Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1522057 (Colitis)
 3,500 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reactive oxygen and nitrogen species have been implicated as mediators of mucosal injury in inflammatory bowel disease. This study investigated hydroxyl radical (.OH) generation in the inflamed colon of dextran sulfate sodium (DSS)-induced colitis by measuring the .OH-specific product of salicylate hydroxylation, 2,3-dihydroxybenzoic acid (DHB). Colitis was induced in 6-7 week old CBA/H male mice by supplementing the drinking water with 5% DSS for 7 days. On the last day of dextran exposure, mice were injected with salicylate (SAL) (100 mg/kg i.p.) 60 min before sacrifice, and mucosal homogenates were assayed for SAL and 2,3-DHB by HPLC with fluorescence and electrochemical detection. Mucosal 2,3-DHB levels in mice exposed to 5% DSS were increased by 83% (p < .005); however, SAL levels were also elevated by 182% (p < .001). This translated to a 34% decrease in the ratio 2,3-DHB:SAL in inflamed mucosa, possibly indicating greater catabolism or decreased production of 2,3-DHB. In vitro investigation of the stability of DHBs and SAL in the presence of oxidants of inflammatory lesions revealed that 2,3-DHB and 2,5-DHB were rapidly degraded by hypochlorous acid (HOCl), with initial decomposition rates of 190 and 281 nmol/min, respectively (100microM DHB with 200microM HOCl). Methionine prevented decomposition of DHBs in vitro; however, in mice with 5% DSS-induced colitis, where mucosal myeloperoxidase activity was ten-fold control levels (p < .001), administration of methionine (up to 200 mg/kg i.p.) with SAL was ineffective at increasing the ratio 2,3-DHB:SAL. SAL was also degraded in vitro by HOCl (4.7 nmol/min) resulting in the formation of new fluorescent species which may be useful as indicators of HOCl-mediated injury. Salicylate hydroxylation was unable to provide conclusive evidence supporting a role for .OH in the tissue injury of DSS-induced colitis, as metabolic disturbances in the diseased animals other than changes in .OH generation may have altered 2,3-DHB levels. This problem is relevant to any study involving the in vivo use of trapping molecules. In particular, the susceptibility of 2,3-DHB to degradation by HOCl brings into question the usefulness of salicylate hydroxylation for measurement of .OH-generation in any neutrophilic inflammatory lesion.
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PMID:Salicylate hydroxylation as an indicator of hydroxyl radical generation in dextran sulfate-induced colitis. 968 Jan 76

Adrenocorticotrophic hormone (ACTH) and corticosteroids have no maintenance values for inflammatory bowel disease but serve to reduce the severity of disease. The effectiveness of intravenous corticotrophin versus hydrocortisone in ulcerative colitis has been determined including whether previous steroid therapy influenced the better response to one rather than the other, but no such studies have ever been done in Crohn's disease. Eighty-eight patients hospitalized with moderate-to-severe Crohn's disease (Present-Korelitz [P-K] Index -3 to -2 and the International Organisation for the Study of Inflammatory Bowel Disease-Crohn's & Colitis Foundation of America [IOIBD-CCFA] Index, mean 14, range 5-23) were treated in a prospective, randomized, double-blind clinical trial to receive either continuous intravenous infusion of 120 U/day of ACTH (44 patients) or hydrocortisone 300 mg/day (44 patients). Patients were also subdivided into those who received oral steroids during the 30 days prior to intravenous therapy and those who had not. Response was followed on a daily basis and tabulated at 3, 5, and 10 days. Patients were followed from 1-3 years to determine the later status. After 10 days of intravenous therapy 36 of 44 patients (82%) who received ACTH and 41 of 44 patients (93%) who received hydrocortisone fully responded (P-K index +3 and IOIBD-CCFA Index mean of 3). At the end of the study, response to intravenous ACTH and hydrocortisone was not statistically different whether or not patients received oral steroids during the 30 days prior to admission, although the response to IV ACTH tended to be faster at 3 days in those who had received previous steroid therapy. Intravenous ACTH and hydrocortisone are equally effective in achieving therapeutic goals in patients with Crohn's disease who have not achieved results with oral medications. Moreover the response rate was high (mean 88%), serving to buy time for establishment of successful maintenance programs of treatment with oral 5-ASA and immunosuppressive drugs for 69% of patients at 1-3 years.
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PMID:Intravenous corticotrophin vs. hydrocortisone in the treatment of hospitalized patients with Crohn's disease: a randomized double-blind study and follow-up. 974 Oct 18

Increased expression of intercellular adhesion molecule-1 (ICAM-1) in the colon of inflammatory bowel disease (IBD) has been reported. We evaluated the effects of monoclonal antibodies to ICAM-1 on acute colitis induced by dextran sodium sulphate (DSS) in rats. Colitis was induced by feeding rats 3% DSS for 7 days. Anti-ICAM-1 antibody or vehicle alone was injected intraperitoneally in rats daily from day 0 to day 6. On day 7 the rats were killed and colitis was evaluated histologically. Prophylactic treatment with anti-ICAM-1 significantly attenuated colonic damage, neutrophil infiltration and the shortening of the colon in DSS colitis. Our findings demonstrate that ICAM-1 plays an important role in this model of inflammatory bowel disease. Although this study does not directly address the effect of anti-ICAM-1 therapy in IBD, our findings encourage experiments using therapies that target ICAM-1 in rats with already developed disease.
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PMID:Effects of the anti-ICAM-1 monoclonal antibody on dextran sodium sulphate-induced colitis in rats. 979 95

In response to requests from the members of the local Crohn's and Colitis Foundation chapter, a nurse-facilitated support group was formed. Its goals were to provide support and information for people coping with inflammatory bowel disease (IBD). Despite the interest expressed by the membership, attendance at the monthly meetings was sporadic and sparse. Eventually the group ceased to exist. To understand why the group dissolved, each member was interviewed and asked the following open-ended questions: (1) What did you want from a support group? (2) Why did you not attend meetings regularly? (3) What, if anything, would have kept you coming to the group? Despite coping with IBD, most people described a normal life in which support from the family and established relationships was sufficient to meet their needs. Extra support, such as group support, was only perceived to be needed at certain key times. Innovative methods for providing support, when needed, are discussed.
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PMID:The birth and dissolution of an inflammatory bowel disease support group: lessons in providing support. 984 75

The etiology of inflammation, edema, and smooth muscle contraction characteristic of inflammatory bowel disease is not clearly understood. There is evidence that several neuropeptides, including substance P (SP), may play a role. In this study we evaluated the ability of a SP-antagonist (SR140333) to modify the course of experimental colitis induced in the rat by trinitrobenzene sulfonic acid (TNB). Colitis was induced in 24 rats using TNB applied by intrarectal enema. Twelve TNB-treated rats received SR140333, 0.1 mg/kg intraperitoneally, 30 min before the administration of TNB and every 48 hr until death. Twelve rats receiving only intrarectal 0.9% saline served as controls. Rats of each group were killed after 14 days. At day 14, the control group showed no signs of inflammation whereas the TNB-treated rats without SR140333 treatment exhibited a well-established colitis. The TNB-treated group had a higher level of inflammation, as seen histologically and by the significantly greater weight of colon strips, compared to the controls (0.30 +/- 0.09 g vs 0.13 +/- 0.03 g, P < 0.001) and to the SR140333-treated rats (0.30 +/- 0.09 g vs 0.14 +/- 0.05 g, P < 0.001). In addition, smooth muscle contractility was significantly reduced in the inflamed colons of TNB-treated rats when compared with the controls (carbachol: 42.7 +/- 20.3 vs 254.2 +/- 69.78 mg/mm2; SP: 18.5 +/- 10.02 vs 89.45 +/- 23.17 mg/mm2; KCl: 11.4 +/- 2.2 vs 98.32 +/- 33.57 mg/mm2, P < 0.01). However, SR140333-treated rats showed a recovery from inflammation and motor alterations caused by TNB (carbachol: 150.9 +/- 46.1 mg/mm2, P < 0.01; SP: 32.5 +/- 9.4 mg/mm2, P < 0.05; KCl: 125.7 +/- 36.1 mg/mm2, P < 0.01). In conclusion, treatment with SP antagonist SR140333 reduces the severity of colitis and has beneficial effects on the concomitant alterations of contractility. Thus, the blockade of substance P may represent a possibility in the treatment of intestinal inflammation.
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PMID:SR140333, a substance P receptor antagonist, influences morphological and motor changes in rat experimental colitis. 1006 35

Nitric oxide (NO) has been implicated in the pathogenesis of inflammatory bowel disease since increased NO production is observed in this disease. NO can react with superoxide to generate peroxynitrite which causes and/or exacerbates colitis. Peroxynitrite, in turn, nitrates tyrosine residues to form nitrotyrosine which can be identified immunohistochemically. We investigated the distribution of neuronal and inducible nitric oxide synthase (iNOS) and nitrotyrosine over time in experimental colitis. Colitis was induced by intracolonic administration of trinitrobenzene sulphonic acid (TNBS) in rats. Animals were killed 1, 2, 7 and 14 days after treatment. Myeloperoxidase activity was used as an index of inflammation, and tissues were examined using immunohistochemistry. Neuronal NOS immunoreactivity was present throughout the colon, and was only slightly reduced 1 day after the induction of colitis. Conversely, iNOS immunoreactivity almost absent in controls dramatically increased in the mucosa and submucosa at the early stages of inflammation. iNOS was present in monocytes and macrophages and also another unidentified cell type. Seven and 14 days after the induction of colitis, iNOS was also found in nerves in the circular muscle and in the myenteric plexus. Nitrotyrosine immunoreactivity present in a few cells in the normal mucosa also increased 1 day after the induction of colitis and decreased thereafter. The pattern of distribution of nitrotyrosine immunoreactivity was distinct from that of iNOS. The increase of iNOS expression at the early stage of inflammation may play a role in causing tissue injury via peroxynitrite formation. The expression of iNOS seen in the enteric nerves in the later stage of inflammation correlates temporally with the beginning of tissue repair and with the re-innervation and compensatory growth of nerves. NO may potentially play a physiological as well as pathological role in experimental colitis.
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PMID:Temporal distribution of neuronal and inducible nitric oxide synthase and nitrotyrosine during colitis in rats. 1035 44

Biopsy specimens from patients with inflammatory bowel disease have demonstrated an up-regulation of P-selectin, suggesting a role for P-selectin in intestinal inflammation. We examined the role of P-selectin in experimental intestinal inflammation using mice deficient in P-selectin alone or in combination with either ICAM-1 or E-selectin. Colitis was induced using acetic acid or trinitrobenzene sulfonic acid (TNBS). Damage scores and neutrophil infiltration 24 h post acetic acid were not different between wild-type and P-selectin- or P-selectin/ICAM-1-deficient mice, whereas P/E-selectin-deficient mice had enhanced leukocyte recruitment and damage. At 72 h an attenuation in damage scores and a slight decrease in neutrophil infiltration was observed in the P- and P/ICAM-deficient animals. The P/E-selectin-deficient mice maintained enhanced leukocyte recruitment and damage. In wild-type mice P-selectin expression was elevated 48 and 72 h post acetic acid-induced inflammation. Surprisingly, P-selectin or P-selectin/ICAM-1 deficiency did not improve the inflammation induced by TNBS over 7 days. In fact, increased mortality was observed. Anti-adhesion therapy may play only a limited, beneficial role and often a detrimental role in intestinal inflammation.
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PMID:Intestinal inflammation in adhesion molecule-deficient mice: an assessment of P-selectin alone and in combination with ICAM-1 or E-selectin. 1041 Sep 91

Colitis in experimental animals or idiopathic inflammatory bowel disease, such as ulcerative colitis or Crohn's disease in humans, is associated with reduced muscle contraction. This is predicted to be due to disturbance of Ca2+ homeostasis in the inflamed muscle cell. However, the underlying molecular mechanism remains to be elucidated. Since the catalytic alpha-1 subunit of the L-type Ca2+ channel regulates Ca2+ influx, levels of the alpha-1 mRNA and protein were examined. Colitis induced by intrarectal administration of trinitrobenzenesulfonic acid was monitored by measuring the myeloperoxidase activity and histology. The levels of mRNA and protein were estimated using RT-PCR and immunoblotting. Myeloperoxidase activity increased in the inflamed colon, and the lamina propria and muscle layers showed infiltration of inflammatory cells and loss of crypts. Two alternatively spliced alpha-1 mRNA isoforms were detected in the colonic muscle. The ratio of unspliced to spliced mRNA isoforms remained unaltered in inflamed muscle. In contrast, the level of corresponding protein isozymes decreased in the colitic animals. Thus colitis-induced reduction in the alpha-1 protein may account for the reduced colonic contractility seen in colitis.
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PMID:Molecular basis of altered contractility in experimental colitis: expression of L-type calcium channel. 1049 28

The present study was designed to investigate inflammation-induced changes in smooth muscle responses to acetylcholine and the tachykinins that may contribute to the abnormal motility associated with inflammatory bowel disease. Colitis was induced in male Sprague-Dawley rats by intrarectal administration of trinitrobenzenesulphonic acid in ethanol. After either 4 h (acute) or 7 days (chronic) the distal colon was taken for in vitro measurement of smooth muscle tension and histological assessment. Acute colitis featured injury and neutrophilic infiltration confined to the mucosa while chronic inflammation showed marked injury, lymphocytic infiltration and muscle thickening. Acute inflammation increased responses to substance P and acetylcholine but decreased responses to neurokinin A. The enhanced response to substance P was dependent on nerves, while the decreased response to neurokinin A reflected a reduction in activity at the level of the smooth muscle. In the saline group, there was evidence of cholinergic interaction with substance P, but not neurokinin A. Substance P modulation of cholinergic nerves was absent in acute inflammation. Responses to all neurotransmitters were decreased in the chronic stage. These data demonstrate progressive changes in the smooth muscle function during acute and chronic colitis that may contribute to the abnormal motility associated with inflammatory bowel disease.
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PMID:Progressive alterations in circular smooth muscle contractility in TNBS-induced colitis in rats. 1052 Jan 66

The sodium-hydrogen exchanger isoform, NHE-3 is essential for the absorption of sodium and water from intestine. Whether this protein plays any role in inflammatory bowel disease is less understood. To address this issue, NHE-3 mRNA and protein levels were estimated in the terminal ileum and colon of the rats having colitis induced with trinitrobenzenesulphonic acid (TNBS). The effect of garlic (Allium sativum) was also evaluated on the expression of NHE-3. The animals were treated with garlic extract intraperitoneally starting 2 h before the TNBS administration until day 4 post-TNBS administration and were sacrificed on day 5. In control animals, the levels of NHE-3 in colon was higher than the ileum. As a result of colitis, the levels of NHE-3 protein and mRNA increased both in the colon and terminal ileum. Garlic treatment of the colitic animals resulted in a selective suppression of NHE-3 in the terminal ileum. Colitis caused an induction of the myeloperoxidase activity, the marker of inflammation in the colon but not in the ileum. These findings suggest that induction of NHE-3 is not primarily due to inflammation. Selective suppression of this protein in ileum by garlic may cause loss of sodium chloride and water during colitis.
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PMID:Altered expression of the Na+/H+ exchanger isoform-3 in experimental colitis: effect of garlic. 1056 86


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