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Hyperplasia was induced by physical and chemical means. The resulting goitres were examined by electron microscopy, and the basement membranes were analyzed by stereological methods. The basement membrane in experimental colloid goitre was found to be significantly thinner than its control. A consideration of the course of the various goitres and of the chemical nature of basement membranes leads to the conclusion that the thinning of the basement membrane was the result of stretching. / Science, Faculty of / Zoology, Department of / Graduate

Three approaches were made to study the interrelations between thyroid function and vitamin A in avian metabolism. These were a histological assessment of the activity of the thyroid gland as it is affected by hypervitaminosis A, the effect of hypervitaminosis A on the incubation time of eggs injected with different levels of vitamin A alcohol and palmitate, and finally the effects of hypervitaminosis A on thyroidal uptake and release of radioiodine by chickens. These studies yielded the following observations. CI) Histological -measurements indicated that dietary hypervitaminosis A can depress the secretion of thyroid stimulating hormone. (2) The effect of hypervitaminosis A on thyroid activity as affected by environmental temperature. (3) Vitamin A palmitate and alcohol prolong incubation time. The alcohol form has, in addition, an adverse effect on embryonic development which is manifested in hemorrhaging and malformation of the embryo. (4) Vitamin A in excess may either depress or stimulate thyroidal uptake of radioiodine depending upon an unidentified component of the environment. (5) Vitamin A in excess affects the endocrine system. This is indicated by an increase in size of the thyroid and adrenal glands and a decrease in size of combs and testes. / Land and Food Systems, Faculty of / Graduate

Orientador: Laura Sterian Ward / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-27T08:20:48Z (GMT). No. of bitstreams: 1 Marcello_MarjoryAlana_D.pdf: 3126956 bytes, checksum: ea75ec396afc3fdc6448f9bd6ee786dc (MD5) Previous issue date: 2015 / Resumo: A incidência da obesidade, bem como do câncer diferenciado de tireoide (CDT), tem aumentado exponencialmente em todo o mundo e existem sólidos indícios de que essas duas condições se associam. Diversos estudos demonstram que adipocinas como adiponectina, leptina e resistina e também a grelina podem ser o elo entre essas doenças. O objetivo deste trabalho foi de verificar os perfis antropométrico e molecular das adipocinas: adiponectina, leptina, resistina e grelina de pacientes com diversos tipos de nódulos tireoidianos e compará-los a indivíduos saudáveis, buscando encontrar o elo entre a obesidade e o CDT, além de identificar possíveis marcadores de diagnóstico, evolução e prognóstico para o CDT. Estudamos pacientes com CDT, pacientes com nódulos tireoidianos benignos e indivíduos controle saudáveis. Todos foram entrevistados quanto a seus hábitos alimentares e rotina, além de passarem por avaliação antropométrica completa. Para investigar o perfil molecular da adiponectina, leptina, resistina e grelina, investigamos as concentrações séricas dessas citocinas através da técnica de ELISA, genotipamos os pacientes para 21 SNPs nos genes que codificam as adipocinas e tambem seus receptores através da técnica Taqman SNP Genotyping, analisamos ainda, espécimes cirúrgicos dos pacientes quanto a produção de RNAm dessas adipocinas. Demonstramos que o excesso de peso aumenta o risco de desenvolvimento de CDT em quase 4 vezes e esse risco pode aumentar ainda mais com a ingesta excessiva de calorias, associada ao consumo excessivo de carboidratos e proteínas. As concentrações séricas das adipocinas podem ser excelentes marcadores de diagnostico entre nódulos tireoidianos malignos e benignos, sendo que a acurácia do teste utilizando a leptina e resistina chegou a 100%. A herança genetica dos polimorfismos rs7799039 em LEP, rs1137101 em LEPR e rs2232165 em GHSR aumentou o risco de desenvolvimento de CDT em 4, 11 e 22 duas vezes, respectivamente. Além disso, a herança de SNPs em LEP (rs7799039, rs2167270), ADIPOQ - rs12629945, ADIPOR1 ¿ rs2232853 e rs1342387, ADIPOR2 - rs1058322 e GHSR - rs2232165 alterou as concentrações séricas de leptina, adiponectina e grelina. Demonstramos, ainda, que embora a célula tireoidiana não seja a principal produtora de adipocinas, a adiponectina e seus receptores, o receptor da leptina, e a grelina e seu receptor são produzidos por células tumorais tireoidianas, uma vez que encontramos RNAm para todas essas citocinas nos tecidos analisados, sugerindo que essas adipocinas desempenham um papel importante nesses tecidos. Concluímos que indivíduos portadores de nódulos tireoidianos, especialmente os indivíduos portadores de CDT possuem um perfil antropométrico e molecular (em relação às adipocinas) diferenciado, sendo que aqueles que estão mais fora do peso considerado adequado estão mais suscetíveis ao desenvolvimento do CDT, assim como aqueles que apresentam alterações genéticas e/ou de expressão da adiponectina, leptina, resistina e grelina. Sugerimos que é possível traçar um perfil do individuo portador de CDT em relação a sua constituição física, seus hábitos alimentares e também o seu perfil molecular a adiponectina, leptina, resistina e grelina, que foram identificadas como boas candidatas a marcadores moleculares para o CDT, além de serem potenciais links entre a obesidade, inflamação e CDT / Abstract: The incidence of obesity and of differentiated thyroid cancer (DTC) has increased exponentially over the world and there are strong indications that these two conditions are combined. Several studies have shown that adipokines such as adiponectin, resistin, leptin and ghrelin may be the link between these diseases. The objective of this investigation was to study the molecular profile of adipokines: adiponectin, leptin, resistin and ghrelin and its relationship with the anthropometric features of patients with various types of thyroid nodules in order to investigate the link between obesity and neoplasms and identify possible markers of diagnosis, evolution and prognosis for DTC. A group of patients with DTC, patients with benign thyroid nodules and healthy control subjects were interviewed about their eating habits and routine, and went through a complete anthropometric assessment. The serum concentrations of adiponectin, leptin, resistin, and ghrelin were measured by ELISA. Patients were genotyped for 21 SNPs in genes encoding adipokines and their receptors using Taqman SNP Genotyping technique. In addition, surgical specimens were investigated for mRNA of these adipokines. We demonstrated that being overweight increases the risk of developing CDT almost 4 times and this risk may increase when there is excess intake of calories associated with excessive consumption of carbohydrates and proteins. Serum concentrations of adipokines were excellent markers of nodules malignancy diagnosis, with a 100% accuracy using leptin and resistin. The genetic inheritance of polymorphisms rs7799039 in LEP rs1137101 and rs2232165 in LEPR in GHSR increased the risk of developing CDT 4, 11 and 22 times, respectively. In addition, SNPs heritage in LEP (rs7799039, rs2167270), ADIPOQ - rs12629945, ADIPOR1 - rs2232853 and rs1342387, ADIPOR2 - rs1058322 and GHSR - rs2232165 altered sérum concentrations of leptin, adiponectin and ghrelin. Also, we showed that although the thyroid cell is not the main producer of adipokines, adiponectin, leptin, and ghrelin resitina are produced by thyroid câncer cells, findng mRNA for all cytokines in the tissues analyzed, suggesting that they play an important role in tumorigenesis or thyroid tumor proliferation. We conclude that individuals with thyroid nodules, especially individuals with DTC have diferente anthropometric and molecular adipokine profiles that increases the susceptibility to DTC as well as genetic changes and / or expression of adiponectin, leptin, resistin and ghrelin. We suggest that it is possible to draw a CDT carrier Individual profile for body constitution, eating habits and molecular profile of adiponectin, leptin, resistin and ghrelin may identify individuals at risk for DTC, and are a potential link between obesity, inflammation, and DTC / Doutorado / Clinica Medica / Doutora em Clínica Médica

Human vocalization has always been considered in the context of communication. In recent years, mechanical forces have been shown to have a wide variety of effects on biological systems. Since the vocal cords produce measurable vibrations to the surrounding tissue, including the thyroid, I hypothesize that vocalization could mechanically stimulate thyroid epithelial cells. The data presented in this dissertation highlight some of the important factors for thyroid hormone synthesis. I was able to show that mechanical stimulation provided from vocalization has a similar response as hormonal stimulation on the thyroid. I also demonstrated that this response is dependent on the dosage of the oscillation. Insight into thyroid stimulation via mechanical forces may be useful for a range of medical issues spanning from hypothyroidism to astronauts travelling in space.