The data indicate that peripheral nerve injury changes not only protein expression
C646 chemical structure but also protein subcellular distribution in dorsal horn cells. These changes might participate in the central mechanism that underlies the maintenance of neuropathic pain.”
“The cortical cholinergic innervation, which is important for memory and cognition, has been implicated in schizophrenia. To experimentally analyze such a possible role of the cholinergic system, we have used the dissociative drug phencyclidine (PCP), known to produce schizophrenia-like psychosis in humans, to model aspects of schizophrenia in rats. We previously showed that induced cortical cholinergic hypofunction leads to enhanced PCP-induced locomotor activity and attenuated social interaction. After PCP, rats lacking cortical cholinergic innervation also
show impaired declarative memory. To Galunisertib directly study the role of the basalo-cortical cholinergic projections for PCP-induced neural activation in different cortical areas, we have now monitored the rapid (30 and 60 min) effects of low doses of PCP (2 and 3 mg/kg) on neural activation as reflected by transcriptional activation of c-fos in cortical areas, using quantitative in situ hybridization. We find an almost pan-cortical neural induction of c-fos mRNA with doses of PCP low enough not to alter levels of either BDNF or Nogo receptor mRNA levels. Specific unilateral lesioning of the uncrossed cholinergic projections to the cortical mantle by 192-IgG-saporin immunotoxin delivery to nc basalis (NBM) caused a striking ipsilateral decrease of the PCP-induced cortical c-fos mRNA induction, www.selleck.cn/products/sc75741.html restricted to areas which had become effectively denervated. Because PCP at low doses is unlikely to directly influence cortical neurons, we suggest that it acts by activation of the cholinergic input, which in turn leads to cortical c-fos mRNA increases. Our results are compatible with a role for the cholinergic system in symptoms of schizophrenia,
by showing that the basalocortical cholinergic projections are needed in order for PCP to have full activating effects on cortical neurons. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Treatment of multiple myeloma has evolved over the last decade, most notably with the introduction of highly effective novel agents. It is now possible to aim for deep disease responses in a greater number of patients in an attempt to prolong remission duration and survival. Initially introduced in the relapsed setting, the novel agents, namely thalidomide, bortezomib and lenalidomide, are now being increasingly incorporated into upfront treatment strategies, raising questions about the feasibility of ‘retreatment’ with such agents. Also, in a disease that is characterized by multiple relapses, the ‘sequencing’ of the different effective options is an important question.