Induction of Neuronal Death by Microglial AGE-Albumin: Implications for Alzheimer’s Disease

Advanced glycation end products (AGEs) have long been considered as potent molecules promoting neuronal cell death and contributing to neurodegenerative disorders such as Alzheimer’s disease (AD). In this study, we demonstrate that AGE-albumin, the most abundant AGE product in human AD brains, is synthesized in activated microglial cells and secreted into the extracellular space. The rate of AGE-albumin synthesis in human microglial cells is markedly increased by amyloid-β exposure and oxidative stress. Exogenous AGE-albumin upregulates the receptor protein for AGE (RAGE) and augments calcium influx, leading to apoptosis of human primary neurons. In animal experiments, soluble RAGE (sRAGE), pyridoxamine or ALT-711 prevented Aβ-induced neuronal death in rat brains. Collectively, these results provide evidence for a new mechanism by which microglial cells promote death of neuronal cells through synthesis and secretion of AGE-albumin, thereby likely contributing to neurodegenerative diseases such as AD

Evaluation of a bifocal reflector on a clinical lithotripter

Purpose: To perform in vitro and in vivo tests using a clinical lithotripter in order to determine whether a bifocal reflector is more efficient and produces the same or less tissue damage than a conventional ellipsoidal reflector for electrohydraulic lithotripters. Materials and Methods: A standard ellipsoidal and a novel bifocal reflector were tested on a Tripter Compact lithotripter (Direx Medical Systems, Petach Tikva, Israel). The bifocal reflector was constructed by joining two sectors of two rotationally symmetrical ellipsoidal reflectors having different distances between their foci. The F1 foci of the sectors coincided, creating a separation between the F2 foci. The fragmentation efficiency of the reflectors was compared using kidney-stone models. Shockwave-induced trauma was evaluated in vivo by treating both kidneys of six healthy dogs. One kidney was exposed to shockwaves generated with the conventional reflector, and the other kidney was treated using the bifocal reflector. Pressure measurements were obtained for both reflectors using needle hydrophones. Results: The new design appeared to be more efficient than the conventional reflector in breaking up kidney-stone models. Tissue damage did not increase when using the bifocal reflector. Conclusion: The use of bifocal, instead of standard ellipsoidal, reflectors should be considered as an alternative to improve extracorporeal shockwave lithotripsy