Thesis (M. Phil.)--University of Hong Kong, 2008. / Includes bibliographical references (leaves 97-112) Also available online.

Thesis (Ph. D.)--University of Canterbury, 2009. / Typescript (photocopy). "January, 2009." Includes bibliographical references (p. 213-227). Also available via the World Wide Web.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2010.

Thesis (Ph.D.) - University of Queensland, 2005. / Includes bibliography.

Thesis (Ph. D.)--Ohio State University, 2005. / Title from first page of PDF file. Document formatted into pages; contains xvi, 204 p.; also includes graphics (some col.). Includes bibliographical references (p. 196-204). Available online via OhioLINK's ETD Center

Thesis (Ph. D.)--University of Iowa, 2007. / Supervisor: Aloysius Klingelhutz. Includes bibliographical references (leaves 132-153).

Ph.D.

Submitted by JONLENO COUTINHO PAIVA PITOMBO null (jomtombo@hotmail.com) on 2016-05-23T15:01:17Z No. of bitstreams: 1 Jonleno Coutinho P Pitombo.pdf: 2907326 bytes, checksum: b153a02592cf15ac920e757f91e472b8 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-05-25T16:58:23Z (GMT) No. of bitstreams: 1 pitombo_jcp_me_arafo.pdf: 2907326 bytes, checksum: b153a02592cf15ac920e757f91e472b8 (MD5) / Made available in DSpace on 2016-05-25T16:58:23Z (GMT). No. of bitstreams: 1 pitombo_jcp_me_arafo.pdf: 2907326 bytes, checksum: b153a02592cf15ac920e757f91e472b8 (MD5) Previous issue date: 2016-03-21 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Os mecanismos de ação dos andrógenos sobre homeostase e regulação das células que participam do turnover ósseo em fêmeas ainda são pouco compreendidos. Este trabalho teve como principal objetivo avaliar a participação de andrógenos na diferenciação e atividade de osteoclastos in vitro. Células totais de medula óssea de fêmur e tíbia de camundongos fêmeas foram utilizadas como fonte de células precursoras de osteoclastos, sendo cultivadas utilizando-se α-MEM suplementado e em presença de RANK-L (30ng/mL) e M-CSF (50ng/mL). As células foram tratadas com testosterona (T) diidrotestosterona (DHT) e antagonistas de receptores de hormônios sexuais, como flutamida (FLU) e fulvestranto (FUL). O anastrozol (ANA) foi usado para inibição da enzima aromatase e o etanol (0,01%) foi utilizado como controle. Após cinco dias, as células foram fixadas, coradas com TRAP e contadas, considerando-se células TRAP-positivas com 3 ou mais núcleos. Para o ensaio de atividade, foram utilizadas placas revestidas com fosfato de cálcio inorgânico e a área de reabsorção foi calculada com o auxílio de software. O estágio de diferenciação osteoclástica foi avaliado por RT-qPCR e a modulação da expressão de receptores para hormônios sexuais foi avaliada por Western Blot. Os andrógenos (T e DHT) não exerceram efeitos sobre a diferenciação e atividade de osteoclastos (ANOVA; p>0,05). Por outro lado, os tratamentos com ANA, FLU e FUL, associados ou não a T, regularam positivamente a diferenciação e atividade de osteoclastos. A expressão gênica de RANK, Catepsina K, NFATc1 e β3 integrina não foi alterada pelos tratamentos propostos (ANOVA; p>0,05). Além disso, os tratamentos com T, DHT, FLU e FUL modularam a expressão proteica do receptor de andrógeno (AR) e dos receptores de estrógeno (ERα e ERβ) por Western Blot. Tomados em conjunto, nossos resultados indicam que os andrógenos exercem limitada participação na diferenciação e atividade de osteoclastos de camundongos fêmeas e que este processo é mediado, ao menos em parte, por ações indiretas da T e pela modulação de receptores de hormônios sexuais. / The action mechanisms of androgens on homeostasis and the regulation of cells that participate in bone turnover in females are still poorly understood. This study had as main objective to evaluate the participation of androgens in the differentiation and activity of in vitro osteoclasts. Total bone marrow cells from femur and tibia of female mice were used as a source of precursor cells of osteoclasts, they were cultivated using supplemented α-MEM and in the presence of RANK-L (30ng/mL) and M-CSF (50ng/mL). The cells were treated with testosterone (T), dihydrotestosterone (DHT) and antagonists of sexual hormone receptors such as flutamide (FLU) and fulvestrant (FUL). Anastrozole (ANA) was used for inhibiting the aromatase enzyme and ethanol (0.01%) was used as a control. After five days, the cells were fixed, colored with TRAP and counted, considering TRAP-positive cells those ones containing 3 or more nuclei. For the activity assay, were used plaques covered with inorganic calcium phosphate and the area of reabsorption was calculated with the assistance of a software. The osteoclast differentiation stage was evaluated by RT-qPCR and the modulation of the expression of receptors for sexual hormones was assessed by Western Blotting. The androgens (T and DHT) did not exert effects in differentiation and activity of osteoclasts (ANOVA, p> 0.05). On the other hand, the treatments with ANA, FLU and FUL, associated or not to T, positively regulated the differentiation and activity of osteoclasts. The genic expression of RANK, Cathepsin K, NFATc1 and β3 integrin was not altered by the proposed treatments (ANOVA, p> 0.05). Moreover, the treatments with T, DHT, FLU and FUL modulated the protein expression of the androgen receptor (AR) and of the estrogen receptors (ERα and ERβ) by Western Blotting. Taken together, our results indicate that the androgens exert limited participation in differentiation and activity of osteoclasts of female mice and that this process is mediated, at least in part, by indirect actions of T and by the modulation of sexual hormone receptors. / CNPq: 133815/2014-5 / FAPESP: 2013/12014-6

Alzheimer’s disease (AD) is a neurodegenerative disease with characteristic amyloid, neurofibrillary tangles, and neuronal death in the brain. The major component of amyloid is monomeric amyloid beta (Aβ) protein, as well as its oligomers and large fibrils. Aβ, especially oligomeric Aβ, causes neurotoxicity. The aim of the present study was to investigate how Aβ is metabolized in the presence of microglia cells. We have used a cellular model to study the phagocytosis and degradation of Aβ by BV-2, a murine microglia cell line. We also examined if amylin, a pancreatic peptide, influences the metabolism of Aβ by BV-2 cells. Through Western blot analysis, we observed the phagocytosis of Aβ by BV-2 cells. In our investigation of the role of amylin, we observed a trend in our finding that amylin increased phagocytosis in BV-2 cells and decreased aggregation in the culture medium. Our data demonstrate that amylin may modulate microglia function in the AD brain and has potential to become therapeutic for the disease.

L'auteur n'a pas fourni de résumé de moins de 4000 caractères en français / L'auteur n'a pas fourni de résumé de moins de 4000 caractères en anglais