Attenuation of ischemic liver injury by prostaglandin E<inf>1</inf> analogue, misoprostol, and prostaglandin I<inf>2</inf> analogue, OP-41483

Background: Prostaglandin has been reported to have protective effects against liver injury. Use of this agent in clinical settings, however, is limited because of drugrelated side effects. This study investigated whether misoprostol, prostaglandin E1 analogue, and OP-41483, prostaglandin I2 analogue, which have fewer adverse effects with a longer half-life, attenuate ischemic liver damage. Study Design: Thirty beagle dogs underwent 2 hours of hepatic vascular exclusion using venovenous bypass. Misoprostol was administered intravenously for 30 minutes before ischemia and for 3 hours after reperfusion. OP-41483 was administered intraportally for 30 minutes before ischemia (2 μg/kg/min) and for 3 hours after reperfusion (0.5 μg/kg/min). Animals were divided into five groups: untreated control group (n = 10); high-dose misoprostol (total 100 μg/kg) group (MP-H, n = 5); middle-dose misoprostol (50 μg/kg) group (MP-M, n = 5); low-dose misoprostol (25 μg/kg) group (MP-L, n = 5); and OP-41483 group (OP, n = 5). Animal survival, hepatic tissue blood flow (HTBF), liver function, and histology were analyzed. Results: Two-week animal survival rates were 30% in control, 60% in MP-H, 100% in MP-M, 80% in MP-L, and 100% in OP. The treatments with prostaglandin analogues improved HTBF, and attenuated liver enzyme release, adenine nucleotrides degradation, and histologic abnormalities. In contrast to the MP-H animals that exhibited unstable cardiovascular systems, the MP- M, MP-L, and OP animals experienced only transient hypotension. Conclusions: These results indicate that misoprostol and OP-41483 prevent ischemic liver damage, although careful dose adjustment of misoprostol is required to obtain the best protection with minimal side effects

Attenuation of ischemic liver injury by monoclonal anti-endothelin antibody, awETN40

Background: Enhanced production of endothelin-1 (ET1), vasoconstrictive 21 amino acids produced by endothelial cells during ischemia and after reperfusion of the liver, is known to cause sinusoidal constriction and microcirculatory disturbances, which lead to severe tissue damage. Using a 2- hour hepatic vascular exclusion model in dogs, we tested our hypothesis that neutralization of ET-1 by monoclonal anti-ET-1 and anti-ET-2 antibody (AwETN40) abates vascular dysfunction and ameliorates ischemia/reperfusion injury of the liver. Study Design: After skeletonization, the liver was made totally ischemic by cross-clamping the portal vein, the hepatic artery, and the vena cava (above and below the liver). Venovenous bypass was used to decompress splanchnic and inferior systemic congestion. AwETN40, 5 mg/kg, was administered intravenously 10 minutes before ischemia (treatment group, n = 5). Nontreated animals were used as controls (control group, n = 10). Animal survival, hepatic tissue blood flow, liver function tests; total bile acid, high-energy phosphate, ET-1 levels, and liver histopathology were studied. Results: Treatment with AwETN40 improved 2-week animal survival from 30% to 100%. Hepatic tissue blood flow after reperfusion was significantly higher in the treatment group. The treatment significantly attenuated liver enzyme release, total bile acid, and changes in adenine nucleotides. Immunoreactive ET-1 levels in the hepatic venous blood of the control group showed a significant increase and remained high for up to 24 hours after reperfusion. Histopathologic alterations were significantly lessened in the treatment group. Conclusions: These results indicate that ET-1 is involved in ischemia/reperfusion injury of the liver, which can be ameliorated by the monoclonal anti-ET-1 and antiET-2 antibody AwETN40

Relaxation of a Single Knotted Ring Polymer

The relaxation of a single knotted ring polymer is studied by Brownian dynamics simulations. The relaxation rate lambda_q for the wave number q is estimated by the least square fit of the equilibrium time-displaced correlation function to a double exponential decay at long times. The relaxation rate distribution of a single ring polymer with the trefoil knot appears to behave as lambda_q=A(1/N^)x for q=1 and lambda_q=A'(q/N)^x' for q=2 and 3, where x=2.61, x'=2.02 and A>A'. The wave number q of the slowest relaxation rate for each N is given by q=2 for small values of N, while it is given by q=1 for large values of N. This crossover corresponds to the change of the structure of the ring polymer caused by the localization of the knotted part to a part of the ring polymer.Comment: 13 pages, 5 figures, uses jpsj2.cl

Preclinical correction of human Fanconi anemia complementation group A bone marrow cells using a safety-modified lentiviral vector.

One of the major hurdles for the development of gene therapy for Fanconi anemia (FA) is the increased sensitivity of FA stem cells to free radical-induced DNA damage during ex vivo culture and manipulation. To minimize this damage, we have developed a brief transduction procedure for lentivirus vector-mediated transduction of hematopoietic progenitor cells from patients with Fanconi anemia complementation group A (FANCA). The lentiviral vector FancA-sW contains the phosphoglycerate kinase promoter, the FANCA cDNA, and a synthetic, safety-modified woodchuck post transcriptional regulatory element (sW). Bone marrow mononuclear cells or purified CD34(+) cells from patients with FANCA were transduced in an overnight culture on recombinant fibronectin peptide CH-296, in low (5%) oxygen, with the reducing agent, N-acetyl-L-cysteine (NAC), and a combination of growth factors, granulocyte colony-stimulating factor (G-CSF), Flt3 ligand, stem cell factor, and thrombopoietin. Transduced cells plated in methylcellulose in hypoxia with NAC showed increased colony formation compared with 21% oxygen without NAC (P&lt;0.03), showed increased resistance to mitomycin C compared with green fluorescent protein (GFP) vector-transduced controls (P&lt;0.007), and increased survival. Thus, combining short transduction and reducing oxidative stress may enhance the viability and engraftment of gene-corrected cells in patients with FANCA

Improved control of exogenous attention in action video game players

Action video game players (VGPs) have demonstrated a number of attentional advantages over non-players. Here, we propose that many of those benefits might be underpinned by improved control over exogenous (i.e., stimulus-driven) attention. To test this we used an anti-cueing task, in which a sudden-onset cue indicated that the target would likely appear in a separate location on the opposite side of the fixation point. When the time between the cue onset and the target onset was short (40 ms), non-players (nVGPs) showed a typical exogenous attention effect. Their response times were faster to targets presented at the cued (but less probable) location compared with the opposite (more probable) location. VGPs, however, were less likely to have their attention drawn to the location of the cue. When the onset asynchrony was long (600 ms), VGPs and nVGPs were equally able to endogenously shift their attention to the likely (opposite) target location. In order to rule out processing-speed differences as an explanation for this result, we also tested VGPs and nVGPs on an attentional blink (AB) task. In a version of the AB task that minimized demands on task switching and iconic memory, VGPs and nVGPs did not differ in second target identification performance (i.e., VGPs had the same magnitude of AB as nVGPs), suggesting that the anti-cueing results were due to flexible control over exogenous attention rather than to more general speed-of-processing differences

An Analysis of the Quantum Penny Flip Game using Geometric Algebra

We analyze the quantum penny flip game using geometric algebra and so determine all possible unitary transformations which enable the player Q to implement a winning strategy. Geometric algebra provides a clear visual picture of the quantum game and its strategies, as well as providing a simple and direct derivation of the winning transformation, which we demonstrate can be parametrized by two angles. For comparison we derive the same general winning strategy by conventional means using density matrices.Comment: 8 Pages, 1 Figure, accepted for publication in the Journal of Physical Society of Japa

One-way quantum computing in a decoherence-free subspace

We introduce a novel scheme for one-way quantum computing (QC) based on the use of information encoded qubits in an effective cluster state resource. With the correct encoding structure, we show that it is possible to protect the entangled resource from phase damping decoherence, where the effective cluster state can be described as residing in a Decoherence-Free Subspace (DFS) of its supporting quantum system. One-way QC then requires either single or two-qubit adaptive measurements. As an example where this proposal can be realized, we describe an optical lattice setup where the scheme provides robust quantum information processing. We also outline how one can adapt the model to provide protection from other types of decoherence.Comment: 9 pages, 4 figures, RevTeX