Profile of idursulfase for the treatment of Hunter syndrome

Simona Sestito, Ferdinando Ceravolo, Michele Grisolia, Elisa Pascale, Licia Pensabene, Daniela Concolino Department of Pediatrics, University Magna Graecia of Catanzaro, Catanzaro, Italy Abstract: Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare X-linked lysosomal storage disorder caused by deficiency of the enzyme iduronate-2-sulfatase (IDS). Enzyme replacement therapy (ERT) with recombinant human IDS, available since 2005, is currently the most appropriate treatment for this progressive, multisystemic, chronic, and life-threatening disease. Efficacy and safety of therapy with idursulfase have been assessed in several clinical trials, and confirmed in many clinical reports. Long-term follow-up of patients receiving ERT has demonstrated the importance of an early onset of treatment with idursulfase, before irreversible pathological changes occur. Intravenously administered idursulfase is not able to cross the blood–brain barrier, so neurological signs and symptoms cannot benefit from ERT, still remaining a major challenge in the treatment of MPS II. Keywords: MPS II, glycosaminoglycans, enzyme replacement therapy, ER

Dynamic fuel retention in tokamak wall materials: An in situ laboratory study of deuterium release from polycrystalline tungsten at room temperature

International audienceRetention of deuterium ion implanted in polycrystalline tungsten samples is studied in situ in an ultra-high vacuum apparatus equipped with a low-flux ion source and a high sensitivity thermo-desorption setup. Retention as a function of ion fluence was measured in the 10^17 -10^21 D+/m^2 range. By combining this new fluence range with the literature in situ experimental data, we evidence the existence of a retention = fluence^ 0.645±0.025 relationship which describes deuterium retention behavior on polycrystalline tungsten on 8 orders of magnitude of fluence. Evolution of deuterium retention as a function of the sample storage time in vacuum at room temperature was followed. A loss of 50% of the retained deuterium is observed when the storage time is increased from 2 h to 135 h. The role of the surface and of natural bulk defects on the deuterium retention/release in polycrystalline tungsten is discussed in light of the behavior of the single desorption peak obtained with Temperature Programmed Desorption

Assessment of the genotoxic impact of pesticides on farming communities in the countryside of Santa Catarina State, Brazil

The aim of this study was to assess the use of pesticides on farms located in the Lambedor River watershed in Guatambu, State of Santa Catarina, as well as to determine, by micronucleus testing, the risk of genotoxic impact. Samples from locally collected Cyprinus carpio, Hypostomus punctatus, Rhamdia quelen and Oreochromis niloticus gave evidence of a mean increase in micronuclei frequency from 6.21 to 13.78 in 1,000 erythrocytes, a clear indication of the genotoxic potenciality of pesticide residues in regional dams, and their significant contribution to local environmental contamination

Tritium retention in W plasma-facing materials : Impact of the material structure and helium irradiation

This article has an erratum: DOI 10.1016/j.nme.2020.100729Plasma-facing materials for next generation fusion devices, like ITER and DEMO, will be submitted to intense fluxes of light elements, notably He and H isotopes (HI). Our study focuses on tritium (T) retention on a wide range of W samples: first, different types of W materials were investigated to distinguish the impact of the pristine original structure on the retention, from W-coated samples to ITER-grade pure W samples submitted to various annealing and manufacturing procedures, along with monocrystalline W for reference. Then, He and He-D irradiated W samples were studied to investigate the impact on He-damages such as nano-bubbles (exposures in LHD or PSI-2) on T retention. We exposed all the samples to tritium gas-loading using a gentle technique preventing any introduction of new damage in the material. Tritium desorption is measured by Liquid Scintillation counting (LSC) at ambient and high temperatures (800 degrees C). The remaining T inventory is then measured by sample full dissolution and LSC. Results on T inventory on He exposed samples highlighted that in all cases, tritium desorption as a gas (HT) increases significantly due to the formation of He damages. Up to 1.8 times more T can be trapped in the material through a competition of various mechanisms, but the major part of the inventory desorbs at room temperature, and so will most likely not take part to the long-term trapped inventory for safety and operational perspectives. Unfortunately, investigation of "as received" industrial W (used for the making of plasma-facing materials) highlighted a strong impact of the pre existing defects on T retention: up to 2.5 times more T is trapped in "as received W" compared to annealed and polish W, and desorbs only at 800 degrees C, meaning ideal W material studies may underestimate T inventory for tokamak relevant conditions.Peer reviewe

Control of magnetic anisotropy by orbital hybridization in (La0.67Sr0.33MnO3)n/(SrTiO3)n superlattice

The asymmetry of chemical nature at the hetero-structural interface offers an unique opportunity to design desirable electronic structure by controlling charge transfer and orbital hybridization across the interface. However, the control of hetero-interface remains a daunting task. Here, we report the modulation of interfacial coupling of (La0.67Sr0.33MnO3)n/(SrTiO3)n superlattices by manipulating the periodic thickness with n unit cells of SrTiO3 and n unit cells La0.67Sr0.33MnO3. The easy axis of magnetic anisotropy rotates from in-plane (n = 10) to out-of-plane (n = 2) orientation at 150 K. Transmission electron microscopy reveals enlarged tetragonal ratio > 1 with breaking of volume conservation around the (La0.67Sr0.33MnO3)n/(SrTiO3)n interface, and electronic charge transfer from Mn to Ti 3d orbitals across the interface. Orbital hybridization accompanying the charge transfer results in preferred occupancy of 3d3z2-r2 orbital at the interface, which induces a stronger electronic hopping integral along the out-of-plane direction and corresponding out-of-plane magnetic easy axis for n = 2. We demonstrate that interfacial orbital hybridization in superlattices of strongly correlated oxides may be a promising approach to tailor electronic and magnetic properties in device applications