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1. Kizlik-Masson, Claire. Anticorps anti-FP4/héparine et protéases : nouvelles stratégies thérapeutiques dans les thrombopénies induites par l'héparine : Anti-PF4/heparin antibodies and proteasis : new therapeutic strategies for heparin-induced thrombocytopenia.

Degree: Docteur es, Sciences de la vie et de la santé, 2018, Université François-Rabelais de Tours

Les Thrombopénies Induites par l’Héparine (TIH) sont une complication sévère des traitements par l’héparine dues à des IgG qui ciblent le facteur plaquettaire 4 modifié par l’héparine (FP4/H) et induisent une activation cellulaire via FcγRIIA, conduisant à des complications thrombotiques. Nous avons caractérisé 5B9, IgG1 monoclonale chimérique anti-FP4/H mimant parfaitement les anticorps de TIH et qui est donc un excellent outil pour étudier la physiopathologie des TIH. La pathogénicité des anticorps (Ac) de TIH implique leur fixation aux FcγR. Nous avons montré que le clivage de la région charnière des IgG de TIH par IdeS inhibe ces interactions IgG-FcγR et supprime la pathogénicité des Ac. Nous avons aussi construit un Antibody-Drug Conjugate (ADC) antithrombotique, en bioconjuguant le tirofiban (inhibiteur de l’agrégation plaquettaire) et 5B9 déglycosylé grâce à un linker clivable par la thrombine, protéase générée en excès lors d’une TIH.

Heparin Induced Thrombocytopenia (HIT) is a rare but severe complication of heparin treatments. HIT is due to IgG antibodies specific to platelet factor 4 modified by heparin (PF4/H), which activate blood cells, (especially platelets) after binding to FcγRIIA, this process explaining frequent thrombotic complications. We characterized 5B9, a chimeric IgG1 targeting PF4/H and which fully mimics human HIT antibodies. Therefore, 5B9 is a perfect tool for studying the physiopathology of HIT. IgG antibodies to PF4/H are pathogenic by interacting with FcγR. In this regard, we showed that cleavage by IdeS, a bacterial protease, of the hinge of anti-PF4/H IgG, fully suppressed their pathogenicity. Furthermore, we designed an antithrombotic Antibody-Drug Conjugate that combined tirofiban, a GPIIbIIIa inhibitor with deglycosylated 5B9 using a thrombin cleavable linker.

Advisors/Committee Members: Pouplard, Claire (thesis director).

Subjects/Keywords: Thrombopénie induite par l’Héparine; FcγR; Anticorps; Protéases; IdeS; Antithrombotique Antibody- Drug Conjugate; Heparin-Induced Thrombocytopenia; FcγR; Antibody; Proteases; IdeS; Antithrombotic Antibody- Drug Conjugate (ADC)

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APA (6th Edition):

Kizlik-Masson, C. (2018). Anticorps anti-FP4/héparine et protéases : nouvelles stratégies thérapeutiques dans les thrombopénies induites par l'héparine : Anti-PF4/heparin antibodies and proteasis : new therapeutic strategies for heparin-induced thrombocytopenia. (Doctoral Dissertation). Université François-Rabelais de Tours. Retrieved from http://www.theses.fr/2018TOUR3313

Chicago Manual of Style (16th Edition):

Kizlik-Masson, Claire. “Anticorps anti-FP4/héparine et protéases : nouvelles stratégies thérapeutiques dans les thrombopénies induites par l'héparine : Anti-PF4/heparin antibodies and proteasis : new therapeutic strategies for heparin-induced thrombocytopenia.” 2018. Doctoral Dissertation, Université François-Rabelais de Tours. Accessed November 20, 2019. http://www.theses.fr/2018TOUR3313.

MLA Handbook (7th Edition):

Kizlik-Masson, Claire. “Anticorps anti-FP4/héparine et protéases : nouvelles stratégies thérapeutiques dans les thrombopénies induites par l'héparine : Anti-PF4/heparin antibodies and proteasis : new therapeutic strategies for heparin-induced thrombocytopenia.” 2018. Web. 20 Nov 2019.

Vancouver:

Kizlik-Masson C. Anticorps anti-FP4/héparine et protéases : nouvelles stratégies thérapeutiques dans les thrombopénies induites par l'héparine : Anti-PF4/heparin antibodies and proteasis : new therapeutic strategies for heparin-induced thrombocytopenia. [Internet] [Doctoral dissertation]. Université François-Rabelais de Tours; 2018. [cited 2019 Nov 20]. Available from: http://www.theses.fr/2018TOUR3313.

Council of Science Editors:

Kizlik-Masson C. Anticorps anti-FP4/héparine et protéases : nouvelles stratégies thérapeutiques dans les thrombopénies induites par l'héparine : Anti-PF4/heparin antibodies and proteasis : new therapeutic strategies for heparin-induced thrombocytopenia. [Doctoral Dissertation]. Université François-Rabelais de Tours; 2018. Available from: http://www.theses.fr/2018TOUR3313

2. Moita, Isadora da Silva. Caracteriza??o qu?mica das cascas das sementes de esp?cies do g?nero Theobroma.

Degree: 2019, Universidade Federal do Amazonas

As esp?cies Theobroma grandiflorum, T. cacao e T. subincanum pertencem ao g?nero Theobroma da fam?lia Sterculiaceae. Quimicamente, as esp?cies do g?nero s?o caracterizadas por apresentar triterpenos, esteroides, flavonoides e alcaloides pur?nicos. Estudos realizados no Grupo de Pesquisa de Qu?mica de Biomol?culas da Amaz?nia (Q-BiomA), relataram perfil qu?mico rico em compostos fen?licos nas cascas das sementes de T. grandiflorum. Estes resultados motivaram a execu??o do presente trabalho de compara??o de esp?cies de Theobroma com caracter?sticas f?sicas e qu?micas semelhantes e avalia??o da atividade antioxidante das esp?cies. Os extratos hidroalcoolicos das cascas das sementes das tr?s esp?cies, foram obtidos por macera??o exaustiva, a esp?cie T. grandiflorum apresentou maior rendimento. O perfil cromatogr?fico dos extratos e fra??es foram avaliado por CCDAE, onde foi poss?vel sugerir a presen?a de diferentes flavonoides. A an?lise por EM no modo negativo, evidenciou a semelhan?a das esp?cies T. grandiflorum e T. subincanum. As fa??es foram analisadas por CLUAE-DAD em uma corrida em modo gradiente de 20min, foi poss?vel observar a presen?a da teacrina, ao se comparar os dados obtidos com o padr?o de teacrina, nas esp?cies T. grandiflorum e T. subincanum. Os resultados obtidos das an?lises realizadas com todas as fra??es das esp?cies em estudo, por CLUAE-EMAR/MS2, permitiram identificar diferentes subst?ncias fen?licas: em T. subincanum foram detectados como principais ?ons, m/z 179 (?cido cafeico), m/z 191 (?cido isoc?trico), m/z 329 (?cido vanilico glucos?deo) m/z 431 (vitexina), m/z 477 (hipoleatina-8-O- O-?-D-glucoron?deo), m/z 557 (hipoleatina-8- O-?-D- glucoron?deo 3??-O-sulfato), m/z 461 (isoscutelare?na-8-O-?-D-glucoron?deo), m/z 541 (teograndina I), estas subst?ncias foram relatadas pela primeira vez na esp?cie. A metabol?mica global foi aplicada com m?todos de an?lises de PCA e HCA, onde foi poss?vel confirmar a similaridade de todas as fra??es analisadas, entre as esp?cies T.grandiflorum e T. subincanum e a diferencia??o da esp?cie T. cacao. O extrato hidroalcoolico de T. grandiflorum foi o mais ativo quantitativamente frente aos dois radicais livres, DPPH (44,50 ? 3,35 ?g/mL ? DP) e ABTS (72,17 ? 0,76 ?g/mL ? DP). A utiliza??o de diferentes t?cnicas cromatogr?ficas e diferentes detectores, confirmou a semelhan?a do perfil qu?mico das cascas das sementes das esp?cies T. grandiflorum e T. subincanum, sendo este o ?nico trabalho comparativo das cascas das sementes, um res?duo de ind?strias de alimentos, envolvendo diferentes t?cnicas cromatogr?ficas.

The species Theobroma grandiflorum, T. cacao and T. subincanum belong to the genus Theobroma of the family Sterculiaceae. Chemically, the species of the genus are characterized by presenting purine triterpenes, steroids, flavonoids and alkaloids. Studies conducted by the Amazon Biomolecule Chemistry Research Group (Q-BiomA) reported a chemical profile rich in phenolic compounds in the T. grandiflorum seed husks. These results motivated the execution of the…

Advisors/Committee Members: Veiga Junior, Valdir Flor?ncio da, 018.728.677.90, http://lattes.cnpq.br/0581412073128121, Yamaguchi, Klenicy Kazumy de Lima, http://lattes.cnpq.br/9935066425464773, Nunomura, Rita de Cassia Saraiva, http://lattes.cnpq.br/4964432473792729, Rocha, Waldireny Caldas, http://lattes.cnpq.br/0161052060648197, [email protected].

Subjects/Keywords: Theobroma; Flavon?ides; Antioxidantes; CI?NCIAS EXATAS E DA TERRA: QU?MICA; Theobroma; Flavonoides; Atividade antioxidante; Metaboloma global

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Moita, I. d. S. (2019). Caracteriza??o qu?mica das cascas das sementes de esp?cies do g?nero Theobroma. (Masters Thesis). Universidade Federal do Amazonas. Retrieved from https://tede.ufam.edu.br/handle/tede/7444

Chicago Manual of Style (16th Edition):

Moita, Isadora da Silva. “Caracteriza??o qu?mica das cascas das sementes de esp?cies do g?nero Theobroma.” 2019. Masters Thesis, Universidade Federal do Amazonas. Accessed November 20, 2019. https://tede.ufam.edu.br/handle/tede/7444.

MLA Handbook (7th Edition):

Moita, Isadora da Silva. “Caracteriza??o qu?mica das cascas das sementes de esp?cies do g?nero Theobroma.” 2019. Web. 20 Nov 2019.

Vancouver:

Moita IdS. Caracteriza??o qu?mica das cascas das sementes de esp?cies do g?nero Theobroma. [Internet] [Masters thesis]. Universidade Federal do Amazonas; 2019. [cited 2019 Nov 20]. Available from: https://tede.ufam.edu.br/handle/tede/7444.

Council of Science Editors:

Moita IdS. Caracteriza??o qu?mica das cascas das sementes de esp?cies do g?nero Theobroma. [Masters Thesis]. Universidade Federal do Amazonas; 2019. Available from: https://tede.ufam.edu.br/handle/tede/7444

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