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“The neuronal mechanisms underlying the pathophysiology of bipolar disorder (BD) have not been fully characterized. The aim of this study was to compare metabolite levels in the hippocampus and the orbitofrontal cortex in a

homogenous population of 12 euthymic patients with well-established BD and 12 age- and sex-matched healthy comparison subjects. Using a GE Signa, 3-Tesla scanner, we performed proton magnetic resonance spectroscopy (H-MRS) to examine levels of N-acetyl aspartate, glutamate and choline-containing compounds. learn more Choline-containing compounds were significantly increased in the hippocampus and the orbitofrontal cortex in BD patients relative to control subjects. Significant elevations of glycerophosphocholine + phosphocholine (GPC + PCh) were measured in the hippocampus and the orbitofrontal cortex of patients. As choline is a marker of membrane phospholipid metabolism, the elevated choline PS-341 purchase in patients may indicate increased membrane breakdown in the brain regions examined. Abnormal neuronal loss within the hippocampus and

orbitofrontal cortex further supports previous work suggesting that these regions are involved in the pathophysiology of BD. (C) 2008 Elsevier Ireland Ltd. All rights reserved.”
“Notch-stimulated signaling cascade results in transcriptional regulation of genes involved in cell fate decision, apoptosis and proliferation and has been implicated in various malignancies. Here, we investigated the impact of MRK003, an inhibitor of this pathway, on myeloma and lymphoma cells. We first studied the expression patterns of notch receptors and ligands on multiple myeloma (MM) and non-Hodgkin’s lymphoma (NHL) cell lines. Next, we used a c-secretase inhibitor, MRK003 to test the importance of notch-stimulated click here pathways in MM and NHL disease biology. We observed expression of notch receptors and ligands on MM and NHL cell lines.

MRK003 treatment induced caspase-dependent apoptosis and inhibited proliferation of MM and NHL cell lines and patient cells. Examination of signaling events after treatment showed time-dependent decrease in levels of the notch intracellular domain, Hes1 and c-Myc. MRK003 downregulated cyclin D1, Bcl-Xl and Xiap levels in NHL cells and p21, Bcl-2 and Bcl-Xl in MM cells. In addition, MRK003 caused an upregulation of pAkt, indicating crosstalk with the PI3K/Akt pathway. We evaluated MRK003 in combination with Akt1/2 kinase inhibitor and observed synergy in killing MM and NHL cell lines examined. Leukemia (2012) 26, 340-348; doi:10.1038/leu.2011.192; published online 9 August 2011″
“Dopaminergic neurotransmission is thought to be involved in reward-related incentive learning and addictive behaviour. Amphetamine will alter glycogen synthase kinase-3 beta (GSK-3 beta) activity by increasing dopamine transporter efflux rates. We investigated the hypothesis that Wnt signalling will be altered in rat nucleus accumbens within 15 min of injection of amphetamine compared with saline.