These sites were also sensitive to the alpha 1 subunit-preferring agonist zolpidem. Our data suggest a species difference in the expression profiles of the alpha 1 and gamma 2 subunits in the locus coeruleus, with the sedation-related benzodiazepine sites being more important in man than rodents. This may explain the repeated failures in the transition of novel

drugs with a promising neuropharmacological profile in rodents to human clinical usage, due to intolerable sedative effects. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Reactive oxygen species play an important role both in physiological and pathophysiological reactions. The aim of this study was to determine the role of free radicals and antioxidants in the development of visceral pain. Visceral pain was produced by colorectal distension (CRD) in adult rats. CRD was caused Forskolin by insertion of a lubricated latex balloon into the descending colon and rectum followed by inflation to 80 mm Hg for 10 min. During CRD, visceral pain

was rated on 0-3.5 point scale. Oxidative stress was determined indirectly R428 purchase by measurement of free radical scavenging enzymes (glutathione peroxidase (GPx) and superoxide dismutase (SOD)) in the blood, liver and brain. Following CRD we observed (1) all rats expressed signs of visceral pain (overall rating was 1.83), (2) SOD and GPx levels were increased in the liver and blood, and decreased in the brain samples and (3) administration of the antioxidant Trolox, a water-soluble derivate of vitamin E, prior to CRD, prevented SOD and GPx changes in the liver, blood and brain, but did not affect pain scores. It was concluded, that CRD as a model of visceral pain, increases oxidative stress in animals, which could be prevented by prior administration of antioxidants; however, antioxidants did not attenuate signs of visceral pain caused by

CRD. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Endosomal sorting complex required for transport (ESCRT)-III subunit charged multivesicular body protein 2B (CHMP2B) is involved in the degradation of proteins in the endocytic eFT-508 and autophagic pathways. Mutations in the CHMP2B gene are reportedly associated with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) characterised by accumulation of ubiquitinated protein aggregates in affected neurons, suggesting a relationship between protein accumulation and efficient autophagic degradation. This study investigated CHMP2B immunoreactivity in the hippocampus of patients with Alzheimer’s disease (AD), revealing intense labeling of intraneuronal dot-like structures by antibody to CHMP2B.