Containing Non-Steroidal Anti-Inflammatory Drugs (NSAIDs, Metformin, or Psychotropic Drugs.

    Directory of Open Access Journals (Sweden)

    Patricia McGettigan

    2015-05-01

    Full Text Available In 2012, an Indian parliamentary committee reported that manufacturing licenses for large numbers of fixed dose combination (FDC drugs had been issued by state authorities without prior approval of the Central Drugs Standard Control Organization (CDSCO in violation of rules, and considered that some ambiguity until 1 May 2002 about states' powers might have contributed. To our knowledge, no systematic enquiry has been undertaken to determine if evidence existed to support these findings. We investigated CDSCO approvals for and availability of oral FDC drugs in four therapeutic areas: analgesia (non-steroidal anti-inflammatory drugs [NSAIDs], diabetes (metformin, depression/anxiety (anti-depressants/benzodiazepines, and psychosis (anti-psychotics.This was an ecologic study with a time-trend analysis of FDC sales volumes (2007-2012 and a cross-sectional examination of 2011-2012 data to establish the numbers of formulations on the market with and without a record of CDSCO approval ("approved" and "unapproved", their branded products, and sales volumes. Data from the CDSCO on approved FDC formulations were compared with sales data from PharmaTrac, a database of national drug sales. We determined the proportions of FDC sales volumes (2011-2012 arising from centrally approved and unapproved formulations and from formulations including drugs banned/restricted internationally. We also determined the proportions of centrally approved and unapproved formulations marketed before and after 1 May 2002, when amendments were made to the drug rules. FDC approvals in India, the United Kingdom (UK, and United States of America (US were compared. For NSAID FDCs, 124 formulations were marketed, of which 34 (27% were centrally approved and 90 (73% were unapproved; metformin: 25 formulations, 20 (80% approved, five (20% unapproved; anti-depressants/benzodiazepines: 16 formulations, three (19% approved, 13 (81% unapproved; anti-psychotics: ten formulations, three (30

  3. Oxicam structure in non-steroidal anti-inflammatory drugs is essential to exhibit Akt-mediated neuroprotection against 1-methyl-4-phenyl pyridinium-induced cytotoxicity.

    Science.gov (United States)

    Tasaki, Yoshikazu; Yamamoto, Joe; Omura, Tomohiro; Noda, Toshihiro; Kamiyama, Naoya; Yoshida, Koichi; Satomi, Machiko; Sakaguchi, Tomoki; Asari, Masaru; Ohkubo, Tomoko; Shimizu, Keiko; Matsubara, Kazuo

    2012-02-15

    In the treatment of Parkinson's disease, potent disease-modifying drugs are still needed to halt progressive dopaminergic neurodegeneration. We have previously shown that meloxicam, an oxicam non-steroidal anti-inflammatory drug (NSAID), elicits a potent neuroprotective effect against 1-methyl-4-phenyl pyridinium (MPP(+))-induced toxicity in human dopaminergic SH-SY5Y neuroblastoma cells. This cyclooxygenase-independent neuroprotection of meloxicam is mediated via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway; however, the specific chemical structure involved in inducing neuroprotection remains unresolved. In this study, we therefore investigated the structure-specific for eliciting the neuroprotective effect by examining a series of NSAIDs against MPP(+) toxicity in SH-SY5Y cells. Three oxicam-bearing NSAIDs showed potent neuroprotective effects, although none of the other 10 oxicam-nonbearing NSAIDs (3 salicylates, 6 coxibs and 1 polyphenol) or 3 piroxicam analogs (including ampiroxicam, a precursor of piroxicam) exerted any neuroprotection. Tenoxicam and piroxicam prevented MPP(+)-induced reduction of phosphorylated Akt levels in cells: a protective mechanism similar to that of meloxicam. Therefore, the oxicam structure was likely to be responsible for exhibiting the neuroprotection by sustaining survival-signaling in dopaminergic cells. The present results raise the possibility that the oxicam-bearing NSAIDs may serve as potential therapeutic drugs to retard or terminate progression of Parkinson's disease via a novel mechanism. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. A questionnaire-based survey on the prescription of non-steroidal anti-inflammatory drugs by physicians in East Asian countries in 2007.

    Science.gov (United States)

    Arakawa, Tetsuo; Fujiwara, Yasuhiro; Sollano, Jose D; Zhu, Qi; Kachintorn, Udom; Rani, Abdul Aziz; Hahm, Ki-Baik; Takahashi, Shin-ichi; Joh, Takashi; Kinoshita, Yoshikazu; Matsumoto, Takayuki; Naito, Yuji; Takeuchi, Koji; Yamagami, Hirokazu; Agustanti, Nenny; Xiong, Huifang; Chen, Xi; Jang, Eun Jung; Furuta, Kenji; Terano, Akira

    2009-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin are widely used clinically but increase the risk of gastrointestinal (GI) complications. To examine the current prescription of NSAIDs and comedication to prevent GI complications from NSAIDs within East Asia by means of a questionnaire survey. Representative members of the Committee of the International Gastrointestinal Consensus Symposium provided a questionnaire to physicians in 6 East Asian countries. A total of 1,568 physicians participated in this survey. Most physicians prescribed nonselective NSAIDs, cyclooxygenase-2 inhibitors (COXIBs) or aspirin for more than 5 patients per week in all countries, with the exception of the prescription of COXIBs in Japan. Of the nonselective NSAIDs, the drug most frequently prescribed as a first choice was loxoprofen (34%), which was mainly prescribed in Japan, followed by diclofenac (30%). The frequency of prescription of comedication with nonselective NSAIDs was higher compared with that for selective COXIBs or aspirin. Physicians in the northern region (China, Japan and Korea) preferred mucoprotective drugs for comedication with NSAIDs or aspirin, while those in southern region (Indonesia, Philippines and Thailand) frequently used proton-pump inhibitors. Among East Asian countries, there are both similarities and differences in the prescription of NSAIDs and of comedication to prevent GI complications.

  5. Sulindac, a nonsteroidal anti-inflammatory drug, selectively inhibits interferon-γ-induced expression of the chemokine CXCL9 gene in mouse macrophages

    International Nuclear Information System (INIS)

    Sakaeda, Yoshiichi; Hiroi, Miki; Shimojima, Takahiro; Iguchi, Mayumi; Kanegae, Haruhide; Ohmori, Yoshihiro

    2006-01-01

    Sulindac, a non-steroidal anti-inflammatory drug, has been shown to exert an anti-tumor effect on several types of cancer. To determine the effect of sulindac on intracellular signaling pathways in host immune cells such as macrophages, we investigated the effect of the drug on interferon gamma (IFNγ)-induced expression of signal transducer and activator of transcription 1 (STAT1) and other genes in mouse macrophage-like cell line RAW264.7 cells. Sulindac, but not aspirin or sodium salicylate, inhibited IFNγ-induced expression of the CXC ligand 9 (CXCL9) mRNA, a chemokine for activated T cells, whereas the interferon-induced expression of CXCL10 or IFN regulatory factor-1 was not affected by sulindac. Luciferase reporter assay demonstrated that sulindac inhibited IFNγ-induced promoter activity of the CXCL9 gene. Surprisingly, sulindac had no inhibitory effect on IFNγ-induced STAT1 activation; however, constitutive nuclear factor κB activity was suppressed by the drug. These results indicate that sulindac selectively inhibited IFNγ-inducible gene expression without inhibiting STAT1 activation

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

    Directory of Open Access Journals (Sweden)

    Elif Borekci

    2017-09-01

    Results: The frequency of prescription of NSAI drug in our hospital were found 34,5%. In the internal and surgical departments, respectively, most often diclofenac (23.1% and dexketoprofen (43.5% were being prescribed. The most frequent cause of prescribing was joint pain (57,7% in the internal departments and postoperative pain (73,9% in the surgical departments. Conclusion: Unnecessary use of NSAI drugs should be avoided because of the high side effect risk despite it's efficacy and benefits and our knowledge of these drugs we prescribe frequently must be updated. [J Contemp Med 2017; 7(3.000: 203-207

  7. P-glycoprotein Modulates Morphine Uptake into the CNS: A Role for the Non-steroidal Anti-inflammatory Drug Diclofenac

    Science.gov (United States)

    Sanchez-Covarrubias, Lucy; Slosky, Lauren M.; Thompson, Brandon J.; Zhang, Yifeng; Laracuente, Mei-Li; DeMarco, Kristin M.; Ronaldson, Patrick T.; Davis, Thomas P.

    2014-01-01

    Our laboratory has previously demonstrated that peripheral inflammatory pain (PIP), induced by subcutaneous plantar injection of λ-carrageenan, results in increased expression and activity of the ATP-dependent efflux transporter P-glycoprotein (P-gp) that is endogenously expressed at the blood-brain barrier (BBB). The result of increased P-gp functional expression was a significant reduction in CNS uptake of morphine and, subsequently, reduced morphine analgesic efficacy. A major concern in the treatment of acute pain/inflammation is the potential for drug-drug interactions resulting from P-gp induction by therapeutic agents co-administered with opioids. Such effects on P-gp activity can profoundly modulate CNS distribution of opioid analgesics and alter analgesic efficacy. In this study, we examined the ability of diclofenac, a non-steroidal anti-inflammatory drug (NSAID) that is commonly administered in conjunction with the opioids during pain therapy, to alter BBB transport of morphine via P-gp and whether such changes in P-gp morphine transport could alter morphine analgesic efficacy. Administration of diclofenac reduced paw edema and thermal hyperalgesia in rats subjected to PIP, which is consistent with the known mechanism of action of this NSAID. Western blot analysis demonstrated an increase in P-gp expression in rat brain microvessels not only following PIP induction but also after diclofenac treatment alone. Additionally, in situ brain perfusion studies showed that both PIP and diclofenac treatment alone increased P-gp efflux activity resulting in decreased morphine brain uptake. Critically, morphine analgesia was significantly reduced in animals pretreated with diclofenac (3 h), as compared to animals administered diclofenac and morphine concurrently. These novel findings suggest that administration of diclofenac and P-gp substrate opioids during pain pharmacotherapy may result in a clinically significant drug-drug interaction. PMID:24520393

  8. P-glycoprotein modulates morphine uptake into the CNS: a role for the non-steroidal anti-inflammatory drug diclofenac.

    Science.gov (United States)

    Sanchez-Covarrubias, Lucy; Slosky, Lauren M; Thompson, Brandon J; Zhang, Yifeng; Laracuente, Mei-Li; DeMarco, Kristin M; Ronaldson, Patrick T; Davis, Thomas P

    2014-01-01

    Our laboratory has previously demonstrated that peripheral inflammatory pain (PIP), induced by subcutaneous plantar injection of λ-carrageenan, results in increased expression and activity of the ATP-dependent efflux transporter P-glycoprotein (P-gp) that is endogenously expressed at the blood-brain barrier (BBB). The result of increased P-gp functional expression was a significant reduction in CNS uptake of morphine and, subsequently, reduced morphine analgesic efficacy. A major concern in the treatment of acute pain/inflammation is the potential for drug-drug interactions resulting from P-gp induction by therapeutic agents co-administered with opioids. Such effects on P-gp activity can profoundly modulate CNS distribution of opioid analgesics and alter analgesic efficacy. In this study, we examined the ability of diclofenac, a non-steroidal anti-inflammatory drug (NSAID) that is commonly administered in conjunction with the opioids during pain therapy, to alter BBB transport of morphine via P-gp and whether such changes in P-gp morphine transport could alter morphine analgesic efficacy. Administration of diclofenac reduced paw edema and thermal hyperalgesia in rats subjected to PIP, which is consistent with the known mechanism of action of this NSAID. Western blot analysis demonstrated an increase in P-gp expression in rat brain microvessels not only following PIP induction but also after diclofenac treatment alone. Additionally, in situ brain perfusion studies showed that both PIP and diclofenac treatment alone increased P-gp efflux activity resulting in decreased morphine brain uptake. Critically, morphine analgesia was significantly reduced in animals pretreated with diclofenac (3 h), as compared to animals administered diclofenac and morphine concurrently. These novel findings suggest that administration of diclofenac and P-gp substrate opioids during pain pharmacotherapy may result in a clinically significant drug-drug interaction.

  9. P-glycoprotein modulates morphine uptake into the CNS: a role for the non-steroidal anti-inflammatory drug diclofenac.

    Directory of Open Access Journals (Sweden)

    Lucy Sanchez-Covarrubias

    Full Text Available Our laboratory has previously demonstrated that peripheral inflammatory pain (PIP, induced by subcutaneous plantar injection of λ-carrageenan, results in increased expression and activity of the ATP-dependent efflux transporter P-glycoprotein (P-gp that is endogenously expressed at the blood-brain barrier (BBB. The result of increased P-gp functional expression was a significant reduction in CNS uptake of morphine and, subsequently, reduced morphine analgesic efficacy. A major concern in the treatment of acute pain/inflammation is the potential for drug-drug interactions resulting from P-gp induction by therapeutic agents co-administered with opioids. Such effects on P-gp activity can profoundly modulate CNS distribution of opioid analgesics and alter analgesic efficacy. In this study, we examined the ability of diclofenac, a non-steroidal anti-inflammatory drug (NSAID that is commonly administered in conjunction with the opioids during pain therapy, to alter BBB transport of morphine via P-gp and whether such changes in P-gp morphine transport could alter morphine analgesic efficacy. Administration of diclofenac reduced paw edema and thermal hyperalgesia in rats subjected to PIP, which is consistent with the known mechanism of action of this NSAID. Western blot analysis demonstrated an increase in P-gp expression in rat brain microvessels not only following PIP induction but also after diclofenac treatment alone. Additionally, in situ brain perfusion studies showed that both PIP and diclofenac treatment alone increased P-gp efflux activity resulting in decreased morphine brain uptake. Critically, morphine analgesia was significantly reduced in animals pretreated with diclofenac (3 h, as compared to animals administered diclofenac and morphine concurrently. These novel findings suggest that administration of diclofenac and P-gp substrate opioids during pain pharmacotherapy may result in a clinically significant drug-drug interaction.

  10. The impact of combinations of non-steroidal anti-inflammatory drugs and anti-hypertensive agents on blood pressure.

    Science.gov (United States)

    Kalafutova, Stanislava; Juraskova, Bozena; Vlcek, Jiri

    2014-01-01

    Nowadays NSAIDs are the most frequently used groups of drugs, especially because of their availability. Their consumption is high among older people, who are much more sensitive to the side effects, and who are often also taking other drugs which can interact with them. Moreover, the majority of the older population is suffering from hypertension. This could well explain the commonly encountered experience of drug interaction between NSAIDs and antihypertensive drugs, which is very common in clinical practice. The severity of this drug interaction is classified as class C, with a recommendation to monitor therapy. However, even a minor long-term increase in blood pressure can significantly increase the risk of cardiovascular mortality, while mortality rates can possibly be reduced by sufficiently effective treatment of hypertension. Therefore, in clinical practice, this type of interaction should not be overlooked as a major cause of failure of hypertension treatment in older patients, as well in many cases in general. The present article focusses on the mechanism and the degree of influence on the blood pressure of particular types of antihypertensive agents used in combination with NSAID. Not all groups of antihypertensive drugs are affected to the same degree; some are more affected, and others, such as calcium channel blockers, are not affected at all. Similarly, not every NSAID increases blood pressure. Many studies, some of which are analyzed in this article, present evidence of the degree of the influence NSAIDs have on blood pressure.

  11. Synergistic Interplay of Medicinal Chemistry and Formulation Strategies in Nanotechnology - From Drug Discovery to Nanocarrier Design and Development.

    Science.gov (United States)

    Sunoqrot, Suhair; Hamed, Rania; Abdel-Halim, Heba; Tarawneh, Ola

    2017-01-01

    Over the last few decades, nanotechnology has given rise to promising new therapies and diagnostic tools for a wide range of diseases, especially cancer. The unique properties of nanocarriers such as liposomes, polymeric nanoparticles, micelles, and bioconjugates have mainly been exploited to enhance drug solubility, dissolution, and bioavailability. The most important advantage offered by nanotechnology is the ability to specifically target organs, tissues, and individual cells, which ultimately reduces the systemic side effects and improves the therapeutic index of drug molecules. The contribution of medicinal chemistry to nanotechnology is evident in the abundance of new active molecules that are being discovered but are faced with tremendous delivery challenges by conventional formulation strategies. Additionally, medicinal chemistry plays a crucial role in all the steps involved in the preparation of nanocarriers, where structure-activity relationships of the drug molecule as well as the nanocarrier are harnessed to enhance the design, efficacy, and safety of nanoformulations. The aim of this review is to provide an overview of the contributions of medicinal chemistry to nanotechnology, from supplying drug candidates and inspiring high-throughput nanocarrier design strategies, to structure-activity relationship elucidation and construction of computational models for better understanding of nanocarrier physicochemical properties and biological behavior. These two fields are undoubtedly interconnected and we will continue to see the fruits of that communion for years to come. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Energy Technology Data Exchange (ETDEWEB)

    Nadanaciva, Sashi [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States); Aleo, Michael D. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Strock, Christopher J. [Cyprotex US, Watertown, MA 02472 (United States); Stedman, Donald B. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Wang, Huijun [Computational Sciences, Pfizer Inc., Groton, CT 06340 (United States); Will, Yvonne, E-mail: yvonne.will@pfizer.com [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States)

    2013-10-15

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  14. Non-steroidal anti-inflammatory drugs disturb the osmoregulatory, metabolic and cortisol responses associated with seawater exposure in rainbow trout.

    Science.gov (United States)

    Gravel, Amélie; Wilson, Jonathan M; Pedro, Dalila F N; Vijayan, Mathilakath M

    2009-05-01

    While detectable levels of non-steroidal anti-inflammatory drugs (NSAIDs) have been reported in various aquatic habitats, little is known about the mechanism of action of these pharmaceutical drugs on organisms. Recently we demonstrated that NSAIDs disrupt corticosteroidogenesis in rainbow trout (Oncorhynchus mykiss). As cortisol is a seawater adapting hormone, we hypothesized that exposure to NSAIDs will impair the hyposmoregulatory capacity of this species in seawater. Trout were exposed to either waterborne salicylate or ibuprofen in fresh water for four days and the salinity switched to 50% seawater for two days, followed by 100% seawater and sampled two days later. NSAIDs disturbed the seawater-induced elevation in plasma osmolality and concentrations of Cl(-) and K(+), but not Na(+) in rainbow trout. This was accompanied by enhanced gill glycolytic capacity and reduced liver glycogen content in seawater with NSAIDs, suggesting enhanced metabolic demand to fuel ion pumps. While salicylate did not affect gill Na(+)/K(+)-ATPase activity, ibuprofen inhibited the seawater-induced elevation in gill Na(+)/K(+)-ATPase activity. The drugs also further enhanced the seawater-induced elevation in plasma cortisol concentration; this response was greater with salicylate compared to ibuprofen. There were no changes in the transcript levels of key proteins involved in steroidogenesis with NSAIDs, whereas gill and brain GR protein expression expression was reduced with salicylate. Altogether, salicylate and ibuprofen exposures impaired the hyposmoregulatory capacity of rainbow trout in seawater, but the mode of action of the two drugs in bringing about these changes appears distinct in trout.

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

    Directory of Open Access Journals (Sweden)

    Alejo J Nevado-Holgado

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

  16. Nonsteroidal Anti-inflammatory Drugs Utilization Patterns among the Elderly with Osteoarthritis at Primary Ambulatory Care Units in Busan Metropolitan City, Korea.

    Science.gov (United States)

    Choi, Nam Kyong; Kim, Yooni; Lee, Seung Mi; Park, Byung Joo

    2004-05-01

    To investigate the utilization patterns of non-steroidal anti-inflammatory drugs (NSAIDs) among the elderly with osteoarthritis (OA) undergoing primary ambulatory care in Busan metropolitan city, Korea. OA patients, aged 65 years and over, were identified from the Korean National Health Insurance Review Agency drug prescription database. The subjects had at least one episode of claim for OA (ICD-10-CM: M15-M19) between August 1, 2000 and February 28, 2002. Trends in the determinations of NSAIDs utilization were identified using chi-squared tests for trend. There were 47, 711 osteoarthritic patients. The total number of visits by these patients was 177, 443, with a total frequency for NSAID prescriptions of 214, 952. Seventy-nine percent of the OA patients were female. NSAIDs were prescribed on 133, 284 visits (75.1%) and the proportion of prescriptions was significantly increased with age. Only the proportion of visit when NSAIDs were prescribed decreased, from 65.1 to 43.5%, during the study period (p< 0.001). However, the proportion of combined treatments with anti-ulcer drugs was increased. The use of NSAIDs injections was decreased. Of the individual NSAIDs, diclofenac (28.7% of total frequency of NSAID prescriptions), piroxicam (15.0%) and talniflumate (8.7%), were the most frequently prescribed. Among the NSAIDs prescribed OA visits, 45.7% used two or more NSAIDs. The total proportion of NSAIDs prescribed to the osteoarthritic patients was higher than in other studies. The decline in the use of NSAIDs during the study period, and the frequent selection of safer medications, such as combination therapy with anti-ulcer drug, may reflect the risk awareness of the use of NSAIDs.

  17. Maintenance treatment with esomeprazole following initial relief of non-steroidal anti-inflammatory drug-associated upper gastrointestinal symptoms: the NASA2 and SPACE2 studies

    Science.gov (United States)

    Hawkey, Christopher J; Talley, Nicholas J; Scheiman, James M; Jones, Roger H; Långström, Göran; Næsdal, Jorgen; Yeomans, Neville D

    2007-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclo-oxygenase-2 (COX-2) inhibitors, cause upper gastrointestinal (GI) symptoms that are relieved by treatment with esomeprazole. We assessed esomeprazole for maintaining long-term relief of such symptoms. Six hundred and ten patients with a chronic condition requiring anti-inflammatory therapy who achieved relief of NSAID-associated symptoms of pain, discomfort, or burning in the upper abdomen during two previous studies were enrolled and randomly assigned into two identical, multicentre, parallel-group, placebo-controlled studies of esomeprazole 20 mg or 40 mg treatment (NASA2 [Nexium Anti-inflammatory Symptom Amelioration] and SPACE2 [Symptom Prevention by Acid Control with Esomeprazole] studies; ClinicalTrials.gov identifiers NCT00241514 and NCT00241553, respectively) performed at various rheumatology, gastroenterology, and primary care clinics. Four hundred and twenty-six patients completed the 6-month treatment period. The primary measure was the proportion of patients with relapse of upper GI symptoms, recorded in daily diary cards, after 6 months. Relapse was defined as moderate-to-severe upper GI symptoms (a score of more than or equal to 3 on a 7-grade scale) for 3 days or more in any 7-day period. Esomeprazole was significantly more effective than placebo in maintaining relief of upper GI symptoms throughout 6 months of treatment. Life-table estimates (95% confidence intervals) of the proportion of patients with relapse at 6 months (pooled population) were placebo, 39.1% (32.2% to 46.0%); esomeprazole 20 mg, 29.3% (22.3% to 36.2%) (p = 0.006 versus placebo); and esomeprazole 40 mg, 26.1% (19.4% to 32.9%) (p = 0.001 versus placebo). Patients on either non-selective NSAIDs or selective COX-2 inhibitors appeared to benefit. The frequency of adverse events was similar in the three groups. Esomeprazole maintains relief of NSAID-associated upper GI symptoms in patients taking continuous

  18. Cymbopogon citratus as source of new and safe anti-inflammatory drugs: bio-guided assay using lipopolysaccharide-stimulated macrophages.

    Science.gov (United States)

    Francisco, Vera; Figueirinha, Artur; Neves, Bruno Miguel; García-Rodríguez, Carmen; Lopes, Maria Celeste; Cruz, Maria Teresa; Batista, Maria Teresa

    2011-01-27

    anti-inflammatory drug. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

    Honoré, B; Brodersen, R

    1984-01-01

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

  20. Neutrophil migration towards C5a and CXCL8 is prevented by non-steroidal anti-inflammatory drugs via inhibition of different pathways

    Science.gov (United States)

    Bertolotto, Maria; Contini, Paola; Ottonello, Luciano; Pende, Aldo; Dallegri, Franco; Montecucco, Fabrizio

    2014-01-01

    BACKGROUND AND PURPOSE Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to induce PG-independent anti-inflammatory actions. Here, we investigated the role of three different NSAIDs (naproxen, ibuprofen and oxaprozin) on neutrophil responses to CXCL8 and C5a. EXPERIMENTAL APPROACH Human neutrophils were isolated from healthy volunteers by dextran and Ficoll-Hypaque density gradients. Neutrophils were pre-incubated with different concentrations (1–100 µM) of NSAIDs or kinase inhibitors. Neutrophil degranulation into supernatants was tested by elisa and zymography. Neutrophil chemotaxis was determined using Boyden chambers. F-actin polymerization was determined by Alexa-Fluor 488-conjugated phalloidin fluorescent assay. Integrin expression was assessed by flow cytometry. The phosphorylation of intracellular kinases was studied by Western blot. KEY RESULTS Pretreatment with NSAIDs did not affect neutrophil degranulation, but inhibited neutrophil migration and polymerization of F-actin, in response to CXCL8 and C5a. Pretreatment with different NSAIDs prevented C5a-induced integrin (CD11b) up-regulation, while only ibuprofen reduced CXCL8-induced CD11b up-regulation. Pre-incubation with naproxen or oxaprozin, but not ibuprofen, inhibited the PI3K/Akt-dependent chemotactic pathways. Both endogenous (released in cell supernatants) or exogenous (added to cell cultures) PGE2 did not affect C5a- or CXCL8-induced activities. Short-term incubation with NSAIDs did not affect neutrophil PGE2 release. CONCLUSION AND IMPLICATIONS Treatment with NSAIDs reduced C5a- and CXCL8-induced neutrophil migration and F-actin polymerization via different mechanisms. Inhibition by ibuprofen was associated with integrin down-regulation, while naproxen and oxaprozin blocked the PI3K/Akt pathway. Both NSAID actions were independent of COX inhibition and PGE2 release. PMID:24597536

  1. Status of non-steroidal anti-inflammatory drugs use and its association with chronic kidney disease: a cross-sectional survey in China.

    Science.gov (United States)

    Pan, Yujing; Zhang, Luxia; Wang, Fang; Li, Xiaomei; Wang, Haiyan

    2014-10-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to be associated with adverse effects including kidney injury, while relevant studies from developing countries are limited. We aimed to explore the status of NSAIDs use in China, as well as cross-sectional association between NSAIDs intake and presence of chronic kidney disease (CKD). A national representative sample of 47,204 adults in China was used. Prevalence of regular NSAIDs use was reported. Age- and sex- matched controls of NSAIDs users were then selected. The association between NSAIDs use and kidney injury were analyzed using logistic regression. Altogether 1129 participants reported regular use of NSAIDs, with the adjusted prevalence of 3.6% (95% CI, 3.2%-3.9%). And 76.9% of them (n = 868) had taken phenacetin-containing analgesics, with an adjusted prevalence of 3.2% (95% CI, 2.9%-3.5%). After adjusting for potential confounders, long-term NSAIDs intake (≥ 48 months) was associated with eGFR < 60 mL/min per 1.73 m2, with an OR of 2.36 (95% CI, 1.28-4.37). Regular use of NSAIDs, especially phenacetin-containing drugs, is prevalent in China. And long-term NSAIDs intake (≥ 48 months) was independently associated with reduced renal function. © 2014 Asian Pacific Society of Nephrology.

  2. The nonsteroidal anti-inflammatory drug tolfenamic acid inhibits BT474 and SKBR3 breast cancer cell and tumor growth by repressing erbB2 expression.

    Science.gov (United States)

    Liu, Xinyi; Abdelrahim, Maen; Abudayyeh, Ala; Lei, Ping; Safe, Stephen

    2009-05-01

    Tolfenamic acid (TA) is a nonsteroidal anti-inflammatory drug that inhibits pancreatic cancer cell and tumor growth through decreasing expression of specificity protein (Sp) transcription factors. TA also inhibits growth of erbB2-overexpressing BT474 and SKBR3 breast cancer cells; however, in contrast to pancreatic cancer cells, TA induced down-regulation of erbB2 but not Sp proteins. TA-induced erbB2 down-regulation was accompanied by decreased erbB2-dependent kinase activities, induction of p27, and decreased expression of cyclin D1. TA also decreased erbB2 mRNA expression and promoter activity, and this was due to decreased mRNA stability in BT474 cells and, in both cell lines, TA decreased expression of the YY1 and AP-2 transcription factors required for basal erbB2 expression. In addition, TA also inhibited tumor growth in athymic nude mice in which BT474 cells were injected into the mammary fat pad. TA represents a novel and promising new anticancer drug that targets erbB2 by decreasing transcription of this oncogene.

  3. Knowledge and Use of, and Attitudes toward, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in Practice: A Survey of Ontario Physiotherapists.

    Science.gov (United States)

    Green, Maggie; Norman, Kathleen E

    Purpose: To investigate Ontario physiotherapists' knowledge and use of, and attitudes toward, non-steroidal anti-inflammatory drugs (NSAIDs) to identify whether there is a need for physiotherapists to receive education specific to NSAIDs. Method: An existing survey instrument was modified and tested by five Ontario physiotherapists. The final version was distributed electronically to approximately 4,400 Ontario Physiotherapy Association members as a self-administered online questionnaire. Results: A total of 294 physiotherapists responded to the survey (response rate=6.7%). Respondents demonstrated variability in their knowledge of NSAID contraindications, side effects, and drug interactions. Most respondents (62.6%) were incorrect or unsure about where and how to obtain most NSAIDs, and most demonstrated incorrect or uncertain knowledge of the relevant legislation. Despite this lack of knowledge, 50% of respondents recommend NSAIDs to their patients. Conclusions: Many Ontario physiotherapists who participated in this survey recommend NSAIDs to their patients despite having a variable understanding of the legislation and medication-related factors. A lack of thorough knowledge of risks and contraindications has implications for patient safety. Physiotherapists who incorporate medications into their practice should access comprehensive information on appropriate NSAID use and should inform themselves about legislative restrictions to ensure that associated treatment is provided in a manner that is evidence based, safe, and in keeping with regulatory boundaries.

  4. Effects of nonsteroidal anti-inflammatory drugs on the expression and function of P-glycoprotein/MDR1 in Caco-2 cells.

    Science.gov (United States)

    Takara, Kohji; Hayashi, Ryuhei; Kokufu, Misato; Yamamoto, Kazuhiro; Kitada, Noriaki; Ohnishi, Noriaki; Yokoyama, Teruyoshi

    2009-01-01

    The aim of this study was to examine the effects of 16 kinds of nonsteroidal anti-inflammatory drugs (NSAIDs) on P-glycoprotein/MDR1 in Caco-2 cells as an intestinal epithelial cell model. Cells were treated with NSAIDs for 24 hours, and then, the expression of MDR1 mRNA was evaluated by reverse-transcriptase polymerase chain reaction. The function of MDR1 in cells pretreated with NSAIDs for 48 hours was evaluated by measuring the cellular amount of rhodamine123, which is a substrate of MDR1. The expression of MDR1 mRNA was increased by diclofenac, fenbufen, indomethacin, and nimesulide and the tended to be increased by meloxicam, mepirizole, and sulindac. However, pretreatment for 48 hours with diclofenac, indomethacin, or nimesulide, but not fenbufen, resulted in a significant increase in the amount of rhodamine123 accumulated. Although NSAIDs without effects on the expression of MDR1 mRNA altered the accumulation of rhodamine123 significantly, the efflux of rhodamine123 from cells was unchanged. In conclusion, the expression of MDR1 mRNA in Caco-2 cells was demonstrated to be increased by treatment with some NSAIDs, although the transport function of MDR1 was unchanged. These findings imply that the NSAIDs did not cause the drug interaction via MDR1 induction.

  5. Dilemma of Timing of Administration of Non-Steroidal Anti-inflammatory Agents in Relation to Food in the Prevention of Drug Induced Gastritis: Debusting the Myth.

    Science.gov (United States)

    Udaykumar, Padmaja; Udaykumar, K; Scandashree, K; Anurag, K

    2016-01-01

    We aimed to identify the signals that indicate the possible benefits of administering Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) at the initiation of meal, compared to immediately after food. This was a randomized, controlled, pilot study in 160 patients who received only NSAIDs for various pain conditions. Patients were randomized to Group I (control group) -NSAID After Food (AF), Group II-NSAID Before Food (BF), Group III-NSAID BF for 2 days and then crossed over to AF for next two days (CO-1) and Group IV-NSAID AF for 2 days and then crossed over to BF for next two days (C0-2 group). Group III & Group IV were given a washout period of 48 hours after the initial two days of treatment. All were followed up for the next 2 drug free days. Patients were observed for the development of gastritis (epigastric distress, epigastric pain, nausea, fullness of stomach, repeated reflux) throughout the study. Symptoms of gastritis were seen in 6.45% (2/31) and 36.11% (13/36) patients in group I and II, respectively. There was no statistically significant difference in the development of gastritis in AF group. However, statistically significant difference (Pgastritis. Administering NSAIDs at the initiation of meal is better tolerated as indicated by the lower incidence of gastritis. If proved in larger population, routine concurrent administration of medication for prevention of gastritis can be avoided.

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

    Directory of Open Access Journals (Sweden)

    Richard H Hunt

    2003-01-01

    Full Text Available Traditional nonsteroidal anti-inflammatory drugs (NSAIDs are known to cause gastritis, gastric and duodenal ulcers, and gastrointestinal (GI blood loss, as well as alterations in small bowel permeability. Patients at a high risk for these complications include those who are older than 60 years of age, those with a previous history of complicated peptic disease and bleeding, and those who take high dose or multiple NSAIDs, including low dose aspirin, corticosteroids or anticoagulants. The introduction of selective inhibitors of cyclo-oxygenase-2 (COX-2 has provided effective treatment of inflammatory arthritis and musculoskeletal pain, with dramatic reductions in the risk of GI adverse events. The two most widely prescribed coxibs are celecoxib and rofecoxib, and others are being developed. Endoscopic studies have revealed that coxibs are only half as likely to induce upper GI ulceration than are traditional NSAIDs, and are as safe as placebo. Furthermore, the newer drugs do not cause excessive blood loss from the GI tract and do not affect small bowel permeability. The Vioxx Gastrointestinal Outcomes Research Study (VIGOR revealed that the incidence of myocardial infarction was significantly lower with naproxen than rofecoxib, although this study was not designed to look at this endpoint. Coxibs are an important addition to the pharmacotherapy of inflammatory disease.

  7. Magnetic solid-phase extraction of non-steroidal anti-inflammatory drugs from environmental water samples using polyamidoamine dendrimer functionalized with magnetite nanoparticles as a sorbent.

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    Alinezhad, Heshmatollah; Amiri, Amirhassan; Tarahomi, Mehrasa; Maleki, Behrooz

    2018-06-01

    A novel polyamidoamine dendrimer functionalized with Fe 3 O 4 nanoparticles (Fe 3 O 4 @PAMAM) had been fabricated and used as magnetic solid-phase extraction (MSPE) adsorbent. The Fe 3 O 4 @PAMAM nanocomposites were characterized by X-ray powder diffraction, Fourier transform infrared spectroscopy, field-emission scanning electron spectroscopy, elemental analytical, and thermal gravimetric analysis. The MSPE method coupled with high-performance liquid chromatography with an ultraviolet detection system was applied for the separation/analysis of non-steroidal anti-inflammatory drugs (NSAIDs). Major parameters affecting the extraction efficiency of the selected drugs were optimized. Under optimal conditions, the enrichment factors for the proposed method were 701835. The linear range, limit of detection, correlation coefficient (r), and relative standard deviation (RSD) were found to be 0.15-500 ng mL -1 , 0.050.08 ng mL -1 , 0.99320.9967, and 4.5-7.0% (n = 5, 0.2, 10 and 300 ng mL -1 ), respectively. The method was successfully applied to the determination of NSAIDs in the real water samples. The recoveries of spiked water samples were in the range of 93.6-98.9% with RSDs varying from 6.1% to 9.0%, showing the good accuracy of the method. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Supramolecular chiro-biomedical assays and enantioselective HPLC analyses for evaluation of profens as non-steroidal anti-inflammatory drugs, potential anticancer agents and common xenobiotics.

    Science.gov (United States)

    Ali, Imran; Hussain, Iqbal; Saleem, Kishwar; Aboul-Enein, Hassan Y; Bazylak, Grzegorz

    2008-06-01

    The permanent world-wide increase in therapeutic administration of racemic profens as easy available non-prescribed analgesic drugs and a common first-choice anti-inflammatory agents was recently linked with renewed interest in their beneficial use, also as enantiopure formulations, to treat and/or prevent a variety of human malignancies including its four major types as colorectal, breast, lung, and prostate cancer. This underlies the continuous need of selecting perfectly suited chiral separation methods of profens capable to determine nanolevels of a distomer in presence of the eutomer in a variety of complex biological and environmental media. Thus, current improvements for direct enantiomeric separations of profens by well defined supramolecular-based chiral HPLC and recently developed monolithic, combinatorial, bimodal and polymeric chiral stationary phases employing a modern supramolecular chirality concepts has been outlined in this review. The use of diverse supramolecular approaches for chiral HPLC as an easy accessible tool enabling fast development of nanoscale enantioselective, high-throughput and gradient screening procedures for in situ monitoring of stereoselective ADME properties of profens in range of anticancer drug discovery technologies has been also addressed.

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

    Science.gov (United States)

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

    2016-09-01

    Non-steroidal anti-inflammatory drug, Diclofenac, targeting COX have shown promise in the treatment of Acanthamoeba keratitis, but the underlying mechanisms remain unknown. Using various NSAIDs, Diclofenac sodium, Indomethacin, and Acetaminophen, here we determined the effects of NSAIDs on the biological properties of Acanthamoeba castellanii belonging to the T4 genotype. Using amoebicidal assays, the results revealed that Diclofenac sodium, and Indomethacin affected growth of A. castellanii. In contrast, none of the compounds tested had any effect on the viability of A. castellanii. Importantly, all NSAIDs tested abolished A. castellanii encystation. This is a significant finding as the ability of amoebae to transform into the dormant cyst form presents a significant challenge in the successful treatment of infection. The NSAIDs inhibit production of cyclo-oxegenase, which regulates the synthesis of prostaglandins suggesting that cyclooxygenases (COX-1 and COX-2) and prostaglandins play significant role(s) in Acanthamoeba biology. As NSAIDs are routinely used in the clinical practice, these findings may help design improved preventative strategies and/or of therapeutic value to improve prognosis, when used in combination with other anti-amoebic drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2017-12-01

    Full Text Available Paeoniflorin-6′-O-benzene sulfonate (code: CP-25 was the chemistry structural modifications of Paeoniflorin (Pae. CP-25 inhibited B cells proliferation stimulated by B cell activating factor belonging to the TNF family (BAFF or Tumor necrosis factor alpha (TNF-alpha. CP-25, Rituximab and Etanercept reduced the percentage and numbers of CD19+ B cells, CD19+CD20+ B cells, CD19+CD27+ B cells and CD19+CD20+CD27+ B cells induced by BAFF or TNF-alpha. There was significant difference between CP-25 and Rituximab or CP-25 and Etanercept. CP-25 down-regulated the high expression of BAFFR, BCMA, and TACI stimulated by BAFF or TNF-alpha. The effects of Rituximab and Etanercept on BAFFR or BCMA were stronger than that of CP-25. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2, and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha. These results suggest that CP-25 regulated moderately activated B cells function by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.

  11. CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents.

    Science.gov (United States)

    Zhang, Feng; Shu, Jin-Ling; Li, Ying; Wu, Yu-Jing; Zhang, Xian-Zheng; Han, Le; Tang, Xiao-Yu; Wang, Chen; Wang, Qing-Tong; Chen, Jing-Yu; Chang, Yan; Wu, Hua-Xun; Zhang, Ling-Ling; Wei, Wei

    2017-01-01

    Paeoniflorin-6'- O -benzene sulfonate (code: CP-25) was the chemistry structural modifications of Paeoniflorin (Pae). CP-25 inhibited B cells proliferation stimulated by B cell activating factor belonging to the TNF family (BAFF) or Tumor necrosis factor alpha (TNF-alpha). CP-25, Rituximab and Etanercept reduced the percentage and numbers of CD19 + B cells, CD19 + CD20 + B cells, CD19 + CD27 + B cells and CD19 + CD20 + CD27 + B cells induced by BAFF or TNF-alpha. There was significant difference between CP-25 and Rituximab or CP-25 and Etanercept. CP-25 down-regulated the high expression of BAFFR, BCMA, and TACI stimulated by BAFF or TNF-alpha. The effects of Rituximab and Etanercept on BAFFR or BCMA were stronger than that of CP-25. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2, and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha. These results suggest that CP-25 regulated moderately activated B cells function by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.

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

    Directory of Open Access Journals (Sweden)

    Diana Pérez-Alzate

    2016-07-01

    Full Text Available In subjects with non-steroidal anti-inflammatory drugs (NSAIDs- exacerbated respiratory disease (NERD symptoms are triggered by acetyl salicylic acid (ASA and other strong COX-1 inhibitors, and in some cases by weak COX-1 or by selective COX-2 inhibitors. The mechanism involved is related to prostaglandin pathway inhibition and leukotriene release. Subjects who react to a single NSAID and tolerate others are considered selective responders, and often present urticaria and/or angioedema and anaphylaxis (SNIUAA. An immunological mechanism is implicated in these reactions. However, anecdotal evidence suggests that selective responders who present respiratory airway symptoms may also exist.Our objective was to determine if subjects might develop selective responses to NSAIDs/paracetamol that manifest as upper/lower airways respiratory symptoms. For this purpose we studied patients reporting asthma and/or rhinitis induced by paracetamol or a single NSAID that tolerated ASA. An allergological evaluation plus controlled challenge with ASA was carried out. If ASA tolerance was found, we proceeded with an oral challenge with the culprit drug. The appearance of symptoms was monitored by a clinical questionnaire and by measuring FEV1 and/or nasal airways volume changes pre and post challenge. From a total of 21 initial cases, we confirmed the appearance of nasal and/or bronchial manifestations in ten, characterised by a significant decrease in FEV1% and/or a decrease in nasal volume cavity after drug administration. All cases tolerated ASA.This shows that ASA tolerant subjects with asthma and/or rhinitis induced by paracetamol or a single NSAID without skin/systemic manifestations exist. Whether these patients represent a new clinical phenotype to be included within the current classification of hypersensitivity reactions to NSAIDs requires further investigation.

  13. Sub-lethal effects induced by a mixture of three non-steroidal anti-inflammatory drugs (NSAIDs) on the freshwater bivalve Dreissena polymorpha.

    Science.gov (United States)

    Parolini, Marco; Binelli, Andrea

    2012-03-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the sixth top-selling drugs worldwide and are commonly found in freshwater ecosystems in the high ng/l to low μg/l range. Recent studies have investigated both the acute and the chronic toxicity of single NSAIDs on different biological models, but these studies have completely neglected the fact that, in the environment, non-target organisms are exposed to mixtures of drugs that have unforeseeable toxicological behavior. This work investigated the sub-lethal effects induced by a mixture of three common NSAIDs, namely, diclofenac, ibuprofen and paracetamol, on the freshwater bivalve, the zebra mussel (Dreissena polymorpha). The mussels were exposed to three different environmental concentrations of the mixture (Low, Mid and High). A multi-biomarker approach was used to highlight cyto-genotoxic effects and the imbalance of the oxidative status of the treated specimens. The Neutral Red Retention Assay (NRRA) was used as a biomarker of cytotoxicity, whereas the activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione S-transferase were measured to assess the role played by the oxidative stress enzymes. In addition, the single cell gel electrophoresis assay, the DNA Diffusion assay and the micronucleus test were used to investigate possible genotoxic effects. According to our NRRA results, each treatment was able to induce a significant cellular stress in bivalves, probably due to the raise of oxidative stress, as indicated by the alteration of enzyme activities measured in treated specimens. Moreover, the mixture induced significant enhancements of DNA fragmentation, which preluded fixed genetic damage, as highlighted by the increase of both apoptotic and micronucleated cells.

  14. Intravenous self-administration of benzydamine, a non-steroidal anti-inflammatory drug with a central cannabinoidergic mechanism of action.

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    Avvisati, Riccardo; Meringolo, Maria; Stendardo, Emiliana; Malavasi, Elisa; Marinelli, Silvia; Badiani, Aldo

    2018-03-01

    Benzydamine (BZY) is a non-steroidal anti-inflammatory drug used for the topical treatment of inflammations of the oral and vaginal mucosae. Virtually nothing is known about the central pharmacological actions of BZY. Yet there are reports of voluntary systemic overdosage of BZY in drug addicts, resulting in a euphoric, hallucinatory state. In the present study, we investigated the reinforcing properties of BZY in a rat self-administration paradigm. We found that BZY has a powerful reinforcing effect and that this effect is greatly facilitated in animals that already had substance experience, having previously self-administered heroin and cocaine, indicating cross sensitization between BZY and other common drugs of abuse. We then assessed the effect of BZY on prelimbic cortex-to-nucleus accumbens glutamatergic transmission, using field recordings in rat parasagittal brain slices. BZY dose-dependently reduced both field excitatory post synaptic potential amplitude and paired pulse ratio, suggesting a presynaptic mechanism of action. Similarly to the in vivo paradigm, also the electrophysiological effects of BZY were potentiated in slices from animals that had undergone cocaine and heroin self-administration. Furthermore, BZY-induced Long Term Depression (LTD)-like responses in the prelimbic cortex-to-nucleus accumbens circ