Etude et modulation du microenvironnement des purinorécepteurs de mort P2X7 par des formulations lipidiques et biopolymères afin de réguler les mécanismes de prolifération et de dégénérescence cellulaire sur des modèles dermatologiques (cicatrisation et mélanome)

Le purinorécepteur P2X7 joue un rôle majeur dans les phénomènes de dégénérescences (Alzheimer, DMLA) et mort cellulaires. Récemment des études ont montré que l activation basale de ce récepteur est indispensable dans le processus de cicatrisation et de prolifération cellulaire. Nous avons essayé de mieux comprendre le paradoxe de cette activation du récepteur P2X7 qui oriente vers la prolifération et même les métastases tumorales, mais aussi vers les mécanismes de dégénérescence cellulaire. L'influence du microenvironnement (Lipides, matrice extracellulaire, oxygène) apparait essentielle pour comprendre ces différents effets. Notre premier objectif a été d étudier l impact de la modulation du microenvironnement du récepteur P2X7 par des composants de la matrice extracellulaire. Ainsi, sur un modèle de cicatrisation cutanée, nous avons mis en évidence l impact de la taille des fragments du hyaluronate de sodium (composant prédominant dans la matrice extracellulaire). Nos résultats ont montré que l activation du récepteur P2X7 dépend du poids moléculaire du hyaluronate de sodium. Notre deuxième objectif a été de moduler le microenvironnement lipidique du récepteur P2X7. Nous avons sélectionné une huile riche en acides gras insaturés et avons ainsi étudié son effet sur l activation du récepteur P2X7. Sur nos modèles de cicatrisation, nous avons mis en évidence qu une modulation du microenvironnement lipidique du récepteur P2X7 influence son activation. D autre part la modulation du microenvironnement lipidique sur des cellules tumorale de mélanome active les voies de dégénérescence ouvrant la perspective de nouvelles stratégies thérapeutiques.The purinoceptor P2X7 plays a role in cytotoxic degenerative processus (Alzheimer, AMD) and cell death. Recent studies have shown that basal activation of this receptor is essential in the healing process and cell proliferation. We tried to understand the paradox that activation of P2X7 receptor that directs to the same proliferation and tumor metastasis, but also to the mechanisms of cell degeneration. The influence of the microenvironment (lipids, extracellular matrix, oxygen) appears essential to understand these effects. Our first objective was to study the impact of the modulation of P2X7 receptor microenvironment by extracellular matrix components. On cell monolayer model of wound healing we have highlighted the impact hyaluronan molecular weight (predominant component in the extracellular matrix). Our results showed that activation of P2X7 receptor is dependent on hyaluronan molecular weight. Our second objective was to modulate lipid microenvironment P2X7 receptor. We selected an oil rich in unsaturated fatty acids and thus have studied its effect on the activation of P2X7 receptor. In our models of healing and melanoma cell, we have demonstrated that modulation of lipid microenvironment affects P2X7 activation.PARIS5-Bibliotheque electronique (751069902) / SudocPARIS-BIUM-Bib. électronique (751069903) / SudocSudocFranceF

New approach to modulate retinal cellular toxic effects of high glucose using marine epa and dha

<p>Abstract</p> <p>Background</p> <p>Protective effects of omega-3 fatty acids against cellular damages of high glucose were studied on retinal pigmented epithelial (RPE) cells.</p> <p>Methods</p> <p>Retinal epithelial cells were incubated with omega-3 marine oils rich in EPA and DHA and then with high glucose (25 mM) for 48 hours. Cellular responses were compared to normal glucose (5 mM): intracellular redox status, reactive oxygen species (ROS), mitochondrial succinate deshydrogenase activity, inflammatory cytokines release and caveolin-1 expression were evaluated using microplate cytometry, ELISA and flow cytometry techniques. Fatty acids incorporation in retinal cell membranes was analysed using chromatography.</p> <p>Results</p> <p>Preincubation of the cells with fish oil decreased ROS overproduction, mitochondrial alterations and TNFα release. These protective effects could be attributed to an increase in caveolin-1 expression induced by marine oil.</p> <p>Conclusion</p> <p>Marine formulations rich in omega-3 fatty acids represent a promising therapeutic approach for diabetic retinopathy.</p

Per os administered refined olive oil and marine PUFA-rich oils reach the cornea: possible role on oxidative stress through caveolin-1 modulation

<p>Abstract</p> <p>Background</p> <p>Olive oil and fish oils are known to possess beneficial properties for human health. We investigated whether different oils and fatty acids alone were able to decrease oxidative stress induced on corneal cells.</p> <p>Methods</p> <p>In our <it>in vivo </it>study, rats were fed with marine oils rich in polyunsaturated fatty acids (PUFA) or refined olive oil during 28 days. At the end of the protocol, corneas were analysed for their fatty acids composition to study the incorporation of fatty acids in cell membranes. In our <it>in vitro </it>study, a human corneal cell line was incubated with marine oils or refined olive oil and subjected to oxidative stress (tBHP 50 μM, 1 hour). Effects on reactive oxygen species generation, mitochondria and caveolin-1 expression were studied using microcytofluorometry, flow cytometry and confocal microscopy.</p> <p>Results</p> <p>Our results indicate that dietary oils changed the fatty acids composition of corneal cell membranes. According to our results, PUFA-rich oils and refined olive oil (free of antioxidants) blocked reactive oxygen species production. Oleic acid, the major fatty acid of olive oil, also decreased oxidative stress. Moreover, oleic acid modified caveolin-1 expression. Antioxidant properties of oleic acid could be due to disruption of membrane microdomains such as caveolae.</p> <p>Conclusion</p> <p>Oleic acid, a potential potent modulator of oxidative stress, could be added to PUFA-rich oils to prevent oxidative stress-linked corneal pathology.</p

The ELAN Architecture: ELAN Deliverables WP3

The ELAN project is a distributed language resources system, offering access to existing resources to their potential users throughout Europe. In order to serve the electronic multilingual resource market, our task is to specify and elaborate a network of inter-connected resource servers. This documentdefines the technical specifications of each nodes that form the ELAN network: the user interface of the ELAN client; the resource servers and the network management unit

A general XML-based distributed software architecture for accessing and sharing ressources

Colloque avec actes et comité de lecture.International audienceThis paper presents a general xml-based distributed software architecture in the aim of accessing and sharing resources in an opened client/server environment. The paper is organized as follows : First, we introduce the idea of a "General Distributed Software Architecture". Second, we describe the general framework in which this architecture is used. Third, we describe the process of information exchange and we introduce some technical issues involved in the implementation of the proposed architecture. Finally, we present some projects which are currently using, or which should use, the proposed architecture

Conjunctival Proinflammatory and Proapoptotic Effects of Latanoprost and Preserved and Unpreserved Timolol: An Ex Vivo and In Vitro Study

PURPOSE. To compare the toxicity of latanoprost and preserved and unpreserved timolol on conjunctival cells. Expression of inflammatory markers and MUC5AC-related mucin production were evaluated by impression cytology in a case-control ex vivo study. The proapoptotic effect of the same drugs was also evaluated in vitro in a conjunctival cell line and compared with that of benzalkonium chloride (BAC). METHODS. Impression cytology (IC) specimens were obtained from a series of normal subjects and from patients with glaucoma treated for at least 1 year with latanoprost eye drops or preserved or unpreserved timolol. All groups were comparable in age and duration of treatment. Expression of HLA-DR, intercellular adhesion molecule (ICAM)-1, and mucin was evaluated in a masked manner by flow cytometry. For the in vitro study, a human conjunctiva-derived cell line was treated with 0.02% BAC-containing latanoprost or timolol, unpreserved timolol, or 0.02% BAC alone for 15 minutes, followed or not by 4 or 24 hours of cell recovery in normal medium. Cell viability and chromatin condensation were evaluated using microplate cold light cytofluorometry with the neutral red and the Hoechst 33342 tests, respectively. The Hoechst-neutral red ratio was defined for the apoptosis assay, and cytoskeleton changes were assessed by confocal microscopy. RESULTS. No difference was found between normal eyes and those receiving unpreserved timolol. Preserved latanoprost and timolol significantly increased the inflammatory marker expression and decreased MUC5AC expression, but to a significantly higher extent in the preserved timolol group compared with latanoprost. In vitro, 0.02% BAC-containing timolol and latanoprost triggered conjunctival cell apoptosis-however, to a significantly lesser extent than did 0.02% BAC alone. Unpreserved timolol did not cause any cell toxicity. CONCLUSIONS. These ex vivo and in vitro studies demonstrate that BAC-containing latanoprost and timolol exhibit higher proinflammatory and proapoptotic effects on conjunctival cells than does unpreserved timolol. Latanoprost caused less toxicity, however, than preserved timolol, and both drugs were less toxic than BAC alone. These results suggest a potential protective effect of the prostaglandin analogue and to a lesser extent of timolol against the toxicity of BAC in conjunctival cells. (Invest Ophthalmol Vis Sci

Учет материально-производственных запасов на примере ООО "Доминанта-мебель"

В данной работе рассматриваются теоретические основы и учет материальных затрат в ООО "Доминанта мебель". Даны рекомендации по совершенствованию учета и управлению материальными затратами.In this paper, we consider the theoretical basis and accounting of material costs in Dominanta Mebel. Recommendations are given for improving the accounting and management of material costs in the enterprise