Sodium nitrite protects against kidney injury induced by brain death and improves post-transplant function.

Renal injury induced by brain death is characterized by ischemia and inflammation, and limiting it is a therapeutic goal that could improve outcomes in kidney transplantation. Brain death resulted in decreased circulating nitrite levels and increased infiltrating inflammatory cell infiltration into the kidney. Since nitrite stimulates nitric oxide signaling in ischemic tissues, we tested whether nitrite therapy was beneficial in a rat model of brain death followed by kidney transplantation. Nitrite, administered over 2 h of brain death, blunted the increased inflammation without affecting brain death-induced alterations in hemodynamics. Kidneys were transplanted after 2 h of brain death and renal function followed over 7 days. Allografts collected from nitrite-treated brain-dead rats showed significant improvement in function over the first 2 to 4 days after transplantation compared with untreated brain-dead animals. Gene microarray analysis after 2 h of brain death without or with nitrite therapy showed that the latter significantly altered the expression of about 400 genes. Ingenuity Pathway Analysis indicated that multiple signaling pathways were affected by nitrite, including those related to hypoxia, transcription, and genes related to humoral immune responses. Thus, nitrite therapy attenuates brain death-induced renal injury by regulating responses to ischemia and inflammation, ultimately leading to better post-transplant kidney function.

Should pancreatectomy with islet cell autotransplantation in patients with chronic alcoholic pancreatitis be abandoned?

BACKGROUND: Pancreatectomy or drainage has been advocated for pain due to chronic pancreatitis. Islet cell autotransplantation (IAT) may improve quality of life (QOL); optimal patient selection has not been established. STUDY DESIGN: Outcomes of 100 patients who underwent pancreatectomy with islet isolation between 2005 and 2012 were assessed by etiology (alcoholic pancreatitis [AP] 30%, and nonalcoholic pancreatitis [NAP] 70%). Insulin requirement, Short Form-36, and McGill Pain Questionnaires were assessed. Data were analyzed using SASv9.2. RESULTS: Of the 100 patients, isolation was unsuccessful in 9 patients due to fibrosis. Alcoholic pancreatitis was associated with 7 of 9 failed isolations (23% vs 3%, p < 0.01), and all of these patients are now diabetic. Ninety-one patients (age 44 years, follow-up 19 months, 23% AP) underwent resection with IAT. Total islet yield (islet cell equivalents [IEQ]) and IEQ/kg body weight were less for patients with AP (81,000 vs 150,000, p < 0.01; 1,260 vs 2,190, respectively, p = 0.01) overall and more specifically, for total pancreatectomy (92,000 vs 188,000, respectively, p = 0.02). Twenty-eight (34%) of all patients who had resections and 15% of those undergoing total pancreatectomy are insulin free. Multivariate analysis identified AP as an independent predictor of insulin units/day (p = 0.01). Complete pre- and postoperative QOL and pain surveys were available on 69 patients. Patients with AP had less QOL improvement (1 of 8 vs 5 of 8 domains, p < 0.01) and "present pain" improvement at 2 years from preoperative levels in those with NAP; no improvement in QOL was seen in those with AP (NAP 2.7 to 1.2, p < 0.01; AP 2.7 to 2.2, p > 0.05). CONCLUSIONS: After pancreatic resection with planned IAT, AP resulted in failed isolations, lower yields, higher insulin requirements, poor long-term QOL improvement, and no improvement in pain scores compared with NAP. Further studies should define criteria for resection and IAT for patients with alcoholic chronic pancreatitis.

Enhanced rat islet function and survival in vitro using a biomimetic self-assembled nanomatrix gel.

Peptide amphiphile (PA) is a peptide-based biomaterial that can self-assemble into a nanostructured gel-like scaffold, mimicking the chemical and biological complexity of natural extracellular matrix. To evaluate the capacity of the PA scaffold to improve islet function and survival in vitro, rat islets were cultured in three different groups--(1) bare group: isolated rat islets cultured in a 12-well nontissue culture-treated plate; (2) insert group: isolated rat islets cultured in modified insert chambers; (3) nanomatrix group: isolated rat islets encapsulated within the PA nanomatrix gel and cultured in modified insert chambers. Over 14 days, both the bare and insert groups showed a marked decrease in insulin secretion, whereas the nanomatrix group maintained glucose-stimulated insulin secretion. Moreover, entire islets in the nanomatrix gel stained positive for dithizone up to 14 days, indicating better maintained glucose-stimulated insulin production. Fluorescein diacetate/propidium iodide staining results also verified necrosis in the bare and insert groups after 7 days, whereas the PA nanomatrix gel maintained islet viability after 14 days. Thus, these results demonstrate the potential of PAs as an intermediary scaffold for increasing the efficacy of pancreatic islet transplantation.