Submitted by JÚLIO HEBER SILVA (julioheber@yahoo.com.br) on 2017-04-13T17:22:48Z No. of bitstreams: 2 Dissertação - Gabriela Hadler Gabriel - 2017.pdf: 1069284 bytes, checksum: 7c190e383bf6069f54d2eff26158427f (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-04-17T11:13:33Z (GMT) No. of bitstreams: 2 Dissertação - Gabriela Hadler Gabriel - 2017.pdf: 1069284 bytes, checksum: 7c190e383bf6069f54d2eff26158427f (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-04-17T11:13:33Z (GMT). No. of bitstreams: 2 Dissertação - Gabriela Hadler Gabriel - 2017.pdf: 1069284 bytes, checksum: 7c190e383bf6069f54d2eff26158427f (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-03-09 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Osteosarcoma is the main primary bone tumor, with unfavorable prognosis, high mortality and high incidence of metastases. The treatment of choice is the removal of the tumor associated with combined chemotherapy, whose adverse effects allude to the increasing need to develop new drugs. The plants constitute a large natural reserve of compounds that have medicinal and therapeutic properties, such as lapachol and its derivative, β-lapachone. The aim of this study was to evaluate the cytotoxic effects of β-lapachone in osteosarcoma cells cultured in vitro. Cells were cultured and treated with β-lapachone at different concentrations and times of exposure. Tripan blue exclusion, tetrazolium reduction and cell survival assay methods were performed to evaluate the effects of the compound on the cells. Cells treated with 0,1μM β-lapachone showed lower initial cytotoxicity in the 24h time, whereas those submitted to 1,0μM showed less viability after 72h of treatment. Cytotoxicity increased as the concentration and time of exposure increased. The lowest IC50 (0,148μM) was observed in treated cells for 72h. Cell growth after treatment was lower in the 1.0μl group after 72h and the highest cell growth was observed under a concentration of 0.1μl after 24h. There was no difference between groups for cell proliferation after treatment, and the cell survival fraction was lower after 72h of exposure. It was concluded that β-lapachone has cytotoxic effects on osteosarcoma cells cultured in vitro. / O osteossarcoma é o principal tumor ósseo primário, com prognóstico desfavorável, alta mortalidade e elevada incidência de metástases. O tratamento de escolha é remoção do tumor associada à quimioterapia combinada, cujos efeitos adversos aludem à necessidade crescente de desenvolver novos medicamentos. As plantas constituem grandes reservas naturais de compostos que possuem propriedades medicinais e terapêuticas, como o lapachol e seu derivado, a β lapachona. O objetivo desse estudo foi avaliar os efeitos citotóxicos da β lapachona em células de osteossarcoma cultivadas in vitro. As células foram cultivadas e tratadas com a β lapachona em diferentes concentrações e tempos de exposição. Foram realizados os métodos de exclusão com azul de Tripan, redução do tetrazólio e ensaio de sobrevivência celular para avaliar os efeitos do composto sobre as células. As células tratadas com 0,1μM de β lapachona apresentaram menor citotoxicidade inicial, no tempo de 24h, enquanto aquelas submetidas a 1,0μM apresentaram menor viabilidade após 72h de tratamento. A citotoxicidade aumentou de acordo com o aumento da concentração e tempo de exposição. O menor IC50 (0,148μM) foi observado nas células tratadas por 72h. O crescimento celular após o tratamento foi menor grupo sob concentração de 1,0µl após 72h e o maior crescimento celular foi observado sob concentração de 0,1µl após 24h. Não houve diferença entre grupos quanto à proliferação celular após o tratamento tendo a fração de sobrevivência das células sido menor após 72h de exposição. Concluiu-se que β lapachona apresenta efeitos citotóxicos em células de osteossarcoma cultivadas in vitro.

Tumorous total endoprosthesis of hip joint is used for reconstruction of the limb affected by bone tumor and to regain its functnion. Longterm load conditions must be considered by the reconstruction and the joint mobility must be enabled. Suitability of the endoprosthesis depends on its construction considering shape, material and with this related mechanical properties. This thesis deals with creation of computational model and stress-strain analysis of tumorous total endoprosthesis of hip joint. There are two different types of endoprosthesis modeled in this thesis, each with three different length of resected bone replacement. Based on stress-strain analysis an assessment of possible limit states is made.

Les données de la littérature concernant la tolérance à long terme du traitement par hormone de croissance (GH) recombinante sont très réduites. L’objectif du travail rapporté dans cette thèse porte sur l’analyse de la morbidité chez 6874 patients de l’étude SAGhE traités en France dans le cadre d’un déficit idiopathique en GH ou d’une petite taille constitutionnelle, avec les 3 axes de travail suivants : Risque neurovasculaire : Utilisant des données de référence issues de 2 registres de population, nous avons montré une augmentation du risque d’accident vasculaire cérébral (SIR à 3.5 ou 4.4 selon le registre considéré), et plus particulièrement d’hémorragies sous-arachnoïdiennes (SIR 5.7 ou 6.3). Risque de diabète : Utilisant les prescriptions d’antidiabétiques fournies par le SNIIRAM au sein de notre cohorte, nous n’avons pas mis en évidence d’augmentation de la prévalence du diabète traité (SPR 1.0). Risque de cancer : En comparaison au registre de référence du réseau FRANCIM, il n’y a pas de différence significative dans le risque de survenue d’un cancer (SIR 0.7). En revanche, le risque de développer une tumeur osseuse est 3.5 fois plus élevé chez les sujets exposés à l’hormone de croissance dans l’enfance. Les évènements ont été identifiés à partir de trois sources : a) RNIPP et CépiDC pour la connaissance du statut vital et les causes de décès si le sujet est décédé, b) Questionnaire de santé envoyé aux sujets non décédés, c) Données SNIIRAM à partir d’une extraction spécifique basée sur les identifiants des sujets de notre cohorte, permettant d’obtenir les codes CIM-10 des déclarations d’Affection Longue Durée, les codages PMSI entre 2008 et 2010 correspondant aux hospitalisations, et les prescriptions d’antidiabétiques. / The literature is scarce regarding the long term effect of synthetic growth hormone (GH) treatment. The objective of this thesis was to analyse the morbidity of 6874 patients from the French SAGhE study treated by GH for short stature, focusing on three themes: Neurovascular risk: Using two population-based registries, we showed an increase in the risk of stroke (SIR 3.5 to 4.4 according the registry used), more specifically for the subarachnoid hemorrhage (SIR 5.7 or 6.3). Risk of diabetes : Using the antidiabetic drugs deliveries obtained from the French national health insurance database, no difference in the risk of treated diabetes was found (SPR 1.0). Risk of cancer : Compared with the French population-based registries of cancer, no significant difference in the risk of cancer was found (SIR 0.7), but the excess risk for bone tumor is 3.5 . Events were identified from three sources : a) Information on vital status collected from the Répertoire National d’Identification des Personnes Physiques and cause of death as indicated on death certificate, b) Health questionnaire sent to all living patients, c) Data extracted from the French national health insurance information, including the French hospital discharge database, also called Programme de Médicalisation des Systèmes d’Information from 2008 to December 2010, long-lasting affection statements, and antidiabetics drugs deliveries.