Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009324 (ulcerative colitis)
 17,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a double-blind study comprising 33 patients (24 males and 9 females) the effects of sulfasalazine enema (3%) in acute left-sided ulcerative colitis was tested. The success rate of 73.6% is comparable with the results achieved with the oral treatment. The rate of side effects however was markedly reduced (no side effects occurred in our patients). Compared to the SASP-therapy with suppositories, the enema had the advantage of being applicable to more proximal parts of the colon.
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PMID:[Sulfasalazine enema in acute left-sided ulcerative colitis (author's transl)]. 610 6

SASP, the drug most widely used for the treatment of Crohn's disease and ulcerative colitis, is a competitive inhibitor of intestinal folate metabolism and transport. Some of the therapeutic effects of the drug could be related to antifolate actions on lymphocytes, which predominate in the inflammatory reaction in inflammatory bowel diseases. Experiments were designed to examine the effect of SASP on folate-dependent systems in cultured lymphocytes. In rat spleen lymphocytes, THF-dependent conversion of glycine to serine was inhibited by SASP, with 50% inhibition occurring at 0.1 mM. Further evidence of folate antagonism was obtained with the dU suppression test, which depends on the function of a folate-dependent pathway in the de novo synthesis of DNA. Folate antagonists like methotrexate or folate depletion reduces the incorporation of dU into DNA and thus favors incorporation of [3H]thymidine into DNA by an alternate pathway. SASP inhibited the folate-dependent pathway in proliferating virally transformed human lymphocytes (Raji cells). To confirm that SASP acts as a folate antagonist in this system, THF was demonstrated to partly reverse the action of SASP. The significance of this antifolate action by SASP in intact lymphocytes deserves further study in relation to the actions of SASP in patients with inflammatory bowel disease.
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PMID:Antifolate actions of sulfasalazine on intact lymphocytes. 611 49

Sulfasalazine (SASP) consists of salicylic acid azo linked at the 5-position to a pyridine-containing sulfonamide. This drug, currently used in inflammatory bowel disease treatment, is reductively cleaved by anaerobic bacteria in the lower bowel to 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP). Recent reports indicate that 5-ASA is the active therapeutic moiety and that SP is responsible for a variety of adverse clinical side effects. Water-soluble polymer 7, which contains salicylate residues azo linked at the 5-position to an inert polymer backbone, has been synthesized for the site-specific reductive release of 5-ASA in the lower bowel. Preparations of 7 deliver (chemical reduction) greater than 1.96 mmol of 5-ASA/g of polymer. In vitro studies with the polymer in anaerobic rat cecal bacteria demonstrated a reduction rate of approximately 1 mu equiv of azo bond h-1 (mL of cecal content)-1. A pharmacokinetic comparison of polymer and SASP showed similar deliveries of 5-ASA and metabolites to the lower bowel, blood, and urine of orally dosed rats. Polymer 7 proved more active than SASP or 5-ASA in the guinea pig ulcerative colitis model. Potential therapeutic advantages of 7 include nonabsorption/nonmetabolism in the small intestine, direct 5-ASA release at the disease site, and nonabsorption/nonmetabolism of the reduction-released carrier polymer.
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PMID:A polymeric drug for treatment of inflammatory bowel disease. 613 12

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

In this study SASP metabolite levels were measured in colonic mucosal specimens and plasma samples from 31 patients with ulcerative colitis (UC) under treatment with the drug. Colonic tissue specimens were obtained by endoscopically guided biopsy and plasma was isolated from peripheral blood. Measurements were performed by HPLC according to the procedure of Fischer et al. The levels of 5-ASA and SP in either of colonic tissue or plasma were significantly lower than those of Ac-5-ASA and Ac-SP, respectively. The tissue level of 5-ASA had a significant correlation to the dosage of 5-ASA. The tissue levels of 5-ASA and Ac-5-ASA were low in an active stage of UC than during a remission period and the difference observed with respect to the latter metabolite was significant. These findings suggest that acetylation of 5-ASA is inhibited in the colonic mucosa in an active stage of the disease.
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PMID:[Localization of salazopyrin in colonic mucosa patients with ulcerative colitis]. 809 55

In vitro effects of cytokines and therapeutic drugs on antibody dependent cellular cytotoxicity (ADCC) mediated by anticolon antibody were investigated in serum samples from patients with ulcerative colitis. A 51Cr release assay was used to examine ADCC activity with the colon cancer cell line, colo 205, as the target and peripheral blood mononuclear cells as the effector. High ADCC activity was shown in 13 of 32 (41%) patients with ulcerative colitis. This ADCC activity was inhibited by protein A treatment of the serum samples. Interleukin 2 (IL2) activated effector cells could enhance ADCC activity, but interferon-gamma (IFN-gamma) or tumour necrosis factor-alpha (TNF-alpha) had no effect on the cytotoxic activity of effector cells. Treatment of target cells with IFN-gamma increased the vulnerability of these cells to ADCC with a large increase of intercellular adhesion molecule-1 (ICAM-1) expression on their surface. Monoclonal antibodies to ICAM-1 inhibited this IFN-gamma enhanced ADCC activity. Interestingly, prednisolone (PSL) reduced ADCC activity, but sulphasalazine (SASP) or 5-aminosalicylic acid (5-ASA) did not. These results suggest that IL2 and IFN-gamma could enhance colonic epithelial cell injury mediated by the ADCC mechanism in ulcerative colitis and that ADCC enhanced by cytokines is restored by PSL treatment.
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PMID:Interleukin 2 and interferon-gamma augment anticolon antibody dependent cellular cytotoxicity in ulcerative colitis. 810 Feb 5

In a double-blind, single-center, 1-year prospective trial, we compared a pH-dependent Eudragit L-coated formulation of oral 5-aminosalicylic acid (5-ASA) (Claversal), 0.5 g b.i.d., and sulfasalazine (SASP), 1 g b.i.d., in the prophylactic treatment of quiescent ulcerative colitis. Forty-four patients received 5-ASA and 44 received SASP. Clinical, sigmoidoscopic, and histologic findings were assessed at 6 and 12 months. The two groups were comparable in all pretrial characteristics. No significant difference was observed in the relapse rate in the two groups either after 6 months [5-ASA 20.5%, SASP 27.5%, p = 0.32, 95% confidence interval (CI) 0.28 +/- 0.13] or after 12 months (5-ASA 38.4%, SASP 51%, p = 0.18, 95% CI 0.38 +/- 0.1). We conclude that (a) 5-ASA was as effective as SASP in maintaining remission of ulcerative colitis; (b) the relapse rate was, however, higher than expected in both groups; (c) the incidence of side effects was similar with both treatments.
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PMID:Coated oral 5-aminosalicylic acid (Claversal) is equivalent to sulfasalazine for remission maintenance in ulcerative colitis. A double-blind study. 858 1

5-[4-(2-Carboxyethylcarbamoyl)phenylazo]salicylic acid disodium salt dihydrate (CAS 80573-04-2, BX661A) is developed as a therapeutic agent for ulcerative colitis. To clarify its mechanism of action, the effects of BX661A and its metabolites 5-aminosalicylic acid (5-ASA) and 4-aminobenzoyl-beta-alanine (4-ABA) on reactive oxygen species: superoxide radicals (O2-) generated by hypoxanthine and xanthine oxidase, hydrogen peroxide (H2O2), hypochlorite radicals (OCl-) and hydroxyl radicals (OH.), were investigated and compared with the effects of 2-hydroxy-5-[[4-[(2-pyridinylamino)sulfonyl]phenyl]azo]-benzoic acid (CAS 599-79-1, salazosulfapyridine, SASP) and its metabolite 4-amino-N-2-pyridinyl-benzenesulfonamide (CAS 144-83-2, sulfapyridine, SP). 1. BX661A, SASP and 5-ASA inhibited O2- radical production in a concentration-dependent manner (IC50 = 0.14, 0.13 and 0.19 mmol/l, respectively). The effects of 4-ABA and SP on O2- radical production were weak (IC50 = > 10 and > 3 mmol/l, respectively). In contrast, superoxide dismutase inhibited O2- radical production in a concentration-dependent manner (IC50 = 1.7 U/ml). 2. BX661A, SASP, 4-ABA and SP had no H2O2 scavenging effects. 5-ASA scavenged H2O2, but its maximal scavenging action was 51.3%. In contrast, catalase scavenged H2O2 in a concentration-dependent manner (IC50 = 0.47 U/ml). 3. BX661A, SASP and 5-ASA scavenged OCl- radicals in a concentration-dependent manner (IC50 = 69.5, 73.8 and 21.7 mumol/l, respectively). 4-ABA and SP had no OCl- radical scavenging effects. In contrast, nordihydroguaiaretic acid (NDGA) scavenged OCl- radicals in a concentration-dependent manner (IC50 = 8.7 mumol/l). 4. BX661A and SASP scavenged OH. radicals in a concentration-dependent manner; the maximal scavenging values were 39.5 (10 mmol/l) and 48.6% (3 mmol/l), respectively. 4-ABA and SP had no OH. radical scavenging effects. In contrast, 5-ASA scavenged OH. radical in a concentration-dependent manner (IC50 = 1.46 mmol/l). These results suggest that BX661A has O2- and OCl- radical scavenging effects and that 5-ASA has O2-, OCl- and OH. radical scavenging effects. Therefore, these effects may be partially involved in the therapeutic effects of BX661A on ulcerative colitis.
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PMID:Effects of BX661A, a new therapeutic agent for ulcerative colitis, on reactive oxygen species in comparison with salazosulfapyridine and its metabolite sulfapyridine. 982 18

5-[4-(2-Carboxyethylcarbamoyl)phenylazo]salicylic acid disodium salt dihydrate (CAS 80573-04-2, BX661A) is developed as a therapeutic agent for ulcerative colitis. To clarify the mechanisms of action of BX661A, the effects of BX661A and its metabolites 5-aminosalicylic acid (5-ASA) and 4-aminobenzoyl-beta-aline (4-ABA) on polymorphonuclear (PMN) leukocyte chemotaxis and production of reactive oxygen species (ROS) from PMN cells were investigated and compared with the effects of 2-hydroxy-5-[[4-[(2-pyridinylamino)sulfonyl]phenyl]azo]-benzoic acid (CAS 599-79-1, SASP) and its metabolite 4-amino-N-2-pyridinyl-benzenesulfonamide (CAS 144-83-2, SP). 1. BX661A, SASP and SP concentration-dependently inhibited guinea pig PMN cell chemotaxis induced by zymosan-activated serum (IC50 = 1.39, 2.17 mmol/l, respectively) and by N-formyl-methionyl-leucyl-phenylalanine (FMLP) with IC50 values of 0.55, 0.06 and 0.66 mmol/l, respectively. 5-ASA and 4-ABA weakly affected the PMN cell chemotaxis induced by zymosan-activated serum (both IC50 values > or = 10 mmol/l) and by FMLP (IC50 > or = 10 and 8.05 mmol/l, respectively). 2. BX661A, SASP and SP concentration-dependently inhibited human PMN cell chemotaxis induced by FMLP with IC50 values of 0.68, 0.05 and 2.68 mmol/l, respectively, but both IC50 values of 5-ASA and 4-ABA were > 10 mmol/l. 3. BX661A, SASP, 5-ASA, 4-ABA and SP inhibited ROS production from rat PMN cells stimulated by FMLP in a concentration-dependent manner (IC50 = 58.4, 27.5, 0.61, 1242 and 13.9 mmol/l, respectively). 4. BX661A, SASP, 5-ASA, 4-ABA and SP inhibited ROS production from human PMN cells stimulated by FMLP in a concentration-dependent manner (IC50 = 67.4, 46.1, 0.69, 748 and 8.31 mumol/l, respectively). These results suggest that BX661A itself has inhibitory effects against PMN cell chemotaxis and ROS production from PMNs and that 5-ASA, which is the active moiety of BX661A, has a potent inhibitory effect against ROS production from PMNs. Therefore, these effects may be partially involved in the therapeutic effects of BX661A on ulcerative colitis.
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PMID:Effects of BX661A, a new therapeutic agent for ulcerative colitis, on chemotaxis and reactive oxygen species production in polymorphonuclear leukocytes in comparison with salazosulfapyridine and its metabolite sulfapyridine. 989 31

Sulfasalazine (SASP), since 60 years standard in the treatment of ulcerative colitis, is a double molecule where 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP) are linked together by an azobond. Bacterial splitting of SASP within the colon allows delivery of 5-ASA for its topical action (prodrug system). To target 5-ASA without the less tolerable SP down to the lower intestine new prodrugs have been developed and, in addition, mesalazine is offered which contains 5-ASA prepared as a delayed release preparation. A clinical comparison (metaanalysis) tended towards superiority of the new prodrugs and mesalazine over SASP for inducing remission, while SASP was more effective in maintaining remission. Only few studies exist comparing the efficacy of the new drugs and mesalazine. To date a slight superiority of the new prodrugs is implied. With the exception of SASP safety profiles do not significantly differ between the different drugs containing 5-ASA.
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PMID:[Clinical effect of various 5-ASA preparations in ulcerative colitis]. 1019 45


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