A novel role for ceramide synthase 6 in mouse and human alcoholic steatosis.

Perilipin 2 (PLIN2) is a lipid-droplet protein that is up-regulated in alcoholic steatosis and associated with hepatic accumulation of ceramides, bioactive lipids implicated in alcoholic liver disease pathogenesis. The specific role of ceramide synthetic enzymes in the regulation of PLIN2 and promotion of hepatocellular lipid accumulation is not well understood. We examined the effects of pharmacologic ceramide synthesis inhibition on hepatic PLIN2 expression, steatosis, and glucose and lipid homeostasis in mice with alcoholic steatosis and in ethanol-incubated human hepatoma VL17A cells. In cells, pharmacologic inhibition of ceramide synthase reduced lipid accumulation by reducing PLIN2 RNA stability. The subtype ceramide synthase (CerS)6 was specifically up-regulated in experimental alcoholic steatosis in vivo and in vitro and was up-regulated in zone 3 hepatocytes in human alcoholic steatosis. In vivo ceramide reduction by inhibition of de novo ceramide synthesis reduced PLIN2 and hepatic steatosis in alcohol-fed mice, but only de novo synthesis inhibition, not sphingomyelin hydrolysis, improved glucose tolerance and dyslipidemia. These findings implicate CerS6 as a novel regulator of PLIN2 and suggest that ceramide synthetic enzymes may promote the earliest stage of alcoholic liver disease, alcoholic steatosis.-Williams, B., Correnti, J., Oranu, A., Lin, A., Scott, V., Annoh, M., Beck, J., Furth, E., Mitchell, V., Senkal, C. E., Obeid, L., Carr, R. M. A novel role for ceramide synthase 6 in mouse and human alcoholic steatosis.

Controlled colonic insufflation by a remotely triggered capsule for improved mucosal visualization.

BACKGROUND AND STUDY AIMS: Capsule endoscopy is an attractive alternative to colorectal cancer screening by conventional colonoscopy, but is currently limited by compromised mucosal visibility because of the lack of safe, controlled colonic insufflation. We have therefore developed a novel system of untethered, wireless-controlled carbon dioxide (CO2) insufflation for use in colonic capsule endoscopy, which this study aims to assess in vivo. MATERIAL AND METHODS: This observational, nonsurvival, in vivo study used five Yorkshire-Landrace cross swine. A novel insufflation capsule was placed in the porcine colons, and we recorded volume of insufflation, time, force, visualization, and a pathologic assessment of the colon. RESULTS: The mean (standard deviation [SD]) diameter of insufflation was 32.1 (3.9) mm. The volume of CO2 produced successfully allowed complete endoscopic visualization of the mucosa and safe proximal passage of the endoscope. Pathologic examination demonstrated no evidence of trauma caused by the capsule. CONCLUSIONS: These results demonstrate the feasibility of a novel method of controlled colonic insufflation via an untethered capsule in vivo. This technological innovation addresses a critical need in colon capsule endoscopy.

Same-day booking: success in a Canadian family practice.

PROBLEM BEING ADDRESSED: Patients in a family practice had to wait 6 weeks for an appointment. OBJECTIVE OF PROGRAM: To improve patient care by facilitating access to timely appointments. PROGRAM DESCRIPTION: An FP from Halifax, NS, implemented advanced access in her practice. Advanced access is a same-day booking system, which has been shown to reduce or eliminate patient backlogs without the addition of resources. Theoretically, it can be put into effect in any practice with a stable backlog (which indicates that supply and demand are well matched). The first step to implement the advanced access system was to clear the existing appointment backlog. During a 6-week "boot camp" period, all prebooked patients and patients who called requesting same-day appointments were seen (between 50 and 60 patients per day). Same-day appointment rules apply to almost all patients. Staff begin accepting calls at 8:00 AM, and patients request the most convenient time available. CONCLUSION: Baseline and postimplementation data are not available, as this was not a formal research study. Nevertheless, this FP from Halifax who implemented advanced access experienced the following in her practice: elimination of patient backlog, fewer no-shows, patients' happiness with the system, increase in physician and staff morale, and stability in physician income. Formal feasibility studies and research evaluating patient outcomes, cost effectiveness, and physician and patient satisfaction in a variety of practice settings would help Canadian FPs decide if same-day booking could be successfully implemented in their practices.