Développement de nouveaux ligands peptidiques radiomarqués pour l'oncologie nucléaire : application au ciblage tumoral des récepteurs de la cholécystokinine/gastrine

Le récepteur de la cholécystokinine/gastrine (RCCK2) est (sur)exprimé dans de nombreux cancers et tumeurs endocrines. Par modélisation moléculaire, nous avons designé et modifié de nouveaux dérivés de la cholécystokinine ciblant ce récepteur. Ces dérivés ont été couplés à deux nouveaux chélateurs permettant de réaliser plusieurs modalités d'imagerie. Les évaluations in vitro et chez l'animal de ces radioligands peptidiques marqués à l'111indium ont révélé une meilleure fixation tumorale et une diminution significative de la fixation rénale comparé à un radioligand CCK de référence couplé au CHX-A''-DTPA. Les résultats supérieurs obtenus avec ces radioligands valident notre approche de drug design ainsi que l'intérêt des nouveaux chélateurs et indiquent que ces radiopharmaceutiques sont très prometteurs pour une utilisation en radiothérapie interne vectorisée.The cholecystokinin/gastrin receptor (RCCK2) is (over)expressed in various cancers and endocrine tumors. Via molecular modelling, we have designed and modified new cholecystokinin targeting RCCK2 derivatives. These derivatives were coupled to new multi-modality imaging chelators. In vitro and animal evaluations of these peptidic 111In-radioligands showed a better tumoral targeting and a significant renal fixation decrease compared to the CCK reference radioligand coupled to CHX-A''-DTPA. The results obtained with our radioligands validate the drug design concept and show that these radiopharmaceuticals seem to be promising for internal radiotherapy

In vivo kinetics of [bêta]-glucosidase towards glucovanillin and related phenolic glucosides in heat-treated vanilla pod (Vanilla planifolia, Orchidaceae)

Introduction . The traditional curing of vanilla pods includes “killing” and sweating steps when pods are exposed to heat (35–65 °C) for various lengths of time. Although it is known that liberation of vanillin and other phenolics from their non-aromatic glucosides is due to the action of an endogenous β -glucosidase, its in vivo kinetics remained unknown. Materials and methods . Mature green vanilla pods were pretreated for 2 h at 50 °C, 55 °C and 60 °C, then stored for 118 days at 27 °C. Phenolic glucosides and their aglycons were extracted at regular intervals during the storage period and analyzed by HPLC. Results and discussion . All phenolic β -glucosides were slowly hydrolyzed during the storage period with production of vanillin, p -hydroxybenzaldehyde, vanillic acid, and other unknown aglycons. Most of the β -glucosidase was heat-denatured by the pretreatment, and analysis of its kinetic parameters showed that it adopts, in vivo , an allosteric mode of functioning with a lower affinity for glucovanillin than in vitro , where it behaves as a Michaelian enzyme. Conclusion . Extensive research is needed to confirm the allosteric mechanism of the vanilla β -glucosidase in vivo . (Résumé d'auteur

Fate of yeast and grape pectic polysaccharides of a young red wine in the cross-flow microfiltration process

Cross-flow microfiltration of a young red wine through a mineral membrane of zirconium oxide (average pore size 0.2 μm) laid over a support of agglomerated microporous carbon reduced by 44 % the concentration of the starting wine in soluble polysaccharides. These carbohydrate polymers were mainly constituted of mannose, arabinose, galactose and galacturonic acid associated with minor amounts of rhamnose, glucose, xylose and fucose. The polysaccharides from starting wine and final permeate were separated by gel filtration on Ultrogel AcA 34 (exclusion limit for globular proteins 750,000) in at least four fractions (I-IV) of respective Kav 0.22, 0.50, 0.75 and 0.90. Each polysaccharidic population contained various proportions of yeast mannans, while grape polysaccharides were unequally distributed, fraction I containing neutral type II arabinogalactans and fractions II to IV being complex mixtures of type II arabinogalactans, arabinans and degraded forms of acidic rhamnogalactumnans (pectins). Losses due to microfiltration were positively correlated to hydrodynamic volume (molecular weight) of molecules: (I) "" 79 %, (II) "" 58 %, (III) "" 38 % and (IV) no loss. Yeast and grape polysaccharides coexisting in a given fraction (having the same Kav) were not equally affected by the microfiltration process, yeast mannans passing preferentially the membrane, while grape polymers were more retained. This differential retention was only observed in fractions of high molecular weights (I and II) and was discussed in relation with possible modifications at the molecular level (size and shape of polysaccharides) occurring in the concentration polarisation layer. Application of a back-flush pulse destined to unplug the membrane resulted in a reenrichment of the permeate in the polysaccharides present in the starting wine at a 82 % level

Influence du procédé de dépulpage de la drupe de Coffea arabica L. sur la fermentation

Au cours du traitement de postrécolte du café Arabica, l'eau utilisée a une influence directe sur les paramètres physico-chimiques, microbiologiques et biochimiques de la fermentation. Elle intervient lors du dépulpage et du transport des drupes dépulpées jusqu'à la cuve de fermentation, solubilise alors les sucres simples du mucilage, ralentit la croissance microbienne et en conséquence l'acidification du milieu fermentaire. Le dépulpage et le transport du café avec ou sans eau ne modifient pas la composition biochimique du café vert. Par ailleurs, les propriétés organoleptiques à la tasse ont été jugées identiques. Les technologies moins polluantes, dépulpage et transport sans eau des drupes dépulpées, permettent aux producteurs de contrôler la durée et l'acidité produite. En revanche, il est nécessaire de réduire le temps de fermentation car le pH devient plus rapidement acide. Des durées prolongées pourraient provoquer des surfermentations et développer des mauvais goûts. (Résumé d'auteur

Ultrastructural Study of Yam Tuber as Related to Postharvest Hardness

Usually, parenchyma cell walls of monocotyledons do not develop secondary walls; however a few days after harvesting, the yam tuber of Dioscorea dumetorum starts to harden. Two or three weeks Iater, hardness is so pronounced that the tubers cannot be eaten, even after a long cooking time. Cytochemical studies using autofluorescence or some fluorescent dyes, such as phloroglucinol hydrochloride showed that the thin, and flexible cell walls of parenchyma tubers very quickly became fully lignified after harvesting. Ultrastructura 1 stud ies of the hardened ce 11 wa 11 s showed very thick secondary wa 11 s and very deep pit apertures. These secondary walls reacted strong ly with li gn in reactants such as potassium permanganate. The use of a radioactive (l \u27• C) ce llulose precursor, uri dine- 5\u27-d ipho sphateglucose, confirmed the formation of such secondary walls. The lignification started from the corners of the cells around intercellular spaces and proceeded along the walls

La production biologique de porcs en Europe - Gestion de la santé des porcs dans les élevages de production

Les éleveurs de porcs biologiques ont développé en Europe différents systèmes de logement qui dépendent de la disponibilité des terres, des caractéristiques du sol et du climat, des traditions et des schémas de certification. Ce guide décrit les principaux systèmes de logement des porcs biologiques. Il compare les avantages et les inconvénients de chacun et donne des recommandations aux éleveurs pour mieux agir sur la santé des animaux

Evaluation of the technical and environmental performances of extraction and purification processes of arabinoxylans from wheat straw and bran

A process for hemicelluloses fractionation and purification from wheat straw and bran has been investigated and technical considerations (yields, purity) have been coupled to environmental characterizations (water consumption, carbon dioxide emissions) in order to develop an environment-friendly process. Extraction by twin-screw extrusion gave a yield in arabinoxylans equal to 8.5 % (weight of (arabinose + xylose) in the extract after fractionation/dry weight of the destarched bran). The extraction of 86 kg of straw and bran (with a ratio 6.2:1) with 5.8 kg of NaOH in pellet form resulted in the production of a complex extract containing 1.0 kg of arabinoxylan polymer, which required concentration and purification steps. Evaporation (EV) followed by ethanol precipitation (P) and freeze-drying (FD), gave a yield in hemicellulosic powder of 36.5 % (dry weight of powder/dry weight of extract after liquid/solid separation) with a total sugar content equal to 48.4 % but also used a large amount of ethanol. The other studied purification process was based on a combination of ultrafiltration (UF), anion exchange chromatography (CHR) and spray-drying (SD). It gave a yield in hemicellulosic powders of 24.6 % and a total sugar content equal to 28.7 %. The technical performances of the second process appear to be less attractive but with a lower energetic and ethanol consumption. Thus secondly the environmental impacts (water consumption and CO2 emission) of the ultrafiltration step were quantified. Life Cycle Assessment data (Ecoinvent) were used to convert materials used for the infrastructure and energy consumed during functioning into carbon dioxide emissions and water consumptions. Results have shown that environmental impacts due to the operating conditions are higher than those relative to raw material involved in the installation. The study showed that this kind of approach allows the determination of optimum conditions for the ultrafiltration step