Vectorisation intra-oculaire [Drug delivery to target the posterior segment of the eye].

Retinal diseases are nowadays the most common causes of vision threatening in developed countries. Therapeutic advances in this field are hindered by the difficulty to deliver drugs to the posterior segment of the eye. Due to anatomical barriers, the ocular biodisponibility of systemically administered drugs remains poor, and topical instillation is not adequate to achieve therapeutic concentrations of drugs in the back of the eye. Ocular drug delivery has thus become one of the main challenges of modern ophthalmology. A multidisciplinary research is being conducted worldwide including pharmacology, biomaterials, ophthalmology, pharmaceutics, and biology. New promising fields have been developed such as implantable or injectable slow release intravitreal devices and degradable polymers, dispersed polymeric systems for intraocular drug delivery, and transscleral delivery devices such as iontophoresis, osmotic pumps or intra-scleraly implantable materials. The first clinical applications emerging from this research are now taking place, opening new avenues for the treatment of retinal diseases

Hard - X-rays selected Active Galactic Nuclei. I. A radio view at high-frequencies

A thorough study of radio emission in Active Galactic Nuclei (AGN) is of fundamental importance to understand the physical mechanisms responsible for the emission and the interplay between accretion and ejection processes. High frequency radio observations can target the nuclear contribution of smaller emitting regions and are less affected by absorption. We present JVLA 22 and 45 GHz observations of 16 nearby (0.003$\le$z$\le$0.3) hard - X-rays selected AGN at the (sub)-kpc scale with tens uJy beam$^{-1}$ sensitivity. We detected 15/16 sources, with flux densities ranging from hundreds uJy beam$^{-1}$ to tens Jy (specific luminosities from $\sim$10$^{20}$ to $\sim$10$^{25}\,W\,Hz^{-1}$ at 22 GHz). All detected sources host a compact core, with 8 being core-dominated at either frequencies, the others exhibiting also extended structures. Spectral indices range from steep to flat/inverted. We interpret this evidence as either due to a core+jet system (6/15), a core accompanied by surrounding star formation (1/15), to a jet oriented close to the line of sight (3/15), to emission from a corona or the base of a jet (1/15), although there might be degeneracies between different processes. Four sources require more data to shed light on their nature. We conclude that, at these frequencies, extended, optically-thin components are present together with the flat-spectrum core. The ${L_R}/{L_X}\sim10^{-5}$ relation is roughly followed, indicating a possible contribution to radio emission from a hot corona. A weakly significant correlation between radio core (22 and 45 GHz) and X-rays luminosities is discussed in the light of an accretion-ejection framework.Comment: Accepted for publication on MNRA

Micro-implant d'acétonide de fluocinolone (ILUVIEN(®)) pour l'oedème maculaire diabétique chronique [Fluocinolone acetonide (ILUVIEN®) micro-implant for chronic diabetic macular edema].

Diabetic macular edema (DME) is a frequent complication of diabetic retinopathy and may cause severe visual loss. In this article, we examine the pathophysiology of DME and review various treatment options, such as laser photocoagulation, anti-vascular endothelial growth factor (VEGF) receptor antibodies, and steroids including ILUVIEN(®), which is a new sustained-release, non biodegradable, injectable, intravitreal micro-implant containing fluocinolone acetonide. The results of the FAME (Fluocinolone Acetonide in Diabetic Macular Edema) studies, conducted to evaluate the efficacy and safety of ILUVIEN(®) in DME, are discussed

Ophtalmologie. Rétinopathie diabétique: nouvelles possibilités thérapeutiques [Diabetic retinopathy: new therapeutic possibilities].

La rétinopathie diabétique touche un nombre croissant de personnes, soit quatre millions en Europe, ce chiffre va probablement doubler d'ici 2030. Si l'on considère que 25-30% de ces patients sont atteints de rétinopathie diabétique, un dépistage et un traitement précoce permettent d'éviter les complications oculaires sévères telles que l'oedème maculaire cystoïde où la rétinopathie diabétique proliférative. Un résumé des dernières données de la littérature ophtalmologique est présenté en insistant sur le rôle de l'anti-VEGF (vascular endothelial growth factor) et des implants intravitréens de corticostéroïdes pour une pathologie oculaire récemment classée dans les pathologies inflammatoires. Diabetic retinopathy affects an increasing number of persons, about 4 millions in Europe, a number that will probably double until 2030. If we consider that 25-30% of patients are affected by diabetic retinopathy, an ophthalmologic screening and early therapy will allow a better visual prognosis and avoid severe ocular complications such as diabetic macular edema and proliferative diabetic retinopathy. A summary of current ophthalmologic literature was performed and was focused on the role of anti-VEGF (vascular endothelial growth factor) therapies and intraocular drug delivery of corticosteroids in a pathology that was recently classified in inflammatory pathologies

Sustained-release steroids for the treatment of diabetic macular edema.

Glucocorticoids have been used for decades in the treatment of ocular disorders via topical, periocular, and more recently intravitreal routes. However, their exact mechanisms of action on ocular tissues remain imperfectly understood. Fortunately, two recently approved intravitreal sustained-release drug delivery systems have opened new perspectives for these very potent drugs. To date, among other retinal conditions, their label includes diabetic macular edema, for which a long-lasting therapeutic effect has been demonstrated both morphologically and functionally in several randomized clinical trials. The rate of ocular complications of intravitreal sustained-release steroids, mainly cataract formation and intraocular pressure elevation, is higher than with anti-vascular endothelial growth factor agents. Yet, a better understanding of the mechanisms underlying these adverse effects and the search for the minimal efficient dose should help optimize their therapeutic window

Glucocorticoids exert direct toxicity on microvasculature: analysis of cell death mechanisms.

Glucocorticoids (GCs) are routinely administered systemically or injected into the eye when treating numerous ocular diseases; however, their toxicity on the retinal microvasculature has not been previously investigated. In this article, the effects of hydrocortisone (Hydro), dexamethasone, dexamethasone-phosphate and triamcinolone acetonide (TA) were evaluated in vitro on human skin microcirculation cells and, bovine endothelial retinal cells, ex-vivo, on flat mounted rat retinas. The degree of GCs induced endothelial cell death varied according to the endothelial cell type and GCs chemical properties. GCs toxicity was higher in skin microvascular endothelial cells and for hydrophobic GC formulations. The mechanism of cell death differed between GCs, Hydro and TA activated the leukocyte elastase inhibitor/L-DNase II pathways but did not activate caspases. The mechanisms of cell death observed in cell cultures were similar to those observed in rat retinal explants. Taken together these results indicate that particular attention should be paid to the potential vascular side effects when administrating GCs clinically and in particular when developing sustained-release intraocular devices

Excess Galactic Molecular Absorption Toward the Radio Galaxy 3C 111

© 2017. The American Astronomical Society. All rights reserved. We show the combined spectral analysis of Chandra high-energy transmission grating and XMM-Newton reflection-grating spectrometer observations of the broad-line radio galaxy 3C 111. This source is known to show excess neutral absorption with respect to the one estimated from 21 cm radio surveys of atomic H i in the Galaxy. However, previous works were not able to constrain the origin of such an absorber as local to our Milky Way or intrinsic to the source (z = 0.0485). The high signal-to-noise grating spectra allow us to constrain the excess absorption as being due to intervening gas in the Milky Way, and we estimate a time-averaged total column density of NH = (7.4 ± 0.1) × 1021 cm-2, a factor of two higher than the tabulated H i value. We recommend using the total average Galactic column density estimated here when studying 3C 111. The origin of the extra Galactic absorption of NH = 4.4 × 1021 cm-2 is likely due to molecular gas associated with the Taurus molecular cloud complex toward 3C 111, which is our nearest star-forming region. We also detect a weak (EW = 16 ± 10 eV) and narrow (FWMH < 5500 km s-1, consistent with optical Hα) Fe Kα emission line at E = 6.4 keV, likely from the torus in the central regions of 3C 111, and we place an upper limit on the column density of a possible intrinsic warm absorber of N H < 2.5 ×1020 cm-2. These complexities make 3C 111 a very promising object for studying both the intrinsic properties of this active radio galaxy and the Galactic interstellar medium, if used as a background source

The Chandra Iron-L X-Ray Line Spectrum of Capella

An analysis of the iron L-shell emission in the publicly available spectrum of the Capella binary system, as obtained by the High Energy Transmission Grating Spectrometer on board the Chandra X-ray Observatory, is presented. The atomic-state model, based on the HULLAC code, is shown to be especially adequate for analyzing high-resolution x-ray spectra of this sort. Almost all of the spectral lines in the 10 - 18 Angstrom wavelength range are identified. It is shown that, for the most part, these lines can be attributed to emission from L-shell iron ions in the Capella coronae. Possibilities for electron temperature diagnostics using line ratios of Fe16+ are demonstrated. It is shown that the observed iron-L spectrum can be reproduced almost entirely by assuming a single electron temperature of kTe= 600 eV. This temperature is consistent with both the measured fractional ion abundances of iron and with the temperature derived from ratios of Fe16+ lines. A volume emission measure of 1053 cm-3 is calculated for the iron L-shell emitting regions of the Capella coronae indicating a rather small volume of 1029 cm3 for the emitting plasma if an electron density of 1012 cm-3 is assumed.Comment: Accepted to Ap