Brain Regional Differences in the Effect of Ethanol on GABA Release from Presynaptic Terminals

Whereas ethanol has behavioral actions consistent with increased GABAergic function, attempts to demonstrate a direct enhancement of GABA-gated currents by ethanol have produced mixed results. Recent work has suggested that a part of the GABAergic profile of ethanol may result from enhanced GABA release from presynaptic terminals. The present study examines the effect of ethanol on GABA release in several brain regions to assess the regional nature of ethanol-induced GABA release. Whole-cell voltage clamp recording of spontaneous inhibitory postsynaptic currents (sIPSCs) from mechanically dissociated neurons and miniature inhibitory postsynaptic currents (mIPSCs) and paired-pulse ratio (PPR) from a slice preparation were used to quantify GABA release. Ethanol produced a concentration-dependent increase in the frequency of sIPSCs recorded from mechanically dissociated cerebellar Purkinje neurons and mIPSCs from substantia nigra neurons without having an effect on sIPSCs recorded from lateral septal or cerebrocortical neurons. This regional difference in the effect of ethanol on GABA release was confirmed with PPR recording from brain slices. These data indicate that ethanol can act on presynaptic terminals to increase GABA release in some brain regions while having little or no effect on GABA release in others. This regional difference is consistent with earlier in vivo studies in which ethanol affected neural activity and sensitivity to GABA in some, but not all, brain sites

Elution of gentamicin and vancomycin from polymethylmethacrylate beads and hip spacers in vivo

Background and purpose Late infections after total hip arthroplasty are still a problem. Treatment procedures include resection arthroplasty with implantation of antibiotic-loaded beads or implantation of an antibiotic-impreganted spacer. However, little is known about antibiotic elution from bone cement beyond the first 2–3 postoperative days in humans

An orifice shape-based reduced order model of patient-specific mitral valve regurgitation

Mitral valve regurgitation (MR) is one of the most prevalent valvular heart diseases. Its quantitative assessment is challenging but crucial for treatment decisions. Using computational fluid dynamics (CFD), we developed a reduced order model (ROM) describing the relationship between MR flow rates, transvalvular pressure differences, and the size and shape of the regurgitant valve orifice. Due to its low computational cost, this ROM could easily be implemented into clinical workflows to support the assessment of MR. We reconstructed mitral valves of 43 patients from 3D transesophageal echocardiographic images and estimated the 3D anatomic regurgitant orifice areas using a shrink-wrap algorithm. The orifice shapes were quantified with three dimensionless shape parameters. Steady-state CFD simulations in the reconstructed mitral valves were performed to analyse the relationship between the regurgitant orifice geometry and the regurgitant hemodynamics. Based on the results, three ROMs with increasing complexity were defined, all of which revealed very good agreement with CFD results with a mean bias below 3% for the MR flow rate. Classifying orifices into two shape groups and assigning group-specific flow coefficients in the ROM reduced the limit of agreement predicting regurgitant volumes from 9.0 ml to 5.7 ml at a mean regurgitant volume of 57 ml

Exploration of analgesia with tramadol in the Coxsackievirus B3 myocarditis mouse model

Infection of mice with Coxsackievirus B3 (CVB3) triggers inflammation of the heart and this mouse model is commonly used to investigate underlying mechanisms and therapeutic aspects for viral myocarditis. Virus-triggered cytotoxicity and the activity of infiltrating immune cells contribute to cardiac tissue injury. In addition to cardiac manifestation, CVB3 causes cell death and inflammation in the pancreas. The resulting pancreatitis represents a severe burden and under such experimental conditions, analgesics may be supportive to improve the animals' well-being. Notably, several known mechanisms exist by which analgesics can interfere with the immune system and thereby compromise the feasibility of the model. We set up a study aiming to improve animal welfare while ensuring model integrity and investigated how tramadol, an opioid, affects virus-induced pathogenicity and immune response in the heart. Tramadol was administered seven days prior to a CVB3 infection in C57BL/6 mice and treatment was continued until the day of analysis. Tramadol had no effect on the virus titer or viral pathogenicity in the heart tissue and the inflammatory response, a hallmark of myocardial injury, was maintained. Our results show that tramadol exerts no disruptive effects on the CVB3 myocarditis mouse model and, therefore, the demonstrated protocol should be considered as a general analgesic strategy for CVB3 infection

Small-scale systems of galaxies. II. Properties of the NGC 4756 group of galaxies

We present results from a study of the NGC 4756 group which is dominated by the elliptical galaxy NGC 5746. The characteristics of the group are investigated through (a) the detailed investigation of the morphological, photometric and spectroscopic properties of nine galaxies among the dominant members of the group (b) the determination of the photometric parameters of the faint galaxy population in an area of 34'x34' centered on NGC 4756 and (c) an analysis of the X-ray emission in the area based upon archival data. The 9 member galaxies are located in the core part of the NGC 4756 group (a strip diameter about 300 kpc in diameter which has a very loose configuration. The central part of the NGC 4756 group contains a significant fraction of early-type galaxies. Three new group members with previously unknown systemic velocities are identified, one of which is a dE. At about 7.5' SW of NGC 4756 a sub-structure of the group is detected, including IC 829, MCG -2-33-35, MCG -2-33-36 and MCG -2-33-38, which meets the Hickson criteria for being a compact group. Most of the galaxies in this sub-structure show interaction signatures. We do not detect apparent fine structure and signatures of recent interaction events in the early-type galaxy population, with the exception of a strong dust lane in the elliptical MCG -2-33-38. This galaxy displays however signatures of nuclear activity. Strong [O III], [N II] and [S II] line emission, combined with comparatively weak, but broad H alpha emission suggest an intermediate Seyfert type classification. Although the area is heavily contaminated by the background cluster Abell 1631, X-ray data suggest the presence of a hot intergalactic medium related to the group to the X-ray emission detected. The present results are discussed in the context of group evolution.Comment: 45 pages including 10 figures and 8 tables accepted for publication in A

Crossing borders of material science – a new approach of aerogel preparation for electron microscopy

A new method for the embedding and preparation of organic aerogels for electron mciroscopic Analysis like Crosssectioning, Lamella preparation, FIB-Tomography and Transmissio Electron Microscop

Minimal Model Holography

We review the duality relating 2d W_N minimal model CFTs, in a large N 't Hooft like limit, to higher spin gravitational theories on AdS_3.Comment: 54 pages, 1 figure; Contribution to J. Phys. A special volume on "Higher Spin Theories and AdS/CFT" edited by M. R. Gaberdiel and M. Vasiliev. v2. minor change

Red Blood Cell and Endothelial eNOS Independently Regulate Circulating Nitric Oxide Metabolites and Blood Pressure

Background: Current paradigms suggest that nitric oxide (NO) produced by endothelial cells (ECs) through endothelial nitric oxide synthase (eNOS) in the vessel wall is the primary regulator of blood flow and blood pressure. However, red blood cells (RBCs) also carry a catalytically active eNOS, but its role is controversial and remains undefined. This study aimed to elucidate the functional significance of RBC eNOS compared with EC eNOS for vascular hemodynamics and nitric oxide metabolism. Methods: We generated tissue-specific loss- and gain-of-function models for eNOS by using cell-specific Cre-induced gene inactivation or reactivation. We created 2 founder lines carrying a floxed eNOS (eNOSflox/flox) for Cre-inducible knockout (KO), and gene construct with an inactivated floxed/inverted exon (eNOSinv/inv) for a Cre-inducible knock-in (KI), which respectively allow targeted deletion or reactivation of eNOS in erythroid cells (RBC eNOS KO or RBC eNOS KI mice) or in ECs (EC eNOS KO or EC eNOS KI mice). Vascular function, hemodynamics, and nitric oxide metabolism were compared ex vivo and in vivo. Results: The EC eNOS KOs exhibited significantly impaired aortic dilatory responses to acetylcholine, loss of flow-mediated dilation, and increased systolic and diastolic blood pressure. RBC eNOS KO mice showed no alterations in acetylcholine-mediated dilation or flow-mediated dilation but were hypertensive. Treatment with the nitric oxide synthase inhibitor Nγ-nitro-l-arginine methyl ester further increased blood pressure in RBC eNOS KOs, demonstrating that eNOS in both ECs and RBCs contributes to blood pressure regulation. Although both EC eNOS KOs and RBC eNOS KOs had lower plasma nitrite and nitrate concentrations, the levels of bound NO in RBCs were lower in RBC eNOS KOs than in EC eNOS KOs. Reactivation of eNOS in ECs or RBCs rescues the hypertensive phenotype of the eNOSinv/invmice, whereas the levels of bound NO were restored only in RBC eNOS KI mice. Conclusions: These data reveal that eNOS in ECs and RBCs contribute independently to blood pressure homeostasis