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      Lubiprostone Decreases the Small Bowel Transit Time by Capsule Endoscopy: An Exploratory, Randomised, Double-Blind, Placebo-Controlled 3-Way Crossover Study

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          Abstract

          The aim of this study was to investigate the usefulness of lubiprostone for bowel preparation and as a propulsive agent in small bowel endoscopy. Six healthy male volunteers participated in this randomized, 3-way crossover study. The subjects received a 24 μg tablet of lubiprostone 60 minutes prior to the capsule ingestion for capsule endoscopy (CE) and a placebo tablet 30 minutes before the capsule ingestion (L-P regimen), a placebo tablet 60 minutes prior to CE and a 24  μg tablet of lubiprostone 30 minutes prior to CE (P-L regimen), or a placebo tablet 60 minutes prior to r CE and a placebo tablet again 30 minutes prior to CE (P-P regimen). The quality of the capsule endoscopic images and the amount of water in the small bowel were assessed on 5-point scale. The median SBTT was 178.5 (117–407) minutes in the P-P regimen, 122.5 (27–282) minutes in the L-P regimen, and 110.5 (11–331) minutes in the P-L regimen ( P = 0.042). This study showed that the use of lubiprostone significantly decreased the SBTT. We also confirmed that lubiprostone was effective for inducing water secretion into the small bowel during CE.

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          Most cited references 34

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          A prospective trial comparing small bowel radiographs and video capsule endoscopy for suspected small bowel disease.

          This study was undertaken to prospectively compare the clinical outcomes of small bowel radiographs with the wireless capsule endoscopy. Twenty-two patients were selected consecutively because of suspected small bowel disease. Two patients were excluded owing to ileal stenosis. Thus, the results of barium follow-through and the Given M2A wireless video capsule (Given Imaging Ltd., Yoqneam, Israel) endoscopy were compared in 20 patients (13 men; mean age, 52.5 yr; range, 29-78 yr). Barium follow-through was normal in 17 patients and showed ileal nodularity in 3 patients. Capsule endoscopy was normal in 3 patients and showed positive findings in the remaining 17 patients. The barium study was considered diagnostic in 4 (20%) patients. The capsule endoscopy was considered diagnostic in 9 (45%) patients, suspicious in 8 (40%) patients, and failed in 3 (15%) patients. For obscure gastrointestinal (GI) bleeding, the diagnostic potential of barium follow-through was much worse as compared with the capsule endoscopy (5% vs. 31%, P < 0.05). Capsule endoscopy was well tolerated and better accepted by patients when compared with the most recently performed endoscopic procedure. The video capsule endoscope was found to be superior to small bowel radiograph for evaluation of small bowel diseases. However, this novel wireless endoscope system needs further assessment because of limitations such as difficulties in interpretation of potentially nonspecific findings.
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            Capsule endoscopy in the evaluation of patients with suspected small intestinal bleeding: Results of a pilot study.

            A video capsule has been developed to acquire photographic images of the small intestine during normal peristaltic motion. Patients between 21 and 80 years of age referred for enteroscopy because of obscure GI bleeding were offered entry into a trial in which they would undergo both capsule endoscopy and subsequent push enteroscopy. Results of capsule examinations were compared with push enteroscopy findings. Capsule endoscopy was performed with the Given M2A video capsule system. Twenty-one patients (12 women, 9 men, average age 61 years) were enrolled, all of whom completed the study. A bleeding site was found in 11 of 20 patients during capsule endoscopy. No additional intestinal diagnoses were made by enteroscopy. The yield of push enteroscopy in the evaluation of obscure bleeding was 30% (6/20), the yield of capsule endoscopy 55% (11/20). This difference did not reach statistical significance (p = 0.0625). Capsule endoscopy found a distal source of bleeding in 5 of 14 patients who had normal push enteroscopic examinations. Patients preferred capsule endoscopy to enteroscopy. This pilot study demonstrates that capsule endoscopy provides excellent visualization of the small intestine, is well tolerated by patients, and is safe. Capsule endoscopy identified small intestinal bleeding sites beyond the range of push enteroscopy.
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              SPI-0211 activates T84 cell chloride transport and recombinant human ClC-2 chloride currents.

              The purpose of this study was to determine the mechanism of action of SPI-0211 (lubiprostone), a novel bicyclic fatty acid in development for the treatment of bowel dysfunction. Adult rabbit intestine was shown to contain mRNA for ClC-2 using RT-PCR, Northern blot analysis, and in situ hybridization. T84 cells grown to confluence on permeable supports were shown to express ClC-2 channel protein in the apical membrane. SPI-0211 increased electrogenic Cl- transport across the apical membrane of T84 cells, with an EC50 of approximately 18 nM measured by short-circuit current (Isc) after permeabilization of the basolateral membrane with nystatin. SPI-0211 effects on Cl- currents were also measured by whole cell patch clamp using the human embryonic kidney (HEK)-293 cell line stably transfected with either recombinant human ClC-2 or recombinant human cystic fibrosis transmembrane regulator (CFTR). In these studies, SPI-0211 activated ClC-2 Cl- currents in a concentration-dependent manner, with an EC50 of approximately 17 nM, and had no effect in nontransfected HEK-293 cells. In contrast, SPI-0211 had no effect on CFTR Cl- channel currents measured in CFTR-transfected HEK-293 cells. Activation of ClC-2 by SPI-0211 was independent of PKA. Together, these studies demonstrate that SPI-0211 is a potent activator of ClC-2 Cl- channels and suggest a physiologically relevant role for ClC-2 Cl- channels in intestinal Cl- transport after SPI-0211 administration.
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                Author and article information

                Journal
                Gastroenterol Res Pract
                Gastroenterol Res Pract
                GRP
                Gastroenterology Research and Practice
                Hindawi Publishing Corporation
                1687-6121
                1687-630X
                2014
                29 December 2014
                : 2014
                Affiliations
                1Hepatology and Gastroenterology, Yokohama City University Hospital, Kanagawa, Yokohama 236-0004, Japan
                2Office of Postgraduate Medical Education, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ku, Kanagawa, Yokohama 236-0004, Japan
                3Division of Gastroenterology, Nippon Medical School, Tokyo 113-8603, Japan
                4Department of General Medicine, Yokohama City University School of Medicine, Kanagawa, Yokohama 236-0004, Japan
                5Department of Gastroenterology, Yokohama City University Hospital, Kanagawa, Yokohama 236-0004, Japan
                Author notes

                Academic Editor: Antoni Castells

                Article
                10.1155/2014/879595
                4295152
                Copyright © 2014 Mizue Matsuura et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Clinical Study

                Gastroenterology & Hepatology

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