Fabio Vistoli

Several properties of pancreatic beta-cells in type 2 diabetes (T2D) were studied by using islets isolated from T2D subjects. Moreover, because metformin has protective effects on nondiabetic beta-cells exposed to high glucose or free fatty acid levels, we investigated its direct action on T2D islet cells. Diabetic islets were characterized by reduced insulin content, decreased amount of mature insulin granules, impaired glucose-induced insulin secretion, reduced insulin mRNA expression, and increased apoptosis with enhanced caspase-3 and -8 activity. These alterations were associated with increased oxidative stress, as shown by higher nitrotyrosine concentrations, increased expression of protein kinase C-beta2 and nicotinamide adenine dinucleotide phosphate reduced-oxidase, and changes in mRNA expression of manganese- superoxide dismutase, Cu/Zn-superoxide dismutase, catalase, and glutathione peroxidase. Twenty-four-hour incubation of T2D islets with metformin was associated with increased insulin content, increased number and density of mature insulin granules, improved glucose-induced insulin release, and increased insulin mRNA expression. Moreover, apoptosis was reduced, with concomitant decrease of caspase-3 and -8 activity. These changes were accompanied by reduction or normalization of several markers of oxidative stress. Thus, T2D islets have several functional and survival defects, which can be ameliorated by metformin; the beneficial effects of the drug are mediated, at least in part, by a reduction of oxidative stress.

BACKGROUND: Laparoscopic pancreaticoduodenectomy is feasible, but requires adaptations to established surgical techniques. The improved dexterity offered by robotic assistance provides the opportunity to see whether laparoscopic pancreaticoduodenectomy can be performed safely when faithfully reproducing the open operation. METHODS: Patients were selected for robotic pancreaticoduodenectomy when generally suitable for laparoscopy. Obese patients were excluded, and those with pancreatic cancer were highly selected. A prospectively designed database was used for data collection and analysis. RESULTS: Of 238 patients undergoing pancreaticoduodenectomy, 34 (14·3 per cent) were operated on robotically. No procedure was converted to conventional laparoscopy or open surgery, despite three patients requiring segmental resection of the superior mesenteric/portal vein and reconstruction. The mean duration of operation was 597 (range 420-960) min. The mean number of lymph nodes retrieved and analysed from patients with neoplasia was 32 (range 15-76). Four patients required blood transfusions and five developed postoperative complications exceeding Clavien-Dindo grade II. There were four grade B pancreatic fistulas. One patient died on postoperative day 40. Excess mean operative cost compared with open resection was €6193. CONCLUSION: Selected patients can safely undergo robotic pancreaticoduodenectomy. The main downsides are high costs and prolonged operating times compared with open resection.

A kidney from a 56-year-old mother was transplanted to her 37-year-old daughter laparoscopically using the daVinci HDSi surgical system. The kidney was introduced into the abdomen through a 7-cm suprapubic incision used also for the uretero-vescical anastomosis. Vascular anastomoses were carried out through a total of three additional ports. Surgery lasted 154 min, including 51 min of warm ischemia of the graft. Urine production started immediately after graft reperfusion. Renal function remains optimal at the longest follow-up of 3 months. The technique employed in this case is discussed in comparison with the only other two contemporary experiences, both from the USA. Furthermore, possible advantages and disadvantages of robotics in kidney transplantation are discussed extensively. We conclude that the daVinci surgical system allows the performance of kidney transplantation under optimal operative conditions. Further experience is needed, but it is likely that solid organ transplantation will not remain immune to robotics.

BACKGROUND: Decreased beta-cell mass, mainly due to apoptosis, is crucial for the development and progression of type 2 diabetes. Chronic exposure to high glucose levels is a probable underlying mechanism, whereas the role of oral anti-diabetic agents (sulphonylureas in particular) is still unsettled. METHODS: To directly investigate more on such issues, we prepared isolated human islets, which were then cultured for 5 days in continuous normal glucose concentration (NG, 5.5 mmol/L) or normal and high (HG, 16.7 mmol/L) glucose levels (alternating every 24 h), with or without the addition of therapeutical concentration (10 micromol L) of gliclazide or glibenclamide. RESULTS: Intermittent high glucose caused a significant decrease of glucose-stimulated insulin secretion, which was not further affected by either sulphonylurea. Apoptosis, as assessed by electron microscopy, was also significantly increased by alternating high glucose exposure, which was accompanied by altered mitochondria morphology and density volume, and increased concentrations of nitrotyrosine, a marker of oxidative stress. Gliclazide, but not glibenclamide, was able to significantly reduce high glucose induced apoptosis, mitochondrial alterations, and nitrotyrosine concentration increase. CONCLUSION: Therefore, gliclazide protected human beta-cells from apoptosis induced by intermittent high glucose, and this effect was likely to be due, at least in part, to the anti-oxidant properties of the molecule.