Protective effects of the dipeptidyl peptidase IV inhibitor sitagliptin in the blood-retinal barrier in a type 2 diabetes animal model

Aim: The aim of this study was to evaluate the efficacy of sitagliptin, a dipeptidyl peptidase IV inhibitor (DPP‐IV), in preventing the deleterious effects of diabetes on the blood–retinal barrier in male Zucker Diabetic Fatty (ZDF) rats. Methods: ZDF rats at 20 weeks of age were treated with sitagliptin (10 mg/kg/day) during 6 weeks. The effect of the drug on glycaemia was assessed by evaluating glycated haemoglobin (HbA1c). The content and/or distribution of tight junction (TJ) proteins occludin and claudin‐5, as well as nitrotyrosine residues, interleukin (IL)‐1β, BAX and Bcl‐2 was evaluated in the retinas by western blotting and/or immunohistochemistry. Retinal cell apoptosis was assessed by the terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labelling (TUNEL) assay. The number of CD34+ cells present in peripheral circulation was assessed by flow cytometry, and endothelial progenitor cells (EPC) adhesion ability to the retinal vessels was evaluated by immunohistochemistry. Results: Sitagliptin improved glycaemic control as reflected by a significant decrease in HbA1c levels by about 1.2%. Treatment with sitagliptin prevented the changes in the endothelial subcellular distribution of the TJ proteins induced by diabetes. Sitagliptin also decreased the nitrosative stress, the inflammatory state and cell death by apoptosis in diabetic retinas. Diabetic animals presented decreased levels of CD34+ cells in the peripheral circulation and decreased adhesion ability of EPC to the retinal vessels. Sitagliptin allowed a recovery of the number of CD34+ cells present in the bloodstream to levels similar to their number in controls and increased the adhesion ability of EPC to the retinal vessels. Conclusions: Sitagliptin prevented nitrosative stress, inflammation and apoptosis in retinal cells and exerted beneficial effects on the blood–retinal barrier integrity in ZDF rat retinas.     

Predicting retinal pigment epithelium remodelling and its functional impact

Graefe's Archive for Clinical and Experimental Ophthalmology - To identify predictive factors for RPE tear remodelling and its correlation with functional and morphological outcomes....     

Endoscopic submucosal dissection for colorectal tumors—1,000 colorectal ESD cases: one specialized institute’s experiences

Purpose

Endoscopic submucosal dissection (ESD) is a very useful endoscopic technique, making it possible to perform en bloc resection regardless of lesion size. Since the introduction of ESD at our hospital, we have performed 1,000 colorectal ESDs during 56 months. The purpose of this study was to evaluate the clinical outcomes of our colorectal ESD experience and to access the efficacy and safety of colorectal ESD.

Methods

Between October 2006 and August 2011, we performed ESD on 1,000 consecutive colorectal tumors in 966 patients. We evaluated the clinical outcomes of all said cases.

Results

The mean resected tumor size was 24.1 ± 13.3 (3–145) mm. Our overall endoscopic en bloc resection rate was 97.5 % (975/1,000), and our R0 resection rate was 91.2 % (912/1,000) respectively. Our perforation rate was 5.3 % (53/1,000). Of these 53 perforations, 50 cases were treated through conservative management with/without endoscopic clipping, whereas the remaining 3 patients received laparoscopic operation. Pathological examination showed adenocarcinoma in 37.2 % of cases (372/1,000) and neuroendocrine tumors in 11.2 % (112/1,000). We recommended additional radical surgery to 82 patients who had a risk of lymph node metastasis. Follow-up colonoscopies were performed on 722 patients. During the median follow-up period of 13 (1–62) months, there were three recurrences (0.4 %).

Conclusions

ESD is technically difficult, with a substantial risk of perforation. However, ESD enabled en bloc resection and pathologically complete resection of large colorectal epithelial tumors and submucosal tumors. As experience with the technique increases, ESD may gradually replace piecemeal endoscopic mucosal resection and radical colon resection in the treatment of colorectal tumors.