HA potently and transiently elevated NT-3 expression and protein levels by more than twofold. In addition to H(1) and H(2) receptors, cultured astrocytes also express H3 receptors, which activate Go proteins to inhibit adenylyl cyclase and modulate MAP kinase activity. Histaminergic stimulation was partly inhibited by selective Bromosporine nmr H(1), H(2), and H(3) antagonists whereas selective H(1), H(2), and H(3) agonists or mediators of the intracellular histaminergic pathways increased NT-3 levels. Inhibitors of PKA, PKC, and CaMK II significantly reduced the HA-induced increase in NT-3 cellular levels whereas the MAP kinase cascade inhibitor completely blocked the stimulatory

action of HA and all selective agonists.

In conclusion, the synthesis of astrocytic NT-3 stimulated by HA is a receptor-mediated process, which is fine-tuned via subtle modulation of parallel histaminergic H(1), H(2), and H(3) pathways that converge at

the level of MAP kinase Selleckchem MLN2238 activity.

This article is part of a Special Issue entitled ‘Trends in Neuropharmacology: In Memory of Erminio Costa’. (C) 2011 Elsevier Ltd. All rights reserved.”
“We have surgically treated 771 patients for thoracic and thoracoabdominal aortic aneurysms since 1983. Our primary effort has been to develop experimentally validated strategies to reduce paraplegia, renal failure, and mortality in these high-risk patients. This approach has Low-density-lipoprotein receptor kinase led to a spinal cord protection protocol that has reduced paraplegia risk by 80% (observed/expected ratio 0.19) with the use of cerebral spinal fluid drainage, moderate hypothermia (31 degrees C-33 degrees C), endorphin receptor antagonist (naloxone), and thiopental burst suppression while optimizing mean arterial pressure (>90 mm Hg) and cardiac index. The elective mortality rate is 2.80% (17% for acute patients), and with rapid renal cooling for renal protection, only 0.88% required permanent dialysis. These results were achieved without the use of assisted circulation. We have reattached intercostal arteries since 2005 using preoperative magnetic

resonance angiographic localization, but it remains unclear whether intercostal reimplantation reduces paraplegia risk, as we had initially proposed. We strongly believe that a consistent anesthetic and postoperative care protocol uniformly built and applied around these principles greatly enhances our surgical outcomes. We also show that improved outcomes with assisted circulation and hypothermic arrest in treatment of thoracoabdominal aortic disease follow similar principles of spinal cord and end-organ protection. (J Thorac Cardiovasc Surg 2010; 140:S136-41)”
“This paper reviews evidence suggesting that nicotine and tobacco smoke profoundly modulate the effects of alcohol on gamma-aminobutyric acid (GABA) neuronal function, specifically at the GABA(A)-benzo-diazepine receptor (GABA(A)-BZR).