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Query: UMLS:C0009324 (ulcerative colitis)
 17,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colonic mucosal lesions, characterized by crypt abscesses and mononuclear cell infiltration, which resemble human ulcerative colitis can be induced in rabbits by short-term (7 to 8 weeks) administration of carrageenan according to our method. In this study experimental epithelial dysplasia of the colon was induced by the p.o. administration of lambda-degraded carrageenan for a much longer period of time. Fifteen rabbits, sensitized i.m. with the same substance 1 week before, were subjected to 12 or 28 months of treatment with 1% carrageenan solution in drinking water. Histological examination disclosed chiefly mild inflammatory changes of the colonic mucosa in all animals and a focal but high-grade dysplasia (nonpolypoid) involving the mucosal epithelium in three of the five animals treated for 28 months. The present observations suggested that epithelial dysplasia of the colon may be caused in association with inflammation and that the pathological condition produced by us can be a useful model of carcinoma in situ possibly resulting from inflammation.
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PMID:Epithelial dysplasia of the rabbit colon induced by degraded carrageenan. 394 2

An ;in-vitro' technique is described for measuring quantitatively the absorption and secretion of water and electrolytes, the short circuiting current, and the simultaneous bidirectional flux rates of ions across the healthy and diseased colonic mucosa. The results show that the normal colon absorbs both sodium and water and secretes potassium. In both ulcerative colitis and Crohn's disease there is a reversal of sodium and water flux and potassium secretion is increased.A measure of the simultaneous bidirectional flux rates under conditions of zero potential has allowed us to use the Ussing equation to analyse some of the factors involved in sodium transport across the healthy and diseased mucosa.
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PMID:The absorption and secretion of water and electrolytes across the healthy and the diseased human colonic mucosa measured in vitro. 464 91

Germfree rats monocontaminated with the anaerobic microorganisms Clostridium difficile or another Clostridium species (strain G 62) produce auto-antibodies to colon antigen. The antigen can be extracted with phenol water from the feces of germfree rats. Antibodies, demonstrable by means of passive hemagglutination of antigen sensitized sheep erythrocytes appear after monocontamination for 35 days or longer. The indirect immunofluorescence techniques, applied to sections of germfree rat colon, gave positive mucosal staining. The staining was similar to that obtained with sera from patients with ulcerative colitis or from rats immunized with rabbit colon. No antibodies were found in the sera of germfree rats, germfree rats monocontaminated with various other bacteria, conventional rats of germfree origin, or conventional Sprague-Dawley rats. Although the anti-colon antibodies of the Clostridium infected rats reacted with the same feces extract as the antibodies of ulcerative colitis patients or of rabbit colon immunized rats, their specificity was different. While the latter cross-react with polysaccharide from E. coli O14, those from the Clostridium-infected exgermfree rats did not. Rats monocontaminated with Cl. difficile also developed antibodies to this organism, but no cross-reaction between Cl. difficile antigen and colon antigen could be demonstrated. This speaks against breakage of tolerance by cross-reacting bacterial antigen as the cause of autoimmunity in these rats. Other possible mechanisms for autoantibody production in this model are immunogenic alteration of gastrointestinal mucins by bacterial degradation, adjuvant effects of bacterial products, or both.
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PMID:Autoantibodies to colon in germfree rats monocontaminated with Clostridium difficile. 488 46

Sera from patients with ulcerative colitis contain antibodies which hemagglutinate sheep red cells, sensitized with phenol-water extracts from. colon, cecum, or feces of germfree rats. Minor concentrations of such antibodies are also present in a certain fraction of normal human sera. Hemagglutination and hemagglutination inhibition experiments with human erythrocytes and with the rat extracts showed that the latter contained an antigen similar to human blood group A antigen. In contrast, a blood group B-like antigen could not be detected in these extracts. However, experiments with eel serum indicated that these extracts also contained an antigen similar to the H antigen of the human ABO system. Absorption of ulcerative colitis sera with human A(1) erythrocytes but not that with B or O erythrocytes gave, in a few cases, a slight reduction of the hemagglutinating titers against rat cecum-sensitized sheep erythrocytes. In contrast, this treatment considerably reduced such titers when found in sera from healthy persons or from patients with unrelated diseases. It could be concluded that the rat extracts also contained a "colon" antigen, detected with antibodies, present at elevated titers, in the sera of ulcerative colitis patients, but not in those of the controls. This colon antigen is immunologically distinct from the blood group antigens studied. Hemagglutination inhibition experiments indicated that A, H and colon antigen were widely distributed throughout the gastrointestinal tract of the germfree rats. The colon antigen was found to be enriched in the extracts from colon, cecum, and feces. Fluorescent antibody staining provided evidence that both the colon antigen and the A antigen were present in similar sites of the colon and cecum mucosa, particularly in goblet cells of the crypts, and in the mucus.
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PMID:Immunological studies in ulcerative colitis. II. "Colon" antigen and human blood group A- and H-like antigens in germfree rats. 532 69

A 5% aqueous solution of degraded carrageenan derived from the red seaweed Eucheuma spinosum was fed to guinea pigs in their drinking water over a period of 20-45 days. Occult blood in the faeces and multiple ulcers in the caecum, colon and rectum occurred in 100% of animals by the 30th day. The clinical and pathological features bear a close resemblance to human ulcerative colitis. The method provides a simple experimental model for the study of various aspects of the pathology of ulcerative lesions in the large intestine as well as the effects of therapeutic agents.
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PMID:Carrageenan-induced ulceration of the large intestine in the guinea pig. 554 64

We have used in vivo rectal dialysis to assess mucosal prostaglandin E2 (PGE2) release and water and electrolyte transport before and 2 weeks after withdrawal of oral sulphasalazine in eight patients with inactive ulcerative colitis. Although rectal mucosal PGE2 release was unaffected by withdrawal of sulphasalazine, significant reductions in mucosal potential difference (P less than 0.01) and net absorption of water (P less than 0.05), sodium (P less than 0.05), and chloride occurred (P less than 0.05). Clinical assessment showed no change in disease activity. Sulphasalazine withdrawal thus has a detrimental effect on large-intestinal salt and water transport, which does not appear to be mediated through changes in net mucosal prostaglandin production.
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PMID:The effect of sulphasalazine withdrawal on rectal mucosal function and prostaglandin E2 release in inactive ulcerative colitis. 611 88

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

Azodisalicylate, a second generation drug of sulfasalazine, delivers twice the amount of 5-aminosalicylic acid to the colonic lumen on a molar basis when split by bacterial azoreductases. In 6 patients with inactive ulcerative colitis, the colonic metabolism of sulfasalazine and azodisalicylate was studied by equilibrium in vivo dialysis of feces to measure the therapeutically relevant concentrations of their metabolites (5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid) in free fecal water. After oral intake of sulfasalazine (2 g/day) the total luminal concentrations of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid determined by high-performance liquid chromatography were higher (median 14 mmol/L) than previously reported and almost doubled (median 25 mmol/L, p less than 0.05) when sulfasalazine was replaced by the same dose of azodisalicylate. In contrast, the corresponding serum concentrations were negligible. After administration of azodisalicylate to 12 healthy volunteers, a similar distribution of the metabolites was found. In nearly all cases, the concentrations of azodisalicylate in fecal dialysates were below the detection limit (6 mumol/L). We conclude, therefore, that oral azodisalicylate is a highly effective means of delivery of 5-aminosalicylic acid to the colonic mucosa. In addition, determination of the active metabolites in free fecal water seems important for the interpretation of results obtained in vitro concerning the mode of drug action.
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PMID:Colonic azodisalicylate metabolism determined by in vivo dialysis in healthy volunteers and patients with ulcerative colitis. 614 4

We have used in vivo rectal dialysis to test the hypothesis that the diarrhoea of patients with active ulcerative colitis (UC) is due to inhibition of large intestinal salt and water absorption by enhanced local mucosal prostaglandin (PG) synthesis. In 28 patients with untreated UC, increased rectal mucosal PGE2 release varied inversely with sodium transport and directly with potassium transport; higher PGE2 release was also associated with lower (i.e. less negative) potential difference (PD). Disease activity assessed sigmoidoscopically was positively related to PGE2 release, potassium transport and lower PD. Similar relationships were found in 33 patients treated with sulphasalazine and/or corticosteroids and in 9 patients studied serially when on unaltered conventional, or no treatment. In contrast, when 10 patients with UC were given the PG synthesis inhibitor, flurbiprofen, a significant fall in PGE2 release was associated with deteriorations in mucosal PD and transport of sodium and potassium. Increased PG production is therefore unlikely to be a major determinant of the abnormalities of electrolyte transport found in UC. The correlations between mucosal PGE2 release and electrolyte transport were probably due to the relationship of these variables with some other consequence of tissue damage.
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PMID:Relationship between rectal mucosal prostaglandin production and water and electrolyte transport in ulcerative colitis. 614 63

The role of arachidonic acid metabolites and the mode of action of 5-aminosalicylic acid, the active moiety of sulphasalazine and disodium azodisalicylate, in ulcerative colitis remain obscure. Therefore, experiments were performed in which the effects of medication on immunoreactive prostaglandin (PG) E2 concentrations in free faecal water were assessed using the equilibrium in vivo dialysis of faeces. Colonic PGE2 concentrations in patients with active ulcerative colitis (n = 11) ranged from 2035-18,000 pg/ml to be compared with a range of 103-188 pg/ml in healthy volunteers (n = 10; p less than 0.001). In all healthy volunteers PGE2 concentrations decreased slightly (p less than 0.05) after disodium azodisalicylate intake 2 g/day, whereas low dose disodium azodisalicylate (0.25 g/day) caused no change. In patients with ulcerative colitis in complete clinical, sigmoidoscopic, and histologic remission withdrawal of sulphasalazine (2 g/day; n = 6) increased PGE2 concentrations to values above normal levels (p less than 0.05) which returned to pretrial values (p less than 0.05) on disodium azodisalicylate (2 g/day; n = 7). In conclusion, increased PGE2 in free faecal water indicates an abnormality in the colonic mucosa, even in the absence of conventional signs of inflammation. We could not confirm the hypothesis that sulphasalazine and 5-aminosalicylic acid exert their therapeutic effect through promotion of endogenous cytoprotective prostaglandins. In contrast, the observation that raised PGE2 concentrations were normalised by disodium azodisalicylate in patients with inactive ulcerative colitis suggests that subclinical disease activity was decreased by 5-aminosalicylic acid.
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PMID:Effects of sulphasalazine and disodium azodisalicylate on colonic PGE2 concentrations determined by equilibrium in vivo dialysis of faeces in patients with ulcerative colitis and healthy controls. 614 81


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