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Practice recommendation * Though all non-narcotic analgesics have equivalent efficacy against tension-type headache, ibuprofen's generally favorable side-effect profile makes it a reasonable first choice. Whereas quantitative and qualitative analyses of [...]

Nonsteroidal antiinflammatory drugs (NSAIDs) appear to reduce the risk of developing cancer. One mechanism through which NSAIDs act to reduce carcinogenesis is to inhibit the activity of cyclooxygenase-2 (COX-2), an enzyme that is overexpressed in various cancer tissues. Overexpression of COX-2 increases cell proliferation and inhibits apoptosis. However, selective COX-2 inhibitors can also act through COX-independent mechanisms. In this review, we describe the COX-2-independent molecular targets of these COX-2 inhibitors and discuss how these targets may be involved in the anticarcinogenic activities of these selective COX-2 inhibitors. We also compare the concentrations of these inhibitors used in in vitro and in vivo experiments and discuss the implications of the in vitro studies for clinical management of cancer with these drugs.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jtcvs.2005.07.018 Byline: Leah M. Backhus (a), Nicos A. Petasis (b), Jasim Uddin (b), Axel H. Schonthal (c), Robert D. Bart (a), Yuanguang Lin (a), Vaughn A. Starnes (a), Ross M. Bremner (a) Abbreviations: COX-2, cyclooxygenase 2; DMC, 2,5-dimethyl celecoxib; FBS, fetal bovine serum; FITC, fluorescein isothiocyanate; IL, interleukin; MMP, matrix metalloproteinase; MTS, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; NSCLC, non-small cell lung cancer; PBS, phosphate-buffered saline; PGE.sub.2, prostaglandin E.sub.2; RPMI, Roswell Park Memorial Institute Abstract: The cyclooxygenase 2 enzyme has become a therapeutic target in cancer treatment. Cyclooxygenase 2 blockade with selective inhibitors increases apoptosis and decreases the metastatic potential of lung cancer cells. Some of the antitumor effects of these inhibitors may occur through both cyclooxygenase 2-dependent and independent pathways. Our goal was to investigate these pathways using celecoxib (selective cyclooxygenase 2 inhibitor) and 2,5-dimethyl celecoxib, a structural analog modified to eliminate cyclooxygenase 2 inhibitory activity, while potentially maintaining antineoplastic properties. Author Affiliation: (a) Department of Cardiothoracic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, Calif (b) Department of Chemistry, University of Southern California, Los Angeles, Calif (c) Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, Calif. Article History: Received 14 April 2005; Revised 9 June 2005; Accepted 19 July 2005 Article Note: (footnote) L. Backhus is a recipient of the Los Angeles Heart and Lung Research Grant. R. Bremner is a recipient of the Robert E. Gross Research Grant from the Graham Education and Research Foundation of The American Association for Thoracic Surgery. This work was supported in part by a generous grant from the Hastings Foundation.

Background: The relationship between the use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, and the risk of gastric cancer has not been well studied. We performed a systematic review and meta-analysis of published studies to evaluate the association between use of this class of drugs and the risk of gastric cancer. Methods: A fully recursive literature search to January 2003 was conducted in MEDLINE, PubMed, and CANCERLIT to identify potentially relevant case-control or cohort studies. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under a random-effects model. Results: Nine studies (eight case--control and one cohort) with a total of 2831 gastric cancer case patients were identified. NSAID use was associated with a reduced risk of gastric cancer, with a summary odds ratio of 0.78 (95% CI = 0.69 to 0.87). Users of aspirin (OR = 0.73, 95% CI = 0.63 to 0.86) and non-aspirin NSAIDs (OR = 0.74, 95% CI = 0.55 to 1.00) experienced similar magnitudes of risk reduction. Regular users of NSAIDs (OR = 0.57, 95% CI = 0.44 to 0.74) experienced a lower risk of gastric cancer relative to nonusers than did irregular users (OR = 0.76, 95% CI = 0.62 to 0.94; P = .09 versus regular users). A stratified analysis showed that NSAID use was associated with a statistically significant reduction in risk of noncardia gastric cancer (OR = 0.72, 95% CI = 0.58 to 0.89), but not of gastric cancer at the cardia (OR = 0.80, 95% CI = 0.53 to 1.20). There was no evidence that study design or type of control subject substantially influenced the estimate of effects. Conclusion: NSAID use was associated with a decreased risk of gastric cancer in a dose-dependent manner. This finding warrants proper clinical trials in populations with high risk of gastric cancer.

Management of ankylosing spondylitis (AS) is challenged by the progressive nature of the disease. To date, no intervention is available that alters the underlying mechanism of inflammation in AS. Currently [...]

Laboratory studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) may inhibit pancreatic cancer, but epidemiologic data to support this finding are limited. We conducted a prospective study from 1992 through 1999 among 28283 postmenopausal women who lived in Iowa to examine the association between the self-reported use of aspirin and other NSAIDs and the incidence of pancreatic cancer. Eighty incident cases of pancreatic cancer were identified during 7 years of follow-up. The multivariate-adjusted relative risk of pancreatic cancer associated with any current use of aspirin versus no use was 0.57 (95% confidence interval = 0.36 to 0.90). There was a trend of decreasing risk of pancreatic cancer incidence with increasing frequency of aspirin use per week ([P.sub.trend] = .005). Nonaspirin NSAID use was not associated with incident pancreatic cancer. These data indicate that aspirin might be chemopreventive for pancreatic cancer. [J Natl Cancer Inst 2002;94:1168-71]

Background: We have previously reported that nonsteroidal anti-inflammatory drugs inhibit lung tumorigenesis induced by the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in mice. Purpose: The aims of this study were to determine if NNK suppresses humoral (i.e., antibody) and cellular immune responses in mice and if nonsteroidal anti-inflammatory drugs could attenuate these immune responses. Methods: Female A/J mice (7-8 weeks old) were fed nonsteroidal anti-inflammatory drugs starting 2 weeks before the beginning of NNK treatment (9.1 mg per mouse in total) and continuing through the 7 weeks of NNK treatment. Eight groups (two control groups and six experimental groups) of 10 mice each were used per experiment. Animals in the two control groups received the same diet and water as animals in the six experimental groups; one control group received no nonsteroidal anti-inflammatory drugs or NNK and the other control group received only NNK. The primary humoral and cellular immune responses to the various treatments were assayed by the plaqueforming cell technique and by measurement of natural killer cell cytotoxic activity, respectively. At the end of each experiment, the animals were killed, blood was collected, plasma was prepared, and levels of the immune system modulator prostaglandin E, were measured. Results: NNK treatment inhibited the plaque-forming cell response by approximately 50%; this inhibition was attenuated by treatment with sulindac or acetylsalicylic acid (P = .0001 for both). In contrast, treatment with naproxen, which had no chemopreventive (i.e., tumor inhibitory) efficacy, further increased by 26% (P = .05) the immunosuppressive effect of NNK. The cytotoxic activity of splenic natural killer cells against YAC-1 cells was reduced by 60% (P = .002); treatment with acetylsalicylic acid (254 mg/kg of diet) reduced the NNK-induced natural killer cell cytotoxicity inhibition by 50% (P = .02), whereas the administration of the specific cyclooxygenase-2 inhibitor NS-398 (7 mg/kg of diet) resulted in an almost complete recovery (approximately 95%, P = .04) of natural killer cell activity. The prostaglandin [E.sub.2] plasma concentration was approximately 100% greater in NNK-treated mice than in untreated mice. Treatment of the mice with nonsteroidal anti-inflammatory drugs attenuated this elevation (from approximately 25% to 100%), and NS-398 (7 mg/kg of diet) was the most effective (100%). Conclusions and Implications: The ability of various nonsteroidal anti-inflammatory drugs to inhibit NNK-induced carcinogenesis appears to be directly related to the ability of these drugs to inhibit NNK-induced immunosuppression. Our results suggest that the chemopreventive effect of nonsteroidal anti-inflammatory drugs may be mediated through the modulation of prostaglandin [E.sub.2] synthesis.

Two kinds of drugs are usually used to treat rheumatoid arthritis (RA), a form of arthritis in which there is inflammation of the lining of the joint and in which bone loss often occurs. One form of treatment is the nonsteroidal anti-inflammatory drugs (NSAIDs); they have fewer side effects than the corticosteroids, the other common treatment. NSAIDs are considered symptomatic therapy; that is, symptoms such as pain and swelling are relieved without slowing the progression of the disease. NSAIDs are also known to inhibit the synthesis of prostaglandins and thus show a variety of modulating effects on the immune system. This study, part of a multicenter trial of NSAIDs, was designed to see if the improvement in symptoms of RA was associated with changes in the level of T cells and B cells, which are part of the body's immune system. The study lasted for 12 weeks, and 13 of the original 18 RA patients completed it. Six of the patients did not respond to NSAIDs therapy; their symptoms progressed and they were changed to other drugs. Four of the seven patients who did respond to NSAIDs did well with NSAIDs alone. More importantly, while there seemed to be no significant effects on the immune system when the group was considered as a whole, there were effects in those patients who were responders. In these patients, NSAID therapy was accompanied by a decreased number of activated T cells and B cells. The authors note that this effect depends on sustained NSAID therapy, and is associated with clinical improvement. After prolonged treatment in responders, they also found a decrease in rheumatoid factor, which they believe resulted from improved control of the disease. More studies are needed to support or refute this point. The data from this study suggest that treating RA with NSAIDs may have a more profound effect on the disease process than previously suspected. (Consumer Summary produced by Reliance Medical Information, Inc.)

While oral NSAIDs are heavily used in systemic medicine, topical ophthalmic NSAIDs are relatively limited to eye care. The bottom line is that steroids still reign supreme in inflammation control. [...]

* EVIDENCE-BASED ANSWER For proximal saphenous vein thrombosis, anticoagulation is more effective than venous ligation (with or without stripping) in preventing deep venous thrombosis (DVT) and pulmonary embolus (PE) (strength [...]

Byline: PHOTOGRAPHED BY STEVEN KLEIN. COUNTER CULTURE FREQUENTLY POPPING OVER-THE-COUNTER PILLS FOR EVERYDAY ACHES MAY BE MORE DAMAGING THAN THE PAIN ITSELF. JANCEE DUNN REPORTS. Last summer, Sheree Lunn, a [...]

Talk about a headache. Rockefeller University researchers have discovered that nonsteroidal anti-inflammatory drugs, such as aspirin, can blunt the anti-depressive effect of SSRIs, or selective serotonin reuptake inhibitors. NSAIDs may [...]

Erythema Nodosum (EN) is a relatively uncommon disorder in the pediatric population, yet multiple pediatric diseases can lead to EN. The following paper delineates a case report of an adolescent female with EN. The common etiologies, clinical manifestations, and treatment strategies for EN are discussed. References are included in text and listed after the summary., Table of Contents Abstract Name that Bump Physical Exam Differential Diagnosis Etiology and Management of EN Summary References Name that Bump As a Pediatric Nurse Practitioner student on my first [...]

Byline: Hobday, Erin One bottle, two benefits Protecting your heart can painproof your prostate. Taking a daily aspirin can prevent benign prostatic hyperplasia (BPH). Researchers at the Mayo Clinic analyzed [...]

Several changes pertaining to the marketing of Rx NSAIDs have been made by the FDA. Pfizer was asked to withdraw valdecoxib (Bextra) from the market because of its unfavorable risk-versus-benefit [...]

2002 NOV 28 - (NewsRx.com & NewsRx.net) -- The commonly used pain medications acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDS), are associated with an increased risk of high blood pressure in [...]

Byline: Jerry Adler and Anne Underwood It was created to ease the pain of arthritis, by a German chemist whose father was being done in by the treatments available at [...]

SAN DIEGO -- Until data from large primary prevention trials underway prove otherwise, there is no place for the use of anti-inflammatory drugs or estrogen in the prevention or treatment [...]

2001 FEB 22 - (NewsRx.com) -- Taking non-steroidal anti-inflammatory drugs (NSAIDS) during pregnancy does not seem to increase the risk of adverse birth outcome (congenital abnormality, low birth weight, or [...]

When osteoarthritis is severe or inflammatory, physicians may consider using a nonsteroidal anti-inflammatory drug; instead of starting with a trial of acetaminophen, according to recommendations on osteoarthritis of the knee [...]

To stop Alzheimer's disease, a leading theory proposes reducing in-brain buildup of a protein fragment known as beta-amyloid. Scientists struggling to achieve this goal are, for example, testing a vaccine [...]

Cyclooxygenase-2-specific inhibitors are the new NSAIDs on the block. Unlike traditional NSAIDs, which are nonspecific cyclooxygenase (COX) inhibitors, the COX-2 inhibitors selectively block production of pain-mediating prostaglandins while sparing COX-1, [...]

Efforts continue to find anti-inflammatory agents to control Alzheimer's disease, despite a recent finding that rules out using one approach. Low doses of prednisone were ineffective in a double-blind, multicenter [...]

Forty years ago aspirin was the most commonly used painkiller. People stopped using it when they found out it caused problems in ulcer patients, children and daily stress-headache sufferers. They […]

Approximately 6-8% of all persons aged [is greater than] 65 y have Alzheimer disease and the prevalence of the disease is increasing. Any intervention strategy aimed at decreasing risks or delaying the onset of the disease will therefore have a substantial effect on health care costs. Nutrition seems to be one of the factors that may play a protective role in Alzheimer disease. Many studies suggest that oxidative stress and the accumulation of free radicals are involved in the pathophysiology of the disease. Several studies have shown the existence of a correlation between cognitive skills and the serum concentrations of folate, vitamin B12, vitamin B-6, and, more recently, homocysteine. However, nutritional factors have to be studied not alone but with the other factors related to Alzheimer disease: genetics, estrogen, antiinflammatory drag use, and socioeconomic variables. The objective of this article was to review recent studies in this field. Am J Clin Nutr 2000;71 (suppl):643S-9S. KEY WORDS Alzheimer disease, nutrition, estrogen, homocysteine, nonsteroidal antiinflammatory drugs

How to Resist Resistance Dr. John Koella was absolutely correct in his challenge to Dr. Patrick A. Murphy about efforts to curb antibiotic overuse ("Where Drug Resistance Starts," Letters, Sept. [...]

Martin RL, Irrgang JJ, Conti SF (University of Pittsburgh, Pittsburgh, Pa), Foot Ankle Int. 1998;19:803-811. This study was a retrospective correlational study using chart reviews and a mailed survey to [...]

YES Reducing the pain can facilitate return to motion, and early motion speeds recovery. A patient who suffers a soft-tissue injury should not take nonsteroidal anti-inflammatory drugs for the first [...]

PRACTICE CHANGER For patients with acute musculoskeletal injuries, topical NSAIDs are an effective alternative for pain relief. (1) Strength of recommendation B: Based on a meta-analysis of 47 high-quality randomized [...]

IN THE SWIM Building bigger muscles can mean lots of muscle pain. Avoid the NSAIDs and relleve your soreness with a dip in the pool. Bodybuilding is the constant quest [...]