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)

Nitric oxide (NO) is an important mediator of inflammation in several pathological conditions. Patients with lung diseases, like asthma, have higher levels of exhaled NO (eNO) in active disease in comparison with healthy volunteers. Aspirated colonic gas in patients with ulcerative colitis (UC) showed more than 100 times higher levels of NO in comparison with normal subjects. Crohn's disease (CD) and UC are associated with a variety of systemic manifestations, although lung diseases as an extra-intestinal expression of inflammatory bowel disease (IBD) are not well investigated. In some studies, clinical and subclinical pulmonary abnormalities are described in active IBD as well as in the stable situation. The aim of the present study is to evaluate whether eNO is increased in patients with active IBD and to investigate whether there exists a correlation between (1) the eNO levels and the disease activity, and (2) the spirometry and the disease activity in a subgroup of patients. In 31 patients with CD (mean age 36.8 +/- 12.9 years) and 24 patients with UC (mean age 38.0 +/- 14.7 years) the Crohn's Disease Activity Index (CDAI) and Colitis Activity Index (CAI) were measured, respectively. Exhaled NO was measured with a chemiluminescence analyzer, according to standardized criteria. In a subgroup of CD patients, spirometry was also performed according to standardized criteria. The mean CDAI in CD patients was 192.4 +/- 94.3 and their mean eNO value was 13.5 +/- 4.6 ppb. For UC the mean CAI was 6.2 +/- 4.8 and the mean eNO value was 15.8 +/- 6.2 ppb. In a matched control group of 27 healthy, non-smoking volunteers (mean age of 33.7 +/- 13.2 years) the eNO was 10.2 +/- 2.5 ppb (P < 0.05 compared to CD and P < 0.01 compared to UC). There was a disease-activity-related increase of the eNO level in patients with IBD. For patients with UC the correlation coefficient (r = 0.63, P < 0.001) was more pronounced than for CD (r = 0.39, P < 0.05). In 17 patients with CD, spirometry was available at the time of the eNO measurement. We found a significant negative correlation between the CDAI and the FEV1 and FVC in these patients (r = -0.559, P = 0.02 and r = -0.634, P = 0.006, respectively). We conclude that eNO is increased in active IBD and correlates with the activity of the disease; furthermore, we found a negative correlation between spirometry and disease activity in patients with CD. These observations strengthen the arguments that IBD is a systemic disease. Further research is needed to try to explain the significance of an increased eNO in IBD.
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PMID:Activity related increase of exhaled nitric oxide in Crohn's disease and ulcerative colitis: a manifestation of systemic involvement? 1219 39

Inflammatory bowel disease is characterized by oxidative stress, inflammation and tissue damage. Vitamin A is an antioxidant, a regulator of epithelial proliferation and differentiation and vital for optimal immune function. To investigate the effect of vitamin A on the course of colitis, it was induced by administration of trinitrobenzene sulfonic acid (TNBS) into the colons of rats fed for 7 wk vitamin A-deficient (VAD), sufficient (VAS) or supplemented (VASUP) diet, or VAS pair-fed (PF) to the VAD rats. Inflammation and fibrosis were examined by hematoxin and eosin, and Sirius red staining. Activation of nuclear factor-kappaB (NF-kappaB) and oxidative stress were determined by electrophoretic mobility shift and plasma malondialdehyde (MDA) and RBC Cu/Zn-superoxide dismutase activity, respectively. Vitamin A deficiency in the noncolitic rats impaired food consumption and weight gain (P < 0.05) and increased plasma MDA, (P = 0.01) activity of NF-kappaB (P < 0.05) and deposition of collagen in the colon. Our data suggest that vitamin A deficiency induces colonic inflammation. Colitis is amplified by deficiency and ameliorated by supplementation of the vitamin. These findings have implications for the management of inflammatory bowel disease.
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PMID:Vitamin A deficiency exacerbates inflammation in a rat model of colitis through activation of nuclear factor-kappaB and collagen formation. 1222 Dec 39

Inflammatory bowel diseases are immune-mediated disorders. Dietary restriction and NK1.1+ liver-associated lymphocytes (LAL) are considered to be involved in immunomodulation of autoimmune diseases. Our aim was to evaluate the effect of caloric restriction on experimental colitis and to determine NK1.1+ LAL function in immunoregulation. Experimental colitis was induced in C57 black mice by intracolonic instillation of trinitrobenzene sulfonic acid. Caloric restriction to 60% of the daily requirement was started 2 weeks prior to, or simultaneously with, colitis induction and continued throughout the study. Control mice were fed ad libitum. Colitis was assessed by standard clinical and macroscopic scores. To determine the mechanism involved in immunomodulation, liver lymphocytes were isolated and analyzed for NK1.1+ T-cell markers by FACS. T-cell function was evaluated by T-cell proliferation. Serum cytokines were measured by ELISA. Dietary restriction to 60% markedly ameliorated experimental colitis in both groups. These mice gained weight and showed improved macroscopic parameters of colitis. NK1.1+ LAL numbers increased fourfold and NKT cytotoxicity twofold in caloric-restricted mice. The antigen-specific T-cell proliferation index decreased (from 4.45 in controls to 1.15), and IFN-gamma and IL-12 serum levels decreased (from 290 to 200 pg and from 122 to 53 pg, respectively) in caloric-restricted mice. Our conclusion was that dietary restriction induced immunomodulation of experimental colitis and ameliorated the disease. This effect was mediated via an increase in NK1.1+ T lymphocytes, which may play a critical role in keeping the T-cell balance in immunoregulation.
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PMID:Immunomodulation of experimental colitis via caloric restriction: role of Nk1.1+ T cells. 1248 93

1. Inflammatory bowel disease (IBD) is characterized by oxidative and nitrosative stress, leukocyte infiltration, and increased expression of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) in the colon. Recent evidence also suggests that the cyclopentenone prostaglandin (PG) 15-deoxy-delta(12,14)-PGJ(2) (15d- PGJ(2)) functions as an early anti-inflammatory signal. 2. The aim of the present paper is to investigate the effects of 15d-PGJ(2) in rats subjected to experimental colitis. 3. Colitis was induced in rats by intra-colonic instillation of dinitrobenzene sulphonic acid (DNBS). 15d-PGJ(2) was administered daily as intraperitoneal injection (20 or 40 microg kg(-1)). On day 4, animals were sacrificed and tissues were taken for histological and biochemical analysis. 4. 15d-PGJ(2) significantly reduced the degree of haemorrhagic diarrhoea and weight loss caused by administration of DNBS. 15d-PGJ(2) also caused a substantial reduction of (i) the degree of colonic injury, (ii) the rise in myeloperoxidase (MPO) activity (mucosa), (iii) the increase in the tissue levels of malondialdehyde (MDA) and (iv) of the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). 5. Furthermore, 15d-PGJ(2) reduced the increase in immunohistochemical staining for (i) inducible nitric oxide synthase (iNOS), (ii) nitrotyrosine and (iii) poly (ADP-ribose) polymerase (PARP), as well as (iv) the increased expression of ICAM-1 caused by DNBS in the colon. 6. Electrophoresis mobility shift assay (EMSA) of inflamed colon revealed that 15d- PGJ(2) also caused a substantial reduction of the activation of nuclear factor-kappaB (NF-kappaB). Furthermore, 15d-PGJ(2) stimulates the activation of heat shock protein 72 (hsp72) in the inflamed colon, as assessed by Western blot analysis. 7. In conclusion, 15d-PGJ(2) reduces the development of experimental colitis.
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PMID:The cyclopentenone prostaglandin 15-deoxy-delta(12,14)- PGJ2 attenuates the development of colon injury caused by dinitrobenzene sulphonic acid in the rat. 1259 22

The Crohn's and Colitis Foundation of Canada (CCFC) has established a national bank for tissue, serum and blood from patients with inflammatory bowel disease (IBD). Investigators from across the country submit material to the bank together with clinical data. Investigators may access their own patient information from the bank for their own study purposes, but the distribution of tissue is restricted to specific CCFC-funded projects. Currently, tissues are being collected from newly diagnosed, untreated IBD patients to support a recent initiative aimed at characterizing microbes in colonic and ileal biopsies from such patients. In the future, criteria for the submission of tissue will be tailored to specific research questions. This bank is believed to be the first national bank of its kind dedicated to research in Crohn's disease and ulcerative colitis
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PMID:The establishment of a national tissue bank for inflammatory bowel disease research in Canada. 1260 47

5-HT released from enterochromaffin cells acts on enteric nerves to initiate motor reflexes. 5-HT's actions are terminated by a serotonin reuptake transporter (SERT). In this study, we tested the hypothesis that inflammation leads to altered mucosal 5-HT signaling. Colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS), and experiments were conducted on day 6. 5-HT content, number of 5-HT-immunoreactive cells, and the proportion of epithelial cells that were 5-HT-immunoreactive increased twofold in colitis. The amount of 5-HT released under basal and stimulated conditions was significantly increased in colitis. SERT inhibition increased the 5-HT concentration in media bathing-stimulated control tissue to a level comparable to that of the stimulated colitis tissue. mRNA encoding SERT and SERT immunoreactivity were reduced during inflammation. Slower propulsion and reduced sensitivity to 5-HT-receptor antagonism were observed in colitis. These data suggest that colitis alters 5-HT signaling by increasing 5-HT availability while decreasing 5-HT reuptake. Altered 5-HT availability may contribute to the dysmotility of inflammatory bowel disease, possibly due to desensitization of 5-HT receptors.
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PMID:Serotonin availability is increased in mucosa of guinea pigs with TNBS-induced colitis. 1264 22

The use of biologics has promising potential in the treatment of inflammation. Studies with cultured cells and mouse models of disease have ascribed proinflammatory and anti-inflammatory functions to oncostatin M (OSM) and the related cytokine, interleukin-6 (IL-6). Here, we examined the effect of systemic administration of adenoviral (Ad) vectors encoding either murine OSM (AdMuOSM) or murine IL-6 (AdMuIL-6) in a mouse model of colitis. BALB/c mice were treated with a 5-day course of 4% dextran-sodium sulfate (DSS) water with or without administration of adenoviral vectors (i.p. or i.m. at 10(7) plaque-forming units [pfu]) given as a cotreatment or therapy. The deletion variant of the adenovirus served as a control for adenoviral infection. Colitis was assessed by (1) morphology (damage score, macrophage infiltration, apoptosis) and (2) function (myeloperoxidase activity and Ussing chamber analysis of epithelial ion transport). Infection with adenovirus alone did not affect colonic form or function. AdMuOSM (either i.p. or i.m.) significantly reduced the severity of the DSS-induced colitis. There was less damage, reduced macrophage infiltration, fewer apoptotic bodies, and a significant improvement in stimulated ion transport in colonic tissues from the treated mice. No benefit of AdMuIL-6 treatment was observed in this model system. Thus, systemic administration of AdMuOSM given as a cotreatment and to a lesser extent as a therapy was found to be of benefit in DSS-induced colitis, a murine model of inflammatory bowel disease (IBD).
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PMID:Adenoviral transfer of the murine oncostatin M gene suppresses dextran-sodium sulfate-induced colitis. 1285 31

The gut mucosa is a major site of contact with antigens from food and microbiota. Usually, these daily contacts with natural antigens do not result in inflammatory reactions; instead they result in a state of systemic hyporesponsiveness named oral tolerance. Inflammatory bowel diseases (IBD) are associated with the breakdown of the immunoregulatory mechanisms that maintain oral tolerance. Several animal models of IBD/colitis are available. In mice, these include targeted disruptions of the genes encoding cytokines, T cell subsets or signaling proteins. Colitis can also be induced by intrarectal administration of chemical substances such as 2,4,6-trinitrobenzene sulfonic acid in 50% ethanol. We report here a novel model of colitis induced by intrarectal administration of 50% ethanol alone. Ethanol-treated mice develop an inflammatory reaction in the colon characterized by an intense inflammatory infiltrate in the mucosa and submucosa of the large intestine. They also present up-regulation of both interferon gamma (IFN-gamma) and interleukin-4 (IL-4) production by cecal lymph node and splenic cells. These results suggest a mixed type of inflammation as the substrate of the colitis. Interestingly, cells from mesenteric lymph nodes of ethanol-treated mice present an increase in IFN-gamma production and a decrease in IL-4 production indicating that the cytokine balance is altered throughout the gut mucosa. Moreover, induction of oral tolerance to ovalbumin is abolished in these animals, strongly suggesting that ethanol-induced colitis interferes with immunoregulatory mechanisms in the intestinal mucosa. This novel model of colitis resembles human IBD. It is easy to reproduce and may help us to understand the mechanisms involved in IBD pathogenesis.
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PMID:Ethanol-induced colitis prevents oral tolerance induction in mice. 1293 90

The proinflammatory cytokines interleukin (IL)-1beta and IL-18 are supposed to play a crucial role in the pathogenesis of human inflammatory bowel disease. To exert biological activity, the precursors of both IL-1beta and IL-18 need to be cleaved by the interleukin-1beta-converting enzyme (ICE). IL-18 induces the synthesis of IFN-gamma in T cells and NK cells. In the present study, we investigated the effect of the specific ICE inhibitor pralnacasan in dextran sulfate sodium-induced murine colitis. Colitis was induced in BALB/c mice by 3.5% dextran sulfate sodium dissolved in drinking water for 10 days. Pralnacasan was administered either intraperitoneally or orally every day. To assess in vivo efficacy, a clinical disease activity score was evaluated daily. Colon length, expression of IL-18 in colonic tissue, expression of interferon-gamma (IFN-gamma) in paraaortal lymphocytes, and systemic production of IFN-gamma in splenocytes were analyzed post mortem. Intraperitoneally administered pralnacasan significantly reduced the clinical score compared with the dextran sulfate sodium control group from day 6 to day 10. Oral administration of pralnacasan also significantly reduced the clinical score at days 8 and 9. Administration of pralnacasan i.p. reduced the expression of intracolonic IL-18 significantly. Furthermore, pralnacasan reduced the number of IFN-gamma-positive lymphocytes in paraaortal lymph nodes. IFN-gamma synthesis in stimulated splenocytes was significantly suppressed in all pralnacasan-treated groups. No side effects of pralnacasan were observed. In conclusion, pralnacasan is effective in the prevention of dextran sulfate sodium-induced colitis. This effect is probably mediated by suppression of the proinflammatory cytokines IL-18, IL-1beta, and IFN-gamma.
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PMID:The interleukin-1 beta-converting enzyme inhibitor pralnacasan reduces dextran sulfate sodium-induced murine colitis and T helper 1 T-cell activation. 1461 Feb 33

Given the early onset, the chronic and recurrent nature of their disease and their normal life expectancy, patients with inflammatory bowel disease (IBD) may need considerable health care. The purpose of this study is to validate the Greek translation of the QUOTE-IBD questionnaire (GR-QUOTE-IBD). For that purpose we assessed its construct validity, and reliability. Fifty patients (33 ulcerative colitis, 17 Crohn's disease) completed the GR-QUOTE-IBD and visual-analogue scales (VAS) for the patients' evaluation of the quality of separate care dimensions, and of the total care. A subgroup of 33 patients (64%) completed the GR-QUOTE-IBD for a second time. Quality of life was assessed by the short version of the IBDQ. Clinical activity was assessed by Harvey-Bradshaw index and Colitis Activity Index. Correlations among all care dimensions and VAS were positive and highly significant (p<0.001). The total care and all eight dimensional care scores (quality impact and importance) had no significant differences between the baseline and the follow-up visit. Similarly, the correlation coefficients between the scores of the two occasions were all positive (close to one) and highly significant (p<0.001). The GR-QUOTE-IBD proved to be a valid and reliable instrument, applicable in international clinical studies.
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PMID:Validation of a reliable instrument (QUOTE-IBD) for assessing the quality of health care in Greek patients with inflammatory bowel disease. 1467 22


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