Glucotoxicity and lipotoxicity contribute to the impaired -cell function observed in type 2 diabetes. Here we examine the effect of saturated and monounsaturated fatty acids at different glucose concentrations on human -cell turnover and secretory function. Exposure of cultured human islets to saturated fatty acid and/or to an elevated glucose concentration for 4 days increased -cell DNA fragmentation and decreased -cell proliferation. In contrast, the monounsaturated palmitoleic acid or oleic acid did not affect DNA fragmentation and induced -cell proliferation. Moreover, each monounsaturated fatty acid prevented the deleterious effects of both palmitic acid and high glucose concentration. The cell-permeable ceramide analogue C 2 -ceramide mimicked both the palmitic acid-induced -cell apoptosis and decrease in proliferation. Furthermore, the ceramide synthetase inhibitor fumonisin B1 blocked the deleterious effects of palmitic acid on -cell turnover. In addition, palmitic acid decreased Bcl-2 expression and induced release of cytochrome c from the mitochondria into the cytosol, which was prevented by fumonisin B1 and by oleic acid. Finally, each monounsaturated fatty acid improved -cell secretory function that was reduced by palmitic acid and by high glucose. Thus, in human islets, the saturated palmitic acid and elevated glucose concentration induce -cell apoptosis, decrease -cell proliferation, and impair -cell function, which can be prevented by monounsaturated fatty acids. The deleterious effect of palmitic acid is mediated via formation of ceramide and activation of the apoptotic mitochondrial pathway, whereas Bcl-2 may contribute to the protective effect of monounsaturated fatty acids.
SPA right hemicolectomy is feasible and safe when performed by experienced laparoscopic surgeons. SPA right hemicolectomy may have the advantage over NOTES approach to offer the safety of laparoscopic colectomy especially for haemostasis and anastomosis. It has to be determined whether or not this approach would offer benefit to patients, except in cosmesis, compared to standard laparoscopic right hemicolectomy.
Three risk factors for anastomotic leak have been identified, one is patient-related (ASA score), one is disease-related (rectal location), the third being surgery-related (prolonged operative time). These factors should be considered in perioperative decision-making regarding defunctioning stoma formation.
Embryological and physiological data suggest that proximal (in relation to the splenic flexure) and distal parts of the colon represent distinct anatomical and functional entities. Since 1990, molecular biologists have identified two distinct pathways, microsatellite instability (MSI) and chromosomal instability (CIN), which are involved in the pathogenesis of colon cancer (CC). Thus, a new paradigm has emerged with the discovery that CC is a heterogeneous disease; furthermore recent data have demonstrated that these two distinct pathways in colorectal carcinogenesis are characterized by a different clinical outcome. The implications for the clinicians are twofold; (1) tumors originating from the proximal colon have a better prognosis due to a high percentage of MSI-positive lesions; and (2) location of the neoplasm in reference to the splenic flexure should be documented before group stratification in ongoing trials of adjuvant chemotherapy for CC. In the future, clinical decision-making regarding adjuvant chemotherapy might be stratified according to the MSI status of cancers located proximally to the splenic flexure.
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