Interpretation The results of our study support the further assessment of AMG 145 in long-term studies with larger and more diverse populations including patients with documented statin intolerance.”
“Alpha-synuclein (alpha-syn) is mainly a presynaptic protein that has been
Tubastatin A implicated in Parkinson’s disease and various other neurodegenerative disorders. Evidence obtained in knockout mice suggests that alpha-syn controls plasticity of dopamine (DA) overflow in presynaptic terminals. It is also believed that asyn spreads and may seed its aggregates from cell to cell. The effects of exogenously applied alpha-syn on dopaminergic neurotransmission have not been studied. We addressed this issue
by microinjecting human eFT-508 alpha-syn protein into the dorsal striatum of wild-type and alpha-syn knockout mice and monitoring stimulated DA overflow with constant potential amperometry. The evoked DA overflow was decreased in knockout mice six days after alpha-syn microinjection. The maximal velocity of DA re-uptake was reduced in both genotypes. Similar results were not seen when the effects of microinjected alpha-syn were studied immediately after the treatment, but instead there was a trend toward an increase in both stimulated DA overflow and maximal velocity of DA re-uptake. We conclude that locally applied human alpha-syn affects DA overflow and the effects depend on the presence of endogenous alpha-syn. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“Background. For the emerging DSM-V, it has been recommended that dimensional and categorical methods be used simultaneously in diagnostic classification; however, little is known about this combined approach for abuse and dependence.
Method. Using data (n=37 708) from the 2007 National Survey on Drug Use and Health (NSDUH), DSM-IV criteria for prescription opioid abuse and dependence FAD among non-prescribed opioid users (n=3037) were examined using factor analysis (FA), latent class analysis (LCA, categorical), item response
theory (IRT, dimensional), and factor mixture (hybrid) approaches.
Results. A two-class factor mixture model (FMM) combining features of categorical latent classes and dimensional IRT estimates empirically fitted more parsimoniously to abuse and dependence criteria data than models from FA, LCA and IRT procedures respectively. This mixture model included a severely affected group (7%) with a comparatively moderate to high probability (0.32-0.88) of endorsing all abuse and dependence criteria items, and a less severely affected group (93%) with a low probability (0.003-0.16) of endorsing all criteria. The two empirically defined groups differed significantly in the pattern of non-prescribed opioid use, co-morbid major depression, and substance abuse treatment use.