Ischemia is a primary cause of neuronal death in retinal diseases. The repertoire of expressed transmitter receptors would determine the neurons' responses to ischemic damage, and peptidergic receptors may be involved. With a new in vitro model of the ischemic mouse retina, we investigated whether an altered expression of somatostatin receptors could modulate retinal responses to ischemia. We used retinas of somatostatin receptor 1 (sst(1)) knock out (KO) mice, where sst(2) are over-expressed and over-functional, and of sst(2) KO mice. TUNEL analysis of ischemic retinas showed a marked reduction of cell death in sst(1) KO retinas, while there were no differences between wild-type (WT) and sst(2) KO retinas. In addition, caspase-3 mRNA expression was also reduced in sst(1) KO as compared to WT retinas. An immunohistochemical analysis demonstrated that different cell populations responded differently to the ischemic insult, and that the persistence of some immunohistochemical markers was greater in sst(1) KO than in WT or in sst(2) KO retinas. In particular, rod bipolar cell survival was markedly improved in sst(1) KO retinas, while it was dramatically decreased in sst(2) KO retinas. Furthermore, consistent with a role of glutamate excitotoxicity in ischemia-induced neuronal death, retinal glutamate release was observed to increase under ischemic conditions, but this increase was significantly reduced in sst(1) KO retinas. These observations demonstrate that an increased presence of functional sst(2) protects against retinal ischemia, thus implementing the background for the use of sst(2) analogs in therapies of retinal diseases such as glaucoma or diabetic retinopathy.

The metabolite euplotin C (EC), isolated from the marine ciliate Euplotes crassus, is a powerful cytotoxic and pro-apoptotic agent in tumour cell lines. For instance, EC induces the rapid depletion of ryanodine Ca(2+) stores, the release of cytochrome c from the mitochondria, and the activation of caspase-3, leading to apoptosis. The purpose of this study was to gain further insight into the mechanisms of EC-induced apoptosis in rat pheochromocytoma PC12 cells. We found that EC increases Bax/Bcl-2 ratio and that Bax is responsible of the EC-induced dissipation of the mitochondrial membrane potential (Deltapsi(m)). In addition, EC induces the generation of reactive oxygene species (ROS) without involvement of p53. The inhibition of ROS generation prevents, at least in part, the pro-apoptotic effects of EC as well as the effects of EC on Bax, Deltapsi(m) and intracellular free Ca(2+), indicating a cross-talk between different pathways. However, definition of the effector cascade turns out to be more complex than expected and caspase-independent mechanisms, acting in parallel with caspases, should also be considered. Among them, EC increases the expression/activity of calpains downstream of ROS generation, although calpains seem to exert protective effects.

Introduction: In the last years due to miniaturization of endoscopic instruments and percutaneous surgery, endourology has become very popular in paediatric urinary stone managment. We reported our single-centre experience in retrograde endoscopic procedures in children. Results and complications of URS/RIRS are discussed. Materials and methods: We retrospectively reviewed our experience in patients ≤ 16 years old affected by urinary stones who underwent URS/RIRS procedures performed by two surgeons with expertise in endourology. A total of 30 renal Units (RUs) underwent endoscopic procedures (URS, RIRS or both). Surgical complications according to the ClavienDindo’s classification and stone-free rate were evaluated at 3 months follow-up. Success of URS was defined as stone-free status after single procedure while RIRS success rate was considered as presence of residual stone fragments smaller than 4 mm at first procedure. Results: The mean age of our patients was 8 years, range 2- 16 years. A total of 30 renal units (RUs) underwent 40 endourological procedures (23 URS and 17 RIRS; 10 children underwent both procedures at the same time). 17/30 (56.6%) RUs were pre-stented before surgery. The stone-free status was achieved in 23/30 renal units treated, with a 76.6% success rate. The remaining 7 patients had residual stones greater than 4 mm and underwent further treatments. After a second surgery the stone-free rate turned out to be 93.3% (28/30 renal units). Conclusions: Rigid and flexible ureteroscopy (URS/RIRS) is a reliable technique for treatment of < 2 cm urinary stones in paediatric age group. It shows low rate of major complications and promising results in terms of stone-free rate.

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