Diabetes is a risk factor for Alzheimer’s disease and it is associated with significant memory loss. In the present study, we hypothesized that the soluble epoxide hydrolase (sEH) inhibitor N-[1-(1-oxopropyl)-4-piperidinyl]-N’-[4-(trifluoromethoxy)phenyl)-urea (also known as TPPU) could alleviate diabetes-aggravated Alzheimer’s disease-like symptoms by improving memory and cognition, and reducing the oxidative stress and inflammation associated with this condition. Also, we evaluated the effect of edaravone, an antioxidant on diabetes-induced Alzheimer’s-like complications and the additive effect of docosahexaenoic acid (DHA) on the efficacy of TPPU. Diabetes was induced in male Sprague-Dawley rats by intraperitoneally administering streptozotocin (STZ). Six weeks after induction of diabetes, animals were either treated with vehicle, edaravone (3 or 10 mg/kg), TPPU (1 mg/kg) or TPPU (1 mg/kg) + DHA (100 mg/kg) for 2 weeks. The results demonstrate that the treatments increased the memory response of diabetic rats, in comparison to untreated diabetic rats. Indeed, DHA + TPPU were more effective than TPPU alone in reducing the symptoms monitored. All drug treatments reduced oxidative stress and minimized inflammation in the brain of diabetic rats. Expression of the amyloid precursor protein (APP) was increased in the brain of diabetic rats. Treatment with edaravone (10 mg/kg), TPPU or TPPU + DHA minimized the level of APP. The activity of acetylcholinesterase (AChE) which metabolizes acetylcholine was increased in the brain of diabetic rats. All the treatments except edaravone (3 mg/kg) were effective in decreasing the activity of AChE and TPPU + DHA was more efficacious than TPPU alone. Intriguingly, the histological changes in hippocampus after treatment with TPPU + DHA showed significant protection of neurons against STZ-induced neuronal damage. Overall, we found that DHA improved the efficacy of TPPU in increasing neuronal survival and memory, decreasing oxidative stress and inflammation possibly by stabilizing anti-inflammatory and neuroprotective epoxides of DHA. In the future, further evaluating the detailed mechanisms of action of sEH inhibitor and DHA could help to develop a strategy for the management of Alzheimer’s-like complications in diabetes.

Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy remains a challenging procedure even for the more experienced endoscopists. We present a unique case of an ERCP performed in a patient with prior Whipple surgery, where biliary access was obtained via an endoscopic ultrasound (EUS)-guided rendezvous technique, and cannulation was ultimately done using a modified therapeutic endoscope with successful biliary drainage.

Ulcerative colitis (UC) is a risk factor for the development of inflammation-associated dysplasia or colitis-associated neoplasia (CAN). This transformation results from chronic inflammation, which induces changes in epithelial proliferation, survival, and migration via the induction of chemokines and cytokines. There are notable differences in genetic mutation profiles between CAN in UC patients and sporadic colorectal cancer in the general population. Colonoscopy is the cornerstone for surveillance and management of dysplasia in these patients. There are several modalities to augment the quality of endoscopy for the better detection of dysplastic or neoplastic lesions, including the use of high-definition white-light exam and image-enhanced colonoscopy, which are described in this review. Clinical practice guidelines regarding surveillance strategies in UC have been put forth by various GI societies, and overall, there is agreement between them except for some differences, which we highlight in this article. These guidelines recommend that endoscopically detected dysplasia, if feasible, should be resected endoscopically. Advanced newer techniques, such as endoscopic mucosal resection and endoscopic submucosal dissection, have been utilized in the treatment of CAN. Surgery has traditionally been the mainstay of treating such advanced lesions, and in cases where endoscopic resection is not feasible, a proctocolectomy, followed by ileal pouch-anal anastomosis, is generally recommended. In this review we summarize the approach to surveillance for cancer and dysplasia in UC. We also highlight management strategies if dysplasia is detected.

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