Up-regulation of brain-derived neurotrophic factor in primary afferent pathway regulates colon-to-bladder cross-sensitization in rat

Background In humans, inflammation of either the urinary bladder or the distal colon often results in sensory cross-sensitization between these organs. Limited information is known about the mechanisms underlying this clinical syndrome. Studies with animal models have demonstrated that activation of primary afferent pathways may have a role in mediating viscero-visceral cross-organ sensitization. Methods Colonic inflammation was induced by a single dose of tri-nitrobenzene sulfonic acid (TNBS) instilled intracolonically. The histology of the colon and the urinary bladder was examined by hematoxylin and eosin (H&E) stain. The protein expression of transient receptor potential (TRP) ion channel of the vanilloid type 1 (TRPV1) and brain-derived neurotrophic factor (BDNF) were examined by immunohistochemistry and/or western blot. The inter-micturition intervals and the quantity of urine voided were obtained from analysis of cystometrograms. Results At 3 days post TNBS treatment, the protein level of TRPV1 was increased by 2-fold (p \u3c 0.05) in the inflamed distal colon when examined with western blot. TRPV1 was mainly expressed in the axonal terminals in submucosal area of the distal colon, and was co-localized with the neural marker PGP9.5. In sensory neurons in the dorsal root ganglia (DRG), BDNF expression was augmented by colonic inflammation examined in the L1 DRG, and was expressed in TRPV1 positive neurons. The elevated level of BDNF in L1 DRG by colonic inflammation was blunted by prolonged pre-treatment of the animals with the neurotoxin resiniferatoxin (RTX). Colonic inflammation did not alter either the morphology of the urinary bladder or the expression level of TRPV1 in this viscus. However, colonic inflammation decreased the inter-micturition intervals and decreased the quantities of urine voided. The increased bladder activity by colonic inflammation was attenuated by prolonged intraluminal treatment with RTX or treatment with intrathecal BDNF neutralizing antibody. Conclusion Acute colonic inflammation increases bladder activity without affecting bladder morphology. Primary afferent-mediated BDNF up-regulation in the sensory neurons regulates, at least in part, the bladder activity during colonic inflammation

Microbeam x-ray absorption spectroscopy study of chromium in large-grain uranium dioxide fuel

Synchrotron-based microprobe x-ray absorption spectroscopy (XAS) has been used to study the local atomic structure of chromium in chromia-doped uranium dioxide (UO2) grains. The specimens investigated were a commercial grade chromia-doped UO2 fresh fuel pellet, and materials from a spent fuel pellet of the same batch, irradiated with an average burnup of ~40 MW d kg-1. Uranium L3-edge and chromium K-edge XAS have been measured, and the structural environments of central uranium and chromium atoms have been elucidated. The Fourier transform of uranium L3-edge extended x-ray absorption fine structure shows two well-defined peaks of U-O and U-U bonds at average distances of 2.36 and 3.83 Å. Their coordination numbers are determined as 8 and 11, respectively. The chromium Fourier transform extended x-ray absorption fine structure of the pristine UO2 matrix shows similar structural features with the corresponding spectrum of the irradiated spent fuel, indicative of analogous chromium environments in the two samples studied. From the chromium XAS experimental data, detectable next neighbor atoms are oxygen and uranium of the cation-substituted UO2 lattice, and two distinct subshells of chromium and oxygen neighbors, possibly because of undissolved chromia particles present in the doped fuels. Curve-fitting analyses using theoretical amplitude and phase-shift functions of the closest Cr-O shell and calculations with ab initio computer code FEFF and atomic clusters generated from the chromium-dissolved UO2 structure have been carried out. There is a prominent reduction in the length of the adjacent Cr-O bond of about 0.3 Å in chromia-doped UO2 compared with the ideal U-O bond length in standard UO2 that would be expected because of the change in effective Coulomb interactions resulting from replacing U4+ with Cr3+ and their ionic size differences. The contraction of shortest Cr-U bond is ~0.1 Å relative to the U-U bond length in bulk UO2. The difference in the local chromium environment between fresh and irradiated UO2 is discussed based on the comparison of quantitative structural information obtained from the two chromia-doped fuel samples analyzed

Dopant solubility and lattice contraction in gadolinia and gadolinia-chromia doped UO2 fuels

Gadolinia doped UO 2 fuel is widely used as burnable neutron absorber in Light Water Reactors to reduce power peaking and excess reactivity during the first reactor cycle of fresh fuel assemblies. The thermal conductivity of gadolinia doped fuel is substantially lower than that of standard UO 2. To maintain safety margins later in life, some design or operating restrictions can be defined, for example to compensate higher fission gas release levels. Development of large grain U/Gd fuel by suitable doping, e.g. Cr 2O 3, could offer a solution to such restrictions, but solid state information about the double doped (U 1-x-yGd xCr y)O 2 system is very scarce. In the present paper, we present X-ray diffraction and microstructure results of standard U/Gd fuel and chromia doped U/Gd fuel manufactured by powder metallurgy. The dissolution of chromium in (U 1-xGd x)O 2 as a function of Gd content, the role of free UO 2 and the lattice contraction at different Gd and Cr doping levels of (U 1-x-yGd xCr y)O 2 is studied both for the single doped and double doped system. On the basis of lattice contraction and precise measurements of the composition of the solid solution phases, the evolution of theoretical density with dopant concentration is derived. © 2012 Elsevier B.V. All rights reserved.status: publishe

Cr-coated cladding development at Framatome

International audienceFramatome is actively developing an evolutionary enhanced Accident Tolerant Fuel (E-ATF) design showing enhanced performance in both nominal and accidental conditions: Cr-coated M5 cladding combined with Cr$_2$O$_3$-doped UO$_2$ fuel. The Cr-coated M5 cladding consists of a thin, dense and extremely adherent chromium layer deposited on the external surface of the M5 cladding. The main advantage of this solution is that it significantly reduces the high temperature steam oxidation, and thus limits the heat and hydrogen production usually observed in the oxidation reaction of steam with zirconium. Furthermore, recent out-of-pile results have shown improved behavior of the Cr-coated cladding with respect to debris fretting, which suggests that this solution will enhance the reliability of fuel. Additionally, Framatome has developed a large scale Cr-coating deposition to demonstrate the feasibility of PVD deposition on full length tubes and to use this facility to produce the Cr-coated cladding tubes for Lead Fuel Rod (LFR) irradiations such as the one planned for insertion in 2019

Development of Cr-coated Zirconium Alloy Cladding for Enhanced Accident Tolerance

International audienceDuring the Fukushima Daiichi accident in 2011 the fuel rods underwent the degradation stages of a severe accident, including the rapid oxidation of zirconium, which led on the one hand to the production of large quantities of hydrogen, and on the other hand to additional heat production. Reducing the susceptibility of the cladding to the high temperature oxidation in steam can improve greatly the accident tolerance of the cladding and thus help reduce the risk of core meltdown. The worldwide research and development effort of the fuel nuclear industry to increase fuel margins in severe accidents is referenced as the development of Enhanced Accident Tolerant Fuels (EATF).In this context AREVA NP, along with CEA and EDF, is developing, among others, a chromium (Cr) coating (5-20$\mu$m thick) on zirconium alloy cladding. The coating is deposited on the cladding surface by Physical Vapor Deposition (PVD) and forms a dense and adherent protective layer. It preserves the good mechanical behavior of the current cladding in normal operating conditions while significantly improving the oxidation behavior in accidental conditions. This behavior is being evaluated through out-of-pile corrosion and mechanical tests at the AREVA NP Technical and Research Centers. The corrosion behavior was evaluated through autoclave tests in both PWR water chemistry at 360°C and in 415°C steam to increase the corrosion kinetics. In both cases very small weight gain was measured on the order of 1mg/dm$^2$ and remains stable throughout the length of the tests.This development is a part of the worldwide AREVA NP effort to improve the accident tolerance of the fuel through several projects and partnerships, in both Europe and the USA. In the USA, AREVA NP is strongly involved in the Department of Energy (DOE) program whose goal is to insert EATF solutions in US Light Water Reactors (LWRs) by 2022. In Europe, AREVA NP is on one side developing two cladding solutions (Cr-coated zirconium and SiC/SiC composite sandwich cladding) with the CEA and EDF, and on the other side is forming a partnership with the Gösgen utility to irradiate some EATF concepts under representative Pressurized Water Reactor (PWR) conditions

Interactive involvement of brain derived neurotrophic factor, nerve growth factor, and calcitonin gene related peptide in colonic hypersensitivity in the rat

BACKGROUND AND AIMS: Neutrophins are involved in somatic and visceral hypersensitivity. The action of nerve growth factor (NGF) on sensory neurones contributes to the development of referred colonic hypersensitivity induced by trinitrobenzene sulfonic acid (TNBS). Based on data on brain derived neurotrophic factor (BDNF) and calcitonin gene related peptide (CGRP) in pain, the aims of the present study were: (1) to investigate the involvement of BDNF and CGRP in this model of referred colonic hypersensitivity, (2) to test the effect of exogenous BDNF and CGRP on the colonic pain threshold, and (3) to investigate the relationship between BDNF, NGF, and CGRP by testing antineurotrophin antibodies or h‐CGRP 8–37 (a CGRP antagonist) on bowel hypersensitivity induced by these peptides. METHODS: Colonic sensitivity was assessed using a colonic distension procedure. RESULTS: Anti‐BDNF antibody and h‐CGRP 8–37 reversed the induced decrease in colonic threshold (33.4 (2.1) and 40.3 (4.1) mm Hg, respectively, compared with a vehicle score of approximately 18 mm Hg; p<0.001). BDNF (1–100 ng/rat intraperitoneally) induced a significant dose dependent decrease in colonic reaction threshold in healthy rats. This effect was reversed by an anti‐BDNF antibody and an anti‐NGF antibody (33.4 (0.6) v 18.7 (0.7) mm Hg (p<0.001), anti‐NGF v vehicle). NGF induced colonic hypersensitivity was reversed by h‐CGRP 8–37 but not by the anti‐BDNF antibody. Finally, antineurotrophin antibody could not reverse CGRP induced colonic hypersensitivity (at a dose of 1 µg/kg intraperitoneally). CONCLUSION: Systemic BDNF, NGF, and CGRP can induce visceral hypersensitivity alone and interactively. This cascade might be involved in TNBS induced referred colonic hypersensitivity in which each of these peptides is involved

Irradiation effects and micro-structural changes in large grain uranium dioxide fuel investigated by micro-beam X-ray diffraction

Microstructural changes in a set of commercial grade UO2 fuel samples have been investigated using synchrotron based micro-focused X-ray fluorescence (μ-XRF) and X-ray diffraction (μ-XRD) techniques. The results are associated with conventional UO2 materials and relatively larger grain chromia-doped UO2 fuels, irradiated in a commercial light water reactor plant (average burn-up: 40 MW d kg−1). The lattice parameters of UO2 in fresh and irradiated specimens have been measured and compared with theoretical predictions. In the pristine state, the doped fuel has a somewhat smaller lattice parameter than the standard UO2 as a result of chromia doping. Increase in micro-strain and lattice parameter in irradiated materials is highlighted. All irradiated samples behave in a similar manner with UO2 lattice expansion occurring upon irradiation, where any Cr induced effect seems insignificant and accumulated lattice defects prevail. Elastic strain energy densities in the irradiated fuels are also evaluated based on the UO2 crystal lattice strain and non-uniform strain. The μ-XRD patterns further allow the evaluation of the crystalline domain size and sub-grain formation at different locations of the irradiated UO2 pellets

Role of electronic excitations on xenon migration in UO2

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