Éditeur(s) : HAL CCSD E Schweizerbart Science Publishers
Résumé : International audience
Mass balance calculations have been performed through a comparison of published graphical and statistical approaches applied to two contrasted geological settings: (i) the development of a greenschist-facies ductile shear-zone that recorded a weak volume change but significant mass transfers, and (ii) the formation of exoskarns in metacarbonate xenoliths that recorded a large volume decrease related to huge mass transfers. The comparison of the four mass-balance approaches shows that, if uncertainties are ignored, (1) they yield similar results concerning the mobile vs immobile behaviour of many components; (2) they yield similar mass-change values on bulk rock and on individual chemical elements (bulk-rock mass-change values differ by a maximum of ca. 15 % between graphical and statistical treatments of the metacarbonate xenolith evolution). The main difference concerns the uncertainties on mass changes (for bulk rocks and individual elements), which are much larger with the graphical than with the statistical approaches when uncertainties on chemical elements are taken into account, as they should be.The main advantage of the graphical methods is their rapid implementation and the clarity of the diagrams. Their main disadvantages are that uncertainties on each chemical element and bulk compositions are not taken into account and the difficulty in choosing an accurate immobility field to precisely define errors. Graphical methods need to be completed by a statistical treatment that gives absolute mass transfer results. The statistical approaches have the advantage of taking into account the chemical heterogeneities of the compared populations, in conjunction to a precise data treatment. The statistical treatment is an important and necessary step to decipher and to be pertinent in interpreting mobility/immobility of chemical elements, and, thus, in the absolute quantification of mass and volume changes.
ISSN: 0935-1221

hal-01260258
https://hal.archives-ouvertes.fr/hal-01260258
DOI : 10.1127/ejm/2015/0027-2475

Résumé : Once fished, the shrimps must be cooled quickly in water cooled in order to slow down all chemical and bacteriological activities. In addition, in order to avoid blackening (mélanose) shrimps (céphalothorax and legs) it is necessary to treat those with an antioxydant product. The product currently used to inhibit this enzymatic change is the soda niétabisuifite (Na-> S7 O5), until now, after being fished. the shrimps were directly soaked in a cooled water tank, containing the pesticide. The solution of treatment was progressively prepared needs. The concentration of this one was approximately 2 to 3% of métabisulfite, that is to say 6 to 9 G of SO2 per liter for a starting product containing 320 G of SO2 approximately. In order to preserve a good quality of the liquid of treatment it was essential to often renew it (every 400 to 500 kg) what was not always the case, the métabisulfite being often added progressively with the liking of the appointed person with the treatment of shrimps. In order to cure this delicate problem of renewal of vat and uniformity of the treatment, the SODACAL obtained the system of treatment by sprinkling.
Une fois pêchées, les crevettes doivent être refroidies rapidement dans de l'eau réfrigérée afin de ralentir toutes activités chimiques et bactériologiques. D'autre part, afin d'éviter le noircissement (mélanose) des crevettes (céphalothorax et pattes) il est nécessaire de traiter celles-ci avec un produit anti-oxydant. Le produit actuellement utilisé pour inhiber cette altération enzymatique est le niétabisuifite de soude (Na-> S7 O5), jusqu'à maintenant, après avoir été pêchées. les crevettes étaient directement trempées dans une cuve d'eau réfrigérée, contenant le produit de traitement. La solution de traitement était préparée au fur et à mesure des besoins. La concentration de celle-ci était d'environ 2 à 3 % de métabisulfite, soit 6 à 9 g de SO2 par litre pour un produit de départ contenant 320 g de SO9 environ. Afin de conserver une bonne qualité du liquide de traitement il était indispensable de le renouveler souvent (tous les 400 à 500 kg) ce qui n'était pas toujours le cas, le métabisulfite étant souvent rajouté au fur et à mesure au gré de la personne préposée au traitement des crevettes. Afin de remédier à ce problème délicat de renouvellement de bac et d'uniformité du traitement, la SODACAL s'est dotée du système de traitement par aspersion.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/1991/rapport-1648.pdf
http://archimer.ifremer.fr/doc/00000/1648/

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Silane coating of fibers is a promising process for improving durability and adhesion of vegetable fibers used as reinforcement material in a cementitious matrix. The work presented in this paper gives an insight into the effect of combining pyrolysis treatment with silane treatment. Indeed, this study focuses on silane treatment of unpyrolyzed and pyrolyzed sugar cane bagasse fibers with an alkyltrialkoxysilane (RSi(OR′)3), S1 or a dialkyldialkoxysilane (R2Si(OR″)2), S2. The silane solutions used vary from 0.5% to 8% by volume. This paper describes the effect of two silane compounds on parameters such as the porosity, dimension, morphology and hygroscopic character of silane-coated sugar cane bagasse fibers. Preliminary studies on natural fiber reinforced composite setting time show the importance of the silane chemistry/structure, for fiber treatments with silane solution containing up to 6% (volume percent) silane. In the case of composites reinforced with unpyrolyzed bagasse fibers, setting time increases with silane coating. Combining pyrolysis and silane treatment improve the water resistance of the fibers, which become more hydrophobic.
ISSN: 1359-835X

hal-00809830
https://hal.univ-antilles.fr/hal-00809830
DOI : 10.1016/j.compositesa.2008.05.013

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Various bagasse fibre/cement composites have been prepared, the fibres having a random distribution in the composites. The influence of different parameters on the setting of the composite material has been studied: (1) botanical components of the fibre, (2) thermal or chemical treatment of the fibre, (3) bagasse fibre content and (4) added water percentage. This study shows a retarding effect of lignin on the setting of the composite, for small amount of heat-treated bagasse (200 °C) the behaviour of the composite is closely the same as the classical cement or cellulose/cement composite.
ISSN: 0958-9465

hal-00809715
https://hal.univ-antilles.fr/hal-00809715
DOI : 10.1016/S0958-9465(02)00003-3

Éditeur(s) : HAL CCSD Royal Society of Chemistry
Résumé : International audience
A full equilibrium treatment of molecular aggregation is presented for prototypes of 1D and 3D aggregates, with and without nucleation. By skipping complex kinetic parameters like aggregate size-dependent diffusion, the equilibrium treatment allows to predict directly time-independent quantities such as critical concentrations. The relationships between the macroscopic equilibrium constants for the different paths are first established by statistical corrections and so as to comply with the detailed balance constraints imposed by nucleation, and the composition of the mixture resulting from homogeneous aggregation is then analyzed using the polylogarithm function. Several critical concentrations are distinguished: the residual monomer concentation in equilibrium (RMC) and the critical nucleation concentration (CNC), that is the threshold concentration of total subunits necessary for initiating aggregation. When increasing the concentration of total subunits, the RMC converges more strongly to its asymptotic value, the equilibrium constant of depolymerization, for 3D aggregates and in case of nucleation. The CNC moderately depends on the number of subunits in the nucleus, but sharply increases with the difference between the equilibrium constants of polymerization and nucleation. As the RMC and CNC can be numerically but not analytically determined, ansatz equations connecting them to thermodynamic parameters are proposed
PCCP : Physical chemistry chemical physics

Droits : info:eu-repo/semantics/OpenAccess
hal-01565995
https://hal.archives-ouvertes.fr/hal-01565995
https://hal.archives-ouvertes.fr/hal-01565995/document
https://hal.archives-ouvertes.fr/hal-01565995/file/Aggregates_in_equilibrium.pdf
DOI : 10.1039/c6cp08369b

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
This paper presents the effects of chemical and thermal treatments on the strength of vegetable fibers that were being considered as reinforcements in cementitious matrix composites for affordable housing. These include vegetable fibers extracted from banana trunks and sugar cane residues. The results suggested that pyrolysis increased the fiber strength, at least by a factor three. Acid attack generally degraded the strengths, while alkali attack had only a limited effect. Pyrolyzed banana leaves, coconut coir, and coconut sheaths fibers were also tested. The implications of the results were discussed for the development of strong cementitious matrix composites.
ISSN: 1042-6914

hal-00809827
https://hal.univ-antilles.fr/hal-00809827
DOI : 10.1080/10426910601063386

Éditeur(s) : HAL CCSD
Résumé : International audience
Objective Oxidative stress, excess production of reactive oxygen species (ROS) and intense colonization of the respiratory tract by microorganisms are described in CF patients, leading to an influx in macrophages. This results in activation of NADPH oxidase that yields ROS, initiating the oxidative burst responsible for pathogen destruction. We showed that phagocytosis was altered in CF macrophages, yet oxidative status in this cell was not defined. The objective of this study is to draw a link between oxidative stress and plasma membrane integrity in CF macrophages, since lipid peroxidation is known to alter cell membrane. Methods Peripheral blood monocytes-derived macrophages were obtained from CF patients and healthy subjects. Plasma membrane fluidity was assessed with di4-ANEPPDHQ and oxidative status was measured with ROS indicating probes. Results In CF macrophages, membrane fluidity was increased whereas lipid peroxidation was diminished. Surprisingly, general oxidative status remained similar to the one observed in non-CF macrophages. Also, CF macrophages did not abolish chemically induced-oxidative stress. In non-CF macrophages, treatment with cholesterol slightly increased membrane fluidity whereas LPS treatment had no effect. Conclusion CF macrophages displayed an increased membrane fluidity associated with a decreased lipid peroxidation. This raises the hypothesis that membrane alteration in CF macrophages may be due to other mechanism than oxidative stress. Nevertheless, since the killing capacity of CF macrophage is defective, a deregulation of O•−2 production is very likely, suggesting alteration of NADPH oxidase or mitochondrial dysfunction
the 38th European Cystic Fibrosis Conference
Vienne, Austria

hal-01162769
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162769
DOI : 10.1016/S1569-1993(15)30217-4

Éditeur(s) : HAL CCSD Instituto Oswaldo Cruz, Ministério da Saúde
Résumé : International audience
This study examined whether the antidermatophytic activity of essential oils (EOs) can be used as an indicator for the discovery of active natural products against Leishmania amazonensis. The aerial parts of seven plants were hydro-distilled. Using broth microdilution techniques, the obtained EOs were tested against three strains of dermatophytes (Trichophyton mentagrophytes, Microsporum gypseum and Microsporum canis). To compare the EOs antifungal and antiparasitic effects, the EOs activities against axenic amastigotes of L. amazonensis were concurrently evaluated. For the most promising EOs, their antileishmanial activities against parasites infecting peritoneal macrophages of BALB/c mice were measured. The most interesting antifungal candidates were the EOs from Cymbopogon citratus, Otacanthus azureus and Protium heptaphyllum, whereas O. azureus, Piper hispidum and P. heptaphyllum EOs exhibited the lowest 50% inhibitory concentration (IC 50) values against axenic amastigotes, thus revealing a certain correspondence between both activities. The P. hispidum EO was identified as the most promising product in the results from the infected macrophages model (IC 50 : 4.7 µg/mL, safety index: 8). The most abundant compounds found in this EO were sesquiter-penes, notably curzerene and furanodiene. Eventually, the evaluation of the antidermatophytic activity of EOs appears to be an efficient method for identifying new potential drugs for the treatment of L. amazonensis.
ISSN: 0074-0276

Droits : http://creativecommons.org/licenses/by/
hal-01230471
http://hal.upmc.fr/hal-01230471
http://hal.upmc.fr/hal-01230471/document
http://hal.upmc.fr/hal-01230471/file/0074-0276-mioc-0140332.pdf
DOI : 10.1590/0074-02760140332

Résumé : This study contributes to inventory programme on emerging pollutants in French waters and to the general reflection which will enable to update the list of relevant substnaces to be included in the new monitoring programmes to come. This work concerns the coastal part of the inventory programme on marine waters and sediments of France and five overseas french departments (OFD). In this goal, passive sampling techniques and direct extraction techniques have been tested through the implementation of in situ systems integrators POCIS (Polar Organic Chemical Integrative Sampler) and the extraction by SBSE bars (Stir bar sorptive extraction) directly in the waters sampled. Finally, analyzes of sediment completed the acquisition of data. Arount 40 stations were sampled for shore waters and sediments were collected from 7 stations in France and 5 stations in the OFD (one station/OFD). In analytical terms, 1054 analyzes were carried out on POCIS membranes and only 64 data exceeded the limit of detection (LD), 12726 analyzes came from SBSE extractions and 304 were above the LD and 1536 analyzes in sediment showed that 237 data were above the limit of quantification (LQ). Finally, 169 different substances were investigated and 68 of them were detected at least once in water or sediment. The lack of replicates for POCIS analyzes and those in the sediment limited the statistical treatment of data. The results were used to determine the level of contamination, the detection frequency (FD), the distribution of substances between France and OFD, the comparison with environmental thresholds (the PNEC) and the origin/use of the substances. In littoral waters, 32 substances were identified and 19 were quantified. In the sediment, 47 substances were quantified. Nine substances were detected in both water and sediment. In France, the 15 substances that were quantified at higher frequencies (> 50 %, one out of 2 sites) were quantified in sediments. These are the congeners of PAHs (11 substances), organic forms of tin (2 substances), diethyl lead and 209 PBDE congener. In the OFD, the 22 substances that were quantified at higher frequencies (> 50 %, one out of 2 sites) were measured in sediments. These are congeners of PAHs (13 substances) , alkylphenols ( 3 molecules: the mono and diethoxyate nonylphenol and the 4-ter butylphenol ), the organic forms of tin (2 substances), products of metabolism insecticide DDT ( 2 products), diethyl lead and the 209 PBDE congener. The study of the highest concentrations distribution of substances between France and OFD shows that the 5 (among 19 molecules) highest concentrations in water and the 6 (among 47 molecules) highest concentrations in sediments are found in OFD. Reference to PNEC indicates that four pesticides in water and 11 different substances in sediments exceed the environmental thresholds. Substances with highest detection frequency are found in the sediment. The distribution of data by use or nature of the substance shows that plasticizers and pesticides predominate in raw water, both in France and overseas departments while PAHs in sediments dominate in France and in OFD.
Cette étude contribue au programme d’inventaire des substances chimiques émergentes dans les eaux françaises et à la réflexion qui doit permettre d’actualiser la liste des substances pertinentes à surveiller de manière régulière dans le cadre des nouveaux programmes de surveillance. Ce travail concerne la partie littorale de l’inventaire, sur les eaux brutes et les sédiments de la métropole et des 5 DOM. Dans ce cadre, des techniques d’échantillonnage passif (EP) et d’extraction directe ont été testées grâce à la mise en place in situ de systèmes intégrateurs POCIS (Polar Organic Chemical Integrative Sampler) et à l’extraction par des barres SBSE (Stir Bar Sorptive Extraction) directement dans les eaux échantillonnées. Enfin des analyses de sédiments ont complété l’acquisition des données. L’eau d’une quarantaine de stations a été échantillonnée et des sédiments ont été prélevés sur 7 stations en métropole et dans 5 stations dans les DOM (une station par DOM). En termes analytiques, 1054 analyses ont été réalisées sur les membranes POCIS et 64 dépassaient la limite de détection (LD), 12726 analyses ont concerné les extractions par SBSE pour 304 résultats situés au dessus de la LD et 1536 analyses effectuées dans le sédiment ont donné 237 valeurs supérieures à la limite de quantification (LQ). Au bilan 169 substances différentes ont été recherchées et 68 d’entre elles ont été détectées au moins une fois dans l’eau brute ou le sédiment. L’absence de réplicats pour les analyses POCIS et celles dans le sédiment a limité le traitement statistique des données. Les résultats ont permis de déterminer le niveau de contamination, la fréquence de détection (FD), la distribution métropole/DOM des substances, la comparaison avec les seuils environnementaux (PNEC) et l’origine des substances. Dans l’eau 32 substances ont été identifiées et 19 ont été quantifiées. Dans le sédiment 47 substances sont quantifiées .Neuf substances sont détectées à la fois dans l’eau et le sédiment. En métropole, les 15 substances quantifiées aux plus hautes fréquences (> 50%, soit un site sur 2) sont quantifiées dans les sédiments. Ce sont les congénères de la famille des HAP (11 substances), des formes organiques de l’étain (2 substances), le plomb diéthyle et le congénère 209 des PBDE. Dans les DOM, les 22 substances quantifiées aux plus hautes fréquences (> 50%, soit un site sur 2) sont mesurées dans les sédiments. Ce sont des congénères de la famille des HAP dans (13 substances), des alkylphénols (3 substances : nonylphénols mono et diéthoxylés et 4-ter butylphénol), des formes organiques de l’étain (2 substances), des produits de métabolisation de l’insecticide DDT (2 produits), du plomb diéthyle et du congénère 209 des PBDE. L’étude de la répartition des plus fortes concentrations entre la métropole et les DOM montre que les 5 (sur 19) concentrations les plus élevées mesurées dans l’eau et les 6 (sur 47) plus fortes concentrations mesurées dans les sédiments sont trouvées dans les DOM. Les substances mesurées aux fortes fréquences sont observées dans le sédiment. La référence à la PNEC indique le dépassement de la norme pour 4 pesticides dans l’eau brute et 11 substances diverses dans les sédiments. L’exploitation des données par usage ou nature des substances montre que les plastifiants et les pesticides sont majoritaires dans les eaux brutes, à la fois en métropole et dans les DOM alors que ce sont les HAP qui dominent dans les sédiments, en métropole et dans les DOM.

Droits : 2014 ONEMA, Ifremer
http://archimer.ifremer.fr/doc/00259/36994/35483.pdf
http://archimer.ifremer.fr/doc/00259/36994/

Résumé : The conservation of crawfish requires the use of chemical substances making it possible to limit blackening. This phenomenon this blackening (melanine) is due to the coordinated action of three elements: - oxygen, - an enzyme (cupro-protein), - a suitable substrate, tyrosin or the dihydroxyphénylalanine. The absence of the one of them allows a notorious reduction in the phenomenon. Several antioxydant products, were used to prevent the formation of the mélanine. The métabisutfite of soda or potassium as well as soda bisulfite in acid solution, are currently used to treat crawfish and shrimps. Several methods of use of these pesticides exist, we propose in this report to present the principal ones, as well as the control methods making it possible to check the quality of the treatment.
La conservation des langoustines nécessite l'utilisation de substances chimiques permettant de limiter le noircissement. Ce phénomène ce noircissement (mélanine) est due à l'action coordonnée de trois éléments : - l'oxygène, - une enzyme (cupro-protéine), - un substrat convenable, la tyrosine ou la dihydroxyphénylalanine. L'absence de l'une d'entre elles permet une diminution notoire du phénomène. Plusieurs produits anti-oxydants, ont été utilisés pour prévenir la formation de la mélanine. Le métabisutfite de soude ou de potassium ainsi que le bisulfite de soude en solution acide, sont actuellement utilisés pour traiter les langoustines et les crevettes. Plusieurs méthodes d'utilisation de ces produits de traitement existent, nous nous proposons dans ce rapport de présenter les principales, ainsi que les méthodes de contrôle permettant de vérifier la qualité du traitement.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/1991/rapport-1586.pdf
http://archimer.ifremer.fr/doc/00000/1586/

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
The implication of oxidative stress as primary mechanism inducing doxorubicin (DOX) cardiotoxicity is still questionable as many in vitro studies implied supra-clinical drug doses or unreliable methodologies for reactive oxygen species (ROS) detection. The aim of this study was to clarify whether oxidative stress is involved in compliance with the conditions of clinical use of DOX, and using reliable tools for ROS detection. We examined the cytotoxic mechanisms of 2 μM DOX 1 day after the beginning of the treatment in differentiated H9c2 rat embryonic cardiac cells. Cells were exposed for 2 or 24 h with DOX to mimic a single chronic dosage or to favor accumulation, respectively. We found that apoptosis was prevalent in cells exposed for a short period with DOX: cells showed typical hallmarks as loss of anchorage ability, mitochondrial hyperpolarization followed by the collapse of mitochondrial activity, and nuclear condensation. Increasing the exposure period favored a shift to necrosis as the cells preferentially exhibited early DNA impairment and nuclear swelling. In either case, measuring the fluorescence lifetime of 1-pyrenebutyric acid or the intensities of dihydroethidium or amplex red showed a consistent pattern in ROS production which was a slight increased level far from representative of an oxidative stress. Moreover, pre-treatment with dexrazoxane provided a cytoprotective effect although it failed to detoxify ROS. Our data support that oxidative stress is unlikely to be the primary mechanism of DOX cardiac toxicity in vitro.
ISSN: 0300-8177

hal-01285736
https://hal-univ-perp.archives-ouvertes.fr/hal-01285736
DOI : 10.1007/s11010-016-2653-x

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Cyanobacteria are ubiquitous microorganisms considered as important contributors to the formation of Earth's atmosphere and nitrogen fixation. However, they are also frequently associated with toxic blooms. Indeed, the wide range of hepatotoxins, neurotoxins and dermatotoxins synthesized by these bacteria is a growing environmental and public health concern. This paper provides a state of the art on the occurrence and management of harmful cyanobacterial blooms in surface and drinking water, including economic impacts and research needs. Cyanobacterial blooms usually occur according to a combination of environmental factors e.g., nutrient concentration, water temperature, light intensity, salinity, water movement, stagnation and residence time, as well as several other variables. These environmental variables, in turn, have promoted the evolution and biosynthesis of strain-specific, gene-controlled metabolites (cyanotoxins) that are often harmful to aquatic and terrestrial life, including humans. Cyanotoxins are primarily produced intracellularly during the exponential growth phase. Release of toxins into water can occur during cell death or senescence but can also be due to evolutionary-derived or environmentally-mediated circumstances such as allelopathy or relatively sudden nutrient limitation. Consequently, when cyanobacterial blooms occur in drinking water resources, treatment has to remove both cyanobacteria (avoiding cell lysis and subsequent toxin release) and aqueous cyanotoxins previously released. Cells are usually removed with limited lysis by physical processes such as clarification or membrane filtration. However, aqueous toxins are usually removed by both physical retention, through adsorption on activated carbon or reverse osmosis, and chemical oxidation, through ozonation or chlorination. While the efficient oxidation of the more common cyanotoxins (microcystin, cylindrospermopsin, anatoxin and saxitoxin) has been extensively reported, the chemical and toxicological characterization of their by-products requires further investigation. In addition, future research should also investigate the removal of poorly considered cyanotoxins (β-methylamino-alanine, lyngbyatoxin or aplysiatoxin) as well as the economic impact of blooms.
Environment International

hal-00875835
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00875835
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00875835/document
DOI : 10.1016/j.envint.2013.06.013
PUBMED : 23892224

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Abstract This work shows the preparation, characterisation and testing of TiO2 membranes dip-coated on commercial α-Al2O3 tubes for desalination. TiO2 thin films (∼400 nm) were synthesised from titanium propoxide and exposed to a gentle thermal treatment to control particle and pore sizes (dp ∼ 4 nm). The TiO2 membranes were tested for brackish (0.3 wt%), sea water (3.5 wt%) and brine concentrations (7.5 and 10 wt%) up to 75°C in a pervaporation setup. Water fluxes as high as 10.5 kg m-2 h-1 were achieved for brackish concentrations, whilst values of up to 4.0 and 6.0 kg m-2 h-1 were measured for the highest brine concentration (10 wt%). Concentration and temperature polarisation both affected the water fluxes, particularly for brine solutions, though the latter was more dominant. Salt rejection remained very high at ∼99% for all tested conditions, thus demonstrating the feasibility of mesoporous inorganic TiO2 structures for desalination and brine processing. The TiO2 membranes proved to be stable for long term (>350 h) testing even under thermal cycling conditions. © 2015 Elsevier B.V. All rights reserved.
ISSN: 1383-5866

hal-01683212
https://hal.univ-antilles.fr/hal-01683212
DOI : 10.1016/j.seppur.2015.04.028

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Hepatic drug transporters are now recognized as major actors of hepatobiliary elimination of drugs. Characterization of their regulatory pathways is therefore an important issue. In this context, the present study was designed to analyze the potential regulation of human hepatic transporter expression by protein kinase C (PKC) activation. Treatment by the reference PKC activator phorbol 12-myristate 13-acetate (PMA) for 48 h was shown to decrease mRNA expression of various sinusoidal transporters, including OATP1B1, OATP2B1, NTCP, OCT1 and MRP3, but to increase that of OATP1B3, whereas mRNA expression of canalicular transporters was transiently enhanced (MDR1), decreased (BSEP and MRP2) or unchanged (BCRP) in human hepatoma HepaRG cells. The profile of hepatic transporter mRNA expression changes in PMA-treated HepaRG cells was correlated to that found in PMA-exposed primary human hepatocytes and was similarly observed in response to the PKC-activating marketed drug ingenol mebutate. It was associated with concomitant repression of OATP1B1 and OATP2B1 protein expression and reduction of OATP, OCT1, NTCP and MRP2 activity. The use of chemical PKC inhibitors further suggested a contribution of novel PKCs isoforms to PMA-mediated regulations of transporter mRNA expression. PMA was finally shown to cause epithelial-mesenchymal transition (EMT) in HepaRG cells and exposure to various additional EMT inducers, i.e., hepatocyte growth factor, tumor growth factor-β1 or the HNF4α inhibitor ≡I6015, led to transporter expression alterations highly correlated to those triggered by PMA. Taken together, these data highlight PKC-dependent regulation of human hepatic drug transporter expression, which may be closely linked to EMT triggered by PKC activation
ISSN: 0006-2952

hal-01216205
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01216205
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01216205/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01216205/file/Protein%20kinase%20C-dependent%20regulation.pdf
DOI : 10.1016/j.bcp.2015.10.007

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
During the treatment process of drinking water, disinfectants (chlorine, ozone, chlorine dioxide) react on water containing organic matter and bromide to produce disinfection by-products at trace levels. Among them, five of the nine existing halo-acetic acids (HAAs) are commonly found in drinking water (monochloroacetic acid (MCAA), dichloroacetic acid (DCAA), monobromoacetic acid (MBAA), dibromoacetic acid (DBAA), and Trichloroacetic acid (TCAA)), including four classified in the 2B IARC group of potential carcinogens (BCAA, DBAA, DCAA, TCAA). With respect to drinking water quality, guidelines are proposed by WHO (2006) and water quality standards are imposed in many countries such as less than 100 μg/L for the sum of the five HAAs by US EPA (1998) and Canadian Health Department (2008). For this purpose, two analytical methods are commonly used, GC/MS with derivatization and LC/MS, UV or conductivity. A new method, based on two-dimensional ion chromatography (IC 2D) with suppressed conductivity is proposed. This method presents the main advantage of offering a quick implementation compared to GC or LC methods: direct injection, slight maintenance, lower cost of investment, by leading to good performances (specificity and sensitivity). The use of two different selectivity columns, and the fractionation on the first dimension canceling interferences, improves the specificity. The sensitivity is enabled by interfacing a preconcentration column between the two different internal diameter columns. The analytical conditions are optimized for the analysis of nine HAAs. The performances of the method are evaluated. The optimized method applied to natural water samples demonstrates its ability to quantify HAAs at trace levels in drinking water.
Microchemical Journal

hal-00877151
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00877151
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00877151/document
DOI : 10.1016/j.microc.2013.07.012

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Co-exposure to environmental polycyclic aromatic hydrocarbons (PAHs) and interleukin (IL)-1β induces expression of the tumor-promoting cytokine IL-6 in cancer cells. The present study was designed to determine whether such an IL-6 up-regulation also occurs in response to co-treatment by PAHs and tumor necrosis factor (TNF)-α, an inflammatory cytokine commonly found in tumor microenvironment. Co-exposure to the prototypical PAH benzanthracene (BZA) and TNF-α was found to markedly induce mRNA expression and secretion of IL-6 in human breast cancer cells MCF-7, whereas exposure to either BZA or TNF-α alone was without significant effect. Co-treatment by BZA and TNF-α-containing conditioned media from human inflammatory macrophages similarly up-regulated IL-6 expression in MCF-7 cells. BZA/TNF-α-mediated IL-6 induction in MCF-7 cells was counteracted by silencing aryl hydrocarbon receptor (AhR), known to mediates most of PAH effects. IL-6 up-regulation was moreover associated with NF-κB activation and was abolished by using chemical NF-κB inhibitors or knocking-down expression of the p65/RelA NF-κB subunit. Taken together, these data indicate that co-exposure to BZA/TNF-α induces IL-6 expression by AhR- and NF-κB-dependent pathways in MCF-7 cancer cells. This regulation of IL-6 by environmental PAHs, that is dependent of inflammatory cytokine microenvironment, may contribute to the well-known carcinogenic properties of these organic pollutants.
ISSN: 0009-2797

inserm-00818896
http://www.hal.inserm.fr/inserm-00818896
DOI : 10.1016/j.cbi.2013.01.005
PUBMED : 23396138

Résumé : Le fluide chaud produit par les forages de la centrale géothermique de Bouillante (Guadeloupe) est enrichi en espèces dissoutes telles que la silice qui peuvent précipiter sous forme de dépôts solides lors de son refroidissement et gêner fortement la production électrique. L’un des principaux objectifs de ce travail de thèse a donc été d’améliorer l’état des connaissances sur les conditions physiques, chimiques et cinétiques de la précipitation de la silice amorphe à Bouillante. Après une étude des caractéristiques physico-chimiques des fluides et des dépôts associés au champ de Bouillante, des expériences sur la cinétique de précipitation de la silice, sur site, pour une large gamme de température (25 - 90°C) et de pH (4 - 12) ont été menées et analysées en détail.Pour l’ensemble de ces expériences, seule la polymérisation (réversible) de la silice dissoute, sous forme de suspensions colloïdales très stables en solution, a été observée. La modélisation des données expérimentales de cinétique montre que la vitesse de polymérisation de la silice suit une loi d’ordre 2 vis-à-vis de la silice dissoute jusqu’à l’équilibre en accord avec une dimérisation de la silice. Par contre, durant l’étape initiale de la réaction, une loi d’ordre 4 semble mieux adaptée, suggérant des réactions de polymérisation plus complexes avec formation de tétramères. La température a un effet limité sur la cinétique de polymérisation de la silice comparé à l’effet du pH qui est beaucoup plus important. L’énergie d’activation de la réaction globale est de 41 - 54 kJ pour des pH compris entre 5 et 8.La caractérisation de la silice précipitée a mis en évidence des différences notables entre la structure poreuse de la silice solide prélevée sur les installations de surface et celle de la silice colloïdale obtenue par polymérisation lors des expériences de cinétique, ce qui semble indiquer que des mécanismes différents interviennent dans ces deux contextes de précipitation de la silice dissoute.Le deuxième objectif de cette thèse était d’évaluer la possibilité de valoriser la silice extraite de l’eau géothermale de Bouillante dans un procédé de traitement des eaux naturelles par adsorption. Pour cela, les propriétés d’adsorption de la silice géothermale brute et fonctionnalisée par le poly(ethylèneimine) (ou PEI) ont été étudiées pour deux polluants : un colorant, le bleu de méthylène et un métal lourd, le plomb. Les résultats obtenus montrent que la silice brute possède une grande capacité d’adsorption vis-à-vis du bleu de méthylène. En outre, la fonctionnalisation de la silice par le PEI permet d’améliorer sa capacité d’adsorption vis-à-vis du plomb en solution, en accord avec un modèle cinétique du pseudo-second ordre suggérant une chimisorption. Le modèle d’isotherme de Redlich-Peterson est également en très bon accord avec les données expérimentales.
The hot geothermal fluid produced by the geothermal power plant of Bouillante (Guadeloupe) contains various dissolved components such as silica that can precipitate as solid deposits during their cooling and cause serious problems on the electricity generation. One of the aim of this study is to improve the understanding on the physical, chemical and kinetics conditions of the amorphous silica precipitation in the Bouillante geothermal field. After a study on the physical and chemical characteristics of the Bouillante fluids and deposits which can form during their exploitation, experiments on the kinetics of silica precipitation, on site, under a large range of temperature (25 – 90°C) and pH (4 – 12) have been carried out and analyzed in detail.During on site kinetics experimentations only dissolved silica polymerization (reversible) as colloidal gel, very stable in solution, was observed. Modeling of the experimental data showed that the kinetics polymerization is characterized by a 2-order kinetic law relative to dissolved silica until the equilibrium that is consistent with silica dimerization. On the other side, the initial stage of the reaction is better characterized by a 4-order kinetic law that suggested more complex polymerization reactions with tetramers formation.Temperature has a little effect on the polymerization kinetics compared with the pH which has an effect more important. The activation energy of silica precipitation calculated between 25 and 90°C, is about 41 - 54 kJ for pH ranging to 5 - 8.The characterization of the silica precipitate reveals significant differences in the porous structure of the silica collected on the surface installations and the one obtained from kinetic experiments that suggests different precipitation mechanisms. The second objective of this thesis was to evaluate the possibility to promote geothermal silica for the treatment of natural waters containing contaminants by adsorption. Adsorption properties of the untreated and functionalized by poly(ethylèneimine) (ou PEI) geothermal silica have been investigated for two pollutants: a colorant, the methylene blue and a heavy metal, the lead.Results showed that untreated silica has a great adsorption capacity concerning the methylene blue. Besides, silica functionalization by the PEI allows improving the adsorption capacity for lead in solution. The adsorption kinetics curves followed a pseudo-second order model consistent with a chimisorption. The isotherm model of Redlich-Peterson fitted well the experimental data.

http://www.theses.fr/2014AGUY0698/document

Éditeur(s) : HAL CCSD
Résumé : IPC: C07D 311/60 (2006.01), A61K 31/352 (2006.01), A61P 29/00 (2006.01), A61P 35/00 (2006.01), A61P 37/00 (2006.01), C07D 311/64 (2006.01), C07D 335/06 (2006.01), C07D 407/04 (2006.01), C07D 409/04 (2006.01)
The invention relates to new PI3K/AKT/mTOR inhibitors of formula (I) and their use for the prevention and/or the treatment of a disease selected from the group consisting of: inflammatory diseases, autoimmune diseases, neurodegenerative diseases, cancers, transplant rejection, diseases characterized by a premature aging and tuberous sclerosis.
L'invention concerne de nouveaux inhibiteurs de PI3K/AKT/mTOR, et leur utilisation pour la prévention et/ou le traitement d'une maladie choisie dans le groupe constitué par: des maladies inflammatoires, des maladies auto-immunes, des maladies neurodégénératives, des cancers, un rejet de greffe, des maladies caractérisées par un vieillissement prématuré ou la sclérose tubéreuse.
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139914

Patent N° : WO 2015044229 / EP 2853530
hal-01139914
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139914

Éditeur(s) : HAL CCSD
Résumé : International audience
Necroptosis is a regulated form of cell death involved in several disease models including in particular liver diseases. Receptor-interacting protein kinases, RIPK1 and RIPK3, are the main serine/threonine kinases driving this cell death pathway. We screened a noncommercial, kinase-focused chemical library which allowed us to identify Sibiriline as a new inhibitor of necroptosis induced by tumor necrosis factor (TNF) in Fas-associated protein with death domain (FADD)-deficient Jurkat cells. Moreover, Sib inhibits necroptotic cell death induced by various death ligands in human or mouse cells while not protecting from caspase-dependent apoptosis. By using competition binding assay and recombinant kinase assays, we demonstrated that Sib is a rather specific competitive RIPK1 inhibitor. Molecular docking analysis shows that Sib is trapped closed to human RIPK1 adenosine triphosphate-binding site in a relatively hydrophobic pocket locking RIPK1 in an inactive conformation. In agreement with its RIPK1 inhibitory property, Sib inhibits both TNF-induced RIPK1-dependent necroptosis and RIPK1-dependent apoptosis. Finally, Sib protects mice from concanavalin A-induced hepatitis. These results reveal the small-molecule Sib as a new RIPK1 inhibitor potentially of interest for the treatment of immune-dependent hepatitis. © 2017 Federation of European Biochemical Societies
ISSN: 1742464X

hal-01616420
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616420
DOI : 10.1111/febs.14176
PUBMED : 28715128

Éditeur(s) : HAL CCSD
Résumé : Hepatitis C virus (HCV) is one of the leading causes of hepatocellular carcinoma. Therapeutic treatment against the virus has been recently improved by a tritherapy including pegylated interferon, ribavirin and antiviral protease. Nevertheless, the importance of side effects and the emergence of resistant mutants require the development of new antivirals. In this context, our team has recently discovered that Type III phosphatidylinositol 4-kinases (PI4KIIIα and PI4KIIIβ) are essential for the propagation of the virus in a human hepatic cell line at the entry and replication steps. To further characterize these potential therapeutic targets, we investigate the implication of these kinases during the HCV entry, using primary human hepatocytes, a model closer to the in vivo conditions. Two lines of research were developed: Verification of the importance of the kinase activity of PI4KIIIs during HCV entry in primary human hepatocytes, through a chemical approach; Validation of the involvement of these kinases and their enzymatic activity during viral entry through a genetic approach based on RNA interference and phenotype rescue. In parallel, we studied the expression of PI4KIIIα in liver diseases. Our results suggest the involvement of PI4KIIIα in HCV entry; the involvement of PI4KIIIIβ needs to be confirmed. The analysis of PI4KIIIα expression in hepatocellular carcinoma led us to propose this kinase as a new molecular marker, which could improve the already established prognosis models and could lead to the development of new therapeutic approaches.
Le virus de l’hépatite C (VHC) est l’un des principaux facteurs étiologiques du carcinome hépatocellulaire. Le traitement des hépatites virales C a été récemment amélioré grâce à une trithérapie (interféron, ribavirine et anti-protéase virale). Néanmoins l’importance des effets secondaires et l’émergence de mutants résistants nécessitent de découvrir de nouveaux antiviraux. Dans ce contexte, notre équipe a récemment découvert que les phosphatidylinositol 4-kinases de type III (PI4KIIIα et PI4KIIIβ) étaient indispensables à la propagation du virus dans une lignée hépatique humaine, et ce, à 2 étapes de son cycle biologique : l’entrée et la réplication. L’objectif du présent travail était de poursuivre la validation de ces nouvelles cibles thérapeutiques potentielles, en approfondissant nos connaissances sur la dépendance du virus à l’égard de ces kinases au cours de son entrée. Pour cela, nous avons utilisé le modèle des hépatocytes humains primaires, système in vitro plus proche du contexte physiologique que les modèles utilisés jusqu’à présent et qui étaient basés sur l’exploitation de lignées. Deux axes ont été développés : Vérification de l’importance de l’activité kinase des PI4KIIIs au cours de l’entrée du VHC dans les hépatocytes humains primaires, à travers une approche chimique ; Validation de l’implication de ces kinases et de leur activité enzymatique au cours de l’entrée virale grâce à une approche génétique basée sur l’ARN interférence et la restauration de phénotype. En parallèle, nous avons étudié l’expression de PI4KIIIα au cours de pathologies hépatiques. Nos résultats suggèrent une implication de PI4KIIIα au cours de l’entrée du VHC dans les hépatocytes humains primaires, mais restent à confirmer quant à l’implication de PI4KIIIβ. Par ailleurs, l’analyse de l’expression de PI4KIIIα dans le carcinome hépatocellulaire (CHC) conduit à proposer cette kinase comme un nouveau marqueur moléculaire, qui pourrait améliorer les modèles de pronostic déjà établis et pourrait conduire au développement de nouvelles approches thérapeutiques pour les patients atteints d’un CHC, quelque soit l’étiologie.
https://tel.archives-ouvertes.fr/tel-00950335

Droits : info:eu-repo/semantics/OpenAccess
NNT : 2013REN1B006
tel-00950335
https://tel.archives-ouvertes.fr/tel-00950335
https://tel.archives-ouvertes.fr/tel-00950335/document
https://tel.archives-ouvertes.fr/tel-00950335/file/ILBOUDOAdeodat.pdf