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Antiinflammatory Drugs (antiinflammatory + drug)
Kinds of Antiinflammatory Drugs Selected AbstractsNitric Oxide-Donating Non-Steroidal Antiinflammatory Drugs: The Case of Nitroderivatives of Aspirin.CHEMINFORM, Issue 37 2003Valerio Chiroli Abstract For Abstract see ChemInform Abstract in Full Text. [source] Antiulcerogenic activity of the essential oil of Baccharis dracunculifolia on different experimental models in ratsPHYTOTHERAPY RESEARCH, Issue 10 2009Juliane Jose Massignani Abstract Baccharis dracunculifolia DC (Asteraceae), a native plant from Brazil, commonly known as ,Alecrimdo-campo' is widely used in folk medicine to treat inflammation, hepatic disorders and stomach ulcers, and it is the most important botanical source of Southeastern Brazilian propolis, known as green propolis. Its essential oil is composed of non-oxygenated and oxygenated terpenes. In this work, the effects of the essential oil obtained from the aerial parts of B. dracunculifolia on gastric ulcers were evaluated. The antiulcer assays were undertaken using the following protocols in rats: nonsteroidal antiinflammatory drug (NSAID)-induced ulcer, ethanol-induced ulcer, stress-induced ulcer, and determination of gastric secretion using ligated pylorus. The treatment in the doses of 50, 250 and 500 mg/kg of B. dracunculifolia essential oil significantly diminished the lesion index, the total lesion area and the percentage of lesions in comparison with both positive and negative control groups. With regard to the model of gastric secretion a reduction of gastric juice volume and total acidity was observed, as well as an increase in the gastric pH. No sign of toxicity was observed in the acute toxicity study. Considering the results, it is suggested that the essential oil of B. dracunculifolia could probably be a good therapeutic agent for the development of new phytotherapeutic medicine for the treatment of gastric ulcer. Copyright © 2009 John Wiley & Sons, Ltd. [source] In vivo microfocal computed tomography and micro,magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the ratARTHRITIS & RHEUMATISM, Issue 9 2010Michael D. Jones Objective To determine whether treatment with an antiresorptive drug in combination with an antiinflammatory drug reduces periarticular bone and soft tissue adaptations associated with the progression of posttraumatic secondary osteoarthritis (OA). Methods We used in vivo microfocal computed tomography (micro-CT) to map bony adaptations and in vivo micro,magnetic resonance imaging (micro-MRI) to examine joint inflammation in a rat model of surgically induced OA secondary to knee triad injury. We examined the arthroprotective effects of the bisphosphonates alendronate and risedronate and the nonsteroidal antiinflammatory drug (NSAID) meloxicam. Results Micro-CT revealed reduced levels of periarticular trabecular bone loss in animals with knee triad injury treated with the bisphosphonate drugs alendronate or risedronate, or the NSAID meloxicam, compared with untreated animals. Alendronate treatment reduced bony osteophyte development. While risedronate as a monotherapy did not positively impact osteophytogenesis, combination therapy with risedronate and meloxicam reduced osteophyte severity somewhat. Micro-MRI revealed an increased, diffuse water signal in the epiphyses of untreated rats with knee triad injury 8 weeks after surgery, suggestive of a bone marrow lesion,like stimulus. In contrast, meloxicam-treated rats showed a significant reduction in fluid signal compared with both bisphosphonate-treated groups 8 weeks after surgery. Histologic analysis qualitatively confirmed the chondroprotective effect of both bisphosphonate treatments, showing fewer degradative changes compared with untreated rats with knee triad injury. Conclusion Our findings indicate that select combinations of bisphosphonate and NSAID drug therapy in the early stages of secondary OA preserve trabecular bone mass and reduce the impact of osteophytic bony adaptations and bone marrow lesion,like stimulus. Bisphosphonate and NSAID therapy may be an effective disease-modifying drug regimen if administered early after the initial injury. [source] Efficacy of traditional and biologic agents in different clinical phenotypes of adult-onset Still's diseaseARTHRITIS & RHEUMATISM, Issue 8 2010Stefano Franchini Objective To evaluate the efficacy of antiinflammatory agents, steroids, immunosuppressants, and biologic agents in patients with adult-onset Still's disease (AOSD) who have either chronic articular disease or nonchronic disease. Methods Forty-five patients with AOSD were seen and followed up for at least 2 years at our institution, from 1991 to 2008. The majority of patients were treated with several therapeutic regimens; a total of 152 efficacy trials were administered. Data regarding the type of medication, the dosage used, and the outcome of these trials were collected and analyzed. Results Our data showed that the efficacy of monotherapy with a nonsteroidal antiinflammatory drug was very low (16%) and confirmed good efficacy of steroid therapy (63%), particularly in patients without chronic articular disease (78%). Patients whose disease did not respond to steroid therapy at the time of disease onset were at risk of the subsequent development of chronic arthritis. Disease-modifying antirheumatic drug (DMARD) monotherapy was successful in controlling steroid-resistant or steroid-dependent disease in 60% of patients. Methotrexate and cyclosporine showed the best response rates. The combination of high-dose steroids and cyclosporine was administered to successfully control some acute life-threatening complications. Only 6 patients had disease that was both steroid resistant and DMARD resistant. Treatment with biologic agents eventually led to satisfactory control of disease manifestations in 5 (83%) of these 6 patients. Conclusion Steroids were less effective in patients with chronic articular disease than in those with nonchronic disease. The administration of DMARDs early after disease onset could be beneficial in patients with steroid-resistant disease who are at risk of the development of chronic articular disease. Biologic agents proved to be highly effective in both steroid-resistant and DMARD-resistant AOSD. [source] Nonsteroidal antiinflammatory drugs and prostaglandin E2 modulate the synthesis of osteoprotegerin and RANKL in the cartilage of patients with severe knee osteoarthritisARTHRITIS & RHEUMATISM, Issue 2 2010Juan Moreno-Rubio Objective Although the osteoprotegerin (OPG)/RANK/RANKL system is the main modulator of bone remodeling, it remains unclear whether it is regulated in cartilage during osteoarthritis (OA). The aim of this study was to examine whether nonsteroidal antiinflammatory drug (NSAID) treatment modulates the synthesis of OPG and RANKL in the cartilage of patients with OA, and to investigate whether prostaglandin E2 (PGE2) modifies this system in human OA chondrocytes in culture. Methods A 3-month clinical trial was carried out in 20 patients with severe knee OA, all of whom were scheduled to undergo knee replacement surgery. Ten of these patients were treated with celecoxib, and the other 10 patients, who did not want to be treated, served as the control group. After surgery, cartilage was processed for molecular biology studies. We also used human OA chondrocytes to examine the effects of PGE2 on OPG/RANKL synthesis, examining which surface receptors were affected by PGE2. Results In patients with OA, celecoxib decreased RANKL synthesis in the cartilage, thereby increasing the OPG:RANKL ratio. In human OA chondrocytes in culture, PGE2 elicited a dose- and time-dependent increase in the synthesis of RANKL, the extent of which was greater than that of OPG. Confocal microscopy revealed that PGE2 induced RANKL transport to the cell membrane. Only EP2/EP4 agonists reproduced the effects of PGE2 on OPG and RANKL induction. Conclusion Long-term NSAID treatment inhibited the resorptive signal synthesized by chondrocytes. In vitro, PGE2 regulated the expression and release of these key mediators of bone metabolism by articular chondrocytes. The role of OPG/RANK/RANKL in OA cartilage metabolism is still unknown, although the synthesis of these proteins would enable the cartilage to control the activity of subchondral bone cells. [source] Determinants and sequelae associated with utilization of acetaminophen versus traditional nonsteroidal antiinflammatory drugs in an elderly populationARTHRITIS & RHEUMATISM, Issue 11 2002Elham Rahme Objective Acetaminophen is recommended as initial therapy for patients with arthritis, particularly those at increased risk of nonsteroidal antiinflammatory drug (NSAID),induced gastrointestinal (GI) side effects. However, higher doses of acetaminophen inhibit prostaglandin synthesis and have been associated with GI events. This study was undertaken to compare the observed and adjusted rates of GI events (hospitalizations, ulcers, dyspepsia, GI prophylaxis) occurring with higher versus lower doses of acetaminophen. Methods This was a retrospective cohort study of subjects ages ,65 years who received a prescription for acetaminophen or NSAID between 1994 and 1996. Pharmaceutical and medical records were reviewed for 1 year of historical data prior to the index prescription of acetaminophen or non-aspirin NSAID. Risk factors for GI events were identified based on the historical data. To further control for bias, patients were categorized by propensity score (the likelihood of receiving acetaminophen, given defined risk factor values). Records were then reviewed for the duration of the index prescription or 30 days, whichever was less, to generate data on the occurrence of GI events. Determinants of acetaminophen utilization were identified using logistic regression, and rates of GI events for each therapy were examined using Poisson regression analyses, controlling for duration of exposure, individual risk factors, and propensity scores. Results The study included 26,978 patients in the NSAID cohort and 21,207 in the acetaminophen cohort. Determinants of acetaminophen utilization compared with NSAIDs (odds ratio [95% confidence interval]) included recent hospitalization (8.6 [7.7,9.5]), concomitant anticoagulation therapy (3.2 [2.7,3.8]), age >85 years (2.3 [2.1,2.4]), and history of prior GI events, especially those requiring hospitalization (14.6 [11.7,18.7]). Unadjusted rates of GI hospitalization, ulcer, and dyspepsia were higher for patients in the acetaminophen cohort than for those in the NSAID cohort. The occurrence of GI events in acetaminophen-treated patients was dose dependent, with rate ratios (compared with high-dose NSAIDs and adjusted for risk susceptibility) ranging from 0.6 (95% confidence interval 0.5,0.7) for ,650 mg/day to 1.0 (0.9,1.1) for >3,250 mg/day. Conclusion In this cohort, acetaminophen utilization is more common in patients at higher risk of GI events. After adjustment for risk susceptibility, patients receiving higher doses of acetaminophen have higher rates of GI events compared with those receiving lower doses. [source] Knee pain reduces joint space width in conventional standing anteroposterior radiographs of osteoarthritic kneesARTHRITIS & RHEUMATISM, Issue 5 2002Steven A. Mazzuca Objective A suspected, but heretofore undemonstrated, limitation of the conventional weight-bearing anteroposterior (AP) knee radiograph, in which the joint is imaged in extension, for studies of progression of osteoarthritis (OA) is that changes in knee pain may affect extension, thereby altering the apparent thickness of the articular cartilage. The present study was undertaken to examine the effect of changes in knee pain of varying magnitudes on radiographic joint space width (JSW) in the weight-bearing extended and the semiflexed AP views, in which radioanatomic positioning of the knee was carefully standardized by fluoroscopy. Methods Fifteen patients with knee OA underwent a washout of their analgesic/nonsteroidal antiinflammatory drug (NSAID) agents (duration 5 half-lives), after which standing AP and semiflexed AP knee radiographs of both knees were obtained. Examinations were repeated 1,12 weeks later (median 4.5 weeks, mean 6.0 weeks), after resumption of analgesic/NSAID therapy. Knee pain was measured with the pain subscale of the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index (Likert scale). JSW was measured with a pair of calipers and a magnifying lens. Mixed model analyses of variance were used to test the significance of changes in pain and JSW within and between 2 groups of knees with mild-to-moderate radiographic severity of OA: (a) "flaring knees," in which the patient rated standing knee pain as severe or extreme after the washout and in which pain decreased to any degree after resumption of analgesics and/or NSAIDs (n = 12) and (b) "nonflaring knees," in which standing knee pain was absent, mild, or moderate after the washout or did not decrease after resumption of treatment (n = 15). Results After reinstitution of treatment, WOMAC pain scores decreased significantly in both flaring and nonflaring knees (,44%; P < 0.0001 and ,18%; P < 0.01, respectively). After adjustment for the within-subject correlation between knees, mean JSW (±SEM) in the extended view of the flaring OA knee increased significantly from the first to second examination (0.20 ± 0.06 mm; P = 0.005). In contrast, the change in adjusted mean JSW in the extended view of the nonflaring OA knee was negligible (,0.04 ± 0.04 mm) and significantly smaller than that observed in flaring knees (P < 0.01). Mean JSW in the semiflexed AP view was unaffected by the severity or responsiveness of standing knee pain in flaring and nonflaring OA knees. Conclusion JSW in weight-bearing extended-view radiographs of highly symptomatic OA knees can be altered significantly by changes in joint pain. In clinical trials and in epidemiologic studies of OA progression that use this radiographic technique, longitudinal variations in pain may confound changes in the apparent thickness of the articular cartilage. [source] Stereospecificity and stereoselectivity of flobufen metabolic profile in male rats in vitro and in vivo: Phase I of biotransformationCHIRALITY, Issue 10 2001Vladimír Wsól Abstract Flobufen (F) is the original nonsteroidal antiinflammatory drug (NSAID) containing two enantiomers. The aim of this investigation was to elucidate the biotransformation pathway of F at chiral level in phase I of biotransformation. Stereoselectivity and stereospecificity of the respective enzymes were studied in male rats in vitro (microsomal and cytosolic fractions, hepatocytes suspension) and in vivo. The rac -F, (+)-R-F and (,)-S-F were used as substrates. Amounts of F enantiomers, 4-dihydroflobufen diastereoisomers (DHF) and other metabolites (M-17203, UM) were determined with a chiral HPLC method in two chromatographic runs on R,R-ULMO and allyl-terguride bonded columns. Stereoselective biotransformation of the two enantiomers of F was observed at all tested levels and significant bidirectional chiral inversion of enantiomers of F was observed in hepatocytes. Mean enantiomeric ratios of F concentrations (S-/R-), after rac -F incubations, ranging from 1.09 in cytosolic fraction to 18.23 in hepatocytes. Stereospecificity of the respective F reductases was also observed. (2R;4S)-DHF and (2S;4S)-DHF are the principal metabolites of F in microsomes and hepatocytes. Neither DHF diastereoisomers nor M-17203 were found in cytosolic fraction. Only the nonchiral metabolite, M-17203, was found in all urine and feces samples after oral administration of F. Chirality 13:754,759, 2001. © 2001 Wiley-Liss, Inc. [source] Biotransformation of flobufen enantiomers in ruminant hepatocytes and subcellular fractionsCHIRALITY, Issue 10 2001Lenka Skálová Abstract Flobufen (F), a new antiinflammatory drug, has one chiral and one prochiral center in its structure. Reduction of rac - F, the principal biotransformation pathway, leads to the formation of four diastereoisomers of 4-dihydroflobufen (DHF). F was chosen as a model substrate for interspecies comparison of activity, stereospecificity, and stereoselectivity of biotransformation enzymes in fallow bucks, red deer stags, and roe bucks in vitro. Formation of F metabolites was examined in hepatocyte suspension and in subcellular fractions of liver homogenate. (+)-R -F, (,)-S -F and rac - F were used as substrates. After incubation of substrates, the amounts and ratios of DHF diastereoisomers and F enantiomers were assessed by HPLC, with (R,R)-ULMO and terguride-bonded columns. Considerable interspecies differences in stereoselectivity and stereospecificity of F reductases were found at the cellular and subcellular levels, although these ruminants are closely related. Chiral inversion of F enantiomers to their antipodes was detected in vitro in all ruminants tested, but individual species also differed in the direction and rate of this inversion. Chirality 13:760,764, 2001. © 2001 Wiley-Liss, Inc. [source] Inflammation and the etiology of type 2 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2006Åke Sjöholm Type 2 diabetes is increasingly common worldwide and is beginning to strike younger age groups. Almost 90% of all patients with diabetes show insulin resistance, which also precedes the first symptoms of diabetes. The mechanisms underlying the development of insulin resistance are not well understood. In recent years, several studies have been published that implicate subclinical chronic inflammation as an important pathogenetic factor in the development of insulin resistance and type 2 diabetes. This opens new perspectives for diagnosis and treatment of early insulin resistance and incipient glucose intolerance. Surrogate markers for this low-grade chronic inflammation include CRP, IL-6 and TNF-,. Some antidiabetic agents, for example, glitazones that reduce insulin resistance, and insulin itself, reduce inflammation. Conversely, antiinflammatory drugs (ASA/NSAID) may improve glucose tolerance. Vasoactive drugs that are often prescribed to people with diabetes, for example, statins and ACE inhibitors/angiotensin receptor antagonists, also counteract inflammation and reduce the risk of type 2 diabetes. More specific and sensitive biomarkers should be identified, which may predict early disturbances in insulin sensitivity and cardiovascular risk. Also, inflammatory signalling pathways need to be explored in greater detail, and may form the basis of drugable targets against the epidemic of insulin resistance and atherosclerosis. Copyright © 2005 John Wiley & Sons, Ltd. [source] Effects of a new 1,3,4-thiadiazolium mesoionic compound, MI-D, on the acute inflammatory responseDRUG DEVELOPMENT RESEARCH, Issue 4 2004Júlio C. Cardoso Abstract A new mesoionic compound, 4-phenyl-5-(4-nitro-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine (MI-D), is described along with some of its biological properties. Its effects on hepatic metabolism, on O and nitric oxide (NO) production, and in in vivo models for potential antinociceptive, antipyretic, and antiinflammatory activities were determined. In perfused rat liver, MI-D (25 µM) stimulated glycogenolysis (95%), and inhibited oxygen uptake (37%) with affecting glycolysis. In phorbol 12-myristate 13-acetate-stimulated macrophages, O generation was reduced (95%) by MI-D (15 µM), whereas the production of NO was unaffected. MI-D (2 mg/kg) inhibited (55%) the number of abdominal writhings induced by acetic acid. At 1 mg/kg, MI-D inhibited the febrile response (5 h) induced by lipopolysaccharide (LPS) and was also effective against a preexisting febrile response. Treatment with MI-D (1 mg/kg) reduced by 67% prostaglandin (PGE2) levels in the cerebrospinal fluid of LPS-exposed mice, and at a higher dose (8 mg/kg) MI-D inhibited paw edema formation (2 h) induced by carrageenan. MI-D has a spectrum of activities similar to other nonsteroidal antiinflammatory drugs, qualifying it as a potential anti-inflammatory drug. Drug Dev. Res. 61:207,217, 2004. © 2004 Wiley-Liss, Inc. [source] Nonsteroidal antiinflammatory drugs as therapeutic agents for Alzheimer's diseaseDRUG DEVELOPMENT RESEARCH, Issue 3 2002Todd E. Golde One feature of the end-stage pathology of Alzheimer's disease (AD) is the presence of numerous inflammatory markers associated with the amyloid , protein (A,) deposits in the brain. Experimental data strongly suggests that A, aggregates can incite an inflammatory response, but there are also data suggesting that inflammation can promote A, production and deposition. Thus, antiinflammatory drugs may have some role in AD therapy. This idea is supported by epidemiologic data, which shows that long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) confers protection from the development of AD. Significantly, oral salicylates have not been consistently shown to confer protection. Such studies have raised questions regarding the target or targets of NSAIDs that account for their apparent protection from AD. We have recently found that some NSAIDs have a novel mechanism of action, namely, selective lowering of the pathogenic A,42 peptide, that could contribute to their efficacy in AD. Further study will be needed to determine if the classic antiinflammatory properties of NSAIDs, the A,42-lowering property, another known or unknown property, or a combination of these contributes to NSAIDs apparent ability to protect individuals from the development of AD. Drug Dev. Res. 56:415,420, 2002. © Wiley-Liss, Inc. [source] Development of antiinflammatory therapy for Alzheimer's diseaseDRUG DEVELOPMENT RESEARCH, Issue 3 2002Paul S. Aisen Abstract Inflammatory mechanisms are active in the Alzheimer's disease (AD) brain. Studies that range from epidemiological surveys to therapeutic trials in transgenic mice provide growing support for the theory that antiinflammatory drugs may be useful in the prevention and/or treatment of the disease. Randomized controlled trials in humans have not yet confirmed this theory. However, prevention and treatment trials continue to test specific antiinflammatory strategies for AD. Drug Dev. Res. 56:421,427, 2002. © 2002 Wiley-Liss, Inc. [source] Eradication of Helicobacter pylori Does Not Reduce the Incidence of Gastroduodenal Ulcers in Patients on Long-term NSAID Treatment: Double-Blind, Randomized, Placebo-Controlled TrialHELICOBACTER, Issue 5 2007Helena T.J.I. De Leest Abstract Background:,,Helicobacter pylori and nonsteroidal antiinflammatory drugs (NSAIDs) are the major causes of gastroduodenal ulcers. Studies on the benefit of eradication of H. pylori in NSAID users yielded conflicting results. Objective:, To investigate whether H. pylori eradication in patients on long-term NSAIDs reduces the incidence of gastroduodenal ulcers. Methods:, Patients on long-term NSAID treatment and who are H. pylori positive on serologic testing, were randomly assigned to either H. pylori eradication (omeprazole, amoxicillin, and clarithromycin) or placebo. Primary endpoint was the presence of endoscopic gastric or duodenal ulcers 3 months after randomization. Results:, One hundred sixty-five (48%) of a total of 347 patients were on gastroprotective medication. At endoscopy, gastroduodenal ulcers were diagnosed in 6 (4%) and 8 (5%) patients in the eradication and placebo group, respectively (p = .65). During follow-up of 12 months, no symptomatic ulcers or ulcer complications developed. No significant differences were found in the development of gastroduodenal erosions, dyspepsia, or in quality of life. Conclusion:,H. pylori eradication therapy in patients on long-term NSAID treatment had no beneficial effect on the occurrence of ulcers, erosions, or dyspepsia. Ulcer rates in both study arms are remarkably low, in both patients with and without gastroprotective therapy. [source] Polymorphisms in PTGS1, PTGS2 and IL-10 do not influence colorectal adenoma recurrence in the context of a randomized aspirin intervention trialINTERNATIONAL JOURNAL OF CANCER, Issue 9 2007Richard A. Hubner Abstract Regular use of aspirin and other nonsteroidal antiinflammatory drugs reduces both the development of colorectal neoplasia and recurrence of colorectal adenoma (CRA). Modulation of the effects of aspirin by genetic factors has been reported, potentially allowing targeting of treatment to individuals most likely to gain benefit. Prostaglandin H synthase 1 (PTGS1) and PTGS2 are key enzymes in prostaglandin synthesis and are inhibited by aspirin, whilst interleukin-10 (IL-10) is an important antiinflammatory cytokine. We investigated whether functional genetic polymorphisms in the PTGS1, PTGS2 and IL-10 genes influence CRA recurrence in individuals participating in a randomized aspirin intervention trial. DNA was available for genotyping from 546 patients who received aspirin (300 mg daily) or placebo for a mean 41-months' duration. Homozygote carriers of variant alleles for the PTGS1 50C>T, PTGS2 ,765G>C and IL-10 ,592C>A polymorphisms did not have a significantly altered risk of CRA recurrence (relative risk [RR] = 0.91; 95% confidence interval [CI]: 0.14,6.07, RR = 1.32; 95%CI: 0.66,2.62 and RR = 1.24; 95% CI: 0.74,2.07, respectively). There were also no significant interactions between aspirin intervention and genotype in determining recurrence risk. These data indicate that these polymorphisms are unlikely to influence CRA recurrence and cannot be used to identify individuals who derive benefit from aspirin intervention. © 2007 Wiley-Liss, Inc. [source] Nonsteroidal antiinflammatory drug use and risk of bladder cancer in the health professionals follow-up studyINTERNATIONAL JOURNAL OF CANCER, Issue 10 2007Jeanine M. Genkinger Abstract Nonsteroidal antiinflammatory drugs (NSAIDs) use, particularly aspirin, may lower the risk of several cancers, including bladder. NSAIDs may reduce development of bladder tumors by decreasing inflammation, inhibiting cycloxygenase-2, inhibiting proliferation and inducing apoptosis of cancer cells. However, acetaminophen, a major metabolite of phenacetin, may be positively associated with bladder cancer risk. Results from case-control studies on NSAIDs and acetaminophen use and bladder cancer risk are inconsistent. We investigated the association between NSAID and acetaminophen use and bladder cancer risk in a large cohort of US males. Among 49,448 men in the Health Professionals Follow-Up Study, 607 bladder cancer cases were confirmed during 18 years of follow-up. Relative risks (RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models. Multivariate RR were adjusted for age, current smoking status, pack years, geographic region and fluid intake. No significant associations were observed for regular aspirin (,2 tablets per week), (RR = 0.99, 95% CI 0.83,1.18), ibuprofen (RR = 1.11, 95% CI 0.81,1.54), acetaminophen (RR = 0.96, 95% CI 0.67,1.39) or total NSAID use (not including acetaminophen; RR = 1.01, 95% CI 0.85,1.20) and bladder cancer risk compared with nonuse. Consistent use (over 6 years) of aspirin, ibuprofen, acetaminophen and total NSAIDs, compared to nonuse, was not associated with bladder cancer risk. No association was observed between aspirin frequency and dose and bladder cancer risk. We observed no effect-modification by smoking, age or fluid intake. Our results suggest that regular NSAID or acetaminophen use has no substantial impact on bladder cancer risk among men. © 2007 Wiley-Liss, Inc. [source] Effect of NSAIDs on the recurrence of nonmelanoma skin cancerINTERNATIONAL JOURNAL OF CANCER, Issue 3 2006Maria V. Grau Experimental studies have consistently shown a protective effect of nonsteroidal antiinflammatory drugs (NSAIDs) against nonmelanoma skin cancers (NMSC). However, little human epidemiological research has been done in this regard. We used data from the Skin Cancer Chemoprevention Study to explore the association of NSAID use and with the risk of basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC). 1,805 subjects with a recent history of NMSC were randomized to placebo or 50 mg of daily ,-carotene. Participants were asked about their use of over-the-counter and prescription medications at baseline and every 4 months during the trial. Skin follow-up examinations were scheduled annually with a study dermatologist; confirmed lesions were the endpoints in the study. We used a risk set approach to the analysis of grouped times survival data and unconditional logistic regression to compute odds ratios [ORs] for various exposures to NSAIDs. The use of NSAIDs was reported in over 50% of questionnaires. For BCC, NSAIDs exhibited a weak protective effect in crude analyses, which attenuated markedly after adjustment. For SCC, the use of NSAIDs in the year previous to diagnosis reduced the odds by almost 30% (adjusted OR= 0.71, 95% CI 0.48,1.04). When we accounted for frequency of use, results for BCC were not striking, and there were inconsistent suggestions of an inverse association with SCC. There were some indications of a modest, nonsignificant reduction on the number of BCCs and SCCs with NSAID use. Our data suggest a weak and inconsistent chemopreventive effect of NSAIDs on BCC and SCC. © 2006 Wiley-Liss, Inc. [source] An unusual cause of dizziness in bulimia nervosa: A case reportINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 4 2005Randy A. Sansone MD Abstract Objective The current article describes the case of a 23<->year<->old female with purging<->type bulimia nervosa who was evaluated by her primary care physician for dizziness and lightheadedness. Methods After laboratory studies were performed by her primary care physician, the patient was admitted to the hospital because of severe anemia. The patient had been taking nonsteroidal antiinflammatory drugs <(>NSAIDS<)> at prescribed doses for shin splints that were secondary to jogging and developed gastric erosion. Results Endoscopic examination showed that she had diffuse gastritis with linear, streaky ulcerations throughout the body of the stomach. Discussion Lightheadedness is a common clinical symptom among individuals with eating disorders, but is typically related to dehydration, malnutrition, hypometabolism, andor combinations of these factors. Clinicians need to consider NSAID use, which may cause erosive gastritis, blood loss, and lightheadedness. © 2005 by Wiley Periodicals, Inc. [source] Persistent Nonmalignant Pain and Analgesic Prescribing Patterns in Elderly Nursing Home ResidentsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2004(See editorial comments by Dr. Debra Weiner on pp 1020, 1022) Objectives: To determine the prevalence of analgesics used, their prescribing patterns, and associations with particular diagnoses and medications in patients with persistent pain. Design: Cross-sectional study. Setting: Nursing homes from 10 U.S. states. Participants: A total of 21,380 nursing home residents aged 65 and older with persistent pain. Measurements: Minimum Data Set (MDS) assessments on pain, analgesics, cognitive, functional, and emotional status were summarized. Logistic regression models identified diagnoses associated with different analgesic classes. Results: Persistent pain as determined using the MDS was identified in 49% of residents with an average age of 83; 83% were female. Persistent pain was prevalent in patients with a history of fractures (62.9%) or surgery (63.6%) in the past 6 months. One-quarter received no analgesics. The most common analgesics were acetaminophen (37.2%), propoxyphene (18.2%), hydrocodone (6.8%), and tramadol (5.4%). Only 46.9% of all analgesics were given as standing doses. Acetaminophen was usually prescribed as needed (65.6%), at doses less than 1,300 mg per day. Nonsteroidal antiinflammatory drugs (NSAIDs) were prescribed as a standing dose more than 70% of the time, and one-third of NSAIDs were prescribed at high doses. Conclusion: In nursing home residents, persistent pain is highly prevalent, there is suboptimal compliance with geriatric prescribing recommendations, and acute pain may be an important contributing source of persistent pain. More effective provider education and research is needed to determine whether treatment of acute pain could prevent persistent pain. [source] Kinetics and mechanism of sodium N -halo- p -toluenesulfonamides oxidation of diclofenac in alkaline mediumAICHE JOURNAL, Issue 12 2009Puttaswamy Abstract Diclofenac belongs to a class of drugs called nonsteroidal antiinflammatory drugs. The kinetics and mechanism of oxidation of diclofenac by sodium N -halo- p -toluenesulfonamides viz., chloramine-T and bromamine-T in NaOH medium have been studied at 293 K. Under comparable experimental conditions, reactions with both the oxidants follow identical kinetics with a first-order dependence on each [oxidant]o and a fractional-order dependence on each [diclofenac]o and [NaOH]. Activation parameters have been computed. N -hydroxyldiclofenac is identified as the oxidation product of diclofenac. Michaelis-Menten type of mechanism has been suggested. The rate of oxidation of diclofenac is about four-fold faster with bromamine-T when compared with chloramine-T. This may be attributed to the difference in electrophilicities of Cl+ and Br+ ions and also the van der Waal's radii of chlorine and bromine. Plausible mechanism and related rate law have been designed for the observed kinetics. © 2009 American Institute of Chemical Engineers AIChE J, 2009 [source] Dopaminergic neurotoxicity by 6-OHDA and MPP+: Differential requirement for neuronal cyclooxygenase activityJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2005Emilce Carrasco Abstract Cyclooxygenase (COX), a key enzymatic mediator of inflammation, is present in microglia and surviving dopaminergic neurons in Parkinson's disease (PD), but its role and place in the chain of neurodegenerative events is unclear. Epidemiologic evidence showed that regular use of nonsteroidal antiinflammatory drugs (NSAIDs), specifically non-aspirin COX inhibitors like ibuprofen, lowers the risk for PD; however, the putative cause-and-effect relationship between COX activity in activated microglia and neuronal loss was challenged recently. We examined whether neuronal COX activity is involved directly in dopaminergic cell death after neurotoxic insult. Using low concentrations of 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridium ion (MPP+), neurotoxicants used to model selective dopaminergic cell loss in PD, and cultures of embryonic rat mesencephalic neurons essentially devoid of glia, we tested whether the nonselective COX inhibitor ibuprofen attenuated 6-OHDA and MPP+ neurotoxicity. At levels close to its IC50 for both COX isoforms, ibuprofen protected dopaminergic neurons against 6-OHDA but not MPP+ toxicity. Experiments with selective inhibitors of COX-1 (SC-560) and COX-2 (NS-398 and Cayman 10404), indicated that COX-2, but not COX-1, was involved in 6-OHDA toxicity. Accordingly, 6-OHDA, but not MPP+, increased prostaglandin (PG) levels twofold and this increase was blocked by ibuprofen. At concentrations well above its IC50 for COX, ibuprofen also prevented MPP+ toxicity, but had only limited efficacy against loss of structural complexity. Taken together, our data suggest that selective 6-OHDA toxicity to dopaminergic neurons is associated with neuronal COX-2, whereas MPP+ toxicity is COX independent. This difference may be important for understanding and manipulating mechanisms of dopaminergic cell death. © 2005 Wiley-Liss, Inc. [source] BMP-7,induced ectopic bone formation and fracture healing is impaired by systemic NSAID application in C57BL/6-mice,JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2010Alexander S. Spiro Abstract Nonsteroidal antiinflammatory drugs (NSAIDs) are known to potentially impair the fracture healing process. The aim of the present study was to determine if the impairment of bone healing by systemic NSAID application is, at least in part, due to an interaction of NSAIDs with the bone anabolic BMP-7 pathway. Therefore, we first analyzed fracture healing in control and diclofenac-treated mice, where we not only found a significant impairment of fracture healing due to diclofenac treatment as assessed by biomechanical testing and µCT imaging, but also found high coexpression of bone morphogenetic protein-7 (BMP-7) and cyclooxygenase-2 (COX-2) within the fracture callus of both groups. To experimentally address the possible interaction between BMP-7 and COX-2, we then induced ectopic bone formation in control (n,=,10) and diclofenac-treated mice (n,=,10) by application of BMP-7 (recombinant human OP-1, rhOP-1) into the hamstring muscles. After 20 days of treatment, each ectopic bone nodule was analyzed by contact-radiography, µCT, histology, and histomorphometry. Diclofenac application decreased the trabecular number and bone mass in the ectopic bone nodules significantly due to reduced osteoblast number and activity. These data demonstrate that the bone anabolic effect of BMP-7 and fracture healing is impaired by diclofenac application, and suggest that the potential negative impact of NSAIDs on fracture healing is, at least in part, due to interference with BMP-7 signaling. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:785,791, 2010 [source] Deep percutaneous penetration into muscles and jointsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2006Christine M. Lee Abstract The transdermal absorption of drugs and its subsequent deep tissue delivery is a complex process, with many factors influencing the penetration mechanisms. Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used in the treatment of joint and muscle diseases. However, the dangers associated with oral medications highlight the need for alternative methods of targeting and retaining drugs; one such means is through topical delivery. The drug's lipophilicity, permeability, and fraction unbound found in the viable skin are some physiochemical factors influencing the delivery mechanism after transdermal absorption. These and other variables play a role in determining whether the drug reaches the deep tissues via direct penetration or from systemic redistribution. Pharmacokinetic models have been developed to help elucidate the penetration routes and efficacy for various drugs. While there are still uncertainties regarding the deep tissue penetration kinetics, improvements to current research methodologies may bring about a greater understanding of percutaneous absorption into the deep muscle and joints. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1405,1413, 2006 [source] Determination of nonsteroidal antiinflammatory drugs in water samples using liquid chromatography coupled with diode-array detector and mass spectrometryJOURNAL OF SEPARATION SCIENCE, JSS, Issue 17 2005Jolanta Debska Abstract An analytical method for the determination of trace levels of six different nonsteroidal antiinflammatory drugs (NSAIDs) in water samples has been developed and validated. Environmentally relevant pharmaceuticals were chosen according to human consumption in Poland. Final analysis of the target compounds was performed by RP LC,diode-array detection,MS, whereas sample preparation included an SPE step. For this SPE step, a number of packing materials, such as LiChrolut RP-18, calixarene, Strata-X, BAKERBOND Narc-2, BAKERBOND Polar Plus, BAKERBOND styrene divinylbenzene-1, and Discovery DSC-18, were used, and their respective advantages and disadvantages in this study were discussed. The RP-18 phase was found to be the most retentive for all analytes. The detection limits for compounds in surface waters were varied from 0.005 for diflunisal to 0.095 ,g/L for ibuprofen. The average recoveries of NSAIDs from the surface water samples ranged from 80 up to 103%. RSD value is relatively low (from 4% for fenoprofen up to 8% for ibuprofen). The performance of the method was tested with several environmental water samples. [source] The influence of extreme body weight on clinical outcome of patients with venous thromboembolism: findings from a prospective registry (RIETE)JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2005R. BARBA Summary.,Background:,Data evaluating the safety of using weight-based dosing of low-molecular-weight heparin (LMWH) in either underweight or obese patients with venous thromboembolism (VTE) are limited. Thus, recommendations based on evidence from clinical trials might not be suitable for patients with extreme body weight. Patients and Methods:,Patients with objectively confirmed, symptomatic acute VTE are consecutively enrolled into the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry. For this analysis, data from patients in the following ranges of body weight were examined: <50, 50,100, and >100 kg. Patient characteristics, underlying conditions, treatment schedules and clinical outcomes during the first 15 days of treatment were compared. Results:,As of August 2004, 8845 patients with acute VTE were enrolled from 94 participating centers. Of these, 169 (1.9%) weighed <50 kg, 8382 (95%) weighed 50,100 kg and 294 (3.3%) weighed >100 kg. Patients weighing <50 kg were more commonly females, were taking non-steriodal antiinflammatory drugs (NSAIDs), and had severe underlying diseases more often than patients weighing 50,100 kg. Their incidence of overall bleeding complications was significantly higher than in patients weighing 50,100 kg (odds ratio 2.2; 95% CI: 1.2,4.0). Patients weighing >100 kg were younger, most commonly males, and had cancer less often than those weighing 50,100 kg. Incidences of recurrent VTE, fatal pulmonary embolism or major bleeding complications were similar in both groups. Conclusions:,Patients with VTE weighing <50 kg have a significantly higher rate of bleeding complications. The clinical outcome of patients weighing over 100 kg was not significantly different from that in patients weighing 50,100 kg. [source] Sequential clot strength analyses following diclofenac in pediatric adenotonsillectomyPEDIATRIC ANESTHESIA, Issue 11 2007MAIREAD HEANEY FCARCSI FJFICM Summary Background:, Tonsillectomy is a common pediatric surgical procedure resulting in significant postoperative pain. There is ongoing controversy as to the most satisfactory analgesic regimen. Nonsteroidal antiinflammatory drugs (NSAIDs) are an alternative to opioids in this setting. NSAID use in tonsillectomy has been shown to be opioid sparing in the recovery period and to have similar analgesic effects to opioids in pediatric patients. Because of their nonspecific action on the enzyme cyclo-oxygenase there is potential for increased bleeding which has led many practitioners to avoid NSAIDs completely in this patient population potentially resulting in suboptimal pain control. Our aim in this study was to assess the effect of preoperatively administered diclofenac on the blood clot strength in children undergoing (adeno-) tonsillectomy. Methods:, Twenty patients undergoing (adeno-) tonsillectomy were recruited into this prospective observational study. All patients received 2 mg·kg,1 of diclofenac rectally immediately preoperatively. Blood was taken for thromboelastograph analysis pre-diclofenac and 1 and 4 h post-diclofenac administration. Results:, There was a statistically significant increase in maximal clot strength (MA) at 1 and 4 h after diclofenac. Similarly there was a statistically significant reduction in time to initial fibrin formation (R time) post-diclofenac. There was no primary or secondary hemorrhage. Conclusions:, Diclofenac when given preoperatively does not adversely affect clot strength in the immediate postoperative period when the risk of primary hemorrhage is greatest. [source] Pseudoporphyria and Nonsteroidal Antiinflammatory Agents in Children with Juvenile Idiopathic ArthritisPEDIATRIC DERMATOLOGY, Issue 6 2000Bernadette De Silva M.R.C.P. Nonsteroidal antiinflammatory drugs (NSAIDs) are implicated in the etiology of this condition. In a 1-year prospective study of children attending the pediatric rheumatology clinic in Edinburgh we found a prevalence of pseudoporphyria of 10.9% in children taking NSAIDs for juvenile idiopathic arthritis. Naproxen was the most commonly implicated NSAID, independent of dosage. Blue/gray eye color was an independent risk factor for the development of pseudoporphyria. We would advise caution in prescribing naproxen in these children to prevent disfiguring facial scarring. [source] Azorellane diterpenoids from Laretia acaulis inhibit nuclear factor-kappa B activityPHYTOTHERAPY RESEARCH, Issue 11 2007Jorge Borquez Abstract Transcription factor NF- ,B plays a key role in the inducible expression of genes mediating proinflammatory effects, and is thus an important target for the development of antiinflammatory drugs. Laretia acaulis (Cav.) Gill et Hook (Apiaceae) is a medicinal plant used in the high Andes mountains for different ailments such as diabetes, inflammation and for general pain. In addition to the known azorellanol (2) and 7-deacetylazorellanol (4), 13-epiazorellanol (1) was also isolated from the aerial part of this plant. Its structure was based on spectroscopic comparison with azorellanol (2) and by chemical characterization. While compounds 2 and 4 showed potent anti-NF- ,B activity by targeting the activity of the I,B, kinase, compound 1 was completely inactive highlighting the importance of position 13 in the biological activities of this class of tetracyclic diterpenoids. Copyright © 2007 John Wiley & Sons, Ltd. [source] Evidence of effectiveness of herbal antiinflammatory drugs in the treatment of painful osteoarthritis and chronic low back painPHYTOTHERAPY RESEARCH, Issue 7 2007J. E. Chrubasik Abstract Treatment with herbal medicines is very popular in Europe. In order to get information on the evidence of effectiveness of oral herbal medicines in the treatment of pain in the joints or lower back, OVID(MEDLINE), PUBMED and COCHRANE COLLABORATION LIBRARY were searched back to 1985 for systematic reviews. The level of evidence of effectiveness was defined as strong , at least two confirmatory studies demonstrating a clinical relevant effect, moderate , one confirmatory study with a clinical relevant effect and/or multiple exploratory studies of good quality; otherwise the evidence was insufficient or conflicting in the case of inconsistent findings. Fifteen systematic reviews were identified. The evidence of effectiveness was strong for a proprietary unsaponifiable avocado soybean fraction and Harpagophytum preparations containing >50 mg harpagoside in the daily dosage, moderate for ginger and a proprietary rose hip and seed powder, insufficient for Boswellia serrata gum resin and other herbal preparations and inconsistent for a proprietary willow bark extract. Further rigorous studies are required to confirm the usefulness of herbal medicines in the treatment of osteoarthritic complaints and chronic low back pain in order to enable acceptance of the herbal medicines into the treatment guidelines. Copyright © 2007 John Wiley & Sons, Ltd. [source] Canakinumab for the treatment of acute flares in difficult-to-treat gouty arthritis: Results of a multicenter, phase II, dose-ranging study,ARTHRITIS & RHEUMATISM, Issue 10 2010Alexander So Objective To assess the efficacy and tolerability of canakinumab, a fully human anti,interleukin-1, monoclonal antibody, for the treatment of acute gouty arthritis. Methods In this 8-week, single-blind, double-dummy, dose-ranging study, patients with acute gouty arthritis whose disease was refractory to or who had contraindications to nonsteroidal antiinflammatory drugs and/or colchicine were randomized to receive a single subcutaneous dose of canakinumab (10, 25, 50, 90, or 150 mg; n = 143) or an intramuscular dose of triamcinolone acetonide (40 mg; n = 57). Patients assessed pain using a 100-mm visual analog scale. Results Seventy-two hours after treatment, a statistically significant dose response was observed for canakinumab. All canakinumab doses were associated with numerically less pain than triamcinolone acetonide; thus, a dose with equivalent efficacy to triamcinolone acetonide 72 hours after treatment could not be determined. The reduction from baseline in pain intensity with canakinumab 150 mg was greater than with triamcinolone acetonide 24, 48, and 72 hours after treatment (differences of ,11.5 mm [P = 0.04], ,18.2 mm [P = 0.002], and ,19.2 mm [P < 0.001], respectively), and 4, 5, and 7 days after treatment (all P < 0.05). Canakinumab significantly reduced the risk of recurrent flares versus triamcinolone acetonide (P , 0.01 for all doses) (relative risk reduction 94% for canakinumab 150 mg versus triamcinolone acetonide). The overall incidence of adverse events was similar for canakinumab (41%) and triamcinolone acetonide (42%); most were mild or moderate in severity. Conclusion Our findings indicate that canakinumab 150 mg provides rapid and sustained pain relief in patients with acute gouty arthritis, and significantly reduces the risk of recurrent flares compared with triamcinolone acetonide. [source] | |||||||||||||||||||||||||||||||