University of Macau / Faculty of Social Sciences and Humanities / Department of Chinese

Humans have two plasminogen activators (PAs), tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), which generate plasmin to breakdown fibrin and other barriers to cell migration. Both PAs are used as pharmaceuticals but their efficacies are limited by their rapid clearance from the circulation, predominantly by parenchymal cells of the liver. At the commencement of the work presented here, the hepatic receptors responsible for mediating the catabolism of the PAs were little understood. tPA degradation by hepatic cell lines was known to depend on the formation of binary complexes with the major PA inhibitor, plasminogen activator inhibitor type-1 (PAI-1). Initial studies presented here established that uPA was catabolised in a fashion similar to tPA by the hepatoma cell line, HepG2. Other laboratories around this time found that the major receptor mediating the binding and endocytosis of the PAs is Low Density Lipoprotein Receptor-related Protein (LRP1). LRP1 is a giant 600 kDa protein that binds a range of structurally and functionally diverse ligands including, activated α2 macroglobulin, apolipoproteins, β amyloid precursor protein, and a number of serpin-enzymes complexes, including PA??PAI-1 complexes. Further studies for the work presented here centred on this receptor. By using radiolabelled binding assays, ligand blots, and Western blots on cultured cells, the major findings are that: (1) basal LRP1 expression on HepG2 is low compared to a clone termed, HepG2a16, but appears to increase in long term culture; (2) a soluble form of LRP1, which retains ligand-binding capacity, is present in human circulation; (3) soluble LRP1 is also present in cerebral spinal fluid where its role in neurological disorders such as Alzheimer??s disease is a developing area of interest; and (4) the release of LRP1 is a mechanism conserved in evolution, possibly as distantly as molluscs. The discovery, identification, and characterisation of soluble LRP1 introduces this protein in the human circulation, and presents a possible further level of regulation for its associated receptor system.

[pt] A tese apresenta um estudo sobre as toxicomanias pelo viés psicanalítico. O ponto de vista que preside o trabalho é o de que o sujeito toxicômano dirige um apelo ao Outro através do uso da droga para que a função paterna se faça presente. Sob essa perspectiva, o uso da droga comporta uma mensagem dirigida ao Outro para que um corte seja operado na relação sem limites construída com a droga. Não trataremos dos efeitos orgânicos produzidos pelo uso da substância, mas da função sempre singular que a droga pode ocupar um sujeito. No primeiro capítulo, a introdução, será circunscrito o objeto de nosso trabalho: as toxicomanias. Já no segundo capítulo examinaremos o fenômeno das drogas na perversão, na neurose e na psicose. No terceiro capítulo, lançaremos um olhar sobre o uso da droga através dos conceitos de supereu, satisfação pulsional, ideal do eu e pulsão de morte. No quarto capítulo estudaremos o significante na dialética do desejo a fim de localizar o lugar da droga para o sujeito. Trabalharemos também a construção das relações de dependência que antecedem a dependência à droga em si e como o uso da mesma pode servir como um apelo ao pai. Em seguida, partindo da hipótese de que a fragilidade ou inoperância da função paterna propicia a compulsão ao objeto droga como um modo de dar conta da angústia provocada pelos efeitos da castração, investigaremos a problemática da droga a partir do significante Nome-do-Pai e da Metáfora paterna. / [en] The thesis presents a study of addictions through the psychoanalytic point of view. The view that presides the study is that the fellow addict runs an appeal to the Other through the use of the drug to make the paternal function present. From this perspective, the drug contains a message addressed to another so that a cut should be operated in the relationship without limits built with the drug. It will not treat the organic effects produced by the use of the substance, but the unique function that the drug might occupy a person. In the first chapter, the introduction, the object of the work will be circumscribed: the addictions. In the second chapter it will examine the phenomenon of drugs in perversion, in neurosis and psychosis. In the third chapter, it will launch a glimpse into the drug through the concepts of superego, drive satisfaction, ego ideal and the death drive. In the fourth chapter it will present the construction of dependence relations in addictions and how drug use can serve as a call to a father. We will also study the signifier in the dialectic of the desire in order to locate the place of the drug to the addict. Then, assuming that the weakness or ineffectiveness of the paternal function provides the compulsion to object drug as a way to solve the anguish caused by the effects of castration, it will investigate the drug problem from the significant Name of the Father and the paternal metaphor.