β-Hydroxy-β-Methylbutyrate (HMB) Promotes Neurite Outgrowth in Neuro2a Cells

β-Hydroxy-β-methylbutyrate (HMB) has been shown to enhance cell survival, differentiation and protein turnover in muscle, mainly activating phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinases/ extracellular-signal-regulated kinases (MAPK/ERK) signaling pathways. Since these two pathways are related to neuronal survival and differentiation, in this study, we have investigated the neurotrophic effects of HMB in mouse neuroblastoma Neuro2a cells. In Neuro2a cells, HMB promotes differentiation to neurites independent from any effects on proliferation. These effects are mediated by activation of both the PI3K/Akt and the extracellular-signal-regulated kinases (ERK1/2) signaling as demonstrated by the use of specific inhibitors of these two pathways. As myocyte-enhancer factor 2 (MEF2) family of transcription factors are involved in neuronal survival and plasticity, the transcriptional activity and protein levels of MEF2 were also evaluated. HMB promoted MEF2-dependent transcriptional activity mediated by the activation of Akt and ERK1/2 pathways. Furthermore, HMB increases the expression of brain glucose transporters 1 (GLUT1) and 3 (GLUT3), and mTOR phosphorylation, which translates in a higher protein synthesis in Neuro2a cells. Furthermore, Torin1 and rapamycin effects on MEF2 transcriptional activity and HMB-dependent neurite outgrowth support that HMB acts through mTORC2. Together, these findings provide clear evidence to support an important role of HMB in neurite outgrowth.This project has been funded by Abbott Nutrition R&D

Autobahn corpse with lacerations on the neck-result of traffic accident, suicide of homicide?

A55-year-old man was found lifeless next to his car on an autobahn. On the left side of the neck there were huge gaping laceration type wounds. During the autopsy the injuries were found to partially have fine abrasions at the border and irregular margins of the wounds. The cause of death was named as injury-related polytrauma with inhalation of blood. During the further investigations atruck was seized, which showed sharp-edged damage to the metal on the right front of the vehicle. The injuries on the corpse were consistent with the ragged damaged edges on the truck so that this could be interpreted as aform of unusual and accident-related contact of the man with the truck

Sudden death of a young adult with coronary artery vasculitis, coronary aneurysms, parvovirus B19 infection and Kawasaki disease

We present a case of a 20-year-old man who suffered from Kawasaki disease (KD) associated with a florid parvovirus infection, and who died suddenly from thrombotic occlusion of the coronary arteries. The autopsy revealed several aneurysms of the coronary arteries, a chronic vasculitis and a myofibroblast proliferation leading to focal luminal narrowing. The inflammatory response as well as the detection of the viral particles by PCR in blood and in the lesional tissue demonstrated a possible cause by Parvovirus infection. The expression of endoglin on endothelial cells of neoangiogenesis indicates the involvement of the TGF-beta pathway, necessary for maintaining chronic inflammation. In addition, a possible connection between the intake of methylphenidate, arteritis and a possible pre-existing heart disease must be discussed. Furthermore, KD must also be considered as a cause of sudden death in the adult population