Characterization of a new aerosol antibiotic/adjuvant combination for the treatment of P. aeruginosa lung infections

International audienceThe lack of novel classes of antibiotics as well as the constant increase of multidrug resistant bacteria are leaving the clinicians disarmed to treat bacterial infections, especially those caused by Gram-negative pathogens. Among all the investigated solutions, the design of adjuvants able to enhance antibiotics activities appears to be one of the most promising. In this context, a polyamino-isoprenyl derivative has been recently identified to be able to potentiate, at a very low concentration the activity of doxycycline against P. aeruginosa bacterial strains by increasing its intracellular concentration. On the other hand, since aerosol therapy allows a rapid drug administration and targets the respiratory system by avoiding the first pass effect and minimizing undesirable systemic effects, we have developed the first adjuvant/antibiotic combination in an aerosolized form and demonstrated the feasibility of such an approach. Thus, combination aerosol droplets have been demonstrated in sizes suitable for inhalation (3.4 and 4.4 μm mass median aerodynamic diameter and 54 and 60% of the aerodynamic particle size distribution less than 5 μm, as measured for the adjuvant NV716 and doxycycline, respectively and with properties (stoichiometric 1:1 ratio of NV716 salt to drug) that would support further development as an inhaled dosage form. Taken together, our results suggest that these molecules could be successfully delivered at the requested concentration in the lungs and then able to decrease drug consumption as well as increase treatment efficacy

Mise au point de la quantification d’un marqueur précoce de stress cellulaire chez les larves aquatiques de Cloeon dipterum (Ephemeroptera, Baetidae) collectées en région Méditerranéenne

National audienceThe aim of this study is to calibrate a biomarker of cellular stress, the heat shock protein (HSP70) induction, in aquatic invertebrates collected in a little Mediterranean run-off, as a tool for early ecological risk assessment. Larvae of the Ephemeroptera Cloeon dipterum (L., 1761), present all over the year and in a suitable amount, are chosen as biological model. The development of the biomarker quantification allows choosing the stage 5 and older larvae for this calibration. As the larvae are obtained in absence of natural thermal stress and from a run-off where sediment pollutant concentrations do not exceed the threshold above which adverse effects frequently occurred, the « Consensus-based PEC » (Probable Effect Concentration) (Mac Donald et al., 2000), the measured HSP70 concentrations reflect a basal level.L’objectif de cette étude est de calibrer un biomarqueur de stress cellulaire, l’induction des protéines de choc thermique HSP70, chez des invertébrés aquatiques prélevés dans une roubine méditerranéenne, pour une utilisation comme outil de diagnostic précoce du risque écologique. Les premiers prélèvements permettent de retenir les larves de l’éphéméroptère Cloeon dipterum (L., 1761) comme modèle d’étude car elles sont les seules à y être présentes toute l’année et en quantité suffisante. La mise au point de la quantification du biomarqueur permet de sélectionner les larves de stade 5 et au-delà pour cette calibration. Les taux de HSP70 mesurés correspondent à des concentrations basales car obtenues chez des larves en absence de stress thermique naturel et dans un milieu où les polluants ne dépassent pas le « PEC » (Probable Effect Concentration), seuil au dessus duquel il est probable d’observer des effets toxiques (Mac Donald et al., 2000)

Feasibility of an inhaled antibiotic/adjuvant dry powder combination using an experimental design approach

International audienc

PCBs and DDTs in Stenella coeruleoalba dolphins from the French Mediterranean coastal environment (2007-2009): Current state of contamination

International audienceOrganochlorinated compounds including PolyChloroBiphenyles, Dichloro-DiphenylTrichloroethan and metabolites are determinated in Stenella coeruleoalba (n = 37) stranded on the french Mediterranean coasts from 2007 till 2009. Studies are carried out on lung, muscle, kidney, liver, and blubber. The sought-after compounds are all detected to variable levels in each tissue and organ. In general, total PCBs are the most abondant, followed by total DDTs. The concentration (in ng g(-1) of lipid weight) in blubber of S. coeruleoalba, varied from 2,052 to 158,992 for PCBs and from 1,120 to 45,779 for DDTs. The ratios DDE/tDDTs are higher than 80% in almost all samples. The overall results of this work, compared to previous studies concerning the Mediterranean Sea, seems to confirm the tendency to a decrease of the contamination by organics compounds for the cetaceans in the Western Mediterranean Sea. (C) 2012 Elsevier Ltd. All rights reserved

Contaminant signatures and stable isotope values qualify European conger (Conger conger) as a pertinent bioindicator to identify marine contaminant sources and pathways

International audienceTo evaluate the capacity of the European conger (Conger conger) as a reliable bioindicator to investigate marine contaminant sources and pathways, the muscles of 24 individuals caught in a semi-enclosed industrialized bay (Gulf of Fos, France) were analyzed for numerous organic compounds, metal elements, and stable isotopes. The contaminant levels were elevated to moderate, which relates to the great anthropic pressure from the surrounding industries and maritime traffic. Stable isotope analyses finely discriminated between three geographical areas and between two age groups. Mercury (Hg) and arsenic (As) concentrations (nd-1.35 mg.kg −1 and 5.94-60.1 mg.kg −1 wet weight (ww), respectively), as well as chlorination by-products, were elevated in particular areas, identifying specific industrial sources. Levels of Σ 42 PCB (7.15-28.67 µg.kg −1 ww), Σ 16 PAH (3.64-9.48 µg.kg −1 ww) and Σ 10 pesticides (1.91-18.42 µg.kg −1 ww) in fish muscles, as expected, did not differ among sites

Trends of banned pesticides and PCBs in different tissues of striped dolphins (Stenella coeruleoalba) stranded in the Northwestern Mediterranean reflect changing contamination patterns

Although banned for years, organochlorine pesticides and PCBs continue to affect aquatic life, dolphins being particularly exposed. The concentrations of 31 PCB congeners, and 15 banned pesticides or metabolites were measured in 5 tissues of 68 striped dolphins stranded in the Northwestern Mediterranean coast in 2010–16. The results were compared to historical data (1988–2009) and, even though there is a slow decreasing trend, the levels in the 2010–2016 samples were still elevated based on common cetacean toxicological thresholds. A transition period in 2007–08, probably caused by a morbillivirus epizootic amplified the stranding, espacially of highly contaminated specimens. From 2010, higher proportions in parent compounds towards metabolites were observed yet again. These changing patterns were likely reflect the exposure of dolphins to the remobilization of pollutants from contaminated soils and sediments, with a prominent role of rivers. This should lead to an even slower decline of these contaminants that could last for decades, requiring new efforts to reduce their dispersal to aquatic ecosystems

Characterization of atmospheric emission sources in lichen from metal and organic contaminant patterns

International audienceLichen samples from contrasted environments, influenced by various anthropic activities, were investigated focusing on the contaminant signatures according to the atmospheric exposure typologies. Most of the contaminant concentrations measured in the 27 lichen samples, collected around the industrial harbor of Fos-sur-Mer (France), were moderate in rural and urban environments, and reached extreme levels in industrial areas and neighboring cities (Al up to 6567 mg k

Spatial variability of metallic and organic contamination of anguilliform fish in New Caledonia

International audienceNew Caledonia is one of the main hot spots of biodiversity on the planet. Large amounts of contaminants are discharged into the lagoon as a result of increasing anthropogenic activities such as intense mining, urbanization and industrialization. Concentrations of 14 trace elements and 26 persistent organic pollutants (POPs: PCBs and pesticides) were measured in the muscles of two anguilliform fish species, over a coast to barrier reef gradient in two lagoon areas differently exposed to anthropic disturbances. This study emphasizes the high trace element contamination status of anguilliform fish and also highlights slight but perceptible organic pollution. The contamination extends throughout the lagoon, from coast to barrier reef, even in areas remote from emission points. High levels of trace elements, especially those linked to mining activities (i.e. Co, Cr, Fe, Mn and Ni), were detected in coastal sites. Furthermore the large dispersion of most POPs throughout the entire lagoon poses the question of their potential toxicity on marine organisms from numerous habitats. Our results underline the need for long term monitoring of various contaminants over large spatial and time scales