Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial.

Rachmilewitz, Daniel

doi:10.1136/bmj.298.6666.82

Cited by 988 publications

(663 citation statements)

References 28 publications

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“…Diagnosis of Crohn ' s disease was ascertained according to the usual clinical criteria, 38 and the site and extent of the disease were confirmed by endoscopy, histology, and enteroclysis in all patients. Diagnosis of ulcerative colitis was ascertained according to the usual clinical criteria, 39 and the site and extent of the disease were confirmed by endoscopy and histology. None of the IBD patients had been ever treated with cyclosporine, methotrexate, infliximab, or adalimumab.…”

Section: Methodsmentioning

confidence: 99%

The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease

et al. 2011

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Activation of cannabinoid receptors (CBs) by endocannabinoids impacts on a number of gastrointestinal functions. Recent data indicate that CB1 agonists improve 2,4-dinitrobenzene sulfonic acid-induced colitis in mice, thus suggesting a role for the endocannabinoid agonist anandamide (AEA) in protecting the gut against inflammation. We here examined the gut endocannabinoid system in inflammatory bowel disease (IBD) patients, and investigated the ex vivo and in vitro effects of the non-hydrolysable AEA analog methanandamide (MAEA) on the mucosal proinflammatory response. The content of AEA, but not of 2-arachidonoyl-glycerol and N-palmitoylethanolamine, was significantly lower in inflamed than uninflamed IBD mucosa, and this was paralleled by lower activity of the AEA-synthesizing enzyme N-acyl-phosphatidylethanolamine-specific phospholipase D and higher activity of the AEA-degrading enzyme fatty acid amide hydrolase. MAEA significantly downregulated interferon-γ and tumor necrosis factor-α secretion by both organ culture biopsies and lamina propria mononuclear cells. Although these results are promising, further studies are needed to determine the role of cannabinoid pathways in gut inflammation.[...

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Section: Methodsmentioning

confidence: 99%

The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease

et al. 2011

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“…The extension and location of UC and CD, disease severity of UC and CD, and behavior of CD were stratified in accordance with Montreal classification (16) with Czin 8 slight modification. A high clinical activity index (CAI>5) for UC (17) and a high Crohn's disease activity index (CDAI>150) (18) were regarded as active phase patients.…”

Section: Subjectsmentioning

confidence: 99%

Haplotypes of PADI4 susceptible to rheumatoid arthritis are also associated with ulcerative colitis in the Japanese population

Chen

Isomoto

Narumi

et al. 2008

Clinical Immunology

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Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory disorder characterized by intractable inflammation specific to the gastrointestinal tract. The precise etiology of IBD remains unknown. Recently, haplotypes of peptidylarginine deiminase type 4 (PADI4) have been identified as the rheumatoid arthritis (RA)-susceptible gene. PADI4 is located at 1p36, which is one of chromosomal loci susceptible for IBD. Then, we examined whether haplotypes and diplotypes of PADI4 are associated with IBD in the Japanese population. We studied haplotypes of PADI4 in 114 patients with UC, 83 patients with CD, and 200 gender-matched healthy controls by PCR-restriction fragment length polymorphism. Frequencies and distributions of haplotypes and diplotypes were compared statistically between patients and controls by logistic regression analysis. The frequency of haplotype 1 was significantly decreased in patients with UC, compared to that in controls (P = 0.037; odds ratio (OR) = 0.702). In contrast, the frequency of haplotype 2 in patients with UC was significantly higher than that in controls (P = 0.003; OR = 1.722). Moreover, of a total of 114 patients with UC, 15 (13.2%) had a diplotype homozygous for haplotype 2, the frequency being significantly higher than in controls (9/200, 4.5%; P = 0.008, OR = 3.215). Our results indicate that Czin 4 haplotype 1 of PADI4 is associated with non-susceptibility to UC, whereas haplotype 2 is susceptible to UC. Thus, it is likely that PADI4 is one of genetic determinants of UC in the Japanese population.

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“…All patients were over 18 y old, free of intestinal surgery including cholecystectomy, and without antibiotic use for more than 6 mo. Basic demographic and medical information was collected and for patients with CD or UC a disease activity index calculated-the Harvey Bradshaw index (79) for CD and simple clinical colitis activity index for UC (80). Patients with IBD had active disease as defined by a Harvey Bradshaw index of greater than 5 for CD and simple clinical colitis activity index of greater than 4 for UC.…”

Section: Methodsmentioning

confidence: 99%

Functional metagenomic discovery of bacterial effectors in the human microbiome and isolation of commendamide, a GPCR G2A/132 agonist

Cohen

Kang

Chu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

158

151

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The trillions of bacteria that make up the human microbiome are believed to encode functions that are important to human health; however, little is known about the specific effectors that commensal bacteria use to interact with the human host. Functional metagenomics provides a systematic means of surveying commensal DNA for genes that encode effector functions. Here, we examine 3,000 Mb of metagenomic DNA cloned from three phenotypically distinct patients for effectors that activate NF-κB, a transcription factor known to play a central role in mediating responses to environmental stimuli. This screen led to the identification of 26 unique commensal bacteria effector genes (Cbegs) that are predicted to encode proteins with diverse catabolic, anabolic, and ligand-binding functions and most frequently interact with either glycans or lipids. Detailed analysis of one effector gene family (Cbeg12) recovered from all three patient libraries found that it encodes for the production of N-acyl-3-hydroxypalmitoyl-glycine (commendamide). This metabolite was also found in culture broth from the commensal bacterium Bacteroides vulgatus, which harbors a gene highly similar to Cbeg12. Commendamide resembles long-chain N-acyl-amides that function as mammalian signaling molecules through activation of G-protein–coupled receptors (GPCRs), which led us to the observation that commendamide activates the GPCR G2A/GPR132. G2A has been implicated in disease models of autoimmunity and atherosclerosis. This study shows the utility of functional metagenomics for identifying potential mechanisms used by commensal bacteria for host interactions and outlines a functional metagenomics-based pipeline for the systematic identification of diverse commensal bacteria effectors that impact host cellular functions.

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Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial.

Cited by 988 publications

References 28 publications

The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease

The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease

Haplotypes of PADI4 susceptible to rheumatoid arthritis are also associated with ulcerative colitis in the Japanese population

Functional metagenomic discovery of bacterial effectors in the human microbiome and isolation of commendamide, a GPCR G2A/132 agonist

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