Orientador: Ary Fernandes Junior / Resumo: Espécies vegetais são fontes de moléculas biologicamente ativas que têm um importante papel no desenvolvimento de novos fármacos e, portanto, suas propriedades merecem ser investigadas. Apesar de serem espécies aromáticas e apresentarem um potencial farmacológico, algumas atividades biológicas dos óleos essenciais das folhas de Protium heptaphyllum, Hedyosmum brasiliense, Blepharocalyx salicifolius, Baccharis dracunculifolia e Nectandra megapotamica ainda não foram avaliadas. O objetivo deste trabalho foi verificar a ação citotóxica, antileishmania e antimicrobiana destes óleos essenciais com o intuito de estabelecer espécies vegetais com potencial uso na elaboração de fármacos ou como terapias complementares aos tratamentos convencionais de doenças de impacto em saúde pública. Os óleos essenciais foram obtidos por destilação de folhas frescas por arraste de vapor, a composição química determinada por análises de cromatografia gasosa/espectrometria de massas, as atividades biológicas testadas utilizando o método de microdiluição e a verificação dos mecanismos de morte celular feita por citometria de fluxo. B. salicifolius e B. dracunculifolia apresentaram elevado rendimento (0,86% e 0,89% respectivamente) quando comparado aos demais óleos essenciais avaliados. H. brasiliense e B. salicifolius apresentaram resultados promissores sobre linhagens tumorais Ehrlich (51,59 e 42,04 μg mL-1) e MDA-MB-231 (62,40 e 46,60 μg mL-1), com maior ação seletiva para estes tipos celulares se c... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: lant species are sources of biologically active molecules that play an important role in the development of new drugs, and therefore, their properties deserve to be investigated. In this regard, Protium heptaphyllum, Hedyosmum brasiliense, Blepharocalyx salicifolius, Baccharis dracunculifolia and Nectandra megapotamica are aromatic species with pharmacological potential, producing essential oils whose biological activities had not yet been investigated. The aim of this work was to assess any cytotoxic, antileishmania, or antimicrobial action of these essential oils to determine those plant species with potential in the elaboration of drugs or in complementary treatments of diseases with an impact on public health. Essential oils were obtained from fresh leaves by steam distillation. Chemical composition was determined by gas chromatography/mass spectrometry. Biological activities were assessed using the microdilution method while cell death was checked by flow cytometry. B. salicifolius and B. dracunculifolia presented high yields (0.86% and 0.89%, respectively) relative to the other species assessed. H. brasiliense and B. salicifolius showed promising action on Ehrlich (at 51.59 and 42.04 μg mL-1 concentration respectively) and MDA-MB-231 tumor lines (at 62.40 and 46.60 μg mL-1 concentration respectively), with less selective action against normal MCF-10A breast cells (at > 512 and 314.44 μg mL-1 concentration respectively). Flow cytometry results showed that B. salicifolius... (Complete abstract click electronic access below) / Doutor

Thesis (MSc (Radiography))--Cape Peninsula University of Technology, 2018 / Background: Breast cancer is one of the most commonly diagnosed among woman in South Africa, and a more resilient effort should be focused on treatment improvements. Worldwide, proton therapy is increasingly used as a radiation treatment alternative to photon therapy for breast cancer, mostly to decrease the risk for radiation-induced cardiovascular toxicity. This in vitro study aims to determine a better understanding of the radiosensitivity of both tumour and normal breast cell lines to clinical proton irradiation. In addition, we propose to investigate whether the increase in linear energy transfer (LET) towards the distal part of the proton beam results in an increase in relative biological effectiveness (RBE) for both cell lines. Methods: Malignant (MCF-7) and non-malignant (MCF-10A) breast cells were irradiated at different water equivalent depths in a 200 MeV proton beam at NRF iThemba LABS using a custom-made Perspex phantom: the entrance plateau, 3 points on the Bragg peak, the D80% and the D40%. A cytokinesis-block Micronucleus (CBMN) assay was performed and Micronuclei (MNi) were manually counted in binucleated cells (BNCs) using fluorescent microscopy. Reference dosimetry was carried out with a Markus chamber and irradiations were performed with a clinical proton beam generated at NRF iThemba LABS that was degraded to a R50 (half-value depths) range of 120 mm, with a field size of 10 cm x 10 cm and a 50 mm SOBP. The phantom could be adjusted to accommodate different perspex plates depending on the depth required within the proton beam. Cells were then exposed to 0.5, 1.0, 2.0, 3.0 and 4.0 Gy doses for each cell line independently and for each dose point. Results and Discussion: For the CBMN results, a program was developed on Matlab platform to calculate the 95% confidence ellipse on the co-variance parameters α and β. These values were determined by fitting the linear quadratic dose response curve to the average number of radiation induced MNi per 1000 BN cells. The ellipse region around a coordinate (the average MN frequency) for both MCF-7 and MCF-10A cells at the plateau region was defined by the mean estimate of the α-value and the β-value that were plotted on the X-axis and Y-axis respectively. The ratio of the two parameters, α/β, is a measure of the impact of fractionation to determine the biological effective dose. In fractionated proton therapy, the MCF10A cells will repair less between two fractions compared to the MCF7 cells. This is not an indication of therapeutic gain from a fractioned treatment protocol. For this reason, the hypofractionated stereotactic treatment protocols that can be applied with protons could be to the befit of the breast cancer patient. The above argument is based only on the radiosensitivity of the two cell lines exposed in the plateau region. Further analysis of the 95% confidence ellipse of both cell lines also showed a clear increase of the alpha value toward the distal portion of the beam and indicates an increase in energy transfer in this region. The gradual increase in α and β parameters with depth for protons for both cells is of clinical importance, since it implicates a non-homogeneous dose within the targeted area and an unwanted high dose behind the targeted area. Distal energy modulation could be investigated especially with larger breast tumours. RBE was calculated as the ratio of the dose at the different positions to the dose at the entrance plateau position (reference) to obtain an equal level of biological effect. A statistically significant difference in radiosensitivity could be observed between malignant and non-malignant cells at all positions (p<0.05). The variation in RBE was between 0.99 to 1.99 and 0.92 to 1.6 for the MCF-7 and MCF10A cell respectively. Conclusions: There is a variation in RBE along the depth-dose profile of a clinical proton beam. In addition, there is difference in radiosensitivity between the cancerous cells and the normal breast cells. While this study highlights a variation in sensitivity between cells it could be used by the modelling community to further develop biologically motivated treatment planning for proton therapy.