Aspect psychosomatique des parodontites chroniques

Stress, a term constantly redefined in the scientific community, is nevertheless an important factor and confirmed in the etiology and the development of many inflammatory diseases, including periodontal disease. ln this thesis, we present succinctly the periodontal structures, then we will look at the etiology of periodontal disease and its pathogenicity in order to understand the key players and mechanisms. We will conduct an overview of the history of the concept of stress as a mediator of the disease, with an overview of current models for understanding how stress mechanisms interact to regulate the onset and progression of the disease and we will develop a partial list of studies and their conclusions.Finally, and finally we will see the importance of taking into account the patient's response as part of a proces' of chronic periodontitisLe stress, un terme constamment redéfinie dans la communauté scientifique, est néanmoins un facteur confirmée et important dans l'étiologie et le développement de nombreuses maladies inflammatoires, y compris les maladies parodontales. Dans cette thèse, nous présentons de manières succinctes les structures parodontales, puis nous nous pencherons sur l'étiologie de la maladie parodontale ainsi que sa pathogénicité afin d'en comprendre les principaux intervenants et les mécanismes. Nous effectuerons un survol de l'histoire de la notion de stress en tant que médiateur de la maladie, avec un aperçu des modèles actuels pour comprendre comment les mécanismes de stress interagissent pour réguler l'apparition et l'évolution de la maladie et nous dresserons une liste non exhaustive des études réalisées et de leurs conclusions. Enfin, et pour finir, nous verrons l'importance que revêt la prise en compte de la réaction du patient dans le cadre d'un processus de traitement d'une parodontite chroniqueMONTPELLIER-BU Médecine UPM (341722108) / SudocMONTPELLIER-BU Odontologie (341722110) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Synthesis and In Vitro Comparison of DOTA, NODAGA and 15-5 Macrocycles as Chelators for the 64Cu-Labelling of Immunoconjugates

International audienceThe development of 64 Cu-based immuno-PET radiotracers requires the use of copperspecific bifunctional chelators (BFCs) that contain functional groups allowing both convenient bioconjugation and stable copper complexes to limit in vivo bioreduction, transmetallation and/or transchelation. The excellent in vivo kinetic inertness of the pentaazamacrocyclic [ 64 Cu]Cu-15-5 complex prompted us to investigate its potential for the 64 Cu-labelling of monoclonal antibodies (mAbs), compared with the well-known NODAGA and DOTA chelators. To this end, three NODAGA, DOTA and 15-5-derived BFCs, containing a pendant azadibenzocyclooctyne moiety, were synthesised and a robust methodology was determined to form covalent bonds between them and azide-functionalised trastuzumab, an anti-HER2 mAb, using strain-promoted azide-alkyne cycloaddition. Unlike the DOTA derivative, the NODAGA-and 15-5-mAb conjugates were radiolabelled with 64 Cu, obtaining excellent radiochemical yields, under mild conditions. Although all the radioimmunoconjugates showed excellent stability in PBS or mouse serum, [ 64 Cu]Cu-15-5-and [ 64 Cu]Cu-NODAGA-trastuzumab presented higher resistance to transchelation when challenged by EDTA. Finally, the immunoreactive fraction of the radioimmunoconjugates (88-94%) was determined in HER-2 positive BT474 human breast cancer cells, confirming that the bioconjugation and radiolabelling processes implemented had no significant impact on antigen recognition