WorldWideScience

Sample records for antiinflammatory drug chemistry

  1. Click chemistry-based synthesis of water-dispersible hydrophobic magnetic nanoparticles for use in solid phase extraction of non-steroidal anti-inflammatory drugs

    International Nuclear Information System (INIS)

    Magnetic nanoparticles (MNPs), prepared via thiol-ene click chemistry and containing both diol and octadecyl groups, are shown to possess both hydrophobic and hydrophilic functionalities. They display excellent dispersibility in water and also are capable of extracting non-steroidal anti-inflammatory drugs (NSAIDs) from water samples. The MNPs can be magnetically separated, and the NSAIDs eluted with acetonitrile-water (9:1, v:v) and submitted to high performance liquid chromatographic analysis. Extraction variables, such as the kind of ion-pairing reagents, amount of MNPs, pH of sample solution, extraction and desorption time, volume of desorption solvent and salt addition, were optimized. Under optimum conditions, the method has a wide analytical range (from 5 to 800 ng∙mL-1), good reproducibility with intra-day and inter-day relative standard deviations of <19.2 % (for n = 6), and low detection limits of 0.32 to 1.44 ng∙mL-1 for water samples. The results demonstrate that the material possesses good water compatibility, thus warranting ease of operation and good reproducibility. (author)

  2. Nonsteroid Anti-inflammatory Drugs and Kidney

    Directory of Open Access Journals (Sweden)

    Yaşar Yıldırım1

    2016-03-01

    Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs are often used in the treatment of chronic and acute pain and inflammation as an analgesic and anti-inflammatory agent. They inhibit the synthesis of prostaglandins which have influence on glomerular capillaries, vasa recta and tubular functions. They lead to significant complications such as hyperkalemia, hyponatremia, edema and hypertension. Usage of NSAIDs is a risk factor for acute kidney injury in some conditions such as advanced age, dehydration, vomiting, diuretics, ACE/ARB therapy, heart failure, nephrotic syndrome, cirrhosis and chronic kidney disease. Acute interstitial nephritis is not dependent on the drug dose and it is characterized by immunological inflammatory reaction and a decrease in creatinine clearance. Besides the classical findings, glomerules can be involved and minimal change disease or membranous glomerulonephritis can develop. Analgesic nephropathy is characterized by interstitial nephritis and papillary necrosis. Metabolites of NSAIDs are accumulated in renal medulla which has lowest oxygen pressure in kidney and they disrupt the renal parencymal perfusion by vasoconstriction. Respectively, papillar necrosis, glomerular sclerosis, interstitial fibrosis and cortical atrophy can develop insidiously.

  3. Colitis caused by non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    Ravi, S.; Keat, A. C.; Keat, E. C.

    1986-01-01

    Four cases of acute proctocolitis associated with non-steroidal anti-inflammatory drug therapy are presented. The drugs implicated were flufenamic acid, mefenamic acid, naproxen and ibuprofen. After resolution of symptoms and signs of proctocolitis three of the four patients were subsequently rechallenged with the implicated drug: in each there was a rapid relapse. PMID:3774712

  4. Colitis caused by non-steroidal anti-inflammatory drugs.

    OpenAIRE

    Ravi, S.; Keat, A C; Keat, E C

    1986-01-01

    Four cases of acute proctocolitis associated with non-steroidal anti-inflammatory drug therapy are presented. The drugs implicated were flufenamic acid, mefenamic acid, naproxen and ibuprofen. After resolution of symptoms and signs of proctocolitis three of the four patients were subsequently rechallenged with the implicated drug: in each there was a rapid relapse.

  5. Gastrointestinal Complications of Nnon-Steroidal Anti-Inflammatory Drugs

    OpenAIRE

    MH. Moradi Nejad

    2002-01-01

    Non-steroid anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in rheumatic disorders. This group of drugs has been associated with various degrees of gastroduodenopathy (GD), which is due to inhibition of prostaglandin (PG) synthesis. There are several differences between their side effect in stomach and in duodenum. But all these drugs have gastrointestinal side effect. Several studies on preventing NSAIDs GD have been performed in Europe and north America. There are se...

  6. 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 a...

  7. Nonsteroidal antiinflammatory drug-induced intestinal inflammation in humans

    Energy Technology Data Exchange (ETDEWEB)

    Bjarnason, I.; Zanelli, G.; Smith, T.; Prouse, P.; Williams, P.; Smethurst, P.; Delacey, G.; Gumpel, M.J.; Levi, A.J.

    1987-09-01

    This study examines the effects of nonsteroidal antiinflammatory drugs on the small intestine in humans. Using an /sup 111/In-leukocyte technique in patients with rheumatoid arthritis (n = 90) and osteoarthritis (n = 7), it appears that nonsteroidal antiinflammatory drugs cause small intestinal inflammation in two-thirds of patients on long-term treatment and on discontinuation, the inflammation may persist for up to 16 mo. The prevalence and magnitude of the intestinal inflammation was unrelated to the type and dose of nonsteroidal drugs and previous or concomitant second-line drug treatment. There was a significant inverse correlation (r = -0.29, p less than 0.05) between fecal /sup 111/In excretion and hemoglobin levels in patients treated with nonsteroidal antiinflammatory drugs. The kinetics of fecal indium 111 excretion in patients treated with nonsteroidal antiinflammatory drugs was almost identical to that of patients with small bowel Crohn's disease. Eighteen patients on nonsteroidal antiinflammatory drugs underwent a radiologic examination of the small bowel and 3 were found to have asymptomatic ileal disease with ulceration and strictures. Nineteen patients on nonsteroidal antiinflammatory drugs, 20 healthy controls, and 13 patients with Crohn's ileitis underwent a dual radioisotopic ileal function test with tauro 23 (/sup 75/Se) selena-25-homocholic acid and cobalt 58-labeled cyanocobalamine. On day 4, more than half of the patients with rheumatoid arthritis had evidence of bile acid malabsorption, but the ileal dysfunction was much milder than seen in patients with Crohn's ileitis.

  8. What makes a good anti-inflammatory drug target?

    Science.gov (United States)

    Simmons, David L

    2006-03-01

    This review focuses on the major, 'successful' target families in inflammation and attempts to identify some of the key features of what makes a good anti-inflammatory target. The review is based on a systematic analysis of approved anti-inflammatory drugs grouped according to their drug-target family. The cytokine family is a drug-dense area. They have yielded and continue to yield a rich stream of drugs. As in other therapeutic areas, G-protein-coupled receptors (GPCRs), also known as seven-transmembrane pass receptors, have provided significant drug targets. In addition, the superfamilies of cell adhesion molecules and co-stimulatory molecules, which have special relevance to immune processes, have begun to provide the first approved drugs and might yield many more. The recent, rapid increase in the number of defined targets in the immune system -- leukocyte surface antigens, cytokines, GPCRs, adhesion molecules and co-stimulatory molecules -- will ensure a rich stream of future anti-inflammatory drug targets. PMID:16580598

  9. The Use of Nonsteroidal Anti-Inflammatory Drugs in Sports.

    Science.gov (United States)

    Calabrese, Leonard H.; Rooney, Theodore W.

    1986-01-01

    Recent advances in the understanding of the mechanism of action and clinical pharmacology of the new nonsteroidal anti-inflammatory drugs (NSAIDs) can help practitioners decide which to use and how to administer them. Indications for and effects of NSAIDs are described. (MT)

  10. Nonsteroidal Anti-Inflammatory Drug Hypersensitivity in Preschool Children

    OpenAIRE

    Kidon Mona; Kang Liew; Chin Chiang; Hoon Lim; Hugo,, Argentiniensis, (ca. 1210-ca. 1270)

    2007-01-01

    Although extensively studied in adults, nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity in children, especially in young children, remains poorly defined. Pediatricians, prescribing antipyretics for children, rarely encounter significant problems, but the few epidemiologic studies performed show conflicting results. Although it is clear that some patients with acetylsalicylic acid (ASA)-sensitive asthma have their clinical onset of disease in childhood and bronchoconstriction af...

  11. 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)....

  12. Optimisation of solid phase extraction of selected non-steroidal anti-inflammatory drugs by capillary zone electrophoresis

    Czech Academy of Sciences Publication Activity Database

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

    Greece, 2014. [International Symposium on Environmental Pollution and its Impact on Life in the Mediterranean Region /16./. 24.09.2014-27.09.2014, Ioannina] Institutional support: RVO:68081715 Keywords : solid phase extraction * capillary electrophoresis * non-steroidal anti-inflammatory drugs Subject RIV: CB - Analytical Chemistry, Separation

  13. Anti-inflammatory drug delivery from hyaluronic acid hydrogels.

    Science.gov (United States)

    Hahn, Sei K; Jelacic, Sandra; Maier, Ronald V; Stayton, Patrick S; Hoffman, Allan S

    2004-01-01

    Two different types of hyaluronic acid (HA) hydrogels were synthesized by crosslinking HA with divinyl sulfone (DVS) and poly(ethylene glycol)-divinyl sulfone (VS-PEG-VS). Vitamin E succinate (VES), an anti-inflammatory drug, and bovine serum albumin (BSA), a model of anti-inflammatory protein drugs, were loaded into the gels and their release kinetics were measured in vitro. VES and BSA released with a burst from both HA hydrogels during the first few hours, and release continued gradually for several days. The rate of release from HA-VS-PEG-VS-HA hydrogels was faster than that from HA-DVS-HA hydrogels, presumably due to the lower crosslink density in the former. The anti-inflammatory action of released VES was tested by incubating peripheral blood mononuclear cells (PBMC) on HA hydrogels with and without VES in the gel. The number of cells adhering on HA hydrogels was very low compared to that on tissue culture polystyrene (TCPS), which might be one of the important advantages of using HA hydrogels for implant coatings or tissue engineering applications. ELISA test results showed that the tumor necrosis factor-alpha (TNF-alpha) concentration was very low in the supernatant of the wells containing the HA hydrogel with VES in contact with the activated macrophages compared to that without VES. This is probably the effect of the released VES reducing the production of anti-inflammatory cytokine, TNF-alpha. HA hydrogels containing anti-inflammatory drugs may have potential for use in tissue engineering and also as biocompatible coatings of implants. PMID:15503629

  14. Anti-inflammatory drugs and experimental bronchitis.

    Science.gov (United States)

    Jeffery, P K

    1986-01-01

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

  15. Gastrointestinal and Cardiovascular Risk of Nonsteroidal Anti-inflammatory Drugs

    OpenAIRE

    Abdulwahed Al-Saeed

    2011-01-01

     Nonsteroidal anti-inflammatory drugs (NSAIDs) confer a gastrointestinal (GI) side effect profile and concerns regarding adverse cardiovascular effects have emerged associated with considerable morbidity and mortality. NSAIDs are highly effective in treating pain and inflammation, but it is well recognized that these agents are associated with substantial gastrointestinal toxicity. Cyclo-oxygenase-2 inhibitors may also reduce the risk for gastrointestinal events, although they may increase ca...

  16. Non Steroidal Anti-Inflammatory Drugs and Inflammatory Bowel Disease

    OpenAIRE

    Amir Klein; Rami Eliakim

    2010-01-01

    Inflammatory Bowel Diseases (IBD) are an immune mediated chronic or relapsing disorders of the gastrointestinal (GI) tract. IBD is characterized by a chronic intestinal inflammatory process with various components contributing to the pathogenesis of the disease including environmental factors such as smoking or use of Non Steroidal Anti-Inflammatory Drugs (NSAIDS). NSAIDS are among the most commonly used medications for the treatment of various inflammatory conditions. The main factor limitin...

  17. Acetylsalicylic-acid-containing drugs and nonsteroidal anti-inflammatory drugs available in Canada

    OpenAIRE

    Brigden, M; Smith, R E

    1997-01-01

    A large number of drugs containing acetylsalicylic acid (ASA) and nonsteroidal anti-inflammatory drugs (NSAIDs) are available by prescription and over the counter in Canada. The possibility of serious side effects and drug interactions is therefore high. The authors have compiled a comprehensive list of products containing these drugs from information supplied by pharmaceutical databases, independent marketing researchers and Health Canada's Drug Directorate. Physicians should ensure that add...

  18. Concentrations of acidic antiinflammatory drugs in gastric mucosa.

    Science.gov (United States)

    Frey, H H; El-Sayed, M A

    1977-12-01

    In rats, the concentrations of the acidic antiinflammatory drugs salicylic acid, acetylsalicylic acid, phenylbutazone, flufenamic acid and indomethacin in the glandular portion of the gastric mucosa were determined 30 and 60 min after oral or subcutaneous administration. In another series of experiments, solutions of the drugs were introduced into the ligated stomach and the concentrations in the mucosa and in the contents of the stomach were determined after 60 min. The ratio between the concentrations in the musoca and those in serum or gastric contents were much lower than expected according to the distribution by passive non-ionic diffusion. This apparent discrepancy may be explained as a result of a drug-induced damage to the mucosal cell allowing free diffusion of ionized drug across the cell membrane. PMID:603322

  19. Multiple cutaneous sensitization to nonsteroidal anti-inflammatory drugs.

    Science.gov (United States)

    Gonzalo, M A; Revenga, F

    1996-01-01

    The use of topical nonsteroidal anti-inflammatory drugs is widespread (particularly in countries bordering the Mediterranean). Compared to their wide use, the incidence of published adverse cutaneous effects appears minimal, although they are increasing. Most of them are a form of allergic contact dermatitis (ACD). Multiple sensitization and/or cross-reactions are rarely reported. Interestingly, our patient presented ACD with diclofenac and etofenamate (both from different chemical groups) and, furthermore, patch tests were positive with bencydamine and indomethacin (both indolacetic acid derivatives), piroxicam and fepradinol. We think that our results could not be explained due to cross-reactivity, and that multiple sensitization was more likely. PMID:8864624

  20. 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

  1. 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; Laura L. Valdez-Velazquez; 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 ...

  2. Effect of nonsteroidal antiinflammatory drugs on the C-reactive protein level in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Tarp, Simon; Bartels, Else M.; Bliddal, Henning;

    2012-01-01

    To evaluate the effects of oral nonsteroidal antiinflammatory drugs (NSAIDs) on C-reactive protein (CRP) levels in rheumatoid arthritis (RA) patients, with a prespecified focus on the different NSAIDs.......To evaluate the effects of oral nonsteroidal antiinflammatory drugs (NSAIDs) on C-reactive protein (CRP) levels in rheumatoid arthritis (RA) patients, with a prespecified focus on the different NSAIDs....

  3. Radiation chemistry applied to drug design

    International Nuclear Information System (INIS)

    Radiation chemistry can contribute to drug design by quantifying redox properties of drugs and where free radicals are suspected intermediates in drug action, radiation can be used to generate these putative species and help characterise relevant reactions. Steady radiolysis produces radicals at a readily-varied but quantified rate; pulse radiolysis with fast spectrophotometric and/or conductimetric detection enables the kinetic properties of radicals to be monitored directly. Using these methods, radical intermediates from drugs with specific cytotoxicity towards hypoxic cells have been shown to react rapidly with oxygen. Radical oxidants from activated neutrophils include superoxide and hydroxyl radicals, and radiation-chemical methods have an important role to play in rational drug design to exploit such oxidative chemistry. Antioxidants can also be evaluated quantitatively by radiolysis methods; the conjugation reactions of thiyl radicals with thiolate and oxygen are now recognised to be major contributions of pulse radiolysis to thiol biochemistry. (author)

  4. Radiation chemistry applied to drug design

    Energy Technology Data Exchange (ETDEWEB)

    Wardman, P.; Candeias, L.P.; Everett, S.A. (Mount Vernon Hospital, Northwood (United Kingdom). Cancer Research Campaign Gray Lab.); Tracy, M. (SRI International, Menlo Park, CA (United States))

    1994-01-01

    Radiation chemistry can contribute to drug design by quantifying redox properties of drugs and where free radicals are suspected intermediates in drug action, radiation can be used to generate these putative species and help characterise relevant reactions. Steady radiolysis produces radicals at a readily-varied but quantified rate; pulse radiolysis with fast spectrophotometric and/or conductimetric detection enables the kinetic properties of radicals to be monitored directly. Using these methods, radical intermediates from drugs with specific cytotoxicity towards hypoxic cells have been shown to react rapidly with oxygen. Radical oxidants from activated neutrophils include superoxide and hydroxyl radicals, and radiation-chemical methods have an important role to play in rational drug design to exploit such oxidative chemistry. Antioxidants can also be evaluated quantitatively by radiolysis methods; the conjugation reactions of thiyl radicals with thiolate and oxygen are now recognised to be major contributions of pulse radiolysis to thiol biochemistry. (author).

  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. Non-steroidal Anti-inflammatory Drugs in Raptors

    Science.gov (United States)

    Oaks, J. Lindsay; Meteyer, Carol U.

    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.

  7. Topical nonsteroidal anti-inflammatory drugs for osteoarthritis.

    Science.gov (United States)

    Barthel, H Richard; Axford-Gatley, Robert A

    2010-11-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are mainstays of the treatment of osteoarthritis (OA) but have dose- and age-related risks of gastrointestinal, cardiovascular, and renal adverse events (AEs). As a result, US and international guidelines recommend caution when prescribing oral NSAIDs, particularly in older patients and those with significant comorbidities. For OA of the hands and knees, topical NSAIDs provide efficacy similar to oral NSAIDs, with far less systemic distribution. Treatment-related cardiovascular, renal, and other serious AEs with topical NSAIDs have not been reported. At present, only 2 topical NSAIDs are approved in the United States for the treatment of OA: diclofenac sodium 1% gel for hand or knee OA and diclofenac sodium 1.5% in 45.5% dimethylsulfoxide solution for knee OA. Clinical trial data for these products have demonstrated efficacy superior to placebo or similar to oral diclofenac with AE profiles similar to placebo, except for application site reactions. In large double-blind trials, gastrointestinal AEs were infrequent and did not include ulcers, perforations, or bleeding. The purpose of this brief review is to examine the data from controlled double-blind trials evaluating the use of topical NSAIDs in patients with OA. Articles included were identified via a search of PubMed covering the period from January 1, 2005 through March 31, 2010. Reference lists from OA treatment guidelines and meta-analyses were reviewed for additional citations of importance. PMID:21084786

  8. Frequency of nonsteroidal anti-inflammatory drug-associated ulcers.

    Science.gov (United States)

    Hiraishi, Hideyuki; Oki, Ryo; Tsuchida, Kohei; Yoshitake, Naoto; Tominaga, Keiichi; Kusano, Koji; Hashimoto, Takashi; Maeda, Mitsunori; Sasai, Takako; Shimada, Tadahito

    2012-06-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for treatment of orthopedic diseases, inflammatory diseases, etc., and low-dose aspirin is a common antiplatelet therapy given mainly for secondary prevention of atherothrombosis (e.g., myocardial infarction and cerebral infarction). As to the history of NSAID-induced gastric mucosal injury in Japan, the first case of an aspirin-induced gastric ulcer was reported as early as 1934. Based on a meta-analysis of risk factors for peptic ulcers, Helicobacter pylori infection and NSAIDs are the main etiologies of peptic ulcers. NSAIDs alone increase the odds ratio for ulcer development to 19.4 and that for ulcer bleeding to 4.85. In fact, the Japan Rheumatism Foundation reported in 1991 that active gastric ulcers and active duodenal ulcers were detected in 15.5 and 1.9 % of 1008 patients, respectively, taking oral NSAIDs for 3 months or longer. In Japan, which is becoming an increasingly aged society, the numbers of patients taking NSAIDs and low-dose aspirin are expected to increase dramatically in the future. It is hoped that accumulation of evidence on gastrointestinal risk will allow many patients to rationally avoid gastrointestinal complications while receiving the benefits of NSAIDs and low-dose aspirin. PMID:26182316

  9. Nonsteroidal Anti-Inflammatory Drug Hypersensitivity in Preschool Children

    Directory of Open Access Journals (Sweden)

    Kidon Mona

    2007-12-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with severe renal complications, including acute renal failure, reduced glomerular filtration rate and interstitial nephritis. Caution against NSAIDs is therefore recommended in advanced chronic kidney disease. In this study...

  11. Non steroidal antiinflammatory drugs may be harmful to normal kidneys: experimental surgery model*

    OpenAIRE

    Hur, E; Duman, E.; Bozkurt, D.; Sozmen, E; Sen, S.; Taskin, H; Timur, O; Kaya, SO; Duman, S.

    2012-01-01

    Background and aim: The exact effect of analgesics on normal kidneys is not known yet. We aimed to evaluate the impression of non steroidal antiinflammatory drugs (NSAID) used post-operatively on kidneys, in rat (tracheotomy) model.

  12. Acute gastrointestinal permeability responses to different non-steroidal anti-inflammatory drugs

    OpenAIRE

    Smecuol, E; Bai, J.; Sugai, E; Vazquez, H.; Niveloni, S; Pedreira, S; Maurino, E; Meddings, J

    2001-01-01

    BACKGROUND AND AIMS—Non-steroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal damage both in the upper and lower gastrointestinal tract. New anti-inflammatory drugs have been developed in an attempt to improve their gastrointestinal side effect profile. Our objective was to compare the effect on gastrointestinal permeability of acute equieffective doses of four different NSAIDs; three were designed to reduce gastrointestinal mucosal injury.
MATERIALS—Healthy volunteers underwent s...

  13. Effect of non-steroidal anti-inflammatory drugs on colon carcinoma Caco-2 cell responsiveness to topoisomerase inhibitor drugs

    OpenAIRE

    Ricchi, P; Matola, T Di; Ruggiero, G; D. Zanzi; Apicella, A; Di Palma, A; M. Pensabene; S. Pignata; Zarrilli, R; Acquaviva, A M

    2002-01-01

    Numerous studies demonstrate that the chemopreventive effect of non-steroidal anti-inflammatory drugs on colon cancer is mediated through inhibition of cell growth and induction of apoptosis. For these effects non-steroidal anti-inflammatory drugs have been recently employed as sensitising agents in chemotherapy. We have shown previously that treatments with aspirin and NS-398, a cyclo-oxygenase-2 selective inhibitor, affect proliferation, differentiation and apoptosis of the human colon aden...

  14. Cardiovascular complications of non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    Fosslien, Egil

    2005-01-01

    Coxibs, such as rofecoxib, celecoxib, and valdecoxib, selectively inhibit cyclooxygenase (COX)-2, the mainly inducible, pro-inflammatory COX isoform. Unlike traditional non-steroidal anti-inflammatory drugs (NSAIDs) most coxibs do not significantly inhibit COX-1 and are therefore less toxic to the gastrointestinal tract. Hence, coxibs widely replaced traditional NSAIDs for treatment of arthritis and other painful inflammatory conditions. In many, but not all, clinical studies, coxibs became associated with higher risks of myocardial infarction (MI) and stroke. Several mechanisms may be involved in the pathogenesis of such complications. First, selective inhibition of COX-1 lowers platelet synthesis of thromboxane (TXA(2)), a thrombogenic and atherogenic eicosanoid. Selective inhibition of COX-2 limits endothelial cell synthesis of prostacyclin (PGI(2)), an arachidonic acid product that opposes the effects of thromboxane. In apoE-/- mice, interruption of TXA(2) signaling by deletion of its receptor (TP) limits atherogenesis, whereas interruption of PGI2 signaling by deletion of its receptor (IP) accelerates atherogenesis. This suggests that selective inhibition of COX-2 can disrupt the physiological balance between thromboxane and prostacyclin and thus increase atherosclerosis, thrombogenesis, and the risk of cardiovascular complications. Second, COX inhibition can raise levels of arachidonic acid, which can inhibit mitochondrial oxidative phosphorylation (OXPHOS) and increase OXPHOS generation of reactive oxygen species. Several NSAIDs, including coxibs and meloxicam, directly uncouple or inhibit OXPHOS. Studies of apoE-/- mice indicate that mitochondrial dysfunction plays an early role in atherogenesis. Third, many NSAIDs exhibit COX-independent properties. For example, in animal models, short-term treatment with celecoxib reduces monocyte chemotaxis by reducing expression of monocyte chemoattractant protein (MCP)-1. However, long-term treatment results in the

  15. Structural investigation of chitosan-based microspheres with some anti-inflammatory drugs

    Science.gov (United States)

    Dreve, Simina; Kacso, Iren; Popa, Adriana; Raita, Oana; Dragan, Felicia; Bende, A.; Borodi, Gh.; Bratu, I.

    2011-06-01

    The use of chitosan as an excipient in oral formulations, as a drug delivery vehicle for ulcerogenic anti-inflammatory drugs and as base in polyelectrolyte complex systems, to prepare solid release systems as sponges was investigated. The preparation by double emulsification of chitosan hydrogels carrying diclofenac, acetyl-salycilic acid and hydrocortisone acetate as anti-inflammatory drugs is reported. The concentration of anti-inflammatory drug in the chitosan hydrogel generating the sponges was 0.08 mmol. Chitosan-drug loaded sponges with anti-inflammatory drugs were prepared by freeze-drying at -60 °C and 0.009 atm. Structural investigations of the solid formulations were done by Fourier-transformed infrared and ultraviolet-visible spectroscopy, spectrofluorimetry, differential scanning calorimetry and X-ray diffractometry. The results indicated that the drug molecules are forming temporary chelates in chitosan hydrogels and sponges. Electron paramagnetic resonance demonstrates the presence of free radicals in a wide range and the antioxidant activity for chitosan-drug supramolecular cross-linked assemblies.

  16. ROLE OF ANTI-INFLAMMATORY DRUGS IN TRAUMATIC ARDS

    OpenAIRE

    Siddani; Rakesh; Pudi Rama

    2014-01-01

    ALI/ARDS is an acute pathological process with dynamic and complex inflammatory response. In traumatic ARDS inflammatory response plays major role in outcomes. Anti-inflammatory agents may play major role in recovery. We report successful management of early traumatic ARDS with lung protective strategy along with Ant-inflammatory agents. Larger trails are needed to assess Ant-inflammatory agents in ALI/ARDS.

  17. Over-the-Counter Monocyclic Non-Steroidal Anti-Inflammatory Drugs in Environment—Sources, Risks, Biodegradation

    OpenAIRE

    Marchlewicz, Ariel; Guzik, Urszula; Wojcieszyńska, Danuta

    2015-01-01

    Recently, the increased use of monocyclic non-steroidal anti-inflammatory drugs has resulted in their presence in the environment. This may have potential negative effects on living organisms. The biotransformation mechanisms of monocyclic non-steroidal anti-inflammatory drugs in the human body and in other mammals occur by hydroxylation and conjugation with glycine or glucuronic acid. Biotransformation/biodegradation of monocyclic non-steroidal anti-inflammatory drugs in the environment may ...

  18. AMP-activated protein kinase is activated by non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    King, Tanya S; Russe, Otto Quintus; Möser, Christine V; Ferreirós, Nerea; Kynast, Katharina L; Knothe, Claudia; Olbrich, Katrin; Geisslinger, Gerd; Niederberger, Ellen

    2015-09-01

    AMP-activated kinase (AMPK) is a cellular energy sensor, which is activated in stages of increased adenosine triphosphate (ATP) consumption. Its activation has been associated with a number of beneficial effects such as decrease of inflammatory processes and inhibition of disease progression of diabetes and obesity. A recent study suggested that salicylate, the active metabolite of the non-steroidal anti-inflammatory drug (NSAID) acetyl-salicylic acid (aspirin), is able to activate AMPK pharmacologically. This observation raised the question whether or not other NSAIDs might also act as AMPK activators and whether this action might contribute to their cyclooxygenase (COX)-independent anti-inflammatory properties. In this study, we investigated mouse and human neuronal cells and liver tissue of mice after treatment with various NSAIDs. Our results showed that the non-selective acidic NSAIDs ibuprofen and diclofenac induced AMPK activation similar to aspirin while the COX-2 selective drug etoricoxib and the non-opioid analgesic paracetamol, both drugs have no acidic structure, failed to activate AMPK. In conclusion, our results revealed that AMPK can be activated by specific non-steroidal anti-inflammatory drugs such as salicylic acid, ibuprofen or diclofenac possibly depending on the acidic structure of the drugs. AMPK might therefore contribute to their antinociceptive and anti-inflammatory properties. PMID:26049010

  19. [The mode of anti-inflammatory action of a topical non-steroidal anti-inflammatory drug, etofenamate].

    Science.gov (United States)

    Nakamura, H; Motoyoshi, S; Ishii, K; Seto, Y; Shimoda, A; Kadokawa, T

    1987-01-01

    In order to ascertain the mode of anti-inflammatory action of a topical non-steroidal anti-inflammatory drug, etofenamate which is a diethylene glycol ester of flufenamic acid, the in vitro test for the mechanism of the action were carried out. Etofenamate (3 microM) was hydrolysed to flufenamic acid at a rate of 39.5% and 57.0% of the dose during 30 and 60 min incubation, respectively, when incubated with rat peritoneal macrophages stimulated with starch and bacto peptone in phosphate-buffered saline. PGE2 generation by these cells in MEM medium was dose-relatedly inhibited with etofenamate as well as flufenamic acid at the dosage range of 1 to 30 microM. This suggests that unchanged etofenamate is active, since the highest conversion rate of etofenamate to flufenamic acid was 15% of the dose during the incubation. Etofenamate produced a dose-related inhibition against lipoxygenase prepared from peritoneal polymorphonuclear leucocytes of guinea pigs, and its activity (IC50 = 5.3 X 10(-5) M) was stronger than that of caffeic acid; flufenamic acid was inactive. Inhibitory activity of etofenamate was one-third or less that of flufenamic acid against the hypotonic-hyperthermic lysis of rat erythrocytes and heat-denaturation of bovine serum albumin. From these results, it was suggested that topically applied etofenamate produces its anti-inflammatory action through prostaglandin synthesis inhibition by flufenamic acid produced in the inflammatory tissue and inhibition of prostaglandin synthesis by macrophages and lipoxygenase inhibition by unchanged etofenamate. PMID:2883093

  20. Direct toxicity of nonsteroidal antiinflammatory drugs for renal medullary cells

    OpenAIRE

    Rocha, Gerson M.; Michea, Luis F.; Peters, Eugenia M.; Kirby, Martha; Xu, Yuhui; Ferguson, Douglas R.; Burg, Maurice B.

    2001-01-01

    Antipyretic analgesics, taken in large doses over a prolonged period, cause a specific form of kidney disease, characterized by papillary necrosis and interstitial scarring. Epidemiological evidence incriminated mixtures of drugs including aspirin (ASA), phenacetin, and caffeine. The mechanism of toxicity is unclear. We tested the effects of ASA, acetaminophen (APAF, the active metabolite of phenacetin), caffeine, and other related drugs individually and in combination...

  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...... endpoint of cardiovascular death, myocardial infarction and stroke were 0.48 (95% CI 0.17-1.38) and 0.50 (95% CI 0.26-0.97). CONCLUSION: In this nationwide study of patients with severe psoriasis, systemic anti-inflammatory treatment with biological agents or methotrexate was associated with lower...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Psoriasis is a common disease and is associated with cardiovascular diseases. Systemic anti-inflammatory drugs may reduce risk of cardiovascular events. We therefore examined the rate of cardiovascular events, i.e. cardiovascular death, myocardial infarction and stroke, in patients with...... severe psoriasis treated with systemic anti-inflammatory drugs. METHODS: Individual-level linkage of administrative registries was used to perform a longitudinal nationwide cohort study. Time-dependent multivariable adjusted Cox regression was used to estimate hazard ratios (HRs) with 95% confidence...... factor inhibitors (HR 0.46; CI 0.22-0.98) were linked to reduced event rates, whereas the interleukin-12/23 inhibitor ustekinumab (HR 1.52; CI 0.47-4.94) was not. CONCLUSION: Systemic anti-inflammatory treatment with methotrexate was associated with significantly lower rates of cardiovascular events...

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

    DEFF Research Database (Denmark)

    Klein, Mads; Gögenur, Ismail; Rosenberg, Jacob

    2012-01-01

    Anastomotic leakage (AL) is the most important and one of the most serious complications after colorectal resections with primary anastomosis. Any factors that contribute to increase the risk of AL should be identified and - if possible - eliminated. Non-steroidal anti-inflammatory drugs (NSAIDs...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    Epidemiologic studies investigating the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on breast cancer have yielded conflicting results. We examined the association between use of aspirin and nonaspirin NSAIDs and breast cancer risk among 28 695 women in the Danish Diet, Cancer and...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely consumed among athletes worldwide in relation to muscle injury and soreness. This review aims to provide an overview of studies investigating their effects on skeletal muscle, in particular the repair processes in injured muscle. Muscle...

  7. Experimental study of anti-inflammatory activity of the new combined with drug urolytolytic action

    OpenAIRE

    Iermolenko T.I.

    2015-01-01

    Herbal medicines provide their versatile complex influence on the course of the pathological process in the kidneys due to biologically active compounds. Specifically, they cause the direct impact on the concrements formation. The search of drugs which would contain high biological compounds of plant origin is an actual issue of modern pharmacology. The aim of investigation was to study the anti-inflammatory activity of the new combined drug of urolytolytic action, which includes the total pl...

  8. Experimental study of anti-inflammatory activity of the new combined with drug urolytolytic action.

    OpenAIRE

    Iermolenko, T. I.

    2015-01-01

    Herbal medicines provide their versatile complex influence on the course of the pathological process in the kidneys due to biologically active compounds. Specifically, they cause the direct impact on the concrements formation. The search of drugs which would contain high biological compounds of plant origin is an actual issue of modern pharmacology. The aim of investigation was to study the anti-inflammatory activity of the new combined drug of urolytolytic action, which includes the total pl...

  9. Recognizing the Risks of Chronic Nonsteroidal Anti-Inflammatory Drug Use in Older Adults

    OpenAIRE

    Marcum, Zachary A.; Hanlon, Joseph T.

    2010-01-01

    Older adults commonly take nonsteroidal anti-inflammatory drugs (NSAIDs) chronically. Studies of older adults show that chronic NSAID use increases the risk of peptic ulcer disease, acute renal failure, and stroke/myocardial infarction. Moreover, chronic NSAID use can exacerbate a number of chronic diseases including heart failure and hypertension, and can interact with a number of drugs (eg, warfarin, corticosteroids). Preferred analgesics in older adults that may have a lower risk of these ...

  10. Experimental study of anti-inflammatory activity of the new combined with drug urolytolytic action

    Directory of Open Access Journals (Sweden)

    Iermolenko T.I.

    2015-06-01

    Full Text Available Herbal medicines provide their versatile complex influence on the course of the pathological process in the kidneys due to biologically active compounds. Specifically, they cause the direct impact on the concrements formation. The search of drugs which would contain high biological compounds of plant origin is an actual issue of modern pharmacology. The aim of investigation was to study the anti-inflammatory activity of the new combined drug of urolytolytic action, which includes the total plant extract and succinate buffer complex. Materials and methods: aseptic exudative inflammation was caused by subplantar introduction of 0,1 ml of 1% solution of λ-karahenin in the right hind paw of rats, the investigated drug was administered at doses 1, 2 and 4 ml/kg. The influence of the studied drug was evaluated in terms of swelling limbs volume. It is shown that the severity of antiexudative action of flarosukcine had dose-dependent nature, increasing from dose of 1,0 ml/kg to 2,0 ml/kg (by 5,5%. Further dose increase to 4,0 ml/kg, was not defined by significant increase of activity. Anti-inflammatory activity of the drug ranged from 25 to 33%, which can be regarded as quite distinct, since in pharmacological study of anti-inflammatory drugs pharmacological activity level of at least 20% is significant.

  11. 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

    BACKGROUND: Nonsteroidal anti-inflammatory drugs can increase bleeding and thrombosis, but little is known about the cerebrovascular safety of these drugs, especially among healthy people. AIMS: The aim of this study was to examine the risk of ischemic and hemorrhagic stroke associated with the use...... admissions for five-years and no important prescription claims for two-years was selected. Case crossover and Cox proportional hazard models were used to analyze the relationship between nonsteroidal anti-inflammatory drug utilization and specific cerebrovascular risk (fatal or non-fatal ischemic or...... 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...

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Hugh; James; Freeman

    2012-01-01

    Aspirin and non-steroidal anti-inflammatory drugs (NSAIDS) may prevent sporadic colonic neoplasia and reduce the polyp burden in familial adenomatous polyposis. A 41-year-old pharmacologist with no family history of intestinal polyps or cancer chronically consumed daily aspirin and other non-steroidal anti-inflammatory drugs for decades despite recurrent and multiple gastric ulcers. A cancerous polyp in the colon was endoscopically resected. Over the next 2 decades, almost 50 adenomatous polyps were removed from the rest of his colon and duodenum, typical of an attenuated form of adenomatous polyposis. Chronic and habitual use of aspirin or NSAIDS may have important significance in delaying the appearance of adenomas. The observations here emphasize the important implications for clinical risk assessment in screening programs designed to detect or prevent colon cancer.

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

    Institute of Scientific and Technical Information of China (English)

    Mario Guslandi

    2012-01-01

    Intestinal bacteria play a role in the development of non-steroidal anti-inflammatory drugs (NSAID)-induced small intestinal injury.Agents such as probiotics,able t omodify the gut ecology,might theoretically be useful in preventing small intestinal damage induced by NSAIDs.The clinical studies available so far do suggest that some probiotic agents can be effective in this respect.

  15. Inhibition of Monoacylglycerol Lipase Attenuates Nonsteroidal Anti-Inflammatory Drug-Induced Gastric Hemorrhages in Mice

    OpenAIRE

    Kinsey, Steven G.; Daniel K Nomura; O'Neal, Scott T.; Long, Jonathan Z.; Mahadevan, Anu; Cravatt, Benjamin F.; John R Grider; Lichtman, Aron H.

    2011-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used analgesics, but can cause gastric and esophageal hemorrhages, erosion, and ulceration. The endogenous cannabinoid (endocannabinoid; eCB) system possesses several potential targets to reduce gastric inflammatory states, including cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), and enzymes that regulate the eCB ligands 2-arachidonoylglycerol (2-AG) and N-arachidonoyl ethanolamine (anandamide; AEA). In the pres...

  16. COX-Independent Mechanisms of Cancer Chemoprevention by Anti-Inflammatory Drugs

    OpenAIRE

    Gurpinar, Evrim; Grizzle, William E.; Piazza, Gary A.

    2013-01-01

    Epidemiological and clinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase (COX)-2 selective inhibitors, reduce the risk of developing cancer. Experimental studies in human cancer cell lines and rodent models of carcinogenesis support these observations by providing strong evidence for the antineoplastic properties of NSAIDs. The involvement of COX-2 in tumorigenesis and its overexpression in various cancer tissues suggest that inhibition of COX...

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

    OpenAIRE

    Evrim eGurpinar; Grizzle, William E.; Piazza, Gary A.

    2013-01-01

    Epidemiological and clinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase (COX)-2 selective inhibitors, reduce the risk of developing cancer. Experimental studies in human cancer cell lines and rodent models of carcinogenesis support these observations by providing strong evidence for the antineoplastic properties of NSAIDs. The involvement of COX-2 in tumorigenesis and its overexpression in various cancer tissues suggest that inhibition of COX...

  18. 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.

  19. Adult purpura fulminans associated with non-steroidal anti-inflammatory drug use

    Directory of Open Access Journals (Sweden)

    N Kosaraju

    2011-01-01

    Full Text Available Purpura fulminans is an acute illness characterized by rapidly progressive dermal vascular thrombosis, leading to hemorrhagic necrosis of the skin. Here, we describe the case of a healthy woman who developed acute disseminated intravascular coagulation (DIC with purpura fulminans after intramuscular administration of a single dose of ketorolac. Review of literature showed only one case description of non-steroidal anti-inflammatory drug (diclofenac-related purpura fulminans with DIC.

  20. Adult purpura fulminans associated with non-steroidal anti-inflammatory drug use

    OpenAIRE

    N Kosaraju; V Korrapati; Thomas, A; B R James

    2011-01-01

    Purpura fulminans is an acute illness characterized by rapidly progressive dermal vascular thrombosis, leading to hemorrhagic necrosis of the skin. Here, we describe the case of a healthy woman who developed acute disseminated intravascular coagulation (DIC) with purpura fulminans after intramuscular administration of a single dose of ketorolac. Review of literature showed only one case description of non-steroidal anti-inflammatory drug (diclofenac)-related purpura fulminans with DIC.

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

    Directory of Open Access Journals (Sweden)

    Viktoriya Georgievna Barskova

    2011-09-01

    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.

  2. Prescribing pattern of non-steroidal anti-inflammatory drugs at outpatient departments of teaching hospitals

    OpenAIRE

    Md. Shamsur Rahman, Zinnat Ara Begum; and Md. Khoshroz Samad

    2007-01-01

    The prescribing pattern of non-steroidal anti-inflammatory drugs (NSAIDs) in prescriptions prescribed by the qualified medical personnel in the outpatient departments of three selected teaching hospitals in Dhaka city were studied. A total of 600 prescriptions containing NSAIDs were collected. The clinical conditions for which NSAIDs prescribed were identical in all the three hospitals, although there were wide variations in the prescribing pattern with respect to pharmacological sub-classes ...

  3. Preparation of controlled release microspheres using supercritical fluid technology for delivery of anti-inflammatory drugs

    OpenAIRE

    Duarte, Ana Rita C.; Costa, M. S.; Simplicio, A. L.; Cardoso, M. Margarida; Duarte, Catarina M. M.

    2006-01-01

    Ethylcellulose/methylcellulose blends were produced using different precipitation techniques and impregnated with naproxen, a non-steroidal anti-inflammatory drug (NSAID). Solvent-evaporation technique was used not only for the preparation of ethylcellulose/methylcellulose microspheres but also to encapsulate naproxen. Supercritical fluid (SCF) impregnation was also performed to prepare naproxen loaded microspheres. The microspheres, impregnated by the SCF technique, were prepared bo...

  4. A Novel Phenotype of Nonsteroidal Anti-Inflammatory Drug Hypersensitivity The High-Risk Patient

    OpenAIRE

    Sánchez-Borges, Mario; Capriles-Hulett, Arnaldo; Caballero-Fonseca, Fernan

    2009-01-01

    Background Some nonsteroidal anti-inflammatory drug (NSAID)-hypersensitive patients develop adverse reactions when challenged with weak cyclooxygenase 1 (COX-1) inhibitors. Objectives To investigate the prevalence and clinical features of this high-risk population. Materials and methods Patients from 2 outpatient allergy clinics consulting between October 2005 and October 2007 because of adverse reactions to classic NSAIDs were submitted to confirmatory double-blind oral challenges with the s...

  5. Nonsteroidal anti-inflammatory drugs for the prevention of colon cancer.

    OpenAIRE

    Turner, D.; Berkel, H J

    1993-01-01

    OBJECTIVE: To summarize the results of animal and human studies of the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on neoplastic growth in the colon and to outline the possible mechanisms involved. DATA SOURCES: Research articles published in English before June 1992 were identified from MEDLINE. STUDY SELECTION: Nine articles on the polyp-cancer sequence were reviewed, 8 on the apparent pathophysiologic aspects of tumour inhibition by NSAIDs and 22 on animal and human research in...

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

    Argoff CE; Gloth FM

    2011-01-01

    Charles E Argoff1, F Michael Gloth2 1Albany Medical College and Comprehensive Pain Center, Albany Medical Center, Albany, NY, USA; 2Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: Osteoarthritis is common in patients ≥65 years of age. Although nonsteroidal anti-inflammatory drugs (NSAIDs) are often prescribed for osteoarthritis pain, they pose age-related cardiovascular, renal, and gastrointestinal risks. Two topical NSAIDs, diclofenac sodium 1% gel (DSG) and...

  8. Chemotherapeutic properties of phospho-nonsteroidal anti-inflammatory drugs, a new class of anticancer compounds

    OpenAIRE

    Huang, Liqun; Mackenzie, Gerardo G; Sun, Yu; Ouyang, Nengtai; Xie, Gang; Vrankova, Kvetoslava; Komninou, Despina; Rigas, Basil

    2011-01-01

    Non-steroidal anti-Inflammatory drugs (NSAIDs) exhibit antineoplastic properties, but conventional NSAIDs do not fully meet safety and efficacy criteria for use as anti-cancer agents. In this study, we evaluated the chemotherapeutic efficacy of five novel phospho-NSAIDs, each of which includes in addition to the NSAID moiety a diethylphosphate linked through a butane moiety. All five compounds inhibited the growth of human breast, colon and pancreatic cancer cell lines with micromolar potency...

  9. 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.

  10. 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.

  11. Practical guidelines for diagnosing hypersensitivity reactions to nonsteroidal anti-inflammatory drugs.

    Science.gov (United States)

    Ortega, N; Doña, I; Moreno, E; Audicana, M T; Barasona, M J; Berges-Gimeno, M P; Blanca-Lopez, N; Lobera, T; Padial, A; Rosado, A; Torres, M J

    2014-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in hypersensitivity reactions. These reactions include various clinical entities with different mechanisms leading to the release of inflammatory mediators. Characterization of patients based on clinical manifestations and suspected underlying mechanisms is critical for implementation of adequate diagnostic procedures and patient management. Our objectives were to prepare a systematic review of available scientific evidence and to provide general guidelines for the diagnosis and management of patients with hypersensitivity reactions to NSAIDs. We also propose a practical algorithm for the diagnosis of specific types of hypersensitivity to NSAIDs and provide recommendations for the management of hypersensitive patients. PMID:25345301

  12. Prescribing non-steroidal anti-inflammatory drugs: a prospective study of patients' preference

    OpenAIRE

    Scott, D L; Low-Beer, T S; Roden, S.; Takavarasha, L.

    1982-01-01

    Thirty-six patients with rheumatoid arthritis were allocated at random to one of 3 groups prescribed 4 different non-steroidal anti-inflammatory drugs (NSAID). Each drug was given for one week over 4 consecutive weeks in a balanced order. The patients were then asked to select one NSAID for continuation therapy and were followed-up 6 months later. The success of the patient selection method was compared with that of physician selection by retrospectively surveying NSAID prescribing in 164 pat...

  13. EVALUATION OF ANTI-INFLAMMATORY AND ANTI-ARTHRITIC ACTIVITIES OF FLOATING MICROSPHERES OF HERBAL DRUG

    Directory of Open Access Journals (Sweden)

    Kapil Kumar

    2012-01-01

    Full Text Available The aim of the present studies was to prepare and evaluate floating microspheres of curcumin for anti-inflammatory and anti-arthritic effect. Floating microsphere were prepared using hydroxyl propyl methylcellulose (HPMC, ethyl cellulose (EC, polyvinyl pyrrolidone K30 (PVPK30, eudragit RS 100 polymer in different ratio and dichloromethane and heavy liquid paraffin as solvent by emulsion solvent diffusion method. The floating microspheres were evaluated for flow properties based on parameters such as angle of repose and compressibility index, as well as for various other physicochemical properties including particle size, incorporation efficiency, in-vitro floatability, and in-vitro drug release. The shape and surface morphology of the microspheres were characterised by scanning electron microscopy. Scanning electron microscopy showed pores on the surface and interior of the microspheres. Anti-inflammatory, anti-arthritic effect of formulation C4 and E1 were compared with standard market product Indomethacin. The effect of formulation C4 and E1 was evaluated for acute inflammation in carrageenan induced rat paw edema and for chronic inflammation in complete Freud’s adjuvant (CFA induced arthritis in rats. Further histopathological and radiographic evaluation was performed. It may be concluded that Curcumin microspheres would be promising drug delivery system for oral administration of Curcumin to sustained the drug release. Incorporation of herbal drugs in novel drug delivery system may lead to an excellent result.

  14. 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....

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

    Directory of Open Access Journals (Sweden)

    Madalina luiza MOLDOVEANU

    2012-09-01

    Full Text Available With a number of common therapeutic prescriptions, common mechanisms, common pharmacological effects - analgesic, antipyretic and anti-inflammatory (acetaminophen excepted, common side effects (SE (platelet dysfunction, gastritis and peptic ulcers, renal insufficiency in susceptible patients, water and sodium retention, edemas, nephropathies, and only a few different characteristics – different chemical structures, pharmacokinetics and different therapeutic possibility, different selectivities according to cyclooxygenase pathway 1 and 2, non-steroidal anti-inflammatory drugs (NSAIDs similarities are more apparent than differences. Being known that in a correct treatment benefits would exceed risks, the question “Which anti-inflammatory drug presents the lowest risks for a patient?” is just natural. By the Global Risk Method (GRM and the Maximum Risk Method (MRM we have determined the ranking of fourteen NSAIDs considering the risks presented by each particular NSAID. Nimesulide, Etoricoxib and Celecoxib safety level came superior to the other NSAIDs, whereas Etodolac and Indomethacin present an increased side effects risk.

  16. 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.).

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

    Science.gov (United States)

    Rattner, B.A.; Whitehead, M.A.; Gasper, G.; Meteyer, C.U.; Link, W.A.; Taggart, M.A.; Meharg, A.A.; Pattee, O.H.; Pain, D.J.

    2008-01-01

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

  18. Chemistry, pharmacology, and metabolism of emerging drugs of abuse.

    Science.gov (United States)

    Maurer, Hans H

    2010-10-01

    In recent years, besides the classic designer drugs of the amphetamine type, a series of new drug classes appeared on the illicit drugs market. The chemistry, pharmacology, toxicology, metabolism, and toxicokinetics is discussed of 2,5-dimethoxy amphetamines, 2,5-dimethoxy phenethylamines, beta-keto-amphetamines, phencyclidine derivatives as well as of herbal drugs, ie, Kratom. They have gained popularity and notoriety as rave drugs. The metabolic pathways, the involvement of cytochrome P450 isoenzymes in the main pathways, and their roles in hepatic clearance are also summarized. PMID:20683389

  19. Nuclear imaging to support anti-inflammatory drug discovery and development

    International Nuclear Information System (INIS)

    Nuclear medicine contributes important tools to support anti-inflammatory drug discovery and development. The support provided is manifold: new molecular entities (NME, either small molecules or biologics) labeled with radioisotopes can be applied in animal models and humans to measure biodistribution, target engagement, and pharmacokinetics. In addition, nuclear imaging techniques can be used to select or enrich the patient populations in clinical trials, to assess disease activity, target status and distribution and to quantify response to therapeutic interventions. In the first part of this review we will outline how nuclear imaging techniques can be applied to support informed decision making in drug development. In the second part, we will briefly high-light the use of nuclear imaging of inflammation in drug development in selected diseases, specifically rheumatoid arthritis (RA), inflammatory bowel diseases (IBD), atherosclerosis and - as an emerging topic - cancer.

  20. Triblock polymeric micelles as carriers for anti-inflammatory drug delivery.

    Science.gov (United States)

    Yoncheva, Krassimira; Petrov, Petar; Pencheva, Ivanka; Konstantinov, Spiro

    2015-01-01

    This study evaluated the properties of poly(ethylene oxide)-b-poly(n-butyl acrylate)-b-poly(acrylic acid) (PEO-PnBA-PAA) polymeric micelles as carriers for anti-inflammatory drugs (prednisolone and budesonide). The micelles comprising a hydrophobic PnBA core and a PEO/PAA corona showed average diameter less than 40 nm. The size of the drug-loaded micelles did not change during eight hours into media that mimic physiological fluids indicating high colloidal stability. The calculation of Flory-Huggins parameter showed greater compatibility between budesonide and micellar core suggesting its location in the micellar core, whereas prednisolone was located also into the interface layer. This observation correlated further with slower release of budesonide, especially in acid medium (pH = 1.2). The inclusion of budesonide into micelles showed significant protective effect against the cytotoxic damage induced by the co-cultivation of differentiated human EOL-1 and HT-29 cells. This study revealed the capacity of PEO-PnBA-PAA terpolymer as carrier of nanosized micelles suitable for oral delivery of anti-inflammatory drugs. PMID:25539075

  1. [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. PMID:26724872

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Anton V. Kurinnyi

    2016-08-01

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

  4. 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 for...... age, education, gender, and use of benzodiazepines, we found a relative risk (RR) for AD of 0.38 (0.15 to 0.95) when comparing NSAID users (n = 365) to NSAID non-users (n = 5,893). To address confounding by indication or contraindication, we compared NSAID users with a subset of NSAID non-users who...

  5. New nonsteroidal anti-inflammatory drug in the treatment of different ocular pathology

    OpenAIRE

    A. J. Slonimskij; J. B. Slonimskij; A. S. Obrubov

    2016-01-01

    Purpose. Evaluation of efficacy and safety of a new nonsteroidal anti-inflammatory drug (NSAID) Broxinac (bromfenac 0.09 %).Patients and methods.The study included 79 patients with different mainly inflammatory eye pathology. All of them have got the instillation of Broxinac 1 per day. The duration of treatment ranged from 1 to 4 weeks.Results. No corneal complications and allergic reactions during the treatment were observed. Patients did not note any significant discomfort during instillati...

  6. 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.

  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. PMID:27286841

  8. 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.

  9. Use of anti-inflammatory and analgesic drugs in dogs and cats.

    Science.gov (United States)

    Watson, A D; Nicholson, A; Church, D B; Pearson, M R

    1996-09-01

    Responses (486) were collared from a survey of 5054 Australian veterinarians on their use of anti-inflammatory and analgesic drugs in dogs and cats. Almost all respondents used glucocorticoids (usually prednisolone) to treat allergic, pruritic dermatoses in dogs, while two-thirds also gave fatty acid supplements and one-half used antihistamines. Almost 60% of respondents initially injected a glucocorticoid (frequently a long-acting preparation) when treating inflammatory skin diseases in dogs. More than 90% of respondents used glucocorticoids to treat immune-mediated haemolytic anaemia or thrombocytopenia, and about one-third also gave cytotoxic drugs. Administration of prednisolone on alternate days was generally favoured for long-term enteral steroid therapy. Phenylbutazone was the most preferred treatment for painful or inflammatory musculoskeletal disorders of dogs, but aspirin and pentosan polysulphate were also used widely. Regarding the use of analgesics drugs generally, both narcotic analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) were used more widely in dogs than in cats, but alpha-2 agonists were used similarly in both species. The most commonly used narcotic analgesics were pethidine and buprenorphine in both species, while the NSAIDs used most often were flunixin and dipyrone in dogs and ketoprofen in cats. More than 80% of respondents generally used analgesic drugs with potentially painful surgical procedures, with doses given usually before anaesthetic recovery. Analgesic use rates varied with the condition, ranging from 94% for patients with acute severe trauma, through 60% for cruciate ligament repair and 29% for perineal herniorrahphy, to about 5% for ovariohysterectomy and dog castration. The three clinical signs most frequently nominated as indicators of pain in dogs and cats were (in descending order) vocalisation, response to handling or palpating the affected area, and mental depression. Other items mentioned frequently were

  10. Investigation of Anti-Dermatophytic Effects of Non-Steroidal Anti-Inflammatory Drugs on Trichophyton Mentagrophytes and Epidermophyton Floccosum

    OpenAIRE

    Abdul Hussein, Ali; Al-Janabi, S.

    2011-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common pharmacological group that has three primary therapeutic effects including anti-inflammatory, anti-pyrexia, and analgesia. In this study, seven of NSAIDs were tested against two species of skin pathogenic fungi (dermatophytes). Percentage inhibition was determined for effective agents. Diclofenac, Aspirin and Naproxen showed much more ability to inhibit dermatophytes growth. Epidermophyton floccosum revealed susceptibility to ...

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

    Directory of Open Access Journals (Sweden)

    Argoff CE

    2011-09-01

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

  12. Effects of pretreatment with anti-inflammatory drugs on ozone-induced lung damage in rats

    Energy Technology Data Exchange (ETDEWEB)

    Giri, S.N.; Benson, J.; Siegel, D.M.; Rice, S.A.; Schiedt, M.

    1975-12-01

    The effects of pretreatment with acetylsalicylic acid (aspirin), hydrocortisone, indomethacine, and heparin administered ip against the pulmonary edema produced by O/sub 3/-exposure (4 ppm for 4 hr) were studied in rats. These anti-inflammatory drugs were found to alter the injurious effect of O/sub 3/ on lung differently. First, aspirin at the high dose (125 mg/kg) accentuated O/sub 3/-induced lung injury, and had no effect at the low dose (10 mg/kg); second, hydrocortisone (50 mg/kg) failed to have any effect; third, indomethacin at a high dose (20 mg/kg) offered a significant degree of protection, but had no effect at the low dose (2.5 mg/kg); and fourth, heparin (1000 units/kg) also offered a significant degree of protection against the lung damage normally induced by O/sub 3/-exposure. Several mechanisms for the favorable and unfavorable interactions of anti-inflammatory drugs with O/sub 3/-exposure were discussed.

  13. DRUG NEOMYCIN RELEASE FROM CORDIA DICHOTOMA TRANSDERMAL FILM AND ANTIINFLAMMATORY ACTIVITY

    Directory of Open Access Journals (Sweden)

    A A Shahapurkar

    2011-09-01

    Full Text Available Transdermal Films were prepared using 10 % w/v natural polymer (fruit gum of Cordia dichotoma with different percentage of plasticizer (glycerin 0.10, 0.20 and 0.25 % w/v, same percentage of preservative (methyl paraben 0.1 % w/v and drug (neomycin 0.2 % w/v. The films were casted on glass plates and dried under controlled evaporation. Films prepared with 0.20 % w/v of glycerin showed satisfactory drying after 24 h. They were evaluated by the various parameters like thickness, tensile strength, water uptake, folding endurance, piercing load and skin irritation test. In the present study Cordia dichotoma Transdermal film was investigated for Anti-Inflammatory activity in carrageenan-induced rat paw edema. It was compared to control group and with that of standard drug,diclofenac sodium. The neomycin film with 0.20% plasticizer showed significant result.

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

    Institute of Scientific and Technical Information of China (English)

    Yun Dai; Wei-Hong Wang

    2006-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs)including cyclooxygenase 2 (COX-2) selective inhibitors,are potential agents for the chemoprevention of gastric cancer. Epidemiological and experimental studies have shown that NSAID use is associated with a reduced risk of gastric cancer although many questions remain unanswered such as the optimal dose and duration of treatment. The possible mechanisms for the suppressor effect of NSAIDs on carcinogenesis are the ability to induce apoptosis in epithelial cells and regulation of angiogenesis. Both COX-dependent and COX-independent pathways have a role in the biological activity of NSAIDs. Knowledge of how NSAIDs prevent neoplastic growth will greatly aid the design of better chemopreventive drugs and novel treatments for gastric cancer.

  15. 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; Nilsson, F; Jacobsson, L T H

    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...... cardiovascular adverse events in patients exposed to etoricoxib, celecoxib, or nonselective NSAIDs or totally unexposed to NSAIDs. METHODS: We performed a national register-based cohort study on patients with AS or SpA (n = 21,872) identified in the Swedish national patient register from 1987-2009. Treatment...... 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. No...

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

    Directory of Open Access Journals (Sweden)

    Ananya Chatterjee

    2014-01-01

    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are one of the most commonly used therapeutic drug groups used worldwide for curing an array of health problems like pain, inflammation, cardiovascular complications, and many other diseases, but they may cause different side effects including gastroduodenal disorders. So, there is a growing interest and need to search for nontoxic, antiulcer formulations from medicinal plants to treat NSAIDs induced gastric ulcer. Extensive research has reported on many natural plants like Camellia sinensis, Phyllanthus emblica, Myristica malabarica, Piper betle, Picrorhiza kurroa, and so forth, and their active constituents reduced NSAIDs induced gastric ulcer via their antioxidative as well as immunomodulatory activity. Therefore, use of herbal formulations in daily life may prevent NSAIDs induced gastric ulceration and other side effects.

  17. A Novel Loom of Click Chemistry in Drug Discovery

    Directory of Open Access Journals (Sweden)

    Shweta Verma

    2015-11-01

    Full Text Available Click chemistry is an interesting and novel approach for drug discovery, material science, bioconjugation, radiochemistry and nanoscience. It meets an ever-increasing need for rapid reaction as it fulfills the criterion of an ideal synthesis: efficiency, versatility, selectivity and high yield with variety of starting materials. The present review summarizes all the aspects of 1, 3-dipolar cycloaddition reaction “click reaction” between azides and alkynes catalyzed by copper salts. The ease of purification of products and simplicity of this reaction has opened new pathways in generating vast arrays of compounds with biological potential. Many important reactions fit the concept of click chemistry than others such as cycloaddition of unsaturated species. The present review will outline the deeds of click reaction and its medicinal chemistry application in which click chemistry might be relevant in future.

  18. Amides of non-steroidal anti-inflammatory drugs with thiomorpholine can yield hypolipidemic agents with improved anti-inflammatory activity.

    Science.gov (United States)

    Theodosis-Nobelos, Panagiotis; Kourti, Malamati; Gavalas, Antonios; Rekka, Eleni A

    2016-02-01

    Novel amides of non steroidal anti-inflammatory drugs (NSAIDs), α-lipoic acid and indole-3-acetic acid with thiomorpholine were synthesised by a simple method and at high yields (60-92%). All the NSAID derivatives highly decreased lipidemic indices in the plasma of Triton treated hyperlipidemic rats. The most potent compound was the indomethacin derivative, which decreased total cholesterol, triglycerides and LDL cholesterol by 73%, 80% and 83%, respectively. They reduced acute inflammation equally or more than most parent acids. Hence, it could be concluded that amides of common NSAIDs with thiomorpholine acquire considerable hypolipidemic potency, while they preserve or augment their anti-inflammatory activity, thus addressing significant risk factors for atherogenesis. PMID:26750253

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

    International Nuclear Information System (INIS)

    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 (Zeq) 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. • Zeff 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

  20. [Nonsteroid anti-inflammatory drugs (NSAID) and risk of cardiovascular events. Literature review and clinical implications].

    Science.gov (United States)

    Temporelli, Pier Luigi; Zito, Giovanni Battista; Pedretti, Roberto Franco; Belisarii, Franceso Iachini; Putortí, Giuseppe; Faggiano, Pompilio

    2014-09-01

    Non steroid anti-inflammatory drugs (NSAIDs) are largely used for treatment of acute and chronic pain, even for long periods of time (months or years). While it is known that their use is frequently associated with gastrointestinal damage, including major bleedings from peptic ulcer, the risk of cardiovascular events related to NSAID has received much less attention. However, there is a large body of evidence showing that NSAIDs (both "traditional", such as diclofenac or indobufen, and selective cyclooxygenase inhibitors, COX-2) are associated with a significant increase of risk of cardiovascular events, both fatal and nonfatal. Consequently, several options have been proposed for the treatment of pain, including the use of analgesic drugs with different mechanisms of action, such as the opiates. Of interest, the Italian Drug Agency (AIFA) published a few years ago a warning (Nota 66) on the careful prescription of NSAIDs in patients with overt heart disease, such as coronary artery disease and heart failure. Aim of this paper is to present the current status of knowledge on the proper use of NSAIDs and other analgesic drugs in the management of acute and chronic pain. PMID:26058269

  1. Nicolau syndrome after intramuscular injection of non-steroidal anti-inflammatory drugs (NSAID).

    Science.gov (United States)

    Dadaci, Mehmet; Altuntas, Zeynep; Ince, Bilsev; Bilgen, Fatma; Tufekci, Osman; Poyraz, Necdet

    2015-01-01

    Nicolau syndrome is a rare complication of intramuscular injection that leads to local ischemic necrosis of the skin and adipose tissue. In this paper, we discuss etiologies, risk factors, and treatment options for gluteal Nicolau syndrome referring to patients treated in our hospital. Our study includes 17 women who visited our clinic with symptoms of gluteal necrosis secondary to intramuscular injection. The following variables were taken into account: injection site, drug administered, frequency of injections, the person who administered the injections, needle size, and needle tip color. Magnetic resonance images obtained in the aftermath of intramuscular injection application were carefully analyzed for presence of necrosis, cyst formation and the thickness of the gluteal fat tissue layer. Drugs that had been received in intramuscular injection were exclusively non-steroidal anti-inflammatory drugs. Mean patient BMI was 41.8 (all patients were considered as obese), and mean gluteal fat thickness was 54 mm. Standard length of needles (3.8 cm) had been used in procedures. The wounds were treated with primary closure in 11 patients and with local flap therapy in 6 patients. The observed necrosis was a consequence of misplaced gluteal injection, where drugs were injected into the adipose tissue instead of the muscle due to the extreme thickness of the fat layer, on one hand, and the inappropriate length of standard needles, on the other hand. Intramuscular injection should be avoided in obese patients whenever possible: if it is necessary, proper injection technique should be used. PMID:25725145

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

    Directory of Open Access Journals (Sweden)

    Mehmet Dadaci

    2015-01-01

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

  3. Interactions between non-steroidal anti-inflammatory drugs and lipid membranes

    Science.gov (United States)

    Boggara, Mohan; Krishnamoorti, Ramanan

    2008-03-01

    Chronic usage of Non-steroidal anti-inflammatory drugs(NSAIDs) leads to gastrointestinal toxicity and clinical evidences point the cause to direct interactions between NSAIDs and phospholipid membranes. Also, NSAIDs pre-associated with phospholipid vesicles are shown to be safer and therapeutically more effective than unmodified ones. Our initial experiments and simulations on the partitioning of Aspirin and Ibuprofen clearly indicate role played by the drug structure in drug-membrane interactions. Those results motivated systematic molecular dynamics simulations of membranes with NSAIDs of different size, structure and pKa values. Our results suggest high partition coefficients for these NSAIDs in the membrane compared to water and thinning effect on the bilayer. Our small angle neutron scattering and reflectivity studies on DMPC-Ibuprofen systems indicate that the drug affects both ˜5 nm thick bilayer and overall ˜100 nm diameter vesicle, indicating that NSAIDs affect vesicles on various length scales. We will discuss the structural perturbations to membranes due to NSAIDs at clinically relevant molar ratios and their implications on the use of vesicles as delivery vehicles for NSAIDs.

  4. Prescription Nonsteroidal Anti-Inflammatory Medicines

    Science.gov (United States)

    MENU Return to Web version Prescription Nonsteroidal Anti-Inflammatory Medicines Prescription Nonsteroidal Anti-Inflammatory Medicines How do prescription nonsteroidal anti-inflammatory drugs work? Nonsteroidal anti-inflammatory drugs (also called NSAIDs) stop cyclooxygenase ...

  5. 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

  6. Pharmacodynamics and pharmacokinetics of nonsteroidal anti-inflammatory drugs in species of veterinary interest.

    Science.gov (United States)

    Lees, P; Landoni, M F; Giraudel, J; Toutain, P L

    2004-12-01

    This review summarises selected aspects of the pharmacokinetics (PK) and pharmacodynamics (PD) of nonsteroidal anti-inflammatory drugs (NSAIDs). It is not intended to be comprehensive, in that it covers neither minor species nor several important aspects of NSAID PD. The limited objective of the review is to summarise those aspects of NSAID PK and PD, which are important to an understanding of PK-PD integration and PK-PD modelling (the subject of the next review in this issue). The general features of NSAID PK are: usually good bioavailability from oral, intramuscular and subcutaneous administration routes (but with delayed absorption in horses and ruminants after oral dosing), a high degree of binding to plasma protein, low volumes of distribution, limited excretion of administered dose as parent drug in urine, marked inter-species differences in clearance and elimination half-life and ready penetration into and slow clearance from acute inflammatory exudate. The therapeutic effects of NSAIDs are exerted both locally (at peripheral inflammatory sites) and centrally. There is widespread acceptance that the principal mechanism of action (both PD and toxicodynamics) of NSAIDs at the molecular level comprises inhibition of cyclooxygenase (COX), an enzyme in the arachidonic acid cascade, which generates inflammatory mediators of the prostaglandin group. However, NSAIDs possess also many other actions at the molecular level. Two isoforms of COX have been identified. Inhibition of COX-1 is likely to account for most of the side-effects of NSAIDs (gastrointestinal irritation, renotoxicity and inhibition of blood clotting) but a minor contribution also to some of the therapeutic effects (analgesic and anti-inflammatory actions) cannot be excluded. Inhibition of COX-2 accounts for most and possibly all of the therapeutic effects of NSAIDs. Consequently, there has been an intensive search to identify and develop drugs with selectivity for inhibition of COX-2. Whole blood in

  7. Use of nonsteroidal anti-inflammatory drugs in patients with vertebral osteoporotic fractures

    Directory of Open Access Journals (Sweden)

    R. Bortolotti

    2011-09-01

    Full Text Available Objective: The aim of the study was to assess the use of Non Steroidal Anti-Inflammatory Drugs (NSAIDs in patients with a history of osteoporotic vertebral fractures. Methods: We investigated 119 patients with postmenopausal osteoporosis complicated by one or more non recent vertebral fractures. Results: More than 60% of the patients took at least one dose of NSAID weekly. The most prescribed NSAID was nimesulide, at a dose with an exclusively antalgic effect. Patients with wedge fracture and those with a documented vertebral fracture in the last 12 months were those taking NSAIDs more frequently. 77% of the patients that used NSAIDs had concomitant features of osteoarthritis, mainly at the spine or at the knee. The use of NSAIDs was negatively related to the use of specific therapy for osteoporosis, particularly for oral daily tablets. Conclusions: This study highlights the significant use of NSAIDs in patients with osteoporotic vertebral fractures and the overlap between osteoporosis, osteoarthritis and related treatments.

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

    DEFF Research Database (Denmark)

    Brøns, Nanna; Baandrup, Louise; Dehlendorff, Christian; Kjaer, Susanne K

    2015-01-01

    potential confounders. Analyses were stratified by endometrial cancer type, and potential effect modification by parity, obesity, and hormone replacement therapy (HRT) use was investigated. RESULTS: We identified 5,382 endometrial cancer cases and 72,127 controls. Endometrial cancer was not associated with......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...... 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...

  9. 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.

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

    International Nuclear Information System (INIS)

    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. 14C-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 14C-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.

  11. 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...... at baseline, during graded 20-min exercise sessions at 25%, 50% and 75% of the maximal oxygen uptake rate, and subsequently during two 1-h recovery periods. Heart rate, arterial blood pressure, cardiac output and plasma catecholamines at rest and during exercise were not altered by indomethacin or nabumetone...

  12. 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 was...

  13. Nonsteroidal anti-inflammatory drugs in the treatment of low back pain

    Directory of Open Access Journals (Sweden)

    Kuritzky L

    2012-11-01

    Full Text Available Louis Kuritzky George P SamrajDepartment of Community Health and Family Medicine, University of Florida, Gainesville, FL, USAAbstract: Low back pain (LBP is amongst the top ten most common conditions presenting to primary care clinicians in the ambulatory setting. Further, it accounts for a significant amount of health care expenditure; indeed, over one third of all disability dollars spent in the United States is attributable to low back pain. In most cases, acute low back pain is a self-limiting disease. There are many evidence-based guidelines for the management of LBP. The most common risk factor for development of LBP is previous LBP, heavy physical work, and psychosocial risk factors. Management of LBP includes identification of red flags, exclusion of specific secondary causes, and comprehensive musculoskeletal/neurological examination of the lower extremities. In uncomplicated LBP, imaging is unnecessary unless symptoms become protracted. Reassurance that LBP will likely resolve and advice to maintain an active lifestyle despite LBP are the cornerstones of management. Medications are provided not because they change the natural history of the disorder, but rather because they enhance the ability of the patient to become more active, and in some cases, to sleep better. The most commonly prescribed medications include nonsteroidal anti-inflammatory drugs (NSAIDs and muscle relaxants. Although NSAIDs are a chemically diverse class, their similarities, efficacy, tolerability, and adverse effect profile have more similarities than differences. The most common side effects of NSAIDs are gastrointestinal. Agents with cyclo-oxygenase 2 selectivity are associated with reduced gastrointestinal bleeding, but problematic increases in adverse cardiovascular outcomes continue to spark concern. Fortunately, short-term use of NSAIDs for LBP is generally both safe and effective. This review will focus on the role of NSAIDs in the management of LBP

  14. Hypersensitivity to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Cross-Intolerance Reactions.

    Science.gov (United States)

    Blanca-López, N; Cornejo-García, J A; Plaza-Serón, M C; Doña, I; Torres-Jaén, M J; Canto, G; Padilla-España, L; Kidon, M; Perkins, J R; Blanca, M

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are used worldwide and are responsible for several types of drug hypersensitivity reactions (DHRs) in all age groups. The 2 major groups of DHRs to NSAIDs are those induced by immunological mechanisms (selective reactions) and those where inflammatory mediators are released through activation of the prostaglandin-leukotriene pathway without specific immunological recognition (cross-intolerance). In the present review, we focus on cross-intolerance reactions, which are the most frequent DHRs and are becoming a topic of major interest in children and adolescents. Paracetamol and ibuprofen are the drugs that most frequently cause DHRs in children; other NSAIDs are responsible for reactions in adolescents. In vivo and in vitro tests are of limited diagnostic value, with some exceptions for the less common selective reactions. In cross-intolerance, the clinical history and controlled administration are in many instances the only way to establish a diagnosis and look for alternatives. The clinical history is diagnostic when consistent symptoms occur repeatedly after exposure to NSAIDs with different chemical structures. Cutaneous and respiratory symptoms often co-occur in young children. The natural history of these reactions in children is unknown, and some patients can develop tolerance over time. Atopy remains a major risk factor for cross-intolerant reactions. The increasing interest in hypersensitivity to NSAIDs with improvements in patient phenotyping and the information provided by pharmacogenetics will improve our understanding and management of these reactions in the near future. PMID:26310040

  15. Hypersensitivity Reactions to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Selective Reactions.

    Science.gov (United States)

    Blanca-López, N; Cornejo-García, J A; Pérez-Alzate, D; Pérez-Sánchez, N; Plaza-Serón, M C; Doña, I; Torres, M J; Canto, G; Kidon, M; Perkins, J R; Blanca, M

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are used throughout the world to treat pain and inflammation; however, they can trigger several types of drug hypersensitivity reactions (DHRs) in all age groups. Although most such reactions occur through activation of the leukotriene pathway without specific immunological recognition (cross-intolerance), a significant number of DHRs to NSAIDs are due to immunological mechanisms (selective reactions [SRs]). SRs are thought to be induced by specific IgE antibodies or by T cells. In this manuscript, we focus on SRs, which are of great concern in children and adolescents and comprise a heterogeneous set of clinical pictures ranging from mild entities such as urticaria/angioedema to potentially life-threatening conditions such as Stevens-Johnson syndrome/toxic epidermal necrolysis. Paracetamol and ibuprofen are the most frequent elicitors of IgE-mediated SRs, although pyrazolones have also been implicated. T cell-mediated reactions are infrequent in children but have been associated with ibuprofen, naproxen, and dipyrone. In this review, we analyze the available literature on SRs in children and adolescents, with emphasis on epidemiological data, mechanisms, and drugs involved, as well as on diagnostic procedures. PMID:26817135

  16. Nonsteroidal anti-inflammatory drugs and antihypertensives: how do they relate?

    Science.gov (United States)

    Khatchadourian, Zovinar Der; Moreno-Hay, Isabel; de Leeuw, Reny

    2014-06-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely available as over-the-counter medications, despite their numerous side effects and drug interactions. The aim of this article is to increase awareness of the hypertensive potential of NSAIDs and their interference with antihypertensives. Patients with hypertension appear to be more susceptible than normotensive individuals to the blood pressure-increasing effect of NSAIDs. Most studies have found that short-term use of NSAIDs does not pose a major risk for hypertension or increase in cardiovascular disease in healthy individuals. The calcium channel blockers and β-blockers seem to be least affected by the concomitant use of NSAIDs. A dentist must weigh the benefits and disadvantages of using NSAIDs in patients taking antihypertensive drugs. For those who may be at greater risk, such as patients with hypertension and the elderly, careful selection of the class of NSAID and close monitoring are appropriate measures, especially if long-term use is anticipated. PMID:24755117

  17. Adverse drug reactions of nonsteroidal anti-inflammatory drugs in orthopedic patients

    Directory of Open Access Journals (Sweden)

    Alpa Pragnesh Gor

    2011-01-01

    Full Text Available Objectives: To identify the ADRs due to NSAIDs and to know how to monitor the drug′s effect. Materials and Methods: A descriptive study was undertaken in the Orthopedic Outpatients Department of a tertiary care teaching hospital. Hundred patients were enrolled in this study to observe the risk of adverse drug reactions (ADRs due to NSAIDs. All the ADRs were further analyzed in relation to age and sex, type of drug and its pattern. Probability scale was used for the causality assessment of the ADRs. Results: 26% of the 100 patients developed ADR due to NSAIDs. There was not much of a difference in the number of the ADRs in relation to the gender. Diclofenac was the highest prescribed drug (65 patients, followed by paracetamol (12, nimesulide (10, ibuprofen (6, piroxicam (5 and Etoricoxib (2. Diclofenac accounted for the maximum number (73% of ADRs, followed by nimesulide (16%, paracetamol (7%, and Etoricoxib (4%. Conclusion: Pharmacovigilance improves recognition of ADRs by the medical students. It allows the treating physician to identify the ADR associated with drugs, in particular, with the ones considered relatively safe and with those commonly prescribed by the medical and non-health professionals.

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

    OpenAIRE

    Zi Gu; Aihua Wu; Li Li; Zhi Ping (Gordon) Xu

    2014-01-01

    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 hy...

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

    Institute of Scientific and Technical Information of China (English)

    Mario Guslandi

    2006-01-01

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

  20. 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...

  1. Chiral separation of non-steroidal anti-inflammatory drugs by preparative and simulated moving bed chromatography

    OpenAIRE

    Ribeiro, António E.; Gomes, Pedro Sá; Pais, L.S.; A.E. Rodrigues

    2011-01-01

    The work presents modelling, simulation and experimental results for the chiral separation of non-steroidal anti-inflammatory drugs, particularly, the optimization of mobile phase composition under preparative and simulated moving bed chromatography. The experimental separation of two chiral systems (ketoprofen and flurbiprofen enantiomers) will be presented to show how compounds of the same family can lead to different solutions.

  2. Using UV-VIS spectrophotometry for determining ecotoxicity of selected non-steroidal anti-inflammatory drugs

    OpenAIRE

    Čapka, L. (Lukáš); Zlámalová Gargošová, H.; Vávrová, M.

    2015-01-01

    This paper presents the use of UV-VIS spectrophotometry as a means of determining ecotoxicity. The method is based on spectrophotometric measuring of micro-algae Pseudokirchneriella subcapitata in water suspension. Six non-steroidal anti-inflammatory drugs were selected as target compounds.

  3. 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...

  4. 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.

  5. Effects of Aspirin and Other Nonsteroidal Anti-Inflammatory Drugs on Biofilms and Planktonic Cells of Candida albicans

    OpenAIRE

    Alem, Mohammed A. S.; Douglas, L. Julia

    2004-01-01

    Prostaglandins are now known to be produced by Candida albicans and may play an important role in fungal colonization. Their synthesis in mammalian cells is decreased by inhibitors of the cyclooxygenase isoenzymes required for prostaglandin formation. In the present study, a catheter disk model system was used to investigate the effects of nonsteroidal anti-inflammatory drugs (all cyclooxygenase inhibitors) on biofilm formation by three strains of C. albicans. Seven of nine drugs tested at a ...

  6. Drug Design and Analysis In Silico of Sapelenin G, an Acyclic Triterpenoid as Potential Anti-Inflammatory

    OpenAIRE

    Ngabireng Marie. Claude; Menye Cyrille; Kouam F.Simeon; Ntede N .Hyppolite; Tagoudjeu Jacques; Awono Onana

    2013-01-01

    Diverse non-steriodal anti-inflammatory drugs and COX-2 inhibitors are a class of drugs which selectively inhibit COX-2, provide relief from pain and inflammation. However, they lack anti-thrombotic activity and hence lead to cardiovascular and renal liabilities apart from gastrointestinal irritation. To ameliorate this situation, research can be foccuss on the products originating from natural products that could offer better relief from inflammation than the currently used co...

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

    Directory of Open Access Journals (Sweden)

    Evrim eGurpinar

    2013-07-01

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

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    M M Hamzah

    2011-06-01

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

  10. Delayed contact hypersensitivity to non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    Gniazdowska, B; Ruëff, F; Przybilla, B

    1999-02-01

    Several non-steroidal anti-inflammatory drugs (NSAIDs) are available for topical treatment of acute soft tissue trauma or degenerative musculoskeletal disorders; the NSAID bufexamac is mainly used for therapy of chronic inflammatory skin diseases. In order to assess the occurrence of contact allergy to NSAIDs in 371 consecutive patients presenting for diagnosis of presumed contact allergy, patch tests were performed with a standard series and additionally with a series of NSAIDs, comprising acetylsalicylic acid, bufexamac, diclofenac, etofenamate, felbinac, flufenamic acid, ibuprofen, indomethacin, and piroxicam. 17 individuals (4.6%) exhibited delayed hypersensitivity to one of the NSAID preparations: 12 patients (3.2%) had patch test reactions to bufexamac, 2 (0.5%) to etofenamate, 2 (0.5%) to indomethacin, and 1 patient (0.3%) to flufenamic acid. These patch test results corresponded well to the individual history in 11 individuals (including 10 patients with reactions to bufexamac), and in 2 patients the clinical relevance of the reactions was probable. In view of the high frequency of allergic contact reactions to bufexamac, we propose to test this drug particularly in patients with atopic eczema or other chronic eczematous diseases. PMID:10048648

  11. 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.

  12. 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.

  13. 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.

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

    International Nuclear Information System (INIS)

    Of techniques used to evaluate gastrointestinal (GI) bleeding, use of radiochromium (51Cr)-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 51Cr 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

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

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    Alireza Rouhani

    2013-09-01

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

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

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    Alireza Rouhani

    2013-09-01

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

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

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    Chalelgn Kassaw

    2012-01-01

    Full Text Available Background: Non-steroidal anti-inflammatory drugs (NSAIDs are among the widely used drugs and are often used by pregnant women. However, they can have significant teratogenic effects. The aim of the study was to investigate pregnant women′s knowledge about NSAIDs use during pregnancy and their perception and consumption pattern. Materials and Methods: The study was a cross sectional study on women waiting for a consultation in the selected maternity hospitals in Addis Ababa, Ethiopia. The pregnant women were selected randomly and then interviewed by using standardized questionnaires. Result : A total of 224 pregnant women were involved in the study. Out of those, 203 (90.6% of them have taken NSAIDs since the beginning of their pregnancy. About 201 (89.7%, 198 (88.4% and 189 (84.4% of the pregnant women considered that ibuprofen, diclofenac and aspirin are not NSAIDs respectively. Regarding analgesic effect of NSAIDs, 97 (43.3% of the pregnant women believed that NSAIDs are effective for treating pain. Acetaminophen was considered as the most effective treatment for pain by 84 (37.50% of the patients. Conclusion: Acetaminophen is the most common analgesic that was taken by most pregnant women. The knowledge of pregnant women about NSAIDs is poor.

  18. 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.

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

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    N. V. Chichasova

    2016-01-01

    Full Text Available The review gives data on the safety of nimesulide used for the treatment of chronic joint diseases. The first-line treatment at its any stage for joint diseases is nonsteroidal anti-inflammatory drugs (NSAIDs. Questions have recently arisen of the safety of nimesulide; however, epidemiological findings and clinical experience confirm a positive benefit/risk profile of nimesulide in the treatment of acute pain. The International Consensus Meeting (Vienna, 2014 noted that the risk of severe adverse hepatic NSAID reactions was low and the rate of liver damage associated with nimesulide was completely similar to that observed with other NSAIDs. There are data available in the literature on the rate of serious adverse liver reactions to different NSAIDs and paracetamol. The rate of such reactions to all NSAIDs per million patientyears was 1.55 and that to nimesulide was 1.88. The members of the International Consensus Group concluded that nimesulide, if properly used, remained a valuable and safe drug for the treatment of various conditions, characterized by the presence of acute inflammatory pain, by virtue of the rapid onset of analgesic action and an evidence-based positive benefit/risk profile. The long successful experience with nimesulide in our country suggests that the agent may be successfully used to treat chronic and acute pain (including dysmenorrhea in a daily dose of 200 mg/day. The safety profile of the drug is quite satisfactorily for all adverse reactions typical of NSAIDs, including its negative effect on the liver.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

    AIM: The study was to screen the possible risk factors of adverse drug reaction (ADR) induced by non-steroidal anti-inflammatory drugs (NSAIDs) in Shanghai patients with arthropathy. METHODS: The subjects were randomly selected from a database of outpatients with arthropathy from 9 main hospitals in Shanghai. A door to door retrospective epidemiological survey was used to collect demographic information about the patients, both individual and familial. This included data on their medical histories, lifestyle and dietary habits, history of smoking and alcohol consumption, history of drug therapy, quality of life (QOL) prior to NSAIDs intake, history of NSAIDs therapy and its ADR events, etc. Descriptive statistical methods and univariate analysis were also used to identify possible risk factors for ADRs induced by NSAIDs. RESULTS: Of the 1002 patients surveyed, the average length of NSAIDs intake was 2 years. ADR incidence from different NSAIDs was high, in a range from 46.7 %-66.2 %.In general, the candidate risk factors for ADRs were different for each NSAID. Each of the candidate risk factors were defined and studied in order to evaluate its role in the determination of ADRs from NSAIDs. "Family history of ADRs caused by NSAIDs" was found to be a significant risk factor for the four commonly used NSAIDs:meloxicam, diclofenac, nimesulide, and nabumetone. CONCLUSION: A retrospective epidemiological survey was useful in detecting the risk factors for ADRs caused by NSAIDs. The study found that different NSAIDs might have different risk factors and that there is no single risk factor universally applicable to all NSAIDs.

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

    Science.gov (United States)

    Paul, Mithun; Dastidar, Parthasarathi

    2016-01-18

    A new series of Mn(II) coordination polymers, namely, [{Mn(L)(H2 O)2 }⋅2 Nap]∞ (CP1), [{Mn(L)(Ibu)2 (H2 O)2 }]∞ (CP2), [{Mn(L)(Flr)2 (H2 O)2 }]∞ (CP3), [{Mn(L)(Ind)2 (H2 O)2 }⋅H2 O]∞ (CP4), [{Mn2 (L)2 (μ-Flu)4 (H2 O)}⋅L]∞ (CP5), [{Mn2 (L)2 (μ-Tol)4 (H2 O)2 }]∞ (CP6) and [{Mn2 (L)2 (μ-Mef)4 (H2 O)2 }]∞ (CP7) (Nap=naproxen, Ibu=ibuprofen, Flr=flurbiprofen, Ind=indometacin, Flu=flufenamic acid, Tol=tolfenamic acid and Mef=mefenamic acid) derived from various non-steroidal anti-inflammatory drugs (NSAIDs) and the organic linker 1,2-bis(4-pyridyl)ethylene (L) have been synthesized with the aim of being used for cell imaging and drug delivery. Single-crystal X-ray diffraction (SXRD) studies revealed that the NSAID molecules were part of the coordination polymeric network either through coordination to the metal center (in the majority of the cases) or through hydrogen bonding. Remarkably, all the Mn(II) coordination polymers were found to be soluble in DMSO, thereby making them particularly suitable for the desired biological applications. Two of the coordination polymers (namely, CP1 and CP3) reported herein, were found to be photoluminescent both in the solid as well as in the solution state. Subsequent experiments (namely, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), and PGE2 (prostaglandin E2 ) assays) established their biocompatibility and anti-inflammatory response. In vitro studies by using a macrophage cell line (i.e., RAW 264.7) revealed that both CP1 and CP3 were excellent cell imaging agents. Finally, biodegradability studies under simulated physiological conditions in phosphate-buffered saline (PBS) at pH 7.6 showed that slow and sustained release of the corresponding NSAID was indeed possible from both CP1 and CP3. PMID:26660274

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

    Science.gov (United States)

    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. PMID:6983482

  3. Fractals and self-organized criticality in anti-inflammatory drugs

    Science.gov (United States)

    Phillips, J. C.

    2014-12-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) act through inhibiting prostaglandin synthesis, a catalytic activity possessed by two distinct cyclooxygenase (COX-1 and COX-2) isozymes encoded by separate genes. The discovery of COX-2 launched a new era in NSAID pharmacology, resulting in the synthesis, marketing, and widespread use of COX-2 selective inhibitors. Extensive structural studies of the biology of prostaglandin synthesis and inhibition have explained some of the differences between COX-1 and COX-2 functionality, but others are still unexplained. Notably these include molecular differences that cause COX-1 inhibitors to produce a slight decrease, and COX-2 inhibitors to induce a significant increase, in heart attacks and strokes. These differences were unexpected because of the 60% overall COX-1 and COX-2 sequence similarity and the 1-2 conservation of catalytic sites. Hydropathic analysis shows important bicyclic differences between COX-1 and COX-2 on a large scale outside the catalytic pocket. These differences involve much stronger amphiphilic interactions in COX-2 than in COX-1, and may explain the selective antiplatelet effectiveness of COX-2. Success of the non-Euclidean structural analysis is the result of using the new Brazilian hydropathicity scale based on self-organized criticality (SOC) of universal protein modules.

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

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    Huyck Matthew

    2005-01-01

    Full Text Available Abstract Background Nonsteroidal anti-inflammatory drugs (NSAID use may protect against Alzheimer's disease (AD risk. We sought examine the association between NSAID use and risk of AD, and potential effect modification by APOE-ε4 carrier status and ethnicity. Methods The MIRAGE Study is a multi-center family study of genetic and environmental risk factors for AD. Subjects comprised 691 AD patients (probands and 973 family members enrolled at 15 research centers between 1996 and 2002. The primary independent and dependent variables were prior NSAID use and AD case status, respectively. We stratified the dataset in order to evaluate whether the association between NSAID use and AD was similar in APOE-ε4 carriers and non-carriers. Ethnicity was similarly examined as an effect modifier. Results NSAID use was less frequent in cases compared to controls in the overall sample (adjusted OR = 0.64; 95% CI = 0.38–1.05. The benefit of NSAID use appeared more pronounced among APOE-ε4 carriers (adjusted OR = 0.49; 95% CI = 0.24–0.98 compared to non-carriers, although this association was not statistically significant. The pattern of association was similar in Caucasian and African Americans. Conclusions NSAID use is inversely associated with AD and may be modified by APOE genotype. Prospective studies and clinical trials of sufficient power to detect effect modification by APOE-ε4 carrier status are needed.

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

    AIM: To investigate the association between individual or combined use of non-steroidal anti-inflammatory drugs (NSAIDs) or statins and colorectal cancer risk. METHODS: In a population-based case-control study in women, we examined the association between NSAIDs and statin use and the risk of colorectal cancers. We further investigated whether the use of statins modifies the protective effect of NSAIDs. Female cases ( n = 669)of colorectal cancer aged 50-74 years were identified from a statewide registry in Wisconsin during 1999-2001. Community control women ( n = 1375) were randomly selected from lists of licensed drivers and Medicare beneficiaries. Medication use and risk factor information were gathered during a structured telephone interview. A multivariable logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval (CI). RESULTS: Overall, NSAIDs users had a 30% reduction in risk of colorectal cancer (95% CI: 0.56-0.88). Statin use was not associated with colorectal cancer risk (OR = 1.17, 95% CI: 0.74-1.85), regardless of structural type (lipophilic or hydrophilic), duration of use, or recency. There was no evidence of an interaction between NSAIDs and statins and colorectal cancer risk ( P-interaction = 0.28). CONCLUSION: Although our results confirm the inverse association between NSAIDs use and colorectal cancer risk, they do not support a risk reduction in statin users, or an interaction effect of combined NSAIDs and statin use.

  6. Gastrointestinal blood loss induced by three different non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    Bidlingmaier, A; Hammermaier, A; Nagyiványi, P; Pabst, G; Waitzinger, J

    1995-04-01

    A clinical study was performed on 18 healthy volunteers to compare the gastrointestinal daily blood loss induced by oral intake of three different non-steroidal anti-inflammatory drugs, lysine clonixinate (CAS 55837-30-4), ibuprofen (CAS 15687-27-1) and acetylsalicylic acid (CAS 50-78-2 ASA). For quantitative determination of gastrointestinal blood loss, autologous erythrocytes were radiolabelled in vitro with 51Cr and reinfused at study start. The amount of radioactivity excreted in faeces was measured during a placebo baseline phase of three days, a treatment phase of five days with thrice daily dosing of ASA, ibuprofen or lysine clonixinate and a subsequent wash-out phase of five days. The highest increase of mean daily blood loss over baseline was observed after treatment with ASA (+ 1.66 ml/d versus baseline). Treatment with ibuprofen led to an increase of mean daily blood loss by + 0.52 ml/d. During treatment with lysine clonixinate the mean increase of daily blood loss was +0.32 ml/d versus baseline. In the ibuprofen and lysine clonixinate treatment groups the values of mean daily blood loss decreased during the wash-out phase with respect to the verum phase, whereas the mean daily blood loss during the wash-out phase after treatment with ASA even increased in comparison to the verum phase (mean daily blood loss: +2.07 ml/d versus baseline. PMID:7779148

  7. ASPECTS REGARDING THE EFFECT OF ANTIINFLAMMATORY DRUGS ON DELAYED ONSET MUSCLE SORENESS

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    Honceriu C.

    2013-07-01

    Full Text Available The objectives of the study are to investigate the effects of using Diclofenac ointment for delayed onset muscle soreness. The research has been conducted on two groups of junior football players, males, the number of 9 each (control and treated, which has been induced by this type of muscle soreness with specific exercises. The treated group used Diclofenac gel for the relief of musculoskeletal pain. The evaluation of values of muscular strength (Squat Jump, Jump Countermovement, Free Jump, 60 ˝ Free Jump showed statistically significant variations in 48 hours and respectively 6 days compared to baseline measurements for both the control group and to the treaty, the better comparability under the Single Factor ANOVA being for Squat Jump. Force recovery was better for the group treated with Diclofenac for tests performed at 48 hours, and for the control group after 6 days. This suggests that treatment of delayed onset muscle soreness with Diclofenac is effective only for short-term recovery, this anti-inflammatory drug having a dual and antagonistic effect on muscular regeneration.

  8. 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.

  9. Adverse respiratory reactions to aspirin and nonsteroidal anti-inflammatory drugs.

    Science.gov (United States)

    Simon, Ronald A

    2004-01-01

    Aspirin-exacerbated respiratory disease (AERD) is an adult-onset condition that manifests as asthma, rhinosinusitis/nasal polyps, and sensitivity to aspirin and other cyclooxygenase-1 (COX-1)-inhibitor nonsteroidal anti-inflammatory drugs (NSAIDs). There is no cross-sensitivity to highly selective COX-2 inhibitors. AERD is chronic and does not improve with avoidance of COX-1 inhibitors. The diagnosis of AERD is made through provocative challenge testing. Following a positive aspirin challenge, patients can be desensitized to aspirin and NSAIDs. The desensitized state can be maintained indefinitely with continued daily administration. After desensitization, there is an approximately 48-hour refractory period to adverse effects from aspirin. The pathogenesis of AERD remains unknown, but these patients have been shown to have multiple abnormalities in arachidonic acid metabolism and in cysteinyl leukotriene 1 receptors. AERD patients can take up to 650 mg of acetaminophen for analgesic or antipyretic relief. Patients can also use weak COX-1 inhibitors, such as sodium salicylate or choline magnesium trisalicylate. Treatment of AERD patients with antileukotriene medications has been helpful but not preferential when compared with non-AERD patients. An alternative treatment for many AERD patients is aspirin desensitization. This is particularly effective in reducing upper-airway mucosal congestion, nasal polyp formation, and systemic steroids. PMID:14680616

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

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    T A Raskina

    2011-12-01

    Full Text Available Objective: to study the side effect profile of nonsteroidal anti-inflammatory drugs (NSAIDs in patients with rheumatic diseases (RD. Subjects and methods. The study enrolled 373 patients (301 women and 72 men with RD, the mean age of whom was 58.9±1.3 years; the duration of the disease was 6.1±0.7 years. This study was cross-sectional and randomized, by applying a questionnaire for the estimation of the NSAID side effect profile, developed at the Research Institute of Rheumatology, Russian Academy of Medical Sciences. Results and discussion. NSAIDs are an effective agent for the symptomatic treatment of pain and inflammation in most RDs. More than 50% of the patients with RD reported unpleasant sensations in the digestive system. Dyspepsia was present in the absolute majority of RD patients (77.7% of the patients with rheumatoid arthritis; 100% of those with ankylosing spondylitis; 47.8% of those with osteoarthosis who had taken for more than a year

  11. [Effect of nonsteroidal antiinflammatory drugs on colonic lipoxygenase and cyclooxygenase activities from patients with colonic neoplasia].

    Science.gov (United States)

    Di Girolamo, G; Franchi, A; De Los Santos, A R; Martí, M L; Farina, M; Fernández de Gimeno, M A

    2001-01-01

    Lysine clonixinate (LC) is a nonsteroidal anti-inflammatory drug (NSAID) with good gastrointestinal tolerance. Treatment with LC at levels equivalent to those found in plasma following therapeutic doses resulted in significant inhibition of both cyclooxygenase 2 (COX-2) and production of 5 hydroxy-eicosatetraeonic acid (5-HETE) and slightly affected levels of cyclooxygenase 1 (COX-1) in in vitro studies carried out on human tissues. This study deals with the in vivo effect of the drug on human colon segments. Experiment 1: Five patients about to undergo hemicholectomy due to colon neoplasia were treated preoperatively with a continuous infusion of LC, to achieve a steady-state concentration between 4 and 6 mg/ml. Human colon segments from the five patients and from another five control patients receiving no treatment with [14C]-arachidonic acid were incubated. Human colon segments treated with LC showed significant inhibition of PGE2, the only prostaglandin (PG) synthesised by the tissue, as well as of 5-HETE. Experiment 2: Fifteen patients received an i.v. bolus of LC 100 mg (n1 = 5); LC 200 mg (n2 = 5) or indomethacin (INDO) 50 mg (n3 = 5). Both doses of LC showed greater inhibition of PGE2 synthesis than the INDO bolus. Both NSAIDs studied proved to have different effects on the production of 5-HETE; while treatment with LC elicited significant inhibition, levels with INDO remained unchanged. Western blotting analysis showed expression of both COX isoforms in colon segments, COX-2 levels being 20% higher. Both types of in vivo studies conducted continuous infusion and i.v. bolus, revealed that LC exerted significant inhibition of basal synthesis of PGE2 and 5-HETE. PMID:11721323

  12. The influence of non-steroidal anti-inflammatory drugs on the gut microbiome.

    Science.gov (United States)

    Rogers, M A M; Aronoff, D M

    2016-02-01

    The composition of the gut microbiome with the use of non-steroidal anti-inflammatory drugs (NSAIDs) has not been fully characterized. Drug use within the past 30 days was ascertained in 155 adults, and stool specimens were submitted for analysis. Area under the receiver operating characteristic curve (AUC) was calculated in logit models to distinguish the relative abundance of operational taxonomic units (OTUs) by medication class. The type of medication had a greater influence on the gut microbiome than the number of medications. NSAIDs were particularly associated with distinct microbial populations. Four OTUs (Prevotella species, Bacteroides species, family Ruminococcaceae, and Barnesiella species) discriminated aspirin users from those using no medication (AUC = 0.96; 95% CI 0.84-1.00). The microbiome profile of celecoxib users was similar to that of ibuprofen users, with both showing enrichment of Acidaminococcaceae and Enterobacteriaceae. Bacteria from families Propionibacteriaceae, Pseudomonadaceae, Puniceicoccaceae and Rikenellaceae were more abundant in ibuprofen users than in controls or naproxen users. Bacteroides species and Erysipelotrichaceae species discriminated individuals using NSAIDs plus proton-pump inhibitors from those using NSAIDs alone (AUC = 0.96; 95% CI 0.87-1.00). Bacteroides species and a bacterium of family Ruminococcaceae discriminated individuals using NSAIDs in combination with antidepressants and laxatives from those using NSAIDs alone (AUC = 0.98; 95% CI 0.93-1.00). In conclusion, bacteria in the gastrointestinal tract reflect the combinations of medications that people ingest. The bacterial composition of the gut varied with the type of NSAID ingested. PMID:26482265

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

    Directory of Open Access Journals (Sweden)

    Edmond F O'Donnell

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

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

    Science.gov (United States)

    Brune, Kay; Patrignani, Paola

    2015-01-01

    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 minimizing plasma concentrations to permit recovery of COX-mediated prostaglandin production in the vascular wall and other organs. Each patient's clinical background, including gastrointestinal and cardiovascular risk factors, should be taken into account when selecting appropriate NSAIDs. New methods are emerging to assist

  15. 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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Taysa Bervian Bassani

    2015-07-01

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

  17. The Proapoptotic Effect of Traditional and Novel Nonsteroidal Anti-Inflammatory Drugs in Mammalian and Yeast Cells

    OpenAIRE

    Gianluca Farrugia; Rena Balzan

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used to treat pain, fever, and inflammation. However, mounting evidence shows that NSAIDs, such as aspirin, have very promising antineoplastic properties. The chemopreventive, antiproliferative behaviour of NSAIDs has been associated with both their inactivation of cyclooxygenases (COX) and their ability to induce apoptosis via pathways that are largely COX-independent. In this review, the various proapoptotic pathways induced by tr...

  18. Effect of some non-steroidal anti-inflammatory drugs on ouabain-induced arrhythmias in guinea-pigs.

    OpenAIRE

    Tripathi, R. M.; Kaushal, R.

    1988-01-01

    1. Effects of some non-steroidal anti-inflammatory drugs on ouabain-induced arrhythmias in guinea-pigs were studied. 2. Ventricular premature beats, ventricular fibrillation and cardiac arrest were induced in pentobarbitone-anaesthetized guinea-pigs by a slow intravenous infusion of ouabain. 3. Aspirin and indomethacin were found to accord a significant protection to the guinea-pigs against arrhythmias whereas ketoprofen was found to be ineffective. 4. It is concluded that the protective effe...

  19. Meat consumption, non-steroidal anti-inflammatory drugs, and mortality among colorectal cancer patients in the California Teachers Study

    OpenAIRE

    Zell, Jason A.; Ziogas, Argyrios; Bernstein, Leslie; Clarke, Christina A.; Deapen, Dennis; Largent, Joan A.; Neuhausen, Susan L.; Stram, Daniel O.; Ursin, Giske; Anton-Culver, Hoda

    2010-01-01

    A low meat diet and regular non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with decreased mortality among colorectal cancer (CRC) patients. Here we investigated the association between pre-diagnosis usual meat consumption and CRC-specific mortality, and whether meat consumption modifies the previously noted association between NSAID use and CRC-specific mortality among women in the California Teachers Study (CTS) cohort. Women joining CTS in 1995–1996 without prior CRC di...

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

    OpenAIRE

    Lionberger, David R; Brennan, Michael J.

    2010-01-01

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

  1. In Patients Who Underwent Total Thyroidectomy Some Non-Steroidal Antiinflammatory Drugs Effects on Thyroid Replacement Therapy

    OpenAIRE

    Süleyman Kargin; Didem Tastekin; Azamet Cezik; Murat Cakir; Kemal Kılıç; M Sinan Iyisoy; Tevfik Küçükkartallar

    2014-01-01

    Objective Non-steroid anti-inflammatory drugs can change serum thyroid hormone concentrations by binding to serum proteins. If misunderstood, this situation can give way to inappropriate diagnoses and faulty treatment planning for thyroid diseases in clinical practice. The purpose of our study was to investigate the effects of ketoprofen, lornoxicam, and etofenamate, which are frequently used in clinical practice, on thyroid function tests. Methodology The study covered 28 rabbits divided int...

  2. Toxicity of non-steroidal anti-inflammatory drugs to Gyps vultures: a new threat from ketoprofen

    OpenAIRE

    Naidoo, Vinny; Wolter, Kerri; Cromarty, Duncan; Diekmann, Maria; Duncan, Neil; Meharg, Andrew A.; Taggart, Mark A.; Venter, Leon; Cuthbert, Richard

    2009-01-01

    Three Gyps vulture species are on the brink of extinction in South Asia owing to the veterinary non-steroidal anti-inflammatory drug (NSAID) diclofenac. Carcasses of domesticated ungulates are the main food source for Asia's vultures and birds die from kidney failure after consuming diclofenac-contaminated tissues. Here, we report on the safety testing of the NSAID ketoprofen, which was not reported to cause mortality in clinical treatment of scavenging birds and is rapidly eliminated from li...

  3. Cross-reactivity to Acetaminophen and Celecoxib According to the Type of Nonsteroidal Anti-inflammatory Drug Hypersensitivity

    OpenAIRE

    Kim, Yoon-Jeong; Lim, Kyung-Hwan; Kim, Mi-Young; Jo, Eun-Jung; Lee, Suh-Young; Lee, Seung-Eun; Yang, Min-Suk; Song, Woo-Jung; Kang, Hye-Ryun; Park, Heung-Woo; Chang, Yoon-Seok; Cho, Sang-Heon; Min, Kyung-Up; Kim, Sae-Hoon

    2013-01-01

    Purpose Identification of tolerable alternative analgesics is crucial for management in nonsteroidal anti-inflammatory drug (NSAID)-sensitive patients. We investigated cross-reactivity of acetaminophen and celecoxib according to the type of aspirin/NSAID hypersensitivity and aimed to determine the risk factors for cross-intolerance. Methods We retrospectively reviewed the medical records of patients intolerant to aspirin and NSAIDs who had undergone an acetaminophen and/or celecoxib oral prov...

  4. Duodenal histology, ulceration, and Helicobacter pylori in the presence or absence of non-steroidal anti-inflammatory drugs.

    OpenAIRE

    Taha, A S; Dahill, S; Nakshabendi, I.; Lee, F D; Sturrock, R D; Russell, R I

    1993-01-01

    Duodenitis and gastric metaplasia, which is often colonised by Helicobacter pylori (H pylori), are increasingly recognised for their importance in the pathogenesis of duodenal ulcers. The situation is not clear in patients receiving non-steroidal anti-inflammatory drugs (NSAIDs), who have a higher risk of peptic ulceration. The aim of this study was to identify the duodenal histological abnormalities in the presence or absence of NSAIDs, H pylori, and duodenal ulceration. Endoscopic duodenal ...

  5. Mechanisms of Action of Non-Steroidal Anti-Inflammatory Drugs for the Prevention of Alzheimer’s Disease

    OpenAIRE

    Cole, Greg M.; Frautschy, Sally A.

    2010-01-01

    Alzheimer’s disease (AD) is accompanied by an activation of the innate immune system, and many epidemiological studies have shown reduced risk for dementia or AD associated with chronic consumption of non-steroidal anti-inflammatory drugs (NSAIDS). These observations led to animal model studies to test the hypothesis that NSAIDs can be disease-modifying for some aspects of AD pathogenesis. NSAIDS cannot only suppress inflammatory targets, which could contribute to neuroprotection, they also s...

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

    OpenAIRE

    Smolović Brigita; Stanisavljević Dejana; Golubović Mileta; Vučković Ljiljana; Miličić Biljana; Đuranović Srđan

    2014-01-01

    Background/Aim. A high risk of bleeding in Helicobacter pylori (H.pylori)-negative, non-steroidal anti-inflammatory drugs (NSAID)-negative ulcers highlights the clinical importance of analysis of the changing trends of peptic ulcer disease. The aim of the study was to investigate the risk factors for ulcer bleeding in patients with non-H. pylori infection, and with no NSAIDs use. Methods. A prospective study included patients with endoscopically diagnosed u...

  7. Adherence to the preventive strategies for nonsteroidal anti-inflammatory drug- or low-dose aspirin-induced gastrointestinal injuries

    OpenAIRE

    Fujita, Tsuyoshi; Kutsumi, Hiromu; Sanuki, Tsuyoshi; Hayakumo, Takanobu; Azuma, Takeshi

    2013-01-01

    As the aging of the population advances, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and/or low-dose aspirin (LDA) is increasing. Their use is accompanied by a risk of serious complications, such as hemorrhage or perforation of the gastrointestinal tract. Therefore, gastroprotective strategies upon the prescription of NSAIDs/LDA are outlined in several guidelines or recommendations. Because all NSAIDs including cyclooxygenase (COX)-2 inhibitors have cardiovascular (CV) toxicity, ...

  8. In Patients Who Underwent Total Thyroidectomy Some Non-Steroidal Antiinflammatory Drugs Effects on Thyroid Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Süleyman Kargin

    2014-03-01

    Full Text Available Objective Non-steroid anti-inflammatory drugs can change serum thyroid hormone concentrations by binding to serum proteins. If misunderstood, this situation can give way to inappropriate diagnoses and faulty treatment planning for thyroid diseases in clinical practice. The purpose of our study was to investigate the effects of ketoprofen, lornoxicam, and etofenamate, which are frequently used in clinical practice, on thyroid function tests. Methodology The study covered 28 rabbits divided into 4 groups. Groups were administered intramuscular injections daily for 10 days. Thyroid hormones concentrations were tested in the blood samples end of day 10. Results An increase in free thyroxin level in the lornoxicam group was recorded on day 7 in comparison to other groups (p=0.015. There was a statistical decrease regarding thyroid stimulant hormone concentration after day 5 in all three groups (Day 5 p=0.000, day 7 p=0.003, day 10 p=0.00. Conclusion We believe that previous history of non-steroid anti-inflammatory drug use should be taken into consideration within the scope of patients’ anamneses because non-steroid anti-inflammatory drug use can change the results of thyroid function tests and this change may lead to misevaluations and mistreatment not only for patients with thyroid diseases but also for normal patients.

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

    Science.gov (United States)

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

    2013-06-01

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

  10. Enhanced Loading and Release of Non-Steroidal Anti-Inflammatory Drugs from Silica-Based Nanoparticle Carriers.

    Science.gov (United States)

    Mohammadzadeh, Mostafa; Nourbakhsh, Mohammad Sadegh; Khodaverdi, Elham; Hadizadeh, Farzin; Omid Malayeri, Sina

    2016-09-01

    Silica nanoparticles can be potentially considered the carriers of controlled drug systems. In this research, non-steroidal anti-inflammatory drugs were used. Diclofenac sodium and piroxicam were loaded on the considered nanosilica using solvent evaporation method. To prove drug encapsulation on the nanosilica and its rate, infrared spectroscopy, X-ray diffraction, and BET were used, and after proving the existence of the drug in the nanosilica matrix and determining the amount of loading, dissolution test was performed in an environment similar to that of stomach and intestine in terms of pH. Drug loading percentage showed that over 90% of drugs were loaded on nanosilica. Dissolution tests in stomach pH environment showed the control samples (drug without SBA-15) released considerable amount of drugs (about 90%) within first 15 min, when it was about 10-20% for the matrixes. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples. It was indicated nanosilica has the ability of retaining the drugs in acidic pH and prevented their release. Furthermore, the drugs were released in a controlled manner in small intestine, which is the main absorption site. PMID:27062095

  11. 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. PMID:27282396

  12. Consumption patterns of non-steroidal anti-inflammatory drugs by the community without prescription in Dhaka City

    OpenAIRE

    Md. Khoshroz Samad

    2009-01-01

    A cross-sectional study on consumption patterns of non-steroidal anti-inflammatory drugs (NSAIDs) by the community without prescription was conducted in Dhaka Metropolitan City. A total of 608 encounters from 16 pharmacies were interviewed from people found to purchase drugs of the pharmacy from their self demand. The commonest purchased NSAIDs per encounter was paracetamol (37.0%). Ibuprofen (13.8%), diclofenac sodium (12.7%), aspirin (7.4%), naproxen (6.9%) and other group of NSAIDs (22.2%)...

  13. 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. PMID:24981746

  14. Aspirin or Nonsteroidal Anti-inflammatory Drug-Exacerbated Chronic Rhinosinusitis.

    Science.gov (United States)

    Ledford, Dennis K; Lockey, Richard F

    2016-01-01

    Aspirin (ASA)-exacerbated respiratory disease (AERD) is characterized by upper airway congestion due to eosinophilic inflammation of the nasal and sinus membranes and nasal polyposis, associated with increased leukotriene production that is further accentuated by ASA or other nonsteroidal anti-inflammatory drug (NSAID) ingestion. It occurs in 5% to 10% of subjects with chronic rhinosinusitis (CRS) and in 15% to 40% of those with nasal polyposis. Although AERD with CRS is usually associated with asthma, this is not always the case. The eosinophilic airway inflammation and symptoms precede clinical reactions to ASA or other NSAIDs, but ultimately affected subjects experience worsening of symptoms with ingestion of ASA/NSAIDs. The endotypic mechanism for this worsening is related to a chronic increase in leukotriene and a decrease in prostaglandin production, particularly prostaglandin E2, that is further aggravated by the inhibition of cycloxgenase I. IgE does not likely play a role in the pathogenesis of the disease although nasal and sinus staphylococcal infection increases local IgE level and may increase total IgE and specific IgE levels. Genetic studies suggest that multiple genes may be involved, but the genetic abnormalities may differ in affected subjects from different ethnicities and candidate genes have not been confirmed in multiple studies. Genome-wide association studies have not been revealing. The phenotype is recognized by the mucosal inflammation and worsening of symptoms acutely with ASA/NSAID. There is clinical improvement with ASA desensitization followed by regular ingestion of ASA or other NSAIDs. Further understanding of this unique phenotype and endotype of CRS will likely improve the understanding of other eosinophilic airway diseases. PMID:27393773

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

    Directory of Open Access Journals (Sweden)

    N. A. Abdoon

    2006-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    George V. Papatheodoridis; Athanasios J. Archimandritis

    2005-01-01

    Helicobacter pylori (H pylori) infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin at any dosage and formulation represent well-established risk factors for the development of uncomplicated and complicated peptic ulcer disease accounting for the majority of such cases. Although the interaction between H pylori and NSAID/aspirin use in the same individuals was questioned in some epidemiological studies, it has now become widely accepted that they are at least independent risk factors for peptic ulcer disease. According to data from randomized intervention trials, naive NSAID users certainly benefit from testing for H pylori infection and, if positive,H pylori eradication therapy prior to the initiation of NSAID. A similar strategy is also suggested for naive aspirin users, although the efficacy of such an approach has not been evaluated yet. Strong data also support that chronic aspirin users with a recent ulcer complication should be tested for H pyloriinfection and, if positive, receive H pylori eradication therapy after ulcer healing, while they appear to benefit from additional long-term therapy with a proton pump inhibitor (PPI).A similar approach is often recommended to chronic aspirin users at a high risk of ulcer complication. H pylori eradication alone does not efficiently protect chronic NSAID users with a recent ulcer complication or those at a high-risk, who certainly should be treated with long-term PPI therapy, but H pylori eradication may be additionally offered even in this setting. In contrast, testing for H pylorior PPI therapy is not recommended for chronic NSAID/aspirin users with no ulcer complications or those at a low risk of complications.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. The effect of the non-steroidal anti-inflammatory drug diclofenac sodium on thefetuses of albino mice

    Directory of Open Access Journals (Sweden)

    Mohamed A. Shahin, Ramadan A. Ramadan, Samia M. Sakr and Sahar A. Sabry

    2011-07-01

    Full Text Available Introduction: The present study was carried out to evaluate the effect of the non-steroidal anti-inflammatory drug diclofenac sodium (DS on the fetuses of albino mice from the morphological and skeletal points of view. Material and methods: Sixty adult pregnant female mice were used in the present study. They were allocated into 6 groups (10 mice each. The first two groups served as control and were injected intraperitoneally (i.p. with the solvent of the drug, and the 3rd and 5th groups were treated with 1.5 and 3mg/kg body weight of diclofenac sodium for 6 days ( gestation days 1-6 , respectively ; the 4th and 6th groups were treated with 1.5and 3mg/kg body weight of the drug for 8 days ( gestation days 7-14, respectively. Results: The morphological examination of the fetuses of treated groups showed conspicuous decrease in the average body weight and body length in all treated groups. The fetuses maternally treated with the drug showed noticeable external morphological malformations and their skeletons exhibited mild retardation in skeletal elements. In conclusion: The non-steroidal anti-inflammatory drug diclofenac sodium had exerted marked morphological malformations and mild skeletal alterations in mice fetuses maternally treated during different periods of gestation.

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

    Directory of Open Access Journals (Sweden)

    Cristina Theoduloz

    2015-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Brune K

    2015-02-01

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

  1. Open Drug Discovery Teams: A Chemistry Mobile App for Collaboration.

    Science.gov (United States)

    Ekins, Sean; Clark, Alex M; Williams, Antony J

    2012-08-01

    The Open Drug Discovery Teams (ODDT) project provides a mobile app primarily intended as a research topic aggregator of predominantly open science data collected from various sources on the internet. It exists to facilitate interdisciplinary teamwork and to relieve the user from data overload, delivering access to information that is highly relevant and focused on their topic areas of interest. Research topics include areas of chemistry and adjacent molecule-oriented biomedical sciences, with an emphasis on those which are most amenable to open research at present. These include rare and neglected diseases, and precompetitive and public-good initiatives such as green chemistry. The ODDT project uses a free mobile app as user entry point. The app has a magazine-like interface, and server-side infrastructure for hosting chemistry-related data as well as value added services. The project is open to participation from anyone and provides the ability for users to make annotations and assertions, thereby contributing to the collective value of the data to the engaged community. Much of the content is derived from public sources, but the platform is also amenable to commercial data input. The technology could also be readily used in-house by organizations as a research aggregator that could integrate internal and external science and discussion. The infrastructure for the app is currently based upon the Twitter API as a useful proof of concept for a real time source of publicly generated content. This could be extended further by accessing other APIs providing news and data feeds of relevance to a particular area of interest. As the project evolves, social networking features will be developed for organizing participants into teams, with various forms of communication and content management possible. PMID:23198003

  2. 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.

  3. Nonsteroidal Anti-inflammatory Drugs and the Risk for Anastomotic Failure

    Science.gov (United States)

    Hakkarainen, Timo W.; Steele, Scott R.; Bastaworous, Amir; Dellinger, E. Patchen; Farrokhi, Ellen; Farjah, Farhood; Florence, Michael; Helton, Scott; Horton, Marc; Pietro, Michael; Varghese, Thomas K.; Flum, David R.

    2015-01-01

    IMPORTANCE Nonsteroidal anti-inflammatory drugs (NSAIDs) have many physiologic effects and are being used more commonly to treat postoperative pain, but recent small studies have suggested that NSAIDs may impair anastomotic healing in the gastrointestinal tract. OBJECTIVE To evaluate the relationship between postoperative NSAID administration and anastomotic complications. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of 13 082 patients undergoing bariatric or colorectal surgery at 47 hospitals in Washington State from January 1, 2006, through December 31, 2010, using data from the Surgical Care and Outcomes Assessment Program linked to the Washington State Comprehensive Abstract Reporting System. EXPOSURE NSAID administration beginning within 24 hours after surgery. MAIN OUTCOMES AND MEASURES We used multivariate logistic regression modeling to assess the risk for anastomotic complications (reoperation, rescue stoma, revision of an anastomosis, and percutaneous drainage of an abscess) through 90 days after bariatric and colorectal surgery involving anastomoses. RESULTS Of the 13 082 patients (mean [SD] age, 58.1 [15.8] years; 60.7% women), 3158 (24.1%) received NSAIDs. The overall 90-day rate of anastomotic leaks was 4.3% for all patients (151 patients [4.8%] in the NSAID group and 417 patients [4.2%] in the non-NSAID group; P = .16). After risk adjustment, NSAIDs were associated with a 24% increased risk for anastomotic leak (odds ratio, 1.24 [95% CI, 1.01–1.56]; P = .04). This association was isolated to nonelective colorectal surgery, for which the leak rate was 12.3% in the NSAID group and 8.3% in the non-NSAID group (odds ratio, 1.70 [95% CI, 1.11–2.68]; P = .01). CONCLUSIONS AND RELEVANCE Postoperative NSAIDs were associated with a significantly increased risk for anastomotic complications among patients undergoing nonelective colorectal resection. To determine the role of NSAIDs in colorectal surgery, future evaluations should consider

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

    Directory of Open Access Journals (Sweden)

    Fujiwara Yoshinori

    2008-02-01

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

  5. Urinary PGE-M levels are associated with risk of colorectal adenomas and chemopreventive response to anti-inflammatory drugs.

    Science.gov (United States)

    Bezawada, Navya; Song, Mingyang; Wu, Kana; Mehta, Raaj S; Milne, Ginger L; Ogino, Shuji; Fuchs, Charles S; Giovannucci, Edward L; Chan, Andrew T

    2014-07-01

    Prostaglandin E2 (PGE2) promotes colorectal carcinogenesis. Overall, systemic PGE2 production can be assessed by measuring its major metabolite, PGE-M, in urine. We examined the potential role of PGE-M as a biomarker for colorectal adenoma risk and chemopreventive response to anti-inflammatory drugs. We conducted a prospective case-control study nested within the Nurses' Health Study. Among women who previously provided a urine sample, we identified 420 cases diagnosed with colorectal adenoma during follow-up and matched them to 420 endoscopy-negative controls. We measured urinary PGE-M using an LC/MS assay. Compared with women in the lowest quartile of urinary PGE-M, women in the highest quartile had a multivariate OR of 1.40 (95% confidence interval (CI), 0.92-2.14) for any adenoma; 0.91 (95% CI, 0.48-1.72) for low-risk adenoma (solitary adenoma aspirin/NSAIDs per week) was associated with a significant reduction in adenoma risk (multivariate OR, 0.61; 95% CI, 0.43-0.87) in women with high baseline PGE-M (quartiles 2-4), but not low PGE-M (quartile 1).Urinary PGE-M is associated with an increased risk of high-risk adenoma. Anti-inflammatory drugs seem to reduce adenoma risk among women with high, but not low PGE-M. Urinary PGE-M may serve as a biomarker to define subsets of the population who may obtain differential chemopreventive benefit from anti-inflammatory drugs. PMID:24824037

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

    DEFF Research Database (Denmark)

    Kjaer, B; Struve, C; Friis, T;

    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 of...... investigating the anti-angiogenic efficiency of NSAID-HSA conjugates in vitro, three NSAIDs, aspirin, ibuprofen, and naproxen were conjugated to HSA using different concentrations of their N-hydroxysuccinimide esters. Conjugation ratios from 10 to 50 were achieved and the conjugates retained a growth inhibitory...

  7. Effects of non-steroidal anti-inflammatory drugs and prostaglandins on alkali secretion by rabbit gastric fundus in vitro

    OpenAIRE

    Rees, W D W; Gibbons, L C; Turnberg, L A

    1983-01-01

    The effects of non-steroidal anti-inflammatory drugs and prostaglandins E2 and F2α on the secretory and electrical activity of isolated rabbit fundic mucosa have been studied. Spontaneous acid secretion was inhibited by serosal side application of sodium thiocyanate (6×10−2M) and the resulting alkali secretion measured by pH stat tiration. Serosal side application of indomethacin (10−5M) or aspirin (3×10−3M) inhibited alkali secretion (0·55±0·06 to 0·12±0·06 μmol/cm2/h, n=6, p

  8. 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...... 1995-May 1997) was updated through June 2006, using a nationwide prescription database. CRC incidence was ascertained from nationwide registers. Cox proportional hazards regression was used to compute confounder-adjusted incidence rate ratios (RRs) and 95% confidence intervals (CIs). From 51,053 cohort...

  9. 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...

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

    Directory of Open Access Journals (Sweden)

    Ega Durgashivaprasad

    2014-01-01

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

  11. The usage pattern of Anti-inflammatory drugs-steroidal and non-steroidal- in patients referred to13 Aban pharmacy in Sari

    Directory of Open Access Journals (Sweden)

    Shahram Ala

    2009-01-01

    Full Text Available (Received 12 September, 2009 ; Accepted 18 November, 2009AbstractIn the present study, the usage pattern of Anti-inflammatory drugs-steroidal and non-steroidal- in patients referred to 13 Aban Pharmacy in Sari was evaluated. The results show a high rate of anti-inflammatory drug prescriptions, mainly by general practitioners with ibuprofen, diclofenac and mefenamic acid being the most widely used NSAIDs and prednisolone, dexamethasone and betamethasone being the most prescribed corticosteroids respectively. Training physicians regarding the rational use of anti-inflammatory drug prescriptions may be effective in modifying the usage pattern of these drugs and avoiding the risks associated with their heavy usage.J Mazand Univ Med Sci 2009; 19(72: 82-84 (Persian.

  12. Expression of pleiotrophin, an important regulator of cell migration, is inhibited in intestinal epithelial cells by treatment with non-steroidal anti-inflammatory drugs

    Science.gov (United States)

    Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs for the suppression of inflammation and pain. However, the analgesic properties of NSAIDs are also associated with significant negative side effects, most notably in the gastrointestinal (GI) tract. Increasingly, evi...

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

    OpenAIRE

    M M Hamzah

    2011-01-01

    Summary: This work was suggested on the basis of presence of curcuminoids in curcuma and the presence of flavonoidal constituent in acacia and lupinus. The aim of this study was to study their possible anti-inflammatory effect by separately formulation of the three extracts in a suitable gel formula for topical administration and comparison of the prepared gels with a standard gel in the market (diclosal Emulgel) by using the carrageenan induced paw edema model in albino rats. The extracts we...

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

    OpenAIRE

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

    2014-01-01

    Background: Volatile oils obtained from lemon grass [Cymbopogon citratus (DC.) Stapf, Poaceae family] are used in traditional medicine as remedies for the treatment of various diseases.Aims: In the present study, lemon grass essential oil (LGEO) was evaluated for its in vivo topical and oral anti-inflammatory effects, and for its in vitro antifungal activity using both liquid and vapor phases.Methods: The chemical profile of LGEO as determined by gas chromatography–mass spectrometry analysis ...

  15. Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure

    DEFF Research Database (Denmark)

    Gislason, Gunnar H; Rasmussen, Jeppe N; Abildstrøm, Steen;

    2009-01-01

    BACKGROUND: Accumulating evidence indicates increased cardiovascular risk associated with nonsteroidal anti-inflammatory drug (NSAID) use, in particular in patients with established cardiovascular disease. We studied the risk of death and hospitalization because of acute myocardial infarction and...... heart failure (HF) associated with use of NSAIDs in an unselected cohort of patients with HF. METHODS: We identified 107,092 patients surviving their first hospitalization because of HF between January 1, 1995, and December 31, 2004, and their subsequent use of NSAIDs from individual-level linkage of...... nationwide registries of hospitalization and drug dispensing by pharmacies in Denmark. Data analysis was performed using Cox proportional hazard models adjusted for age, sex, calendar year, comorbidity, medical treatment, and severity of disease, and propensity-based risk-stratified models and case...

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

    Science.gov (United States)

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

    2016-06-01

    Scientists have always been trying to use artificial zeolites to make modified-release drug delivery systems in the gastrointestinal tract. An ideal carrier should have the capability to release the drug in the intestine, which is the main area of absorption. Zeolites are mineral aluminosilicate compounds with regular structure and huge porosity, which are available in natural and artificial forms. In this study, soaking, filtration and solvent evaporation methods were used to load the drugs after activation of the zeolites. Weight measurement, spectroscopy FTIR, thermogravimetry and scanning electronic microscope were used to determine drug loading on the systems. Finally, consideration of drug release was made in a simulated gastric fluid and a simulated intestinal fluid for all matrixes (zeolites containing drugs) and drugs without zeolites. Diclofenac sodium (D) and piroxicam (P) were used as the drug models, and zeolites X and Y as the carriers. Drug loading percentage showed that over 90% of drugs were loaded on zeolites. Dissolution tests in stomach pH environment showed that the control samples (drug without zeolite) released considerable amount of drugs (about 90%) within first 15 min when it was about 10-20% for the matrixes. These results are favorable as NSAIDs irritate the stomach wall and it is ideal not to release much drugs in the stomach. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples in intestine pH environment. PMID:26705687

  17. 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.

  18. Pharmacology and potential therapeutic applications of nitric oxide-releasing non-steroidal anti-inflammatory and related nitric oxide-donating drugs

    Science.gov (United States)

    Keeble, J E; Moore, P K

    2002-01-01

    This review examines the biological significance, therapeutic potential and mechanism(s) of action of a range of nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAID) and related nitric oxide-releasing donating drugs (NODD). The slow release of nitric oxide (NO) from these compounds leads to subtle changes in the profile of pharmacological activity of the parent, non-steroidal anti-inflammatory drugs (NSAID). For example, compared with NSAID, NO-NSAID cause markedly diminished gastrointestinal toxicity and improved anti-inflammatory and anti-nociceptive efficacy. In addition, nitroparacetamol exhibits hepatoprotection as opposed to the hepatotoxic activity of paracetamol. The possibility that NO-NSAID or NODD may be of therapeutic benefit in a wide variety of disease states including pain and inflammation, thrombosis and restenosis, neurodegenerative diseases of the central nervous system, colitis, cancer, urinary incontinence, liver disease, impotence, bronchial asthma and osteoporosis is discussed. PMID:12237248

  19. 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…

  20. Gaultherin, a natural salicylate derivative from Gaultheria yunnanensis: towards a better non-steroidal anti-inflammatory drug.

    Science.gov (United States)

    Zhang, Bin; He, Xiao-Li; Ding, Yi; Du, Guan-Hua

    2006-01-13

    One of the major factors limiting the use of non-steroidal anti-inflammatory drugs is gastrointestinal toxicity. Gaultherin, 2-[(6-O-beta-D-Xylopyranosyl-beta-D-glucopyranosyl)oxy] benzoic acid methyl ester, a natural salicylate derivative extracted from Gaultheria yunnanensis, has been shown to have analgesic and anti-inflammatory effects and lack gastric ulcerogenic effect compared to aspirin in our primary study. The aim of this study was to investigate the mechanism of action of gaultherin, which may rely on its active metabolite, and the mechanism responsible for the non-ulcerogenic property. The results showed that gaultherin (200 mg/kg) significantly inhibited the abdominal contractions in the acetic acid-induced writhing test in mice. The anti-inflammatory effect of gaultherin was demonstrated in the croton oil-induced ear edema model in mice. The results showed that gaultherin and equimolar dose of aspirin produced comparable inhibitory effects. The study of the metabolism characters of gaultherin in mice and rats indicated that gaultherin could be metabolically converted to salicylate, which produced the pharmacological effects, and provided effective concentrations for an extended period. In vitro metabolism experiment showed that gaultherin was metabolized by beta-glycosidase produced by human intestinal bacteria and esterases in intestine, blood and liver successively to release salicylate finally. The study suggested gaultherin did not cause gastric ulcer for the reason that it released salicylate in intestine slowly, not in stomach and it left the cyclooxygenase-1 unaffected, which was the source of cytoprotective prostaglandins in gastric epithelium. PMID:16375889

  1. 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.

  2. Bentonite-induced rat paw oedema as a tool for simultaneous testing of prophylactic and therapeutic effects of anti-inflammatory and other drugs.

    Science.gov (United States)

    Marek, J

    1981-01-01

    The possibility of screening simultaneously the prophylactic and therapeutic effects of a single dose of anti-inflammatory drugs was further tested. Bentonite oedema was induced in the left paw (0.05 ml of 5% bentonite gel subcutaneously). After the measurement of its size in the 23rd h, the rats were given the test drugs (i.m. or p.o.) and 1 h thereafter, bentonite oedema was induced in the right paw. Some of the drugs suppressed the oedema both prophylactically and therapeutically (steroidal and some nonsteroidal anti-inflammatory drugs, sodium aurothiomalate etc.), some others suppressed it only prophylactically (some derivatives of pyrazolone etc.) and some of the remaining drugs tested had no effect at all on the oedema after a single administration. Advantages and limitations of this method are discussed. PMID:7220586

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

    Science.gov (United States)

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

    2015-03-29

    Among their beneficial effects, non-steroidal anti-inflammatory drugs may also exert several side effects which depend on the dosage and the type of these medications. The most frequent gastrointestinal side effects usually develop shortly after the beginning of their administration, but others such as cardiovascular interactions (which are present much less frequently than gastrointestinal side effects) can also occur after the beginning of drug administration without a latency period. For a long-term treatment, non-steroidal anti-inflammatory drugs are most frequently used in the elderly population where patients typically have high cardiovascular risk and take other medicines, e.g. low dose acetylsalicylic acid that can interact with non-steroidal anti-inflammatory drugs; in this aspect diclofenac may cause less side effects. In this review, the authors briefly review cardiovascular side effects of non-steroidal anti-inflammatory drugs, the processes which potentially influence them, therapeutic consequences and their interaction with acetylsalicylic acid. PMID:25796279

  4. The Proapoptotic Effect of Traditional and Novel Nonsteroidal Anti-Inflammatory Drugs in Mammalian and Yeast Cells

    Directory of Open Access Journals (Sweden)

    Gianluca Farrugia

    2013-01-01

    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs have long been used to treat pain, fever, and inflammation. However, mounting evidence shows that NSAIDs, such as aspirin, have very promising antineoplastic properties. The chemopreventive, antiproliferative behaviour of NSAIDs has been associated with both their inactivation of cyclooxygenases (COX and their ability to induce apoptosis via pathways that are largely COX-independent. In this review, the various proapoptotic pathways induced by traditional and novel NSAIDs such as phospho-NSAIDs, hydrogen sulfide-releasing NSAIDs and nitric oxide-releasing NSAIDs in mammalian cell lines are discussed, as well as the proapoptotic effects of NSAIDs on budding yeast which retains the hallmarks of mammalian apoptosis. The significance of these mechanisms in terms of the role of NSAIDs in effective cancer prevention is considered.

  5. Site-specific effects of the nonsteroidal anti-inflammatory drug lysine clonixinate on rat brain opioid receptors.

    Science.gov (United States)

    Ortí, E; Coirini, H; Pico, J C

    1999-04-01

    In addition to effects in the periphery through inhibition of prostaglandin synthesis, several lines of evidence suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) act in the central nervous system. The possibility that the central action of NSAIDs involves regulation of opioid receptors was investigated by quantitative autoradiography of mu, delta, and kappa sites in rat brain slices. Increased (p lysine clonixinate. Labeling of delta receptors was lower in the lateral septum, and kappa sites decreased in thalamic nuclei. These effects were not mediated through direct interaction with opioid-binding sites, since receptor-binding assays using rat brain membranes confirmed that clonixinate up to 1 x 10(-4) mol/l does not inhibit mu, delta, and kappa receptor specific binding. Central effects of NSAIDs might, therefore, involve interaction with the opioid receptor system through indirect mechanisms. PMID:10077738

  6. 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

    conception, iii) the risk of adverse birth outcome in women with Crohn's disease according to type of anti-inflammatory drug treatment in pregnancy (sulfasalazine/5-aminosalicylic acid, steroids or azathioprine/6-mercaptopurine), and iv) the impact of disease activity in women with Crohn's disease on adverse......, 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...... 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...

  7. 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.

  8. Ongoing treatment with non-steroidal anti-inflammatory drugs at time of admission is associated with poorer prognosis in patients with first-time acute myocardial infarction

    DEFF Research Database (Denmark)

    Lamberts, M.; Fosbol, E. L.; Olsen, A. M. S.;

    2013-01-01

    Background: Use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with increased cardiovascular morbidity and mortality. The purpose of this study was to examine the effect of ongoing NSAID treatment at time of admission for myocardial infarction (MI) on prognosis. Methods: Al...

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

    NARCIS (Netherlands)

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

    2006-01-01

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

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  11. 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...

  12. 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

  13. 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...

  14. Analysis of Adverse Reaction of Analgesics, Antipyretics and Non-Steroidal Anti-Inflammatory Drugs Prescribed by Physicians of Health Care Facilities in Podilskyi Region during 2015

    OpenAIRE

    Stepaniuk, N. H.; Hladkykh, F. V.; Basarab, O. V.

    2016-01-01

    The problem of medicines rational use exists all over the world. It concerns particularly analgesics, antipyretics and non-steroidal anti-inflammatory drugs (NSAIDs). In Ukraine the side effects caused by non-steroidal antiphlogistics rank the second place according to the prevalence among all registered cases.The objective of the research was to analyze adverse drug reaction report forms concerning adverse reactions caused by the use of NSAIDs, analgesics, antipyretics, and were submitted du...

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

    Directory of Open Access Journals (Sweden)

    Elham Khodaverdi

    2014-05-01

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

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

    Science.gov (United States)

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

    2015-01-01

    Neutrophils form the first line of host defense against infections that combat pathogens using two major mechanisms, the phagocytosis or the release of neutrophil extracellular traps (NETs). The netosis (NET formation) exerts additional, unfavorable effects on the fitness of host cells and is also involved at the sites of lung infection, increasing the mucus viscosity and in the circulatory system where it can influence the intravascular clot formation. Although molecular mechanisms underlying the netosis are still incompletely understood, a role of NADPH oxidase that activates the production of reactive oxygen species (ROS) during the initiation of NETs has been well documented. Since several commonly used drugs can affects the netosis, our current study was aimed to determine the effects of selected mucolytic, anti-inflammatory and cardiovascular drugs on NET formation, with a special emphasis on ROS production and NADPH oxidase activity. The treatment of neutrophils with N-acetylcysteine, ketoprofen and ethamsylate reduced the production of ROS by these cells in a dose-dependent manner. NET formation was also modulated by selected drugs. N-acetylcysteine inhibited the netosis but in the presence of H2O2 this neutrophil ability was restored, indicating that N-acetylcysteine may influence the NET formation by modulating ROS productivity. The administration of ethamsylate led to a significant reduction in NET formation and this effect was not restored by H2O2 or S. aureus, suggesting the unexpected additional side effects of this drug. Ketoprofen seemed to promote ROS-independent NET release, simultaneously inhibiting ROS production. The results, obtained in this study strongly suggest that the therapeutic strategies applied in many neutrophil-mediated diseases should take into account the NET-associated effects. PMID:26291043

  17. 75 FR 47604 - Guidance for Industry on Drug Substance Chemistry, Manufacturing, and Controls Information...

    Science.gov (United States)

    2010-08-06

    ... availability of a guidance for industry 169 entitled ``Drug Substance Chemistry, Manufacturing, and Controls... Federal Register of June 1, 2006 (71 FR 31194), FDA published the notice of withdrawal and revision of... HUMAN SERVICES Food and Drug Administration (formerly 2003D-0571) Guidance for Industry on...

  18. 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.

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

    International Nuclear Information System (INIS)

    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.

  20. 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. PMID:27020471

  1. The antiinflammatory drug sulfasalazine inhibits tumor necrosis factor alpha expression in macrophages by inducing apoptosis

    NARCIS (Netherlands)

    Rodenburg, R.J.T.; Ganga, A.; Lent, P.L.E.M. van; Putte, L.B.A. van de; Venrooij, W.J. van

    2000-01-01

    Objective. Sulfasalazine (SSZ) is a commonly used drug in the treatment of inflammatory diseases such as rheumatoid arthritis and Crohn's disease. In both diseases, the proinflammatory cytokine tumor necrosis factor α (TNFα) plays a prominent role. In these studies, we investigated the mechanism by

  2. The pharmaceutical biochemistry group: where pharmaceutical chemistry meets biology and drug delivery

    OpenAIRE

    Kalia, Yogeshvar; Perozzo, Remo; Scapozza, Leonardo

    2012-01-01

    Successful drug discovery and development of new therapeutics is a long, expensive multidisciplinary process needing innovation and the integration of smart cutting edge science and technology to overcome the challenges in taking a drug from the bench to the bedside. The research activities of the Pharmaceutical Biochemistry group span the drug discovery and development process, providing an interface that brings together pharmaceutical chemistry, biochemistry, structural biology, computation...

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

    OpenAIRE

    Mehmet Dadaci; Zeynep Altuntas; Bilsev Ince; Fatma Bilgen; Osman Tufekci; Necdet Poyraz

    2015-01-01

    Nicolau syndrome is a rare complication of intramuscular injection that leads to local ischemic necrosis of the skin and adipose tissue. In this paper, we discuss etiologies, risk factors, and treatment options for gluteal Nicolau syndrome referring to patients treated in our hospital. Our study includes 17 women who visited our clinic with symptoms of gluteal necrosis secondary to intramuscular injection. The following variables were taken into account: injection site, drug administered, fre...

  4. Nonsteroidal anti-inflammatory drugs and upper and lower gastrointestinal mucosal damage

    OpenAIRE

    Sostres, Carlos; Gargallo, Carla J.; Lanas, Angel

    2013-01-01

    NSAIDs are among the most commonly used drugs worldwide and their beneficial therapeutic properties are thoroughly accepted. However, they are also associated with gastrointestinal (GI) adverse events. NSAIDs can damage the whole GI tract including a wide spectrum of lesions. About 1 to 2% of NSAID users experienced a serious GI complication during treatment. The relative risk of upper GI complications among NSAID users depends on the presence of different risk factors, including older age (>...

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

    Science.gov (United States)

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

    1997-06-01

    A C-fiber reflex elicited by electrical stimulation within the territory of the sural nerve was recorded from the ipsilateral biceps femoris muscle in anesthetized rats. The temporal evolution of the response was studied using a constant stimulus intensity (3 times threshold), and recruitment curves were built by varying the stimulus intensity from 0 to 7 times threshold. The intrathecal (i.t.) but not i.c.v. administration of aspirin, indomethacin, ketoprofen and lysine clonixinate resulted in dose-dependent depressions of the C-fiber reflex. In contrast, saline was ineffective. Regardless of the route of administration, the drugs never produced disturbances in heart rate and/or acid-base equilibrium. When a constant level of stimulation was used, 500 microg of aspirin i.t. induced a blockade of the reflex immediately after the injection, followed by a partial recovery. Indomethacin produced a stable depression, which reached 80 to 90% with an i.t. dose of 500 microg. Ketoprofen and lysine clonixinate produced a more stable effect; the highest doses (500 microg) produced a steady-state depression of approximately 50% for approximately 30 min. When the recruitment curves were built with a range of nociceptive stimulus intensities, all of the drugs except for indomethacin produced a dose-dependent decrease in the slopes and the areas under the recruitment curves without major modifications in the thresholds; indomethacin also induced a significant dose-related increase in the threshold. The orders of potency for both stimulation paradigms with the i.t. route were the same, namely aspirin > indomethacin > lysine clonixinate > or = ketoprofen. It is concluded that nonsteroidal anti-inflammatory drugs elicit significant antinociceptive effects at a spinal level, which do not depend on the existence of a hyperalgesic or inflammatory state. Such effects were not seen after injections within the lateral ventricle. PMID:9190874

  6. [Differential action of non-steroidal antiinflammatory drugs on human gallbladder cyclooxygenase and lipoxygenase].

    Science.gov (United States)

    Franchi, A; Di Girolamo, G; Farina, M; de los Santos, A R; Martí, M L; Gimeno, M A

    2000-01-01

    Lysine clonixinate (LC) is a non-steroidal antiinflammatory agent (NSAID) with only few adverse effects. This characteristic has prompted us to suggest that its administration, at levels equivalent to those found in human plasma following therapeutic doses, slightly inhibits cyclooxygenase I (COX I). Three experiments were performed. Experiment 1: to study the in vitro effect of LC at concentrations of 4 and 6 micrograms/ml, comparable with those found in plasma following an oral therapeutic dose of 125 mg. Gallbladder tissue segments were incubated with 0.25 microCi of 14C-arachidonic acid and the production of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha) and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) was measured. LC did not affect basal production of any of the 3 prostaglandins (PGs) but at 6 micrograms/ml slightly reduced the levels of 5-hidroxyeicosatetraenoic acid (5-HETE). Experiment 2: LC was administered preoperatively to 6 patients by continuous perfusion, to achieve a steady-state concentration between 4 and 6 micrograms/ml. Gallbladder segments from the 6 treated and another 6 control patients were incubated in 14C-arachidonic acid. Gallbladder segments treated with LC did not show a decreased production of any of the three PGs whereas 5-HETE released to the medium was significantly lower. Experiment 3: 18 patients received an i.v. bolus of LC 100 mg (n1 = 6) or LC 200 mg (n2 = 6) or indomethacin (INDO) 50 mg (n3 = 6). Unlike the administration of INDO bolus, LC in the above doses did not inhibit PG synthesis. Both NSAIDs showed different effects when the production of 5-HETE synthesis was assessed. Treatment with INDO did not alter the production of 5-HETE while LC elicited significant inhibition. The three studies conducted, namely in vitro and in vivo continuous perfusion and i.v. bolus, revealed that LC had no effect on prostaglandin synthesis while reducing significantly the levels of 5-HETE. PMID:11188896

  7. Computational chemistry, data mining, high-throughput synthesis and screening - informatics and integration in drug discovery

    OpenAIRE

    Charles J. Manly

    2001-01-01

    Drug discovery today includes considerable focus of laboratory automation and other resources on both combinatorial chemistry and high-throughput screening, and computational chemistry has been a part of pharmaceutical research for many years. The real benefit of these technologies is beyond the exploitation of each individually. Only recently have significant efforts focused on effectively integrating these and other discovery disciplines to realize their larger potential. This technical not...

  8. [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. PMID:27312831

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

    International Nuclear Information System (INIS)

    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.)

  10. The conjugation of nonsteroidal anti-inflammatory drugs (NSAID to small peptides for generating multifunctional supramolecular nanofibers/hydrogels

    Directory of Open Access Journals (Sweden)

    Jiayang Li

    2013-05-01

    Full Text Available Here we report supramolecular hydrogelators made of nonsteroidal anti-inflammatory drugs (NSAID and small peptides. The covalent linkage of Phe–Phe and NSAIDs results in conjugates that self-assemble in water to form molecular nanofibers as the matrices of hydrogels. When the NSAID is naproxen (1, the resultant hydrogelator 1a forms a hydrogel at a critical concentration (cgc of 0.2 wt % at pH 7.0. Hydrogelator 1a, also acting as a general motif, enables enzymatic hydrogelation in which the precursor turns into a hydrogelator upon hydrolysis catalyzed by a phosphatase at physiological conditions. The conjugates of Phe–Phe with other NSAIDs, such as (R-flurbiprofen (2, racemic flurbiprofen (3, and racemic ibuprofen (4, are able to form molecular hydrogels, except in the case of aspirin (5. After the conjugation with the small peptides, NSAIDs exhibit improved selectivity to their targets. In addition, the peptides made of D-amino acids help preserve the activities of NSAIDs. Besides demonstrating that common NSAIDs are excellent candidates to promote aromatic–aromatic interaction in water to form hydrogels, this work contributes to the development of functional molecules that have dual or multiple roles and ultimately may lead to new molecular hydrogels of therapeutic agents for topical use.

  11. The conjugation of nonsteroidal anti-inflammatory drugs (NSAID) to small peptides for generating multifunctional supramolecular nanofibers/hydrogels.

    Science.gov (United States)

    Li, Jiayang; Kuang, Yi; Shi, Junfeng; Gao, Yuan; Zhou, Jie; Xu, Bing

    2013-01-01

    Here we report supramolecular hydrogelators made of nonsteroidal anti-inflammatory drugs (NSAID) and small peptides. The covalent linkage of Phe-Phe and NSAIDs results in conjugates that self-assemble in water to form molecular nanofibers as the matrices of hydrogels. When the NSAID is naproxen (1), the resultant hydrogelator 1a forms a hydrogel at a critical concentration (cgc) of 0.2 wt % at pH 7.0. Hydrogelator 1a, also acting as a general motif, enables enzymatic hydrogelation in which the precursor turns into a hydrogelator upon hydrolysis catalyzed by a phosphatase at physiological conditions. The conjugates of Phe-Phe with other NSAIDs, such as (R)-flurbiprofen (2), racemic flurbiprofen (3), and racemic ibuprofen (4), are able to form molecular hydrogels, except in the case of aspirin (5). After the conjugation with the small peptides, NSAIDs exhibit improved selectivity to their targets. In addition, the peptides made of D-amino acids help preserve the activities of NSAIDs. Besides demonstrating that common NSAIDs are excellent candidates to promote aromatic-aromatic interaction in water to form hydrogels, this work contributes to the development of functional molecules that have dual or multiple roles and ultimately may lead to new molecular hydrogels of therapeutic agents for topical use. PMID:23766806

  12. [Induction of NAG-1 gene expression in colon cancer cells by non-steroidal anti-inflammatory drugs].

    Science.gov (United States)

    Wang, Chunhui; Ouyang, Qin; Tang, Chengwei; Liu, Rui; Huang, Minghui

    2007-08-01

    This study was conducted to evaluate the growth and NAG-1 gene expression effected by Non-steroidal anti-inflammatory drug (NSAID) on colon cancer cell lines in vitro. The proliferation of colon cancer cells were determined by MTT assay and COX-2 protein expression were detected by Western blot. Total RNA was isolated from three kinds of colon cancer cell lines; the expressions of NAG-1 mRNA in the cells treated with or without NSAIDs were assessed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay. Celecoxib, meloxicam and aspirin were able to inhibit the growth of HT-29, SW480 and LS174-T cells in dose-dependent manner. COX-2 protein expressed in HT-29 and LS174-T, but not in SW480 cells. All of colon cancer cells expressed NAG-1 gene and the level of LS174-T was lower than that of the other two cell lines. NAG-1 expression was increased by treatment with some NSAIDs in all three kinds of colon cancer cells. NSAIDs were able to potentially inhibit the growth of colon cell lines. Induction of NAG-1 gene expression by NSAID was not consistent with COX-2 expression. PMID:17899765

  13. 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.

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

    DEFF Research Database (Denmark)

    Gaist, David; 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 or of...

  15. Analyses of non-steroidal anti-inflammatory drugs in environmental water samples with microemulsion electrokinetic chromatography.

    Science.gov (United States)

    Kuo, Yu-Ling; Liu, Wan-Ling; Hsieh, Shih-Huan; Huang, Hsi-Ya

    2010-01-01

    In this study, a microemulsion electrokinetic chromatography (MEEKC) was used to analyze ten non-steroidal anti-inflammatory drugs (NSAIDs) in water samples. The type and ratio of organic modifiers were found to be the predominant influences on the NSAIDs separation. Subsequently, field-amplified sample injection was coupled with this MEEKC method in order to enhance the detection sensitivity. When both the acid plug (3 s) and water plug (5 s) were placed at the front of the capillary, and the acetonitrile (ACN) solvent was added to the water plug (10% ACN) and the sample matrix (15% ACN), the separation time was shortened to 15 min, as well as the limit of detection (LOD) of these NSAIDs was reduced to the range of 0.03 to 0.3 microg/L, which provided about a 1400-fold to 6100-fold enhancement in LOD. Finally, the proposed on-line concentration MEEKC method also successfully determined the NSAIDs residues in water samples after solid-phase extraction. PMID:20543504

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

    Science.gov (United States)

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

    2016-09-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) represent an effective pain treatment option and therefore one of the most sold therapeutic agents worldwide. The study of the molecular interactions responsible for their physiological activity, but also for their side effects, is therefore important. This report presents data on the interaction of the most consumed NSAIDs (ibuprofen, naproxen and diclofenac) with one main phospholipid in eukaryotic cells, dimyristoylphosphatidylserine (DMPS). The applied techniques are Fourier-transform infrared spectroscopy (FTIR), with which in transmission the gel to liquid crystalline phase transition of the acyl chains in the absence and presence of the NSAID are monitored, supplemented by differential scanning calorimetry (DSC) data on the phase transition. FTIR in reflection (ATR, attenuated total reflectance) is applied to record the dependence of the interactions of the NSAID with particular functional groups observed in the DMPS spectrum such as the ester carbonyl and phosphate vibrational bands. With Förster resonance energy transfer (FRET) a possible intercalation of the NSAID into the DMPS liposomes and with isothermal titration calorimetry (ITC) the thermodynamics of the interaction are monitored. The data show that the NSAID react in a particular way with this lipid, but in some parameters the three NSAID clearly differ, with which now a clear picture of the interaction processes is possible. PMID:27316371

  17. Removal of non-steroidal anti-inflammatory drugs ibuprofen and ketoprofen from water by emulsion liquid membrane.

    Science.gov (United States)

    Dâas, Attef; Hamdaoui, Oualid

    2014-02-01

    In this work, the removal of the worldwide non-steroidal anti-inflammatory drugs ibuprofen (IBP) and ketoprofen (KTP) by emulsion liquid membrane (ELM) was carried out. An ELM system is made up of hexane as diluent, Span 80 as the surfactant and sodium carbonate as the inner aqueous solution. Effect of experimental conditions that affect the extraction of IBP such as surfactant concentration, emulsification time, sulfuric acid concentration in external phase, acid type in external phase, internal phase concentration, type of internal phase, stirring speed, volume ratio of internal phase to membrane phase, treatment ratio, IBP initial concentration, diluent type and salt was investigated. The obtained results showed that by appropriate selection of the operational parameters, it was possible to extract nearly all of IBP molecules from the feed solution even in the presence of high concentration of salt. Under optimum operating conditions, the efficiencies of IBP removal from distilled water (99.3 %), natural mineral water (97.3 %) and sea water (94.0 %) were comparable, which shows that the ELM treatment process represents a very interesting advanced separation process for the removal of IBP from complex matrices such as natural and sea waters. Under the optimized experimental conditions, approximately 97.4 % KTP was removed in less than 20 min of contact time. PMID:24037298

  18. Comprehensive evaluation of imidazole-based polymers for the enrichment of selected non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    Schemeth, Dieter; Kappacher, Christoph; Rainer, Matthias; Thalinger, Ramona; Bonn, Günther K

    2016-06-01

    This study reports the comparison of four manufactured imidazole-based copolymers and two commercially available hydrophilic sorbents for the solid phase extraction (SPE) of selected non-steroidal anti-inflammatory drugs (NSAID). Different hydrophilic copolymers were obtained by a suspension polymerization using a styrene-based and a methacrylate-based cross-linker and by single step modifications for enhancing the ion-exchange character. SPE protocols were optimized for both non-modified and modified sorbents and applied for the enrichment of selected NSAID using all six copolymers. Comparison and evaluation were carried out by determining recovery rates of standard mixtures at different concentration levels ranging from 0.5mgL(-1) to 10mgL(-1) and by the enrichment of spiked human urine at two concentration levels. In order to gain insight into the complexity of the biological sample and its reduction after solid phase extraction, UHPLC-MS analysis and following database comparison was performed for the three mixed-mode strong anion-exchange sorbents. In order to prove the applicability of the modified imidazole-based polymers for the enrichment of NSAID in surface water, river water or groundwater, solid phase extraction was performed with 10ppb of NSAID which resulted into enhanced enrichment by a hundredfold. PMID:27130106

  19. Prevention of heterotopic ossification after total hip replacement. Using nonsteroidal antiinflammatory drugs versus radiation therapy: a prospective randomized trial

    International Nuclear Information System (INIS)

    Purpose: Two prospective trials were undertaken to assess the comparative efficacy of early postoperative irradiation with different radiation doses versus the postoperative use of nonsteroidal antiinflammatory drugs (NSAID) for prevention of heterotopic ossification (HO) following prothetic total hip replacement (THP). Patients and Method: Between 1992 and 1994 585 patients received THP. These patients were randomized in two longitudinal studies each with 3 treatment arms comparing postoperative irradiation with 4x3 Gy (101 patients), 1x5 Gy (93 patients), 1x7 Gy (95 patients) and the postoperative use of the NSAID indometacin for 7 days (113 patients) respectively for 14 days (90 patients) and acetyl salicyl acid (ASS) for 14 days (93 patients). Heterotopic ossification was scored according to the Brooker grading system. One hundred patients receiving no prophylactic therapy after total hip arthroplasty between 1988 and 1992 were analysed and defined as historical control group. Conclusion: Prophylactic irradiation of the operative site after hip replacement is more effective than the use of NSAID. Because no significant difference between the fractionated single dose irradiation was found and the latter is more comfortable for patients and more economical, irradiation with single 7 Gy fraction should be prefered. (orig./MG)

  20. Impact and mechanism of non-steroidal anti-inflammatory drugs combined with chemotherapeutic drugs on human lung cancer-nude mouse transplanted tumors

    Science.gov (United States)

    SUN, WEIYI; CHEN, GANG

    2016-01-01

    The present study aimed to investigate the impact of indomethacin treatment combined with oxaliplatin treatment on the expression of cluster of differentiation 44 variant 6 (CD44v6), matrix metalloproteinase-2 (MMP-2) and survivin in human lung cancer-nude mouse transplanted tumors. The human lung adenocarcinoma (A549)-nude mouse transplanted tumor model was established, and the mice were divided into a control group, an indomethacin treatment group, an oxaliplatin treatment group and an indomethacin-oxaliplatin combination treatment group. The tumor inhibition rate was calculated following sacrificing of the mice. Immunohistochemical staining and fluorescence reverse transcription-quantitative polymerase chain reaction were utilized to detect the protein and messenger (m)RNA expression of CD44v6, MMP-2 and survivin. The tumor inhibition rates of the indomethacin group, the oxaliplatin group and the combination group were 26.67, 47.70 and 68.88%, respectively. The protein and mRNA expression levels of CD44v6, MMP-2 and survivin in the transplanted tumors of each treatment group were reduced compared with the control group (Plung cancer-nude mouse transplanted tumors and the expression of CD44v6, MMP-2 and survivin inside the tumor. The combination of non-steroidal anti-inflammatory drugs with chemotherapeutic drugs may improve the antitumor effects.

  1. Chemistry challenges in lead optimization: silicon isosteres in drug discovery.

    Science.gov (United States)

    Showell, Graham A; Mills, John S

    2003-06-15

    During the lead optimization phase of drug discovery projects, the factors contributing to subsequent failure might include poor portfolio decision-making and a sub-optimal intellectual property (IP) position. The pharmaceutical industry has an ongoing need for new, safe medicines with a genuine biomedical benefit, a clean IP position and commercial viability. Inherent drug-like properties and chemical tractability are also essential for the smooth development of such agents. The introduction of bioisosteres, to improve the properties of a molecule and obtain new classes of compounds without prior art in the patent literature, is a key strategy used by medicinal chemists during the lead optimization process. Sila-substitution (C/Si exchange) of existing drugs is an approach to search for new drug-like candidates that have beneficial biological properties and a clear IP position. Some of the fundamental differences between carbon and silicon can lead to marked alterations in the physicochemical and biological properties of the silicon-containing analogues and the resulting benefits can be exploited in the drug design process. PMID:12821303

  2. 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.

  3. The use of nonsteroidal anti-inflammatory drugs for exercise-induced muscle damage: implications for skeletal muscle development.

    Science.gov (United States)

    Schoenfeld, Brad J

    2012-12-01

    Exercise-induced muscle damage (EIMD) is a common condition resulting from a bout of vigorous exercise, particularly if the individual is unaccustomed to performance of the given movement. Symptoms of EIMD include delayed-onset muscle soreness (DOMS) and a loss of physical function. Nonsteroidal anti-inflammatory drugs (NSAIDs) are routinely prescribed post-exercise to alleviate these symptoms and restore normal physical function. Of potential concern for those who use NSAIDs to treat EIMD is the possibility that they may impair the adaptive response to exercise. Specifically, there is emerging evidence that the action of cyclo-oxygenase (COX) enzymes, and COX-2 in particular, are important and even necessary to achieve maximal skeletal muscle hypertrophy in response to functional overload. Given that NSAIDs exert their actions by blocking COX and thus suppressing prostaglandin production, a theoretical rationale exists whereby these drugs may have detrimental effects on muscle regeneration and supercompensation. Therefore, the purpose of this article is to extensively review the literature and evaluate the effects of NSAIDs on muscle growth and development. Based on current evidence, there is little reason to believe that the occasional use of NSAIDs will negatively affect muscle growth, although the efficacy for their use in alleviating inflammatory symptoms remains questionable. Evidence on the hypertrophic effects of the chronic use of NSAIDs is less clear. In those who are untrained, it does not appear that regular NSAID use will impede growth in the short term, and at least one study indicates that it may in fact have a positive impact. Given their reported impairment of satellite cell activity, however, longer-term NSAID use may well be detrimental, particularly in those who possess greater growth potential. PMID:23013520

  4. Rational use of nonsteroidal anti-inflammatory drugs and proton pump inhibitors in combination for rheumatic diseases

    Directory of Open Access Journals (Sweden)

    Wolfgang W Bolten

    2010-09-01

    Full Text Available Wolfgang W BoltenDivision of Rheumatology, Klaus-Miehlke Klinik, Wiesbaden, GermanyAbstract: Nonsteroidal anti-inflammatory drugs (NSAIDs are successfully used to alleviate pain and inflammation in rheumatic diseases. In an appreciable percentage of cases, the use of systemic NSAIDs is associated with adverse lesions of the gastrointestinal (GI mucosa up to life-threatening perforations, ulcers, and bleeding. Reliable warning signals mostly do not arise. Therefore, it is important to take preventive measures to reduce the GI risk. One established method is to assign cyclooxygenase 2 (COX-2-specific inhibitors (coxibs instead of traditional NSAIDs (tNSAIDs. Coxibs spare in part the endogenous gastroprotective mechanisms. Another reliable choice to improve the GI safety is the comedication of proton pump inhibitors (PPIs to suppress gastric acid. A fixed NSAID/PPI combination ensures expected protective effects by improving patients’ PPI adherence and physicians’ PPI prescription persistence. A fixed combination of enteric-coated naproxen and immediate-release esomeprazole has just been approved by the US Food and Drug Administration. PPI combinations with aspirin, other tNSAIDs, and coxibs are desirable. Patients in all risk groups, even patients at low risk of GI adverse events, benefit from concomitant protective measures. Moreover, the literature suggests that NSAID/PPI combinations are cost effective, including for patients in low-GI-risk groups. Pricing of fixed NSAID/PPI combinations will play a pivotal role for their broad acceptance in the future.Keywords: PPI, NSAID, fixed combination, gastrointestinal, adverse events, prevention

  5. Small Mismatches in Fatty Acyl Tail Lengths Can Effect Non Steroidal Anti-Inflammatory Drug Induced Membrane Fusion.

    Science.gov (United States)

    Majumdar, Anupa; Sarkar, Munna

    2016-06-01

    Biological membranes are made up of a variety of lipids with diverse physicochemical properties. The lipid composition modulates different lipidic parameters, such as hydration, dynamics, lipid packing, curvature strain, etc. Changes in these parameters affect various membrane-mediated processes, such as membrane fusion which is an integral step in many biological processes. Packing defects, which originate either from mismatch in the headgroup region or in the hydrophobic acyl tail region, play a major role in modulating membrane dynamics. In this study, we demonstrate how even a small mismatch in the fatty acyl chain length, achieved by incorporation of low concentrations (up to 30 mol %) of dipalmitoylphosphatidylcholine (DPPC) into dimyristoylphosphatidylcholine (DMPC) small unilamellar vesicles (SUVs), alters several lipidic parameters like packing, dynamics, and headgroup hydration. This in turn affects non steroidal anti-inflammatory drug (NSAID) induced membrane fusion. Dynamic light scattering, differential scanning calorimetry, second-derivative absorption spectrophotometry, and steady-state and time-resolved fluorescence have been used to elucidate the effect of small mismatch in the tails in DMPC/DPPC mixed vesicles and how it modulates membrane fusion induced by the oxicam NSAIDs, meloxicam (Mx), piroxicam (Px), and tenoxicam (Tx). Fusion kinetics was monitored using fluorescence based fusion assays. At low DPPC concentration of 10 mol %, additional fluidization promotes lipid mixing to some extent for Mx, but at higher mol % of DPPC, subsequent increase in rigidity of membrane interior along with increase in headgroup hydration, synergistically inhibits fusion to various extents for the three different drugs, Mx, Px, and Tx. PMID:27153337

  6. Prevention of trauma-induced cochlear fibrosis using intracochlear application of anti-inflammatory and antiproliferative drugs.

    Science.gov (United States)

    Jia, H; François, F; Bourien, J; Eybalin, M; Lloyd, R V; Van De Water, T R; Puel, J-L; Venail, F

    2016-03-01

    Cochlear fibrosis is a common finding following cochlear implantation. Evidence suggests that cochlear fibrosis could be triggered by inflammation and epithelial-to-mesenchymal cell transition (EMT). In this study, we investigate the mechanisms of cochlear fibrosis and the risk/benefit ratio of local administration of the anti-inflammatory drug dexamethasone (DEX) and antimitotic drug aracytine (Ara-C). Cochlear fibrosis was evaluated in cochlear fibrosis models of rat cochlear slices in vitro and in KLH-induced immune labyrinthitis and platinum wire cochlear implantation-induced fibrosis in vivo. Cochleae were invaded with tissue containing fibroblastic cells expressing α-SMA (alpha smooth muscle actin), which along with collagen I, fibronectin, and laminin in the extracellular matrix, suggests the involvement of a fibrotic process triggered by EMT in vitro and in vivo. After perilymphatic injection of an adenoviral vector expressing GFP in vivo, we demonstrated that the fibroblastic cells derived from the mesothelial cells of the scalae tympani and vestibuli. Activation of inflammatory and EMT pathways was further assessed by ELISA analysis of the expression of IL-1β and TGF-β1. Both markers were elevated in vitro and in vivo, and DEX and Ara-C were able to reduce IL-1β and TGF-β1 production. After 5days of culture in vitro, quantification of calcein-positive cells revealed that Ara-C was 30-fold more efficient in preventing fibrosis, and provoked less sensory hair cell loss, than DEX. In KLH-induced immune labyrinthitis and platinum wire-implanted models, Ara-C was more efficient in preventing proliferation of fibrosis with less side effects on hair cells and neurons than DEX. In conclusion, DEX and Ara-C both prevent fibrosis in the cochlea. Analysis of the risk/benefit ratio favors the use of Ara-C for preventing cochlear fibrosis. PMID:26718602

  7. 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

  8. Rethinking Drugs from Chemistry to Therapeutic Opportunities: Pixantrone beyond Anthracyclines.

    Science.gov (United States)

    Menna, Pierantonio; Salvatorelli, Emanuela; Minotti, Giorgio

    2016-08-15

    Pixantrone (6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione) has been approved by the European Medicines Agency for the treatment of refractory or relapsed non-Hodgkin's lymphoma (NHL). It is popularly referred to as a novel aza-anthracenedione, and as such it is grouped with anthracycline-like drugs. Preclinical development of pixantrone was in fact tailored to retain the same antitumor activity as that of anthracyclines or other anthracenediones while also avoiding cardiotoxicity that dose-limits clinical use of anthracycline-like drugs. Preliminary data in laboratory animals showed that pixantrone was active, primarily in hematologic malignancies, but caused significantly less cardiotoxicity than doxorubicin or mitoxantrone. Pixantrone was cardiac tolerable also in animals pretreated with doxorubicin, which anticipated a therapeutic niche for pixantrone to treat patients with a history of prior exposure to anthracyclines. This is the case for patients with refractory/relapsed NHL. Pixantrone clinical development, regulatory approval, and penetration in clinical practice were nonetheless laborious if not similar to a rocky road. Structural and nominal similarities with mitoxantrone and anthracyclines may have caused a negative influence, possibly leading to a general perception that pixantrone is a "me-too" anthracycline. Recent insights suggest this is not the case. Pixantrone shows pharmacological and toxicological mechanisms of action that are difficult to reconcile with anthracycline-like drugs. Pixantrone is a new drug with its own characteristics. For example, pixantrone causes mis-segregation of genomic material in cancer cells and inhibits formation of toxic anthracycline metabolites in cardiac cells. Understanding the differences between pixantrone and anthracyclines or mitoxantrone may help one to appreciate how it worked in the phase 3 study that led to its approval in Europe and how it might work in many more patients in everyday clinical

  9. Nonsteroidal anti-inflammatory drugs and breast cancer risk in the National Institutes of Health–AARP Diet and Health Study

    OpenAIRE

    Gierach, Gretchen L.; James V Lacey; Schatzkin, Arthur; Leitzmann, Michael F.; Richesson, Douglas; Hollenbeck, Albert R.; Brinton, Louise A.

    2008-01-01

    Introduction By inhibiting cyclooxygenase-2, nonsteroidal anti-inflammatory drugs (NSAIDs) decrease aromatase activity and might reduce breast cancer risk by suppressing estrogen synthesis. Epidemiologic evidence for a protective role of NSAIDs in breast cancer, however, is equivocal. Methods We tested NSAID use for its association with breast cancer incidence in the National Institutes of Health–AARP Diet and Health Study, where 127,383 female AARP (formerly known as the American Association...

  10. Dermal Cell Damage Induced by Topical Application of Non-Steroidal Anti-Inflammatory Drugs is Suppressed by Trehalose Co-Lyophilization in Ex Vivo Analysis

    OpenAIRE

    KAYASUGA-KARIYA, Yuko; Iwanaga, Shintaroh; Fujisawa, Ayano; LIN, Lee-Shuan; Suzuki, Shigeki; Chung, Ung-il; Sasaki, Nobuo; Shimohata, Nobuyuki; Mochizuki, Manabu

    2013-01-01

    ABSTRACT Topical administration of non-steroidal anti-inflammatory drugs (NSAIDs) is generally considered safer than oral administration, although the former can occasionally induce cutaneous irritation. We hypothesized that the cutaneous irritation by topical NSAIDs might be suppressed by trehalose, which has protective effects on biological membranes. Using the three-dimensional cultured human skin model, Living Skin Equivalent-high, we found that cutaneous damage due to NSAIDs was reduced ...

  11. Exposure to Non-Steroidal Anti-Inflammatory Drugs during Pregnancy and the Risk of Selected Birth Defects: A Prospective Cohort Study

    OpenAIRE

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

    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 the risk of selected birth defects after prenatal exposure to prescribed and over-the-counter NSAIDs. METHODS AND FINDINGS: We used data on 69,929 women enrolled in the Norwegian Mother and Child C...

  12. Cost Effectiveness Associated with Helicobacter pylori Screening and Eradication in Patients Taking Nonsteroidal Anti-Inflammatory Drugs and/or Aspirin

    OpenAIRE

    Song, Hyun Jin; Kwon, Jin-Won; Kim, Nayoung; Park, Young Soo

    2013-01-01

    Background/Aims This study was performed to investigate the cost effectiveness of Helicobacter pylori screening/eradication in South Korean patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and/or aspirin. Methods A decision Markov model was used to estimate the effectiveness and economic impact of an H. pylori screening/eradication strategy compared to a no-screening strategy among patients who were included in the model at the age of 40 years. Utility weights were applied ...

  13. A review of the benefits and risks of nonsteroidal anti-inflammatory drugs in the management of mild-to-moderate osteoarthritis

    OpenAIRE

    Fendrick, A. Mark; Greenberg, Bruce P

    2009-01-01

    This review is intended to provide physicians with an overview of the benefits and risks associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the management of their patients with mild-to-moderate osteoarthritis (OA). New information on the inflammatory component of OA and the cardiovascular (CV) risk associated with cyclooxygenase (COX)-2-specific inhibitors has prompted efforts to revise the current recommendations for the use of NSAIDs in the treatment of patients wi...

  14. Analysis of the use and adverse effects of non-steroidal anti-inflammatory drugs: A pilot study

    Directory of Open Access Journals (Sweden)

    Perić Aneta

    2006-01-01

    Full Text Available Background/Aim. The use and adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs in outpatients with rheumatic diseases has not yet been studied enough. The aim of this study was to evaluate the data about the efficacy and safety of NSAIDs obtained from the questionnaires submitted to the outpatients receiving these drugs. Methods. The patients who had been prescribed any of NSAIDs within the period from June to September, 2004 were included in the study. The answers obtained from the questionnaires were statistically analyzed by means of χ2-test. Results. At the time of the study, 150 patients had been prescribed ibuprofen or some other NSAID. Out of the total number of dispensed questionnaires (n = 150, only 45 (30% were shown to be correctly filled-in. Their analysis showed that 64.4% of the patients had suffered from rheumatic diseases for more than five years, and had regularly used NSAIDs. The average age of these patients was about 70 years, and the number of females was double as high as that of the males. The most frequently used NSAIDs were diclofenac and ibuprofen (46.14%, and 23.24%, respectively. According to the answers given by the patients, the most often adverse reactions were gastric complaints such as nausea (11.1%, and stomach pain (8.9%. Due to this, the majority of the patients (64.4% used some of the antiulcer drugs, most often ranitidine (31.1%. Conclusion. The results of this pilot study revealed that among the outpatients suffering from rheumatic diseases, the number of females was double as high as the number of males, that these patients were of the mean age of 70 years, and that their diseases lasted longer than five years. Gastric complains such as nausea and gastric pain of mild intensity were the most often adverse effects of NSAIDs reported by our patients. It could be the consequence of the predominant use of diclofenac and ibuprofen, NSAIDs with mild to moderate ulcerogenic potential, as well as the

  15. 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

  16. 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

  17. Combination of click chemistry and controlled radical polymerization for synthesis of advanced polymer drug delivery systems

    Czech Academy of Sciences Publication Activity Database

    Pechar, Michal; Pola, Robert; Braunová, Alena; Laga, Richard; Ulbrich, Karel

    2013-01-01

    Roč. 9, č. 1 (2013), s. 106-107 /3P10/. ISSN 1336-7242. [Zjazd chemikov /65./. 09.09.2013-13.09.2013, Tatranské Matliare] R&D Projects: GA ČR GCP207/12/J030 Institutional support: RVO:61389013 Keywords : polymer conjugates * controlled drug delivery * diagnostics of tumors Subject RIV: CD - Macromolecular Chemistry

  18. Incidence of serious upper gastrointestinal bleeding in patients taking non-steroidal anti-inflammatory drugs in Japan.

    Science.gov (United States)

    Ishikawa, Shigenao; Inaba, Tomoki; Mizuno, Motowo; Okada, Hiroyuki; Kuwaki, Kenji; Kuzume, Toshiaki; Yokota, Hitomi; Fukuda, Yasuyo; Takeda, Kou; Nagano, Hiroshi; Wato, Masaki; Kawai, Kozo

    2008-02-01

    Upper gastrointestinal bleeding is a major adverse event of non-steroidal anti-inflammatory drugs (NSAIDs), and co-administration of proton pump inhibitors and H2 receptor antagonists has been established as a means of preventing such an effect. However, the incidence of bleeding associated with NSAID-induced ulcers under conditions where such strong anti-acid agents are used for prevention has yet to be clarified. We aimed to determine the annual incidence of serious upper gastrointestinal ulcer bleeding among Japanese patients in whom NSAIDs were used in our hospital. Before commencing the study, we recommended to all the physicians in our hospital the best method for caring for NSAID users, focusing on the concomitant use of proton pump inhibitors or H2 receptor antagonists. We conducted a cohort study involving 17,270 patients for whom NSAIDs had been newly prescribed. Bleeding from gastric ulcers was observed in 8 of the 17,270 patients using NSAIDs (0.05%). The pooled incidence rate for bleeding was calculated as 2.65 (95% confidence interval, 2.56-2.74) and 1.29 (1.27-1.31) per 1,000 patient years for low-dose aspirin and non-aspirin NSAID users, respectively. None of the bleeding ulcer patients required blood transfusion or were in serious condition. In conclusion, gastric ulcer bleeding occurred in low-dose aspirin or non-aspirin NSAID users, but its incidence was low and outcomes were not serious when adequate preventive measures were taken. PMID:18323869

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Kai-Yu Ji; Fu-Lian Hu

    2006-01-01

    According to a meta-analysis, H pylori and non-steroidal anti-inflammatory drugs (NSAID) independently and significantly increase the risk of gastroduodenal ulcer and ulcer bleeding. Their coincidence is frequent,demonstration of a possible relationship and consequent attitude is of important implications. But unfortunately,no consensus has been approved in the past years and their interactions are still controversial. H pylori and NSAID are known to share a number of pathogenic mechanisms, but there is no evidence for the significant synergic action between these two risk factors. Their relationship is independent, additive, synergistic or antagonistic without considering the influence of other factors because studies on this subject are different in almost all aspects of their methodology, including the definition of a NSAID user as well as the types,doses, duration and their indications for NSAID use,as well as their end-points, definition of dyspepsia and regimes used for eradication of H pylori. These might contribute to the conflicting results and opinions. H pylori infection in humans does not act synergistically with NSAID on ulcer healing, and there is no need to eradicate it. This notion is supported by the finding that the eradication of H pylori does not affect NSAIDinduced gastropathy treated with omeprazole and that H pylori infection induces a strong cyclooxygenase-2(COX-2) expression resulting in excessive biosynthesis of gastroprotective prostaglandin which in turn counteracts NSAID-induced gastropathy and heals the existing ulcer.Other investigators claimed that H pylori infection acts synergistically with NSAID on ulcer development, and H pylori should be eradicated, particularly at the start of long-term NSAID therapy. Eradication of H pylori prior to NSAID treatment does not appear to accelerate ulcer healing or to prevent recurrent ulcers in NSAID users.However, some recommendations can be drawn from the results of clinical trails.

  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. Equilibrium thermodynamics of the partitioning of non-steroidal anti-inflammatory drugs into human erythrocyte ghost membranes

    International Nuclear Information System (INIS)

    Graphical abstract: Bar diagram representing thermodynamic parameters obtained for the partitioning of NSAIDs into human erythrocyte ghost membranes at physiological pH; 7.4. Highlights: • Partition coefficients of NSAIDs into HEG membranes were determined. • Thermodynamic parameters were evaluated and successfully analyzed. • Partitioning of NSAIDs into HEG membranes was exothermic. • Partitioning of NSAIDs into HEG is spontaneous with negative free energy values. • Identical partitioning enthalpy–entropy driven compensation mechanism was shown. -- Abstract: In this work,second derivative spectrophotometry was applied for determining the partition coefficients (Kps) of four non-steroidal anti-inflammatory drugs (NSAIDs; flufenamic, meclofenamic, mefenamic and niflumic acids) into human erythrocyte ghost (HEG) membranes over a temperature range from (283.2 to 313.2) K. The proposed method allowed the evaluation and direct analyses of thermodynamic parameters; enthalpy (ΔHW→M), Gibbs energy (ΔGW→M) and entropy (ΔSW→M) changes of the partitioning of NSAIDs into HEG membranes. The partitioning of NSAIDs between polar aqueous phase and non-polar lipid bilayer HEG membrane phase was exothermic with negative (ΔHW→M) which compensated for the changes in (ΔSW→M). The negative values of (ΔGW→M) revealed that the partitioning of NSAIDs into HEG, owing to their transfer from polar aqueous phase and non-polar HEG phase is spontaneous. The enthalpy–entropy correlation analysis resulted in a good linearity that suggests an identical partitioning enthalpy–entropy driven compensation mechanism for the studied NSAIDs

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    Pinyi Lu

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

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

    Directory of Open Access Journals (Sweden)

    Smolović Brigita

    2014-01-01

    Full Text Available Background/Aim. A high risk of bleeding in Helicobacter pylori (H.pylori-negative, non-steroidal anti-inflammatory drugs (NSAID-negative ulcers highlights the clinical importance of analysis of the changing trends of peptic ulcer disease. The aim of the study was to investigate the risk factors for ulcer bleeding in patients with non-H. pylori infection, and with no NSAIDs use. Methods. A prospective study included patients with endoscopically diagnosed ulcer disease. The patients were without H. pylori infection (verified by pathohistology and serology and without exposure to NSAIDs and proton pump inhibitors (PPI within 4 weeks before endoscopy. After endoscopy the patients were divided into 2 groups: the study group of 48 patients with bleeding ulcer and the control group of 47 patients with ulcer, but with no bleeding. Prior to endoscopy they had completed a questionnaire about demographics, risk factors and habits. The platelet function, von Willebrand factor (vWF and blood groups were determined. Histopathological analysis of biopsy samples were performed with a modified Sydney system. The influence of bile reflux was analyzed by Bile reflux index (BRI. Results. Age, gender, tobacco and alcohol use did not affect the bleeding rate. The risk of bleeding did not depend on concomitant diseases (p = 0.509 and exposure to stress (p = 0.944. Aspirin was used by 16/48 (33.3% patients with bleeding ulcer, as opposed to 7/47 (14.9% patients who did not bleed (p = 0.036. Abnormal platelet function had 12/48 (25.0% patients who bled, as opposed to 2/47 (4.3% patients who did not bleed (p = 0.004. Patients with BRI < 14 bled in 79.2%, and did not bleed in 57.4% of the cases (p = 0.023. There was no statistical difference between groups in regards to blood groups and range of vWF. Antrum atrophy was found in 14/48 (29.2% patients with bleeding ulcer and in only 5/47 (10.6% patients who had ulcer without bleeding (p = 0.024. Conclusion. Abnormal

  6. Gastrointestinally distributed UDP-glucuronosyltransferase 1A10, which metabolizes estrogens and nonsteroidal anti-inflammatory drugs, depends upon phosphorylation.

    Science.gov (United States)

    Basu, Nikhil K; Kubota, Shigeki; Meselhy, Meselhy R; Ciotti, Marco; Chowdhury, Bhabadeb; Hartori, Masao; Owens, Ida S

    2004-07-01

    Among gastrointestinal distributed isozymes encoded at the UGT1 locus, UDP-glucuronosyltransferase 1A10 (UGT1A10) metabolizes a number of important chemicals. Similar to broad conversion of phytoestrogens (Basu, N. K., Ciotti, M., Hwang, M. S., Kole, L., Mitra, P. S., Cho, J. W., and Owens, I. S. (2004) J. Biol. Chem. 279, 1429-1441), UGT1A10 metabolized estrogens and their derivatives, whereas UGT1A1, -1A3, -1A7, and -1A8 differentially exhibited reduced activity toward the same. UGT1A10 compared with UGT1A7, -1A8, and -1A3 generally exhibited high activity toward acidic nonsteroidal anti-inflammatory drugs and natural benzaldehyde derivatives, while UGT1A3 metabolized most efficiently aromatic transcinnamic acids known to be generated from flavonoid glycosides by microflora in the lower gastrointestinal tract. Finally UGT1A10, -1A7, -1A8, and -1A3 converted plant-based salicylic acids; methylsalicylic acid was transformed at high levels, and acetylsalicylic (aspirin) and salicylic acid were transformed at moderate to low levels. Atypically UGT1A10 transformed estrogens between pH 6 and 8 but acidic structures preferentially at pH 6.4. Furthermore evidence indicates UGT1A10 expressed in COS-1 cells depends upon phosphorylation; UGT1A10 versus its single, double, and triple mutants at three predicted protein kinase C phosphorylation sites incorporated [(33)P]-orthophosphate and showed a progressive decrease with no detectable label or activity for the triple T73A/T202A/S432G-1A10 mutant. Single and double mutants revealed either null/full activity or null/additive activity, respectively. Additionally UGT1A10-expressing cultures glucuronidated 17beta-[(14)C]estradiol, whereas cultures containing null mutants at protein kinase C sites showed no estrogen conversion. Importantly UGT1A10 in cells supported 10-fold higher glucuronidation of 17beta-estradiol than UGT1A1. In summary, our results suggest gastrointestinally distributed UGT1A10 is important for detoxifying

  7. 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

    2012-05-01

    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. PMID:22436506

  8. Use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs in high doses increases mortality and risk of reinfarction in patients with prior myocardial infarction

    DEFF Research Database (Denmark)

    Sørensen, Rikke; Abildstrøm, Steen Zabell; Torp-Pedersen, C.;

    2008-01-01

    The selective cyclooxygenase-2 (COX-2) inhibitors and other nonselective nonsteroidal antiinflammatory drugs (NSAIDs) have been associated with increased cardiovascular risk, but the risk in patients with established cardiovascular disease is unknown. In the present study, we analyzed the risk of...... register of drug dispensing from pharmacies. We found a dose-dependent increase in risk of death for both the selective COX-2 inhibitors and the nonselective NSAIDs (all of the drugs tested). There were trends for increased risk of re-MI associated with the use of both the selective COX-2 inhibitors and...... rehospitalization for acute myocardial infarction (re-MI) and death related to the use of NSAIDs including selective COX-2 inhibitors in patients with a prior myocardial infarction (MI). We included 58,432 patients discharged alive after a first MI, and subsequent use of all NSAIDs was identified from a nationwide...

  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. The efficacy and tolerability of the slow-acting combined agent glucosamine and chondroitin sulfate in gonarthrosis patients tacking no nonsteroidal anti-inflammatory drugs

    OpenAIRE

    A P Rebrov; Romanova, I.A.; I. Z. Gaydukova

    2015-01-01

    Objective: to evaluate the efficacy and tolerability of the combined symptomatic slow-acting combined agent Theraflex in gonarthrosis patients untreated with nonsteroidal antiinflammatory drugs (NSAIDs).Patients and methods. The investigation enrolled 84 patients (78 women and 6 men) aged 55.23±7.36 years with knee arthritis lasting 6.2±0.98 years who were blindly randomized into 2 groups. A study group took Theraflex (chondroitin sulfate 400 mg and glucosamine sulfate 500 mg) with or without...

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

    Directory of Open Access Journals (Sweden)

    W.L.S. Gonçalves

    2007-06-01

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

  12. LPS-Induced Lung Inflammation in Marmoset Monkeys – An Acute Model for Anti-Inflammatory Drug Testing

    OpenAIRE

    Sophie Seehase; Hans-Dieter Lauenstein; Christina Schlumbohm; Simone Switalla; Vanessa Neuhaus; Christine Förster; Hans-Gerd Fieguth; Olaf Pfennig; Eberhard Fuchs; Franz-Josef Kaup; Martina Bleyer; Hohlfeld, Jens M.; Armin Braun; Katherina Sewald; Sascha Knauf

    2012-01-01

    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 ...

  13. Anti-inflammatory drugs interacting with Zn (II) metal ion based on thiocyanate and azide ligands: Synthesis, spectroscopic studies, DFT calculations and antibacterial assays

    Science.gov (United States)

    Chiniforoshan, Hossein; Tabrizi, Leila; Hadizade, Morteza; Sabzalian, Mohammad R.; Chermahini, Alireza Najafi; Rezapour, Mehdi

    2014-07-01

    Zinc (II) complexes with non-steroidal anti-inflammatory drugs (NSAIDs) naproxen (nap) and ibuprofen (ibu) were synthesized in the presence of nitrogen donor ligands (thiocyanate or azide). The complexes were characterized by elemental analysis, FT-IR, 1H NMR and UV-Vis spectroscopes. The binding modes of the ligands in complexes were established by means of molecular modeling of the complexes, and calculation of their IR, NMR and absorption spectra at DFT (TDDFT)/B3LYP level were studied. The experimental and calculated data verified monodentate binding through the carboxylic oxygen atoms of anti-inflammatory drugs in the zinc complexes. The calculated 1H, FT-IR and UV-Vis data are in better agreement with the experimental results, and confirm the predicted tetrahedral structures for the Zn (II) complexes. In addition to DFT calculations of complexes, natural bond orbital (NBO) was performed at B3LYP/6-31+G(d,p) level of theory. Biological studies showed the antibacterial activity of zinc complexes against Gram-positive and Gram-negative bacterial strains.

  14. Suppression of postoperative pain by the combination of a nonsteroidal anti-inflammatory drug, flurbiprofen, and a long-acting local anesthetic, etidocaine.

    Science.gov (United States)

    Dionne, R A; Wirdzek, P R; Fox, P C; Dubner, R

    1984-04-01

    The analgesic efficacy of the combination of a nonsteroidal anti-inflammatory drug, flurbiprofen, and a long-acting local anesthetic, etidocaine, was evaluated for the suppression of acute postoperative pain. Subjects having two impacted third molars removed at two appointments received either the experimental combination or standard treatment in a randomized, crossover design. The experimental treatment consisted of 100 mg flurbiprofen 30 minutes before surgery, 1.5% etidocaine with 1:200,000 epinephrine five minutes before surgery, and 100 mg flurbiprofen three hours after surgery. Standard treatment consisted of 10 mg oxycodone plus 650 mg acetaminophen 30 minutes before surgery, 2% lidocaine with 1:100,000 epinephrine five minutes before surgery, and a second dose of the oxycodone-acetaminophen combination three hours after surgery. Pain intensity was rated hourly from one to seven hours after surgery, using a variety of ordinal and analog scales. The flurbiprofen-etidocaine combination resulted in significantly less postoperative pain than the oxycodone plus acetaminophen-lidocaine combination on all four analgesic scales used and was preferred by the majority of the patients. This study shows that pretreatment with a nonsteroidal anti-inflammatory drug, flurbiprofen, in combination with a long-acting local analgesic, etidocaine, suppresses pain to a greater extent than a potent opiate mild/analgesic combination and lidocaine without an increase in side-effect liability. PMID:6586802

  15. Non Peptic Ulcer Upper Gastrointestinal Bleeding in Patients Treated with Non-Steroidal Anti-inflammatory Drugs for Musculo-articular Disorders

    Directory of Open Access Journals (Sweden)

    Simona Mureşan

    2015-08-01

    Full Text Available Introduction: Complications in the evolution of digestive tract benign pathology leads to symptoms: hemorrhagic, occlusive or perforative syndrome. Method: We present three cases of gastrointestinal (GI hemorrhage with a different pathology and rarely seen in clinical practice in patients treated with non-steroidal anti-inflammatory drugs for muscular-articular pathology. Cases’ presentation: (1 A 47 years old man known with recurrent episodes of upper GI bleeding was admitted for a new massive hemorrhage; the emergency laparotomy revealed a splenic arteriovenous fistula penetrating the Wirsung duct. A splenopancreatectomy was performed with uneventful recovery. (2 A 57 years old woman with chronic anemia, nausea, weight loss and vomiting was admitted for intermittent recurrent episodes of melena. The exploratory laparotomy revealed several jejunal diverticulum with active bleeding; a segmental enterectomy was performed with uneventful recovery. (3 A 24 year old patient was admitted for massive inaugural melena. The upper GI tract endoscopy was negative; due to hemorrhagic shock an emergency exploratory laparotomy was performed and revealed a jejunal GIST. The resection was performed with uneventful recovery. The histo-pathologic exam confirmed a benign GIST. Conclusions: During Non-Steroidal Anti-inflammatory Drugs (NSAID therapy anemia and upper GI bleeding are usually considered as common disorders related with peptic ulcer. However NSAID therapy can hide another more complex causes of bleeding. In majority of cases the bleeding is brutal and surgical approach remains the only alternative to perform the diagnosis and to cure the patient.

  16. Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs after acute myocardial infarction

    DEFF Research Database (Denmark)

    Gislason, Gunnar H; Jacobsen, Søren; Rasmussen, Jeppe Nørgaard;

    2006-01-01

    BACKGROUND: The selective cyclooxygenase-2 (COX-2) inhibitors and other nonselective nonsteroidal antiinflammatory drugs (NSAIDs) have been associated with increased cardiovascular risk, but the risk in patients with established cardiovascular disease is unknown. We analyzed the risk of...... of the drugs. There were trends for increased risk of rehospitalization for MI associated with the use of both the selective COX-2 inhibitors and the nonselective NSAIDs. CONCLUSIONS: Selective COX-2 inhibitors in all dosages and nonselective NSAIDs in high dosages increase mortality in patients with...... rehospitalization for acute myocardial infarction (MI) and death related to the use of NSAIDs including selective COX-2 inhibitors in patients with prior MI. METHODS AND RESULTS: All patients with first-time MI between 1995 and 2002 as well as all prescription claims for NSAIDs after discharge were identified from...

  17. Rule of five in 2015 and beyond: Target and ligand structural limitations, ligand chemistry structure and drug discovery project decisions.

    Science.gov (United States)

    Lipinski, Christopher A

    2016-06-01

    The rule of five (Ro5), based on physicochemical profiles of phase II drugs, is consistent with structural limitations in protein targets and the drug target ligands. Three of four parameters in Ro5 are fundamental to the structure of both target and drug binding sites. The chemical structure of the drug ligand depends on the ligand chemistry and design philosophy. Two extremes of chemical structure and design philosophy exist; ligands constructed in the medicinal chemistry synthesis laboratory without input from natural selection and natural product (NP) metabolites biosynthesized based on evolutionary selection. Exceptions to Ro5 are found mostly among NPs. Chemistry chameleon-like behavior of some NPs due to intra-molecular hydrogen bonding as exemplified by cyclosporine A is a strong contributor to NP Ro5 outliers. The fragment derived, drug Navitoclax is an example of the extensive expertise, resources, time and key decisions required for the rare discovery of a non-NP Ro5 outlier. PMID:27154268

  18. 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: 0.378, year: 2014

  19. PEGylation of Biopharmaceuticals: A Review of Chemistry and Nonclinical Safety Information of Approved Drugs.

    Science.gov (United States)

    Turecek, Peter L; Bossard, Mary J; Schoetens, Freddy; Ivens, Inge A

    2016-02-01

    Modification of biopharmaceutical molecules by covalent conjugation of polyethylene glycol (PEG) molecules is known to enhance pharmacologic and pharmaceutical properties of proteins and other large molecules and has been used successfully in 12 approved drugs. Both linear and branched-chain PEG reagents with molecular sizes of up to 40 kDa have been used with a variety of different PEG derivatives with different linker chemistries. This review describes the properties of PEG itself, the history and evolution of PEGylation chemistry, and provides examples of PEGylated drugs with an established medical history. A trend toward the use of complex PEG architectures and larger PEG polymers, but with very pure and well-characterized PEG reagents is described. Nonclinical toxicology findings related to PEG in approved PEGylated biopharmaceuticals are summarized. The effect attributed to the PEG part of the molecules as observed in 5 of the 12 marketed products was cellular vacuolation seen microscopically mainly in phagocytic cells which is likely related to their biological function to absorb and remove particles and macromolecules from blood and tissues. Experience with marketed PEGylated products indicates that adverse effects in toxicology studies are usually related to the active part of the drug but not to the PEG moiety. PMID:26869412

  20. [Role of anti-inflammatory drugs in the treatment of acute coronary syndromes. From athero-inflammation to athero-thrombosis].

    Science.gov (United States)

    Altman, Raúl; Scazziota, Alejandra

    2003-01-01

    Coronary thrombosis is the most important cause of morbidity and mortality and the most severe manifestation of atherosclerosis. Knowledge of the pathophysiology of atheroma formation and the causes of atheroma accidents have allowed the development of new therapeutic measures for reducing thrombotic events after a coronary episode. Treating the thrombosis after plaque rupture is useful, but a late measure once coronary flow is disturbed. Therefore, treatment at an earlier stage, which we call athero-inflammation, a central event in atheroma progression leading to atherothrombosis, seems wise. There is evidence of an inflammatory component in the pathogenesis of atheroma rupture in acute coronary events. Earlier studies of anti-inflammatory medication have not demonstrated a reduction in thrombotic complications after an acute coronary episode. However, there are pathophysiological arguments and clinical findings that suggest that it would be advisable to include anti-inflammatory medications, especially those that inhibit preferentially COX-2, in the therapeutic arsenal for this pathology. We postulated that blocking athero-inflammation could prevent thrombosis. A pilot study was carried out in 120 patients with acute coronary syndrome without ST-segment elevation in which 60 patients were treated with meloxicam, a preferential COX-2 inhibitor. All patients received heparin and aspirin. During the stay in the coronary care unit, as well as after 90 days, meloxicam lowered composite outcomes (myocardial infarction, death and revascularization procedures) compared with the control group. These results and available pathophysiological and clinical evidence support the hypothesis of potential benefits of non-steroidal anti-inflammatory drugs with preferential inhibitory activity on COX-2 in patients with acute coronary syndromes. More trials are needed to confirm their preventive effect. PMID:12549993

  1. Chemistry

    International Nuclear Information System (INIS)

    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 UF3 and dissolved UF4, and, in some cases, between the dissolved uranium fluorides and graphite, and the UC2. Several aspects of coolant-salt chemistry are under investigation. Hydroxy and oxy compounds that could be formed in molten NaBF4 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 U4+/U3+ ratios in fuel salt was tested in a forced-convection loop over a six-month period. (LK)

  2. Effect of increase in orientational order of lipid chains and head group spacing on non steroidal anti-inflammatory drug induced membrane fusion.

    Science.gov (United States)

    Roy, Sutapa Mondal; Bansode, Amol S; Sarkar, Munna

    2010-12-21

    Membrane fusion is a key event in many biological processes. The fusion process, both in vivo and in vitro, is induced by different agents which include mainly proteins and peptides. For protein- and peptide-mediated membrane fusion, conformational reorganization serves as a driving force. Small drug molecules do not share this advantage; hence, drug induced membrane fusion occurring in absence of any other fusogenic agent and at physiologically relevant concentration of the drugs is a very rare event. To date, 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 fusion at very low drug to lipid ratio without the aid of any other fusogenic agent. In our continued effort to understand the interplay of different physical and chemical parameters of both the participating drugs and the membrane on the mechanism of this drug induced membrane fusion, we present here the effect of increase in orientational order of the lipid chains and increase in head group spacing. This is achieved by studying the effect of low concentration cholesterol (gel to fluid transition temperature, is mainly known to increase orientational order of the lipid chains and increase head group spacing. To isolate the effect of these parameters, small unilameller vesicles (SUVs) formed by dimyristoylphosphatidylcholine (DMPC) with an average diameter of 50-60 nm were used as simple model membranes. 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. Differential scanning calorimetry (DSC) was used to study the effect of drugs in the presence of cholesterol on the chain-melting temperature which reflects the fluidization effect of the hydrophobic tail region of the bilayer. Our results show contradictory effect of low concentration

  3. Condition of sale of non-steroidal anti-inflammatory drugs authorized for marketing in colombia. strategy of rational use

    OpenAIRE

    Solano Roa, Magda Vianneth; Garavito Cárdenas, Giovanny

    2013-01-01

    The commercialization status (otc, under medical prescription, under special monitoring or for hospital use only) sets out the circumstances under which it may be publicized and marketed a drug. The otc does not involve consulting the health team, who do not participate in the selection of the drug, its dispensing or therapeutic monitoring. Present work through an observational, descriptive, cross-sectional study from the universe of Colombian drug approvals, identify and describe the variati...

  4. Surface chemistry dependent "switch" regulates the trafficking and therapeutic performance of drug-loaded carbon nanotubes.

    Science.gov (United States)

    Das, Manasmita; Singh, Raman Preet; Datir, Satyajit R; Jain, Sanyog

    2013-04-17

    The present study explores the possibility of exploiting surface functionality as one of the key regulators for modulating the intracellular trafficking and therapeutic performance of drug loaded carbon nanotubes (CNTs). In line with that approach, a series of biofunctionalized multiwalled carbon nanotubes (f-CNTs 1-6) decorated with various functional molecules including antifouling polymer (PEG), tumor recognition modules (folic acid/hyaluronic acid/estradiol), and fluorophores (rhodamine B isothiocyanate/Alexa Fluor) were synthesized. By loading different anticancer agents (methotrexate (MTX), doxorubicin (DOX), and paclitaxel (PTX)) onto each functionalized CNT preparation, we tried to elucidate how the surface functional molecules associated with each f-CNT influence their therapeutic potential. We observed that antiproliferative or apoptotic activity of drug-loaded CNTs critically depends on their mechanistic pathway of cellular internalization and intracellular trafficking, which in turn had an intimate rapport with their surface chemistry. To our knowledge, for the first time, we have embarked on the possibility of using a surface chemistry dependent "switch" to remote-control the second and third order targeting of chemotherapeutic agents supramolecularly complexed/adsorbed on CNTs, which in turn is expected to benefit the development of futuristic nanobots for cancer theranostics. PMID:23517108

  5. pH-sensitive interpenetrating polymer network microspheres of poly(vinyl alcohol) and carboxymethyl cellulose for controlled release of the nonsteroidal anti-inflammatory drug ketorolac tromethamine.

    Science.gov (United States)

    Kondolot Solak, Ebru; Er, Akın

    2016-05-01

    In this study, we aimed to produce pH-sensitive microspheres for the controlled release of the nonsteroidal anti-inflammatory drug, ketorolac tromethamine (KT). For this purpose, an interpenetrating polymer network (IPN) of microspheres of poly(vinyl alcohol) (PVA)/sodium carboxymethyl cellulose (NaCMC) were prepared, based on different formulations using glutaraldehyde (GA) (0.66 M) and hydrochloric acid (HCl) (3%, v/v). The preparation conditions of the microspheres were optimized by considering the percentage of entrapment efficiency and swelling capacity of the microspheres, and their release data. The effects of PVA and NaCMC ratio on the release of KT for over a period of 6 h, at three pH values (1.2, 6.8, and 7.4), have been discussed. PMID:25619756

  6. 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)

    Olsen, Anne-Marie Schjerning; 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...

  7. Potential of prescription registries to capture individual-level use of aspirin and other nonsteroidal anti-inflammatory drugs in Denmark

    DEFF Research Database (Denmark)

    Schmidt, Morten; Hallas, Jesper; Friis, Søren

    2014-01-01

    BACKGROUND: Due to over-the-counter availability, no consensus exists on whether adequate information on nonsteroidal anti-inflammatory drug (NSAID) use can be obtained from prescription registries. OBJECTIVES: To examine utilization of aspirin and nonaspirin NSAIDs in Denmark between 1999 and 2012...... and to quantify the proportion of total sales that was sold on prescription. METHOD: Based on nationwide data from the Danish Serum Institute and the Danish National Prescription Registry, we retrieved sales statistics for the Danish primary health care sector to calculate 1-year prevalences of...... prescription users of aspirin or nonaspirin NSAIDs, and to estimate the corresponding proportions of total sales dispensed on prescription. RESULTS: Both low-dose aspirin and nonaspirin NSAIDs were commonly used in the Danish population between 1999 and 2012, particularly among elderly individuals. The 1-year...

  8. 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...... 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...

  9. 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)

    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 p27kip1 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 p27kip1 and cyclin D2 in hOBs. We conclude that the changes in expressions of regulators of cell cycle (p27kip1 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

  10. The thermodynamic dissociation constants of four non-steroidal anti-inflammatory drugs by the least-squares nonlinear regression of multiwavelength spectrophotometric pH-titration data.

    Science.gov (United States)

    Meloun, Milan; Bordovská, Sylva; Galla, Lubomír

    2007-11-30

    The mixed dissociation constants of four non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen, diclofenac sodium, flurbiprofen and ketoprofen at various ionic strengths I of range 0.003-0.155, and at temperatures of 25 degrees C and 37 degrees C, were determined with the use of two different multiwavelength and multivariate treatments of spectral data, SPECFIT/32 and SQUAD(84) nonlinear regression analyses and INDICES factor analysis. The factor analysis in the INDICES program predicts the correct number of components, and even the presence of minor ones, when the data quality is high and the instrumental error is known. The thermodynamic dissociation constant pK(a)(T) was estimated by nonlinear regression of (pK(a), I) data at 25 degrees C and 37 degrees C. Goodness-of-fit tests for various regression diagnostics enabled the reliability of the parameter estimates found to be proven. PALLAS, MARVIN, SPARC, ACD/pK(a) and Pharma Algorithms predict pK(a) being based on the structural formulae of drug compounds in agreement with the experimental value. The best agreement seems to be between the ACD/pK(a) program and experimentally found values and with SPARC. PALLAS and MARVIN predicted pK(a,pred) values with larger bias errors in comparison with the experimental value for all four drugs. PMID:17825517

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

    Pain is a sensation related to potential or actual damage in some tissue of the body. The mainstay of medical pain therapy remains drugs that have been around for decades, like non-steroidal anti-inflammatory drugs (NSAIDs), or opiates. However, adverse effects of opiates, particularly tolerance, limit their clinical use. Several lines of investigations have shown that systemic (intraperitoneal) administration of NSAIDs induces antinociception with some effects of tolerance. In this review, we report that repeated microinjection of NSAIDs analgin, clodifen, ketorolac and xefocam into the central nucleus of amygdala, the midbrain periaqueductal grey matter and nucleus raphe magnus in the following 4 days result in progressively less antinociception compared to the saline control testing in the tail-flick reflex and hot plate latency tests. Hence, tolerance develops to these drugs and cross-tolerance to morphine in male rats. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, the periaqueductal grey-rostral ventro-medial part of medulla circuit should be viewed as a pain-modulation system. These data are important for human medicine. In particular, cross-tolerance between non-opioid and opioid analgesics should be important in the clinical setting.

  12. 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)

    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

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

    Directory of Open Access Journals (Sweden)

    Nicola Marchi

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

  14. Chemistry

    International Nuclear Information System (INIS)

    Research progress is reported in programs on fuel-salt chemistry, properties of compounds in the Li--Te system, Te spectroscopy UF4--H equilibria, porous electrode studies of molten salts, fuel salt-coolant salt reactions, thermodynamic properties of transition-metal fluorides, and properties of sodium fluoroborate. Developmental work on analytical methods is summarized including in-line analysis of molten MSBR fuel, analysis of coolant-salts for tritium, analysis of molten LiF--BeF2--ThF4 for Fe and analysis of LiF--BeF--ThF4 for Te

  15. PHARMACEUTICS, ETHNOPHARMACOLOGY, CHEMISTRY AND PHARMACOLOGY OF AYURVEDIC MARINE DRUGS: A REVIEW

    Directory of Open Access Journals (Sweden)

    Satadru Palbag

    2013-06-01

    Full Text Available Ayurveda is the ancient thought and treatise that deals with the knowledge of living a healthy life. There are several types of medicaments that are being used in the Ayurvedic mode of treatment. The source of these drugs is diverse and belongs to different category. The category ranges from plants and animals to minerals, and encircles around different types of species of plants and animals with vivid habitats.In the course of last thirty years, marine organisms have been proven to be a rich source of wide range of worthy compounds for medicine. In Ayurveda there is a wide range of marine drugs like Mukta, Varatika, Praval, Agnijvar, Samudra phena, etc that are useful in the management of numerous diseases like paralysis, hyperacidity, cancer, dyspepsia, eye diseases, etc. This review makes a humble effort to summarize and gather knowledge about different types of marine drugs that are described and explained in Ayurvedic system of medicine, its traditional processing and chemistry, ethno pharmacology and pharmacological role.

  16. Co-delivery of antigen and a lipophilic anti-inflammatory drug to cells via a tailorable nanocarrier emulsion.

    Science.gov (United States)

    Chuan, Yap Pang; Zeng, Bi Yun; O'Sullivan, Brendan; Thomas, Ranjeny; Middelberg, Anton P J

    2012-02-15

    Nanotechnology promises new drug carriers that can be tailored to specific applications. Here we report a new approach to drug delivery based on tailorable nanocarrier emulsions (TNEs), motivated by a need to co-deliver a protein antigen and a lipophilic drug for specific inhibition of nuclear factor kappa B (NF-κB) in antigen presenting cells (APCs). Co-delivery for NF-κB inhibition holds promise as a strategy for the treatment of rheumatoid arthritis. We used a highly surface-active peptide (SAP) to prepare a nanosized emulsion having defined surface properties predictable from the SAP sequence. Incorporating the lipophilic drug into the oil phase at the time of emulsion formation enabled its facile packaging. The SAP is depleted from bulk during emulsification, allowing simple subsequent addition of the drug-loaded oil-in-water emulsion to a solution of protein antigen. Decoration of emulsion surface with antigen was achieved via electrostatic deposition. In vitro data showed that the TNE prepared this way was internalized and well-tolerated by model APCs, and that good suppression of NF-κB expression was achieved. This work reports a new type of nanotechnology-based carrier, a TNE, which can potentially be tailored for co-delivery of multiple therapeutic components, and can be made using simple methods using only biocompatible materials. PMID:22153851

  17. 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)

    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

  18. 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.

  19. Enantioselective analysis of non-steroidal anti-inflammatory drugs in freshwater fish based on microextraction with a supramolecular liquid and chiral liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Caballo, Carmen; Sicilia, Maria Dolores; Rubio, Soledad

    2015-06-01

    Toxicity of pharmaceuticals to aquatic biota is still largely unknown, and no research on the stereoselective toxicity of chiral drugs to these organisms has been undertaken to date. Because of the lack of analytical methods available for this purpose, this manuscript deals, for the first time, with the enantioselective analysis of the non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen, naproxen and ketoprofen in freshwater fish. The method was based on the microextraction of NSAIDs from fish muscle with a supramolecular liquid made up of inverted hexagonal aggregates of decanoic acid, their enantiomeric separation by liquid chromatography onto a (R)-1-naphthylglycine and 3,5-dinitrobenzoic acid stationary phase and quantification by tandem mass spectrometry. Limits of quantitation (LOQs) for NSAID enantiomers were in the range 1.7-3.3 ng g(-1). Absolute recoveries were from 97 to 104 %, which indicated the high extraction efficiency of the supramolecular solvent. Extraction equilibrium conditions were reached after 10 min which permitted fast sample treatment. Relative standard deviations for enantiomers in fish muscle were always below 6 %. Isotopically labelled internal standards were used to compensate for matrix interferences. The method in-house validation was carried out with the Oncorhynchus mykiss species, and it was applied to the determination of NSAID enantiomers in different fortified freshwater fish species (Alburnus alburnus, Lepomis gibbosus, Micropterus salmoides, O. mykiss and Cyprinus carpio). PMID:25869485

  20. Effects of systemic non-steroidal anti-inflammatory drugs on nociception during tail ischaemia and on reperfusion hyperalgesia in rats.

    Science.gov (United States)

    Gelgor, L.; Butkow, N.; Mitchell, D.

    1992-01-01

    1. We have investigated the effects of five non-steroidal anti-inflammatory drugs (NSAIDs) on nociception during ischaemia and on reperfusion hyperalgesia in rats. 2. We induced tail ischaemia in conscious rats by applying a tourniquet at the base of the tail until the rats exhibited co-ordinated escape behaviour when we released the tourniquet. 3. We assessed hyperalgesia by measuring the tail flick latency following tail immersion in water at 49 degrees C, before applying and immediately after releasing the tourniquet, and then at 30 min intervals for 2 h. 4. Intraperitoneal injection of NSAIDs prior to applying the tourniquet had no effect on the co-ordinated escape behaviour during ischaemia, nor on tail flick latency in the absence of prior ischaemia. However all the drugs attenuated reperfusion hyperalgesia in a log dose-dependent manner. Doses required to abolish hyperalgesia, were indomethacin 5 mg kg-1, diclofenac sodium 42 mg kg-1, ibuprofen 54 mg kg-1, dipyrone 168 mg kg-1 and paracetamol 170 mg kg-1. 5. We conclude that the mechanisms underlying nociception during ischaemia are not the same as those underlying reperfusion hyperalgesia. Moreover our procedure provides a rapid and more humane method for measuring the antinociceptive potency of NSAIDs. PMID:1559131

  1. Modulating the Innate Immune Response to Influenza A Virus: Potential Therapeutic Use of Anti-Inflammatory Drugs

    OpenAIRE

    Ramos, Irene; Fernandez-Sesma, Ana

    2015-01-01

    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 are consequences 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 poten...

  2. Herbal diterpenoids induce growth arrest and apoptosis in colon cancer cells with increased expression of the nonsteroidal anti-inflammatory drug-activated gene.

    Science.gov (United States)

    Ko, Joshua K S; Leung, Wan C; Ho, Wai K; Chiu, Pauline

    2007-03-15

    Novel chemotherapeutic agents derived from active phytochemicals could be used as adjuvants and improve the anti-carcinogenicity of standard drug treatments. However, their precise mechanisms of action are sometimes unclear. In this study, the anti-carcinogenic effect of the herbal diterpenoid pseudolaric acid B (PAB) on the growth and apoptosis of colon cancer cells was investigated, and to compare that with the more toxic compound triptolide. PAB induced growth inhibition and apoptosis in HT-29 cells, which were associated with cell cycle arrest at the G(2)/M phase, modulation of cyclin expression and downregulation of the protooncogene c-myc. In addition, PAB also inhibited bcl-x(L) expression, induced cleavage of procaspase-3 and its substrate poly(ADP-ribose) polymerase (PARP), which together caused DNA fragmentation and nuclear chromatin condensation. Concomitantly, the modulation of the growth-related and apoptotic factors by PAB was accompanied by the increased protein and gene expression of the nonsteroidal anti-inflammatory drug-activated gene (NAG-1), which occurred along with cyclooxygenase-2 inhibition. The effects of PAB on PARP cleavage and NAG-1 overexpression were not reversible upon removal of the drug from the culture medium. Similar cytotoxic and pro-apoptotic effects were also attained by treating the HT-29 cells with another diterpenoid triptolide, but its actions on cell cycle progression and on the upstream transcriptional regulation of NAG-1 both took place in a less coherent manner. These findings exemplify the potential of herbal terpenoids, particularly PAB, in modulating colon cancer carcinogenesis through known molecular targets and precise mechanism of action. PMID:17258704

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

    Science.gov (United States)

    Pérez-Alzate, Diana; Blanca-López, Natalia; Doña, Inmaculada; Agúndez, José A.; García-Martín, Elena; Cornejo-García, José A.; Perkins, James R.; Blanca, Miguel; Canto, Gabriela

    2016-01-01

    In subjects with non-steroidal anti-inflammatory drugs (NSAIDs)- exacerbated respiratory disease (NERD) symptoms are triggered by acetyl salicylic acid (ASA) and other strong COX-1 inhibitors, and in some cases by weak COX-1 or by selective COX-2 inhibitors. The mechanism involved is related to prostaglandin pathway inhibition and leukotriene release. Subjects who react to a single NSAID and tolerate others are considered selective responders, and often present urticaria and/or angioedema and anaphylaxis (SNIUAA). An immunological mechanism is implicated in these reactions. However, anecdotal evidence suggests that selective responders who present respiratory airway symptoms may also exist. Our objective was to determine if subjects might develop selective responses to NSAIDs/paracetamol that manifest as upper/lower airways respiratory symptoms. For this purpose, we studied patients reporting asthma and/or rhinitis induced by paracetamol or a single NSAID that tolerated ASA. An allergological evaluation plus controlled challenge with ASA was carried out. If ASA tolerance was found, we proceeded with an oral challenge with the culprit drug. The appearance of symptoms was monitored by a clinical questionnaire and by measuring FEV1 and/or nasal airways volume changes pre and post challenge. From a total of 21 initial cases, we confirmed the appearance of nasal and/or bronchial manifestations in ten, characterized by a significant decrease in FEV1% and/or a decrease in nasal volume cavity after drug administration. All cases tolerated ASA. This shows that ASA tolerant subjects with asthma and/or rhinitis induced by paracetamol or a single NSAID without skin/systemic manifestations exist. Whether these patients represent a new clinical phenotype to be included within the current classification of hypersensitivity reactions to NSAIDs requires further investigation. PMID:27489545

  4. Chemistry

    International Nuclear Information System (INIS)

    Research and development activities dealing with the chemical problems related to design and ultimate operation of molten-salt reactor systems are described. An experimental test stand was constructed to expose metallurgical test specimens to Te2 vapor at defined temperatures and deposition rates. To better define the chemistry of fluoroborate coolant, several aspects are being investigated. The behavior of hydroxy and oxy compounds in molten NaBF4 is being investigated to define reactions and compounds that may be involved in corrosion and/or could be involved in methods for trapping tritium. Two corrosion products of Hastelloy N, Na3CrF6 and Na5Cr3F14, were identified from fluoroborate systems. The evaluation of fluoroborate and alternate coolants continued. Research on the behavior of hydrogen and its isotopes is summarized. The solubilities of hydrogen, deuterium, and helium in Li2BeF4 are very low. The sorption of tritium on graphite was found to be significant (a few milligrams of tritium per kilogram of graphite), possibly providing a means of sequestering a portion of the tritium produced. Development of analytical methods continued with emphasis on voltammetric and spectrophotometric techniques for the in-line analysis of corrosion products such as Fe2+ and Cr3+ and the determination of the U3+/U4+ ratio in MSBR fuel salt. Similar studies were conducted with the NaBF4--NaF coolant salt. Information developed during the previous operation of the CSTF has been assessed and used to formulate plans for evaluation of in-line analytical methods in future CSTF operations. Electroanalytical and spectrophotometric research suggests that an electroactive protonic species is present in molten NaBF4--NaF, and that this species rapidly equilibrates with a volatile proton-containing species. Data obtained from the CSTF indicated that tritium was concentrated in the volatile species. (JGB)

  5. Synthesis and pharmacological evaluation of antiinflammatory mutual amide prodrugs

    Directory of Open Access Journals (Sweden)

    D T Makhija

    2013-01-01

    Full Text Available Nonsteroidal antiinflammatory drugs have been widely used for the management of inflammation, pain and nociception. Gastric intolerance caused by most of the nonsteroidal antiinflammatory drugs used today restricts their use. Several approaches have been proposed to modify the parent nonsteroidal antiinflammatory drugs molecule in order to reduce their gastric toxicity. Oral prodrug approach is one of such approaches. In the present work three nonsteroidal antiinflammatory drugs viz. ibuprofen, diclofenac, and flurbiprofen were conjugated with sulfonamides like sulphamethoxazole and sulphanilamide via amide bond using dicyclohexylcarbodiimide coupling reaction. The synthesized prodrugs were screened for their analgesic and antiinflammatory activity using Eddy′s hot plate, acetic acid-induced writhing and carrageenan-induced rat paw edema method, respectively. These prodrugs were also evaluated for their ulcerogenic potential. All synthesized prodrugs were found to be less ulcerogenic than their parent nonsteroidal antiinflammatory drugs and showed better activity profile in terms of analgesic and antiinflammatory activity as compared to their respective parent drugs.

  6. 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....

  7. In Vivo Bioorthogonal Chemistry Enables Local Hydrogel and Systemic Pro-Drug To Treat Soft Tissue Sarcoma.

    Science.gov (United States)

    Mejia Oneto, Jose M; Khan, Irfan; Seebald, Leah; Royzen, Maksim

    2016-07-27

    The ability to activate drugs only at desired locations avoiding systemic immunosuppression and other dose limiting toxicities is highly desirable. Here we present a new approach, named local drug activation, that uses bioorthogonal chemistry to concentrate and activate systemic small molecules at a location of choice. This method is independent of endogenous cellular or environmental markers and only depends on the presence of a preimplanted biomaterial near a desired site (e.g., tumor). We demonstrate the clear therapeutic benefit with minimal side effects of this approach in mice over systemic therapy using a doxorubicin pro-drug against xenograft tumors of a type of soft tissue sarcoma (HT1080). PMID:27504494

  8. In Vivo Bioorthogonal Chemistry Enables Local Hydrogel and Systemic Pro-Drug To Treat Soft Tissue Sarcoma

    Science.gov (United States)

    2016-01-01

    The ability to activate drugs only at desired locations avoiding systemic immunosuppression and other dose limiting toxicities is highly desirable. Here we present a new approach, named local drug activation, that uses bioorthogonal chemistry to concentrate and activate systemic small molecules at a location of choice. This method is independent of endogenous cellular or environmental markers and only depends on the presence of a preimplanted biomaterial near a desired site (e.g., tumor). We demonstrate the clear therapeutic benefit with minimal side effects of this approach in mice over systemic therapy using a doxorubicin pro-drug against xenograft tumors of a type of soft tissue sarcoma (HT1080).

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Tabrizi, Leila; Chiniforoshan, Hossein; McArdle, Patrick

    2015-02-01

    The interaction of Cd(II) with the non-steroidal anti-inflammatory drug diclofenac sodium (Dic) leads to the formation of the complex [Cd2(L)41.5(MeOH)2(H2O)]n(L = Dic), 1, which has been isolated and structurally characterized by X-ray crystallography. Diclofenac sodium and its metal complex 1 have also been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines, MCF-7 (breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma), and a mouse fibroblast L-929 cell line. The results of cytotoxic activity in vitro expressed as IC50 values indicated the diclofenac sodium and cadmium chloride are non active or less active than the metal complex of diclofenac (1). Complex 1 was also found to be a more potent cytotoxic agent against T-24 and MCF-7 cancer cell lines than the prevalent benchmark metallodrug, cisplatin, under the same experimental conditions. The superoxide dismutase activity was measured by Fridovich test which showed that complex 1 shows a low value in comparison with Cu complexes. The binding properties of this complex to biomolecules, bovine or human serum albumin, are presented and evaluated. Antibacterial and growth inhibitory activity is also higher than that of the parent ligand compound.

  11. The prediction and long-term maintenance of low disease activity during therapy with disease modifying anti-inflammatory drugs for rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    E.L. Luchikhina

    2014-05-01

    Full Text Available Therapy with biological agents (biologics over the past few years has become an important part of the strategy of medical treatment of patients with rheumatoid arthritis who respond insufficiently to the disease modifying anti-inflammatory drugs. The possibility to predict response to biologics is of special importance. Factors associated with good response to TNF-inhibitors are very different: age, liver and kidney function, body mass index, concomitant therapy, immunogenicity, the presence of ACPA and the rheumatoid factor, the cytokine profile, genetics, smoking, previous therapy by biologics etc. Another factor that significantly affects the long-term prognosis of biologic therapy is the primary response to treatment. Inhibitors of TNF-α as a whole is characterized by the development of the most marked clinical response within the first 12–24 weeks of treatment that can sustain for 12 months or more. Certolizumab pegol is characterized by rapid development of marked clinical response to treatment against disease activity and function with maintaining consistent improvement over the years, and the prognosis can be determined in most patients by the response to therapy in the first 12 weeks. We present a clinical case. 

  12. Single-drop microextraction combined in-line with capillary electrophoresis for the determination of nonsteroidal anti-inflammatory drugs in urine samples.

    Science.gov (United States)

    García-Vázquez, Alejandro; Borrull, Francesc; Calull, Marta; Aguilar, Carme

    2016-01-01

    This study describes a method to determine nonsteroidal anti-inflammatory drugs (NSAIDs) in urine samples based on the use of single-drop microextraction (SDME) in a three-phase design as a preconcentration technique coupled in-line to capillary electrophoresis. Different parameters affecting the extraction efficiency of the SDME process were evaluated (e.g. type of extractant, volume of the microdroplet, and extraction time). The developed method was successfully applied to the analysis of human urine samples with LODs ranging between 1.0 and 2.5 μg/mL for all of the NSAIDs under study. This method shows RSD values ranging from 8.5 to 15.3% in interday analysis. The enrichment factors were calculated, resulting 27-fold for ketoprofen, 14-fold for diclofenac, 12-fold for ibuprofen, and 44-fold naproxen. Samples were analyzed applying the SDME-CE method and the obtained results presented satisfactory recovery values (82-115%). The overall method can be considered a promising approach for the analysis of NSAIDs in urine samples after minimal sample pretreatment. PMID:26530782

  13. The efficacy and tolerability of the slow-acting combined agent glucosamine and chondroitin sulfate in gonarthrosis patients tacking no nonsteroidal anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    A. P. Rebrov

    2015-01-01

    Full Text Available Objective: to evaluate the efficacy and tolerability of the combined symptomatic slow-acting combined agent Theraflex in gonarthrosis patients untreated with nonsteroidal antiinflammatory drugs (NSAIDs.Patients and methods. The investigation enrolled 84 patients (78 women and 6 men aged 55.23±7.36 years with knee arthritis lasting 6.2±0.98 years who were blindly randomized into 2 groups. A study group took Theraflex (chondroitin sulfate 400 mg and glucosamine sulfate 500 mg with or without acetaminophen. A comparison group received acetaminophen only. At baseline and 3 and 6 months after treatment, the investigators assessed changes in the magnitude of osteoarthritis (OA using WOMAC and Lequen's indices, evaluated the therapeutic efficiency rated by a patient and a physician according to the visual analogue scale, and took into account adverse reactions (AR.Results. All the patients taking Theraflex for 6 months showed a positive effect in substantially lowering WOMAC and Lequen's indices and reducing pain and needs for analgesics as compared to both the values at baseline and those obtained in the patients receiving acetaminophen only.Conclusion. In osteoarthritis patients untreated with NSAIDs, Theraflex treatment was associated with a reduction in pain syndrome and stiffness and with better function and lower needs for analgesics. Six-month Theraflex therapy did not cause serious ARs, as well as in patients having controlled gastrointestinal and renal diseases and hypertension

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

    Science.gov (United States)

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

    2011-06-01

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

  15. Effect of intracapsular steroid injection in combination with arthrocentesis followed by mouth opening exercises and nonsteroidal anti-inflammatory drug treatment for closed lock

    International Nuclear Information System (INIS)

    Recent biochemical studies of synovial fluids indicate that temporomandibular joint (TMJ) symptoms are caused by intra-articular inflammation. There are various ways to manage such disorders. Arthrocentesis is one effective treatment for closed lock. The aim of this study was to evaluate the efficacy of arthrocentesis (steroid injection) followed by mouth opening exercises during non-steroidal anti-inflammatory drug (NSAID) therapy as a primary treatment for closed lock. The ultimate goal was to increase the improvement rate and the number of patients with no TMJ dysfunction. Subjects were selected from a series of patients with newly diagnosed closed lock who presented at Aichi-Gakuin University Hospital between January 2003 and December 2004. Sixty-two patients were confirmed to have closed lock with MRI. The patients underwent two consecutive sessions of arthrocentesis at a 2 week interval and were followed up every 2 weeks for 12 weeks. NSAID administration and mouth opening exercises were performed daily until the patient's symptoms improved. The improvement rate was calculated as the percentage of improved cases among the total number of cases in each group. The improvement rates were 27%, 43%, 56%, 62%, 65%, and 71% after 2, 4, 6, 8, 10, and 12 weeks, respectively. Improvement to a TMJ classification of no dysfunction was achieved in 11% of the patients. This combination therapy (steroid injection) is an effective primary treatment because the improvement rate was as higher as 71%, and 11% of all patients had improved to a TMJ classification of no dysfunction. (author)

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

    Directory of Open Access Journals (Sweden)

    Bai Han

    2012-08-01

    Full Text Available Abstract Background Chronic pancreatitis is characterized by progressive fibrosis, pain and loss of exocrine and endocrine functions. The long-standing chronic pancreatitis and its associated pancreatic fibrosis are the most common pathogenic events involved in human pancreatic carcinogenesis, but the therapeutic strategies to chronic pancreatitis and the chemoprevention of pancreatic carcinogenesis are very limited. Methods We investigated the effect of sulindac, a non-steroidal anti-inflammatory drug (NSAID, on inhibition of chronic pancreatitis in a caerulein induced chronic pancreatitis mouse model. Results Sulindac significantly reduced the severity of chronic pancreatitis including the extent of acini loss, inflammatory cell infiltration and stromal fibrosis. The protein expression of phosphorylation of MEK/ERK was inhibited in the chronic pancreatic tissues by sulindac treatment as measured by Western blot assay. The levels of inflammatory cytokines including TNF-α and MCP-1 were also significantly decreased with sulindac treatment, as well as the expression of TGF-β, PDGF-β, SHH and Gli in the chronic pancreatic tissue detected by qPCR assay and confirmed by western blot assay. The activation of pancreatic satellet cells was also inhibited by sulindac as measured by the activity of α-smooth muscle actin (α-SMA in the pancreatic tissue of chronic pancreatitis. Conclusions Sulindac is a promising reagent for the treatment of chronic pancreatitis via inhibition of inflammatory cell infiltration and stromal fibrosis, the inhibitory effect of sulindac on chronic pancreatitis may through targeting the activation ERK/MAPK signaling pathway.

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

    Directory of Open Access Journals (Sweden)

    Blanca L Valle

    Full Text Available Epidemiological studies have shown that the regular use of non-steroidal anti-inflammatory (NSAIDs drugs is associated with a reduced risk of various cancers. In addition, in vitro and experiments in mouse models have demonstrated that NSAIDs decrease tumor initiation and/or progression of several cancers. However, there are limited preclinical studies investigating the effects of NSAIDs in ovarian cancer. Here, we have studied the effects of two NSAIDs, diclofenac and indomethacin, in ovarian cancer cell lines and in a xenograft mouse model. Diclofenac and indomethacin treatment decreased cell growth by inducing cell cycle arrest and apoptosis. In addition, diclofenac and indomethacin reduced tumor volume in a xenograft model of ovarian cancer. To identify possible molecular pathways mediating the effects of NSAID treatment in ovarian cancer, we performed microarray analysis of ovarian cancer cells treated with indomethacin or diclofenac. Interestingly, several of the genes found downregulated following diclofenac or indomethacin treatment are transcriptional target genes of E2F1. E2F1 was downregulated at the mRNA and protein level upon treatment with diclofenac and indomethacin, and overexpression of E2F1 rescued cells from the growth inhibitory effects of diclofenac and indomethacin. In conclusion, NSAIDs diclofenac and indomethacin exert an anti-proliferative effect in ovarian cancer in vitro and in vivo and the effects of NSAIDs may be mediated, in part, by downregulation of E2F1.

  18. Optimisation by response surface methodology of microextraction by packed sorbent of non steroidal anti-inflammatory drugs and ultra-high performance liquid chromatography analysis of dialyzed samples.

    Science.gov (United States)

    D'Archivio, Angelo Antonio; Maggi, Maria Anna; Ruggieri, Fabrizio; Carlucci, Maura; Ferrone, Vincenzo; Carlucci, Giuseppe

    2016-06-01

    A procedure based on microextraction by packed sorbent (MEPS) followed by ultra-high performance liquid chromatography (UHPLC) with photodiode array (PDA) detection has been developed for the analysis of seven selected non steroidal anti-inflammatory drugs (NSAIDs) in human dialysates. The influence on MEPS efficiency of pH of the sample, pH of the washing solvent and methanol content in the hydro-alcoholic elution mixture has been investigated by response surface methodology based on a Box-Behnken design of experiments. Among the above factors, pH of sample is the variable that mostly influences MEPS recovery. UHPLC separation of the NSAIDs was completed within less than 4min under isocratic elution conditions on a Fortis SpeedCore C18 column (150×4.6mm I.D., 2.6μm) using acetonitrile-phosphate buffer as the mobile phase. Calibration curves of the NSAIDs were linear over the concentration range 0.025-15μg/mL, with correlation coefficients≥0.998. Intra- and inter-assay relative standard deviations were NSAIDs. PMID:27017570

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

    Directory of Open Access Journals (Sweden)

    Tett Susan E

    2008-09-01

    Full Text Available Abstract Background Cross national drug utilization studies can provide information about different influences on physician prescribing. This is important for medicines with issues around safety and quality of use, like non selective non-steroidal anti-inflammatory drugs (ns-NSAIDs and cyclo-oxygenase-2 (COX-2 inhibitors. To enable comparison of prescription medicine use across different jurisdictions with a range of population sizes, data first need to be compared within Australia to understand whether use in a smaller sub-population may be considered as representative of the total use within Australia. The aim of this study was to compare the utilization of non selective NSAID, COX-2 inhibitors and paracetamol between Queensland and Australia. Method Dispensing data were obtained for concession beneficiaries for Australia for ns-NSAIDs, COX-2 inhibitors and paracetamol subsidized by the PBS over the period 1997–2003. The same data were purchased for Queensland. Data were converted to Defined Daily Dose (DDD/1000 beneficiaries/day (World Health Organization anatomical therapeutic chemical classification, 2005. Results Total NSAID and paracetamol consumption were similar in Australia and Queensland. Ns-NSAID use decreased sharply with the introduction of COX-2 inhibitors (from approximately 80 to 40 DDD/1000 beneficiaries/day. Paracetamol was constant (approximately 45 DDD/1000 beneficiaries/day. COX-2 inhibitors consumption was initially higher in Queensland than in the whole of Australia. Conclusion Despite initial divergence in celecoxib use between Queensland and Australia, the use of ns-NSAIDs, COX-2 inhibitors and paracetamol overall, in concession beneficiaries, was comparable in Australia and Queensland.

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

    Directory of Open Access Journals (Sweden)

    Svenja Illien-Junger

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

  1. Synthesis and characterization of layered double hydroxides (LDH) intercalated with non-steroidal anti-inflammatory drugs (NSAID)

    International Nuclear Information System (INIS)

    Layered double hydroxides (LDHs) with the hydrotalcite type structure and a Mg:Al ratio of two have been prepared, with salicylate or naproxen in the interlayer. Two synthetic routes have been used: reconstruction from a mildly calcined hydrotalcite-CO3 precursor, and a coprecipitation method with chlorides of the metals. The solids have been characterized using several physicochemical techniques, i.e., powder X-ray diffraction, FTIR and 13C CP/MAS NMR spectroscopies and thermal analysis (thermogravimetric and differential thermal analyses). The gallery height determined is in all cases larger than the size of the drug, 11.5A for salicylate and 15.8 and 16.6A for naproxen, depending on the specific synthesis route followed. Experimental data suggest the anion molecules form a tilted bilayer, with the carboxylate groups pointing towards the brucite-like layers. The solids are stable up to 230oC and their evolution from 350oC upwards is very similar to that observed for a carbonate-containing hydrotalcite, forming mostly amorphous solids with a large specific surface area

  2. Intestinal toxicity of non-steroideal anti-inflammatory drugs with differential cyclooxigenase inhibition selectivity Toxicidad intestinal de los fármacos antiinflamatorios no esteroideos con una selectividad diferenciada en la inhibición de la ciclooxigenasa

    OpenAIRE

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

    2007-01-01

    The present study was designed to investigate the gastrointestinal side effects of cycloxygenase (COX) inhibitor with varying selectivity, called the non-steroidal antiinflammatory drugs (NSAIDs) viz., non-selective COX-1 & 2 inhibitor -aspirin, prefentially selective COX-2 inhibitor- nimesulide and highly selective COX-2 inhibitor- celecoxib. Treatment with NSAIDs exhibited a decrease in the activity of rat intestinal brush border membrane associated enzymes such as sucrase, lactase, maltase...

  3. Anti-inflammatory Activity.

    Science.gov (United States)

    2016-01-01

    Inflammation is the body's first response to infection or injury and is critical for both innate and adaptive immunity. It can be considered as part of the complex biological response of vascular tissues to harmful stimuli such as pathogens, damaged cells, or irritants. The search for natural compounds and phytoconstituents that are able to interfere with these mechanisms by preventing a prolonged inflammation could be useful for human health. Here, the anti-inflammatory properties of plant-based drugs are put together with both in vitro and acute (carrageenan, egg albumin and croton oil) and chronic (cotton pellet) in vivo models. PMID:26939273

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

    Directory of Open Access Journals (Sweden)

    McQuay Henry J

    2007-08-01

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

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

    Science.gov (United States)

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

    2013-01-01

    Pharmaceutical residues are ubiquitous in rivers, lakes, and at coastal waters affected by discharges from municipal wastewater treatment plants. In this study, the presence of 17 different pharmaceuticals and six different phase I metabolites was determined in the bile of two wild fish species, bream (Abramis brama) and roach (Rutilus rutilus). The fish were caught from a lake that receives treated municipal wastewater via a small river. Prior to analyses, the bile content was enzymatically hydrolyzed to convert the glucuronide metabolites into the original pharmaceuticals or phase I metabolites. The solid phase extracts of hydrolyzates were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the multiple reaction monitoring mode. The anti-inflammatory drug naproxen could be detected in all the six bream and roach bile samples. Diclofenac was found in five of the bream and roach samples, while ibuprofen was detected in three bream and two roach samples. The observed bile concentrations of diclofenac, naproxen, and ibuprofen in bream ranged from 6 to 95 ng mL(-1), 6 to 32 ng mL(-1), and 16 to 34 ng mL(-1), respectively. The corresponding values in roach samples ranged from 44 to 148 ng mL(-1), 11 to 103 ng mL(-1) and 15 to 26 ng mL(-1), respectively. None of the other studied compounds could be detected. The study shows that pharmaceuticals originating from wastewater treatment plant effluents can be traced to the bile of wild bream and roach living in a lake where diclofenac, naproxen, and ibuprofen are present as pollutants. PMID:23186122

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

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    Paino I.M.M.

    2005-01-01

    Full Text Available The release of reactive oxygen specie (ROS by activated neutrophil is involved in both the antimicrobial and deleterious effects in chronic inflammation. The objective of the present investigation was to determine the effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs (NSAIDs on the production of ROS by stimulated rat neutrophils. Diclofenac (3.6 µM, indomethacin (12 µM, naproxen (160 µM, piroxicam (13 µM, and tenoxicam (30 µM were incubated at 37ºC in PBS (10 mM, pH 7.4, for 30 min with rat neutrophils (1 x 10(6 cells/ml stimulated by phorbol-12-myristate-13-acetate (100 nM. The ROS production was measured by luminol and lucigenin-dependent chemiluminescence. Except for naproxen, NSAIDs reduced ROS production: 58 ± 2% diclofenac, 90 ± 2% indomethacin, 33 ± 3% piroxicam, and 45 ± 6% tenoxicam (N = 6. For the lucigenin assay, naproxen, piroxicam and tenoxicam were ineffective. For indomethacin the inhibition was 52 ± 5% and diclofenac showed amplification in the light emission of 181 ± 60% (N = 6. Using the myeloperoxidase (MPO/H2O2/luminol system, the effects of NSAIDs on MPO activity were also screened. We found that NSAIDs inhibited both the peroxidation and chlorinating activity of MPO as follows: diclofenac (36 ± 10, 45 ± 3%, indomethacin (97 ± 2, 100 ± 1%, naproxen (56 ± 8, 76 ± 3%, piroxicam (77 ± 5, 99 ± 1%, and tenoxicam (90 ± 2, 100 ± 1%, respectively (N = 3. These results show that therapeutic levels of NSAIDs are able to suppress the oxygen-dependent antimicrobial or oxidative functions of neutrophils by inhibiting the generation of hypochlorous acid.

  7. Naproxen, a Nonsteroidal Anti-Inflammatory Drug, Can Affect Daily Hypobaric Hypoxia-Induced Alterations of Monoamine Levels in Different Areas of the Brain in Male Rats.

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    Goswami, Ananda Raj; Dutta, Goutam; Ghosh, Tusharkanti

    2016-06-01

    Goswami, Ananda Raj, Goutam Dutta, and Tusharkanti Ghosh. Naproxen, a nonsteroidal anti-inflammatory drug can affect daily hypobaric hypoxia-induced alterations of monoamine levels in different areas of the brain in male rats. High Alt Med Biol. 17:133-140, 2016.-The oxidative stress (OS)-induced prostaglandin (PG) release, in hypobaric hypoxic (HHc) condition, may be linked with the changes of brain monoamines. The present study intends to explore the changes of monoamines in hypothalamus (H), cerebral cortex (CC), and cerebellum (CB) along with the motor activity in rats after exposing them to simulated hypobaric condition and the role of PGs on the daily hypobaric hypoxia (DHH)-induced alteration of brain monoamines by administering, an inhibitor of PG synthesis, naproxen. The rats were exposed to a decompression chamber at 18,000 ft for 8 hours per day for 6 days after administration of vehicle or naproxen (18 mg/kg body wt.). The monoamine levels (epinephrine, E; norepinephrine, NE; dopamine, DA; and 5-hydroxytryptamine, 5-HT) in CC, CB, and H were assayed by high-performance liquid chromatography (HPLC) with electrochemical detection, and the locomotor behavior was measured by open field test. The NE and DA levels were decreased in CC, CB, and H of the rat brain in HHc condition. The E and 5-HT levels were decreased in CC, but in H and CB, they remained unaltered in HHc condition. These DHH-induced changes of monoamines in brain areas were prevented after administration of naproxen in HHc condition. The locomotor behavior remained unaltered in HHc condition and after administration of naproxen in HHc condition. The DHH-induced changes of monoamines in the brain in HHc condition are probably linked with PGs that may be induced by OS. PMID:26894935

  8. Changes of nitric oxide system and lipid peroxidation parameters in the digestive system of rats under conditions of acute stress, and use of nonsteroidal anti-inflammatory drugs

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    Fomenko Iryna

    2015-03-01

    Full Text Available The use of nonsteroidal anti-inflammatory drugs (NSAIDs in combination with being physiologically stressed often occurs in in the course of different pathologies. This situation may result in the alteration of digestive system functioning. The effect of stress brings about changes in the activity of nitric oxide synthase (NOS, arginase, cyclooxygenase (COX and lipid peroxidation, whereas the use of NSAIDs interrupts the multiple functions of the cell via the inhibition of prostaglandins (PGs synthesis. Taking into account that NOS and COX-systems are connected in their regulation, the aim of the study was to determine the role played by NOS and lipid peroxidation under conditions of the combined action of NSAIDs and stress. In our study, male rats were used. The NSAIDs (naproxen - a non-selective COX inhibitor, celecoxib - a selective COX-2 blocker, and the compound 2A5DHT (which is the active substance of dual COX, and the lipoxygenase (LOX inhibitor, darbufelone were all administered at a dose 10 mg/kg, prior to water restraint stress (WRS. WRS brought about an increase of inducible NOS (iNOS activity in the intestinal mucosal and muscular membranes, as well as in the pancreas. Because of this, constitutive NOS izoform (cNOS and arginase activities decreased. Moreover, the MDA concentration increased, indicating the development of oxidative stress. In our work, pretreatment with naproxen, as in the WRS model, engendered a decrease in iNOS activity. What is more, administration of Celecoxib did not change iNOS activity, as compared to WRS alone, and it showed a tendency to reduce lipid peroxidation. In addition, 2A5DHT prior WRS brought about a decrease of iNOS activity, with the subsequent rise of cNOS activity. Of note, MDA concentration decreased in all studied organs, indicating the reduction of lipid peroxidation under the action of the darbufelone active substance.

  9. Structural and binding studies of C-terminal half (C-lobe) of lactoferrin protein with COX-2-specific non-steroidal anti-inflammatory drugs (NSAIDs).

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    Mir, Rafia; Singh, Nagendra; Vikram, Gopalakrishnapillai; Sinha, Mau; Bhushan, Asha; Kaur, Punit; Srinivasan, Alagiri; Sharma, Sujata; Singh, Tej P

    2010-08-15

    Three COX-2-specific non-steroidal anti-inflammatory drugs (NSAIDs), etoricoxib, parecoxib, and nimesulide are widely prescribed against inflammatory conditions. However, their long term administration leads to severe conditions of cardiovascular complications and gastric ulceration. In order to minimize these side effects, C-terminal half (C-lobe) of colostrum protein lactoferrin has been indicated to be useful if co-administered with NSAIDs. Lactoferrin is an 80kDa glycoprotein with two similar halves designated as N- and C-lobes. Since NSAID-binding site is located in the C-terminal half of lactoferrin, C-lobe was prepared from lactoferrin by limited proteolysis using proteinase K. The incubation of lactoferrin with serine proteases for extended periods showed that N-lobe was completely digested but C-lobe was resistant for more than 72h indicating its long half life in the animal gut. The solution studies have shown that COX-2-specific NSAIDs bind to C-lobe with binding constants ranging from 10(-4) to 10(-5)M showing significant affinities for sequestering these compounds. In order to understand the mode of binding and sequestering properties, the complexes of C-lobe with all these three compounds, etoricoxib, parecoxib, and nimesulide were prepared and the structures of their complexes with C-lobe were determined at 2.2, 2.9, and 2.7A resolutions, respectively. The analysis of the structures of complexes of C-lobe with NSAIDs clearly show that all the three compounds bind firmly at the same ligand-binding site in the C-lobe revealing the details of the interactions between C-lobe and NSAIDs. The mode of binding of COX-2-specific NSAIDs to C-lobe is similar to that of the binding of COX-2 non-specific NSAIDs to C-lobe. PMID:20515646

  10. Non-steroidal anti-inflammatory drug use, hormone receptor status, and breast cancer-specific mortality in the Carolina Breast Cancer Study.

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    Allott, E H; Tse, C-K; Olshan, A F; Carey, L A; Moorman, P G; Troester, M A

    2014-09-01

    Epidemiologic studies report a protective association between non-steroidal anti-inflammatory drug (NSAID) use and hormone receptor-positive breast cancer risk, a finding consistent with NSAID-mediated suppression of aromatase-driven estrogen biosynthesis. However, the association between NSAID use and breast cancer-specific mortality is uncertain and it is unknown whether this relationship differs by hormone receptor status. This study comprised 935 invasive breast cancer cases, of which 490 were estrogen receptor (ER)-positive, enrolled between 1996 and 2001 in the Carolina Breast Cancer Study. Self-reported NSAID use in the decade prior to diagnosis was categorized by duration and regularity of use. Differences in tumor size, stage, node, and receptor status by NSAID use were examined using Chi-square tests. Associations between NSAID use and breast cancer-specific mortality were examined using age- and race-adjusted Cox proportional hazards analysis. Tumor characteristics did not differ by NSAID use. Increased duration and regularity of NSAID use was associated with reduced breast cancer-specific mortality in women with ER-positive tumors (long-term regular use (≥8 days/month for ≥ 3 years) versus no use; hazard ratio (HR) 0.48; 95 % confidence interval (CI) 0.23-0.98), with a statistically significant trend with increasing duration and regularity (p-trend = 0.036). There was no association for ER-negative cases (HR 1.19; 95 %CI 0.50-2.81; p-trend = 0.891). Long-term, regular NSAID use in the decade prior to breast cancer diagnosis was associated with reduced breast cancer-specific mortality in ER-positive cases. If confirmed, these findings support the hypothesis that potential chemopreventive properties of NSAIDs are mediated, at least in part, through suppression of estrogen biosynthesis. PMID:25151293

  11. Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the colon and rectum: a meta-analysis

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    García Rodríguez Luis A

    2003-10-01

    Full Text Available Abstract Background Observational studies have consistently shown that aspirin and non-steroidal anti-inflammatory drug (NSAID use is associated with a close to 50% reduced risk of colorectal cancer. Studies assessing the effects of NSAIDs on other cancers have shown conflicting results. Therefore, we conducted a meta-analysis to evaluate the relationship between NSAID use and cancer other than colorectal. Methods We performed a search in Medline (from 1966 to 2002 and identified a total of 47 articles (13 cohort and 34 case-control studies. Overall estimates of the relative risk (RR were calculated for each cancer site using random effects models. Results Aspirin use was associated with a reduced risk of cancer of the esophagus and the stomach (RR, 0.51; 95%CI (0.38–0.69, and 0.73; 95%CI (0.63–0.84. Use of NSAIDs was similarly associated with a lower risk of esophageal and gastric cancers (RR,0.65; 95% CI(0.46–0.92 and RR,0.54; 95%CI (0.39–0.75. Among other cancers, only the results obtained for breast cancer were fairly consistent in showing a slight reduced risk among NSAID and aspirin users (RR, 0.77; 95%CI (0.66–0.88, and RR, 0.77; 95%CI (0.69–0.86 respectively. Conclusions The results of this meta-analysis show that the potential chemopreventive role of NSAIDs in colorectal cancer might be extended to other gastrointestinal cancers such as esophagus and stomach. Further research is required to evaluate the role of NSAIDs at other cancers sites.

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

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

    2016-01-01

    The YacK gene from Yersinia enterocolitica strain 7, cloned in pET28a vector and expressed in Escherichia coli BL21 (DE3), showed laccase activity when oxidized with 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and guaiacol. The recombinant laccase protein was purified and characterized biochemically with a molecular mass of ≈58 KDa on SDS-PAGE and showed positive zymogram with ABTS. The protein was highly robust with optimum pH 9.0 and stable at 70 °C upto 12 h with residual activity of 70%. Kinetic constants, Km values, for ABTS and guaiacol were 675 μM and 2070 μM, respectively, with corresponding Vmax values of 0.125 μmol/ml/min and 6500 μmol/ml/min. It also possess antioxidative property against BSA and Cu(2+)/H2O2 model system. Constant pH MD simulation studies at different protonation states of the system showed ABTS to be most stable at acidic pH, whereas, diclofenac at neutral pH. Interestingly, aspirin drifted out of the binding pocket at acidic and neutral pH, but showed stable binding at alkaline pH. The biotransformation of diclofenac and aspirin by laccase also corroborated the in silico results. This is the first report on biotransformation of non-steroidal anti-inflammatory drugs (NSAIDs) using recombinant laccase from gut bacteria, supported by in silico simulation studies. PMID:26631965

  13. Role of small intestinal bacterial overgrowth in severe small intestinal damage in chronic non-steroidal anti-inflammatory drug users.

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    Muraki, Motoko; Fujiwara, Yasuhiro; Machida, Hirohisa; Okazaki, Hirotoshi; Sogawa, Mitsue; Yamagami, Hirokazu; Tanigawa, Tetsuya; Shiba, Masatsugu; Watanabe, Kenji; Tominaga, Kazunari; Watanabe, Toshio; Arakawa, Tetsuo

    2014-03-01

    OBJECTIVE. Enteric bacteria play a significant role in the pathogenesis of non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal damage. However, the association between small intestinal bacterial overgrowth (SIBO) and NSAID-induced small intestinal damage remains unclear. The aim of the study was to examine the association between SIBO and the presence of NSAID-induced severe small intestinal damage or its symptoms in chronic NSAID users. MATERIALS AND METHODS. Forty-three patients who had been using NSAIDs for over 3 months were enrolled. They were examined by capsule endoscopy and a lactulose hydrogen breath test (LHBT). We defined severe small intestinal damage as the presence of more than four small erosions or large erosions/ulcers. The LHBT result was considered positive if there was an increase in the level of breath hydrogen gas of >20 ppm above baseline. RESULTS. Out of 43 patients, 22 (51%) had severe small intestinal damage. The LHBT was positive in 5 of 21 patients (24%) without severe small intestinal damage and in 13 of 21 patients (59%) with severe small intestinal damage. Multiple logistic regression analysis showed that an LHBT-positive result was significantly associated with increased odds ratio for severe small intestinal damage (OR, 6.54; 95% CI, 1.40-30.50). There was no significant difference in the presence of symptoms between the LHBT-positive and LHBT-negative patients with severe small intestinal damage. CONCLUSION. SIBO might have a role in the development of severe small intestinal damage in chronic NSAID users. PMID:24417613

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

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    Wen-Chan Tsai

    Full Text Available The objective of this case-control study was to investigate the risk of cardiovascular disease (CVD following non-steroidal anti-inflammatory drug (NSAID use in patients with ankylosing spondylitis (AS. A total of 10,763 new AS patients were identified from the National Taiwan Health Insurance claims database during the period from 1997 to 2008. In all, 421 AS patients with CVD were recruited as cases, and up to 2-fold as many sex- and age-matched controls were selected. Logistic regression models were used to estimate the odds ratio (OR between NSAID use and CVD incidence. The medication possession rate (MPR was used to evaluate NSAID exposure during the study period. AS patients had increased risk of CVD (OR, 1.68; 95% confidence interval (CI, 1.57 to 1.80. Among frequent (MPR≥80% COX II users, the risks for all types of CVD were ten times lower than those among non-users at 24 months (OR, 0.08; 95% CI, 0.01 to 0.92. Among frequent NSAID users, the risks of major adverse cardiac event (MACE were significantly lower at 12 months (OR, 0.23; 95% CI, 0.07 to 0.76--a trend showing that longer exposure correlated with lower risk. Regarding non-frequent NSAID users (MPR<80%, short-term exposure did carry higher risk (for 6 months: OR, 1.41; 95% CI, 1.07 to 1.86, but after 12 months, the risk no longer existed. We conclude that long-term frequent use of NSAIDs might protect AS patients from CVD; however, NSAIDs still carried higher short-term risk in the non-frequent users.

  15. Observational study of upper gastrointestinal tract bleeding events in patients taking duloxetine and nonsteroidal anti-inflammatory drugs: a case-control analysis

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    Li H

    2014-10-01

    Full Text Available Hu Li, Yingkai Cheng, Jonna Ahl, Vladimir SkljarevskiNeurosciences, Eli Lilly and Company, Indianapolis, IN, USAPurpose: To determine whether the concomitant use of duloxetine with prescription nonsteroidal anti-inflammatory drugs (NSAIDs or aspirin was associated with an increased risk for upper gastrointestinal (UGI bleeding compared with taking these analgesics alone.Methods: Truven Health Analytics MarketScan Research Databases were examined for hospital admissions of adult patients indexed from January 1, 2007–December 31, 2011. Cases were patients with UGI hemorrhage or peptic ulcer disease. Controls were randomly selected from the remaining admissions to match 10:1 with cases based on age, sex, and admission date. Prescription medication exposure groups of interest were: 1 no exposure to duloxetine, NSAIDs or aspirin; 2 duloxetine only; 3 NSAIDs or aspirin only; 4 duloxetine plus NSAIDs or aspirin. Logistic regression and relative excess risk due to interaction was utilized to estimate any increased risk of UGI bleeding for patients prescribed these medications across these groups.Results: There were 33,571 cases and 335,710 controls identified. Comparing exposure group 2 and group 4, the adjusted odds ratio was 1.03 (95% confidence interval [CI], 0.94, 1.12, and the adjusted relative excess risk due to interaction was 0.352 (95% CI: –0.18, 0.72 for risk of UGI bleeding, neither of which support an increased risk or an interaction between duloxetine and prescription NSAID or aspirin for these events.Conclusion: There was no evidence of an increased risk for UGI bleeding when duloxetine was taken with prescription NSAIDs or aspirin. In addition, there was no evidence of an interaction between duloxetine and prescription NSAIDs or aspirin for an increased risk of these events.Keywords: duloxetine, upper gastrointestinal bleeding, NSAIDs, aspirin

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

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    Fatma M Shebl

    Full Text Available BACKGROUND: Chronic inflammation has been linked to cancers, and use of non-steroidal anti-inflammatory drugs (NSAIDs has been associated with reduced risk of several cancers. To further refine the magnitude of NSAID-related associations, in particular for cancers related to inflammation, such as alcohol-, infection-, obesity-, and smoking-related cancers, as well as for less common cancers, we evaluated the use of NSAIDs and cancer risk in a very large cohort. We used propensity scores to account for potential selection bias and hypothesized that NSAID use is associated with decreased cancer incidence. METHODS: We conducted a prospective study among 314,522 participants in the NIH-AARP Diet and Health Study. Individuals who completed the lifestyle questionnaire, which included NSAID use, in 1996-1997 were followed through 2006. Information on cancer incidence was ascertained by linking to cancer registries and vital status databases. FINDINGS: During 2,715,994 person-years of follow-up (median 10.1 person-years, there were 51,894 incident cancers. Compared with non-users of NSAIDs, individuals who reported use in the 12 months prior to interview had a significantly lower risk of all inflammation-related cancer, alcohol-related, infection-related, obesity-related, and smoking-related cancers [hazard ratio (HR (95% CI 0.90 (0.87-0.93, 0.80 (0.74-0.85, 0.82 (0.78-0.87, 0.88 (0.84-0.92, and 0.88 (0.85-0.92 respectively]. CONCLUSIONS: After accounting for potential selection bias, our data showed an inverse association between NSAID use and alcohol-related, infection-related, obesity-related, and smoking-related cancers and support the hypothesis that inflammation is related to an increased risk of certain cancers.

  17. Non-steroidal anti-inflammatory drugs and risk of cerebrovascular events in patients with osteoarthritis: a nested case-control study.

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    Lapi, Francesco; Piccinni, Carlo; Simonetti, Monica; Levi, Miriam; Lora Aprile, Pierangelo; Cricelli, Iacopo; Cricelli, Claudio; Fanelli, Andrea

    2016-02-01

    Recent studies show that the risk of cardiovascular adverse events for certain traditional non-steroidal anti-inflammatory drugs (NSAIDs) is similar to that of rofecoxib. While these results are focused on ischemic cardiomyopathy, there is little evidence concerning the risk of ischemic stroke/transient ischemic attack and hemorrhagic stroke. Additionally, there is no information on nimesulide and ketoprofen, the most frequently prescribed NSAIDs in Italy, along with diclofenac. This study aims to determine whether the use of NSAIDs is associated with an increased risk of cerebrovascular events in Italy. We performed a case-control analysis nested in a cohort of patients with osteoarthritis between 2002 and 2011 who were newly treated with NSAIDs. The patients were followed until December 31, 2012. Conditional logistic regression was used to estimate odds ratios (ORs) with 95 % confidence intervals (95 % CI) of cerebrovascular events (index date) associated with current (until 30 days before the index date), recent (31-365 days) and past (>365 days) use of NSAIDs. Within a cohort of 29,722 patients, 1566 cases (1546 matched with controls) were identified (incidence rate = 11.0/1000 person-years). The overall rate of cerebrovascular event was not elevated with current NSAIDs overall when compared with past use. Among individual NSAIDs, diclofenac and ketoprofen were the molecules significantly associated with an increased rate of cerebrovascular events (OR = 1.53; 95 % CI 1.04-2.24; OR = 1.62; 95 % CI 1.02-2.58, respectively). The most frequent event was hemorrhagic stroke following the use of ketoprofen (OR = 2.09; 95 % CI 1.05-4.15). Diclofenac and ketoprofen seemed to increase the risk of cerebrovascular events. These findings might influence the choice of NSAIDs according to patient characteristics. PMID:26271463

  18. Evaluation of biological endpoints in crop plants after exposure to non-steroidal anti-inflammatory drugs (NSAIDs): implications for phytotoxicological assessment of novel contaminants.

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    Schmidt, Wiebke; Redshaw, Clare H

    2015-02-01

    Human pharmaceuticals have been detected in the terrestrial environment at µg to mg kg(-1) concentrations. Repeated application of sewage sludge (biosolids) and increasing reclaimed wastewater use for irrigation could lead to accumulation of these novel contaminants in soil systems. Despite this, potential phytotoxicological effects on higher plants have rarely been evaluated. These studies aimed to test effects upon germination, development, growth and physiology of two crop plants, namely radish (Raphanus sativus Spakler 3) and lettuce (Lactuca sativa All Year Around), after exposure to different, but structurally related non-steroidal anti-inflammatory drugs (NSAIDs) at environmentally relevant concentrations. A range of biological endpoints comprising biomass, length, water content, specific root and shoot length, root to shoot ratio, daily progress of stages of cell elongation and organ emergence (primary root, hypocotyl elongation, cotyledon emergence, cotyledon opening, and no change), as well as photosynthetic measurements were evaluated. Compounds from the fenamic acid class were found to affect R. sativus root endpoints (root length and water content), while ibuprofen affected early root development of L. sativa. In general, phytotoxicological effects on root endpoints demonstrated that impacts upon higher plants are not only compound specific, but also differ between plant species. It was found that the usage of a wide range of biological endpoints (all simple, cost-effective and ecologically relevant) were beneficial in detecting differences in plant responses to NSAID exposure. Due to paucity and discrepancy within the few previously available phytotoxicological studies with pharmaceuticals, it is now essential to allocate time and resources to consider development of suitable chronic toxicity tests, and some suggestions regarding this are presented. PMID:25463873

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

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    Marleen M H J van Gelder

    Full Text Available 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 the risk of selected birth defects after prenatal exposure to prescribed and over-the-counter NSAIDs. METHODS AND FINDINGS: We used data on 69,929 women enrolled in the Norwegian Mother and Child Cohort Study between 1999 and 2006. Data on NSAID exposure were available from a self-administered questionnaire completed around gestational week 17. Information on pregnancy outcome was obtained from the Medical Birth Registry of Norway. Only birth defects suspected to be associated with NSAID exposure based upon proposed teratogenic mechanisms and previous studies were included in the multivariable logistic regression analyses. A total of 3,023 women used NSAIDs in gestational weeks 0-12 and 64,074 women did not report NSAID use in early pregnancy. No associations were observed between overall exposure to NSAIDs during pregnancy and the selected birth defects separately or as a group (adjusted odds ratio 0.7, 95% confidence interval 0.4-1.1. Associations between maternal use of specific types of NSAIDs and the selected birth defects were not found either, although an increased risk was seen for septal defects and exposure to multiple NSAIDs based on small numbers (2 exposed cases; crude odds ratio 3.9, 95% confidence interval 0.9-15.7. CONCLUSIONS: Exposure to NSAIDs during the first 12 weeks of gestation does not seem to be associated with an increased risk of the selected birth defects. However, due to the small numbers of NSAID-exposed infants for the individual birth defect categories, increases in the risks of specific birth defects could not be excluded.

  20. Non steroidal anti-inflammatory drugs modulate the physicochemical properties of plasma membrane in experimental colorectal cancer: a fluorescence spectroscopic study.

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    Vaish, Vivek; Sanyal, Sankar Nath

    2011-12-01

    According to "fluid-mosaic model," plasma membrane is a bilayer constituted by phospholipids which regulates the various cellular activities governed by many proteins and enzymes. Any chemical, biochemical, or physical factor has to interact with the bilayer in order to regulate the cellular metabolism where various physicochemical properties of membrane, i.e., polarization, fluidity, electrostatic potential, and phase state may get affected. In this study, we have observed the in vivo effects of a pro-carcinogen 1,2-dimethylhydrazine dihydrochloride (DMH) and the two non steroidal anti-inflammatory drugs (NSAIDs); sulindac and celecoxib on various properties of the plasma membrane of colonocytes, i.e., electric potential, fluidity, anisotropy, microviscosity, lateral diffusion, and phase state in the experimentally induced colorectal cancer. A number of fluorescence probes were utilized like membrane fluidity and anisotropy by 1,6-diphenyl-1,3,5-hexatriene, membrane microviscosity by Pyrene, membrane electric potential by merocyanine 540, lateral diffusion by N-NBD-PE, and phase state by Laurdan. It is observed that membrane phospholipids are less densely packed and therefore, the membrane is more fluid in case of carcinogenesis produced by DMH than control. But NSAIDs are effective in reverting back the membrane toward normal state when co-administered with DMH. The membrane becomes less fluid, composed of low electric potential phospholipids whose lateral diffusion is being prohibited and the membrane stays mostly in relative gel phase. It may be stated that sulindac and celecoxib, the two NSAIDs may exert their anti-neoplastic role in colorectal cancer via modifying the physicochemical properties of the membranes. PMID:21725642

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

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    González-Pérez Antonio

    2005-11-01

    Full Text Available Abstract Background Recent data indicate that chronic use of coxibs leads to an increased occurrence of thrombotic cardiovascular events. This raises the question as to whether traditional non-steroidal anti-inflammatory drugs (tNSAIDs might also produce similar hazards. Our aim has been to evaluate the association between the chronic use of tNSAIDs and the risk of myocardial infarction (MI in patients. Methods We performed a nested case-control analysis with 4,975 cases of acute MI and 20,000 controls, frequency matched to cases by age, sex, and calendar year. Results Overall, current use of tNSAID was not associated with an increased risk of MI (RR:1.07;95%CI: 0.95–1.21. However, we found that the relative risk (RR of MI for durations of tNSAID treatment of >1 year was 1.21 (95% CI, 1.00–1.48. The corresponding RR was 1.34 (95% CI, 1.06–1.70 for non-fatal MI. The effect was independent from dose. The small risk associated with long-term use of tNSAIDs was observed among patients not taking low-dose aspirin (RR: 1.29; 95% CI, 1.01–1.65. The effect of long-term use for individual tNSAIDs ranged from a RR of 0.87 (95% CI, 0.47–1.62 with naproxen to 1.38 (95% CI, 1.00–1.90 with diclofenac. Conclusion This study adds support to the hypothesis that chronic treatment with some tNSAIDs is associated with a small increased risk of non-fatal MI. Our data are consistent with a substantial variability in cardiovascular risks between individual tNSAIDs.

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

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

    2014-01-01

    Endocrine disrupting chemicals and non-steroidal anti-inflammatory drugs are two important groups of emerging pollutants due to their toxicological and chemical characteristics and their persistent detection in the aquatic environment. Wastewater treatment plants are a significant pathway for their transfer to the water courses. It is well evidenced that these chemicals are only partially removed through biological treatment of wastewater and therefore being detected in secondary effluents. This work focuses on the evaluation of the efficiency of two well-established disinfection technologies (chlorination and UV irradiation) along with UV/H2O2 and powdered activated carbon (PAC) to remove these chemicals from biologically treated wastewater. Based on the results it is shown that appreciable removal efficiencies due to chlorination should be expected for most of the target compounds, whereas this was not the case for ibuprofen and ketoprofen. With the exemption of diclofenac and ketoprofen direct UV irradiation did not efficiently removed target compounds for UV doses usually applied for disinfection purposes. The application of advanced UV treatment through the addition of H2O2 although resulted in increased removal of the target compounds is not sufficient at moderate UV and H2O2 doses to achieve satisfactory removal efficiencies. PAC use resulted in sufficient removal of target compounds although high PAC doses were required for some chemicals. Comparison of Freundlich isotherms of this study with those of other studies, derived employing water samples, suggested that the water matrix along with the target compounds concentration range can significantly affect the outcome of the experiments. PMID:24645450

  3. Randomized trial comparing preoperative irradiation versus the use of non-steroidal-antiinflammatory drugs for prevention of heterotopic ossification following prosthetic total hip replacement

    International Nuclear Information System (INIS)

    Purpose: In vivo data support the effectiveness of early preoperative irradiation within 4h before operation in suppressing the development of heterotopic ossification (HTO) after total hip replacement (THR). This procedure can entail logistical difficulties. A randomized trial was undertaken to assess the efficacy of late preoperative irradiation in the evening before the day of operation compared with the use of non-steroidal-antiinflammatory drugs (NSAID). Methods: Between 1995 and 1996 103 patients with normal risk factors for HTO following elective hip replacement were randomized to receive preoperative irradiation (single 7Gy fraction) or NSAID (diclofenac-colestyramin). X rays of treated hips were obtained immediately and 6 months after surgery. HTO was scored ascending to the Brooker grading system. A group of 100 patients, who received no prophylactic therapy after THR between 1988 and 1992, were analysed as untreated historical control group. Results: The incidence of HTO was 48% in the irradiation-group (Brooker Score I:52%; II:36%; III:5%; IV:0%), 9,3% in the NSAID-group (Brooker Score I:7,5%; II:1,8%; III:0%; IV:0%) and 65% in the untreated control group (Brooker Score I:26%; II:15%; III:19%; IV:5%). Regarding overall HTO there was a significant difference between the two treatment groups. Analysing the clinically significant HTO (Brooker score III or IV) no significant difference was noted between irradiated patients and patients treated by NSAID, but between the treatment groups and the untreated historical control group. Conclusion: NSAID and late preoperative irradiation can reduce the incidence of clinical significant HTO after THR. with a single 5Gy fraction or use of NSAID

  4. Effects of non-steroidal anti-inflammatory drugs on cell proliferation and death in cultured epiphyseal-articular chondrocytes of fetal rats

    International Nuclear Information System (INIS)

    Previous reports indicated that non-steroidal anti-inflammatory drugs (NSAIDs) suppress bone repair. Our previous study further found that ketorolac delayed the endochondral bone formation, and the critical effective timing was at the early stage of repair. Furthermore, we found that NSAIDs suppressed proliferation and induced cell death of cultured osteoblasts. In this study, we hypothesized that chondrocytic proliferation and death, which plays an important role at the early stage of endochondral bone formation, might be affected by NSAIDs. Non-selective NSAIDs, indomethacin, ketorolac, diclofenac and piroxicam; cyclooxygenase-2 (COX-2) selective NSAIDs, celecoxib and DFU (an analog of rofecoxib); prostaglandins (PGs), PGE1, PGE2 and PGF2α; and each NSAID plus each PG were tested. The effects of NSAIDs on proliferation, cell cycle kinetics, cytotoxicity and cell death of epiphyseal-articular chondrocytes of fetal rats were examined. The results showed that all the tested NSAIDs, except DFU, inhibited thymidine incorporation of chondrocytes at a concentration range (10-8 to 10-4 M) covering the theoretic therapeutic concentrations. Cell cycle was arrested by NSAIDs at the G /G1 phase. Upon a 24 h treatment, LDH leakage and cell death (both apoptosis and necrosis) were significantly induced by the four non-selective NSAIDs in chondrocyte cultures. However, COX-2 inhibitors revealed non-significant effects on cytotoxicity of chondrocytes except higher concentration of celecoxib (10-4 M). Replenishments of PGE1, PGE2 or PGF2α could not reverse the effects of NSAIDs on chondrocytic proliferation and cytotoxicity. In this study, we found that therapeutic concentrations of non-selective NSAIDs caused proliferation suppression and cell death of chondrocytes, suggesting these adverse effects may be one of the reasons that NSAIDs delay the endochondral ossification during bone repair found in previous studies. Furthermore, these effects of NSAIDs may act via PG

  5. Preoperative irradiation versus the use of nonsteroidal anti-inflammatory drugs for prevention of heterotopic ossification following total hip replacement: the results of a randomized trial

    International Nuclear Information System (INIS)

    Purpose: Previous studies showed the effectiveness of early preoperative (4 h before operation) irradiation for prevention of heterotopic ossification (HO) after total hip replacement. This procedure can result in logistic problems, if there is a great distance between the department of radiotherapy and the orthopedic clinic. To avoid these organizational problems a prospective study was undertaken to analyze the effectiveness of preoperative irradiation on the day preceding surgery (16-20 h before operation). Methods and Materials: Between 1995 and 1996, 100 patients were randomized to receive a prophylactic therapy for prevention of heterotopic ossification. Forty-six patients were irradiated with 7 Gy single dose within 16-20 h before operation. Fifty-four patients were treated with nonsteroidal anti-inflammatory drugs (NSAID) ([reg]Voltaren resinat 2 x 75 mg/day for 2 weeks). Heterotopic ossification was scored according to the Brooker Grading system. One hundred patients receiving no prophylactic therapy after total hip arthroplasty between 1988 and 1992 were analyzed and defined as the historical control group. Results: Incidence of heterotopic ossification was 47.8% in the 7 Gy preoperative group (Brooker Score I: 36.9%; II: 8.7%; III: 2.2%; IV: 0%) and 11.1% in the NSAID group (Brooker Score I: 9.3%; II: 1.8%; III: 0%; IV: 0%). Regarding overall heterotopic ossification there was a significant difference between the NSAID group and the 7 Gy group (p 0.05). In the untreated historical control group the incidence of heterotopic ossification was 65% (Brooker Score I: 26%; II: 15%; III: 19%; IV: 5%). Referring to overall and to clinically relevant heterotopic ossification the incidence of HO was greater in the control group than in the prophylacticly treated groups (p < 0.05). Conclusion: Irradiation within 16-20 h before operation and use of NSAID (Voltaren resinat) can reduce the incidence of clinically relevant heterotopic ossification after total hip

  6. Non-steroidal anti-inflammatory drugs for the treatment of pain and immobility-associated osteoarthritis: consensus guidance for primary care

    Directory of Open Access Journals (Sweden)

    Adebajo Ade

    2012-03-01

    Full Text Available Abstract Background Osteoarthritis is a common presentation in primary care, and non-selective non-steroidal anti-inflammatory drugs (sometimes also referred to as traditional NSAIDs or tNSAIDs and selective cyclo-oxygenase 2 inhibitors (COX-2 inhibitors are commonly used to treat it. The UK's National Institute for Health and Clinical Excellence (NICE recommends taking patient risk factors into account when selecting a tNSAID or a COX-2 inhibitor, but GPs have lacked practical guidance on assessing patient risk. Methods A multi-disciplinary group that included primary care professionals (PCPs developed an evidence-based consensus statement with an accompanying flowchart that aimed at providing concise and specific guidance on NSAID use in osteoarthritis treatment. An open invitation to meet and discuss the issue was made to relevant healthcare professionals in South Yorkshire. A round table meeting was held that used a modified nominal group technique, aimed at generating opinions and ideas from all stakeholders in the consensus process. A draft developed from this meeting went through successive revisions until a consensus was achieved. Results Four statements on the use of tNSAIDs and COX-2 inhibitors (and an attached category of evidence were agreed: 1 tNSAIDs are effective drugs in relieving pain and immobility associated with osteoarthritis. COX-2 inhibitors are equally effective; 2 tNSAIDs and COX-2 inhibitors vary in their potential gastrointestinal, liver, and cardio-renal toxicity. This risk varies between individual treatments within both groups and is increased with dose and duration of treatment; 3 COX-2 inhibitors are associated with a significantly lower gastrointestinal toxicity compared to tNSAIDs. Co-prescribing of aspirin reduces this advantage; 4 PPIs should always be considered with a tNSAID and with a COX-2 inhibitor in higher GI risk patients. An accompanying flowchart to guide management was also agreed. Conclusions

  7. Drug: D01252 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 52.gif Anti-inflammatory ATC code: M01AB06 nonsteroidal antiinflammatory drugs (NSAIDs) Anatomical Therapeut...IC PRODUCTS M01A ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS M01AB

  8. Antiinflamatórios não-hormonais: inibidores da ciclooxigenase 2 Nonsteroidal anti-inflammatory drugs: cyclooxygenase 2 inhibitors

    Directory of Open Access Journals (Sweden)

    Maria Odete Esteves Hilário

    2006-11-01

    Full Text Available OBJETIVO: Analisar os antiinflamatórios não-hormonais (AINH inibidores seletivos da Cox 2 quanto ao mecanismo de ação, principais indicações, posologia e efeitos adversos mais comuns. FONTES DOS DADOS: MEDLINE e LILACS, sites da Food and Drug Administration (FDA e da Agência Nacional de Vigilância Sanitária (ANVISA. Foram selecionados os artigos mais importantes, com destaque para as publicações dos últimos 5 anos. SÍNTESE DOS DADOS: As principais indicações dos AINH são o controle da dor e da inflamação aguda e crônica. Não existem evidências que demonstrem maior efetividade de um AINH sobre outro. Até a presente data, nenhum inibidor da Cox2 foi liberado para uso na faixa etária pediátrica. Apenas o meloxicam e o etoricoxibe podem ser prescritos para adolescentes (13 e 16 anos, respectivamente. Os inibidores seletivos da Cox 2 são indicados em pacientes com efeitos adversos comprovadamente relacionados aos AINH não seletivos. Em alguns casos de alergia à aspirina, os Cox 2 seletivos podem ser prescritos, mas seu uso deve ser cuidadoso. Os principais efeitos adversos incluem os cardiovasculares e os fenômenos trombóticos. CONCLUSÕES: Os inibidores seletivos da Cox 2 são medicamentos que vêm sendo utilizados em algumas situações clínicas bem determinadas e podem oferecer algumas vantagens com relação aos AINH não seletivos. No entanto, devido ao custo mais elevado e aos potenciais efeitos adversos cardiovasculares, seu emprego deve ser criterioso.OBJECTIVE: To analyze selective COX 2 inhibitor nonsteroidal anti-inflammatory drugs (NSAID in terms of their mechanism of action, principal indications, posology and most common adverse effects. SOURCES: MEDLINE and LILACS databases and Food and Drug Administration (FDA and National Agency for Sanitary Vigilance (ANVISA - Agência Nacional de Vigilância Sanitária websites. The most important articles were selected and preference was given to articles published

  9. The Side Effects Of The Nonsteroidal Anti-Inflammatory Drug (NSAID Ketoprofen On Histological And Ultrastructural Aspects Of The Kidneys Of Albino Rats

    Directory of Open Access Journals (Sweden)

    Amina M. Farag Allah

    2001-06-01

    Full Text Available The present work deals with the effect of the therapeutic dose of the nonsteroidal anti-inflammatory drug, ketoprofen on the microscopic structure of the kidney of the albino rat. The present study also sheds light on the risk of using over-dosage either by mistake or in an unwise attempt at quick relieving the body pain. The intramuscular therapeutic dose of ketoprofen to albino rat was calculated and was found to equal 13.5 mg /kg body weight. Fifty adult male albino rats, Rattus norvegicus were used in the present study. The rats were equally allocated to five groups, each of 10 rats. Rats of the first group were kept as control. Rats of the second & third groups were injected daily with the therapeutic dose of ketoprofen for four and eight successive weeks respectively. Rats of the fourth & fifth groups were injected daily with double the therapeutic dose of ketoprofen for four and eight successive weeks respectively. In rats given the therapeutic dose of ketoprofen daily for four weeks and sacrificed 24 hours after the last dose, light microscope examination showed that Malpighian corpuscles and the kidney tubules revealed signs of degeneration. In rats given the therapeutic dose of ketoprofen daily for eight weeks the histological changes were in progression. A few numbers of glomeruli were increasingly congested and shrunken into dense masses of unrecognized structural details. The luminal borders of the cells lining the proximal convoluted tubules together with their microvilli were damaged. The electron micrographs of ultrathin sections of kidneys of rats given the therapeutic dose of ketoprofen daily for eight weeks showed that the glomerular capillaries were disorganized and occasionally their lining endothelium showed degeneration. The podocytes showed deteriorated and rarefied cytoplasm; and their primary processes were fragmented. Also, the foot processes appeared occasionally broad. In some cells of proximal convoluted tubules the

  10. Adipose and liver gene expression profiles in response to treatment with a nonsteroidal antiinflammatory drug after calving in grazing dairy cows.

    Science.gov (United States)

    Vailati Riboni, M; Meier, S; Priest, N V; Burke, C R; Kay, J K; McDougall, S; Mitchell, M D; Walker, C G; Crookenden, M; Heiser, A; Roche, J R; Loor, J J

    2015-05-01

    The peripartal or transition period in dairy cattle is often characterized by an inflammatory state that, if not controlled, could be detrimental to production, health, and fertility. Approaches to control the postpartal degree of inflammation include treatments with nonsteroidal antiinflammatory drugs (NSAID) postcalving, which have improved cow production and health. To date, most of the research on NSAID has been conducted in confinement cows that reach milk production levels substantially greater than those on pasture. Furthermore, little data are available on the effect of NSAID on the mRNA expression of inflammation and metabolism-related genes. Transcription regulation is an important mechanism of inflammation and metabolic control. The present study was conducted to examine hepatic and adipose tissue gene expression in response to injections of an NSAID, carprofen, on 1, 3, and 5 d after calving. Grazing Holstein-Friesian cows from a control group and 1 treated with carprofen during the first 5 d postcalving were used. Liver and subcutaneous adipose tissue biopsies were harvested at -1, 1, and 2 wk relative to parturition. More than 30 genes associated with fatty acid oxidation, growth hormone/insulin-like growth factor-1 axis, hepatokines, lipoprotein metabolism, gluconeogenesis, and inflammation were analyzed. After calving, data suggest that both tissues respond to inflammation signals at the onset of lactation. Administration of NSAID led to greater hepatic expression of pyruvate dehydrogenase kinase, isozyme 4 (PDK4), which helps regulate gluconeogenesis, and microsomal triglyceride transfer protein (MTTP), important for the assembly and secretion of very low-density lipoproteins. In adipose tissue, NSAID administration resulted in greater expression of the inflammation-related genes interleukin-1, β (IL1B), interleukin-6 receptor (IL6R), toll-like receptor 4 (TLR4), and chemokine (C-C motif) ligand 5 (CCL5). The data support the role of inflammation

  11. Potentiated clinoptilolite: artificially enhanced aluminosilicate reduces symptoms associated with endoscopically negative gastroesophageal reflux disease and nonsteroidal anti-inflammatory drug induced gastritis

    Directory of Open Access Journals (Sweden)

    Potgieter W

    2014-07-01

    Full Text Available Wilna Potgieter, Caroline Selma Samuels, Jacques Renè SnymanDepartment of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, Gauteng, South AfricaPurpose: The cation exchanger, a potentiated clinoptilolite (Absorbatox™ 2.4D, is a synthetically enhanced aluminosilicate. The aim of this study was to evaluate the possible benefits of a potentiated clinoptilolite as a gastroprotective agent in reducing the severity of clinical symptoms and signs associated with 1 endoscopically negative gastroesophageal reflux disease (ENGORD and 2 nonsteroidal anti-inflammatory drug (NSAID medication.Methods and patients: Two randomized, double-blind, placebo-controlled, pilot studies, the ENGORD and NSAID studies, were conducted. After initial negative gastroscopy, a total of 25 patients suffering from ENGORD were randomized to receive either placebo capsules or 750 mg Absorbatox twice daily for 14 days. The NSAID study recruited 23 healthy patients who received orally either 1,500 mg Absorbatox or placebo three times daily, plus 500 mg naproxen twice daily. Patients underwent gastroscopic evaluation of their stomach linings prior to and on day 14 of the study. Gastric biopsies were obtained and evaluated via the upgraded Sydney system, whereas visible gastric events and status of the gastric mucosa were evaluated via a 0–3 rating scale. During both studies, patients recorded gastric symptoms in a daily symptom diary.Results: In the ENGORD study, patients who received the potentiated clinoptilolite reported a significant reduction (P≤0.05 in severity of symptoms including reduction in heartburn (44%, discomfort (54%, and pain (56%. Symptom-free days improved by 41% compared to the group who received placebo (not significant. This was over and above the benefits seen with the proton pump inhibitor. In the NSAID study, the reduction in gastric symptom severity was echoed in the group who received the potentiated

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  13. Randomized trial comparing early postoperative irradiation vs. the use of nonsteroidal antiinflammatory drugs for prevention of heterotopic ossification following prosthetic total hip replacement

    International Nuclear Information System (INIS)

    Purpose: A randomized trial was undertaken to assess the comparative efficacy of early postoperative irradiation with either 5 or 7 Gy vs. the use of nonsteroidal antiinflammatory drug (NSAID) for prevention of heterotopic ossification (HO) following prothetic total hip replacement (THP). Methods and Materials: Between 1993 and 1994, 301 patients were randomized to receive postoperative irradiation (5 or 7 Gy) or NSAID. One hundred and thirteen patients were treated with NSAID (indometacin 2 x 50 mg/day for 1 week), 93 patients were irradiated with a single 7 Gy fraction, 95 patients with a single 5 Gy fraction. The treatment volume included the soft tissues between the periactebular region of pelvis and the intertrochanteric portion of the femur. X-rays of treated hips were obtained immediately and 6 months after surgery. Heterotopic ossification was scored according to the Brooker Grading system. One hundred patients receiving no prophylactic therapy after total hip arthroplasty between 1988 and 1992, were analyzed and defined as historical control group. Results: Incidence of heterotopic ossification was 16.0% in NSAID-group (Brooker Score I: 8.0%; II: 6.2%; III: 1,8%; IV: 0%), 30.1% in 5 Gy group (Brooker Score I: 24.7%; II: 4.3%; III: 1.1%; IV: 0%), and 11.1% in 7 Gy group (Brooker Score I: 11.6%; II: 0%; III: 0%; IV: 0%). Regarding overall heterotopic ossification there was a significant difference between the NSAID group and the 5 Gy group (p 0.3). Analyzing the clinically significant HO (Brooker Score III and IV) patients irradiated with 7 Gy developed less HO than those treated with NSAID (p = 0.003). Incidence of HO was greater in the untreated historical control group (Brooker Score I: 26%; II: 15%; III: 19%; IV: 5%) than in all three prophylacticly treated groups. Conclusion: Prophylactic irradiation of the operative site after hip replacement with single a 7 Gy fraction is the most effective postoperative treatment schedule in prevention of clinically

  14. On the absorption and emission properties of three new non-steroidal anti-inflammatory drugs-β-cyclodextrin host-guest inclusion complexes: differentiated sensitivity to the microenvironment upon light excitation

    OpenAIRE

    MONTI S; Salemi, M. G.; S. Giuffrida; De Fazio, S; Guidi, G.; Sortino, S.

    1999-01-01

    The effects of β-cyclodextrin (β-CD) complexation on the absorption and emission properties of the non-steroidal anti-inflammatory drugs tolmetin (TM), diflunisal (DF), and fenbufen (FB) have been investigated. The absorption spectra of all these compounds are only slightly affected by the addition of ��-CD. In contrast, the emission properties were markedly influenced by CD complexation and in a different manner for the three compounds due to a differentiated sensitivity of the exci...

  15. Chemopreventive response of diclofenac, a non-steroidal anti-inflammatory drug in experimental carcinogenesis Respuesta quimiopreventiva del diclofenaco, un fármaco antiinflamatorio no esteroideo en la carcinogénesis de colon experimental

    OpenAIRE

    M. Kaur Saini; J Kaur; Sharma, P.; S. Nath Sanyal

    2009-01-01

    The chemopreventive response was evaluated of nonsteroidal anti-inflammatory drug, Diclofenac, a preferential cyclooxygenase-2 (COX-2) inhibitor in 1,2-dimethyhydrazine (DMH)-induced colon cancer in rat model. The signs of neoplasm were evident in the animals receiving 30mg of DMH per kg body weight in a weekly s.c injection for six weeks. The putative biomarker of carcinogenesis was visible in the form of multiple plaque lesions in DMH treatment and then regression seen in those animals whic...

  16. Non-steroidal anti-inflammatory drugs activate NADPH oxidase in adipocytes and raise the H2O2 pool to prevent cAMP-stimulated protein kinase a activation and inhibit lipolysis

    OpenAIRE

    Vázquez-Meza, Héctor; de Piña, Martha Zentella; Pardo, Juan Pablo; Riveros-Rosas, Héctor; Villalobos-Molina, Rafael; Piña, Enrique

    2013-01-01

    Background Non-steroidal anti-inflammatory drugs (NSAIDs) —aspirin, naproxen, nimesulide, and piroxicam— lowered activation of type II cAMP-dependent protein kinase A (PKA-II) in isolated rat adipocytes, decreasing adrenaline- and dibutyryl cAMP (Bt2cAMP)-stimulated lipolysis. The molecular bases of insulin-like actions of NSAID were studied. Results Based on the reported inhibition of lipolysis by H2O2, catalase was successfully used to block NSAID inhibitory action on Bt2cAMP-stimulated lip...

  17. Click chemistry for attachment of targeting moieties to polymer drug carriers

    Czech Academy of Sciences Publication Activity Database

    Pola, Robert; Pechar, Michal; Ulbrich, Karel

    Herceg Novi: Materials Research Society of Serbia , 2013. s. 140. [Annual Conference YUCOMAT 2013 /15./. 02.09.2013-06.09.2013, Herceg Novi] R&D Projects: GA MŠk EE2.3.30.0029 Institutional support: RVO:61389013 Keywords : HPMA * peptides * "click" chemistry Subject RIV: CE - Biochemistry

  18. Antiinflammatory activity of Piper longum fruit oil

    Directory of Open Access Journals (Sweden)

    Kumar A

    2009-01-01

    Full Text Available In the present study, antiinflammatory activity of the Piper longum dried fruit′s oil was studied in rats using the carrageenan-induced right hind paw edema method. The activity was compared with that of standard drug ibuprofen. The dried fruit′s oil inhibited carrageenan-induced rat paw edema. The results indicated that the dried fruit′s oil produced significant (p< 0.001 antiinflammatory activity when compared with the standard and untreated control.

  19. Cymbopogon citratus as source of new and safe anti-inflammatory drugs: Bio-guided assay using lipopolysaccharide-stimulated macrophages

    OpenAIRE

    Francisco, Vera; García-Rodríguez, Carmen

    2011-01-01

    [Ethnopharmacological relevance]: Aqueous extracts of Cymbopogon citratus (Cy) leaves are used in traditional medicine for the treatment of inflammatory conditions, however, little is known about their mechanism of action. [Aim of the study]: The aim of this study is to explore the anti-inflammatory properties of Cymbopogon citratus leaves and their polyphenol-rich fractions (PFs), as well its mechanism of action in murine macrophages. [Materials and methods]: A lipid- and e...

  20. [Cheek perforation of dental origin and the effect of anti-inflammatory drug treatment during self-medication. Apropos of a case].

    Science.gov (United States)

    Kouame, P; Souaga, K; Amantchi, D

    1999-06-01

    Complications of dental caries not treated and mal-treated are frequent in Africa (cellulitis, osteitis, etc...). Patients consult late due to effective automedication with anti-inflammatory agents but the continuing pathological process leading to fistulae, perforation and persistent pain are finally the reasons of consultation. We present a case of a young Ivorian student of 22 years we have received after one year of erratic treatment with a right jaw perforation. PMID:11372091

  1. Molecular interactions between some non-steroidal anti-inflammatory drugs (NSAID's) and bovine (BSA) or human (HSA) serum albumin estimated by means of isothermal titration calorimetry (ITC) and frontal analysis capillary electrophoresis (FA/CE).

    Science.gov (United States)

    Ràfols, Clara; Zarza, Sílvia; Bosch, Elisabeth

    2014-12-01

    The interactions between some non-steroidal anti-inflammatory drugs, NSAIDs, (naproxen, ibuprofen and flurbiprofen) and bovine (BSA) or human (HSA) serum albumin have been examined by means of two complementary techniques, isothermal titration calorimetry (ITC) and frontal analysis/capillary electrophoresis (FA/CE). It can be concluded that ITC is able to measure with high precision the strongest drug-albumin interactions but the higher order interactions can be better determined by means of FA/CE. Then, the combination of both techniques leads to a complete evaluation of the binding profiles between the selected NSAIDs and both kind of albumin proteins. When BSA is the binding protein, the NSAIDs show a strong primary interaction (binding constants: 1.5 × 10(7), 8 × 10(5) and 2 × 10(6) M(-1) for naproxen, ibuprofen and flurbiprofen, respectively), and also lower affinity interactions of the same order for the three anti-inflammatories (about 1.7 × 10(4) M(-1)). By contrast, when HSA is the binding protein two consecutive interactions can be observed by ITC for naproxen (9 × 10(5) and 7 × 10(4) M(-1)) and flurbiprofen (5 × 10(6) and 6 × 10(4) M(-1)) whereas only one is shown for ibuprofen (9 × 10(5) M(-1)). Measurements by FA/CE show a single interaction for each drug being the ones of naproxen and flurbiprofen the same that those evaluated by ITC as the second interaction events. Then, the ability of both techniques as suitable complementary tools to establish the whole interaction NSAIDs-albumin profile is experimentally demonstrated and allows foreseeing suitable strategies to establish the complete drug-protein binding profile. In addition, for the interactions analyzed by means of ITC, the thermodynamic signature is established and the relative contributions of the enthalpic and entropic terms discussed. PMID:25159405

  2. Triggered Drug Release from an Antibody-Drug Conjugate Using Fast "Click-to-Release" Chemistry in Mice.

    Science.gov (United States)

    Rossin, Raffaella; van Duijnhoven, Sander M J; Ten Hoeve, Wolter; Janssen, Henk M; Kleijn, Laurens H J; Hoeben, Freek J M; Versteegen, Ron M; Robillard, Marc S

    2016-07-20

    The use of a bioorthogonal reaction for the selective cleavage of tumor-bound antibody-drug conjugates (ADCs) would represent a powerful new tool for ADC therapy, as it would not rely on the currently used intracellular biological activation mechanisms, thereby expanding the scope to noninternalizing cancer targets. Here we report that the recently developed inverse-electron-demand Diels-Alder pyridazine elimination reaction can provoke rapid and self-immolative release of doxorubicin from an ADC in vitro and in tumor-bearing mice. PMID:27306828

  3. CHEMISTRY OF HYALURONIC ACID AND ITS SIGNIFICANCE IN DRUG DELIVERY STRATEGIES: A REVIEW

    OpenAIRE

    R. Khan*, B. Mahendhiran and V. Aroulmoji

    2013-01-01

    Hyaluronic acid is an important naturally occurring polysaccharide present in extracellular matrices. The network-forming, viscoelastic and the charge characteristics of hyaluronic acid are important to many biochemical functions of living tissues. Its involvement in many diseases such as cancer, arthritis and osteoporosis, and the fact that it has specific protein receptors present on the cell surfaces, has given new impetus in drug design and synthesis of hyaluronic acid-drug conjugates. As...

  4. Synthesis and evaluation of sensitizer drug photorelease chemistry: Micro-optic method applied to singlet oxygen generation and drug delivery

    Science.gov (United States)

    Ghosh, Goutam

    This thesis summarizes a new micro-optic method for singlet oxygen generation and sensitizer drug delivery, which include i) synthesis and evaluation of a first generation device for drug delivery from native and fluorinated silica probe tips, ii) synthesis of PEG conjugated sensitizers to study phototoxicity in ovarian cancer cells, and iii) synthesis and evaluation of tris-PEGylated chlorin conjugated fluorinated silica for its future integration into the device to use as a 2nd generation device. A first generation micro-optic device was developed that works by sparging O2 gas and light generating cytotoxic singlet oxygen that cleaves the covalently attached drug (sensitizer) from the probe tip at the distal end of the fiber. The aim is to develop a 1st and 2nd generation device for site specific delivery of photosensitizer and singlet oxygen to overcome the challenges involved in systemic administration of the sensitizer. Synthesis and evaluation of drug (pheophorbide-a) delivery applying micro-optic method from native and fluorinated silica probe tip was achieved. The amount of sensitizer photocleavage depends on the loading level of sensitizer onto the probe tips. We also found that photorelease efficiency depends on the nature of the solvents where sensitizer is photocleaved. For example, no photorelease was observed in an aqueous solvent where sensitizer remained adsorbed to the native silica probe-tip. But, 90% photocleavage was obtained in octanol. A significant amount of photosensitizer (formate ester of pyropheophorbide- a) diffused into the liposome when photocleavage study was carried out in liposome. Substantial increase of photorelease was observed in organic solvent when pyropheophorbide-a (PPa) sensitizer was attached to the partially fluorinated porous Vycor glass. We also explored sensitizer photorelease from the fluorinated silica surface at various temperatures and we found that autocatalytic photorelease happened at room temperature and above

  5. Brain Chemistry and Behaviour: An Update on Neuroscience Research and Its Implications for Understanding Drug Addiction

    Science.gov (United States)

    Robinson, Emma S. J.

    2011-01-01

    Psychiatric disorders such as drug addiction represent one of the biggest challenges to society. This article reviews clinical and basic science research to illustrate how developments in research methodology have enabled neuroscientists to understand more about the brain mechanisms involved in addiction biology. Treating addiction represents a…

  6. Evaluation of innovative stationary phase ligand chemistries and analytical conditions for the analysis of basic drugs by supercritical fluid chromatography.

    Science.gov (United States)

    Desfontaine, Vincent; Veuthey, Jean-Luc; Guillarme, Davy

    2016-03-18

    Similar to reversed phase liquid chromatography, basic compounds can be highly challenging to analyze by supercritical fluid chromatography (SFC), as they tend to exhibit poor peak shape, especially those with high pKa values. In this study, three new stationary phase ligand chemistries available in sub -2μm particle sizes, namely 2-picolylamine (2-PIC), 1-aminoanthracene (1-AA) and diethylamine (DEA), were tested in SFC conditions for the analysis of basic drugs. Due to the basic properties of these ligands, it is expected that the repulsive forces may improve peak shape of basic substances, similarly to the widely used 2-ethypyridine (2-EP) phase. However, among the 38 tested basic drugs, less of 10% displayed Gaussian peaks (asymmetry between 0.8 and 1.4) using pure CO2/methanol on these phases. The addition of 10mM ammonium formate as mobile phase additive, drastically improved peak shapes and increased this proportion to 67% on 2-PIC. Introducing the additive in the injection solvent rather than in the organic modifier, gave acceptable results for 2-PIC only, with 31% of Gaussian peaks with an average asymmetry of 1.89 for the 38 selected basic drugs. These columns were also compared to hybrid silica (BEH), DIOL and 2-EP stationary phases, commonly employed in SFC. These phases commonly exhibit alternative retention and selectivity. In the end, the two most interesting ligands used as complementary columns were 2-PIC and BEH, as they provided suitable peak shapes for the basic drugs and almost orthogonal selectivities. PMID:26895829

  7. Sulfur Containing Scaffolds in Drugs: Synthesis and Application in Medicinal Chemistry

    Science.gov (United States)

    Feng, Minghao; Tang, Bingqing; Liang, Steven H.; Jiang, Xuefeng

    2016-01-01

    The impact of the development of sulfur therapeutics is instrumental to the evolution of the pharmaceutical industry. Sulfur-derived functional groups can be found in a broad range of pharmaceuticals and natural products. For centuries, sulfur continues to maintain its status as the dominating heteroatom integrated into a set of 362 sulfur-containing FDA approved drugs (besides oxygen or nitrogen) through the present. Sulfonamides, thioethers, sulfones and Penicillin are the most common scaffolds in sulfur containing drugs, which are well studied both on synthesis and application during the past decades. In this review, these four moieties in pharmaceuticals and recent advances in the synthesis of the corresponding core scaffolds are presented. PMID:26369815

  8. Click chemistry, 3D-printing, and omics: the future of drug development

    OpenAIRE

    Kurzrock, Razelle; Stewart, David J.

    2015-01-01

    Genomics is a disruptive technology, having revealed that cancers are tremendously complex and differ from patient to patient. Therefore, conventional treatment approaches fit poorly with genomic reality. Furthermore, it is likely that this type of complexity will also be observed in other illnesses. Precision medicine has been posited as a way to better target disease-related aberrations, but developing drugs and tailoring therapy to each patient's complicated problem is a major challenge. O...

  9. Sulfur Containing Scaffolds in Drugs: Synthesis and Application in Medicinal Chemistry

    OpenAIRE

    Feng, Minghao; Tang, Bingqing; Liang, Steven H.; Jiang, Xuefeng

    2016-01-01

    The impact of the development of sulfur therapeutics is instrumental to the evolution of the pharmaceutical industry. Sulfur-derived functional groups can be found in a broad range of pharmaceuticals and natural products. For centuries, sulfur continues to maintain its status as the dominating heteroatom integrated into a set of 362 sulfur-containing FDA approved drugs (besides oxygen or nitrogen) through the present. Sulfonamides, thioethers, sulfones and Penicillin are the most common scaff...

  10. Click chemistry, 3D-printing, and omics: the future of drug development.

    Science.gov (United States)

    Kurzrock, Razelle; Stewart, David J

    2016-01-19

    Genomics is a disruptive technology, having revealed that cancers are tremendously complex and differ from patient to patient. Therefore, conventional treatment approaches fit poorly with genomic reality. Furthermore, it is likely that this type of complexity will also be observed in other illnesses. Precision medicine has been posited as a way to better target disease-related aberrations, but developing drugs and tailoring therapy to each patient's complicated problem is a major challenge. One solution would be to match patients to existing compounds based on in silico modeling. However, optimization of complex therapy will eventually require designing compounds for patients using computer modeling and just-in-time production, perhaps achievable in the future by three-dimensional (3D) printing. Indeed, 3D printing is potentially transformative by virtue of its ability to rapidly generate almost limitless numbers of objects that previously required manufacturing facilities. Companies are already endeavoring to develop affordable 3D printers for home use. An attractive, but as yet scantily explored, application is to place chemical design and production under digital control. This could be accomplished by utilizing a 3D printer to initiate chemical reactions, and print the reagents and/or the final compounds directly. Of interest, the Food and Drug Administration (FDA) has recently approved a 3D printed drug-levetiracetam-indicated for seizures. Further, it is now increasingly clear that biologic materials-tissues, and eventually organs-can also be "printed." In the near future, it is plausible that high-throughput computing may be deployed to design customized drugs, which will reshape medicine. PMID:26734837

  11. Thyroid hormone synthesis and anti-thyroid drugs: A bioinorganic chemistry approach

    Indian Academy of Sciences (India)

    Gouriprasanna Roy; G Mugesh

    2006-11-01

    Hydrogen peroxide, generated by thyroid oxidase enzymes, is a crucial substrate for the thyroid peroxidase (TPO)-catalysed biosynthesis of thyroid hormones, thyroxine (T4) and triiodothyronine (T3) in the thyroid gland. It is believed that the H2O2 generation is a limiting step in thyroid hormone synthesis. Therefore, the control of hydrogen peroxide concentration is one of the possible mechanisms for the inhibition of thyroid hormone biosynthesis. The inhibition of thyroid hormone synthesis is required for the treatment of hyperthyroidism and this can be achieved by one or more anti-thyroid drugs. The most widely used anti-thyroid drug methimazole (MMI) inhibits the production of thyroid hormones by irreversibly inactivating the enzyme TPO. Our studies show that the replacement of sulphur in MMI by selenium leads to a selone, which exists predominantly in its zwitterionic form. In contrast to the sulphur drug, the selenium analogue (MSeI) reversibly inhibits the peroxidase-catalysed oxidation and iodination reactions. Theoretical studies on MSeI reveal that the selenium atom in this compound carries a large negative charge. The carbon-selenium bond length in MSeI is found to be close to single-bond length. As the selenium atom exhibits a large nucleophilic character, the selenium analogue of MMI may scavenge the hydrogen peroxide present in the thyroid cells, which may lead to a reversible inhibition of thyroid hormone biosynthesis.

  12. Click chemistry, 3D-printing, and omics: the future of drug development

    Science.gov (United States)

    Kurzrock, Razelle; Stewart, David J.

    2016-01-01

    Genomics is a disruptive technology, having revealed that cancers are tremendously complex and differ from patient to patient. Therefore, conventional treatment approaches fit poorly with genomic reality. Furthermore, it is likely that this type of complexity will also be observed in other illnesses. Precision medicine has been posited as a way to better target disease-related aberrations, but developing drugs and tailoring therapy to each patient's complicated problem is a major challenge. One solution would be to match patients to existing compounds based on in silico modeling. However, optimization of complex therapy will eventually require designing compounds for patients using computer modeling and just-in-time production, perhaps achievable in the future by three-dimensional (3D) printing. Indeed, 3D printing is potentially transformative by virtue of its ability to rapidly generate almost limitless numbers of objects that previously required manufacturing facilities. Companies are already endeavoring to develop affordable 3D printers for home use. An attractive, but as yet scantily explored, application is to place chemical design and production under digital control. This could be accomplished by utilizing a 3D printer to initiate chemical reactions, and print the reagents and/or the final compounds directly. Of interest, the Food and Drug Administration (FDA) has recently approved a 3D printed drug—levetiracetam—indicated for seizures. Further, it is now increasingly clear that biologic materials—tissues, and eventually organs—can also be “printed.” In the near future, it is plausible that high-throughput computing may be deployed to design customized drugs, which will reshape medicine. PMID:26734837

  13. 多种教学方法在解热镇痛抗炎药教学中的应用%The Application of Multiple Teaching Methods in the Teach-ing of Antipyretic Analgesic and Anti-inflammatory Drugs

    Institute of Scientific and Technical Information of China (English)

    杨薪正

    2014-01-01

    药理学是一门桥梁学科,是多学科的融合。药品种类繁多、作用机制复杂、理论性强、不易理解、难记忆。本文通过比较法、图片演示法、歌诀法、教学简笔画法等教学方法在解热镇痛抗炎药教学中的应用,阐述灵活掌握教学方法对引导学生主动学习,提高药理学教学质量的重要性。%Pharmacology is a subject just like a bridge, as it is multidisciplinary integration. It includes variety of drugs, complex mechanism of drug action, and a higher theoretical level, so it is difficult in understanding and remembering. Through adopting comparison method, image presentation method, method of for-mulas and stick figure method in the teaching of antipyretic anal-gesic and anti-inflammatory drugs, it proves a view that master-ing the teaching methods flexibly plays a significant role in in-structing students' active study and improving the quality of pharmacology teaching.

  14. ANTI-INFLAMMATORY ACTIVITY OF 3-[(5-SUBSTITUED-1, 3, 4 OXADIAZOLE-2-YL METHYL AMINO]-2-METHYL QUINAZOLIN-4(3H-ONES

    Directory of Open Access Journals (Sweden)

    Ramesh Dhani

    2012-12-01

    Full Text Available The process of establishing a new drug is exceedingly complexioned involves the talents of people from a variety of disciplines including Pharmaceutical chemistry, biochemistry, physiology, pharmacology, pharmaceutics and medicine. Quinazolinone is a heterocyclic chemical compound. There are two structural isomers, 2-quinazolinone and 4-quinazolinone, with the 4-isomer being the more common. Various novel classes of structurally different quinazolinones have been designed and synthesized depicting potential interventions such as antibacterial, antifungal, antiviral, anticonvulsant, anti-inflammatory, antihistaminic, anticancer CNS depressant, and so on. All the synthesized quinazolinone derivatives were confirmed preliminarily by M.P and TLC and further all the synthesized compounds were screened for anti-inflammatory activity using Phenyl butazone as the standard and carragennin induced paw oedema model used for anti-inflammatory activity.

  15. Protein redox chemistry: post-translational cysteine modifications that regulate signal transduction and drug pharmacology

    Directory of Open Access Journals (Sweden)

    Revati eWani

    2014-10-01

    Full Text Available The perception of reactive oxygen species (ROS has evolved over the past decade from agents of cellular damage to secondary messengers which modify signaling proteins in physiology and the disease state (e.g. cancer. New protein targets of specific oxidation are rapidly being identified. One emerging class of redox modification occurs to the thiol side chain of cysteine residues which can produce multiple chemically-distinct alterations to the protein (e.g. sulfenic/sulfinic/sulfonic acid, disulfides. These post-translational modifications (PTM are shown to affect the protein structure and function. Because redox-sensitive proteins can traffic between subcellular compartments that have different redox environments, cysteine oxidation enables a spatio-temporal control to signaling. Understanding ramifications of these oxidative modifications to the functions of signaling proteins is crucial for understanding cellular regulation as well as for informed-drug discovery process. The effects of EGFR oxidation of Cys797 on inhibitor pharmacology are presented to illustrate the principle. Taken together, cysteine redox PTM can impact both cell biology and drug pharmacology.

  16. Thiazolidinone motif in anticancer drug discovery. Experience of DH LNMU medicinal chemistry scientific group

    Directory of Open Access Journals (Sweden)

    Subtel’na I. Yu.

    2011-04-01

    Full Text Available The aim was analysis of 4-thiazolidinones and related heterocyclic systems anticancer activity data and formation of some rational design directions of potential anticancer agents. Synthetic research carried out in Danylo Halytsky Lviv National Medical University (DH LNMU allowed us to propose a whole number of new molecular design directions of biological active 4-thiazolidinones and related heterocyclic systems, as well as obtain directed library that numbers over 5000 of novel compounds. At the present time in vitro anticancer activity screening was carried out for more than 1000 compounds (US NCI protocol (Developmental Therapeutic Program, among them 167 compounds showed high antitumor activity level. For the purpose of optimization and rational design of highly active molecules with optimal «drug-like» characteristics and discovering of possible mechanism of action SAR, QSAR analysis and molecular docking were carried out. The ultimate aim of the project is creating of innovative synthetic drug with special mechanism of action and sufficient pharmacological and toxicological features. Some aspects of structure–activity relationships were determined and structure design directions were proposed. The series of active compounds with high anticancer activity and/or selectivity levels were selected.

  17. Development and optimisation of SPE/CZE method for the analysis of non-steroidal anti- inflammatory drugs from water

    Czech Academy of Sciences Publication Activity Database

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

    Praha: Česká společnost chemická, 2009. Roč. 105, č. 18 (2011), s. 960-960. ISSN 0009-2770. [Meeting on Chemistry and Life /5./. 14.09.2011-16.09.2011, Brno] Institutional research plan: CEZ:AV0Z40310501 Keywords : solid phase extraction * capillary electrophoresis * non-steroidal anti-inflammatory drugs Subject RIV: CB - Analytical Chemistry, Separation

  18. A cluster randomised stepped wedge trial to evaluate the effectiveness of a multifaceted information technology-based intervention in reducing high-risk prescribing of non-steroidal anti-inflammatory drugs and antiplatelets in primary medical care: the DQIP study protocol

    OpenAIRE

    Dreischulte Tobias; Grant Aileen; Donnan Peter; McCowan Colin; Davey Peter; Petrie Dennis; Treweek Shaun; Guthrie Bruce

    2012-01-01

    Abstract Background High-risk prescribing of non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelet agents accounts for a significant proportion of hospital admissions due to preventable adverse drug events. The recently completed PINCER trial has demonstrated that a one-off pharmacist-led information technology (IT)-based intervention can significantly reduce high-risk prescribing in primary care, but there is evidence that effects decrease over time and employing additional pharmac...

  19. Site-selective protein-modification chemistry for basic biology and drug development

    Science.gov (United States)

    Krall, Nikolaus; da Cruz, Filipa P.; Boutureira, Omar; Bernardes, Gonçalo J. L.

    2016-02-01

    Nature has produced intricate machinery to covalently diversify the structure of proteins after their synthesis in the ribosome. In an attempt to mimic nature, chemists have developed a large set of reactions that enable post-expression modification of proteins at pre-determined sites. These reactions are now used to selectively install particular modifications on proteins for many biological and therapeutic applications. For example, they provide an opportunity to install post-translational modifications on proteins to determine their exact biological roles. Labelling of proteins in live cells with fluorescent dyes allows protein uptake and intracellular trafficking to be tracked and also enables physiological parameters to be measured optically. Through the conjugation of potent cytotoxicants to antibodies, novel anti-cancer drugs with improved efficacy and reduced side effects may be obtained. In this Perspective, we highlight the most exciting current and future applications of chemical site-selective protein modification and consider which hurdles still need to be overcome for more widespread use.

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

    Directory of Open Access Journals (Sweden)

    Patricia McGettigan

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

  1. Preparation, spectroscopic, thermal, antihepatotoxicity, hematological parameters and liver antioxidant capacity characterizations of Cd(II), Hg(II), and Pb(II) mononuclear complexes of paracetamol anti-inflammatory drug

    Science.gov (United States)

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

    2014-10-01

    Keeping in view that some metal complexes are found to be more potent than their parent drugs, therefore, our present paper aimed to synthesized Cd(II), Hg(II) and Pb(II) complexes of paracetamol (Para) anti-inflammatory drug. Paracetamol complexes with general formula [M(Para)2(H2O)2]·nH2O have been synthesized and characterized on the basis of elemental analysis, conductivity, IR and thermal (TG/DTG), 1H NMR, electronic spectral studies. The conductivity data of these complexes have non-electrolytic nature. Comparative antimicrobial (bacteria and fungi) behaviors and molecular weights of paracetamol with their complexes have been studied. In vivo the antihepatotoxicity effect and some liver function parameters levels (serum total protein, ALT, AST, and LDH) were measured. Hematological parameters and liver antioxidant capacities of both Para and their complexes were performed. The Cd2+ + Para complex was recorded amelioration of antioxidant capacities in liver homogenates compared to other Para complexes treated groups.

  2. 非甾体类抗炎药物对骨折愈合影响的研究进展%The Effect of Non-Steroidal Anti-Inflammatory Drugs on the Bone Fracture Healing Progress

    Institute of Scientific and Technical Information of China (English)

    陈坚; 李义凯; 张佩

    2014-01-01

    Non-steroidal anti-inflammatory drugs(NSAIDs)are widely used in clinical,especial y selective cyclo-oxygenase-2(COX-2) inhibitors,having less gastrointestinal adverse effects.However,recently some studies showing the drugs may delay the bone frature healing progress have raised concerns.Use of NSAIDs in the treatment of pain, heterotopic ossification,ankylosing spondylitis should be cautious,keeping in mind its benefits and adverse.The purpose of the present review article is thorough review and analysis the animal studies and clinical trials.%非甾体类抗炎药物在临床上广泛应用,特别是对胃肠道副作用小的环氧化酶-2(COX-2)抑制剂,但近年一些研究显示,其可能会延缓骨折的愈合过程,引起了临床医生的注意,镇痛、异位骨化、强直性脊柱炎的治疗策略可能会发生改变。本文通过文献回顾,就目前可获得动物或者临床观察数据结果作一综述。

  3. Speciation study of the anti-inflammatory drug tenoxicam (Htenox) with Cu(II): X-ray crystal structure of [Cu(tenox)(2)(py)(2)].EtOH.

    Science.gov (United States)

    Moya-Hernández, M R; Mederos, A; Domínguez, S; Orlandini, A; Ghilardi, C A; Cecconi, F; González-Vergara, E; Rojas-Hernández, A

    2003-06-01

    A speciation study was carried out in aqueous solution of the anti-inflammatory drug tenoxicam (Htenox), under quasi-physiological conditions (temperature of 37 degrees C and ionic strength 0.15 M NaCl) in order to determine the acidity constants from spectrophotometric studies, the pK(a) values found being pK(1)=1.143+/-0.008 and pK(2)=4.970+/-0.004. Subsequently, the spectrophotometrical speciation of the different complexes of Cu(II) with the drug was performed under the same conditions of temperature and ionic strength, observing the formation of Cu(Htenox)(2)(2+) with log beta(212)=20.05+/-0.01, Cu(tenox)(2) with log beta(012)=13.6+/-0.1, Cu(Htenox)(2+) with log beta(111)=10.52+/-0.08, as well as Cu(tenox)(+) with log beta(011)=7.0+/-0.2, all of them in solution, and solid species Cu(tenox)(2)(s) with an estimated value of log beta(012)(s) approximately 18.7. The crystalline structure of the complex [Cu(tenox)(2)(py)(2)]. EtOH, was also determined, and it was observed that tenoxicam employs the oxygen of the amide group and the pyridyl nitrogen to bond to the cation. PMID:12763657

  4. Efficacy of triple therapy and sequential therapy in the eradication of Helicobacter pylor in patients receiving long-term non-steroidal anti-inflammatory drugs treatnent

    Institute of Scientific and Technical Information of China (English)

    黄鑫薪

    2013-01-01

    Objective To explore the efficacy of triple therapy and sequential therapy in the eradication of Helicobacter pylori(Hp) in patients receiving long-term non-steroidal antiinflammatorv drugs(NSAID) treatment. Methods Patients receiving long-term NSAID treatment were enrolled

  5. Analgesic drugs

    OpenAIRE

    Kerec Kos, Mojca

    2015-01-01

    In the management of pain analgesic drugs are chosen regarding the intensity and type of pain. The selection of analgesic drug depends on pharmacokinetic properties of the drug and available pharmaceutical dosage forms. Beside non-opioid analgesics (non-steroidal antiinflammatory drugs, acetaminophen), opioid analgesic drugs have an important role in the treatment of pain. Pri zdravljenju bolečine izberemo analgetik glede na jakost in vrsto bolečine. Na izbiro ustreznega analgetika vplivaj...

  6. Experimental study of the action of COX-2 selective nonsteroidal anti-inflammatory drugs and traditional anti-inflammatory drugs in bone regeneration Estudo experimental da ação dos anti-inflamatórios não hormonais inibidores seletivos da ciclooxigenase 2 (COX-2 e anti-inflamatórios tradicionais na regeneração óssea

    Directory of Open Access Journals (Sweden)

    Bruno C. Tiseo

    2006-06-01

    Full Text Available OBJECTIVE: The aim of this study is to compare the effects of traditional nonsteroidal anti-inflammatory drugs with nonsteroidal anti-inflammatory drugs that are selective cyclooxygenase-2 (COX-2 inhibitors in the process of bone regeneration in a rat model. MATERIALS AND METHODS: Forty-four Wistar strain rats were subjected to osteotomy of the right femur and randomly divided into 3 groups according to the drug to be given (diclofenac, rofecoxib, or placebo. Each group was divided into 2 subgroups according to the time to euthanasia after the surgery. The animals of Subgroup 1 were submitted to euthanasia 2 weeks after surgery, and those of Subgroup 2, underwent euthanasia 4 weeks after surgery. Radiographic examinations and bone callus histomorphometry were analyzed. RESULTS: No intergroup statistical difference was found in the bone callus area or in bone formation area 2 and 4 weeks after surgery. Intra-group analysis concerning the bone neoformation area inside the callus showed a significant difference within the diclofenac group, which presented less tissue. CONCLUSIONS: Fracture consolidation in Wistar rats occurs within less than 2 weeks, and the use of nonsteroidal anti-inflammatory drugs does not significantly influence this process.OBJETIVO: Comparar os efeitos do uso de antiinflamatórios não-esteróides tradicionais (AINES e AINES que são inibidores seletivos da ciclooxigenase-2 (COX-2, no processo de regeneração óssea em ratos. MATERIAL E MÉTODO: Quarenta e quatro ratos da linhagem Wistar submetidos a osteotomia do femur direito e divididos em três grupos, conforme o medicamento que receberam (diclofenaco, rofecoxib e placebo. Cada grupo foi dividido em dois subgrupos, conforme o tempo até o sacrifício, após a cirurgia. Os animais do subgrupo 1 foram sacrificados duas semanas após a cirurgia e os do subgrupo 2, quatro semanas após a cirurgia. Foram analisados exames radiográficos e a histomorfometria do calo

  7. Chemical gastritis and Helicobacter pylori related gastritis in patients receiving non-steroidal anti-inflammatory drugs: comparison and correlation with peptic ulceration.

    OpenAIRE

    Taha, A S; Nakshabendi, I.; Lee, F D; Sturrock, R D; Russell, R I

    1992-01-01

    AIMS: To evaluate the prevalence and significance of chemical gastritis, in comparison with gastritis related to Helicobacter pylori in patients receiving non-steroidal anti inflammatory drugs (NSAIDs). METHODS: Two hundred and eighteen patients were studied, 174 of whom were taking NSAIDs. Chemical gastritis was defined as the presence of foveolar hyperplasia, muscle fibres in the lamina propria, oedema and vasodilation, in the absence of a chronic inflammatory cell infiltrate. RESULTS: Chem...

  8. Electro-oxidation of some non-steroidal anti-inflammatory drugs on an alumina nanoparticle-modified glassy carbon electrode

    OpenAIRE

    TABESHNIA, Mahla; HELI, Hossein; Jabbari, Ali

    2010-01-01

    The electro-oxidation of mefenamic acid, diclofenac, and indomethacin on glassy carbon and alumina nanoparticle-modified glassy carbon electrodes in a phosphate buffer solution at physiological pH was studied. The techniques of cyclic voltammetry, chronoamperometry, impedance spectroscopy, and steady state polarization measurements were applied. The drugs were irreversibly oxidized on bath electrodes via an anodic peak and the process was controlled by diffusion in the bulk of soluti...

  9. Engineering of a novel hybrid enzyme: an anti-inflammatory drug target with triple catalytic activities directly converting arachidonic acid into the inflammatory prostaglandin E2

    Science.gov (United States)

    Ruan, Ke-He; Cervantes, Vanessa; So, Shui-Ping

    2009-01-01

    Cyclooxygenase isoform-2 (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1) are inducible enzymes that become up-regulated in inflammation and some cancers. It has been demonstrated that their coupling reaction of converting arachidonic acid (AA) into prostaglandin (PG) E2 (PGE2) is responsible for inflammation and cancers. Understanding their coupling reactions at the molecular and cellular levels is a key step toward uncovering the pathological processes in inflammation. In this paper, we describe a structure-based enzyme engineering which produced a novel hybrid enzyme that mimics the coupling reactions of the inducible COX-2 and mPGES-1 in the native ER membrane. Based on the hypothesized membrane topologies and structures, the C-terminus of COX-2 was linked to the N-terminus of mPGES-1 through a transmembrane linker to form a hybrid enzyme, COX-2-10aa-mPGES-1. The engineered hybrid enzyme expressed in HEK293 cells exhibited strong triple-catalytic functions in the continuous conversion of AA into PGG2 (catalytic-step 1), PGH2 (catalytic-step 2) and PGE2 (catalytic-step 3), a pro-inflammatory mediator. In addition, the hybrid enzyme was also able to directly convert dihomo-gamma-linolenic acid (DGLA) into PGG1, PGH1 and then PGE1 (an anti-inflammatory mediator). The hybrid enzyme retained similar Kd and Vmax values to that of the parent enzymes, suggesting that the configuration between COX-2 and mPGES-1 (through the transmembrane domain) could mimic the native conformation and membrane topologies of COX-2 and mPGES-1 in the cells. The results indicated that the quick coupling reaction between the native COX-2 and mPGES-1 (in converting AA into PGE2) occurred in a way so that both enzymes are localized near each other in a face-to-face orientation, where the COX-2 C-terminus faces the mPGES-1 N-terminus in the ER membrane. The COX-2-10aa-mPGES-1 hybrid enzyme engineering may be a novel approach in creating inflammation cell and animal models, which

  10. Effects of intravenous nonsteroidal antiinflammatory drugs on a C-fiber reflex elicited by a wide range of stimulus intensities in the rat.

    Science.gov (United States)

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

    1996-03-01

    A C-fiber reflex elicited by electrical stimulation within the territory of the sural nerve, was recorded from the ipsilateral biceps femoris muscle in anesthetized rats. The temporal evolution of the response was studied using a constant stimulus intensity (3 x threshold) and recruitment curves were built by varying stimulus intensity from 0 to 7 x threshold. The i.v. administration of aspirin, indomethacin, ketoprofen, paracetamol (= acetaminophen) and lysine clonixinate resulted in dose-dependent depressions of the C-fiber reflex by up to 30 to 40%. By contrast, saline was ineffective. High doses of the effective drugs that produced large disturbances in heart rate and/or acid-base equilibrium were not considered in the pharmacological analysis. When a constant level of stimulation was used, different dose-dependent profiles of drug action were observed. Aspirin induced a slow and gradual depression, although indomethacin, ketoprofen and paracetamol produced a peak effect within the first 10-min period and then reached a steady state phase for up to 30 min. The depressive effects of lysine clonixinate appeared more stable. When recruitment curves were built with a range of nociceptive stimulus intensities, all the drugs produced a dose-dependent decrease in the slopes and the areas under the recruitment curves without any major modification in the thresholds. The order of potency was the same for both stimulation paradigms, e.g., aspirin lysine clonixinate = ketoprofen < indomethacin. It is concluded that NSAID elicit significant antinociceptive effects at a central level, which do not depend on the existence of a hyperalgesic or inflammatory state. PMID:8786556

  11. Enhancement of antinociception by coadminstration of minocycline and a non-steroidal anti-inflammatory drug indomethacin in naïve mice and murine models of LPS-induced thermal hyperalgesia and monoarthritis

    Directory of Open Access Journals (Sweden)

    Masocha Willias

    2010-12-01

    Full Text Available Abstract Background Minocycline and a non-steroidal anti-inflammatory drug (NSAID indomethacin, have anti-inflammatory activities and are both used in the management of rheumatoid arthritis. However, there are no reports on whether coadministration of these drugs could potentiate each other's activities in alleviating pain and weight bearing deficits during arthritis. Methods LPS was injected to BALB/c mice intraperitoneally (i.p. to induce thermal hyperalgesia. The hot plate test was used to study thermal nociception in naïve BALB/c and C57BL/6 mice and BALB/c mice with LPS-induced thermal hyperalgesia and to evaluate antinociceptive effects of drugs administered i.p. Monoarthritis was induced by injection of LPS intra-articularly into the right hind (RH limb ankle joint of C57BL/6 mice. Weight bearing changes and the effect of i.p. drug administration were analyzed in freely moving mice using the video-based CatWalk gait analysis system. Results In naïve mice indomethacin (5 to 50 mg/kg had no significant activity, minocycline (25 to 100 mg/kg produced hyperalgesia to thermal nociception, however, coadministration of minocycline 50 mg/kg with indomethacin 5 or 10 mg/kg produced significant antinociceptive effects in the hot plate test. A selective inhibitor of COX-1, FR122047 (10 mg/kg and a selective COX-2 inhibitor, CAY10404 (10 mg/kg had no significant antinociceptive activities to thermal nociception in naïve mice, however, coadministration of minocycline, with CAY10404 but not FR122047 produced significant antinociceptive effects. In mice with LPS-induced hyperalgesia vehicle, indomethacin (10 mg/kg or minocycline (50 mg/kg did not produce significant changes, however, coadministration of minocycline plus indomethacin resulted in antinociceptive activity. LPS-induced RH limb monoarthritis resulted in weight bearing (RH/left hind (LH limb paw pressure ratios and RH/LH print area ratios deficits. Treatment with indomethacin (1 mg/kg or

  12. Kaempferol and inflammation: From chemistry to medicine.

    Science.gov (United States)

    Devi, Kasi Pandima; Malar, Dicson Sheeja; Nabavi, Seyed Fazel; Sureda, Antoni; Xiao, Jianbo; Nabavi, Seyed Mohammad; Daglia, Maria

    2015-09-01

    Inflammation is an important process of human healing response, wherein the tissues respond to injuries induced by many agents including pathogens. It is characterized by pain, redness and heat in the injured tissues. Chronic inflammation seems to be associated with different types of diseases such as arthritis, allergies, atherosclerosis, and even cancer. In recent years natural product based drugs are considered as the novel therapeutic strategy for prevention and treatment of inflammatory diseases. Among the different types of phyto-constituents present in natural products, flavonoids which occur in many vegetable foods and herbal medicines are considered as the most active constituent, which has the potency to ameliorate inflammation under both in vitro and in vivo conditions. Kaempferol is a natural flavonol present in different plant species, which has been described to possess potent anti-inflammatory properties. Despite the voluminous literature on the anti-inflammatory effects of kaempferol, only very limited review articles has been published on this topic. Hence the present review is aimed to provide a critical overview on the anti-inflammatory effects and the mechanisms of action of kaempferol, based on the current scientific literature. In addition, emphasis is also given on the chemistry, natural sources, bioavailability and toxicity of kaempferol. PMID:25982933

  13. Click chemistry as a powerful and chemoselective tool for the attachment of targeting ligands to polymer drug carriers

    Czech Academy of Sciences Publication Activity Database

    Pola, Robert; Braunová, Alena; Laga, Richard; Pechar, Michal; Ulbrich, Karel

    2014-01-01

    Roč. 5, č. 4 (2014), s. 1340-1350. ISSN 1759-9954 Grant ostatní: AV ČR(CZ) Praemium Academiae Institutional support: RVO:61389013 Keywords : click chemistry * RAFT polymerization * hydrophilic polymers Subject RIV: CD - Macromolecular Chemistry Impact factor: 5.520, year: 2014

  14. Analysis of non-steroidal anti-inflammatory drugs in milk using QuEChERS and liquid chromatography coupled to mass spectrometry: triple quadrupole versus Q-Orbitrap mass analyzers.

    Science.gov (United States)

    Rúbies, Antoni; Guo, Lili; Centrich, Francesc; Granados, Mercè

    2016-08-01

    We developed a Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) method for the high throughput determination of 10 non-steroidal anti-inflammatory drugs (NSAIDs) in milk samples using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) with a triple quadrupole (QqQ) instrument and an electrospray ionization (ESI) source. The new extraction procedure is highly efficient, and we obtained absolute recoveries in the range 78.1-97.1 % for the extraction and clean-up steps. Chromatographic separation is performed in the gradient mode with a biphenyl column and acidic mobile phases consisting of water and acetonitrile containing formic acid. The chromatographic run time was about 12 min, and NSAID peaks showed a good symmetry factor. For MS/MS detection, we used multiple reaction monitoring (MRM) mode, using ESI in both positive and negative modes. Our method has been validated in compliance with the European Commission Decision 657/2002/EC, and we obtained very satisfactory results in inter-laboratory testing. Furthermore, we explored the use of a hybrid high resolution mass spectrometer, combining a quadrupole and an Orbitrap mass analyzer, for high resolution (HR) MS/MS detection of NSAIDs. We achieved lower NSAID quantification limits with Q-Orbitrap high resolution mass spectrometry (HRMS/MS) detection than those achieved with the QqQ instrument; however, its main feature is its very high selectivity, which makes HRMS/MS particularly suitable for confirmatory analysis. PMID:27325465

  15. The pharmacology and activity of non-steroidal anti-inflammatory drugs (NSAIDs: a review of their use as an adjuvant treatment in patients with HBV and HCV chronic hepatitis

    Directory of Open Access Journals (Sweden)

    Sirio Fiorino

    2013-03-01

    Full Text Available Introduction: Different DNA and RNA viruses exploit common strategies to support their persistence and replication in infected individuals. In particular, the hepatitis B virus (HBV and the hepatitis C virus (HCV cause major health problems worldwide. These pathogens exert an immunosuppressive role by inducing the persistent activation of cyclooxygenase-2 (COX-2 and an increased synthesis of prostaglandin E2 (PGE2. The suppression of this proinflammatory network by non-steroidal anti-inflammatory drugs (NSAIDs has been proposed as a therapeutic approach to decrease viral replication. Materials and methods: In this review, the role of inflammation in the support of viral replication and NSAIDs and ketoprofen pharmacology are briefly discussed. In addition, studies that have investigated the use of NSAIDs for the treatment of HBV and HCV chronic hepatitis, which were identified by a systematic literature search of PubMed and MEDLINE, are reported. Results: To date, pegylated-interferon (PEG-IFN and/or nucleot(side analogues and PEG-IFN and ribavirin remain the standard therapy for HBV and HCV chronic hepatitis, respectively. Discussion: The use of NSAIDs in patients with chronic viral hepatitis has only a ‘‘historical’’ interest. Nevertheless, the possible usefulness of ketoprofen with PEG-IFN and ribavirin for HCVinfected patients, non-responders to standard therapy or with genotype 1, should be evaluated in future clinical studies.

  16. Metabolomic analysis of glycerophospholipid signatures of inflammation treated with non-steroidal anti-inflammatory drugs-induced-RAW264.7 cells using (1)H NMR and U-HPLC/Q-TOF-MS.

    Science.gov (United States)

    Wu, Xia; Cao, Han; Zhao, Lifang; Song, Jianao; She, Yuqi; Feng, Yifan

    2016-08-15

    Non-destructive proton nuclear magnetic resonance ((1)H NMR) spectroscopy and highly sensitive ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (U-HPLC/Q-TOF-MS) coupled to data processing methods were applied to analyze the metabolic profiling changes of glycerophospholipids (GPLs) in RAW264.7 cells from inflammation to prognosis. Analysis of (1)H NMR was shown that the models were grouped successfully, illustrating that all of them had significant differences. Based on the highly simple, accurate, non-targeted and non-destructively advantages of (1)H NMR, it could be used as a new screening tool of anti-inflammatory drugs in the metabolic profiling of GPLs. 58 GPLs were identified by U-HPLC/Q-TOF-MS, and 19 components were firstly identified in this study compared with our previous results. In addition, ten potential biomarkers were proved, of which phosphatidylcholine (PC) (16:0/18:1) and (18:0/18:1) changed consistently in three drug-induced groups and might be the important biomarkers. Compared with (1)H NMR, U-HPLC/Q-TOF-MS showed higher sensitivity and specificity and was more suitable for the determination of biomarkers apart from the deficiency of time-consuming sample preparation steps and unambiguous metabolite identification. Therefore, it is feasible to analyze the changes of GPLs during inflammation by combining (1)H NMR spectroscopy with U-HPLC/Q-TOF-MS. The metabolic profiling of GPLs provides valuable evidence for inflammation diagnosis and prognosis, and might unravel the mechanisms involved in inflammation progression. PMID:27371817

  17. The Role of Analytical Chemistry in Drug Research and Development%分析化学在药物研发中的任务和作用

    Institute of Scientific and Technical Information of China (English)

    陈丹华

    2014-01-01

    药品质量包括身份、纯度、强度、疗效、稳定性和安全性.分析化学与药品质量直接相关.本文结合作者在药物分析化学方面的研究成果和长期体会,论述分析化学在药物研究与开发方面的任务和作用.%Drug quality includes identity,purity,strength,safety,efficacy,and stability.Analytical chemistry is directly related to the quality of the drug.Analytical scientists are fully responsible in identification,purity determination,assay,reference standard selection and characterization,physical form characterization,purification and stability study.They also play important roles in other areas of drug development by working together with synthetic chemists,pharmacologists,toxicologists,formulators,regulatory and quality assurance personnel.This article discusses the role,responsibility and importance of analytical chemistry in drug research and development with examples of author's own research results and pharmaceutical experience.

  18. Strictures, diaphragms, erosions or ulcerations of ischemic type in the colon should always prompt consideration of nonsteroidal anti-inflammatory drug-induced lesions

    Institute of Scientific and Technical Information of China (English)

    Manfred Stolte; Diana Karimi; Michael Vieth; Hildegard Volkholz; Klaus Dirschmid; Sigrid Rappel; Birgit Bethke

    2005-01-01

    AIM: To investigate whether NSAIDs/ASA lesions in the colon can histologically be diagnosed on the basis of ischemic necrosis similar to biopsy-based diagnosis of NSAIDs/ASA-induced erosions and ulcers of the stomach.METHODS: In the period between 1997 and 2002, we investigated biopsy materials obtained from 611 patients (415 women, 196 men, average age 60.5 years) with endoscopic focal erosions, ulcerations, strictures or diaphragms in the colon. In the biopsies obtained from these lesions, we always established the suspected diagnosis of NSAID-induced lesions whenever necroses of the ischemic type were found. Together with the histological report, we endosed a questionnaire to investigate the use of medication.The data provided by the questionnaire were then correlated with the endoscopic findings, the location, number and nature of the lesions, and the histological findings.RESULTS: At the time of their colonoscopy, 86.1% of the patients had indeed been taking NSAID/ASA medication for years (43.9%) or months (29.5%). The most common indication for the use of these drugs was pain (64.3%),and the most common indication for colonoscopy was bleeding (55.5%). Endoscopic inspection revealed multiple erosions and/or ulcers in 60.6%, strictures in 15.8%, and diaphragms in 3.0% of the patients. The lesions were located mainly in the right colon including the transverse colon (79.9%). A separate analysis of age and sex distribution,endoscopic and histological findings for NSAIDs alone,ASA alone, combined NSAID/ASA, and for patients denying the use of such drugs, revealed no significant differences among the groups.CONCLUSION: This uncontrolled retrospective study based on the histological finding of an ischemic necrosis shows that the histologically suspected diagnosis of NSAID-induced lesions in the colon is often correct. The true diagnostic validity of this finding and the differentiation from ischemic colitis should, however, be investigated in a prospective

  19. RESEARCH AND PROGRESS IN REMOVAL OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) IN WASTEWATER TREATMENT PLANTS%污水处理系统中非甾体抗炎镇痛药(NSAIDs)去除的研究

    Institute of Scientific and Technical Information of China (English)

    严清; 高旭; 彭绪亚

    2012-01-01

    PhACs(pharmaceutically active compounds)作为一类“新兴”污染物,由于持续不断地排放及对人类和野生生物的潜在毒性风险,引起了科学界和公众的广泛关注,成为当前环境科学与工程领域的研究热点.NSAIDs( nonsteroidal anti-inflammatory drugs)作为PhACs的一大组成部分,在水环境中普遍检出.本文以非甾体抗炎药( NSAIDs)为研究对象,综述了它们在常规城市污水处理过程中的去除特性.由于污水处理厂的不完全去除是水环境中PhACs的主要来源途径,出水的深度处理工艺的研究与开发势在必行.文章第二部分重点探讨了目前国内外研究的几种去除NSAIDs的不同的深度处理工艺,最后对PhACs污染的研究方向进行了展望.%Pharmaceutical active compounds (PhACs) which was a class of emerging contaminance had raised worldwide concern from scientists and the public during recent years and regarded as "pseudopersistent", due to their continual discharge and their potential toxic effects on wildlife and humans. Because of incomplete treatment of conventional sewage treatment plants, sewage effluents are widely recognized as the main source of PhACs, A large fraction of PhAC pollution in water was composed of nonsteroidal anti-inflammatory drags (NSAIDs) which were usually detected in the aquatic environment. The first part of this paper reviewed the removal characteristics of NSAIDs residues in conventional sewage treatment plants, the second part focuses on the advanced treatment processes that were promising solutions to the ultimate degradation and/or conversion of such medical residues in sewage effluents, finally, the future research direction was prospected.The aim of this paper was to provide theoretical guidance and reference for the research and development of PhACs reduction and advanced treatment technologies.

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

    OpenAIRE

    Mital N Manvar; Dr.T. R. Desai

    2015-01-01

    Currently used steroidal and non steroidal anti-inflammatory drugs have severe side effects. These side effects are very difficult to manage than the disease itself. Hence, there is to search new safe resources to cure such diseases that the use of plant based drugs. This study deals with anti-inflammatory evaluation of the hydroalcoholic extract of Ipomoea aquatica leaves as well as their possible mechanism of action. A carrageenan‐induced rat paw oedema model was used for anti-inflammatory ...

  1. Systematic review of herbals as potential anti-inflammatory agents: Recent advances, current clinical status and future perspectives

    Directory of Open Access Journals (Sweden)

    Sarwar Beg

    2011-01-01

    Full Text Available Many synthetic drugs reported to be used for the treatment of inflammatory disorders are of least interest now a days due to their potential side effects and serious adverse effects and as they are found to be highly unsafe for human assistance. Since the last few decades, herbal drugs have regained their popularity in treatment against several human ailments. Herbals containing anti-inflammatory activity (AIA are topics of immense interest due to the absence of several problems in them, which are associated with synthetic preparations. The primary objective of this review is to provide a deep overview of the recently explored anti-inflammatory agents belonging to various classes of phytoconstituents like alkaloids, glycosides, terpenoids, steroids, polyphenolic compounds, and also the compounds isolated from plants of marine origin, algae and fungi. Also, it enlists a distended view on potential interactions between herbals and synthetic preparations, related adverse effects and clinical trials done on herbals for exploring their AIA. The basic aim of this review is to give updated knowledge regarding plants which will be valuable for the scientists working in the field of anti-inflammatory natural chemistry.

  2. Synthesis, structural characterization, in vitro antimicrobial and anticancer activity studies of ternary metal complexes containing glycine amino acid and the anti-inflammatory drug lornoxicam

    Science.gov (United States)

    Mahmoud, Walaa H.; Mohamed, Gehad G.; El-Dessouky, Maher M. I.

    2015-02-01

    Mixed ligand complexes were synthesized using lornoxicam (LOR) as the primary ligand and glycine amino acid (HGly) as the secondary ligand. They were characterized by FT-IR, UV-Vis, mass, 1H NMR, ESR spectral studies, TG-DTG, X-ray powder diffraction and physical analytical studies. From the molar conductance, magnetic moment and electronic spectral data of the synthesized complexes, general formulae of [M(LOR)2(Gly)]·Xn·yH2O where M = Cr(III) (X = Cl, n = 2, y = 3), Mn(II) (X = Cl, n = 1, y = 1), Co(II) (X = BF4, n = 1, y = 0), Ni(II) (X = Cl, n = 1, y = 0), Cu(II) (X = BF4, n = 1, y = 2) and Zn(II) (X = BF4, n = 1, y = 2) and (M = Fe(II) (X = BF4, n = 1, y = 1) and Fe(III) (X = Cl, n = 2, y = 1) with an octahedral structure were proposed. Thermal analyses show that the complexes lose water molecules of hydration initially and subsequently expel anionic parts and organic ligands in continuous steps. The kinetic parameters namely E, ΔH∗, ΔS∗ and ΔG∗ illustrate the spontaneous association of the metal and ligands in the formation of the complexes. The antimicrobial efficiency of the LOR and HGly ligands and the ternary complexes were examined by in vitro method against various pathogenic bacterial and fungal strains. The metal complexes were found to possess efficient antimicrobial properties compared to lornoxicam and most of these complexes could turn out to be excellent models for the design of effective antibiotic drug substances. Also, the two ligands, in comparison to ternary metal complexes are screened for their anticancer activity against breastic cancer cell line. The results showed that the metal complexes be more active than the parent LOR and glycine free ligands except Cr(III) ternary complex which was found to be inactive.

  3. Pomegranate seed oil nanoemulsions improve the photostability and in vivo antinociceptive effect of a non-steroidal anti-inflammatory drug.

    Science.gov (United States)

    Ferreira, Luana Mota; Sari, Marcel Henrique Marcondes; Cervi, Verônica Ferrari; Gehrcke, Mailine; Barbieri, Allanna Valentini; Zborowski, Vanessa Angonesi; Beck, Ruy Carlos Ruver; Nogueira, Cristina Wayne; Cruz, Letícia

    2016-08-01

    The combination of pomegranate seed oil and ketoprofen in nanoemulsions aiming to improve the antinociceptive effect was evaluated according to the writhing test and Complete Freud's Adjuvant induced paw inflammation in mice. The formulations showed adequate characteristics and improved ketoprofen's photostability against UVC radiation exposure. The dialysis bag technique showed that 100% of the drug was released from the nanoemulsions after 3h and the oil amount had no influence on the releasing. Furthermore, time- and dose-response curves were obtained to determine the antinociceptive effect of the formulations. In the post-test, the nanoemulsion containing ketoprofen significantly reduced abdominal constrictions in time-response curve, showing effect up to 12h while the free ketoprofen showed effect up to 3h. In addition, the blank nanoemulsion presented a reduction of abdominal constriction up to 1h of pre-treatment. Regarding the dose-response curve, the free ketoprofen presents effect at 0.5mg/Kg dose and nanoemulsion at 1.0mg/Kg dose. Time- and dose-response curves were performed to determine the antinociceptive effect in inflammatory pain. After the evaluation of mechanical allodynia testing at the Von Frey Hair, the free ketoprofen showed effect up to 6h while nanoemulsions presented effect up to 10h. Moreover, acute toxicity was performed with ALT and AST activity evaluations and urea levels. After 7 days of treatment, no toxic effects for nanoemulsions were found. In conclusion, ketoprofen-loaded pomegranate seed oil nanoemulsions presented adequate characteristics and a high antinociceptive activity in the animal models tested. PMID:27088191

  4. 2011-2013年非甾体消炎药使用情况分析%Analysis of the Use of Non Steroidal Anti-inflammatory Drugs in 2011-2013

    Institute of Scientific and Technical Information of China (English)

    左拥军; 李永兵

    2015-01-01

    Objective To investigate the use of non steroidal anti-inflammatory drugs (NSAIDs) in 2011-2013. Methods Col ect January 2011 to December 2013 Puyang People's Hospital information system (HIS) NSAIDs drug data,including drug name,specifications,annual sales,sales amount,etc,statistics NSAIDs drug use frequency,average daily cost.Results Before three sort of 2011—2013 NSAIDs drug sales amount are paracetamol and pseudoephe-drine dry suspension,aspirin and celecoxib capsules;2011—2013 NSAIDs DDDs of the both aspirin enteric coated tablets (imports),aspirin enteric coated tablets (made in China),celecoxib celecoxib capsules;celecoxib capsules DDC was the highest,fol owed by Ganmaoling granules;2011—2013 COX-1 selective inhibitor,non selective COX inhibitors of sales amount, DDDs increased year by year;selective COX-2 inhibitor of the consumption sum,DDDs and DDC value is stable. Conclusion NSAIDs drug use is basical y rational,traditional NSAIDs is stil in a dominant position,the specific COX-2 inhibitor and other new NSAIDs drugs have been widely used,has a good application prospect.%目的:探讨2011—2013年非甾体消炎药(NSAIDs)的使用情况。方法收集2011年1月至2013年12月濮阳市人民医院信息系统(HIS)NSAIDs数据,包括药物名称、规格剂型、年销售量、销售金额等,统计NSAIDs的用药频度、日均费用。结果2011—2013年NSAIDs销售金额排序前3名的均为氨酚麻美干混悬剂、阿司匹林肠溶片、塞来昔布胶囊;2011—2013年NSAIDs DDDs排序前3位的均为阿司匹林肠溶片(进口)、阿司匹林肠溶片(国产)、塞来昔布胶囊;塞来昔布胶囊的DDC最高,其次为感冒灵颗粒;2011—2013年COX-1选择性抑制剂、非选择性COX抑制剂的销售金额、DDDs逐年增高;选择性COX-2抑制剂的销售金额、DDDs及DDC比较稳定。结论 NSAIDs使用基本合理,传统NSAIDs仍处于主导地位,特异性COX-2抑制剂等新型NSAIDs

  5. ASSESSMENT OF RISK FOR GASTROINTESTINAL AND CARDIOVASCULAR COMPLICATIONS ASSOCIATED WITH THE USE OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS IN THE CIS POPULATION: PRELIMINARY DATA OF THE CORONA-2 EPIDEMIOLOGICAL SURVEY

    Directory of Open Access Journals (Sweden)

    A. E. Karateev

    2014-01-01

    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are able to effectively control the major symptoms of rheumatic diseases and widely used in real clinical practice. However, they may cause serious gastrointestinal (GI and cardiovascular (CV events. The prevention of these events is based on the estimation of whether risk factors (RFs are present.Objective: to estimate the presence of RFs in patients needing NSAIDs.Subjects and methods. A cross-sectional epidemiological survey was performed, during which 2021 physicians from 9 CIS countries questioned for 2 weeks at least 10 patients needing NSAIDs. The inclusion criterion was severe musculoskeletal pain (>40 mm on a 100-mm visual analogue scale (VAS or use of NSAIDs at the examination. Data were obtained on 21,185 patients (57.5% women and 42.5% men (mean age 50.5±14.1 years who had predominantly dorsalgia (56.6% and osteoarthritis (23.5%. The mean pain value was 62.2±25.2 mm.Results. 1.7, 11.3, and 25.3% of patients had history of gastrointestinal bleeding, ulcer, or dyspepsia, respectively; people over 65 years of age constituted 16.8%; those who took low-dose aspirin (LDA – 20.0%. The total number of patients at high risk for GI events was 29.0%. There were also common CV RFs: myocardial infarction or stroke (7.8%, coronary heart disease (17.8%, hypertension (37.7%, and diabetes mellitus (8.1%. The total number of patients at high risk for CV events (without SCOR assessment was 23.0%. Many high-risk patients who has already used NSAIDs received no effective prevention. Thus, 62.2% of the patients at high GI risk took gastroprotective drugs; 53.2% of those at high CV risk used LDA.Conclusion. A large number of patients needing active analgesic therapy have a serious risk for drug-induced complications. This limits the possibility of using NSAIDs and determines the need for effective prevention or use of alternative methods for analgesia.

  6. The attitudes of owners and veterinary professionals in the United Kingdom to the risk of adverse events associated with using non-steroidal anti-inflammatory drugs (NSAIDs) to treat dogs with osteoarthritis.

    Science.gov (United States)

    Belshaw, Zoe; Asher, Lucy; Dean, Rachel S

    2016-09-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed by veterinary surgeons for the treatment of canine osteoarthritis, and affected dogs may receive these drugs for long periods of time. Whilst short term administration of NSAIDs to dogs is linked to adverse events such as gastrointestinal haemorrhage and renal injury, reports of adverse events associated with their long-term administration are limited in the veterinary literature. This study aimed to investigate the attitudes towards the long term use of NSAIDs for canine osteoarthritis held by three groups who manage osteoarthritic dogs in the United Kingdom: dog owners, veterinary surgeons and veterinary nurses. A qualitative methodology was adopted, using semi-structured interviews and focus groups. Thematic analysis of these data identified three themes: awareness of potential risks; recognition of adverse events; and influence of risk perception on the use of NSAIDs. Awareness of, and concern about, the risk of adverse events associated with NSAID administration to dogs with osteoarthritis was high in all groups, with veterinary surgeons being one of a variety of information sources used by owners to acquire this knowledge. Veterinary surgeons described difficulty in recognising, managing and avoiding adverse events associated with NSAIDs. When adverse events occurred, a wide range of management approaches were adopted ranging from a brief drug respite to permanent cessation of administration of any NSAIDs to that dog. Commonly employed approaches to minimise risk included dose reduction and screening blood tests. This study describes a high level of concern about the risks associated with long term NSAID administration to dogs with osteoarthritis and highlights a diverse range of strategies employed to minimise these risks. The evidence base for these strategies is poor, and this may present a risk to animal welfare if the affected dogs are not receiving adequate analgesia. In order to

  7. Genetically Encoded Azide Containing Amino Acid in Mammalian Cells Enables Site-Specific Antibody-Drug Conjugates Using Click Cycloaddition Chemistry.

    Science.gov (United States)

    VanBrunt, Michael P; Shanebeck, Kurt; Caldwell, Zachary; Johnson, Jeffrey; Thompson, Pamela; Martin, Thomas; Dong, Huifang; Li, Gary; Xu, Hengyu; D'Hooge, Francois; Masterson, Luke; Bariola, Pauline; Tiberghien, Arnaud; Ezeadi, Ebele; Williams, David G; Hartley, John A; Howard, Philip W; Grabstein, Kenneth H; Bowen, Michael A; Marelli, Marcello

    2015-11-18

    Antibody-drug conjugates (ADC) have emerged as potent antitumor drugs that provide increased efficacy, specificity, and tolerability over chemotherapy for the treatment of cancer. ADCs generated by targeting cysteines and lysines on the antibody have shown efficacy, but these products are heterogeneous, and instability may limit their dosing. Here, a novel technology is described that enables site-specific conjugation of toxins to antibodies using chemistry to produce homogeneous, potent, and highly stable conjugates. We have developed a cell-based mammalian expression system capable of site-specific integration of a non-natural amino acid containing an azide moiety. The azide group enables click cycloaddition chemistry that generates a stable heterocyclic triazole linkage. Antibodies to Her2/neu were expressed to contain N6-((2-azidoethoxy)carbonyl)-l-lysine at four different positions. Each site allowed over 95% conjugation efficacy with the toxins auristatin F or a pyrrolobenzodiazepine (PBD) dimer to generate ADCs with a drug to antibody ratio of >1.9. The ADCs were potent and specific in in vitro cytotoxicity assays. An anti Her2/neu conjugate demonstrated stability in vivo and a PBD containing ADC showed potent efficacy in a mouse tumor xenograph model. This technology was extended to generate fully functional ADCs with four toxins per antibody. The high stability of the azide-alkyne linkage, combined with the site-specific nature of the expression system, provides a means for the generation of ADCs with optimized pharmacokinetic, biological, and biophysical properties. PMID:26332743

  8. Drug: D01271 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Therapeutic category: 2649 ATC code: M01AB17 M02AA09 nonsteroidal antiinflammatory drugs (NSAIDs) Therapeut...1 ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS M01A ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS...fexamac (JAN/INN) M02 TOPICAL PRODUCTS FOR JOINT AND MUSCULAR PAIN M02A TOPICAL PRODUCTS FOR JOINT AND MUSCULAR PAI

  9. Primary treatment for temporomandibular joint osteoarthritis. Combination therapy with two consecutive arthrocenteses (steroid injection) followed by mouth-opening exercises and non-steroidal anti-inflammatory drug administration

    International Nuclear Information System (INIS)

    Arthrocentesis is the surgical treatment of choice for temporomandibular joint (TMJ) disorders. Many studies of arthrocentesis have been performed, with excellent clinical outcomes. No previous study has used multiple arthrocenteses to treat the dysfunctional TMJ. This study evaluated the efficacy of two consecutive arthrocenteses (steroid injection) followed by mouth-opening exercises during non-steroidal anti-inflammatory drug (NSAID) administration as a primary treatment for TMJ osteoarthritis. Subjects in this study were selected from a consecutive series of new patients with unilateral moderate to severe TMJ dysfunction at TMD Clinic, Aichi-Gakuin University Hospital during a year. Twenty-eight patients with MRI documentation of osteoarthritis underwent two consecutive arthrocenteses with steroid injection at a 2-week interval followed by mouth-opening exercises and treatment with the NSAID, Etodolac. The patients were postoperatively examined every 2 weeks for 12 weeks. The patients were clinically evaluated on the basis of visual analog scales (0-100) and the range of motion. Factors that affected the clinical outcome of TMJ function were assessed. Of the 28 patients who underwent two consecutive arthrocenteses, 21 (75%) showed substantial improvement on follow-up at 12 weeks. The range of motion (median) increased from 28 mm to 41 mm. Visual analog scale pain-scores on mouth opening and chewing significantly decreased from 50 and 60 to 24 and 22, respectively. The disturbance score for activities of daily life also decreased from 55 to 18. A longer duration of TMJ symptoms before the procedure was found to affect outcome. (author)

  10. Gas chromatography-flame ionization determination of benzaldehyde in non-steroidal anti-inflammatory drug injectable formulations using new ultrasound-assisted dispersive liquid-liquid micro extraction

    International Nuclear Information System (INIS)

    Summary: In this study, simple and efficient ultrasound-assisted dispersive liquid-liquid micro extraction combined with gas chromatography (GC) was developed for the preconcentration and determination of benzaldehyde in injectable formulations of the non-steroidal anti-inflammatory drugs, diclofenac, Vitamin B-complex and Voltaren injection solutions. Fourteen microliters of toluene was injected slowly into 10 mL home-designed centrifuge glass vial containing an aqueous sample without salt addition that was located inside the ultrasonic water bath. The formed emulsion was centrifuged and 2 macro L of separated toluene was injected into a gas chromatographic system equipped with a flame ionization detector (GC-FID) for analysis. Several factors influencing the extraction efficiency as the nature and volume of organic solvent, extraction temperature, ionic strength and centrifugation time were investigated and optimized. Using optimum extraction conditions a detection limit of 0.3 macro g L/sup -1/ and a good linearity in a calibration range of 2.0-1000 macro g L/sup -1/ were achieved for analyte. This proposed method was successfully applied to the analysis of benzaldehyde in three injection formulations and relative standard deviation (RSD) of analysis (n=3), before spiking with standard benzaldehyde were 3.3, 2.0 and 1.3% for Na-diclofenac, vitamin B-complex and voltaren, respectively and after spiking of standard benzaldehyde (0.3 mg L/sup -1/), the RSD were 6.5, 3.6 and 2.8% for Na-diclofenac, vitamin B-complex and voltaren, respectively. (author)

  11. Nonsteroidal anti-inflammatory drug (NSAID associated fixed drug eruption (FDE in children attending dermatology OPD of a tertiary care hospital of Eastern India: a cross-sectional observational study

    Directory of Open Access Journals (Sweden)

    Ranjita Santra

    2014-02-01

    Conclusions: 20 new cases of NSAID-induced FDEs over a period of 6 months suggest that this is not a rare entity as was presumed. There is a growing need for a strict monitoring of such off label offending drugs, known to cause ADRs especially among pediatric patients to ensure safe and rational therapeutics. [Int J Basic Clin Pharmacol 2014; 3(1.000: 211-214

  12. NSAIDs (Nonsteroidal Anti-inflammatory Drugs)

    Science.gov (United States)

    ... High Impact Rheumatology Faculty Rheumatology Image Library Image Competition Recorded Sessions Webinar Archives Certification RhMSUS RhMSUS Process ... For most people with arthritis, being physically active, eating right and keeping a healthy weight are good ...

  13. Exploring Drug Diffusion through a Membrane: A Physical Chemistry Experiment for Health and Life Sciences Undergraduate Students

    Science.gov (United States)

    Ribeiro, Isabel A. C.; Faustino, Ce´lia M. C.; Guedes, Rita C.; Alfaia, Anto´nio J. I.; Ribeiro, Maria H. L.

    2015-01-01

    The transport of molecules across biological membranes are critical for most cellular processes. Membrane permeability is also a key determinant for drug absorption, distribution, and elimination. Diffusion, that is, the migration of matter down a concentration gradient, is a simple mechanism by which both endogenous and drug molecules can enter…

  14. Medicinal plants with anti-inflammatory activities.

    Science.gov (United States)

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

    2016-06-01

    Medicinal plants have been the main remedy to treat various ailments for a long time and nowadays, many drugs have been developed from traditional medicine. This paper reviews some medicinal plants and their main constituents which possess anti-inflammatory activities useful for curing joint inflammation, inflammatory skin disorders, cardiovascular inflammation and other inflammatory diseases. Here, we provide a brief overview of quick and easy reading on the role of medicinal plants and their main constituents in these inflammatory diseases. We hope that this overview will shed some light on the function of these natural anti-inflammatory compounds and attract the interest of investigators aiming at the design of novel therapeutic approaches for the treatment of various inflammatory conditions. PMID:26221780

  15. Green chemistry: A tool in Pharmaceutical Chemistry

    Directory of Open Access Journals (Sweden)

    Smita Talaviya

    2012-07-01

    Full Text Available Green chemistry expresses an area of research developing from scientific discoveries about pollution awareness and it utilizes a set of principles that reduces or eliminates the use or generation of hazardous substances in all steps of particular synthesis or process. Chemists and medicinal scientists can greatly reduce the risk to human health and the environment by following all the valuable principles of green chemistry. The most simple and direct way to apply green chemistry in pharmaceuticals is to utilize eco-friendly, non-hazardous, reproducible and efficient solvents and catalysts in synthesis of drug molecules, drug intermediates and in researches involving synthetic chemistry. Microwave synthesis is also an important tool of green chemistry by being an energy efficient process.

  16. Surface chemistry essentials

    CERN Document Server

    Birdi, K S

    2013-01-01

    Surface chemistry plays an important role in everyday life, as the basis for many phenomena as well as technological applications. Common examples range from soap bubbles, foam, and raindrops to cosmetics, paint, adhesives, and pharmaceuticals. Additional areas that rely on surface chemistry include modern nanotechnology, medical diagnostics, and drug delivery. There is extensive literature on this subject, but most chemistry books only devote one or two chapters to it. Surface Chemistry Essentials fills a need for a reference that brings together the fundamental aspects of surface chemistry w

  17. Extracting physical chemistry from mechanics: a new approach to investigate DNA interactions with drugs and proteins in single molecule experiments

    CERN Document Server

    Rocha, M S

    2015-01-01

    In this review we focus on the idea of establishing connections between the mechanical properties of DNAligand complexes and the physical chemistry of DNA-ligand interactions. This type of connection is interesting because it opens the possibility of performing a robust characterization of such interactions by using only one experimental technique: single molecule stretching. Furthermore, it also opens new possibilities in comparing results obtained by very different approaches, in special when comparing single molecule techniques to ensemble-averaging techniques. We start the manuscript reviewing important concepts of the DNA mechanics, from the basic mechanical properties to the Worm-Like Chain model. Next we review the basic concepts of the physical chemistry of DNA-ligand interactions, revisiting the most important models used to analyze the binding data and discussing their binding isotherms. Then, we discuss the basic features of the single molecule techniques most used to stretch the DNA-ligand complex...

  18. Simultaneous analysis of non-steroidal anti-inflammatory drugs and estrogenic hormones in water and wastewater samples using gas chromatography-mass spectrometry and gas chromatography with electron capture detection

    Energy Technology Data Exchange (ETDEWEB)

    Migowska, Natalia; Caban, Magda; Stepnowski, Piotr; Kumirska, Jolanta, E-mail: kumirska@chem.univ.gda.pl

    2012-12-15

    Non-steroidal anti-inflammatory drugs are the group of pharmaceuticals that is most often found in the environment, whereas estrogenic hormones are considered to be potent endocrine disruptors. However, the fate and persistence of these compounds in the environment are still unclear. In this study we propose two approaches for determining these compounds in environmental water samples: GC-MS using time windows and operating in selected ion-monitoring mode (SIM) and, for the first time, gas chromatography with electron capture detection (GC-ECD). The identification criteria of both methods fulfilled the requirements of Directive 2002/657/EC. The use of time windows improved the sensitivity of GC-MS measurements. In GC-MS analysis the pharmaceuticals were determined as trimethylsilyl, in GC-ECD as pentafluoropropionyl derivatives. The influence of such parameters as the type of reagent, type of solvent, reaction time, reaction temperature and microwave irradiation in a household microwave oven on the efficacy of silylation was investigated. Derivatization using N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and 1% trimethylchlorosilane (TMCS) in pyridine (1:1, v/v) for 30 min in 60 Degree-Sign C was found to be optimal. Optimization of the solid phase extraction procedure (SPE) confirmed that the application of Oasis HLB cartridges, the acidification of loading samples to pH 2 and the use of methanol as eluent gave the best absolute recoveries (ARs) of the target compounds. The following ARs of all the compounds were achieved: 58.2-106.8% in influent wastewater, 77.8-103.4% in effluent wastewater and 81.2-101.9% in surface water samples. Validation of the SPE-GC-MS method enables 13 pharmaceuticals to be determined with MDLs between 3.3 and 343.6 ng/L, depending on the analytes and matrices. GC-ECD analysis enables the determination of 6 pharmaceuticals in surface water samples with MDLs between 0.7 and 5.4 ng/L. The proposed methods were successfully used for

  19. Online eluent-switching technique coupled anion-exchange liquid chromatography–ion trap tandem mass spectrometry for analysis of non-steroidal anti-inflammatory drugs in pig serum.

    Science.gov (United States)

    Chang, Kai Chun; Lin, Jyh Shiun; Cheng, Cheanyeh

    2015-11-27

    A novel method for online extraction, pH-gradient separation, and analysis of nine non-steroidal anti-inflammatory drugs (NSAIDs) was developed by coupling online eluent-switching technique to single anion-exchange chromatographic column/ion trap mass spectrometer (MS) and used for monitoring NSAIDs residues in pig serum. A neutral eluent and a pH-gradient eluent were used for extraction and separation of NSAIDs, respectively. Each of nine NSAIDs has an MS precursor ion of either [M−H]− or [M−Na]−. The extracted ion chromatogram for a specific product ion of each NSAID was used for its quantitative analysis. The dynamic linear ranges of calibration curves were all 0–200 ng mL−1 (R2 > 0.9950). The analysis accuracies estimated by spiking standard concentrations at 20, 100, and 200 ng mL−1 were 80.5–99.9%. The corresponding intra-day and inter-day precisions (RSD%) were 2.5–14.5% and 2.9–15.2%, respectively. The limit of detection/limit of quantitation of NSAIDs were 1.3/4.3, 0.5/1.6, 0.2/0.5, 2.5/8.2, 1.5/4.9, 0.6/2.1, 0.6/2.0, 0.5/1.7, and 0.6/2.1 ng mL−1 for carprofen, diclofenac, flunixin, ibuprofen, ketoprofen, meclofenamic acid sodium, mefenamic acid, niflumic acid, and tolfenamic acid, respectively. After 1 h injection of a dose containing 2 mg kg−1 weight pig of flunixin and tolfenamic acid to the pigs, a residue amount of 3480 ± 36 ng mL−1 and 431 ± 13 ng mL−1, respectively, was reached for the incurred pig serum specimens and both residues were reduced to about 20 ng mL−1 at the time of 24 h. PMID:26601710

  20. Simultaneous analysis of non-steroidal anti-inflammatory drugs and estrogenic hormones in water and wastewater samples using gas chromatography–mass spectrometry and gas chromatography with electron capture detection

    International Nuclear Information System (INIS)

    Non-steroidal anti-inflammatory drugs are the group of pharmaceuticals that is most often found in the environment, whereas estrogenic hormones are considered to be potent endocrine disruptors. However, the fate and persistence of these compounds in the environment are still unclear. In this study we propose two approaches for determining these compounds in environmental water samples: GC–MS using time windows and operating in selected ion-monitoring mode (SIM) and, for the first time, gas chromatography with electron capture detection (GC–ECD). The identification criteria of both methods fulfilled the requirements of Directive 2002/657/EC. The use of time windows improved the sensitivity of GC–MS measurements. In GC–MS analysis the pharmaceuticals were determined as trimethylsilyl, in GC–ECD as pentafluoropropionyl derivatives. The influence of such parameters as the type of reagent, type of solvent, reaction time, reaction temperature and microwave irradiation in a household microwave oven on the efficacy of silylation was investigated. Derivatization using N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and 1% trimethylchlorosilane (TMCS) in pyridine (1:1, v/v) for 30 min in 60 °C was found to be optimal. Optimization of the solid phase extraction procedure (SPE) confirmed that the application of Oasis HLB cartridges, the acidification of loading samples to pH 2 and the use of methanol as eluent gave the best absolute recoveries (ARs) of the target compounds. The following ARs of all the compounds were achieved: 58.2–106.8% in influent wastewater, 77.8–103.4% in effluent wastewater and 81.2–101.9% in surface water samples. Validation of the SPE–GC–MS method enables 13 pharmaceuticals to be determined with MDLs between 3.3 and 343.6 ng/L, depending on the analytes and matrices. GC–ECD analysis enables the determination of 6 pharmaceuticals in surface water samples with MDLs between 0.7 and 5.4 ng/L. The proposed methods were successfully

  1. Pharmacokinetics of aspirin and salicylate in relation to inhibition of arachidonate cyclooxygenase and antiinflammatory activity.

    OpenAIRE

    Higgs, G. A.; Salmon, J. A.; Henderson, B; Vane, J R

    1987-01-01

    Among the nonsteroid antiinflammatory drugs there is generally a close correlation between the potency of their inhibition of arachidonate cyclooxygenase, and thus prostaglandin production, and their antiinflammatory activity. One anomaly in this generalization is that whereas aspirin and salicylate are equipotent as antiinflammatory agents, salicylate is less active than aspirin in inhibiting prostaglandin production in vitro. Using rats, we have now measured the concentrations of aspirin an...

  2. ANTI-INFLAMMATORY AND DIURETIC EFFECT OF PLANT EXTRACTS OF PSEUDARTHRIA VISCIDA (L) WEIGHT & ARN.

    OpenAIRE

    Saravanan C.; Shantha kumar S.; Anandan R.; Narayanaswamy V.B.; Varunraj S.

    2010-01-01

    The ethanolic extracts prepared from aerial parts of Pseudarthria viscida was studied for anti-inflammatory and diuretic activities in albino rats. The results obtained were compared with that of standard drug indomethacin and frusemide for their anti-inflammatory and diuretic activities respectively. The present study demonstrated the diuretic effect of P.viscida by increasing the excretion of Na+, K+ and Cl- ions in the urine. The extract also showed significant anti-inflammatory effect by ...

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

    Directory of Open Access Journals (Sweden)

    Chan Kai-Ming

    2009-10-01

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

  4. Fluorine in medicinal chemistry: a century of progress and a 60-year retrospective of selected highlights.

    Science.gov (United States)

    Filler, Robert; Saha, Rituparna

    2009-08-01

    This perspective explores the origins of both fluorine and medicinal chemistry a century ago and traces the early history of the intersection of these areas and the subsequent roles that fluorine has played in advancing medicinal innovations and diagnoses during the past 60 years. The overview highlights remarkable breakthroughs in many diverse areas of medicinal chemistry, including inter alia, anesthetics, steroidal and nonsteroidal anti-inflammatory drugs, anticancer and antiviral agents, CNS medications, antibacterials and cholesterol biosynthesis inhibitors. The increasing use of fluorine-18-labeled radiotracers in PET for diagnostic imaging of the brain, heart and in oncology is briefly presented. The signature roles of fluorine in medicinal chemistry are now firmly established. The presence of fluorine in pharmaceuticals has had a major impact on a plethora of important medical applications, such as those cited above. Fluorine will very likely continue to contribute significantly by playing multifaceted roles in enhancing future medical advances. PMID:21426080

  5. Chemopreventive response of diclofenac, a non-steroidal anti-inflammatory drug in experimental carcinogenesis Respuesta quimiopreventiva del diclofenaco, un fármaco antiinflamatorio no esteroideo en la carcinogénesis de colon experimental

    Directory of Open Access Journals (Sweden)

    M. Kaur Saini

    2009-12-01

    Full Text Available The chemopreventive response was evaluated of nonsteroidal anti-inflammatory drug, Diclofenac, a preferential cyclooxygenase-2 (COX-2 inhibitor in 1,2-dimethyhydrazine (DMH-induced colon cancer in rat model. The signs of neoplasm were evident in the animals receiving 30mg of DMH per kg body weight in a weekly s.c injection for six weeks. The putative biomarker of carcinogenesis was visible in the form of multiple plaque lesions in DMH treatment and then regression seen in those animals which also received an oral dose of Diclofenac, 8 mg/kg body weight whereas no such macroscopic neoplastic lesions were seen in the animals receiving Diclofenac only or the control animals receiving the vehicle of the drug. Histopathological results showed the presence of early aberrant changes in the form of severe dysplasia and also numerous crypt fissions in the apical surface of the colonic mucosa. A very high expression of COX-2 was seen in the colonic epithelium of DMH-treated rats, as analyzed by immunohistochemistry. Also, the apoptotic events were assessed by terminal deoxynucleotidyl dUTP nick end labeling (TUNEL assay, where the DMH group shows few number of TUNEL positive cells which dramatically increased in the Diclofenac treatment. The results suggest that Diclofenac could be an effective chemopreventive agent in colon cancer, where perhaps apoptosis plays a very dominant end effect in cancer cell killings.Se evaluó la respuesta quimiopreventiva del fármaco antiinflamatorio no esteroideo, diclofenaco, un inhibidor preferente de la ciclooxigenasa-2 (Cox-2, en el cáncer de colon inducido por 1,2-dimetilhidracina (DMH en un modelo de rata. Los signos de neoplasia fueron evidentes en los animales que recibieron 30 mg de DMH por kg de peso corporal mediante inyecciones s.c. semanales durante 6 semanas. El biomarcador putativo de la carcinogénesis fue visible en la forma de múltiples lesiones en placas con el tratamiento de DMH y la posterior regresi

  6. Drug: D07888 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07888 Drug Eltenac (INN); Telzenac (TN) C12H9Cl2NO2S 300.9731 302.1764 D07888.gif Antiinflammatory [veterin...ary] nonsteroidal antiinflammatory drugs (NSAIDs) cyclooxygenase-2 (COX-2) inhibito

  7. Drug: D01963 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 3.gif Analgesic; Anti-inflammatory Nonsteroidal anti-inflammatory drugs (NSAIDs) Acetic acid derivatives CAS...D01963 Drug Ibufenac (JAN/USAN/INN); Dytransin (TN) C12H16O2 192.115 192.2542 D0196

  8. Drug: D04000 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D04000 Drug Enlimomab (USAN/INN) Anti-inflammatory; Monoclonal antibody CD54 (ICAM-1) [HSA:3383] ... toxicity hsa04670(3383) Leukocyte transendothelial migration ... Target-based classification of drugs [BR:br08310] ...

  9. Anti-inflammatory properties of cryptolepine.

    Science.gov (United States)

    Olajide, Olumayokun A; Ajayi, Abayomi M; Wright, Colin W

    2009-10-01

    Cryptolepine is the major alkaloid of the West African shrub, Cryptolepis sanguinolenta. Cryptolepine has been shown to inhibit nitric oxide production, and DNA binding of Nuclear Factor-kappa B following inflammatory stimuli in vitro. In order to validate the anti-inflammatory property of this compound in vivo, we investigated its effects on a number of animal models of inflammation. Cryptolepine (10-40 mg/kg i.p.) produced significant dose-dependent inhibition of the carrageenan-induced rat paw oedema, and carrageenan-induced pleurisy in rats. These effects were compared with those of the non-steroidal anti-inflammatory drug indomethacin (10 mg/kg). At doses of 10-40 mg/kg i.p., cryptolepine inhibited lipopolysaccharide (LPS)-induced microvascular permeability in mice in a dose-related fashion. Oral administration of up to 40 mg/kg of the compound for four consecutive days did not induce gastric lesion formation in rats. Analgesic activity was also exhibited by cryptolepine through a dose-related (10-40 mg/kg i.p.) inhibition of writhing induced by i.p. administration of acetic acid in mice. The results of this study reveal that cryptolepine possesses in vivo anti-inflammatory activity. PMID:19288476

  10. One-Step "Click Chemistry"-Synthesized Cross-Linked Prodrug Nanogel for Highly Selective Intracellular Drug Delivery and Upregulated Antitumor Efficacy.

    Science.gov (United States)

    Zhang, Yu; Ding, Jianxun; Li, Mingqiang; Chen, Xin; Xiao, Chunsheng; Zhuang, Xiuli; Huang, Yubin; Chen, Xuesi

    2016-05-01

    Polymeric prodrugs formed by the conjugation of drugs onto polymers have shown great promise in cancer therapy because of the enhancement of water solubility, elimination of premature drug release, and the improvement of pharmacokinetics. To integrate the two advantages of upregulated stability during circulation and selective release of drug in cancer cells, a pH and reduction dual-sensitive prodrug nanogel (CLP) was synthesized via a simple one step "click chemistry". CLP was spherically shaped with a uniform diameter of 60.6 ± 13.7 nm and exhibited great stability in size against large volume dilution, high salt concentration, and long-time incubation in phosphate-buffered saline. Owing to the presence of hydrazone-bonded doxorubicin (DOX) and disulfide cross-linker, CLP released minimal amount (7.8%) of drug under normal physiological pH (i.e., 7.4) condition. But it released 85.5% of the loaded DOX at endosomal pH (i.e., 5.5) plus the presence of 5.0 mM GSH in 120 h. CLP could be effectively internalized by tumor cells and subsequently release DOX in the intracellular environment, resulting in effective proliferation inhibition of HeLa and MCF-7 cells. Furthermore, compared with free DOX and non-cross-linked prodrug micelle (NCLP), CLP accumulated more in tumor site but less in the normal organs, so that CLP performed the enhanced antitumor efficiency and reduced side-toxicities toward the MCF-7 human breast cancer xenograft nude mouse model. With convenient fabrication, favorable stability, controlled release properties, optimized biodistribution, and enhanced suppression of tumor growth, CLP held great potential for optimal antitumor therapy. PMID:27077549

  11. Anti-inflamatórios não esteroides: Efeitos cardiovasculares, cérebro-vasculares e renais Antiinflamatorios no esteroides: efectos cardiovasculares, cerebrovasculares y renales Nonsteroidal anti-inflammatory drugs: cardiovascular, cerebrovascular and renal effects

    Directory of Open Access Journals (Sweden)

    Michel Batlouni

    2010-04-01

    inhibidores de la ciclo-oxigenase (COX, selectivos o no. Los AINEs no selectivos son los más antiguos, y designados como tradicionales o convencionales. Los AINEs selectivos para la COX-2 se designan COXIBEs. En los últimos años, ha sido cuestionada la seguridad del uso de los AINEs en la práctica clínica, particularmente de los inhibidores selectivos de la COX-2. Las evidencias sobre el aumento del riesgo cardiovascular con el uso de AINEs son todavía incompletas, debido a la ausencia de ensayos randomizados y controlados con poder para evaluar desenlaces cardiovasculares relevantes. Sin embargo, los resultados de estudios clínicos prospectivos y de metaanálisis indican que los inhibidores selectivos de la COX-2 ejercen importantes efectos cardiovasculares adversos, que incluyen aumento del riesgo de infarto del miocardio, accidente cerebrovascular, insuficiencia cardiaca, insuficiencia renal y hipertensión arterial. El riesgo de estos efectos adversos es mayor en pacientes con historia previa de enfermedad cardiovascular o con alto riesgo para desarrollarla. En estos pacientes, el uso de inhibidores de la COX-2 debe ser limitado a aquellos para los que no hay alternativa apropiada y, aun así, solamente en dosis bajas y por el menor tiempo necesario. Aunque los efectos adversos más frecuentes se relacionen a la inhibición selectiva de la COX-2, la ausencia de selectividad para esta isoenzima no elimina completamente el riesgo de eventos cardiovasculares, de modo que todos los fármacos del largo espectro de los AINEs se deben prescribir solamente tras consideración del balance riesgo/beneficio.The nonsteroidal anti-inflammatory drugs (NSAIDs are among the most often prescribed drugs in the world. This heterogeneous class of drugs includes aspirin and several other selective or non-selective cyclooxygenase (COX inhibitors. The non-selective NSAIDs are the oldest ones and are called traditional or conventional NSAIDs. The selective NSAIDs are called COX-2

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

    Directory of Open Access Journals (Sweden)

    Gajendra Naidu

    2014-03-01

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

  13. Antioxidant and antiinflammatory activities of the flowers of Tabernaemontana coronaria (l R.BR

    Directory of Open Access Journals (Sweden)

    Thambi Priya

    2006-01-01

    Full Text Available The ethanol and aqueous extracts of Tabernaemontana coronaria flowers possessed significant in vitro superoxide, hydroxyl radicals, nitric oxide scavenging, and lipid peroxidation inhibiting activities. The antiinflammatory activity of the ethanol extract was evaluated by carrageenan-induced acute and formalin-induced chronic antiinflammatory models in mice. The extract showed remarkable antiinflammatory activity in both models, comparable to the standard reference drug diclofenac. The results suggest that the antiinflammatory activity of the ethanol extract of T. coronaria is possibly attributed to its free radical scavenging properties.

  14. The present status of anti-inflammatory agents in dermatology.

    Science.gov (United States)

    Stüttgen, G

    1988-01-01

    Many classes of drugs exert anti-inflammatory activity through mechanisms which affect all or part of the inflammatory process. Some of these agents are beneficial in the practice of dermatology, while others, such as penicillamine, mast cell blockers and serotonin antagonists, find little or no application. Corticosteroids, for example, are nonspecific in their anti-inflammatory effects and remain a mainstay of therapy, despite their side effect profile. Other drugs, such as the non-steroidal anti-inflammatory agents or gold, can be used in the treatment of diseases associated with rheumatic or autoimmune states. Moreover, antihistamines play an important role in the control of itching, but are mainly indicated in controlling non-dermatological allergic sequelae. Interestingly, chloroquine and dapsone, which were originally developed for use in malaria prophylaxis and leprosy, respectively, have value in treating a wide range of dermatological conditions via mechanisms which include the inhibition of P-450 isoenzymes. In diseases characterised by disturbed cornification (e.g. psoriasis pustulosa), retinoids are of particular value. These drugs are thought to act by inhibition of collagenases, proteases and granulocyte migration. Undoubtedly, further investigation of drug classes such as oxygen radical controllers and immunomodulators will clarify their mechanisms and establish their therapeutic usefulness among the anti-inflammatory agents now available for dermatological use. PMID:3076131

  15. Evaluation of the effects of tumor necrosis factor-а inhibitors versus nonsteroidal anti-inflammatory drugs on spinal inflammatory changes from magnetic resonance imaging data in patients with ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Ekaterina Yuryevna Tyukhova

    2012-01-01

    Full Text Available Objective: to evaluate the time course of inflammatory changes (ICs in the spinal column and sacroiliac articulations (SIA from magnetic resonance imaging (MRI data in patients with ankylosing spondylitis (AS during treatment with tumor necrosis factor-α (TNF-а inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs, which were first used. Subjects and methods. MRI of the most painful part of the spine and SIA was performed in 58 patients with AS at baseline and 12 weeks later. MRI T2 STIR and T1 (SIGNA EXCITE, General Electrics; 0.35 T, matrix 288x192 regimens were used. Bone marrow edema was regarded as active inflammation. Active ICs in the most painful part of the spine were assessed by the AS spinal MRI activity (ASspiMRI-a score and those in SIA by the Leeds scoring system. MRI was interpreted independently by two specialists; one of them did not know about the number of a visit and performed therapy. The patients were divided into two groups: 1 those who first used TNF-а inhibitors and 2 those who were first given NSAIDs. Both groups were matched for demographic indicators. Results. In both groups, the mean pain level in the spinal part under study decreased significantly in both groups: from 5.7±1.7 to 2.3±1.8 in the TNF-а inhibitor group (p = 0.000006 and from 4.8±2.3 to 2.6±2.3 in the NSAID group (р = 0.00001. After 12 weeks of treatment, the patients receiving TNF-а inhibitors (n = 28 showed a considerable reduction in the MRI signs of spinal ICs from 4.8±2.3 to 1.6±1.6 (p = 0.00001; moreover, this trend was more pronounced in patients (n = 17 with more baseline IC foci (≥ 5 than in those (n = 11 with fewer baseline IC foci (< 5 (the mean а was 4.3±1.5 and 1.6±1.4, respectively; р = 0.0003. In the patients taking NSAIDs (n = 30, the decrease in the number of spinal MRI ICs (from 2.8±2.5 to 2.3±2.1 was insignificant (p = 0.17. After 12 weeks, regression of active sacroiliitis was noted in 28 patients from the TNF

  16. Impact of concomitant low-dose aspirin on the safety and tolerability of naproxen and esomeprazole magnesium delayed-release tablets in patients requiring chronic nonsteroidal anti-inflammatory drug therapy: an analysis from 5 Phase III studies.

    Science.gov (United States)

    Angiolillo, Dominick J; Datto, Catherine; Raines, Shane; Yeomans, Neville D

    2014-07-01

    Patients receiving chronic nonsteroidal anti-inflammatory drugs (NSAIDs) and concomitant low-dose aspirin (LDA) are at increased risk of gastrointestinal (GI) toxicity. A fixed-dose combination of enteric-coated (EC) naproxen and immediate-release esomeprazole magnesium (NAP/ESO) has been designed to deliver a proton-pump inhibitor followed by an NSAID in a single tablet. To examine safety data from 5 Phase III studies of NAP/ESO in LDA users (≤ 325 mg daily, administered at any time during the study), and LDA non-users, data were analyzed from 6-month studies assessing NAP/ESO versus EC naproxen in patients with osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis (n = 2), 3-month studies assessing NAP/ESO vs celecoxib or placebo in patients with knee osteoarthritis (n = 2), and a 12-month, open-label, safety study of NAP/ESO (n = 1). In an analysis of two studies, incidences of endoscopically confirmed gastric ulcers (GUs) and duodenal ulcers (DUs) were summarized by LDA subgroups. In the pooled analysis from all five studies, incidences of treatment-emergent adverse events (AEs) (including prespecified NSAID-associated upper GI AEs and cardiovascular AEs), serious AEs, and AE-related discontinuations were stratified by LDA subgroups. Overall, 2,317 patients received treatment; 1,157 patients received NAP/ESO and, of these, 298 received LDA. The cumulative incidence of GUs and DUs in the two studies with 6-month follow-up was lower for NAP/ESO vs EC naproxen in both LDA subgroups [GUs: 3.0 vs 27.9%, respectively, for LDA users, 6.4 vs 22.4%, respectively, for LDA non-users (both P < 0.001); DUs: 1.0 vs 5.8% for LDA users, 0.6 vs 5.3% for LDA non-users]. The incidence of erosive gastritis was lower in NAP/ESO- vs EC naproxen-treated patients for both LDA users [18.2 vs 36.5%, respectively (P = 0.004)] and LDA non-users [19.8 vs 38.5%, respectively (P < 0.001)]. Among LDA users, incidences of NSAID-associated upper GI AEs were: NAP/ESO, 16.1%; EC

  17. Achados clínicos da sensibilidade a analgésicos e antiinflamatórios não-hormonais Clinical findings of sensitivity to analgesics and nonsteroidal antiinflammatory drugs

    Directory of Open Access Journals (Sweden)

    N.A. Rosário

    2000-09-01

    Full Text Available Analgésicos (ANA e antiinflamatórios não-hormonais (AINH podem causar reações que simulam as alérgicas ou agravam asma e urticária. OBJETIVO: Verificar as manifestações clínicas de pacientes com história de reação a analgésicos (ANA e antiinflamatórios não-hormonais (AINH. MÉTODO: Análise e retrospectiva de prontuários de 183 pacientes com história de sensibilidade a ANA e AINH. RESULTADOS: Eram 93 (51% pacientes do sexo feminino e 90 (49% do sexo masculino; 63 (34% com idade igual ou inferior a 15 anos e 120 (66% com idade superior a 15 anos. Havia um predomínio de pacientes do sexo feminino com idade superior a 15 anos que foi estatisticamente significativo (p = 0,02. A idade por ocasião da primeira reação com medicamentos variou de 7 meses a 65 anos (média de 15 anos. Testes cutâneos para aeroalérgenos foram positivos para pelo menos um alérgeno testado em 100/138 (72%. As manifestações clínicas encontradas foram angioedema (86%, urticária (39%, reações sistêmicas (30%, reações nasais e oculares (15% e crise de asma (14%. Não havia diferença quanto à freqüência de sintomas com relação à idade. Havia história familiar de sensibilidade a ANA/AINH em sete pacientes (3,8%. As doenças associadas foram rinite (55%, urticária crônica (47%, asma (37% e conjuntivite (17,5%. As drogas causavam crise de asma com maior freqüência em asmáticos do que em não asmáticos (p = 0,001. Reações repetidas a mais de uma droga ocorreram em 107 (58% pacientes. CONCLUSÕES: Reações a ANA e AINH foram freqüentes em atópicos; crianças e adultos reagiam igualmente; foram mais comuns em adultos do sexo feminino; angioedema palpebral foi a manifestação clínica mais freqüente; broncoespasmo foi mais comum nos asmáticos e a maioria dos pacientes tinha reações repetidas a mais de uma droga.BACKGROUND: Analgesics (ANA and nonsteroidal antiinflammatory drugs (NSAID may simulate an allergic reaction or aggravate

  18. Anti-inflammatory effects ofMorninga oleifera lam extract in rats

    Institute of Scientific and Technical Information of China (English)

    Georgewill OA; Georgewill UO; Nwankwoala RNP

    2010-01-01

    Objective:To investigate the acute and delayed anti-inflammatory effects ofMorning oleifera lam (MOL) crude methanolic extract.Methods: Compared the anti-inflammatory effects of MOL with that of standard anti-inflammatory agents like indomethacin and hydrocortisone using Air Pouch Model.Results: In both acute and delayed inflammation, the MOL extract produced dose dependent anti-inflammatory effect [acute IC50= (399.30 ±5.43) mg/kg; delayed IC50= (510.26±4.53) mg/kg]. The order of anti-inflammatory potency for the three drugs was hydrocortisone> indomethacin > MOL.Conclusions: These observations indicate that MOL possesses potential anti-inflammatory property.

  19. Drug: D01767 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01767.gif Anti-inflammatory ATC code: M01AC02 nonsteroidal antiinflammatory drugs (NSAIDs) cyclooxygenase-1 (COX-1) inhibitor [HSA...D01767 Drug Tenoxicam (JAN/USAN/INN); Tilcotil (TN) C13H11N3O4S2 337.0191 337.3741 ...:5742] [KO:K00509]; cyclooxygenase-2 (COX-2) inhibitor [HSA:5743] [KO:K11987] hsa0059...0(5742+5743) Arachidonic acid metabolism Enzyme: CYP2C9 [HSA:1559] map07219 Cyclo...STEM M01 ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS M01A ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROID

  20. Synthetic Methods, Chemistry, and the Anticonvulsant Activity of Thiadiazoles

    Directory of Open Access Journals (Sweden)

    Bhawna Sharma

    2013-01-01

    Full Text Available The chemistry of heterocyclic compounds has been an interesting field of study for a long time. Heterocyclic nucleus 1,3,4-thiadiazole constitutes an important class of compounds for new drug development. The synthesis of novel thiadiazole derivatives and investigation of their chemical and biological behavior have gained more importance in recent decades. The search for antiepileptic compounds with more selective activity and lower toxicity continues to be an active area of intensive investigation in medicinal chemistry. During the recent years, there has been intense investigation of different classes of thiadiazole compounds, many of which possess extensive pharmacological activities, namely, antimicrobial activity, anticonvulsant, antifungal antidiabetic, anti-inflammatory, antioxidant, and antituberculosis activities, and so forth. The resistance towards available drugs is rapidly becoming a major worldwide problem. The need to design new compounds to deal with this resistance has become one of the most important areas of research today. Thiadiazole is a versatile moiety that exhibits a wide variety of biological activities. Thiadiazole moiety acts as “hydrogen binding domain” and “two-electron donor system.” It also acts as a constrained pharmacophore. On the basis of the reported literature, we study here thiadiazole compounds and their synthetic methods chemistry and anticonvulsant activity.

  1. Cyclization of a cell-penetrating peptide via click-chemistry increases proteolytic resistance and improves drug delivery.

    Science.gov (United States)

    Reichart, Florian; Horn, Mareike; Neundorf, Ines

    2016-06-01

    In this work we report synthesis and biological evaluation of a cell-penetrating peptide (CPP), that is partly cyclized via a triazole bridge. Recently, beneficious properties have been reported for cyclized peptides concerning their metabolic stability and intracellular uptake. A CPP based on human calcitonin was used in this study, and side chain cyclization was achieved via copper catalyzed alkyne-azide click reaction. Cell viability studies in several cell-lines revealed no cytotoxic effects. Furthermore, efficient uptake in breast cancer MCF-7 cells could be determined. Moreover, preliminary studies using this novel peptide as drug transporter for daunorubicin were performed. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID:27197760

  2. Erdosteine: antitussive and anti-inflammatory effects.

    Science.gov (United States)

    Dal Negro, Roberto W

    2008-01-01

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

  3. Drug: D06606 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06606 Drug Ibuprofen lysine ... (USAN); Solufenum; Neoprofen (TN) C13H18O2. C6H14N2O2 352.2362 352. ... ac preparations C01EB16 Ibuprofen D06606 Ibuprofen lysine ... (USAN) USP drug classification [BR:br08302] Analge ... Anti-inflammatory Drugs Ibuprofen D06606 Ibuprofen lysine ... (USAN) Anti-inflammatory Agents Nonsteroidal Anti- ...

  4. Intestinal toxicity of non-steroideal anti-inflammatory drugs with differential cyclooxigenase inhibition selectivity Toxicidad intestinal de los fármacos antiinflamatorios no esteroideos con una selectividad diferenciada en la inhibición de la ciclooxigenasa

    Directory of Open Access Journals (Sweden)

    S. Chopra

    2007-10-01

    Full Text Available The present study was designed to investigate the gastrointestinal side effects of cycloxygenase (COX inhibitor with varying selectivity, called the non-steroidal antiinflammatory drugs (NSAIDs viz., non-selective COX-1 & 2 inhibitor -aspirin, prefentially selective COX-2 inhibitor- nimesulide and highly selective COX-2 inhibitor- celecoxib. Treatment with NSAIDs exhibited a decrease in the activity of rat intestinal brush border membrane associated enzymes such as sucrase, lactase, maltase and alkaline phosphatase as compared to the control in the duodenum, jejunum and ileum. The uptake of D-glucose and L-histidine in the everted intestinal sac was found to be decreased. Also the decease of glucose and histidine uptake was found to be dependent on the substrate concentration, temperature and the time interval of incubation. The physical state and composition of brush border membrane was found to be altered as evident in the FTIR spectrum, by appearance of new peaks while disappearance of certain peaks occurred which were characteristics of the control membrane. The changes in wave number as well as peaks height were also noticed. Alterations in protein profile of the membrane were demonstrated using SDS-PAGE analysis where disappearance of few bands and change in the relative intensities of the bands were noticed and correlated with the alterations that have taken place at the molecular level. Histological studies have depicted a marked decrease in the absorption surface area such as the villi height of the intestinal segment. In addition, crypt number also deceased in the treated animals, an indication that such changes also correlate well with the changes in the transport of the end product nutrients.Se diseñó este estudio para investigar los efectos adversos gastrointestinales de los inhibidores de la ciclooxigenasa (COX con selectividad variable, denominados fármacos antiinflamatorios no esteroideos (AINE, inhibidores no selectivos de la

  5. Bad chemistry

    OpenAIRE

    Petsko, Gregory A

    2004-01-01

    General chemistry courses haven't changed significantly in forty years. Because most basic chemistry students are premedical students, medical schools have enormous influence and could help us start all over again to create undergraduate chemistry education that works.

  6. Anti-inflammatory activity of root of Alpinia galanga willd

    Directory of Open Access Journals (Sweden)

    Asim Kumar Ghosh

    2011-01-01

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

  7. Drug: D08142 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 8142.gif Antiinflammatory; Analgesic ATC code: M01AB09 See Lonazolac [DR:D07265] nonsteroidal antiinflammatory drugs (NSAIDs...HEUMATIC PRODUCTS, NON-STEROIDS M01AB Acetic acid derivatives and related substances M01AB09 Lonazolac D0814

  8. Drug: D01718 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available if Anti-inflammatory Therapeutic category: 1149 nonsteroidal antiinflammatory drugs (NSAIDs) cyclooxygenase-1 (COX-1) inhibitor [HSA...:5742] [KO:K00509] hsa00590(5742) Arachidonic acid metabolism Enzyme: CYP2C9 [HSA:15...zymes Oxidoreductases cyclooxygenase-1 (COX-1) [HSA:5742] [KO:K00509] Mofezolac D01718 Mofezolac (JAN/INN) C

  9. ANTI-INFLAMMATORY, ANTI-ARTHRITIC AND ANALGESIC ACTIVITY OF THE ALCOHOLIC EXTRACT OF THE PLANT URGINEA INDICA KUNTH.

    Directory of Open Access Journals (Sweden)

    Jakir Ahmed Chowdhury et al.

    2011-11-01

    Full Text Available This study was designed to present the observation of the pharmacological properties to the bulb of the plant. The extract of the bulb of Urginea indica Kunth were collected by using of alcoholic extraction. The anti-inflammatory action of the alcoholic Extract of the bulb of the plant Urginea indica was evaluated in rats (female against carrageenan induced edema i.e., using plethysmographic method. Besides this method, this extract was also assessed for Cotton pellet test and Hot plate test for anti-inflammatory and analgesic effects respectively. The effects of the extract were compared with the classical anti-inflammatory drug - Ibuprofen. The crude extract and the standard drug were orally administered. A significant anti-inflammatory effect was produced with the Alcoholic Extract of the plant part. This effect was then compared with the effect from the classical anti-inflammatory drug.

  10. Complex chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bong Gon; Kim, Jae Sang; Kim, Jin Eun; Lee, Boo Yeon

    2006-06-15

    This book introduces complex chemistry with ten chapters, which include development of complex chemistry on history coordination theory and Warner's coordination theory and new development of complex chemistry, nomenclature on complex with conception and define, chemical formula on coordination compound, symbol of stereochemistry, stereo structure and isomerism, electron structure and bond theory on complex, structure of complex like NMR and XAFS, balance and reaction on solution, an organo-metallic chemistry, biology inorganic chemistry, material chemistry of complex, design of complex and calculation chemistry.

  11. Complex chemistry

    International Nuclear Information System (INIS)

    This book introduces complex chemistry with ten chapters, which include development of complex chemistry on history coordination theory and Warner's coordination theory and new development of complex chemistry, nomenclature on complex with conception and define, chemical formula on coordination compound, symbol of stereochemistry, stereo structure and isomerism, electron structure and bond theory on complex, structure of complex like NMR and XAFS, balance and reaction on solution, an organo-metallic chemistry, biology inorganic chemistry, material chemistry of complex, design of complex and calculation chemistry.

  12. Drug: D00425 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 5.gif Anti-inflammatory [DS:H00445 H00630] Therapeutic category: 1149 ATC code: M01AX01 nonsteroidal antiinflammatory drugs (NSAIDs...) cyclooxygenase-2 (COX-2) inhibitor [HSA:5743] [KO:K11987] hsa00590(5743) Arachidoni...c acid metabolism hsa04370(5743) VEGF signaling pathway Enzyme: CYP2J2 [HSA:1573]...M M01 ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS M01A ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROID...310] Enzymes Oxidoreductases cyclooxygenase-2 (COX-2) [HSA:5743] [KO:K11987] Nabu

  13. Mathematical Chemistry

    OpenAIRE

    Trinajstić, Nenad; Gutman, Ivan

    2002-01-01

    A brief description is given of the historical development of mathematics and chemistry. A path leading to the meeting of these two sciences is described. An attempt is made to define mathematical chemistry, and journals containing the term mathematical chemistry in their titles are noted. In conclusion, the statement is made that although chemistry is an experimental science aimed at preparing new compounds and materials, mathematics is very useful in chemistry, among other things, to produc...

  14. Recent advances in the chemistry and biology of pyridopyrimidines.

    Science.gov (United States)

    Buron, F; Mérour, J Y; Akssira, M; Guillaumet, G; Routier, S

    2015-05-01

    The interest in pyridopyrimidine cores for pharmaceutical products makes this scaffold a highly useful building block for organic chemistry. These derivatives have found applications in various areas of medicine such as anticancer, CNS, fungicidal, antiviral, anti-inflammatory, antimicrobial, and antibacterial therapies. This review mainly focuses on the progress achieved since 2004 in the chemistry and biological activity of pyridopyrimidines. PMID:25794791

  15. Staging Anti-Inflammatory Therapy in Alzheimer's Disease

    OpenAIRE

    Lichtenstein, Mathieu P.; Carriba, Paulina; Masgrau, Roser; Pujol, Aurora; Galea, Elena

    2010-01-01

    The use of non-steroidal anti-inflammatory drugs (NSAIDs) in Alzheimer's disease (AD) is controversial because conclusions from numerous epidemiological studies reporting delayed onset of AD in NSAID users have not been corroborated in clinical trials. The purpose of this personal view is to revise the case for NSAIDs in AD therapeutics in light of: (i) the last report from the only primary prevention trial in AD, ADAPT, which, although incomplete, points to significant protection in long-ter...

  16. Anti-inflammatory Agents in the Treatment of Diabetes and Its Vascular Complications.

    Science.gov (United States)

    Pollack, Rena M; Donath, Marc Y; LeRoith, Derek; Leibowitz, Gil

    2016-08-01

    The association between hyperglycemia and inflammation and vascular complications in diabetes is now well established. Antidiabetes drugs may alleviate inflammation by reducing hyperglycemia; however, the anti-inflammatory effects of these medications are inconsistent and it is unknown whether their beneficial metabolic effects are mediated via modulation of chronic inflammation. Recent data suggest that immunomodulatory treatments may have beneficial effects on glycemia, β-cell function, and insulin resistance. However, the mechanisms underlying their beneficial metabolic effects are not always clear, and there are concerns regarding the specificity, safety, and efficacy of immune-based therapies. Herein, we review the anti-inflammatory and metabolic effects of current antidiabetes drugs and of anti-inflammatory therapies that were studied in patients with type 2 diabetes. We discuss the potential benefit of using anti-inflammatory treatments in diabetes and important issues that should be addressed prior to implementation of such therapeutic approaches. PMID:27440839

  17. Antiinflammatory, antinociceptive and antioxidant activities of Phyllanthus acidus L. extracts

    Institute of Scientific and Technical Information of China (English)

    Raja Chakraborty; Biplab De; Nayakanti Devanna; Saikat Sen

    2012-01-01

    Objective: To evaluate analgesic, anti-inflammatory and in vitro antioxidant potential and determine total phenolic, total flavonoid content of leaves extracts of Phyllanthus acidus, a folk medicinal plant of India. Methods: Anti-inflammatory activity was evaluated using carrageenan induced paw oedema, cotton pellet induced granuloma, membrane stabilizing activity method. Analgesic activity of the extracts was estimated against acetic acid induced writhing, tail immersion method, formalin test. Free radical scavenging and antioxidant potential of the extracts of Phyllanthus acidus leaves was performed using several in vitro and ex vivo assay models. Total phenolic and total flavonoid contents of the extracts were determined using standard chemical methods. Results: The extracts exhibited significant anti-inflammatory and analgesic activities at dose dependent manner. Methanol extract at a dose of 500 mg/kg showed superior activity which was comparable with the standard drugs. Ethyl acetate extract showed moderate activity while petroleum ether extract showed least activity. Total phenolic and total flavonoid content in methanol extract were 73.08±0.682 mg GAE/g and 61.28±0.062 mg QE/g respectively. The extracts possess significant antioxidant activity, methanol extract showed highest IC50 value. The contents of flavonoids and phenolic compounds could be correlated with the antioxidant, analgesic and anti-inflammatory activities observed for Phyllanthus acidus leaves. Conclusion:Our findings suggest that Phyllanthus acidus contains potential antioxidant, analgesic and anti-inflammatory compounds which could be tested as drug candidates against oxidative stress, pain and inflammation related pathological diseases.

  18. Drug: D08726 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08726 Mixture, Drug dl-Camphor - methyl salicylate - mentha oil - eucalyptus oil m... anti-inflammatory agents 2649 Others D08726 dl-Camphor - methyl salicylate - mentha oil - eucalyptus oil mixt PubChem: 96025409 ...

  19. Drug: D04594 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ic category of drugs in Japan [BR:br08301] 2 Agents affecting individual organs 22 Respiratory organ agents ...64 Analgesics, anti-itchings, astringents, anti-inflammatory agents 2643 Ammonium agents D04594 Ammonia wate

  20. Drug: D06620 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06620 Mixture, Drug dl-Camphor - ethanol mixt; Camphor (TN) dl-Camphor [DR:D00098], Ethanol [DR ... ringents, anti-inflammatory agents 2645 Peppermint rubber ... and camphor peppermint D06620 dl-Camphor - ethanol ...

  1. Drug: D04761 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D04761 Mixture, Drug d-Camphor - ethanol mixt; Camphor (TN) d-Camphor [DR:D06392], (Ethanol [DR: ... ringents, anti-inflammatory agents 2645 Peppermint rubber ... and camphor peppermint D04761 d-Camphor - ethanol ...

  2. Drug: D06972 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available lgesics, anti-itchings, astringents, anti-inflammatory agents 2649 Others D06972 Shiunkou 5 Crude drugs and Chinese medicine... formulations 52 Traditional Chinese medicines 520 Traditional Chinese medicines 5200 Traditional Chinese medicine

  3. Drug: D07816 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available X18 M01AB05 M02AA15 S01BC03 Indication: For relief of mild to moderate pain, Migraine, Primary dysmenorrhea, Osteoarthritis..., Rheumatoid arthritis nonsteroidal antiinflammatory drugs (NSAIDs

  4. Drug: D07265 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ory ATC code: M01AB09 nonsteroidal antiinflammatory drugs (NSAIDs) Anatomical Therapeutic Chemical (ATC) cla...INFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS M01AB Acetic acid derivativ

  5. Drug: D05729 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ification [BR:br08302] Ophthalmic Agents Ophthalmic Anti-inflammatories Rimexolone D05729 Rimexolone (USP/IN...ticosteroids, plain S01BA13 Rimexolone D05729 Rimexolone (USP/INN) USP drug class

  6. Analgesic and antiinflammatory activity of kaur-16-en-19-oic acid from Annona reticulata L. bark.

    Science.gov (United States)

    Chavan, Machindra J; Kolhe, Dinesh R; Wakte, Pravin S; Shinde, Devanand B

    2012-02-01

    Kaur-16-en-19-oic acid was isolated from the bark of Annona reticulata and studied for its analgesic and antiinflammatory activity. Analgesic activity was assessed using the hot plate test and acetic acid-induced writhing, and the antiinflammatory activity using the carrageenan induced rat paw oedema method. Kaur-16-en-19-oic acid, at doses of 10 and 20 mg/kg, exhibited significant (p < 0.05) analgesic and antiinflammatory activity. These activities were comparable to the standard drugs used, and furthermore the analgesic effect of kaur-16-en-19-oic acid was blocked by naloxone (2 mg/kg) in both analgesic models. PMID:21674631

  7. Variation in postoperative non-steroidal anti-inflammatory analgesic use after colorectal surgery

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Klein, Mads; Burcharth, Jakob;

    2014-01-01

    BACKGROUND: Non-steroid anti-inflammatory drugs (NSAIDs) have been proposed as part of a multimodal postoperative analgesia in patients operated for colorectal cancer. However, whether these drugs are prescribed and taken by the patients have not been evaluated. The aim of this study was to...

  8. Topical ketorolac has no antinociceptive or anti-inflammatory effect in thermal injury

    DEFF Research Database (Denmark)

    Møiniche, S; Pedersen, J L; Kehlet, H

    1994-01-01

    This study investigated the antinociceptive and anti-inflammatory effect of a topical non-steroidal anti-inflammatory drug in human thermal injury. Twelve healthy unmedicated volunteers had identical burn injuries produced on the medial side of both calves with a 49 degrees C 15 x 25 mm thermode...... and MPDT, an increase in EI and development of mechanical hyperalgesia (P < 0.05). Ketorolac gel had no effect on any of the nociceptive or inflammatory variables studies (P > 0.2)....

  9. ANTI-INFLAMMATORY ACTIVITY OF WHOLE PLANT OF POLYGALA ROSMARINIFOLIA WIGHT & ARN (POLYGALACEAE

    Directory of Open Access Journals (Sweden)

    V.R. Mohan et al

    2012-10-01

    Full Text Available In the present study, Polygala rosmarinifolia whole plant was extracted with ethanol and evaluated for anti-inflammatory activity in rats using a carrageenan induced paw edema method. Ethanol extract exhibits potent anti-inflammatory activity at 200mg/kg at 3rd hr after administration is compared with reference standard drug, Indomethacin. Observed pharmacological activity in the present study provides scientific validation of ethnomedicinal use of this plant in treating acute inflammation.

  10. Functional outcomes of rheumatoid arthritis during various proceduresof anti-inflammatory therapy

    OpenAIRE

    Natalya Vladimirovna Chichasova; S A Vladimirov; G R Imametdinova; E V Igolkina; E L Nasonov

    2010-01-01

    Objective. To study the functional outcomes of rheumatoid arthritis (RA) 1, 3, 5, and 8 years after use of various procedures of anti-inflammatory therapy. Subjects and methods. One hundred patients with valid RA were examined. The patients were divided into 3 groups: 1) 38 patients received basic anti-inflammatory drugs (BAIDs) only; 2) 37 patients took BAIDs in combination with glucocorticoids (GCs); 3) 25 patients had synchronous programmed intensive therapy. Results. The early use o...

  11. The Antiinflammatory and Antiarthritic Properties of Ethanol Extract of Hedera helix

    OpenAIRE

    Anuradha Rai

    2013-01-01

    The ethanol Hedera helix plant extract was tested for its antiinflammatory properties. Intraperitoneal injections of 7.5 ml/kg wt ethanol extract showed antiinflammatory activity with 88.89% inhibition as compared to reference drug diclofenac, which showed 94.44% inhibition in formalin-induced paw oedema. As formalin-induced paw oedema closely resembles human arthritis, the antiarthritic property of ethanol extract of Hedera helix was also investigated. The visible reduction in arthritic symp...

  12. ANTI-INFLAMMATORY ACTIVITY OF ETHANOLIC STEM EXTRACTS OF RUBIA CORDIFOLIA LINN. IN RATS

    OpenAIRE

    Tailor Chandra Shekhar; Bahuguna Y M; Singh Vijender

    2010-01-01

    In the present Study of Ethanolic extract of Stem of Rubia cordifolia Linn.(Rubiaceae) was screened for anti-inflammatory activity in carrageenan induced paw oedema rats. The effect was assessed by Difference in paw oedema volume, before & after the low & high dose administration of the extract in Rats. Ethanolic extract of Rubia cordifolia stem (20 & 40 mg./kg./ml.) were administered orally. Anti-inflammatory effects were compared with Standard drug- Indomethacin (10mg./kg/ml.). These observ...

  13. Antiinflammatory activity of tenoxicam gel on carrageenan-induced paw oedema in rats

    OpenAIRE

    Gupta G; Gaud R

    2006-01-01

    Tenoxicam is a nonsteroidal antiinflammatory drug, used in the treatment of inflammatory and degenerative disorders of the musculoskeletal system. It is from the oxicam group of nonsteroidal antiinflammatory agents. It is widely prescribed for the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, gout, extra-articular disorders, bursitis, tendonitis, and nonarticular rheumatic condition. Tenoxicam has some side effects when taken orally, viz., epigastric pain, heartbu...

  14. Antiinflammatory, Diuretic and Antimicrobial Activities of Rungia pectinata Linn. and Rungia repens Nees

    OpenAIRE

    Swain, S. R.; Sinha, B.N; Murthy, P. N.

    2008-01-01

    The hydroalcoholic extracts prepared from leaves of Rungia pectinata and Rungia repens were investigated for antiinflammatory and diuretic activity in wistar rats. The results obtained were compared with that of standard drug aspirin and frusemide for their antiinflammatory and diuretic activity respectively. The acute toxicity study was also carried out using adult swiss albino mice of either sex which indicates the safety of the extracts even at a dose of 4000 mg/kg. R. pectinata showed bet...

  15. Drug: D04022 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D04022 Mixture, Drug Sodium salicylate - dibucaine hydrocholoride - calcium bromide... mixt; Neo vitacain (TN) Sodium salicylate [DR:D00566], Dibcaine hydrochloride [DR:D02220], Calcium bromide ...[DR:D01723] Anti-inflammatory Therapeutic category: 1149 Therapeutic category of drugs in Japan [BR:br08301]... nervous system 114 Antipyretics and analgesics, anti-inflammatory agents 1149 Others D04022 Sodium salicylate - dibucaine hydrocholoride - calcium bromide mixt PubChem: 17398006 ...

  16. Plants and Medicinal Chemistry--2

    Science.gov (United States)

    Bailey, D.

    1977-01-01

    Second of a two part article on the influence of plants on medicinal chemistry. This part considers how drugs work, the attempts to develop anaesthetics safer than cocaine, and useful poisons. (Author/SL)

  17. Drug allergy

    Directory of Open Access Journals (Sweden)

    Warrington Richard

    2011-11-01

    Full Text Available Abstract Drug allergy encompasses a spectrum of immunologically-mediated hypersensitivity reactions with varying mechanisms and clinical presentations. This type of adverse drug reaction (ADR not only affects patient quality of life, but may also lead to delayed treatment, unnecessary investigations, and even mortality. Given the myriad of symptoms associated with the condition, diagnosis is often challenging. Therefore, referral to an allergist experienced in the identification, diagnosis and management of drug allergy is recommended if a drug-induced allergic reaction is suspected. Diagnosis relies on a careful history and physical examination. In some instances, skin testing, graded challenges and induction of drug tolerance procedures may be required. The most effective strategy for the management of drug allergy is avoidance or discontinuation of the offending drug. When available, alternative medications with unrelated chemical structures should be substituted. Cross-reactivity among drugs should be taken into consideration when choosing alternative agents. Additional therapy for drug hypersensitivity reactions is largely supportive and may include topical corticosteroids, oral antihistamines and, in severe cases, systemic corticosteroids. In the event of anaphylaxis, the treatment of choice is injectable epinephrine. If a particular drug to which the patient is allergic is indicated and there is no suitable alternative, induction of drug tolerance procedures may be considered to induce temporary tolerance to the drug. This article provides a backgrounder on drug allergy and strategies for the diagnosis and management of some of the most common drug-induced allergic reactions, such allergies to penicillin, sulfonamides, cephalosporins, radiocontrast media, local anesthetics, general anesthetics, acetylsalicylic acid (ASA and non-steroidal anti-inflammatory drugs.

  18. A cluster randomised stepped wedge trial to evaluate the effectiveness of a multifaceted information technology-based intervention in reducing high-risk prescribing of non-steroidal anti-inflammatory drugs and antiplatelets in primary medical care: The DQIP study protocol

    Directory of Open Access Journals (Sweden)

    Dreischulte Tobias

    2012-03-01

    Full Text Available Abstract Background High-risk prescribing of non-steroidal anti-inflammatory drugs (NSAIDs and antiplatelet agents accounts for a significant proportion of hospital admissions due to preventable adverse drug events. The recently completed PINCER trial has demonstrated that a one-off pharmacist-led information technology (IT-based intervention can significantly reduce high-risk prescribing in primary care, but there is evidence that effects decrease over time and employing additional pharmacists to facilitate change may not be sustainable. Methods/design We will conduct a cluster randomised controlled with a stepped wedge design in 40 volunteer general practices in two Scottish health boards. Eligible practices are those that are using the INPS Vision clinical IT system, and have agreed to have relevant medication-related data to be automatically extracted from their electronic medical records. All practices (clusters that agree to take part will receive the data-driven quality improvement in primary care (DQIP intervention, but will be randomised to one of 10 start dates. The DQIP intervention has three components: a web-based informatics tool that provides weekly updated feedback of targeted prescribing at practice level, prompts the review of individual patients affected, and summarises each patient's relevant risk factors and prescribing; an outreach visit providing education on targeted prescribing and training in the use of the informatics tool; and a fixed payment of 350 GBP (560 USD; 403 EUR up front and a small payment of 15 GBP (24 USD; 17 EUR for each patient reviewed in the 12 months of the intervention. We hypothesise that the DQIP intervention will reduce a composite of nine previously validated measures of high-risk prescribing. Due to the nature of the intervention, it is not possible to blind practices, the core research team, or the data analyst. However, outcome assessment is entirely objective and automated. There will

  19. Anticoagulant Medicine: Potential for Drug-Food Interactions

    Science.gov (United States)

    ... AerobiKa® Cardiology Medications Anticoagulant Medicine Anticoagulants and Drug-Food Interactions COPD Medications Bronchodilators Anti-Inflammatories Antibiotics Managing Your Medications Devices ...

  20. Drug: D00969 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ode: M01AC06 nonsteroidal antiinflammatory drugs (NSAIDs) cyclooxygenase-2 (COX-2) inhibitor [HSA:5743] [KO:...D00969 Drug Meloxicam (JAN/USAN/INN); Mobic (TN) C14H13N3O4S2 351.0347 351.4007 D00...K11987] hsa00590(5743) Arachidonic acid metabolism Enzyme: CYP2C9 [HSA:1559], CYP3A4 [HSA...nd analgesics, anti-inflammatory agents 1149 Others D00969 Meloxicam (JAN/USAN/IN...MMATORY AND ANTIRHEUMATIC PRODUCTS M01A ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS M01AC Oxic

  1. 重视变态反应性结膜炎治疗中非甾体抗炎药物的应用%Consideration of application of non-steroidal anti-inflammatory drugs in the treatment of allergic conjunctivitis

    Institute of Scientific and Technical Information of China (English)

    李莹

    2014-01-01

    近年来随着工业化进程的加快,变态反应性结膜炎的发生率逐渐升高.目前,变态反应性结膜炎的治疗以眼局部治疗为主,主要目的在于针对病因,减轻症状和预防并发症.变态反应性结膜炎的治疗药物包括抗组胺药、肥大细胞稳定剂、双效作用药物(稳定肥大细胞/抗组胺)、非甾体抗炎药(NSAIDs)、糖皮质激素及免疫抑制剂六大类.抗组胺药、肥大细胞稳定剂、双效作用药物的主要作用是减轻眼部瘙痒、结膜充血等症状和体征,也可用于急性变态反应性结膜炎患者,而NSAIDs、糖皮质激素及免疫抑制剂则用于症状严重患者或慢性病例.糖皮质激素类药物治疗变态反应性结膜炎效果显著,可作用于过敏反应的多个环节,但是长期应用可能会导致眼压升高、视力障碍、视野缺损和后囊下白内障,有角膜溃疡的患者更应谨慎使用.免疫抑制剂具有抑制免疫的作用,可抑制局部或机体异常的免疫反应,但由于价格较高及局部刺激性强等不良反应,故也不宜长期应用.NSAIDs具有良好的抗炎效果,作用温和,刺激性小,目前在眼表变态反应性结膜炎中广泛应用.%Allergic conjunctivitis is a very common pathology and its incidence has increased in developing countries with the development of industrialization.At present,the therapy of allergic conjunctivitis is mainly the use of topical eyedrops to eliminate causative factors,relieve symptoms and prevent complications.The drugs used in allergic conjunctivitis have 6 groups,including antihistamine,mastocyte stabilizer,drugs with dual effects (antihistamine and mastocyte stabilizer),non-steroidal anti-inflammatory drugs (NSAIDs),glucocorticoids and immunosuppressors.The goals of topical use of antihistamine,mastocyte stabilizer and drugs of dual effects are to remove the itching and hyperaemia of eye or to treat the patients with acute allergic conjunctivitis; while NSAIDs

  2. Positronium chemistry

    CERN Document Server

    Green, James

    1964-01-01

    Positronium Chemistry focuses on the methodologies, reactions, processes, and transformations involved in positronium chemistry. The publication first offers information on positrons and positronium and experimental methods, including mesonic atoms, angular correlation measurements, annihilation spectra, and statistical errors in delayed coincidence measurements. The text then ponders on positrons in gases and solids. The manuscript takes a look at the theoretical chemistry of positronium and positronium chemistry in gases. Topics include quenching, annihilation spectrum, delayed coincidence

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

    Directory of Open Access Journals (Sweden)

    Rupali Vitthal Sarpate

    2012-01-01

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

  4. Uso de analgésicos e antiinflamatórios em pacientes portadores de polipose nasossinusal eosinofílica tolerantes e intolerantes à aspirina Use of analgesics and anti-inflammatory drugs in patients with eosinophilic nasal polyposis tolerant and intolerant to aspirin

    Directory of Open Access Journals (Sweden)

    Helena M. G. Becker

    2003-06-01

    dipirona e ao álcool, respectivamente, em quase metade e um terço destes pacientes.Following aspirin introduction as medicine, several reports were described concerning adverse reactions after its ingestion. Widal et al. (1922¹ were the first investigators to associate Aspirin intolerance (AI with asthma and nasal polyps (NP followed by Samter & Beers (1967². Such intolerance was manifested mainly by nasal obstruction and/or bronchospasm related to the cyclooxygenase-1 (COX-1 inhibition and consequent overproduction of leukotrienes. This might also be triggered by the administration of other non-steroid anti-inflammatory drugs, acetaminophen, food dyes and additives and alcohol. AIM: To analyze the risks of the analgesics and anti-inflammatory drugs use in patients with eosinophilic nasal polyposis tolerant and intolerant to aspirin. STUDY DESIGN: Transversal cohort study. MATERIAL AND METHOD: 45 patients were selected # 15 suffering from eosinophilic nasosinusal polyposis, tolerant to aspirin (group TA; other 15 with eosinophilic nasosinusal polyposis associated with aspirin intolerance (group AI, and 15 patients without nasosinusal polyposis with septal deviation (control group. The presence of reaction to aspirin, dipyrone, acetaminophen, other non-steroids anti-inflammatory drugs, food dyes and additives, other drugs or chemical substances was detected by inquiry. To exclude aspirin intolerance in TA and control groups, oral provocation test with aspirin was carried out. RESULTS: Bronchospasm was the main aspirin reaction in patients suffering from eosinophilic nasosinusal polyposis and which also showed with ingestion of acetaminophen (20%, alcohol (27%, non-steroids anti-inflammatory drugs (60% and dipyrone (47%. CONCLUSION: In patients with eosinophilic nasosinusal polyposis associated with aspirin intolerance it is important to do the diagnosis of intolerance to other drugs. The use of dipyrone and alcohol is worth attention, once its intolerance was observed

  5. Effect of non-steroidal anti-inflammatory drug etoricoxib on the hematological parameters and enzymes of colon and kidney Efecto del fármaco antiinflamatorio no esteroideo etoricoxib sobre los parámetros hematológicos y las enzimas del colon y el riñón

    Directory of Open Access Journals (Sweden)

    N. Behal

    2009-06-01

    Full Text Available The present study was designed to investigate the effects of a selective COX-2 inhibitor, etoricoxib in rats on the hematological and toxicity parameters in colon and kidney at two different doses of the drug, one within the therapeutic anti-inflammatory range as based on the reported ED50 value (Eto-1 while the other at ten times higher (Eto-2, relative to the toxicity studies which have not been reported so far. The results showed that the control and the drug treated animals achieved similar linear growth rate and also showed no major alterations in the histological parameters in the liver and kidney tissue. The animals treated with lower dose of etoricoxib showed an overall decrease in total leukocytes counts as well as in the number of neutrophils, lymphocytes, monocytes and eosinophills while the higher dose of the drug produced a highly significant increase in all the cell counts. However, the drug treatment at both the dose level produced significant fall in the activities of alkaline phosphatase, sucrase, lactase and maltase in the kidney but increased the activity of alkaline phosphatase in colon. The treatment of etoricoxib did not produce any change in the nitric oxide and citrulline levels in kidney while an increase was noted in the colonic tissue. It was concluded that etoricoxib is a relatively safe drug at its anti-inflammatory ED50 dose in rats when the hematological parameters and the structural and functional characteristics of kidney and colonic tissues were studied.El presente estudio se diseñó para investigar los efectos de un inhibidor selectivo de la COX-2, etoricoxib, sobre los parámetros hematológicos y de toxicidad en colon y riñón de rata, con dos dosis distintas del fármaco, una dentro del rango terapéutico sobre la base del valor ED50 notificado (Eto-1 mientras que la otra fue diez veces superior (Eto-2, relativa a los estudios de toxicidad que aún no han sido publicados. Los resultados mostraron que los

  6. Antiinflammatory constituents of teramnus labialis

    Directory of Open Access Journals (Sweden)

    Sridhar C

    2006-01-01

    Full Text Available Bioassay-guided fractionation, based on antiinflammatory activity of the methanolic extractives of Teramnus labialis led to the isolation and characterization of vitexin, bergenin, daidzin and 3-O-methyl-D- chiro -inositol as active constituents. Vitexin exhibited a dose-dependent inhibitory activity on 5-lipoxygenase enzyme. The isolated constituents were also screened for their antioxidant activity by nitroblue tetrazolium (NBT riboflavin photo reduction method. Vitexin exhibited moderate antioxidant activity. This is the first reported occurrence of vitexin, bergenin, daidzin and 3-O-methyl-D- chiro -inositol in T. labialis.

  7. [Drug-drug interactions in antirheumatic treatment].

    Science.gov (United States)

    Krüger, K

    2012-04-01

    Clinically relevant drug-drug interactions contribute considerably to potentially dangerous drug side-effects and are frequently the reason for hospitalization. Nevertheless they are often overlooked in daily practice. For most antirheumatic drugs a vast number of interactions have been described but only a minority with clinical relevance. Several potentially important drug interactions exist for non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate, azathioprine, mycophenolate-mofetil and especially for cyclosporin A. Most importantly co-medication with methotrexate and sulfmethoxazole trimethoprim as well as azathioprine and allopurinol carries the risk of severe, sometimes life-threatening consequences. Nevertheless, besides these well-known high-risk combinations in each case of polypharmacy with antirheumatic drugs it is necessary to bear in mind the possibility of drug interactions. As polypharmacy is a common therapeutic practice in older patients with rheumatic diseases, they are at special risk. PMID:22527215

  8. Synthesis of Novel Oxazolo[4,5-b]pyridine-2-one based 1,2,3-triazoles as Glycogen Synthase Kinase-3β Inhibitors with Anti-inflammatory Potential.

    Science.gov (United States)

    Tantray, Mushtaq A; Khan, Imran; Hamid, Hinna; Alam, Mohammad Sarwar; Umar, Sadiq; Ali, Yakub; Sharma, Kalicharan; Hussain, Firasat

    2016-06-01

    A novel series of oxazolo[4,5-b]pyridine-2-one based 1,2,3-triazoles has been synthesized by click chemistry approach and evaluated for in vitro GSK-3β inhibitory activity. Compound 4g showed maximum inhibition with IC50 value of 0.19 μm. Keeping in view the effect of GSK-3β inhibition on inflammation, compounds 4g, 4d, 4f, 4i, 4n and 4q exhibiting significant GSK-3β inhibition were examined for in vivo anti-inflammatory activity in rat paw edema model. The compounds 4g, 4d, 4f and 4i showed pronounced in vivo anti-inflammatory activity (76.36, 74.54, 72.72 and 70.90%, respectively, after 5h post-carrageenan administration) and were further found to inhibit the pro-inflammatory mediators, viz. NO, TNF-α, IL-1β, and IL-6 substantially in comparison with indomethacin, an anti-inflammatory drug as well as SB216763, a GSK-3β inhibitor, reported to exert a similar effect. Histopathology studies confirmed the tolerance of gastric mucosa to these compounds. PMID:26804375

  9. Social Chemistry

    OpenAIRE

    Lichtfouse, Eric; Schwarzbauer, Jan; Robert, Didier

    2012-01-01

    International audience This article is both an essay to propose social chemistry as a new scientific discipline, and a preface of the book Environmental Chemistry for a Sustainable World. Environmental chemistry is a fast emerging discipline aiming at the understanding the fate of pollutants in ecosystems and at designing novel processes that are safe for ecosystems. Past pollution should be cleaned, future pollution should be predicted and avoided (Lichtfouse et al., 2005a). Such advices ...

  10. Computational chemistry

    OpenAIRE

    Truhlar, Donald G.; McKoy, Vincent

    2000-01-01

    Computational chemistry has come of age. With significant strides in computer hardware and software over the last few decades, computational chemistry has achieved full partnership with theory and experiment as a tool for understanding and predicting the behavior of a broad range of chemical, physical, and biological phenomena. The Nobel Prize award to John Pople and Walter Kohn in 1998 highlighted the importance of these advances in computational chemistry. With massively parallel computers ...

  11. Bioinorganic Chemistry

    OpenAIRE

    Bertini, Ivano; Gray, Harry B.; Lippard, Stephen J.; Valentine, Joan Selverstone

    1994-01-01

    This book covers material that could be included in a one-quarter or one-semester course in bioinorganic chemistry for graduate students and advanced undergraduate students in chemistry or biochemistry. We believe that such a course should provide students with the background required to follow the research literature in the field. The topics were chosen to represent those areas of bioinorganic chemistry that are mature enough for textbook presentation. Although each chapter presents material...

  12. Technetium chemistry

    International Nuclear Information System (INIS)

    Technetium chemistry is a young and developing field. Despite the limited knowledge of its chemistry, technetium is the workhorse for nuclear medicine. Technetium is also a significant environmental concern because it is formed as a byproduct of nuclear weapons production and fission-power generators. Development of new technetium radio-pharmaceuticals and effective environmental control depends strongly upon knowledge of basic technetium chemistry. The authors performed research into the basic coordination and organometallic chemistry of technetium and used this knowledge to address nuclear medicine and environmental applications. This is the final report of a three-year Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL)

  13. Topical diclofenac versus dexamethasone after strabismus surgery: A double-blind randomized clinical trial of anti-inflammatory effect and ocular hypertensive response

    OpenAIRE

    Khan Hayat; Amitava Abadan

    2007-01-01

    Background: Compared to steroids non-steroidal anti-inflammatory drugs offer comparable anti-inflammatory action without ocular side-effects. Aim: To compare the anti-inflammatory effect and effect on IOP (Goldmann) of topical diclofenac 0.1% with dexamethasone 0.1% after strabismus surgery. Design: Prospective, randomized, double-blind, single-center, clinical trial. Materials and Methods: Forty-three cases of constant horizontal strabismus, qualifying for standard un...

  14. Ammonium glycyrrhizinate-loaded niosomes as a potential nanotherapeutic system for anti-inflammatory activity in murine models

    Directory of Open Access Journals (Sweden)

    Marianecci C

    2014-01-01

    Full Text Available Carlotta Marianecci,1 Federica Rinaldi,1 Luisa Di Marzio,2 Marica Mastriota,3 Stefano Pieretti,3 Christian Celia,2,4 Donatella Paolino,5 Michelangelo Iannone,6,7 Massimo Fresta,5 Maria Carafa11Department of Drug Chemistry and Technologies, University Sapienza of Rome, Rome, 2Department of Pharmacy, University G d'Annunzio of Chieti of Pescara, Chieti, 3Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy; 4Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX, USA; 5Department of Health Sciences, University Magna Graecia of Catanzaro, University Campus S Venuta, Building of BioSciences, Germaneto, 6ARPA Calabria, Environmental Epidemiology Center, 7CNR, Neuroscience Institute, Pharmacology Section, Complesso "Nini Barbieri", Roccelletta di Borgia, ItalyBackground: Liquorice extracts demonstrate therapeutic efficacy in treating dermatitis, eczema, and psoriasis when compared with corticosteroids. In this work, nonionic surfactant vesicles (niosomes, NSVs containing polysorbate 20 (Tween 20, cholesterol, and cholesteryl hemisuccinate at different molar concentrations were used to prepare monoammonium glycyrrhizinate (AG-loaded NSVs. The anti-inflammatory properties of AG-loaded NSVs were investigated in murine models.Methods: The physicochemical properties of the NSVs were characterized using dynamic light scattering. The fluidity of the lipid bilayer was evaluated by measuring the fluorescence intensity of diphenylhexatriene. The drug entrapment efficiency of AG was assessed using high-performance liquid chromatography. The physicochemical stability of the NSVs was evaluated as a function of time using dynamic light scattering combined with Turbiscan Lab® Expert analysis. Serum stability was determined by incubating the NSVs with 10% v/v fetal bovine serum. The cytotoxic effects of the NSVs were investigated in human dermal fibroblasts using the Trypan blue dye

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

    Directory of Open Access Journals (Sweden)

    Latif Abdul

    2010-03-01

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

  16. Good chemistry

    OpenAIRE

    Petsko, Gregory A

    2004-01-01

    The subject matter in chemistry courses reflects almost nothing of the issues that chemists are interested in. It is important to formulate a set of topics - and a Medical College Admissions Test reflecting them - that would leave chemistry departments no choice but to change their teaching.

  17. Anti-inflammatory strategies in the treatment of schizophrenia.

    Science.gov (United States)

    Andrade, Chittaranjan

    2016-01-01

    Schizophrenia is a major mental illness with a lifetime prevalence of about 1%. Antipsychotic drugs, with a primary mechanism of action that involves dopamine receptor blockade, are the mainstay in the treatment of the disorder. However, despite optimum antipsychotic treatment, few patients return to pre-morbid levels; the treatment deficit includes refractory positive symptoms, negative symptoms, mood impairments, cognitive impairments, social impairments, and/or a variety of medication-related adverse effects, including extrapyramidal symptoms, metabolic disturbances, hyperprolactinemia, and others. To address these, antipsychotic treatment has been augmented with psychosocial interventions, cognitive rehabilitation, different kinds of electrical and magnetic brain stimulation, and a large range of drugs from the neuropsychiatric as well as, surprise, the general medical pharmacopeia. The pleomorphic pathophysiology of schizophrenia includes abnormalities in immunological and inflammatory pathways, and so it is not surprising that anti-inflammatory drugs have also been trialed as augmentation agents in schizophrenia. This article critically examines the outcomes after augmentation with conventional anti-inflammatory interventions; results from randomized controlled trials do not encourage the use of either aspirin (1000 mg/day) or celecoxib (400 mg/day), both of which have been studied for this indication during the past decade and a half. PMID:26427750

  18. IN VITRO ANTIINFLAMMATORY ACTIVITY OF FICUS BENGHALENSIS BARK

    Directory of Open Access Journals (Sweden)

    Matpal Mahesh

    2013-07-01

    Full Text Available To evaluate the anti-inflammatory property of the different extract of bark of Ficus benghalensis, family Moraceae is a very large, fast growing, evergreen tree up to 30 meters, with spreading branches and many aerial roots. Leaves stalked, ovate-cordate, 3-nerved, entire, when young downy on both sides; petiole with a broad smooth greasy gland at the apex, compressed, downy; Fruit in axillary pairs, the size of a cherry, round and downy. According to Ayurveda, it is astringent to bowels; useful in treatment of biliousness, ulcers, erysipelas, vomiting, vaginal complains, fever, inflammations, leprosy. According to Unani system of medicine, its latex is aphrodisiac, tonic, vulernary, maturant, lessens inflammations; useful in piles etc. The present study aimed at the evaluation of anti-inflammatory property of the aqueous, chloroform and alcoholic extracts of the bark by in vitro methods. In vitro method was estimated by human red blood cell membrane stabilization (HRBC method. Results showed significant anti-inflammatory property of the different extracts tested. The methanolic extract at a concentration of 200 mg/ml. showed potent activity on comparing with the standard drug diclofenac sodium.

  19. 3-Aminothiophene-2-Acylhydrazones: Non-Toxic, Analgesic and Anti-Inflammatory Lead-Candidates

    Directory of Open Access Journals (Sweden)

    Yolanda Karla Cupertino da Silva

    2014-06-01

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

  20. Synthetic cathinones: chemistry, pharmacology and toxicology of a new class of designer drugs of abuse marketed as "bath salts" or "plant food".

    Science.gov (United States)

    Coppola, M; Mondola, R

    2012-06-01

    In 2000s, many synthetic cathinones have received a renewed popularity as designer drugs of abuse, particularly among young people. Despite being marketed as "bath salts" or "plant food" and labeled "not for human consumption", people utilize these substances for their amphetamine or cocaine like effects. Since the time of their appearance in the recreational drug market, in several countries have been signaled numerous confirmed cases of abuse, dependence, severe intoxication and deaths related to the consumption of synthetic cathinones. The aim of this paper is to summarize the clinical, pharmacological and toxicological information about this new class of designer drugs of abuse. PMID:22459606