Inhibition of plasminogen activator inhibitor-1 attenuates against intestinal fibrosis in mice

Background/Aims@#Intestinal fibrosis is a major complication of Crohn’s disease (CD). The profibrotic protein transforming growth factor-β (TGF-β) has been considered to be critical for the induction of the fibrotic program. TGF-β has the ability to induce not only the expression of extracellular matrix (ECM) including collagen, but also the production of plasminogen activator inhibitor-1 (PAI-1) that prevents enzymatic degradation of the ECM during the onset of fibrotic diseases. However, the significance of PAI-1 in the developing intestinal fibrosis has not been fully understood. In the present study, we examined the actual expression of PAI-1 in fibrotic legion of intestinal inflammation and its correlation with the abnormal ECM deposition. @*Methods@#Chronic intestinal inflammation was induced in BALB/c mice using 8 repeated intrarectal injections of 2,4,6-trinitrobenzene sulfonic acid (TNBS). TM5275, a PAI-1 inhibitor, was orally administered as a carboxymethyl cellulose suspension each day for 2 weeks after the sixth TNBS injection. @*Results@#Using a publicly available dataset (accession number, GSE75214) and TNBS-treated mice, we observed increases in PAI-1 transcripts at active fibrotic lesions in both patients with CD and mice with chronic intestinal inflammation. Oral administration of TM5275 immediately after the onset of intestinal fibrosis upregulated MMP-9 (matrix metalloproteinase 9) and decreased collagen accumulation, resulting in attenuation of the fibrogenesis in TNBS-treated mice. @*Conclusions@#PAI-1-mediated fibrinolytic system facilitates collagen degradation suppression. Hence, PAI-1 inhibitor could be applied as an anti-fibrotic drug in CD treatment.

Removal Of Accidentally Ingested Large Foreign Object Via The Anus After Watchful Waiting

One of the commonest complaints, for which a patient arrives in hospitals, is the presence of foreign body. It could be due to accidental ingestion or any other cause which leads to presences of a foreign body in the gastrointestinal tract. It is believed that foreign objects larger than 5–6 cm in size are unlikely to pass through the duodenum. Here, we describe a case wherein the patient accidentally swallowed a 7-cm-sized mouthguard that could not be removed by emergency upper gastrointestinal endoscopy but was subsequently removed via the anus after a period of watchful waiting