Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009319 (colitis)
 19,384 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxygen-centered radicals, such as superoxide (O2-) and hydroxyl radicals (.OH) generated by phagocytes have been suggested to be involved in the pathogenesis of chronic inflammations of the bowel, such as Crohn's disease and colitis ulcerosa. Recently, sulfasalazine (SASP) and its metabolites have been reported to exert their effects as a direct scavenger of oxygen-centered radicals in the bowel. To scavenge oxygen-centered radicals in vivo, however, SASP and its metabolites have to react with O2- and/or .OH in vitro very rapidly, furthermore they have to reach an appropriate (possible millimolar) concentration range at the site of inflammation. To test this possibility, we investigated the direct O2- and .OH scavenging activity of SASP and its metabolites using the specific electron paramagnetic resonance/spin trapping method, and we compared the 50% inhibition rates of SASP and its metabolites with their known concentrations in the bowel and in the human plasma. It was found that SASP and its metabolites, such as 5-amino-salicylic acid (5-ASA), and acetyl-5-amino-salicylic acid (AC-5-ASA), but not sulfapyridine (SP) and acetyl-sulfapyridine (Ac-SP) have a direct O2- and .OH scavenging activity in vitro systems. Among the compounds, SASP and 5-ASA can reach a concentration which is appropriate to scavenge oxygen-centered radicals in the bowel but not in the human plasma. It was concluded that the in vivo antiinflammatory effects of SASP and its metabolites are, at least partly, due to the direct oxygen-centered scavenging activity of these drugs.
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PMID:The oxygen-centered radicals scavenging activity of sulfasalazine and its metabolites. A direct protection of the bowel. 136 79

The etiopathogenesis of ulcerative colitis (UC) is still largely unknown, although the role of genetic influences now seems to be fairly clear. Diagnosis is based on clinical, endoscopic and histological findings. The most important differential diagnosis of UC is Crohn's disease (CD). UC always first arises in the rectum and can spread continuously to upper parts of the colon. One of the severest complications consists in the development of toxic megacolon, which is seen in 1.6%-8% of cases. Another point is the occurrence of carcinoma in longstanding and extensive UC. The risk of this complication may have been overestimated in earlier studies: A realistic rate could be 0.5%-1% per person and year of pancolitis. However, carcinoma may occur even in less extensive cases. The conclusions which have to be drawn are still controversial. Some authors recommended regular endoscopy with serial biopsies, but others do not. The standard oral therapy is based on sulfasalazine (SASP) and corticosteroids. For topical treatment, 5(4)-amino-salicylic acid has proven to be effective in distal colitis, as has cortisone. Also, oral treatment with 5-ASA preparations seems to be beneficial, even if some of the published studies are open to criticism. Presumably, the drug is more clearly effective at higher doses than those commonly used.
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PMID:Pathogenesis and management of ulcerative colitis. 268 Aug 57

Sulfasalazine (SASP) is frequently used in the treatment of chronic inflammatory bowel disease (IBD), particularly colitis. Because the drug poses a theoretical risk for renal tubular damage, 26 patients, 8-18 years of age, with Crohn's ileocolitis were studied. Thirteen children were receiving SASP while 13 served as disease controls. Renal tubular function was assessed by measurement of urinary beta 2-microglobulin and n-acetylglucosaminidase activity. No abnormalities were found on routine measurement of renal function. Similarly, urinary beta 2-microglobulin and n-acetylglucosaminidase activities were within normal limits for patients receiving SASP, as well as for disease controls. Although there is a theoretical risk for renal tubular damage from the prolonged use of SASP, this study would suggest that IBD patients receiving the drug are at no greater risk for renal injury than their counterparts not receiving the medication.
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PMID:Sulfasalazine and renal tubular function: lack of an effect. 285 19

Assessment of the nature, location and extent of the disease, disease activity and the intestinal and extraintestinal complications and manifestations is an essential prerequisite in the treatment of inflammatory bowel disease. Corticosteroids, sulfasalazine (SASP) and rectal administration of 5-aminosalicylic acid (5-ASA) are effective in the treatment of ulcerative colitis. Oral 5-ASA in the form of a slow-release preparation is probably also effective. Rectal SASP or 5-ASA in addition to corticosteroids is indicated in distal colitis. In severe pancolitis oral or intravenous corticosteroids are required, whilst in less severe forms SASP or 5-ASA can be used. However, the safety of 5-ASA over longer treatment periods has yet to be verified. Surgery is indicated in colitis refractory to maximal treatment over several months. Apart from parenteral or enteral nutrition, treatment with prednisolone is effective in acute exacerbations of Crohn's disease. SASP is possibly effective in colonic disease. The role of 5-ASA has yet to be defined. A prednisolone-induced remission can be maintained by means of low doses of prednisolone. SASP is probably not effective, whilst with 5-ASA conclusive data are missing. Metronidazole and azathioprin are considered to be reserve drugs and can be used in the treatment of fistulae or in order to cut down the dosage of prednisolone during remission. Substitution with vitamins and trace elements is necessary in a large number of patients with Crohn's disease.
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PMID:[Drug therapy of chronic inflammatory intestinal diseases--current status of 5-aminosalicylic acid]. 288 Apr 25

Fifty patients intolerant of or allergic to sulphasalazine (SASP) or sulphonamides were treated with mesalazine. Eighty per cent of patients continued treatment during the time of follow-up (mean, 8.4 months); 14% (7 of 50 patients) had to stop the treatment with mesalazine because of side effects. The patients with allergic reactions, including rash, fever, and systemic manifestations from SASP, were most likely to be intolerant of or allergic to mesalazine (four of seven patients); two of them developed a similar reaction from both SASP and mesalazine. Two patients (2 of 12) with previous haematologic side effects had to discontinue mesalazine treatment, one because of mild neutropaenia and one because of an elevation of liver enzyme values. One patient experienced gastrointestinal side effects from both mesalazine and SASP. Altogether, 4 (4 of 50) patients experienced gastrointestinal symptoms from mesalazine. Two of them had had a flare-up of the symptoms of the colitis when treated with SASP. All side effects were rapidly reversible after withdrawal of the drug. Patients with severe allergic reactions with systemic manifestations from SASP should be treated with caution with 5-aminosalicylic acid preparations.
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PMID:Mesalazine tolerance in patients with inflammatory bowel disease and previous intolerance or allergy to sulphasalazine or sulphonamides. 289 Jan 98

Chronic inflammatory bowel diseases are probably due to stimulation of the intestinal immune system by multiple, so far unknown antigens. Chronic inflammatory bowel diseases can be contained but not healed by corticosteroids, sulfasalazine (SASP), azathioprin and metronidazol. Healing may be expected by direct pharmacological intervention in the intestinal immune system, but these are not yet available. -5-aminosalicylic acid may replace SASP in the treatment of ulcerative colitis. When administered locally 5-ASA may be effective in cases of corticosteroid-resistant distal colitis. Controlled studies are needed before the perspectives for 5-ASA in the treatment of Crohn's disease can be assessed.
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PMID:[Drug treatment of chronic inflammatory intestinal diseases with special reference to 5-azosalicylic acid]. 332 18

Experimental colitis was induced in guinea pigs by administration of 5% degraded carrageenan for 5 days. The prophylactic effect of a slow-release preparation of 5-aminosalicylic acid (5-ASA; 13 mg/100 g/day) was compared with approximately equimolar amounts of salazosulphapyridine (SASP; 26 mg/100 g/day) and placebo. Treatment was started 2 days before initiation of carrageenan administration. The drugs were administered through a chronic gastric fistula. At the end of the study concentrations of 5-ASA and acetylated 5-ASA (Ac-5-ASA) in cecal contents and in plasma were determined. In the placebo group, all guinea pigs developed many small punctiform ulcerations in the cecum (median, 30/cm2). In the 5-ASA group no protective effect was demonstrated, since the number of ulcerations was 37/cm2. The difference is not statistically significant. However, the SASP group presented significantly fewer ulcerations (4/cm2). The concentrations of 5-ASA and/or its acetylated metabolite were several times higher in the cecum content and twice as high in plasma in the SASP group, indicating a difference in the absorption patterns of 5-ASA and the two drugs. These results and the etiological difference between the human ulcerative colitis and the carrageenan model may account for the lack of prophylactic effect of the slow-release 5-ASA in this experiment.
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PMID:The prophylactic effect of 5-aminosalicylic acid and salazosulphapyridine on degraded-carrageenan-induced colitis in guinea pigs. 614 86

Z-103 is a chelate compound consisting of zinc ion and L-carnosine. In this study, we investigated the protective effect of Z-103 against colonic damage induced by 2,4,6-trinitrobenzene sulfonic acid (TNB) in rats. Colonic inflammation was induced by administering TNB dissolved in 50% ethanol (120 mg/ml) in male Wistar rats (total volume of 0.25 ml per rat) following a 48-hour fast. After the administration of TNB, Z-103 was given at a dose of 30 mg/kg per rat for 1 week. A second group of rats received sulfasalazine (SASP) at 300 mg/kg and a third group of rats received 30 mg/kg of ZnSO4 for 1 week. Colonic inflammation was assessed 1 week following TNB administration. Both macro- and microscopic evaluation showed that the inflammatory responses induced by TNB were reduced by treatment with Z-103, SASP and ZnSO4. The score (graded from 0 to 5 according to the macroscopic lesions) and colonic wet weight (distal 8 cm of the colon) were significantly decreased by treatment with Z-103, SASP and ZnSO4. The increase in thiobarbituric acid-reactive substances in the colonic mucosa following TNB administration were inhibited in the Z-103 and SASP groups. These results suggest that Z-103 is as effective against TNB-induced colitis as SASP.
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PMID:Effect of Z-103 on TNB-induced colitis in rats. 938 38

In the present study, we evaluated the effect of 4-methoxy-5-hydroxycanthin-6-one (CAN), a natural alkaloid isolated from Picrasma quassioides (D.Don) Benn., on ulcerative colitis induced by dextran sulfate sodium (DSS) in rats in comparison with the positive control drug, sulfasalazine (SASP). Given orally for several days, CAN significantly reduced the severity of colitis and mitigated changes in colon length, colon mucosa myeloperoxidase (MPO) activity, and the level of tumor necrosis factor-alpha (TNF-alpha) in serum. The effect of CAN was similar to that of SASP. These results suggest that CAN treatment might be an effective therapeutic intervention against ulcerative colitis induced by DSS.
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PMID:Protective effect of 4-methoxy-5-hydroxycanthin-6-one, a natural alkaloid, on dextran sulfate sodium-induced rat colitis. 1908 15

The aim of the study was to investigate the therapeutic effect and mechanism of proanthocyanidins from grape seeds (GSPE) in the treatment of ulcerative colitis (UC). Rats were intragastrically administered different doses of GSPE (100, 200, and 400 mg/kg) per day for 7 days after UC was twice-induced by intracolonic injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS)dissolved in 50% ethanol. Sulfasalazine (SASP) at 200 mg/kg was used as a positive control drug. Macroscopic and microscopic damage scores and changes in weight/length ratio (mg/mm) of colon segments were analyzed. The levels of malonyldialdehyde (MDA), interleukin (IL)-1beta, IL-2, IL-4, and myeloperoxidase (MPO) activity in the colon tissues and MPO activity in the serum were all measured by biochemical methods or double antibody sandwich ELISA methods. Compared with the TNBS control group, GSPE treatment facilitated recovery of pathologic changes in the colon after insult with TNBS, as demonstrated by increased body weight (p < 0.01) and decreased colonic weight/length ratio (p < 0.01); GSPE also notably reduced the colonic macroscopic and microscopic damage scores (p < 0.01). The MPO activity in colon tissues and serum of rats treated with GSPE was significantly lower than that in the TNBS control group. The MDA and IL-1beta levels of colon tissues were also decreased in GSPE groups. The intestinal antiinflammatory effect of GSPE was accompanied by a significant improvement of IL-2 and IL-4 levels in the colon tissues of rats in the high-dose GSPE group (p < 0.05). Compared with the SASP group, GSPE groups had no significant difference in the therapeutic effect (p > 0.05). GSPE exerts a beneficial antiinflammatory effect in the acute phase of TNBS-induced colitis in rats by downregulating some of the mediators involved in the intestinal inflammatory response, inhibiting inflammatory cell infiltration and antioxidation damage, promoting damaged tissue repair to improve colonic oxidative stress, decreasing production of proinflammatory cytokines IL-1beta, and increasing production of antiinflammatory cytokines IL-2 and IL-4.
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PMID:Therapeutic effect and mechanism of proanthocyanidins from grape seeds in rats with TNBS-induced ulcerative colitis. 1908 5


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