Aims of education and well-being as absence of disorder

This thesis offers an original account of what personal well-being can be. Any account of education, it is believed, has to do with and aims at personal well-being. I approach this view on well-being not in a positive but in a negative way. I put forward some items that in certain circumstances can be taken by and called sources or forms of disorder. In the absence of such forms or sources of disorder, I assume that a certain order, prudential or moral, takes place and that constitutes the well-being of the person. The concept of ‘absence of disorder’ is introduced and argued as an educationally appropriate view of personal well-being which is the central educational aim. Therefore, ‘absence of disorder’ is positioned as the central aim of education. This concept is illuminated, for practical reasoning, by a list of seven possible forms of disorder: Comparison, Corruption, Dependency, Division, Fear, Self-disintegration and Violence. As a view of personal well-being, ‘absence of disorder’ is initially rooted in informed desire satisfaction, via the introduction of the concept of entropy. Prudentially, the agent’s informed desire is satisfied by living a life with low build up of entropy or disorder. But, in a second move such a base is also provided by the Levinasinian concept of ‘disinterest’ as a root for ‘what is to be a human’. Such ‘disinterest’ is related to the concepts of love and of ‘action for its own sake’. It is at this final approach that an attempt is made towards the approximation of the ethical and the prudential aspects of social practices. Even if only to some extent successful, the argument is directed to the following conclusion: an education aiming at ‘absence of disorder’ may promote prudential well-being and give us some confidence in simultaneously favouring moral education.

The role of hypoxia in the regulation of membrane transporters

ATP binding cassette (ABC) and solute carrier (SLC) transporters are responsible for the majority of the transcellular movement of various substrates, including drugs, among epithelial cells. Despite the well characterized regulation of influx (SLC) and efflux (ABC) transporters by endogenous mediators, such as inflammatory cytokines, little is known about how changes in oxygen levels may affect expression of these transporters. In this study we showed that the expression of SLC22A4, SLC22A5, SLC22A1, SLC02B1, SLC10A2, ABCC2 and ABCC3 transporters is upregulated by hypoxia in HT29 colon carcinoma cells, but not in HepG2 hepatocarcinoma cells. Moreover, OCTN1 (SLC22A4), OCT1 (SLC22A1) and OATP-B (SLC02B1) transporter expression is also induced by inflammatory cytokines but in a smaller extent than in hypoxia. Furthermore our experiments indicate that there is no cross talk between HIF-1 and NF-κB pathways in HT-29 cells, but these two pathways act simultaneously activating common genes, such as, some SLC and ABC transporters. Our preliminary results from studies with an in vivo murine model of colitis, suggest that HIF-1is stabilized and OCTN1 is strongly induced during severe inflammation, which can be relevant for a recovery from the inflammatory process. We have also been interested in the distribution of HIF-1α variants among different ethnic groups as well as their contribution for cancer risk. Thus, we have demonstrated that there is an ethnicity-related variation in the frequency of the C1772T (P582S) single nucleotide polymorphism (SNP) in the HIF-1α gene. Furthermore, we performed a case-control study in a breast cancer population and our results suggest that there is no association between this SNP or the rare G1790A (A588T) SNP and the incidence of breast cancer. Taken together, the results obtained in this study contribute to a better knowledge of drug influx and efflux during hypoxia and inflammation as well as to the understanding of the pharmacogenetic variability of the HIF-1.