Lazaroid U-74500A for warm ischemia and reperfusion injury of the canine small intestine

BACKGROUND: Although lazaroids have been shown to protect various organs from ischemia/reperfusion injury, results obtained in the small intestine have been conflicting. STUDY DESIGN: The canine small intestine was made totally ischemic for 2 hours by occluding the superior mesenteric artery and the superior mesenteric vein with interruption of the mesenteric collateral vessels. A lazaroid compound, U74500A, or a citrate vehicle was given intravenously to each of the six animals for 30 minutes before intestinal ischemia. Intestinal tissue blood flow, lipid peroxidation, neutrophil infiltration, adenine nucleotides and their catabolites, and histologic changes after reperfusion were determined. RESULTS: Lazaroid treatment attenuated decline of the mucosal and serosal blood flow after reperfusion. Accumulation of lipid peroxidation products and neutrophils in mucosal tissues was markedly inhibited by the treatment. Postischemic energy resynthesis was also augmented by lazaroid. Morphologically, mucosal architectures were better preserved with lazaroid treatment after reperfusion, and recovered to normal by postoperative day 3 in the treated group and by post-operative day 7 in control animals. CONCLUSIONS: Lazaroids protect the canine small intestine from ischemia/reperfusion injury by inhibiting lipid peroxidation and neutrophil infiltration. Dogs are tolerant of 2-hour normothermic complete intestinal ischemia

Vault changes after cyclopentolate instillation in eyes with posterior chamber phakic intraocular lens

Posterior chamber phakic intraocular lens (pIOL) implantation is a common option for correcting moderate-to-high ocular refractive defects. Because this pIOL is implanted on ciliary sulcus, the distance between the back surface of the pIOL and the anterior surface of the crystalline lens, that it is known as vault, should be measured in different conditions to ensure the technique's safety. Cyclopentolate is a drug that dilates the pupil and relaxes accommodation (cycloplegia). It is often used for different ocular examinations and for other medical purposes. However, there is no evidence of the effect of this drug on vault. This study quantified central vault changes associated with cyclopentolate instillation. We measured the vault under normal conditions (pre-cycloplegic instillation) and after instilling cyclopentolate on 39 eyes of 39 patients with implanted pIOL. Our results suggest that cyclopentolate instillation may induce changes to vault in eyes with implanted pIOL. These changes seem safe and are mainly associated with vault under normal conditions, but also with anterior chamber depth, pupillary diameter and pIOL size.- European Fund for Regional Development (FEDER) through the COMPETE Program and the Portuguese Foundation for Science and Technology (FCT) provided financial support in the framework of projects PTDC/SAU-BEB/098391/2008, PTDC/SAU-BEB/098392/2008 and the Strategic Project PEST-C/FIS/UI607/2011

Observation of Mott Transition in VO_2 Based Transistors

An abrupt Mott metal-insulator transition (MIT) rather than the continuous Hubbard MIT near a critical on-site Coulomb energy U/U_c=1 is observed for the first time in VO_2, a strongly correlated material, by inducing holes of about 0.018% into the conduction band. As a result, a discontinuous jump of the density of states on the Fermi surface is observed and inhomogeneity inevitably occurs. The gate effect in fabricated transistors is clear evidence that the abrupt MIT is induced by the excitation of holes.Comment: 4 pages, 4 figure

Overexpression of Reelin Prevents the Manifestation of Behavioral Phenotypes Related to Schizophrenia and Bipolar Disorder

Despite the impact of schizophrenia and mood disorders, which in extreme cases can lead to death, recent decades have brought little progress in the development of new treatments. Recent studies have shown that Reelin, an extracellular protein that is critical for neuronal development, is reduced in schizophrenia and bipolar disorder patients. However, data on a causal or protective role of Reelin in psychiatric diseases is scarce. In order to study the direct influence of Reelin's levels on behavior, we subjected two mouse lines, in which Reelin levels are either reduced (Reelin heterozygous mice) or increased (Reelin overexpressing mice), to a battery of behavioral tests: open-field, black–white box, novelty-suppressed-feeding, forced-swim-test, chronic corticosterone treatment followed by forced-swim-test, cocaine sensitization and pre-pulse inhibition (PPI) deficits induced by N-methyl--aspartate (NMDA) antagonists. These tests were designed to model some aspects of psychiatric disorders such as schizophrenia, mood, and anxiety disorders. We found no differences between Reeler heterozygous mice and their wild-type littermates. However, Reelin overexpression in the mouse forebrain reduced the time spent floating in the forced-swim-test in mice subjected to chronic corticosterone treatment, reduced behavioral sensitization to cocaine, and reduced PPI deficits induced by a NMDA antagonist. In addition, we demonstrate that while stress increased NMDA NR2B-mediated synaptic transmission, known to be implicated in depression, Reelin overexpression significantly reduced it. Together, these results point to the Reelin signaling pathway as a relevant drug target for the treatment of a range of psychiatric disorders

Multi-locus genome-wide association analysis supports the role of glutamatergic synaptic transmission in the etiology of major depressive disorder

Major depressive disorder (MDD) is a common psychiatric illness characterized by low mood and loss of interest in pleasurable activities. Despite years of effort, recent genome-wide association studies (GWAS) have identified few susceptibility variants or genes that are robustly associated with MDD. Standard single-SNP (single nucleotide polymorphism)-based GWAS analysis typically has limited power to deal with the extensive heterogeneity and substantial polygenic contribution of individually weak genetic effects underlying the pathogenesis of MDD. Here, we report an alternative, gene-set-based association analysis of MDD in an effort to identify groups of biologically related genetic variants that are involved in the same molecular function or cellular processes and exhibit a significant level of aggregated association with MDD. In particular, we used a text-mining-based data analysis to prioritize candidate gene sets implicated in MDD and conducted a multi-locus association analysis to look for enriched signals of nominally associated MDD susceptibility loci within each of the gene sets. Our primary analysis is based on the meta-analysis of three large MDD GWAS data sets (total N = 4346 cases and 4430 controls). After correction for multiple testing, we found that genes involved in glutamatergic synaptic neurotransmission were significantly associated with MDD (set-based association P = 6.9 X 10(-4)). This result is consistent with previous studies that support a role of the glutamatergic system in synaptic plasticity and MDD and support the potential utility of targeting glutamatergic neurotransmission in the treatment of MDD