Neutrophil gelatinase–associated lipocalin (NGAL) is a protein belonging to the lipocalin superfamily initially found in activated neutrophils, in accordance with its role as an innate antibacterial ...factor. However, it subsequently was shown that many other types of cells, including in the kidney tubule, may produce NGAL in response to various injuries. The increase in NGAL production and release from tubular cells after harmful stimuli of various kinds may have self-defensive intent based on the activation of specific iron-dependent pathways, which in all probability also represent the mechanism through which NGAL promotes kidney growth and differentiation. NGAL levels predict the future appearance of acute kidney injury after treatments potentially detrimental to the kidney and even the acute worsening of unstable nephropathies. Furthermore, recent evidence also suggests that NGAL somehow may be involved in the pathophysiological process of chronic renal diseases, such as polycystic kidney disease and glomerulonephritis. NGAL levels clearly correlate with severity of renal impairment, probably expressing the degree of active damage underlying the chronic condition. For all these reasons, NGAL may become one of the most promising next-generation biomarkers in clinical nephrology and beyond.
Background. In islet transplantation, the use of dynamic hypothermic preservation techniques is a current challenge. This study compares the efficacy of 3 pancreas preservation methods: static cold ...storage, hypothermic machine perfusion (HMP), and oxygenated HMP. Methods. A standardized human pancreas split model was employed using discarded organs from both donation after brain death (n = 15) and donation after circulatory death (DCD) (n = 9) donors. The pancreas head was preserved using static cold storage (control group), whereas the tail was preserved using the 3 different methods (study group). Data on donor characteristics, pancreas histology, isolation outcomes, and functional tests of isolated islets were collected. Results. Insulin secretory function evaluated by calculating stimulation indices and total amount of secreted insulin during high glucose stimulation (area under the curve) through dynamic perifusion experiments was similar across all paired groups from both DCD and donation after brain death donors. In our hands, islet yield (IEQ/g) from the pancreas tails used as study groups was higher than that of the pancreas heads as expected although this difference did not always reach statistical significance because of great variability probably due to suboptimal quality of organs released for research purposes. Moreover, islets from DCD organs had greater purity than controls ( P ≤ 0.01) in the HMP study group. Furthermore, our investigation revealed no significant differences in pancreas histology, oxidative stress markers, and apoptosis indicators. Conclusions. For the first time, a comparative analysis was conducted, using a split model, to assess the effects of various preservation methods on islets derived from pancreas donors. Nevertheless, no discernible variances were observed in terms of islet functionality, histological attributes, or isolation efficacy. Further investigations are needed to validate these findings for clinical application.
The incidence of severe limb ischemia (SLI) is high among haemodialysis (HD) patients. Limb rescue rate after surgical revascularization is relatively poor compared with patients with normal renal ...function. Prostanoids are an interesting category as adjuvants to revascularization. New vessel growth develops not exclusively by proliferation of endothelial cells in vascular extremities but also by cells mobilized from the bone marrow (HSC), transformed into endothelial progenitor cells (EPC) contributing to both re-endothelialization and neovascularization. Basal number of HSC and EPC is significantly reduced in HD patients and correlated with a subsequent defective neovascularization. The aim of this study was to evaluate the effects of perioperative treatment with iloprost in uremic patients with acute ischemia of lower limbs, undergoing surgical revascularization, on endothelial progenitor cells, hypothesizing a possible biological mechanism induced by the prostanoids. A search was also made for vascular remodeling processes through the analysis of the concentrations of soluble adhesion molecules (i-CAM, v-CAM, e-selectin), biochemical markers of endothelial activation. Thirty HD patients with SLI undergoing peripheral revascularization were enrolled (15 were treated with iloprost and 15 with a placebo). Iloprost was administered as an intra-arterial bolus of 3000 ng over 1 to 3 min immediately after revascularization and in the same affected artery. Serum samples were taken before revascularization (T0), at 6 (T6) and 24 h (T24) after infusion to measure sICAM-1, sE-selectin, and sVCAM-1, and for quantification of HSC and EPC. Progenitors were identified by specific surface markers CD34+, CD133+ and VEGFR2+. Count was conducted using PROCOUNT performed in a TRUCOUNT tube and with a FACSort flow cytometer. Before revascularization, all patients showed a decreased number of HSC and EPC. After 6 h, HSC augmented significantly compared with T0 in both groups. The iloprost group attained a significant increase compared with the placebo group. HSC levels reduced drastically at T24. EPC augmented significantly compared with basal level after 24 h. In the iloprost group, the increase was considerable compared with the placebo group. A close negative correlation, assessed by Pearson coefficient (r), was found between HSC and EPC at T24 in the iloprost group (R = 0.82 P < 0.01). Adhesion molecules had increased levels at T6 and T24 in both groups. Moreover, a close positive correlation, assessed by Pearson coefficient, was found between EPC and adhesion molecules in both groups but the iloprost group maintained a better statistical association. Revascularization stimulated HSC and EPC release from bone marrow but at a different time: HSC increased suddenly at 6 h and diminished to a minimal amount at T24, conversely, EPC increased significantly only at T24. Iloprost treatment was able to amplify this mechanism validating recent findings (North TE et al. , 31 ). Adhesion molecules as markers of endothelial activation and vascular development confirmed this tendency.
