The Effects of Estradiol, Androgens and the Selective Estrogen Modulators: Ospemifene, Raloxifene and Tamoxifen on Explant Cultures of Human Breast Tissue

The impact of menopausal hormone therapy (MHT) on increasing the risk for breast cancer (BC) remains controversial. To understand MHT-elicited cellular breast effects and the potential risks, included with using this therapy, a further investigation into this controversy is the subject of this thesis. In this thesis, to study the effects of estrogen, progestin, androgens and selective estrogen receptor modulators (SERMs), a modified tissue explant culture system was used. The different types of human breast tissues (HBTs) used in this study were normal HBTs, obtained from reduction mammoplasties of premenopausal women (prem-HBTs) or postmenopausal (postm-HBTs) women and peritumoral HBTs (peritum-HBTs) which were obtained from surgeries on postmenopausal BC patients. The explants were cultured up to three weeks in the presence or absence of estradiol (E2), medroxyprogesterone acetate (MPA), testosterone (T), dihydrotestosterone (DHT) and SERMs - ospemifene (OSP), raloxifene (RAL) and tamoxifen (TAM). The cultured HBTs maintained morphological integrity and responded to hormonal treatment in vitro. E2, MPA or E2/MPA increased proliferative activity and was associated with increased cyclin-D1 and caused changes in the cell cycle inhibitors p21 and p27, whereas the androgens T and DHT inhibited proliferation and increased apoptosis in HBT epithelia and opposed E2-stimulated proliferation and cell survival. The postm-HBTs were more sensitive to E2 than prem-HBTs. The effects of OSP, RAL and TAM on HBT epithelium were antiproliferative. E2, androgens and SERMs were associated with marked changes in the proportions of epithelial cells expressing steroid hormone receptors: E2 increased ERα expressing cells and decreased androgen receptor (AR) positive cells, whereas T and DHT had opposite effects. The OSP, RAL and TAM, also decreased a proportion of ERα positive cells in HBT epithelium. At 100 nM, these compounds maintained the relative number of AR positive cells, present at control level, which may partly explain proliferative inhibition. In conclusion, the proliferative activity of E2, in the epithelium of postm-HBTs, is opposed by T and DHT, which suggests that the inclusion of androgens in MHT may decrease the risk for developing BC.

Relação entre a biometria ultrassonográfica ocular e os parâmetros morfométricos do crânio, idade, peso e gênero em gatos domésticos

O exame ultrassonográfico ocular é indispensável no pré-operatório de procedimentos cirúrgicos intraoculares como a facectomia, além de ser uma ferramenta complementar ao exame oftalmológico, em casos de perda da transparência dos meios ópticos. A inexistência de estudos acerca de padrões de normalidades para as medidas do bulbo ocular e de suas estruturas internas nos gatos, cujos valores possibilitam o monitoramento de enfermidades e auxiliam em procedimentos cirúrgicos motivaram este estudo. Utilizaram-se 40 gatos, adultos, machos e fêmeas, livres de enfermidades sistêmica e oftalmológica. Destes, 22 eram da raça persa (grupo braquicefálico - GB) e 18 sem raça definida (grupo não braquicefálico - GNB). A biometria ultrassonográfica ocular transcorneana foi realizada, em modo-B∕A, com o transdutor microlinear de 9 MHz e as medidas D1 (profundidade da câmara anterior), D2 (diâmetro do cristalino), D3 (profundidade da câmara vítrea) e D4 (diâmetro axial do bulbo ocular) aferidas. Ainda, mensuraram-se as distâncias fronto-occipital e bizigomática e o peso desses animais. Os dados obtidos foram analisados pelo teste-t pareado, seguindo-se as análises de variância e covariância, além da regressão linear múltipla relacionando-se as medidas de D1, D2, D3 e D4 às medidas bizigomática e fronto-occipital, como também à idade, ao peso e ao gênero. Obteve-se como resultado a média de D1, D2, D3 e D4, assim como dos diâmetros bizigomático e fronto-occipital, idade e peso, verificando-se diferenças significativas para D4 nas fêmeas de GB. Houve, pela análise de regressão linear, influência do peso, idade e diâmetro fronto-occipital sobre D1, D2 e D4 nos gatos do GB, e dos diâmetros bizigomático sobre D1, D3 e D4 nos gatos do GNB. Conclui-se que houve diferença no diâmetro axial do bulbo ocular nas fêmeas do GB, e que o peso, a idade e os diâmetros cranianos influenciam a biometria ocular dos gatos braquicefálicos e não braquicefálicos.

Clinical and blood gasometric parameters during Vaquejada competition

ABSTRACT: Clinical and complementary analysis are good alternatives to evaluate physiological demand in performance horses. The aim of this study was to assess whether the physical effort variation of the three-day Vaquejada competition (a Brazilian form of bullfighting) reflected in clinical and blood gasometric changes. During the competition eight sprints have been performed on the first day (D1), eight on the second (D2) and three on the last one (D3). Ten horses were evaluated by checking heart and respiratory rates and collecting blood samples for use in portable chemistry analyzer. Through that, it was assessed potential of hydrogen ion (pH), carbon dioxide pressure (pCO2), bicarbonate (HCO3-) and titratable base concentration (cBase). Evaluations were carried with resting of at least twenty hours, before physical activity (D0), as control parameter, and up to thirty minutes after each sprint. Clinical parameters have increased on D1, D2 and D3, when compared to D0, which demonstrated the increased demand for substrate and oxygen to the cells.. Blood gasometric trial showed reductions of all variables, most marked between D1 and D2. It was verified less alteration of all clinical and blood gasometric parameters in D3 against D0. We concluded that the change effort between days of competition influenced the clinical and blood gas parameters, demonstrating appropriate physiological response. The data were presented as mean and standard error of the mean (mean ± SEM) obtained in different days. Normality was confirmed by the Kolmogorov-Sminov test and data were compared by one-way ANOVA, followed by post-test Holm-Sidak (GraphPad Prism 2.6 for Windows, GraphPad Software, San Diego, CA, USA). P≤0.05 was considered as statistically significant.