SUMMARYCytokines such as IL-1, tumour necrosis factor-alpha (TNF-a ), IL-6 and IL-8 are increased in inflamed colonic mucosa after administration of mouse DSS. Nuclear factor kB (NF-kB) is a transcription factor which regulates the expression of these cytokine genes. The effect of intracolonically administered NFkB (p65) antisense phosphorothioate oligonucleotide was examined in mouse DSS-induced colitis using drinking water containing 5% DSS. When antisense oligonucleotide was given on day 0, the disease activity index (DAI) representing clinical symptoms improved and the histological score decreased; furthermore, IL-1, IL-6, and TNF-a concentrations in rectal mucosa were lower compared with the control group. Clinical and histological improvement was also observed when antisense oligonucleotide was begun on day 2 but not on day 7. In addition, the distribution of antisense oligonucleotides was investigated by confocal laser microscopy. In colonic mucosa, oligonucleotides were predominantly localized to cells in the lamina propria, but also in the epithelium. Western blot analysis using homogenized rectal mucosa showed the decreased expression of NF-kB p65 in the antisense oligonucleotide-treated group, although it was increased in the colitis group. These results suggest that intracolonic administration of NF-kB antisense oligonucleotide may be effective in ulcerative colitis.

The pan-colonic NBI system improves the total number of adenomas detected, including significantly more diminutive adenomas, without prolongation of extubation time. These results indicate that routine use of the NBI system for surveillance of diminutive adenomas may be recommended.

Expression of the EP4 receptor, a prostaglandin (PG)E2 receptor subtype, as well as disease suppression by the administration of a selective EP4 agonist (ONO-AE1-329) was investigated in the colorectal mucosa of rats with dextran sodium sulphate (DSS)-induced colitis. Rats were given drinking water containing 3% DSS for 2 weeks. Expression of EP4 receptor mRNA was barely detectable under normal conditions according to reverse transcription-polymerase chain reaction (RT-PCR). By 1 week after the initial administration of DSS, the receptor mRNA was strongly expressed. After ONO-AE1-329 was administered intracolonically to rats with DSS colitis for 7 consecutive days, erosion and ulceration decreased. Peripheral white blood cell (WBC) counts became less elevated. Interleukin (IL)-1b and growth-regulated gene product/cytokine-induced neutrophil chemoattractant (GRO/CINC-1) concentrations in colorectal mucosa were lower than in colitis control group (IL-1b: 12.8 AE 4.6 and 30.8 AE 6.2 mg/mg protein, P < 0.05; GRO/CINC-1: 15.5 AE 3.0 and 39.2 AE 5.4 mg/mg protein, P < 0.05), and the expression of the corresponding cytokine mRNA was strongly suppressed. IL-10 concentration was higher than in control group (14.5 AE 1.7 and 7.9 AE 1.2 mg/mg, P < 0.05), and the mRNA was more strongly expressed. These results suggest that the EP4 receptor is important in colonic inflammation, and that PGE2 suppresses DSS colitis at least partly via the EP4 receptor and the above cytokine changes. Intracolonic administration of selective EP4 agonist might have therapeutic applicability in inflammatory bowel disease such as ulcerative colitis.

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AIM:To evaluate prospectively usefulness of fecal lactoferrin (Lf ) and fecal hemoglobin (Hb) in the diagnosis of colorectal diseases. METHODS:Fecal Lf and Hb were measured using ELISA in 872 patients before they underwent colorectal endoscopy. RESULTS:Lf was positive in 18 (50%) of 36 patients with colorectal cancer, 25 (15.9%) of 157 with colorectal polyps, 29 (46.8%) of 62 with ulcerative colitis, and 25 (62.5%) of 40 (62.5%) with Crohn's disease. The Hbpositive rates were 50%, 12.1%, 41.9% and 32.5%, respectively. Of the 318 patients free of abnormalities by colorectal endoscopy, Lf was positive in 29 (9.1%) and Hb was positive in 15 (4.7%). Among patients with Crohn's disease, the Lf-positive rate was significantly higher than the Hb-positive rate. If either high Lf or Hb levels were considered positive, the positive rates rose to 61.1%, 51.6%, and 67.5% in the colorectal cancer group, ulcerative colitis group, and Crohn's disease group, respectively. If both high Lf and Hb levels were rated positive, the positive predictive values (PPV) were 21% for colorectal cancer, 33% for ulcerative colitis, and 17% for Crohn's disease, and PPV of high Hb level alone was 18%, 25% and 13%, respectively. CONCLUSION:Fecal Lf and Hb were found useful in the detection of colorectal diseases, and the combination of the two measurements appears to increase the sensitivity and efficacy of diagnosis.

In order to investigate the mucosal injury mechanism in UC, we made dextran sulfate sodium (DSS)-induced colitis in rat and examined pathological findings, MPO activity, PGE₂ level, and local mRNA expression and secretion of IL-1β, TNF-α, GRO/CINC-1 and IL-10 in DSS colitis mucosa. Moreover, we estimated the correlation between the severity of mucosal damage and changes of these local inflammatory mediators’ values. Neutrophil infiltration was marked and MPO activity was locally increased in proportion to the severity of mucosal damage. The mRNA expression and secretion of IL-1β, GRO/CINC-1 and IL-10 were increased. Especially, the secretions of IL-1β and GRO/CINC-1 were increased in proportion to the severity of mucosal damage. However, those of TNF-α were not increased in the colitis mucosa. An abnormal macrophage function and the presence of macrophage subtypes producing different cytokines would be predicted from our TNF-α data. The lesion was less severe in the colonic mucosa with higher levels of endogenous PGE₂, while it was more severe in the colonic mucosa with lower levels of endogenous PGE₂, implicating this compound as an inhibitory factor against the development of inflammation in the affected mucosa. Our results suggest that PGE₂ might have therapeutic applicability to UC.

Bowel preparation using 1 L PEG with dimethylpolysiloxane 3 h before CE significantly reduced residue and intraluminal gas bubbles, and was considered to be a useful method for CE.