Simulation numérique de la condensation / évaporation et de la coagulation des nanoparticules

National audienceAware of the risks related to nanoparticles (particles which present at least one dimension less than 100 nanometers), INERIS decided in 2009 to create a research program in order to develop a model that would be able to simulate the dynamic of nanoparticles in both confined and free atmospheres. The distinction with usual models is that we need to follow the evolution of the number of particles together with their the mass : in order to simulate the evolution of nanoparticles, the number is much more relevant. A comparative review of algorithms currently used in air quality models and new algorithms adapted to nanoparticles is presented. This first study addresses condensational growth, evaporation and coagulation. The model is to be integrated in chemistry-transport models (CHIMERE) and in CFD models (code_Saturne EdF).Conscient des risques liés aux nanoparticules (particules dont au moins une des dimensions est inférieure à 100 nanomètres), l'INERIS(1) a engagé en 2009 un programme de recherche en collaboration avec le CEREA(2) afin de développer un modèle capable de simuler les transformations des nanoparticules dans les ambiances intérieures (espaces confinés) comme dans l'atmosphère. En effet, les nanoparticules sont notamment susceptibles de coaguler, de grossir par condensation, et de se déposer sur les parois; ce qui modifie leur granulométrie. Une des problématiques liée à la modélisation des nanoparticules est que leur nombre est déterminant devant leur masse, tout au contraire des particules étudiées jusqu'à présent (particules fines ou grossières dont une des dimensions est supérieure à 100 nanomètre). Différents schémas numériques ont été développés pour simuler la condensation/évaporation d'une population de particules, et un noyau de coagulation issu d'algorithmes usuels a été intégré. L'inter-comparaison de ces schémas met en évidence que certains sont plus adaptés que d'autres pour les nanoparticules. Les algorithmes qui sont appropriés pour toutes les tailles de particules sont présentés. A terme, ce modèle de dynamique des nanoparticules a vocation à être intégré dans des modèles de dispersion atmosphérique (CHIMERE) et des modèles CFD (code_Saturne EdF

Neutralising Antibodies against Ricin Toxin

The Centers for Disease Control and Prevention have listed the potential bioweapon ricin as a Category B Agent. Ricin is a so-called A/B toxin produced by plants and is one of the deadliest molecules known. It is easy to prepare and no curative treatment is available. An immunotherapeutic approach could be of interest to attenuate or neutralise the effects of the toxin. We sought to characterise neutralising monoclonal antibodies against ricin and to develop an effective therapy. For this purpose, mouse monoclonal antibodies (mAbs) were produced against the two chains of ricin toxin (RTA and RTB). Seven mAbs were selected for their capacity to neutralise the cytotoxic effects of ricin in vitro. Three of these, two anti-RTB (RB34 and RB37) and one anti-RTA (RA36), when used in combination improved neutralising capacity in vitro with an IC50 of 31 ng/ml. Passive administration of association of these three mixed mAbs (4.7 µg) protected mice from intranasal challenges with ricin (5 LD50). Among those three antibodies, anti-RTB antibodies protected mice more efficiently than the anti-RTA antibody. The combination of the three antibodies protected mice up to 7.5 hours after ricin challenge. The strong in vivo neutralising capacity of this three mAbs combination makes it potentially useful for immunotherapeutic purposes in the case of ricin poisoning or possibly for prevention

A new algorithm to solve condensation/evaporation for ultra fine, fine, and coarse particles

International audienceA new algorithm for condensation/evaporation has been developed that is accurate for both mass and number concentrations over the full size range of ultra fine, fine, and coarse particles. This new algorithm is compared to several standard sectional and modal algorithms for two case studies. In this algorithm, we use the Euler scheme for the number concentration of ultra fine particles and the Euler scheme for the mass concentration of fine and coarse particles. The results of this study provide useful information to select algorithms in order to correctly simulate aerosol dynamics in air quality models over a wide range of particle sizes

A new algorithm to solve condensation/evaporation growth and coagulation of nanoparticles

We usually define as " nanoparticles ", those particles which present at least one dimension less than 100 nm. Several studies have measured different emission sources of nanoparticles, for indoor and outdoor air. It is also known that these particles are likely to have multiple effects on human health. (Oberdorster et al.(2005)).Aware of the risks related to nanoparticles, INERIS decided in 2009 to create a research program in order to develop a model that would be able to simulate the dynamics of nanoparticles in both confined and free atmospheres. Unlike existing models, it is necessary to follow both numerical and mass concentrations of particles in order to correctly account for the time evolution of nanoparticles and their potential health effects, as the number concentration is much more relevant for nanoparticles. This study addresses condensational growth, evaporation and coagulation. A comparative review of algorithms currently used in air quality models is presented as well as new algorithms adapted to nanoparticles. We use the sectional approach in which the size distribution is discretized into sections characterized by a fixed mean geometrical diameter, particles properties are assumed to be constant over each particle size section. Two different initial particle distributions are used, one from regional pollution in hazy conditions and another one from diesel engine emission measurements. During the simulation of condensational growth, evaporation and coagulation, the size of the particles changes. In order to maintain the fixed mean geometrical diameter of each section, we have to proceed to a redistribution of the particle mass and number concentrations at each time step: particles are then transferred to the section which corresponds to their new diameter. It appears that some of the algorithms used for redistribution are better fitted for nanoparticles, among them we present a new hybrid algorithm based on number redistribution for small sections and mass redistribution for coarse sections. Futur work will consist in including several physical processes specific to nanoparticles such as nucleation and wall deposition

DTPA-Coated Liposomes as a New Delivery Vehicle for Plutonium Decorporation

International audienceAdministration of diethylenetriaminepentaacetic acid (DTPA) is the treatment approach used to promote the decorporation of internalized plutonium. Here we evaluated the efficacy of PEGylated liposomes coated with DTPA, primarily designed to prevent enhanced plutonium accumulation in bones, compared to marketed nonliposomal DTPA and liposomes encapsulating DTPA. The comparative effects were examined in terms of reduction of activity in tissues of plutonium-injected rats. The prompt treatment with DTPA-coated liposomes elicited an even greater efficacy than that with liposome-encapsulated DTPA in limiting skeletal plutonium. This advantage, undoubtedly due to the anchorage of DTPA to the outer layer of liposomes, is discussed, as well as the reason for the loss of this superiority at delayed times after contamination. Plutonium complexed with DTPA-coated liposomes in extracellular compartments was partly diverted into the liver and the spleen. These complexes and those directly formed inside hepatic and splenic cells appeared to be degraded, then released from cells at extremely slow rates. This transitory accumulation of activity, which could not be counteracted by combining both liposomal forms, entailed an underestimation of the efficacy of DTPA-coated liposomes on soft tissue plutonium until total elimination probably more than one month after treatment. DTPA-coated liposomes may provide the best delivery vehicle of DTPA for preventing plutonium deposition in tissues, especially in bone where nuclides become nearly impossible to remove once fixed. Additional development efforts are needed to limit the diversion or to accelerate cell release of plutonium bound to DTPA-coated liposomes, using a labile bond for DTPA attachment

Development and validation of a lateral flow immunoassay for rapid detection of NDM-producing <em>Enterobacteriaceae</em>

International audienceThe global spread of carbapenemase-producing Enterobacteriaceae (CPE) that are often resistant to most, if not all, classes of antibiotics is a major public health concern. The NDM-1 carbapenemase is among the most worrisome carbapenemases given its rapid worldwide spread. We have developed and evaluated a lateral flow immunoassay (LFIA) (called the NDM LFIA) for the rapid and reliable detection of NDM-like carbapenemase-producing Enterobacteriaceae from culture colonies. We evaluated the NDM LFIA using 175 reference enterobacterial isolates with characterized β-lactamase gene content and 74 nonduplicate consecutive carbapenem-resistant clinical isolates referred for expertise to the French National Reference Center (NRC) for Antibiotic Resistance during a 1-week period (in June 2016). The reference collection included 55 non-carbapenemase producers and 120 carbapenemase producers, including 27 NDM producers. All 27 NDM-like carbapenemase producers of the reference collection were correctly detected in less than 15 min by the NDM LFIA, including 22 strains producing NDM-1, 2 producing NDM-4, 1 producing NDM-5, 1 producing NDM-7, and 1 producing NDM-9. All non-NDM-1 producers gave a negative result with the NDM LFIA. No cross-reaction was observed with carbapenemases (VIM, IMP, NDM, KPC, and OXA-48-like), extended-spectrum β-lactamases (ESBLs) (TEM, SHV, and CTX-M), AmpCs (CMY-2, DHA-2, and ACC-1), and oxacillinases (OXA-1, -2, -9, and -10). Similarly, among the 74 referred nonduplicate consecutive clinical isolates, all 7 NDM-like producers were identified. Overall, the sensitivity and specificity of the assay were 100% for NDM-like carbapenemase detection with strains cultured on agar. The NDM LFIA was efficient, rapid, and easy to implement in the routine workflow of a clinical microbiology laboratory for the confirmation of NDM-like carbapenemase-producing Enterobacteriaceae

Determination of drug efficacy to dissolve cobalt oxide particles in cellular models: Towards a therapeutic approach to decrease pulmonary retention

International audienceFollowing accidental inhalation of radioactive cobalt particles, the poorly soluble and highly radioactive Co3O4 particles are retained for long periods in lungs. To decrease their retention time is of crucial importance to minimize radiation-induced damage. As dissolved cobalt is quickly transferred to blood and eliminated by urinary excretion, enhancing the dissolution of particles would favor 60Co elimination. We evaluated the ability of ascorbic acid alone or associated with the chelating agents DTPA1, DFOB2 or EDTA3 to enhance dissolution of cobalt particles after macrophage engulfment, and the drug effects on the translocation of the soluble species CoCl2 through an epithelial barrier. We exposed differentiated THP-1 macrophage-like cells and Calu-3 lung epithelial cells cultured in a bicameral system to cobalt and selected molecules up to 7 days. DTPA, the recommended treatment in man, used alone showed no effect, whereas ascorbic acid significantly increased dissolution of Co3O4 particles. An additional efficacy in intracellular particles dissolution was observed for combinations of ascorbic acid with DTPA and EDTA. Except for DFOB, treatments did not significantly modify translocation of dissolved cobalt across the epithelial lung barrier. Our study provides new insights for decorporating strategies following radioactive cobalt particle intake

Highly Sensitive and Specific Detection of Staphylococcal Enterotoxins SEA, SEG, SEH, and SEI by Immunoassay

International audienceStaphylococcal food poisoning (SFP) is one of the most common foodborne diseases worldwide, resulting from the ingestion of staphylococcal enterotoxins (SEs), primarily SE type A (SEA), which is produced in food by enterotoxigenic strains of staphylococci, mainly S. aureus. Since newly identified SEs have been shown to have emetic properties and the genes encoding them have been found in food involved in poisoning outbreaks, it is necessary to have reliable tools to prove the presence of the toxins themselves, to clarify the role played by these non-classical SEs, and to precisely document SFP outbreaks. We have produced and characterized monoclonal antibodies directed specifically against SE type G, H or I (SEG, SEH or SEI respectively) or SEA. With these antibodies, we have developed, for each of these four targets, highly sensitive, specific, and reliable 3-h sandwich enzyme immunoassays that we evaluated for their suitability for SE detection in different matrices (bacterial cultures of S. aureus, contaminated food, human samples) for different purposes (strain characterization, food safety, biological threat detection, diagnosis). We also initiated and described for the first time the development of monoplex and quintuplex (SEA, SE type B (SEB), SEG, SEH, and SEI) lateral flow immunoassays for these new staphylococcal enterotoxins. The detection limits in buffer were under 10 pg/mL (0.4 pM) by enzyme immunoassays and at least 300 pg/mL (11 pM) by immunochromatography for all target toxins with no cross-reactivity observed. Spiking studies and/or bacterial supernatant analysis demonstrated the applicability of the developed methods, which could become reliable detection tools for the routine investigation of SEG, SEH, and SEI