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  • Adverse vascular effects of phthalates: Possible contribution to hypertension in pregnancy
    Publication . Mariana, Melissa Rodrigues; Oliveira, Maria Elisa Cairrão Rodrigues; Soares, Amadeu Mortágua Velho da Maia; Sousa, Miguel Castelo Branco Craveiro de
    Phthalates are chemical compounds used as plasticizers to increase flexibility and elasticity of rigid polymers and as non-plasticizers as solvents and additives in cosmetics and personal care products. These compounds have low water solubility and since they are not covalently bound to the polymer they are easily released into the environment and absorbed by the human body. Afterwards, phthalates are rapidly metabolized into their respective monoesters being already detected in different biological samples, including blood, urine, saliva, amniotic fluid, umbilical cord blood and breast milk. In addition, phthalates can disrupt the endocrine system by binding to molecular targets and interfering with hormonal homeostasis, thus being classified as endocrine-disrupting compounds (EDCs). Due to these properties and their adverse effects, phthalates were classified as priority environmental pollutants by the United States Environmental Protection Agency (US EPA). Alongside this increase in exposure to phthalates, the incidence of cardiovascular diseases (CVD) has also increased over the years, with the occurrence of hypertensive disorders in pregnancy (HDP) being one of the main causes of maternal and foetal morbidity and mortality. There are several risk factors that influence the development of HDP, including exposure to EDCs, but the mechanisms involved are not yet known. Several studies have also suggested an association with phthalates, in rats they seem to promote changes in the vascular function, to affect the expression of proteins involved in cardiac function, to contribute to increased blood pressure, changes in lipid metabolism, and atherosclerosis. Thus, the aim of this thesis was to investigate how phthalates’ exposure affects the cardiovascular health, focusing on HDP. For that, studies were carried out on rat aorta and the human umbilical artery to evaluate the effects of di(2-ethylhexyl) phthalate (DEHP) and diethyl phthalate (DEP) in the vascular function. In the first study, rat aorta devoid of endothelium was contracted with noradrenaline and potassium chloride (KCl) and then subjected to different concentrations of DEHP (0.001-100 μM) to assess the vascular reactivity. Besides, since Ca2+ levels are the main determinant of contraction and relaxation, DEHP effects on Ca2+ currents were also analysed using the A7r5 cells. The data obtained showed that DEHP caused a concentration-dependent vasorelaxation after contraction with KCl, and, at the highest concentrations, it inhibited both the basal and the BAY K8644-stimulated calcium currents. These results suggest that DEHP induces vasorelaxation of the rat aorta by inhibiting the L-type Ca2+ channels (LTCC). Then, the genomic and non-genomic effects of DEP on the rat aorta were analysed. Using the organ bath technique, DEP (0.001-1000 μM) was analysed after contraction of the arteries with noradrenaline and KCl. Similarly, to understand the possible mechanisms involved, the effects of DEP were analysed on the relaxing effect of nifedipine (NIF - specific calcium channel blocker) and sodium nitroprusside (SNP - soluble guanylate cyclase activator). Besides, through electrophysiology studies the non-genomic (occurring within a few minutes) and genomic (occurring after 24h of exposure) effects of DEP on the Ca2+ currents of the A7r5 cells were investigated. These showed that both the rapid and 24h effects of DEP exposure led to a decrease in LTCC currents, being in agreement with the vasorelaxation obtained through the organ bath experiments. For the first time, the vascular electrophysiological properties of an EDC were analysed after long-term exposure, concluding that DEP promotes an inhibition of the calcium current in the rat aorta, which may be responsible for electrical disturbances such as arrhythmias. To evaluate the effect of phthalates on maternal health, the last experimental work of this thesis analysed the contribution of DEP (0.001-1000 μM) in the development of gestational hypertension. Therefore, human umbilical arteries (HUA) were collected from normotensive and hypertensive pregnant women. To assess the non-genomic vascular effects, the HUA were pre-contracted with serotonin, histamine and KCl and then subjected to DEP, resulting in a vasorelaxation by interfering with Ca2+ channels and serotonin and histamine receptors. On the other hand, to assess the genomic effects, the arteries were incubated with DEP for 24h, and then the effects of NIF and SNP were analysed. The results showed that DEP seemed to act through the NO/sGC/cGMP/PKG signalling pathway, and to interfere with LTCC. In addition, primary culture of HUA smooth muscle cells was also performed for cell viability essays, showing that DEP has no toxic effect on these cells. Overall, this experimental work showed that DEP affects the HUA vascular resistance through disturbances in hormone and calcium homeostasis, suggesting that the development of hypertension in pregnancy may be a consequence of exposure to phthalates. In general, the results obtained show that phthalates modify the vascular homeostasis in both animals and humans, promoting vasorelaxation mainly through the inhibition of Ca2+ channels. This is the first time that an experimental study has been able to establish the link between exposure to DEP and gestational hypertension. We are beginning to unravel the mechanistic pathways involved in the vascular effects of phthalates that explain the pathological functional alterations of hypertension in pregnancy. However, more experimental studies are needed to understand how different classes and mixtures of phthalates affect the cardiovascular health during pregnancy and in future generations.
    2024-12-18Doctoral thesis Embargoed access Show more
  • Reforço sísmico de edifícios tendo em consideração a mitigação de danos nos elementos não estruturais
    Publication . Feliciano, Metusalém Adriano; Pinto, Clemente Martins
    A vulnerabilidade dos elementos não estruturais (ENE) em edifícios sujeitos a sismos é uma preocupação crescente, pois, embora não façam parte do suporte estrutural, também são afetados, comprometendo a segurança e funcionalidade dos edifícios. Esta dissertação investiga o reforço sísmico de edifícios, com foco na mitigação de danos nos ENE, nomeadamente em paredes de preenchimento e divisórias, tetos suspensos e sistemas de envidraçado. O principal objetivo é identificar as vulnerabilidades críticas dos ENE e avaliar a eficácia de estratégias de mitigação de danos face a sismos. A pesquisa inclui um levantamento detalhado de danos típicos em ENE com base em inspeções pós-sísmicas, seguido de uma análise de estratégias de reforço e mitigação, tais como a implementação de folgas sísmicas, conexões deslizantes e o reforço com materiais compósitos. Adicionalmente, examina-se o impacto da flexibilidade estrutural no desempenho dos ENE, demonstrando que, em edifícios com elevada flexibilidade, os ENE são particularmente suscetíveis a falhas. Neste contexto, a aplicação de técnicas de melhoramento específicas revela-se indispensável para assegurar não só a integridade dos ENE, mas também a viabilidade global do edifício, uma vez que a resistência estrutural por si só não é suficiente para garantir a sua funcionalidade após um sismo. Conclui-se que a conjugação de um bom projeto sísmico com técnicas de mitigação adequadas, envolvendo tanto os elementos estruturais como os não estruturais, é fundamental para garantir a segurança dos edifícios, reduzir os custos de reparação e assegurar a sua operacionalidade após um sismo.
    2024-12-18Master thesis Open access Show more
  • Implementation and Evaluation of QUIC protocol on Internet of Things Monitoring Solutions
    Publication . Almeida, Luis Filipe Pereira de; Silva, Bruno Miguel Correia da
    IoT is a technology that ensures the possibility of significantly improving our lives by connecting hardware devices and everyday objects to the internet. Subsequently, these devices will be used to collect, transfer, and analyze vast amount of data, which can then be used to act on our environment or interact with us directly. The market for this technology is rapidly expanding in various sectors such as transportation, manufacturing, healthcare, among others. Due to this, IoT is also undergoing rapid evolution, requiring the development of fast, secure, and reliable communications. In an attempet to address the issues refered before, the use of QUIC in IoT technology is being explored as an alternative to currently used internet transport protocols. Although initially designed to operate in conjunction with HTTP/3, it has features that can benefit IoT, such as low latency compared to the TCP protocol, multiplexing that resolves head-of-line blocking found in TCP, and the use of a connection ID to enable connection migration. This dissertation explores the implementation of the QUIC protocol on IoT monitoring solutions. We aim to develop, implement and evaluate this implementation by comparison to other well known and used IoT-related protocols, such as, HTTP, UDP, MQTT and CoAP. This work explores the use of the QUIC protocol in a real-world scenario. This scenario will be the RuralTHINGS project, which focuses on creating an intelligent system for monitoring health-hazardous gases, such as radon gas and carbon dioxide, in residential areas. The main objectives are to discover the advantages and disadvantages of using the QUIC protocol, the scenarios in which it should be used, and how it compares to other similar protocols.
    2024-12-18Master thesis Open access Show more