Nonsteroidal anti-inflammatory drug-induced diaphragms and ulceration in the colon

Byrne, Michael F.; McGuinness, Jonathan; Smyth, C; Manning, Diarmuid S.; Sheehan, Katherine M.; Bohra, Shravan G; Patchett, Stephen; Murray, Frank E.

doi:10.1097/00042737-200211000-00017

Cited by 28 publications

(32 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Given the high fecundidity and translucency of the zebrafish, this model may afford a high throughput system for characterization of novel PGES inhibitors. 4 COX-1 is expressed constitutively in most cells, whereas COX-2 is most commonly induced by inflammatory cytokines and mitogens. 5 Selective inhibitors of COX-2 were proposed to retain the efficacy of traditional NSAIDs while avoiding the gastrointestinal adverse effects, as this was attributed to inhibition of cytoprotection by products of COX-1 in gastric epithelium.…”

mentioning

confidence: 99%

Prostaglandin E Synthases in Zebrafish

Pini

Großer

Lawson

et al. 2005

ATVB

View full text Add to dashboard Cite

Objective-Prostaglandin E synthases (PGESs) are being explored as antiinflammtory drug targets as alternatives to cyclooxygenase (COX)-2. Located downstream of the cyclooxygenases, PGESs catalyze PGE 2 formation, and deletion of microsomal (m)-PGES-1 abrogates inflammation. We sought to characterize the developmental expression of COX and PGES in zebrafish. Methods and Results-We cloned zebrafish cytosolic (c) and m-PGES orthologs and mapped them to syntenic regions of chromosomes 23 and 5. cPGES was widely expressed during development and was coordinately regulated with zCOX-1 in the inner ear, the pronephros, and intestine. COX-2 and mPGES-1 exhibited restricted expression, dominantly in the vasculature of the aortic arch. However, the enzymes were anatomically segregated within the vessel wall. Experiments with antisense morpholinos and with nonsteroidal antiinflammatory drugs suggest that these genes may not be critical for development. Conclusions-mPGES-1 is developmentally coregulated with COX-2 in vasculature. Given the high fecundidity and translucency of the zebrafish, this model may afford a high throughput system for characterization of novel PGES inhibitors. (Arterioscler Thromb Vasc Biol. 2005;25:315-320.)Key Words: prostaglandin E synthase Ⅲ cyclooxygenase Ⅲ zebrafish Ⅲ Danio rerio Ⅲ vascular biology N onsteroidal antiinflammatory drugs (NSAIDs) have proven effective in ameliorating symptoms in patients with arthritis. 1 These drugs inhibit coincidentally cyclooxygenase (COX)-1 and COX-2, two forms of the prostaglandin (PG) G/H synthase, 2 which catalyze the biotransformation of arachidonic acid into PGG 2 and PGH 2 . These, in turn, are acted on by isomerases and synthases to form PGs. 3 NSAID use is commonly associated with gastric upset and may result in bleeding from both the upper and lower gastrointestinal tract. 4 COX-1 is expressed constitutively in most cells, whereas COX-2 is most commonly induced by inflammatory cytokines and mitogens. 5 Selective inhibitors of COX-2 were proposed to retain the efficacy of traditional NSAIDs while avoiding the gastrointestinal adverse effects, as this was attributed to inhibition of cytoprotection by products of COX-1 in gastric epithelium. 6 This has been borne out in two clinical outcome trials, Vioxx Gastrointestinal Outcomes Research Study (VIGOR) 7 and Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), 8 but not in a third, Celebrex Long-Term Arthritis Safety Study (CLASS). 9 Given the cardiovascular adverse effect profile associated with selective inhibition of COX-2, 10 interest has shifted to enzymes downstream of the COXs as potential targets of novel antiinflammatory interventions, and small molecule inhibitors of PGE synthases are under development.PGE synthases (PGES) transform PGH 2 to PGE 2. These enzymes exist in microsomal (mPGES-1 and mPGES-2) 11,12 and cytosolic (cPGES) 13 forms. Two cytosolic gluthathione S-transferases, 2 and 3, also have the capacity to form PGE 2 . 14 There is some evidence that COX-2 and mPGE...

show abstract

mentioning

confidence: 99%

Prostaglandin E Synthases in Zebrafish

Pini

Großer

Lawson

et al. 2005

ATVB

View full text Add to dashboard Cite

show abstract

“…[4][5][6][7][8][9] Not surprisingly, these side effects are similar to those found in the upper gastrointestinal tract. Hence, similar pathways most likely result in these side effects at various locations in the alimentary tract.…”

mentioning

confidence: 60%

The Role of Arachidonic Acid Regulatory Enzymes in Colorectal Disease

Abir

Alva

Kaminski

et al. 2005

Diseases of the Colon &Amp; Rectum

View full text Add to dashboard Cite

In the new millennium, nonsteroidal anti-inflammatory drugs may be used for chemoprevention of colorectal and other cancers. In addition, they may be used in combination with surgery and chemotherapy to primarily treat colorectal carcinoma. Undoubtedly, the use of novel cyclooxygenase inhibitors with less of a toxicity profile will allow more widespread use of nonsteroidal anti-inflammatory drugs for a variety of diseases. The future of this class of drugs is promising.

show abstract

“…5 However, endoscopy may be normal in NSAID-induced colitis or reveal only nonspecific erosions. 10,11 The endoscopic spectrum in our series included long linear ulcers, discrete punched-out ulceration, and aphthous ulcers. Diaphragm-like strictures, said to be typical of NSAID-induced colitis, 5 were not identified in any of our cases.…”

Section: Discussionmentioning

confidence: 87%

“…NSAID-induced colitis is characterized by low content of inflammation, without architectural distortion which is seen in inflammatory bowel diseases. 10 In a previous study, NSAIDinduced colitis accounted for 10% of newly diagnosed colitis patients. 13 Given the overlap of histologic features in entities such as Crohn's colitis and infectious colitis, it is important that history regarding NSAID ingestion is obtained in every patient.…”

Section: Discussionmentioning

confidence: 94%

Clinical, endoscopic and pathologic spectrum of non-steroidal anti-inflammatory drug-induced colitis

Geramizadeh

Taghavi

Banan

2009

Indian J Gastroenterol

View full text Add to dashboard Cite

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for treatment of arthritis and many other painful conditions. These drugs may cause damage not only to the upper gastrointestinal tract but also to the small and large intestine. This prospective study aimed to determine the presence of colonic lesions among 24 patients who were receiving NSAIDs for more than 3 months, and presented with diarrhea, intractable abdominal pain, and lower GI bleeding. Colonoscopy was done and multiple biopsies from different sites in the colon were obtained. Colonoscopy was normal in 11 (45.8%), showed inflammation or superficial ulcers in 7 (29.1%) and solitary or multiple deep ulcers in 6 (25%). Histology showed erosions in 12 (50%) and lymphocytic colitis in 9 (37.5%); histology was normal in 4 (16.6%). NSAID-induced colonic damage may have clinically significant sequel.

show abstract

Nonsteroidal anti-inflammatory drug-induced diaphragms and ulceration in the colon

Cited by 28 publications

References 31 publications

Prostaglandin E Synthases in Zebrafish

Prostaglandin E Synthases in Zebrafish

The Role of Arachidonic Acid Regulatory Enzymes in Colorectal Disease

Clinical, endoscopic and pathologic spectrum of non-steroidal anti-inflammatory drug-induced colitis

Contact Info

Product

Resources

About