Background: Different abnormalities of T cell effector function distinguish Crohn's disease (CD) from ulcerative colitis (UC). Because cell cycling determines effector function, pathogenic events in CD and UC may depend on cell cycle changes unique to each condition. Methods: Cell cycle kinetics, cycle regulatory molecule expression, apoptosis, caspase and telomerase activity, and cellular expansion were evaluated in CD2 and CD3 activated control, CD, and UC lamina propria T cells. Results: Compared with normal cells, CD T cells cycle faster, express increased phosphorylated Rb and decreased phosphorylated p53 levels, display less caspase activity but more telomerase activity, die less, and undergo vigorous cellular expansion. In contrast, UC T cells cycle slower, express normal levels of phosphorylated Rb and p53, display more caspase activity but have no telomerase activity, die more, and have a limited capacity to expand. Conclusions: T cell cycle abnormalities in CD indicate a state of hyperreactivity compatible with loss of tolerance, but a hyporeactive state compatible with anergy in UC. Thus distinct and divergent T cell cycle characteristics underlie the pathogenesis of the two main forms of inflammatory bowel disease.
ObjectivesPatients with inflammatory bowel disease have a higher risk of thrombosis, which is associated with a higher morbidity and mortality. Most data about VTE are related to hospitalized patients with active disease, but several cases happen in the outpatient setting, and are not covered by current prophylaxis recommendation. As the knowledge of VTE in outpatients is still poor, the aim of this study is to evaluate the risk, clinical data and mortality of thrombosis in patients followed in our center, comparing our findings with the current prophylaxis recommendation.MethodsThe medical electronic chart of 1093 inflammatory bowel disease patients and their image exams were actively searched for words related to thrombosis, followed by charts reviewed to collect information about the event and data regarding clinical settings and thrombosis profile.ResultsOverall, 654 Crohn’s and 439 Colitis patients were included. Thrombosis prevalence was 5.1%,and mortality rate was higher in patients who had suffered thrombosis (10.71% vs. 1.45%, OR 8.0). Half of them developed thrombosis in the outpatient setting, 52% of these had disease activity, 17% had recent hospitalization, and 10% had previous thrombosis. In 27% of cases, diagnosis was done by routine image exams, with no clinical symptoms or previous history of thrombosis. None of them had used thromboprophylaxis. However, a great majority of patients who had thrombosis during hospitalization used heparin prophylaxis.ConclusionInflammatory bowel disease patients who develop thrombosis have an increased mortality risk. A significant proportion of the events happened in patients without a clear thromboprophylaxis recommendation or in those receiving heparin prophylaxis.
The pathogenesis of nonsteroidal anti-inflammatory drug (NSAID) enteropathy is a complex process involving the uncoupling of mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase (COX). Rofecoxib, a selective inhibitor of COX-2, has shown less gastric damage, but the same beneficial effect is not clear in the case of the small bowel. Fifty-seven male Wistar rats (250-350 g) were divided into three groups (N = 19 each) to evaluate the effect of this NSAID on the rat intestine. The groups received 2.5 mg/kg rofecoxib, 7.5 mg/kg indomethacin or water with 5% DMSO (control) given as a single dose by gavage 24 h before the beginning of the experiment. A macroscopic score was used to quantify intestinal lesions and intestinal permeability was measured using [ 51 Cr]-ethylenediaminetetraacetic acid ([ 51 Cr]-EDTA). The extent of intestinal lesion, indicated by a macroscopic score, was significantly lower when rofecoxib was administered compared to indomethacin (rofecoxib = 0.0 vs indomethacin = 63.6 ± 25.9; P < 0.05) and did not differ from control. The intestinal permeability to [ 51 Cr]-EDTA was significantly increased after indomethacin (control = 1.82 ± 0.4 vs indomethacin = 9.12 ± 0.8%; P < 0.0001), but not after rofecoxib, whose effect did not differ significantly from control (control = 1.82 ± 0.4 vs rofecoxib = 2.17 ± 0.4%; ns), but was significantly different from indomethacin (indomethacin = 9.12 ± 0.8 vs rofecoxib = 2.17 ± 0.4%; P < 0.001). In conclusion, the present data show that rofecoxib is safer than indomethacin in rats because it does not induce macroscopic intestinal damage or increased intestinal permeability.
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