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Toshio Watanabe Toshihisa Takeuchi Osamu Handa Yasuhisa Sakata Tetsuya Tanigawa Masatsugu Shiba Yuji Naito Kazuhide Higuchi Kazuma Fujimoto Toshikazu Yoshikawa Tetsuo Arakawa 《PloS one》2015,10(4)
Background
Low-dose aspirin (LDA) frequently causes small bowel injury. While some drugs have been reported to be effective in treating LDA-induced small intestinal damage, most studies did not exclude patients with mild damage thought to be clinically insignificant.Aim
We conducted a multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy of a high dose of rebamipide, a gastroprotective drug, for LDA-induced moderate-to-severe enteropathy.Methods
We enrolled patients who received 100 mg of enteric-coated aspirin daily for more than 3 months and were found to have more than 3 mucosal breaks (i.e., erosions or ulcers) in the small intestine by capsule endoscopy. Eligible patients were assigned to receive either rebamipide 300 mg (triple dose) 3 times daily or placebo for 8 weeks in a 2:1 ratio. Capsule endoscopy was then repeated. The primary endpoint was the change in the number of mucosal breaks from baseline to 8 weeks. Secondary endpoints included the complete healing of mucosal breaks at 8 weeks and the change in Lewis score (an endoscopic score assessing damage severity) from baseline to 8 weeks.Results
The study was completed by 38 patients (rebamipide group: n = 25, placebo group: n = 13). After 8 weeks of treatment, rebamipide, but not placebo, significantly decreased the number of mucosal breaks (p = 0.046). While the difference was not significant (p = 0.13), the rate of complete mucosal break healing in the rebamipide group (32%, 8 of 25) tended to be higher than that in the placebo group (7.7%, 1 of 13). Rebamipide treatment significantly improved intestinal damage severity as assessed by the Lewis score (p = 0.02), whereas placebo did not. The triple dose of rebamipide was well tolerated.Conclusions
High-dose rebamipide is effective for the treatment of LDA-induced moderate-to-severe enteropathy.Trial Registration
UMIN Clinical Trials Registry UMIN000003463 相似文献73.
Taishi Higashi Anna Tajima Naoko Ohshita Tatsunori Hirotsu Irhan Ibrahim Abu Hashim Keiichi Motoyama Sawako Koyama Ruriko Iibuchi Shiuhei Mieda Kenji Handa Tomoaki Kimoto Hidetoshi Arima 《AAPS PharmSciTech》2015,16(6):1290-1298
To achieve the potent therapeutic effects of human immunoglobulin G (IgG), highly concentrated formulations are required. However, the stabilization for highly concentrated human IgG is laborious work. In the present study, to investigate the potentials of polypseudorotaxane (PPRX) hydrogels consisting of polyethylene glycol (PEG) and α- or γ-cyclodextrin (α- or γ-CyD) as pharmaceutical materials for highly concentrated human IgG, we designed the PPRX hydrogels including human IgG and evaluated their pharmaceutical properties. The α- and γ-CyDs formed PPRX hydrogels with PEG (M.W. 20,000) even in the presence of highly concentrated human IgG (>100 mg/mL). According to the results of 1H-NMR, powder X-ray diffraction, and Raman microscopy, the formation of human IgG/CyD PPRX hydrogels was based on physical cross-linking arising from their columnar structures. The release profiles of human IgG from the hydrogels were in accordance with the non-Fickian diffusion model. Importantly, the stabilities of human IgG included into the hydrogels against thermal and shaking stresses were markedly improved. These findings suggest that PEG/CyD PPRX hydrogels are useful to prepare the formulation for highly concentrated human IgG.KEY WORDS: cyclodextrin, human IgG, hydrogel, polypseudorotaxane, stability 相似文献
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S. Koike Y. Handa H. Goto K. Sakai E. Miyagawa H. Matsui S. Ito Y. Kobayashi 《Applied and environmental microbiology》2010,76(6):1887-1894
To estimate the contribution of uncultured bacterial groups to fiber degradation, we attempted to retrieve both ecological and functional information on uncultured groups in the rumen. Among previously reported uncultured bacteria, fiber-associated groups U2 and U3, belonging to the low-GC Gram-positive bacterial group, were targeted. PCR primers and fluorescence in situ hybridization (FISH) probe targeting 16S rRNA genes or rRNA were designed and used to monitor the distribution of targets. The population size of group U2 in the rumen was as high as 1.87%, while that of group U3 was only 0.03%. Strong fluorescence signals were observed from group U2 cells attached to plant fibers in the rumen. These findings indicate the ecological significance of group U2 in the rumen. We succeeded in enriching group U2 using rumen-incubated rice straw as the inoculum followed by incubation in an appropriate medium with an agent inhibitory for Gram-negative bacteria. Consequently, we successfully isolated two strains, designated B76 and R-25, belonging to group U2. Both strains were Gram-positive short rods or cocci that were 0.5 to 0.8 μm in size. Strain B76 possessed xylanase and α-l-arabinofuranosidase activity. In particular, the xylanase activity of strain B76 was higher than that of xylanolytic Butyrivibrio fibrisolvens H17c grown on cellobiose. Strain R-25 showed an α-l-arabinofuranosidase activity higher than that of strain B76. These results suggest that strains B76 and R-25 contribute to hemicellulose degradation in the rumen.Ruminants can utilize plant fiber as an energy source with the aid of a symbiotic relationship with microbes in the rumen. The rumen is a complex microbial ecosystem comprised of bacteria (1010 to 1011 per ml), protozoa (104 to 106 per ml), and fungi (103 to 106 per ml) (8, 23, 39). Of the rumen microbes, bacteria are considered to be primarily responsible for the biological degradation of plant fiber, due to their high fibrolytic activity and large biomass in the rumen. In order to determine the mechanism of plant fiber degradation in the rumen, numerous studies have been performed on both the physiological and ecological characteristics of rumen bacteria (16, 27, 36). In particular, various aspects of bacterial attachment to feed particles have been investigated (19, 21, 25), because attachment to plant fiber is a critical step in initiating fiber degradation (20).Recent advances in molecular techniques have allowed recognition of a predominance of uncultured bacteria in the rumen (6, 24, 33). The majority (77%) of fiber-associated community members are uncultured bacteria, although 17% of cloned bacterial 16S rRNA gene sequences were classified as known fibrolytic species, such as Fibrobacter succinogenes and Butyrivibrio fibrisolvens (12). These findings clearly indicate the possibility for involvement of uncultured bacteria in ruminal fiber degradation. Through the phylogenetic analysis of fiber-associated community members, the unidentified bacterial groups were detected and designated uncultured group 2 (U2) and uncultured group 3 (U3). However, their roles in plant fiber digestion have yet to be determined.The predominance of uncultured bacteria has also been pointed out in other environments (26). Recently, new strategies for cultivation have been introduced to resolve the problem of the bacteria being unculturable. Sait et al. (28) reported that culturing with a polymeric growth substrate and longer incubation time was effective for the isolation of previously uncultured bacteria from soil. Cultivation on low-nutrient medium, using increased incubation times, with simulated natural environments or using a membrane as a solid support for growth has apparently led to improvements in bacterial cultivation (7, 31). On the other hand, the majority of rumen bacteria have yet to be isolated (10) despite great efforts toward the isolation of rumen bacterial strains over the past 50 years. Considering the ecological significance of uncultured rumen bacteria, it is important to cultivate and characterize these bacteria to fully understand the ecology of fiber digestion.In the present study, molecular monitoring tools were developed to obtain ecological information on target uncultured bacterial groups in the rumen. Previously uncultured rumen bacteria were then isolated and characterized to retrieve functional information. 相似文献
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