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Genes belonging to the beta-catenin signalling pathway were analysed in colo-rectal cancer cell lines treated with 5-ASA using a combination of laboratory assays that are able to detect their phenotypic expression and functional activity.
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At 3 weeks nine of 20 patients (45%) in both the bismuth and placebo groups had improved. Ten patients discontinued prematurely because of worse diarrhoea (three in each group) or abdominal cramping after enema use (one from the bismuth group and three from the placebo group). No other side-effects were noted. Serum bismuth concentrations were negligible in all patients.
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The utilization of calcium alginate beads as core carriers for delayed dissolution followed by burst release as a potential method of intestinal site specific drug delivery was investigated. 5-Aminosalicylic acid was spray-coated on dried calcium alginate beads and then coated with different percentages of enteric coating polymer and/or sustained-release polymer. Beads coated with more than 6% (w/w) methacrylic copolymer plastisized with dibutyl sebacate and triethyl citrate resisted release in 2-hr acid fluid challenge and allowed immediate dissolution upon transfer to simulated intestinal fluid. With 6% (w/w) methacrylic copolymer on top of 4% (w/w) ethylcellulose polymer, the major portion of drug did not release in 2 hr of acid treatment or the next 3 hr of simulated intestinal fluid treatment. This dosage form provides the possibility to deliver drug to the lower intestinal tract with minimal early release, followed by sustained release in the colon.
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Radiation proctitis is a well-known complication of abdominal and pelvic radiation. Conventional medical and surgical treatment often is disappointing. 5-Aminosalicylic acid (5-ASA) is the active component in sulfasalazine and is effective in the treatment of distal ulcerative colitis. Four patients with radiation proctitis were treated with 4 g 5-ASA by enema nightly for two to six months. Patients were seen monthly, interviewed, and a sigmoidoscopic exam performed. No change was seen in the degree of mucosal inflammation on follow-up sigmoidoscopic exams. Three patients noted no change in their symptoms of bleeding, pain, or tenesmus. One patient noted initial improvement, but this was not sustained. 5-ASA enemas do not appear to be effective in the treatment of radiation proctitis.
5-Aminosalicylates were frequently prescribed in patients with Crohn's disease in the Swiss IBD cohort. This observation stands in contrast to the scientific evidence demonstrating a very limited role of 5-ASA compounds in the treatment of Crohn's disease.
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CD patients with mild disease were treated with aminosalicylate monotherapy more frequently. These patients, however, tend to have more exacerbations, shorter duration of first remission, and longer total duration of systemic steroid use. Our data support the concept that severity of disease at diagnosis does not reliably predict subsequent clinical course. This study suggests that there is no indication that children with mild CD should be treated differently compared to children with moderate-severe disease.
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Utilization of surveillance colonoscopy in a 2-year period was low, even among high-risk patients. Although specific factors recorded in computerized data were identified to be associated with surveillance, a greater understanding of how patients and physicians decide on surveillance is needed.
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Azoreductase 1 from Pseudomonas aeruginosa strain PAO1 (paAzoR1) catalyses the activation of the prodrug balsalazide and reduces the azo dye methyl red using reduced nicotinamide adenine dinucleotide cofactor as an electron donor. To investigate the mechanism of the enzyme, a Y131F mutation was introduced and the enzymic properties of the mutant were compared with those of the wild-type enzyme. The crystallographic structure of the mutant with methyl red bound was solved at 2.1 A resolution and compared with the wild-type structure. Tyr131 is important in the architecture of the active site but is not essential for enzymic activity.
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Information was retrospectively extracted from the clinical records of patients followed in the IBD Units of nine hospitals in Madrid (n = 5073).
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Metformin enhanced CRC cell death induced by 5-ASA through significant increase in oxidative stress and activation of apoptotic machinery. Moreover, metformin enhanced the anti-inflammatory effect of 5-ASA by decreasing the gene expression of IL-1β, IL-6, COX-2 and TNF-α and its receptors; TNF-R1 and TNF-R2. Significant inhibition of activation of NF-κB and STAT3 transcription factors, and their downstream targets was also observed. Metformin also enhanced the inhibitory effect of 5-ASA on MMP-2 and MMP-9 enzyme activity, indicating a decrease in metastasis.
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For all diseased rats, both mean weight loss and colonic segment weight/bodyweight ratio was significantly higher than that in the sham group. As compared with other groups, body and colonic segment changes as well as histopathological scoring in rats receiving mesalazine enema either solely or in combination with the antibiotics were lower. No bacterial growth was found in the blood, liver and spleen of the rats in the control group while enteric bacteria, mainly Escherichia coli (35%) were the most common bacteria translocated to that in the latter. Antibiotic combination, alone or in combination with mesalazine was effective in reducing the bacterial translocation while mesalazine administration did not properly influence its regression.
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Predictive factors for a mild course of Crohn's disease (CD) may have therapeutic consequences, but as yet have not been identified.
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The effect of mesalazine in treating active Crohn's disease (CD) remains controversial, possibly due to the various formulae of mesalazine used to treat inflammation located in different regions of the digestive tract.
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Topical therapy with mesalazine and/or corticosteroids is the standard treatment for patients with distal ulcerative colitis. Rectal mesalazine is more effective than rectal systemically active corticosteroids or topically active corticosteroids like budesonide. In patients with mild to moderately active distal ulcerative colitis, topical mesalazine is therefore the treatment of choice. Doses of 1 g or higher are equally effective. The period of treatment is important (4 weeks are more effective than 2 weeks). In the case of nonresponse or nontolerability of rectal mesalazine, rectal budesonide is indicated. The standard dose of budesonide is 2 mg/day. This does not usually induce any corticosteroid-associated adverse events. Treatment with rectal mesalazine plus rectal topically active corticosteroids is even more effective than treatment with either substance alone. To overcome adherence problems with rectal therapy, rectal foam preparations have been developed which are usually better tolerated than enemas.