Dexamethasone palmitate large porous particles: A controlled release formulation for lung delivery of corticosteroids

International audienceWe have optimized a formulation of a prodrug of dexamethasone (DXM), dexamethasone palmitate (DXP) for pulmonary delivery as a dry powder. Formulations were prepared by spray drying DXP with 1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC) and Hyaluronic Acid (HA) as excipients. Large porous particles around 13 μm were produced with a tap density of 0.05 g/cm 3 and a Fine particle fraction around 40%. The palmitate moiety favors DXP insertion into DPPC bilayers therefore limiting its in vitro release as shown by differential scanning calorimetry. After administering DXP powder intratracheally to rats by insufflation, bronchoalveolar lavage fluid (BALF) and blood samples were collected up to 24 h and DXP and DXM concentrations were determined by HPLC analysis after extraction. PK parameters were evaluated according to a non-compartmental model. We observe that DXP remains for up to 6 h in the epithelial lining fluid (ELF) of the lungs at very high concentration. In addition, DXP concentration decreases according to two characteristic times. Consequently, DXM can be detected at rather important concentration in ELF up to 24 h. The passage of DXP from the lungs to the bloodstream is very poor whereas DXM seems to be absorbed in the blood more easily. These results suggest that once administered DXP undergoes two different processes: hydrolysis into DXM due to the presence of esterases in the lungs and distribution in the lung tissue. This formulation appears promising to reduce systemic exposure and prolong the effect of the drug locally

Predicting the consequences of indiscriminate poaching on the population persistence of a non-target species of conservation concern

Illegal animal hunting, a contributor to biodiversity loss, occurs along a relative selectivity spectrum from indiscriminate to highly selective. Extensive research has evaluated the impacts of selective hunting on animal populations. In contrast, the ways in which indiscriminate hunting pressure can shape populations of non-target species has not yet received comparable attention. We used empirical field data collection and simulation modelling to predict the persistence of an African lion population (Panthera leo) subject to indiscriminate hunting pressure from non-target subsistence poaching via wire snares in Murchison Falls National Park, Uganda. Our simulation modelling predicted lion population extirpation following a 50 % rise of lethal poaching pressure above the observed levels. When lethal poaching pressure doubled, the lion population was extirpated in ~70 % of our simulations. We then simulated reductions in lethal poaching pressure to quantify the predicted population recovery of lions. We found that the lion population increased by 40 % with reductions in lethal poaching pressure of 50 %. When we removed lethal poaching pressure entirely, the lion population nearly doubled in just 18 years. Our results demonstrate that by reducing the density of wire snares in the study area by just 2.79/km2, the lion population transitioned from being locally extirpated in 67 % of the simulations to reaching carrying capacity inside of two lion generations. We explore how vulnerable even non-target animals are to subsistence poaching and describe the types of applied practices that can be implemented to reduce wire snaring and effectively promote the population recovery of species of conservation concern

Data Mining of Polymer Phase Transitions upon Temperature Changes by Small and Wide-Angle X-ray Scattering Combined with Raman Spectroscopy

The complex physical transformations of polymers upon external thermodynamic changes are related to the molecular length of the polymer and its associated multifaceted energetic balance. The understanding of subtle transitions or multistep phase transformation requires real-time phenomenological studies using a multi-technique approach that covers several length-scales and chemical states. A combination of X-ray scattering techniques with Raman spectroscopy and Differential Scanning Calorimetry was conducted to correlate the structural changes from the conformational chain to the polymer crystal and mesoscale organization. Current research applications and the experimental combination of Raman spectroscopy with simultaneous SAXS/WAXS measurements coupled to a DSC is discussed. In particular, we show that in order to obtain the maximum benefit from simultaneously obtained high-quality data sets from different techniques, one should look beyond traditional analysis techniques and instead apply multivariate analysis. Data mining strategies can be applied to develop methods to control polymer processing in an industrial context. Crystallization studies of a PVDF blend with a fluoroelastomer, known to feature complex phase transitions, were used to validate the combined approach and further analyzed by MVA

Threat analysis for more effective lion conservation

We use comparable 2005 and 2018 population data to assess threats driving the decline of lion Panthera leo populations, and review information on threats structured by problem tree and root cause analysis. We define 11 threats and rank their severity and prevalence. Two threats emerged as affecting both the number of lion populations and numbers within them: livestock depredation leading to retaliatory killing of lions, and bushmeat poaching leading to prey depletion. Our data do not allow determination of whether any specific threat drives declines faster than others. Of 20 local extirpations, most were associated with armed conflicts as a driver of proximate threats. We discuss the prevalence and severity of proximate threats and their drivers, to identify priorities for more effective conservation of lions, other carnivores and their prey

Zn1-xMgxO thin films deposited by original Infrared assisted Spray Chemical Vapor Deposition: evaluation of structural, optical and electrical properties with the aim of provide Cu(In,Ga)Se2 based photovoltaic devices

In this work, magnesium doped zinc oxide (Zn1-xMgxO) thin films were deposited using an original infrared assisted Spray Chemical Vapor Deposition (Spray-CVD) technique on borosilicate glass substrates. With a simple, safe and cost-effective apparatus, Zn1-xMgxO thin films was studied in a range of 0 to 40% in precursor mass ratio r = [Mg]/([Zn]+[Mg]). The optimal deposition temperature was 500°C. X-ray diffraction analysis confirmed the presence of magnesium in the hexagonal Wurtzite crystal lattice of zinc oxide for r values lower than 30%. The optical properties have been investigated by spectrophotometry and showed that the transparency is higher than 80% in the visible and infrared spectral domain for r values lower than 20%. The band gap energy increased from 3.28 to 3.94 eV (0 < r < 40%), and the resistivity of the samples increased from 4.16.10-2 to 7.09.10+3 Ω.cm (Hall effect measurement). Additional characterizations have been realized by X-ray fluorescence (XRF) and energy dispersive X-ray spectrometry (EDX). All results demonstrate that Zn1-xMgxO thin films with r = 20% obtained by our Spray-CVD method is an interesting candidate for buffer layer application in Cu(In,Ga)Se2 based solar cells

International Wildlife Law : Understanding and Enhancing Its Role in Conservation

We gratefully acknowledge valuable input by Kees Bastmeijer, Sanja Bogojevic, Jennifer Dubrulle, and Han Somsen.Peer reviewedPublisher PD

Spectrocolorimetric interpretation of sedimentary dynamics: The new "Q7/4 diagram"

International audienceColour is a fundamental property of sediment and is often used for lithographic description to determine sedimentological structures, facies etc. However, the sedimentary information contained in this parameter is difficult to extract because it is difficult to quantify. Colour can be quantified by spectrocolorimetry which provides very high resolution data quickly and non-destructively. When adapted to sedimentology, spectrocolorimeters prove to be powerful tools due to their low purchase and maintenance costs, and some are portable and easily used in-the-field. Several methods have been used to extract sedimentological data from colorimetric spectra (first derivatives, factorial analysis, etc.). In the present study, we first provide a review of the sedimentological application of spectrophotometers and, after having described these methods, their advantages and disadvantages, we then describe a new tool called the Q7/4 diagram (abscissa L*; Ordinates 700/400 ratio). This new technique permits sedimentological units to be defined, allows the identification of different sediment components and provides 5 distinct poles: Clayey deposits, organic rich deposits (chlorophyll a and by products), altered organic matter deposits, iron rich deposits, carbonated deposits. Coupled with the analysis of first derivative spectra, it is possible to distinguish different pigments linked to the degradation and/or nature of the organic material (Chlorophyll a, melanoidin, etc.), the state of iron oxidation (for example, hematite and goethite-like signatures) and the nature of clays. The Q7/4 diagram permits rapid acquisition of high resolution data on changes of sediment dynamics in geosystems that have been subjected to highly varied climatic/environmental conditions. The instrument is non destructive, easy to use and maintain, portable for use in the field, fast to implement, is capable of high resolution, and has a vast range of possible applications. Spectrocolorimetry appears to provide many advantages and could become an essential and robust tool for preliminary sedimentological studies