Subjects with diarrhea-predominant IBS have increased rectal permeability responsive to tryptase.

BACKGROUND AND AIMS: Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) appear to have increased intestinal permeability; it has been suggested that activation of protease-activated receptor-2 (PAR-2) receptors is responsible for this alteration. The aims of this study are to evaluate (1) if rectal (large bowel) permeability is increased in IBS-D and (2) if tryptase plays a critical role in the altered permeability. METHODS: Rectal biopsies from 20 patients with IBS-D and 30 subjects without the condition (normal controls) were assessed for macromolecular permeability using horseradish peroxidase in Ussing chambers in the basal state and after addition of drugs to the basolateral side. Reverse-transcription polymerase chain reaction (RT-PCR) was performed using colonic biopsy tissues from patients with IBS-D and normal subjects. RESULTS: When tryptase was added to the basolateral (not mucosal) side of normal rectal biopsy tissues, permeability appeared to be proportional to the increase in tryptase concentration (P < 0.05) and was abolished by the addition of tryptase inhibitor (100 µM nafamostat; 1.568 ± 0.874 ng/2 h/mm(2) to 0.766 ± 0.661 ng/2 h/mm(2), n = 14, respectively, P < 0.01). Intestinal permeability in patients with IBS-D was significantly increased compared with controls (0.848 ± 0.0.600 ng/2 h/mm(2), n = 21, P < 0.01). Nafamostat significantly reduced the enhanced permeability in IBS-D (0.934 ± 0.589 ng/2 h/mm(2) to 0.247 ± 0.263 ng/2 h/mm(2), n = 14, respectively, P < 0.05). Transcription levels of PAR2 measured by RT-PCR did not differ between IBS-D and normal subjects. CONCLUSION: Tryptase seems to play an important role in the control of human colonic mucosal permeability, and enhanced tryptase activity was responsible for the increased permeability of rectal mucosa in IBS patients.

Analysis of rectal dynamic and static compliances in patients with irritable bowel syndrome.

AIMS: Our aim was to investigate whether the dynamic and static compliances differ between patients with irritable bowel syndrome (IBS) and normal subjects. MATERIALS AND METHODS: Fifty-five IBS patients (age range 20-65 years, mean age 39.0 years, 28 women and 27 men; 36 diarrhea-predominant IBS (IBS-D) patients and 19 constipation-predominant IBS (IBS-C) patients) with symptoms that fulfilled the Rome-II criteria and 21 healthy controls (age range 25-58 years, mean age 37.8 years; 11 women and ten men) were recruited. The anorectal functions, including dynamic compliance, were evaluated via barostat tests. A power exponential model was used for the evaluation of static compliance. RESULTS: There was no significant difference in dynamic compliance between the normal subjects and the IBS patients (10.3+/-3.1 and 8.9+/-2.9 mmHg, respectively, P>0.05). However, even though no significant difference was detected in the overall shape of the curve (beta; P>0.05), there were significant differences in the kappa and P (half) between the normal subjects and the IBS patients (P<0.05), respectively. When we compared the dynamic and static compliances between the IBS-C and IBS-D patients, there were no significant differences found (P>0.05). CONCLUSIONS: An exponential model provided good fit to the actual data, and there were significant differences in static compliance between the normal subjects and the IBS patients. This result can reveal the altered biomechanical properties of the gut wall in IBS patients.