Made available in DSpace on 2014-06-11T19:23:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-03-02Bitstream added on 2014-06-13T20:29:55Z : No. of bitstreams: 1 cremonini_ccr_me_botfm.pdf: 1144679 bytes, checksum: bf9c1e1e39c197477cae8519b0e360ce (MD5) / Fundação Pio Xii - Barretos / Avaliar a ocorrência e a gravidade das reações adversas agudas (RAA) com o uso do meio de contraste iodado iônico e não-iônico nos pacientes submetidos ao exame de tomografia computadorizada (TC) em hospital nacional terciário oncológico e avaliar neoplasia como possível risco para RAA. Secundariamente, avaliar o impacto do uso seletivo do meio de contraste iodado nos custos. Pacientes submetidos à TC com contraste iodado entre outubro de 2007 e agosto de 2008 foram avaliados quanto à ocorrência e à gravidade das reações adversas agudas aos meios de contrastes iônicos e nãoiônicos. As reações foram categorizadas em leve, moderada ou grave de acordo com o tipo dos sinais e sintomas e classificadas como agudas pelo tempo de ocorrência, desde o momento da injeção até 30 minutos após. Os testes do quiquadrado e exato de Fisher foram utilizados para análise estatística da ocorrência de RAA em relação às variáveis de gênero e idade. O estudo foi aprovado pelo Comitê de Ética local e o Termo de Consentimento Livre Esclarecido foi obtido. Houve 78 RAA ao contraste iodado iônico e 11 ao não-iônico, com uma ocorrência global de 3,3% (78/2.339) e 0,5% (11/2.216), respectivamente. A maioria das reações foi classificada como leve em ambos os grupos, representando 91% (71) no grupo iônico e 81,8% (9) no grupo não-iônico. As demais reações foram do tipo moderada não havendo nenhuma reação grave. Em relação ao início das RAA, 71% e 73% (iônico e não-iônico) ocorreram nos primeiros 5 minutos. A freqüência de RAA no grupo em que recebeu contraste iônico foi maior no sexo feminino (p < 0,001). No grupo não-iônico não houve diferença estatisticamente significativa entre os sexos (p = 1,0). Não houve associação entre a presença de reação aguda e as faixas... / To evaluate the occurrence and severity of acute adverse reactions (AAR) to iodinated ionic and non-ionic contrast media in patients undergoing computerized tomography (CT) at a national tertiary cancer hospital and to evaluate neoplasm as a possible risk for AAR. Secondly, to assess the impact of selective use of iodinated contrast agent costs. Patients who underwent contrast-enhanced CT between October 2007 and August 2008 were evaluated for the presence and severity of acute adverse reactions to ionic and non-ionic contrast media. The reactions were categorized as mild, moderate or severe according to the type of signs and symptoms and classified as acute by the time of occurrence, from the time of the injection up to 30 minutes afterwards. The chi-square and Fisher’s exact were used for statistical analysis of the occurrence of AAR for the variables of gender and age. The study was approved by the local Ethics Committee and informed consent was obtained. There were 78 AAR to ionic iodinated contrast and 11 to non-ionic, with an overall occurrence of 3.3% (78/2339) and 0.5% (11/2216), respectively. Most reactions were classified as mild in both groups, representing 91% (71) in the ionic group and 81.8% (9) in the non-ionic group. All other reactions were moderate and there were no severe reactions. Regarding onset of AAR, 71% and 73% (ionic and non-ionic group) occurred in the first five minutes. The occurrence of AAR in the group who received ionic contrast was higher in females (p <0.001). As for the non-ionic group, there was no significant statistical difference between genders (p = 1.0). There was no association between the presence of acute reaction and the age groups of the population in the ionic contrast group. For the non-ionic group, no statistical analysis was performed as the sample was deemed reduced. Among... (Complete abstract click electronic access below)

Orientador: Euclides Timótio da Rocha / Banca: Fabiano Rubião Lucchesi / Banca: Jorge Elias Junior / Resumo: Avaliar a ocorrência e a gravidade das reações adversas agudas (RAA) com o uso do meio de contraste iodado iônico e não-iônico nos pacientes submetidos ao exame de tomografia computadorizada (TC) em hospital nacional terciário oncológico e avaliar neoplasia como possível risco para RAA. Secundariamente, avaliar o impacto do uso seletivo do meio de contraste iodado nos custos. Pacientes submetidos à TC com contraste iodado entre outubro de 2007 e agosto de 2008 foram avaliados quanto à ocorrência e à gravidade das reações adversas agudas aos meios de contrastes iônicos e nãoiônicos. As reações foram categorizadas em leve, moderada ou grave de acordo com o tipo dos sinais e sintomas e classificadas como agudas pelo tempo de ocorrência, desde o momento da injeção até 30 minutos após. Os testes do quiquadrado e exato de Fisher foram utilizados para análise estatística da ocorrência de RAA em relação às variáveis de gênero e idade. O estudo foi aprovado pelo Comitê de Ética local e o Termo de Consentimento Livre Esclarecido foi obtido. Houve 78 RAA ao contraste iodado iônico e 11 ao não-iônico, com uma ocorrência global de 3,3% (78/2.339) e 0,5% (11/2.216), respectivamente. A maioria das reações foi classificada como leve em ambos os grupos, representando 91% (71) no grupo iônico e 81,8% (9) no grupo não-iônico. As demais reações foram do tipo moderada não havendo nenhuma reação grave. Em relação ao início das RAA, 71% e 73% (iônico e não-iônico) ocorreram nos primeiros 5 minutos. A freqüência de RAA no grupo em que recebeu contraste iônico foi maior no sexo feminino (p < 0,001). No grupo não-iônico não houve diferença estatisticamente significativa entre os sexos (p = 1,0). Não houve associação entre a presença de reação aguda e as faixas... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: To evaluate the occurrence and severity of acute adverse reactions (AAR) to iodinated ionic and non-ionic contrast media in patients undergoing computerized tomography (CT) at a national tertiary cancer hospital and to evaluate neoplasm as a possible risk for AAR. Secondly, to assess the impact of selective use of iodinated contrast agent costs. Patients who underwent contrast-enhanced CT between October 2007 and August 2008 were evaluated for the presence and severity of acute adverse reactions to ionic and non-ionic contrast media. The reactions were categorized as mild, moderate or severe according to the type of signs and symptoms and classified as acute by the time of occurrence, from the time of the injection up to 30 minutes afterwards. The chi-square and Fisher's exact were used for statistical analysis of the occurrence of AAR for the variables of gender and age. The study was approved by the local Ethics Committee and informed consent was obtained. There were 78 AAR to ionic iodinated contrast and 11 to non-ionic, with an overall occurrence of 3.3% (78/2339) and 0.5% (11/2216), respectively. Most reactions were classified as mild in both groups, representing 91% (71) in the ionic group and 81.8% (9) in the non-ionic group. All other reactions were moderate and there were no severe reactions. Regarding onset of AAR, 71% and 73% (ionic and non-ionic group) occurred in the first five minutes. The occurrence of AAR in the group who received ionic contrast was higher in females (p <0.001). As for the non-ionic group, there was no significant statistical difference between genders (p = 1.0). There was no association between the presence of acute reaction and the age groups of the population in the ionic contrast group. For the non-ionic group, no statistical analysis was performed as the sample was deemed reduced. Among... (Complete abstract click electronic access below) / Mestre

L’iode est un composant essentiel aux hormones thyroïdiennes. Les cellules thyroïdiennes captent l’iode circulant et le concentrent vers le colloïde. Il est alors incorporé à la thyroglobuline, protéine précurseur des hormones, par un mécanisme d’organification. La capacité de captation de l’iode par la thyroïde est finement régulée notamment par la « Thyroid Stimulating Hormone » (TSH) mais aussi l’iode circulant. En effet, en cas d’une élévation de l’iode circulant, la thyroïde déclenche un mécanisme d’autorégulation appelée l’effet Wolff-Chaikoff. Ce phénomène se traduit par une limitation transitoire de production des hormones thyroïdiennes qui s’accompagne notamment d’une diminution de l’expression du NIS (Natrium Iodide Symporter), la protéine responsable du transport actif de l’iode dans la thyroïde. Dans cette étude, des approches omiques globales ont été mises à profit pour étudier cette régulation dans le contexte de l’administration d’un produit iodé et de souris invalidées pour un gène codant pour un transporteur de monocarboxylate exprimé dans la thyroïde. Dans la première partie, l’effet des agents de contraste iodés (ICA), couramment utilisés en imagerie médicale, a été étudié. L’administration de ces agents entraine une réduction de la captation de l’iode souvent expliquée par un effet Wolff-Chaikoff associé à un potentiel relargage d’iode. Par une approche de protéomique quantitative global, le protéome de thyroïde de souris, après administration d’ICA, a été comparé au protéome en conditions d’excès d’iode. Après un traitement des données et une analyse bioinformatique, nos résultats mettent en évidence l’existence de peu de mécanismes en commun induits par l’iode et les ICA mais cependant de plus importantes variations d’expression de protéines sont déclenchées uniquement par les ICA. Cette étude est en accord avec une durée plus importante de l’inhibition de la fonction après une administration d’ICA comparée à celle de l’iode stable. Dans la deuxième partie, le rôle de SLC5A8 dans la fonction thyroïdienne et les mécanismes sous-jacents à l’effet Wolff-Chaikoff ont été étudiés chez des souris invalidées pour le gène Slc5a8 (Solute carrier family 5 number 8) et des souris non mutées. SLC5A8 est une protéine membranaire identifiée au laboratoire et exprimée dans la membrane apicale du thyrocyte. Cette protéine catalyse un transport de monocarboxylate dans différents organes mais son rôle dans la thyroïde demeure non élucidé. L’invalidation n’entraine pas d’effet majeur sur la fonction thyroïdienne. En mettant à profit une approche multiomique comparative, combinant la transcriptomique, la protéomique et la métabolomique, les effets de cette invalidation et/ou de la régulation par l’iode de la thyroïde ont été explorés. Le traitement des data révèle de nombreuses voies activées dans les différentes conditions avec des mécanismes de compensation de l’effet de l’invalidation par l’administration d’iode. Les résultats indiquent que la perte de fonction de SLC5A8 affecte l’organification et/ou maturation de la thyroglobuline, le contrôle du stress oxydatif et de l’iode libre dans la thyroïde. / Iodine is an essential component of thyroid hormones. Thyroid cells capture the circulating iodine and concentrate it in the colloid. Then, it is incorporated into the thyroglobulin, the hormone precursor protein, by an organification mechanism. The iodine uptake capacity by the thyroid is finely regulated, not only by the Thyroid Stimulating Hormone (TSH) but also by circulating iodine. Indeed, in case of high circulating iodine, the thyroid actives a self-regulating mechanism called the Wolff-Chaikoff effect. This phenomenon results in a transient limitation of thyroid hormone production which is accompanied by a decrease in the expression of NIS (Natrium Iodide Symporter), the protein that is responsible for the active transport of iodine in the thyroid. In this study, global omics approaches were used to study this regulation in the context of the administration of an iodized product and mice invalidated for a gene coding a monocarboxylate transporter expressed in the thyroid. In the first part, the effect of iodinated contrast media (ICM), commonly used in medical imaging, has been studied. The administration of these agents leads to a reduction in the uptake of iodine often explained by a Wolff-Chaikoff effect associated with an iodine release potential. Through an overall quantitative proteomic approach, the mouse thyroid proteome, after administration of ICM, was compared to the proteome under conditions of excess iodine. In the second part, the role of SLC5A8 in thyroid function and the mechanisms underlying the Wolff-Chaikoff effect were studied in mice invalidated for the Slc5a8 gene (Solute carrier family 5 number 8) and wild type mice. SLC5A8 is a membrane protein identified in the laboratory and expressed in the thyrocyte apical membrane. This protein catalyzes the monocarboxylates transport in different organs but its role in the thyroid remains unsolved. Invalidation does not have a major effect on thyroid function. By using a comparative multiomic approach which combines transcriptomics, proteomics and metabolomics, the effects of this invalidation and / or regulation by iodine in the thyroid have been explored. Data processing reveals many pathways activated under different conditions with mechanisms to compensate for the effect of invalidation by the administration of iodine. The results indicate that the loss of SLC5A8 function affects the organization and / or maturation of thyroglobulin, the control of oxidative stress and of free iodine in the thyroid.