Comparison of Efficacy and Safety between Mosapride and Acotiamide for Japanese patients with Functional Dyspepsia

　Background: 5-HT4 agonists (mosapride) and acetylcholine esterase inhibitor (acotiamide) are prokinetics used to treat functional dyspepsia (FD). However, to date, there has been no direct comparative study between them. The aim of this study was to compare the drugs’ efficacy and safety and to determine their predictive biomarkers.　Methods: The present study was a prospective, randomized, open-labeled, and crossover trial in Japanese FD patients. FD was diagnosed using Rome IV. We performed upper gastrointestinal (GI) endoscopy, GI symptom rating scale, and 8-item Short-Form Health Survey to evaluate the presence of GI disorders, GI symptoms, and quality of life (QOL), respectively. Responders were defined when reporting at least a 40% improvement of the GSRS scores from their baseline.　Results: In total, 60 Japanese FD patients were randomly assigned to the acotiamide preceding group (n = 30) or mosapride preceding group (n = 30), and 51 patients were finally analyzed. Following treatment with both mosapride and acotiamide, GI symptoms and QOL scores improved significantly. The responder rates of mosapride and acotiamide were 37% and 33%, respectively. No severe adverse clinical event developed. The prevalence of H. pylori eradication history was significantly lower in the mosapride responder group than in the nonresponder group (45.9% vs. 14.2%, p = 0.03).　Discussion: Mosapride and acotiamide had similar effects on GI symptoms in FD patients in the absence of severe adverse events. H. pylori infection might impact in the pathogenesis of functional dyspepsia. Further investigation is needed to clarify the difference between mosapride and acotiamide

Epitope mapping for monoclonal antibody reveals the activation mechanism for αVβ3 integrin.

Epitopes for a panel of anti-αVβ3 monoclonal antibodies (mAbs) were investigated to explore the activation mechanism of αVβ3 integrin. Experiments utilizing αV/αIIb domain-swapping chimeras revealed that among the nine mAbs tested, five recognized the ligand-binding β-propeller domain and four recognized the thigh domain, which is the upper leg of the αV chain. Interestingly, the four mAbs included function-blocking as well as non-functional mAbs, although they bound at a distance from the ligand-binding site. The epitopes for these four mAbs were further determined using human-to-mouse αV chimeras. Among the four, P3G8 recognized an amino acid residue, Ser-528, located on the side of the thigh domain, while AMF-7, M9, and P2W7 all recognized a common epitope, Ser-462, that was located close to the α-genu, where integrin makes a sharp bend in the crystal structure. Fibrinogen binding studies for cells expressing wild-type αVβ3 confirmed that AMF-7, M9, and P2W7 were inhibitory, while P3G8 was non-functional. However, these mAbs were all unable to block binding when αVβ3 was constrained in its extended conformation. These results suggest that AMF-7, M9, and P2W7 block ligand binding allosterically by stabilizing the angle of the bend in the bent conformation. Thus, a switchblade-like movement of the integrin leg is indispensable for the affinity regulation of αVβ3 integrin

Evaluation of Performance in Colon Capsule Endoscopy Reading by Endoscopy Nurses

Background. Although there are papers reporting on the accuracy of colon capsule endoscopy (CCE) compared with colonoscopy (CS), there are few reports on the detection rates of significant lesions by endoscopy nurses. We previously reported no significant difference in the detection rates for small bowel capsule endoscopy (SBCE) images among two well-trained physicians and one expert nurse. Objective. To evaluate the reading time and detection rate of the significant lesions of CCE images among novice and trained expert endoscopy nurses and novice physicians. Methods. CCE videos of 20 consecutive patients who performed both CCE and CS with clinically significant localized lesions were selected. Two trained expert endoscopy nurses, untrained two novice physicians, and novice three endoscopy nurses reviewed CCE videos. The detection rate of the lesions and reading time were compared among the three groups and were evaluated by comparison between the first and the second 10 videos. Results. The median reading time was the shortest (19 min) in the trained expert endoscopy nurses and the longest (45 min) in the novice nurses. The number of thumbnails tended to be more in the trained expert endoscopy nurses in the first 10-video reading. Although the detection rates of small polyps (<5 mm) were significantly lower (46.5%, p=0.025) in the novice nurses compared to the others, they were improved (35.2% to 63.5%, p=0.015) in the second 10 videos. The detection rates of tumor lesions by either one of two trained expert endoscopy nurses were higher compared to those by each novice physician. Conclusions. The trained expert endoscopy nurses for CCE reading can reduce physician's time and improve the diagnostic yield

MAb binding to cells expressing domain-swapping chimeras.

<p>The numbers represent the percentage of the cell population stained with each mAb.</p