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Made available in DSpace on 2016-01-13T13:28:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-07-31. Added 1 bitstream(s) on 2016-01-13T13:33:48Z : No. of bitstreams: 1 000855025.pdf: 4770813 bytes, checksum: 8ec3a1e8929ec7fdd27e356ee994e36a (MD5) / Fundação para o Desenvolvimento da UNESP (FUNDUNESP) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A tiouréia (TU) é um composto orgânico, frequentemente utilizado no tratamento de hipertireoidismo. O presente estudo teve como objetivo avaliar os efeitos da tiouréia sobre o crescimento e desenvolvimento de rãs-touro nas fases pré e pósmetamórficas, por meio da deposição de nutrientes corporais, desempenho e análises morfológicas da glândula tireóide, fígado, rins, baço e gônadas. Este trabalho foi dividido em duas fases. Na primeira fase, 7200 girinos foram distribuídos em 12 caixas (500L), em delineamento inteiramente casualizado, e alimentados por 30 dias com ração contendo 0 (T0), 3 (T1), 5 (T2) e 7 mg TU/kg de ração (T3) e três repetições. Na segunda fase, 696 imagos originários da primeira fase foram alojados em 12 baias de 3 m2. A deposição de nutrientes corporais nos tratamentos avaliados encontra-se de acordo com o crescimento normal de girinos de rã-touro. O uso de 7 mg de TU/kg de ração proporcionou o melhor crescimento dos girinos. No tratamento T0, observou-se o desenvolvimento normal da glândula tireóide e nos demais tratamentos, observou-se a hipertrofia da glândula tireóide em função, principalmente, da hipertrofia e hiperplasia das células foliculares. Na segunda fase, observaram-se diversas alterações celulares no fígado, rim e baço. Não foram observados danos celulares ou estruturais nas gônadas. A administração de 7 mg TU/kg na alimentação dos girinos resultou na obtenção de imagos maiores na recria e ao final do período de engorda. O uso de tiouréia durante a fase de girinagem, nas dosagens utilizadas, não causou toxicidade ou qualquer alteração gonadal em animais adultos / Thiourea (TU) is an organic compound often used for treatment of hyperthyroidism. This study aimed to evaluate the effects of thiourea on growth and development of bullfrogs on pre and post-metamorphic phases, by determining the deposition of body nutrients, performance and histological analysis of the thyroid gland, liver, kidneys, spleen and gonads. This work was divided into two phases. In the first phase, 7200 tadpoles were distributed in 12 boxes (500L) in a completely randomized design, and fed for 30 days with feed containing 0 (T0), 3 (T1), 5 (T2), 7 mg TU/kg of feed (T3), and three replicates. In the second phase, 696 juveniles originating from the first phase were housed in 12 pens of 3 m2. The body nutrients deposition obtained is in accordance with the normal growth of bullfrog tadpoles. The use 7 mg TU/kg of feed provided the best growth of the tadpoles. In treatment T0, we observed the normal development of the thyroid gland and in the other treatments there was hypertrophy of the thyroid gland due mainly hypertrophy and hyperplasia of follicular cells. In the second phase, we observed cellular changes in liver, kidney and spleen. In gonads we weren't observed any cellular or structural damage on gonads.The administration of 7 mg TU/kg in the bullfrog tadpoles feed resulted in larger animals on the growing phase and at the end of it. The use of thiourea during tadpole's phase in doses used in this study didn't cause toxicity or gonadal changes in adult animal / FUNDUNESP: 0195/005/14

Made available in DSpace on 2016-09-27T13:40:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-05-27. Added 1 bitstream(s) on 2016-09-27T13:45:15Z : No. of bitstreams: 1 000869033_20170527.pdf: 824646 bytes, checksum: 00f5f8bbdd7abcbefcbd2d042d519568 (MD5) Bitstreams deleted on 2017-06-02T11:56:26Z: 000869033_20170527.pdf,. Added 1 bitstream(s) on 2017-06-02T11:57:14Z : No. of bitstreams: 1 000869033.pdf: 3301498 bytes, checksum: de14b09badf78ded8a950b747525f42b (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O câncer de tireoide (CT) é a neoplasia mais comum do sistema endócrino. O carcinoma papilífero da tireoide (CPT) compreende 80-85% dos casos, seguido dos carcinomas foliculares (CFT), pouco diferenciados (CPDT) e anáplasicos (CAT). O diagnóstico dos CT, principalmente nos casos bem diferenciados, ainda é um desafio devido a semelhanças morfológicas compartilhadas por esses tumores e lesões benignas (LBT). O objetivo desse estudo foi avaliar o perfil de metilação do DNA para identificar marcadores epigenéticos envolvidos no desenvolvimento das lesões benignas e dos diferentes subtipos histológicos de carcinomas. Além disso, buscou-se identificar marcadores prognósticos nos CT. Foram incluídos nesse estudo 17 lesões benignas da tireoide (8 adenomas, 6 bócios tireoideanos e 3 tireoidites), 60 CPT, 8 CFT, 2 carcinomas de células de Hurthle (CCH), 1 CPDT e 3 CAT, além de 50 tecidos não neoplásicos (TN) obtidos dos pacientes que tiveram CPT. As análises de metilação diferencial foram realizadas utilizando a plataforma microarray Infinium® Human Methylation450 BeadChip (Illumina). Na primeira etapa do estudo, os resultados obtidos de sondas diferencialmente metiladas foram utilizados na construção de um algoritmo útil como classificador diagnóstico. Na segunda etapa, o perfil de metilação do DNA das lesões benignas e dos diferentes subtipos tumorais foi comparado aos dados de tecidos não neoplásicos. Somente sondas significativamente alteradas no presente estudo e aquelas confirmadas no GEO (Gene Expression Omnibus) foram selecionadas para a construção de algoritmos. Foram delineados três algoritmos diagnósticos baseados na metilação diferencial de nove sondas selecionadas a partir de área abaixo da curva de 0,75 para o classificador de LBT e 0,90 para os classificadores CFT e CPT além de análise multivariada. Foram também aplicados métodos lineares de classificação. A aplicação do algoritmo... / Thyroid cancer (TC) is the most prevalent type of endocrine cancer. Papillary thyroid carcinoma (PTC) comprises 80-85% of the diagnosed thyroid cancers, followed by follicular (FTC), poorly differentiated (PDTC) and anaplastic carcinomas (ATC). Diagnosis of thyroid carcinomas, especially of well-differentiated carcinomas is a challenge due to morphological similarities between these tumors and benign lesions. The aim of this study was to evaluate the methylation profile to identify diagnostic markers involved in benign lesions and in different histological subtypes of carcinomas. Moreover, a search for reliable molecular prognostic markers was also performed in TC. The study included 17 benign lesions (8 adenomas, 6 goiters and 3 thyroiditis), 60 PTCs, 8 FTCs, 2 Hürthle cell carcinomas (HCC), 1 PDTC and 3 ATC, as well as 50 non-neoplastic tissues (NT) obtained from patients who had PTC. Differential methylation analyzes were performed using the Infinium® Human Methylation450 BeadChip microarray (Illumina). In the first stage of the study, the results of differentially methylated probes were used in the development of diagnostic classifier algorithm. In second step, the methylation profile of benign lesions and tumor subtypes was compared to data from non-neoplastic tissues. Only probes significantly altered in the current study and those confirmed by GEO data (Gene Expression Omnibus) were selected for the development of the algorithms. Three diagnostic algorithms were developed based on differential methylation of nine probes selected from area under the curve of 0.75 for BTL classifier and 0.90 for FTC and PTC classifiers and multivariate analysis. It was also applied linear classification methods. Application of the algorithm diagnosis allowed the correct classification of non-neoplastic tissues, benign and malignant lesions (sensitivity: 91.9% and specificity: 76.5%). The same strategy was performed using the GEO database...

Orientador: Silvia Regina Rogatto / Banca: Patricia Pintor dos Reis / Banca: Miriam Galvonas Jasiulionis / Banca: Janete Maria Cerutti / Banca: Sandra A. Drigo Linde / Resumo: O câncer de tireoide (CT) é a neoplasia mais comum do sistema endócrino. O carcinoma papilífero da tireoide (CPT) compreende 80-85% dos casos, seguido dos carcinomas foliculares (CFT), pouco diferenciados (CPDT) e anáplasicos (CAT). O diagnóstico dos CT, principalmente nos casos bem diferenciados, ainda é um desafio devido a semelhanças morfológicas compartilhadas por esses tumores e lesões benignas (LBT). O objetivo desse estudo foi avaliar o perfil de metilação do DNA para identificar marcadores epigenéticos envolvidos no desenvolvimento das lesões benignas e dos diferentes subtipos histológicos de carcinomas. Além disso, buscou-se identificar marcadores prognósticos nos CT. Foram incluídos nesse estudo 17 lesões benignas da tireoide (8 adenomas, 6 bócios tireoideanos e 3 tireoidites), 60 CPT, 8 CFT, 2 carcinomas de células de Hurthle (CCH), 1 CPDT e 3 CAT, além de 50 tecidos não neoplásicos (TN) obtidos dos pacientes que tiveram CPT. As análises de metilação diferencial foram realizadas utilizando a plataforma microarray Infinium® Human Methylation450 BeadChip (Illumina). Na primeira etapa do estudo, os resultados obtidos de sondas diferencialmente metiladas foram utilizados na construção de um algoritmo útil como classificador diagnóstico. Na segunda etapa, o perfil de metilação do DNA das lesões benignas e dos diferentes subtipos tumorais foi comparado aos dados de tecidos não neoplásicos. Somente sondas significativamente alteradas no presente estudo e aquelas confirmadas no GEO (Gene Expression Omnibus) foram selecionadas para a construção de algoritmos. Foram delineados três algoritmos diagnósticos baseados na metilação diferencial de nove sondas selecionadas a partir de área abaixo da curva de 0,75 para o classificador de LBT e 0,90 para os classificadores CFT e CPT além de análise multivariada. Foram também aplicados métodos lineares de classificação. A aplicação do algoritmo... / Abstract: Thyroid cancer (TC) is the most prevalent type of endocrine cancer. Papillary thyroid carcinoma (PTC) comprises 80-85% of the diagnosed thyroid cancers, followed by follicular (FTC), poorly differentiated (PDTC) and anaplastic carcinomas (ATC). Diagnosis of thyroid carcinomas, especially of well-differentiated carcinomas is a challenge due to morphological similarities between these tumors and benign lesions. The aim of this study was to evaluate the methylation profile to identify diagnostic markers involved in benign lesions and in different histological subtypes of carcinomas. Moreover, a search for reliable molecular prognostic markers was also performed in TC. The study included 17 benign lesions (8 adenomas, 6 goiters and 3 thyroiditis), 60 PTCs, 8 FTCs, 2 Hürthle cell carcinomas (HCC), 1 PDTC and 3 ATC, as well as 50 non-neoplastic tissues (NT) obtained from patients who had PTC. Differential methylation analyzes were performed using the Infinium® Human Methylation450 BeadChip microarray (Illumina). In the first stage of the study, the results of differentially methylated probes were used in the development of diagnostic classifier algorithm. In second step, the methylation profile of benign lesions and tumor subtypes was compared to data from non-neoplastic tissues. Only probes significantly altered in the current study and those confirmed by GEO data (Gene Expression Omnibus) were selected for the development of the algorithms. Three diagnostic algorithms were developed based on differential methylation of nine probes selected from area under the curve of 0.75 for BTL classifier and 0.90 for FTC and PTC classifiers and multivariate analysis. It was also applied linear classification methods. Application of the algorithm diagnosis allowed the correct classification of non-neoplastic tissues, benign and malignant lesions (sensitivity: 91.9% and specificity: 76.5%). The same strategy was performed using the GEO database... / Doutor

Orientadores: Denise Engelbrecht Zantut Wittmann, Sarah Monte Alegre / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-28T02:28:01Z (GMT). No. of bitstreams: 1 Botelho_IlkaMaraBorges_M.pdf: 1340793 bytes, checksum: 6ef5a41b67a7eddca52fc55dea2f96d4 (MD5) Previous issue date: 2014 / Resumo: Introdução: Vitamina D tem sido apontada como importante regulador da resposta imune. Estudos tem demonstrado haver relação entre insuficiência de vitamina D e presença de doenças autoimunes como Tireoidite de Hashimoto (TH). É possível que o processo autoimune na TH seja inibido em diferentes estágios pela vitamina D em sua forma ativa. Nossos objetivos foram estudar a prevalência de insuficiência de vitamina D e a relação de suas concentrações séricas com marcadores de função e autoimunidade tireoideana. Material e Métodos: Amostras de sangue foram coletadas de 54 pacientes com TH e 54 indivíduos saudáveis sem diagnóstico de TH com idade entre 18 e 75 anos. Foram realizadas dosagens séricas de vitamina D (25OHD), TSH, T4 livre, cálcio, fósforo, paratormônio (PTH), anticorpos anti-tireoperoxidase (AcTPO), anti-tireoglobulina (AcTG) e anti-receptor de TSH (TRAb). Volume tireoideano foi estimado por ultrassonografia. Foram coletados dados demográficos, de peso, altura, índice de massa corporal (IMC) e tempo de diagnóstico. Pacientes e indivíduos do grupo de controle foram pareados por idade e sexo. O nível de significância estatística adotado foi 5%. Resultados: Prevalência de insuficiência de vitamina D foi encontrada em 68.5% dos pacientes e em 38.9% dos indivíduos do grupo de controle (p =0,002). Houve uma correlação positiva entre níveis de AcTPO e maior volumetireoideano nos pacientes (r = 0,319; p= 0.019). Não houve correlação entre concentração de vitamina D, TSH, T4livre,TRAb, AcTGe volume tireoideano. Conclusões: Demonstramosmaior prevalência deinsuficiência de vitamina Dem pacientescom tireoidite de Hashimotoem relaçãoa indivíduos de um grupo controlesaudável, não havendo correlaçãocom o estado hormnal tireoideanooumarcadores séricos deautoimunidadeda tireóide.Por sua vez, maior volume da tireóidese associou a maior grau de infiltração inflamatóriaautoimune,refletido pelacorrelaçãocom maiores concentrações AcTPO / Abstract: Introduction: Vitamin D has been pointed out as an important immune response regulator. Studies have shown a relationship between vitamin D insufficiency and the presence of autoimmune diseases such as Hashimoto's Thyroiditis (HT). It's possible that the autoimmune process in HT is inhibited in its different stages by vitamin D on its active form .Our aims were to study the prevalence of vitamin D insufficiency and relationship of the serum concentrations with thyroid function and autoimmunity markers. Material and Methods: Blood samples were collected from 54 patients with HT and 54 healthy individuals without a diagnosis of HT, aged 18 to 75 years. We conducted serum 25OH vitamin D, TSH, free T4, calcium, phosphorus, PTH, TPOAb, TgAb and TRAb. Thyroid volume was estimated by ultrasound. Data on demographic, weight, height, body mass index and time since diagnosis were collected. Patients and control subjects were matched by sexand age. The significance level for statistical analysis was 5%. Results: Prevalence of vitamin D insufficiency was found in 68.5% of patients and in 38.9% of subjects in the control group (p= 0.002). There was a positive correlation between TPOAb and volume in patients (p= 0.019). There was no correlation between vitamin D concentration and thyroid volume, TRAb, TgAb, TSH or free T4. Conclusions: We demonstrated a higher prevalence of vitamin D insufficiency in patients with Hashimoto's thyroiditis compared to individuals of a healthy control group, no correlation with thyroid state hormonal or serum markers of thyroid autoimmunity. In turn, greater thyroid volume was associated with a higher degree of autoimmune inflammatory infiltration, reflected by the correlation with higher concentrations AcTPO / Mestrado / Clinica Medica / Mestra em Ciências

Orientador: Marta Verardino De Stéfani / Banca: Breno Henrique Caneguim / Banca: Cláudia Maris Ferreira Mostério / Banca: Cláudio Ângelo Agostinho / Banca: João Batista Kochenborger Fernandes / Resumo: A tiouréia (TU) é um composto orgânico, frequentemente utilizado no tratamento de hipertireoidismo. O presente estudo teve como objetivo avaliar os efeitos da tiouréia sobre o crescimento e desenvolvimento de rãs-touro nas fases pré e pósmetamórficas, por meio da deposição de nutrientes corporais, desempenho e análises morfológicas da glândula tireóide, fígado, rins, baço e gônadas. Este trabalho foi dividido em duas fases. Na primeira fase, 7200 girinos foram distribuídos em 12 caixas (500L), em delineamento inteiramente casualizado, e alimentados por 30 dias com ração contendo 0 (T0), 3 (T1), 5 (T2) e 7 mg TU/kg de ração (T3) e três repetições. Na segunda fase, 696 imagos originários da primeira fase foram alojados em 12 baias de 3 m2. A deposição de nutrientes corporais nos tratamentos avaliados encontra-se de acordo com o crescimento normal de girinos de rã-touro. O uso de 7 mg de TU/kg de ração proporcionou o melhor crescimento dos girinos. No tratamento T0, observou-se o desenvolvimento normal da glândula tireóide e nos demais tratamentos, observou-se a hipertrofia da glândula tireóide em função, principalmente, da hipertrofia e hiperplasia das células foliculares. Na segunda fase, observaram-se diversas alterações celulares no fígado, rim e baço. Não foram observados danos celulares ou estruturais nas gônadas. A administração de 7 mg TU/kg na alimentação dos girinos resultou na obtenção de imagos maiores na recria e ao final do período de engorda. O uso de tiouréia durante a fase de girinagem, nas dosagens utilizadas, não causou toxicidade ou qualquer alteração gonadal em animais adultos / Abstract: Thiourea (TU) is an organic compound often used for treatment of hyperthyroidism. This study aimed to evaluate the effects of thiourea on growth and development of bullfrogs on pre and post-metamorphic phases, by determining the deposition of body nutrients, performance and histological analysis of the thyroid gland, liver, kidneys, spleen and gonads. This work was divided into two phases. In the first phase, 7200 tadpoles were distributed in 12 boxes (500L) in a completely randomized design, and fed for 30 days with feed containing 0 (T0), 3 (T1), 5 (T2), 7 mg TU/kg of feed (T3), and three replicates. In the second phase, 696 juveniles originating from the first phase were housed in 12 pens of 3 m2. The body nutrients deposition obtained is in accordance with the normal growth of bullfrog tadpoles. The use 7 mg TU/kg of feed provided the best growth of the tadpoles. In treatment T0, we observed the normal development of the thyroid gland and in the other treatments there was hypertrophy of the thyroid gland due mainly hypertrophy and hyperplasia of follicular cells. In the second phase, we observed cellular changes in liver, kidney and spleen. In gonads we weren't observed any cellular or structural damage on gonads.The administration of 7 mg TU/kg in the bullfrog tadpoles feed resulted in larger animals on the growing phase and at the end of it. The use of thiourea during tadpole's phase in doses used in this study didn't cause toxicity or gonadal changes in adult animal / Doutor

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24488号 / 医博第4930号 / 新制||医||1063(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 花川 隆, 教授 渡邉 大, 教授 村井 俊哉 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Oxygen consumption can most readily be related to wet weight. However, the weight of a tadpole increases so long as it is feeding, then decreases during final non-feeding stages. Oxygen uptake may also be related to dry weight, but dry weight increases significantly from early tadpole stages to adult (Funkhouser and Mills, in press). There is change in one factor at the same time the change in the the other factor is in the opposite direction. Total nitrogen content may be used as an index of the metabolizing tissue, but is subject to the same criticism as dry weight (Moore, 1964). Ideally, the animal's respiration should be related to as many criteria as possible. The pattern of thyroid activity during amphibian metamorphosis has been described by a number of investigators using a variety of methods. Histological criteria for the functional activity of the thyroid glad include epithelial cell height, the number of epithelial cells in serial sections of gland, "vacuolization" of the colloid, the number of secretion droplets present in the follicle, the number of mitochondria, and changes in the size of the Golgi apparatus. Not all of these criteria are considered to be of equal validity (Etkin, 1930; Gorbman and Bern, 1962). The amount of iodine accumulate in the follicle has been used as an index of the activity of the gland. Kaye (1961) using radioactive iodine (I131) and radioautography found a 12% increase in I131 accumulation during early metamorphic stages, and a 43% increase during or near the later stages of metamorphosis. The rate of development is significantly increased in normal tadpoles immersed or injected with thyroxine. Kollros (1961) was able to reproduce the normal metamorphic pattern in thyroidectomized Rana pipiens with gradually increasing concentrations of T4. All of these studies indicate that during normal metamorphosis there is a gradual increase in the concentration of thyroid hormone reaching a climax in the last stages and dropping metamorphosis has been assumed to increase because the increase in thyroxine levels accompanying metamorphosis in amphibia would be sufficient to cause a marked increase in metabolic rate in mammals. The latent period between exposure to thyroxine and maximum calorigenic effect has been described for many animals, In man this period is about two weeks (Guyton, 1964). The present study was designed to show that the small increase in oxygen uptake observed in a number of amphibians during metamorphic climax (Table II) is the result of the increase in thyroxine levels in the immediately preceding stages. Oxygen consumption of Hyla regilla was measured from hatching through metamorphosis and correlated with activity of the thyroid gland

An isotopic equilibrium method was employed, based on the chronic feeding of an 125I-labeled diet of known specific activity, to determine the distribution and quantitation of endogenously labeled iodine-containing compounds in the female rat at various periods during gestation and post-parturition. A decrease was associated with gestation in the total iodine, which was significant in all extrathyroidal tissues except the brain and muscle, and a fall in thyroxine concentration which was significant in all extrathyroidal tissues except the heart. The triiodothyronine level decreased from the control values in gestation but not as consistently. There was also a significant decrease in the total iodine and thyroxine in the plasma at this time. Concomitant with this fall in plasma iodinated compounds was a significant increase in the free thyroxine percentage. These changes were paralleled by an increased renal and fecal excretion of iodide. Total iodine, T4, T3, MIT and DIT all increased in the thyroid gland; however, these changes in the latter 3 compounds were statistically insignificant. These findings indicate that during gestation the body stores of iodinated compounds become depleted with the exception of the thyroid, which shows a greater than normal absolute concentration. A postulated increased T4 turnover rate, which could be due to a high maternal deiodination or placental thyroxine permeability and fetal deiodination, could account for the above observations. Following parturition, there was an excessive rebound of the iodinated compounds over an approximate 4 week period towards control values. In the lactating rat, these compounds remained below non-lactating levels until after weaning and then returned to the control levels rapidly. The total iodine levels in the plasma were extremely low during lactation and rose slowly as milk secretion decreased. These postpartum observations were for the most part statistically insignificant although they revealed a definite trend. These low levels of total iodine could be explained by the secretion of iodide by the mammary gland during lactation. There was an increased accumulation of total iodine, T4, T3, MIT and DIT by the thyroid gland during lactation. These data suggest an adaptation of the thyroid to the increased need for T4 to support or control the mammary glands.

Certain aspects of the biochemistry of the thyroid gland have been studied. The techniques of filter paper chromatography and radioautography were used to separate and identify the iodine-containing amino acids of the gland, and were modified somewhat, in order to obtain reliable results. Although a series of preliminary experiments were performed with the thyroid glands of rats in vivo, the main part of this work made use of the in vitro technique. Surviving tissue slices were incubated in the presence of the radioactive tracer, iodine131. Evidence was obtained which indicated that at least two of the amino acids found "free" in the thyroid gland were degraded by the gland to inorganic iodide. The mechanism of action of a number of thyroid gland inhibitors was investigated. It was found that all but two of the materials studied led to the formation in the tissue slices of unidentified iodine—containing materials with the simultaneous disappearence of inorganic iodide. Hence, at least a part of the goitrogenic nature of these inhibitors would appear to be due to the "removal" of iodide. It was found chat one portion of the inhibition caused by 3 - fluorotyrosine could be "reversed" in vitro with tyrosine, interesting sex variations in thyroid gland activity were observed during these experiments. / Thesis / Master of Science (MSc)