Tamoxifen (TAM) is a non-steroidal anti-estrogen used to treat patients with estrogen receptor-positive breast cancer and as a chemopreventive agent against breast cancer in high risk pre- and post-menopausal women. However, recent studies have shown that tamoxifen causes endometrial and hepatic cancer. In this study, we examined the effects of tamoxifen (5, 10, 25 and 50 microM) on the growth and proliferation of nine tumoral cell lines (UACC62, MCF-7, NCI-460, K-562, OVCAR-03, PC-03, HT-29, 786-0, NCI-ADR) and non-tumoral cell lines (3T3, V79, MDCK, VERO). Chinese hamster lung fibroblasts (V79) were the most sensitive lineage to tamoxifen, with 21.6% of the cells showing apoptosis at 50 microM TAM. Microscopic analysis showed that, the cellular transformation caused by TAM in V79 cells was similar to that seen with 7,12-dimethylbenz(a)anthracene, thus indicating the carcinogenicity of TAM.

The aim of this work was to perform a systematic study about the effects induced by chitosan solution concentration and by chitin or glycerol incorporation on dense chitosan membranes with potential use as burn dressings. The membrane properties analyzed were total raw material cost, thickness, morphology, swelling ratio, tensile strength, percentage of strain at break, crystallinity, in vitro enzymatic degradation with lysozyme, and in vitro Vero cells adhesion. While the use of the most concentrated chitosan solution (2.5% w/w) increased membrane cost, it also improved the biomaterial mechanical resistance and ductility, as well as reduced membrane degradation when exposed for 2 months to lysozyme. The remaining evaluated properties were not affected by initial chitosan solution concentration. Chitin incorporation, on the other hand, reduced the membranes cost, swelling ratio, mechanical properties, and crystallinity, resulting in thicker biomaterials with irregular surface more easily degradable when exposed to lysozyme. Glycerol incorporation also reduced the membranes cost and crystallinity and increased membranes degradability after exposure to lysozyme. Strong Vero cells adhesion was not observed in any of the tested membrane formulations. The overall results indicate that the majority of the prepared membranes meet the performance requirements of temporary nonbiodegradable burn dressings (e.g. adequate values of mechanical resistance and ductility, low values of in vitro cellular adhesion on their surfaces, low extent of degradation when exposed to lysozyme solution, and high stability in aqueous solutions).

The aim of this study was to evaluate the effect of scaffolds native or polyanionic collagen matrix (submitted to alkaline treatment for 48 or 96 hours, PCM48 or PCM96, respectively) on the repair of osteoporosis bone fractures resulting from the gonadal hormone alterations caused by ovariectomy in rats undergoing hormone replacement therapy. The physical and mechanical characteristics of bone were analyzed. Macroscopic analysis revealed the absence of pathological alterations in the implanted areas. The percent mineral matter and bone mineral density of the femurs were lower in ovariectomized rats. The mechanical strength of newly formed bone was greater in the area receiving the PCM96 scaffolds compared to the area implanted with the native scaffolds. The PCM96 scaffold is the best choice for bone repair in animals with hormone deficiency since it promotes faster bone growth and good mechanical strength.

Durante o desenvolvimento desta tese de mestrado, muitas pessoas especiais participaram e colaboraram para o êxito deste trabalho. Tenho plena consciência de que sem elas, tudo se tornaria mais difícil. Assim, gostaria de agradecer e dedicar os méritos dessa conquista a essas pessoas que tanto me incentivaram.A Profa. Dra. Selma Candelária Genari, pela sua dedicação e brilhantismo profissional, que se tornou referência para minha formação acadêmica. Agradeço ainda pela sua confiança, compreensão, incentivo e pela convivência de vários anos, que muito contribuiu para minha vida profissional e pessoal. Ao seu marido German e a sua filha Rebeca, que sempre me apoiaram e me ajudaram desde a graduação. Ao Prof. Dr. Arnaldo Rodrigues dos Santos Junior e a Patrícia da Luz Moreira, pela amizade, atenção e colaboração prestadas durante a realização deste trabalho.