Spectral analysis of embolic signals

Tese de dout., Engenharia Electrónica e Computação, Faculdade de Ciências e Tecnologia, Univ. do Algarve, 2005

The role of lymphotoxin-B receptor signaling in t-cell acute lymphoblastic leukemia development

Dissertação de mest., Ciências Biomédicas, Faculdade de Ciências e Tecnologia, Univ. do Algarve, 2010

Comportamento in vitro de formulações lipossomais de um aminoglicosídeo com actividade anti-parasitária: citotoxicidade e interacção lipossoma-célula

Os sistemas de veiculação de fármacos, presentemente, apresentam-se como uma alternativa viável às terapias convencionais. De entre os diversos sistemas de transporte passíveis de associar substâncias farmacologicamente activas, destacam-se os de base lipídica, em particular, os lipossomas, os quais constituem um dos sistemas mais estudados e com maior sucesso, comprovado pelo número de produtos em fase clínica ou já aprovados para utilização em humanos. Os lipossomas são estruturas constituídas por membranas lipídicas organizadas em bicamadas, fechadas e concêntricas, que permitem a encapsulação de moléculas hidrofílicas no espaço interno aquoso e hidrofóbicas na bicamada lipídica. No presente trabalho, foram desenvolvidas metodologias com vista à encapsulação em lipossomas do aminoglicosídeo, a Paromomicina (PRM). Este fármaco está indicado para o tratamento de doenças infecciosas nomeadamente parasitárias e bacterianas. Algumas das principais desvantagens resultantes da sua utilização em clínica são, o reduzido tempo de circulação na corrente sanguínea, rápida excreção renal e consequentemente insuficiente concentração intracelular do fármaco. Como forma de ultrapassar algumas das desvantagens apresentadas, foram desenvolvidas formulações lipossomais de PRM com vista a melhorar o desempenho deste antibiótico. Para tal, foram preparadas e caracterizadas diversas formulações lipossomais de PRM com vista à selecção daquelas que apresentem maiores valores de eficácia de encapsulação (E.E.), e superior estabilidade. Com as formulações seleccionadas foram realizados estudos in vitro de interacção lipossoma-célula, utilizando uma linha celular humana monocítica leucémica, THP-1. De entre as formulações desenvolvidas e seleccionadas para os estudos in vitro de a formulação DPPC:DPPG, foi uma das que apresentou uma E.E. superior a 80% e valores de internalização celular superiores a 90%.

Insights into molecular and cellular events involved in normal and pathological vertebral development and fusion using zebrafish as model organism

The vertebral column and its units, the vertebrae, are fundamental features, characteristic of all vertebrates. Developmental segregation of the vertebral bodies as articulated units is an intrinsic requirement to guarantee the proper function of the spine. Whenever these units become fused either during development or postsegmentation, movement is affected in a more or less severe manner, depending on the number of vertebrae affected. Nevertheless, fusion may occur as part of regular development and as a physiological requirement, like in the tetrapod sacrum or in fish posterior vertebrae forming the urostyle. In order to meet the main objective of this PhD project, which aimed to better understand the molecular and cellular events underlying vertebral fusion under physiological and pathological conditions, a detailed characterization of the vertebral fusion occurring in zebrafish caudal fin region was conducted. This showed that fusion in the caudal fin region comprised 5 vertebral bodies, from which, only fusion between [PU1++U1] and ural2 [U2+] was still traceable during development. This involved bone deposition around the notochord sheath while fusion within the remaining vertebral bodies occur at the level of the notochord sheath, as during the early establishment of the vertebral bodies. A comparison approach between the caudal fin vertebrae and the remaining vertebral column showed conserved features such as the presence of mineralization related proteins as Osteocalcin were identified throughout the vertebral column, independently on the mineralization patterns. This unexpected presence of Osteocalcin in notochord sheath, here identified as Oc1, suggested that this gene, opposing to Oc2, generally associated with bone formation and mature osteoblast activity, is potentially associated with early mineralization events including chordacentrum formation. Nevertheless, major differences between caudal fin region and anterior vertebral bodies considering arch histology and mineralization patterns, led us to use RA as an inductive factor for vertebral fusion, allowing a direct comparison of equivalent structures under normal and fusion events. This fusion phenotype was associated with notochord sheath ectopic mineralization instead of ectopic perichordal bone formation related with increased osteoblast activity, as suggested in previous reports. Additionally, alterations in ECM content, cell adhesion and blood coagulation were discussed as potentially related with the fusion phenotype. Finally, Matrix gla protein, upregulated upon RA treatment and shown to be associated with chordacentrum mineralization sites in regular development, was further described considering its potential function in vertebral formation and pathological fusion. Therefore with this work we propose zebrafish caudal fin vertebral fusion as a potential model to study both congenital and postsegmentation fusion and we present candidate factors and genes that may be further explored in order to clarify whether we can prevent vertebral fusion.

Searching biocompounds in marine natural extracts with potential use in tumor prevention and treatment

Cancer is a multistage process characterized by three stages: initiation, promotion and progression; and is one of the major killers worldwide. Oxidative stress acts as initiator in tumorigenesis; chronic inflammation promotes cancer; and apoptosis inactivation is an issue in cancer progression. In this study, it was investigated the antioxidant, antiinflammatory and antitumor properties of hexane, ether, chloroform, methanol and water extracts of five species of halophytes: A. macrostachyum, P. coronopus, J. acutus, C. edulis and A. halimus. Antioxidant activity was assessed by DPPH• and ABTS•+ methods, and the total phenolics content (TPC) was evaluated by the Folin-Ciocalteau method. The anti-inflammatory activity of the extracts was determined by the Griess method, and by evaluating the inhibition of NO production in LPS-stimulated RAW- 264.7 macrophages. The cytotoxic activity of the extracts against HepG2 and THP1 cell lines was estimated by the MTT assay, and the results obtained were further compared with the S17 non-tumor cell line. The induction of apoptosis of J. acutus ether extract was assessed by DAPI staining. The highest antioxidant activities was observed in C. edulis methanol and the J. acutus ether extracts against the DPPH• radical; and J. acutus ether and A. halimus ether extracts against the ABTS•+ radical. The methanol extracts of C. edulis and P. coronopus, and the ether extract of J. acutus revealed a high TPC. Generally the antioxidant activity had no correlation with the TPC. The A. halimus chloroform and P. coronopus hexane extracts demonstrated ability to reduce NO production in macrophages (> 50%), revealing their anti-inflammatory capacity. The ether extract of J. acutus showed high cytotoxicity against HepG2 cancer cells, with reduced cellular viability even at the lowest concentrations. This outcome was significantly lower than the obtained with the non-tumor cells (S17). This result was complemented by the induction of apoptosis.

Characterization of pro- and anti-angiogenic factors in models of diabetic retinopathy

Dissertação de mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2015

Drug repurposing in the treatment of Melanoma Brain Metastasis

Dissertação de Mestrado, Biologia Molecular e Microbiana, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Differentiation of human pluripotent stem cells to the neuronal dopaminergic fate

Dissertação de Mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2013

Alterações à fisiologia e infeção por Plasmodium berghei do mosquito Anopheles gambiae mediadas pela ativação de recetores GPCR

Dissertação de Mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2015

The impact of Portuguese demographic changes on the demand and supply of blood in the region of Algarve

Dissertação de Mastrado, Gestão de Unidades de Saúde, Faculdade de Economia, Universidade do Algarve, 2016