Submitted by Cátia Araújo (catia.araujo@unipampa.edu.br) on 2017-01-26T11:42:00Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Investigação experimental da relação entre temperatura e impedância elétrica de biomaterial.pdf: 3519740 bytes, checksum: 10be4a8a93b923ea3f3e7c97738e2769 (MD5) / Approved for entry into archive by Cátia Araújo (catia.araujo@unipampa.edu.br) on 2017-01-26T11:42:22Z (GMT) No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Investigação experimental da relação entre temperatura e impedância elétrica de biomaterial.pdf: 3519740 bytes, checksum: 10be4a8a93b923ea3f3e7c97738e2769 (MD5) / Made available in DSpace on 2017-01-26T11:42:22Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Investigação experimental da relação entre temperatura e impedância elétrica de biomaterial.pdf: 3519740 bytes, checksum: 10be4a8a93b923ea3f3e7c97738e2769 (MD5) Previous issue date: 2016-05-31 / O câncer é uma das principais causas de morte no mundo, matando mais de 8 milhões de pessoas por ano, isto faz com que essa doença se torne uma das piores de nossa geração e afetando milhares de famílias mundo afora. Nos países em desenvolvimento esses números se agravam, devido à detecção tardia da doença e a utilização de tratamentos convencionais, que muitas vezes são ineficazes e causam diversos efeitos colaterais. A ablação por radiofrequência (RFA) é um tratamento de combate ao câncer que utiliza energia térmica, gerada pela passagem de uma corrente elétrica a partir de um eletrodo inserido sobre o tumor, para matar as células cancerígenas. Este processo é minimamente invasivo e não apresenta efeitos colaterais significativos, fazendo com que o paciente possa ir para casa um dia após o procedimento. Visando ampliar e facilitar a utilização do RFA foi desenvolvido um software de modelagem matemática que utiliza elementos finitos para simular os resultados da ablação tumoral (RAFEM). Com o auxílio deste software os médicos serão capazes de otimizar os parâmetros do processo, tais como: voltagem, potência e o tempo de aplicação. Experimentos de RFA foram realizados para descobrir parâmetros que influenciam o processo, como a máxima temperatura atingida pelo eletrodo durante o processo. Descobriu-se que a temperatura na ponta do eletrodo ultrapassa os 100°C, causando a necrose do tecido nesta região. A relação entre a temperatura da superfície do eletrodo e tempo de aplicação obtido foi posteriormente utilizado como parâmetro de entrada no software para realizar as simulações. Os resultados obtidos foram validados através da comparação com os dados experimentais obtidos por Mulier et al. (2012). O software RAFEM mostrou-se eficaz na simulação dos efeitos causados pelo processo de RFA, tornando-se uma potencial ferramenta para auxiliar médicos e pacientes no tratamento de combate ao câncer. / Cancer is a leading cause of death worldwide, killing more than 8 million of people a year, making the cancer one of the worst of our generation and affecting thousands of families around the world. In developing countries these numbers become worse, since disease detection is later and only conventional treatments are used, which are often ineffective and cause many collateral effects. Radiofrequency ablation (RFA) is a treatment against cancer that applies thermal energy generated by passing electric current from an electrode inserted in the tumor to kill cancer cells. This procedure is minimally invasive and not presents significant collateral effects, so that the patient can go home one day after the treatment. Aiming to expand and facilitate the use of RFA, mathematical modeling software (RAFEM) that uses finite element method to simulate tumor ablation was developed. With the aid of this software doctors will be able to optimize the process parameters, such as voltage, power and application time. RFA experiments were performed to find out which parameters influence the process, such as the maximum temperature reached by the electrode during the process. It was found that the temperature at the electrode tip exceeds 100°C, causing tissue necrosis in the tip region. The relationship of the electrode surface temperature vs time was used as an input parameter of the software to perform the simulations. The results were validated by comparison with experimental data obtained by Mulier et al. (2015). The RAFEM software was proved to be effective in the simulation of the effects caused by the RFA process. This makes it to be a potential tool to assist doctors and patients in the treatment against cancer.

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La glycogénose de type I (GSDI) est une maladie génétique rare, due à une déficience en glucose-6 phosphatase (G6Pase), enzyme clé de la production endogène de glucose. En plus des hypoglycémies sévères, la perte de l'activité G6Pase conduit à l'accumulation de glycogène, mais aussi de lipides dans le foie et les reins. A long-terme, la plupart des patients développent des tumeurs hépatiques et une maladie rénale chronique (MRC).Le but de cette thèse a été de caractériser les mécanismes moléculaires impliqués dans la carcinogenèse hépatique et la MRC grâce à des modèles murins viables et uniques, avec une délétion de la G6Pase spécifiquement dans le foie ou les reins, reproduisant respectivement toutes les caractéristiques de la pathologie hépatique ou rénale.Au niveau du foie, notre étude a permis de mettre en évidence une reprogrammation métabolique « Warburg-like » très similaire à celle des cellules cancéreuses, associée à une perte des défenses cellulaires et des suppresseurs de tumeur. De plus, nous avons montré que les adénomes hépatocellulaires, se transformant ensuite en carcinomes, se développent en absence de fibrose, en accord avec l'absence d'activation des voies pro-fibrotiques. Au niveau des reins, l'étude de la MRC a mis en évidence le développement de kystes rénaux chez les souris atteintes de GSDI, observés aussi chez les patients à un stade avancé de la MRC. Finalement, une dernière étude portant sur l'activation de l'oxydation des lipides, par un traitement des souris au fénofibrate, a permis de suggérer le rôle délétère de l'accumulation des lipides dans le développement des pathologies hépatique et rénale / Glycogen storage disease type I (GSDI) is a rare genetic disease, due to a deficiency in glucose-6 phosphatase (G6Pase), a key enzyme in the endogenous glucose production. Besides severe hypoglycemia, the loss of G6Pase leads to the accumulation of glycogen and lipids in the liver and kidneys. On the long term, most patients develop hepatic tumors and chronic kidney disease (CKD).The goal of this thesis was to characterize the molecular mechanisms involved in hepatic carcinogenesis and CKD, thanks to viable and unique mouse models with specific deletion of G6Pase in the liver or kidneys, which exhibit all hallmarks of hepatic and renal pathologies, respectively.On a hepatic level, our study allowed us to highlight a « Warburg-like » metabolic reprogramming, very similar to what is observed in cancer cells, associated with a loss of cellular defenses and tumor suppressors. Furthermore, we showed that formation of hepatocellular adenoma, which transform later in carcinoma, occurs in the absence of liver fibrosis, due to the fact that pro-fibrotic pathways are not activated. In the kidneys, the study of CKD highlighted the development of renal cysts in mice with GSDI, as well as in the patients presenting an advanced stage of CKD. Finally, the last study on the activation of the oxidation of lipids, by treating the mice with fenofibrate, allowed us to suggest a deleterious role of lipid accumulation in the development of the hepatic and renal pathologies