Influência do hipogonadismo na histomorfometria e função tireoidiana de ratas hipotireóideas Influence of hypogonadism on the morphology and function of the thyroid from hypothyroid rats

Foram investigadas a morfologia e a função tireoidiana de ratas Wistar, adultas, castradas e não castradas e mantidas em estado hipotireóideo pela administração diária de propiltiouracil por 120 dias. Ratas eutireóideas castradas e não castradas serviram de controle. As tireóides, colhidas ao final do experimento, foram pesadas, processadas histologicamente e submetidas à análise morfométrica, pela qual foi determinada a proporção dos componentes glandulares (epitélio folicular, colóide e estroma). No plasma sangüíneo, colhido também ao final do período experimental, foram determinadas as concentrações de T3 total, T4 livre e TSH. O peso e a histomorfometria da tireóide não sofreu influência da castração e o aumento do componente epitelial e decréscimo da quantidade de colóide só foram detectados no hipotireoidismo. No estado eutireóideo a deficiência dos esteróides sexuais levou ao aumento dos valores de T4 livre e T3 total e no hipotireoidismo, exacerbou a queda de T3 total, mas não a de T4 livre. Os valores de TSH não se alteraram em nenhum dos estados funcionais da glândula ou das gônadas. Conclui-se que o hipogonadismo não modifica a hiperplasia glandular e a queda dos níveis plasmáticos de tiroxina livre induzidos pelo propiltiouracil, mas altera profundamente o comportamento da triiodotironina total de acordo com o estado funcional da tireóide, tudo sem alterar os valores plasmáticos de TSH.<br>The morphology and function of the thyroids of female adult Wistar rats were investigated. The animals were either castrated or intact and kept in a hypothyroid condition by a treatment with propylthiouracil for 120 days. Castrated and intact euthyroid rats were used as controls. The thyroids were collected at the end of the experiment, weighted, histologically processed, and morphometrically evaluated. Proportions of each glandular component, namely, follicular epithelium, colloid, and stroma, were determined. Serum concentrations of total T3, free T4, and TSH were assessed at the end of the experimental period. The weight and the morphometric parameters were not influenced by castration, whereas an increase in the epithelial component associated with a decreased amount of colloid were observed only in hypothyroid animals. Under an euthyroid state, the deficiency of sexual hormones induced an increase in the levels of free T4 and total T3. In hypothyroid animals, withdrawal of sexual hormones caused an exacerbation of the decrease in total T3, but not in free T4. TSH levels were not affected by the thyroid or the functional condition of gonads. In conclusion, hypogonadism did not influence the glandular hyperplasia and decrease in plasmatic levels of free thyroxin induced by propylthiouracil, but markedly changed the profile of total T3 according to the functional condition of the thyroid, in the absence of changes in the plasmatic levels of TSH

Antitumor effects of the proteasome inhibitor bortezomib in medullary and anaplastic thyroid carcinoma cells in vitro

Context: The ubiquitin-proteasome pathway is a major pathway for degradation of intracellular proteins. Proteasome inhibitors constitute a novel class of antitumor agents with preclinical and clinical evidence of activity against hematological malignancies and solid tumors. The proteasome inhibitor bortezomib (PS-341, Velcade) has been approved by the Food and Drug Administration for the treatment of multiple myeloma and is being studied intensely in several other malignancies. Its mechanism of action is complex but appears to include the inhibition of inhibitory-κB degradation, which leads to inactivation of the transcriptional factor nuclear factor-κB (NF-κB). NF-κB has been implicated in the pathophysiology of the most aggressive forms of thyroid carcinoma, i.e. medullary and anaplastic. Objective and Methods: We evaluated the effect of bortezomib on a panel of thyroid carcinoma cell lines, originating from papillary, follicular, anaplastic, and medullary carcinomas. Results: Bortezomib induced apoptosis in medullary and anaplastic cell lines with IC50 values well within the range of clinically achievable concentrations and much lower than respective IC50 values for other solid malignancies. Bortezomib inhibited NF-κB activity; increased p53, p21, and jun expression; and induced caspase-dependent apoptosis. Sensitivity of thyroid carcinoma cells to bortezomib was partially decreased by overexpression of Bcl-2 or treatment with IGF-I, whereas the combination of bortezomib with chemotherapy (doxorubicin) was synergistic. Conclusions: These data provide both insights into the molecular mechanisms of antitumor activity of proteasome inhibitors and the rationale for future clinical trials of bortezomib, alone or in combination with conventional chemotherapy, to improve patient outcome in medullary and anaplastic thyroid carcinomas. Copyright © 2006 by The Endocrine Society

Hipogonadismo e função tireoidiana em ratas hipertireóideas e eutireóideas Hypogonadism and thyroid function in hyper and euthyroid rats

A influência do hipogonadismo sobre a função tireoidiana de ratas hipertireóideas e eutireóideas foi medida com base no perfil sérico dos hormônios tireoidianos, dos esteróides ovarianos e do TSH e na histomorfometria da tireóide. Ratas Wistar, com cinco meses de idade, castradas, foram mantidas em estado eutireóideo ou hipertireóideo por períodos de 30, 60 e 90 dias. Um grupo não castrado foi mantido nas mesmas condições e serviu como controle. O hipertireoidismo foi induzido mediante a administração diária 50µg de L-tiroxina, por sonda gástrica. Ao final de cada período, nove ratas por grupo tiveram suas tireóides inspecionadas, pesadas e processadas para avaliação histomorfométrica e o plasma sangüíneo colhido para dosagem de estradiol, progesterona, T4 total, T4 livre, T3 total e TSH. O hipogonadismo não alterou os valores de T3 total e de TSH, mas aumentou significativamente as concentrações de T4 livre, independente do estado hipertireóideo ou eutireóideo. As concentrações de T4 total sofreram influência da castração apenas no grupo hipertireóideo. O peso das tireóides não sofreu influência do hipogonadismo, mas a altura do epitélio folicular nos animais eutireóideos variou ao longo do experimento, apresentando-se maior aos 30 e 90 dias e menor aos 60 dias. Não se observou correlação entre os níveis de estrógeno e as variáveis estudadas, mas os níveis de progesterona foram inversamente proporcionais à elevação dos níveis de T4 total e T4 livre. Concluiu-se que o hipogonadismo altera a histomorfometria da tireoide em indivíduos eutireóideos, aumenta os valores plasmáticos de T4 livre independentemente do estado funcional da tireóide e potencializa a elevação de T4 total no hipertireoidismo, provavelmente sob influência do hipoprogesteronismo e não do hipoestrogenismo.<br>The effects of hypogonadism on thyroid function of hyper and euthyroid rats were measured based on plasmatic profile of thyroid hormones, ovarian steroids, TSH and thyroid histomorphometry. A group of five-month-old ovariectomized Wistar rats were maintained at hyper or euthyroid state for 30, 60 and 90 days. A group of non castrated was used as control. The hyperthyroidism was induced by gastric infusion of L-tiroxin 50µg daily. At the end of each period nine rats of each group were sacrificed, the blood plasma collected and the thyroid inspected, measured and processed for histomorphometric analyses. In blood plasma the concentrations of estradiol, progesterone, total and free tiroxin, total and free T3 and TSH were determined. The hypogonadism did not alter the values of free T3 and TSH but was able to rise free tiroxin in both hyper and euthyroid states. Total tiroxin levels were affected by castration, but only in the hyperthyroid state. Folicular epithelium height presented variations along the experiment in euthyroid individuals although these did not influence thyroid weight. No correlations between estrogen and any other variables were observed, but the progesterone levels were conversely proportional to the total and free tiroxin levels. It was concluded that hypogonadism alter the histomorphometric patterns of thyroid gland in euthyroid individuals, rise the plasmatic levels of free tiroxin regardless the functional state of thyroid gland and powered the total tyroxin rise in hyperthyroidism, probably due to the influence of hypoprogesteronism but not to the hypoestrogenism

Steps That Lead to the Diagnosis of Thyroid Cancer: Application of Data Flow Diagram

Part 1: Second Artificial Intelligence Applications in Biomedicine Workshop (AIAB 2012)International audienceThe complete hospital information system supports the electronic patient record, which, with the history registration, its laboratory and depiction examinations through the use of expert systems, leads to the immediate and effective diagnosis and treatment of the illness. In this present study with the use of a data flow diagram, which consists of a small indication of the way an expert system based on Artificial Intelligence can be made applicable, the steps which lead to the diagnosis of thyroid cancer will be mentioned, when the patient is admitted to the outpatient Endocrinology department. With the data flow diagram, the users can visualize the way in which the system will operate and what it can achieve. Also it will present the course which the medical professional follows in order to reach the diagnosis of thyroid cancer with the slightest error percentage, using the medical information in the extensive hospital information system