Avaliação da permeabilidade de fármacos antirretrovirais por meio de modelo ex vivo com emprego de segmentos da mucosa bucal de suínos

A via de administração oral é a forma favorita de administração de fármacos em função das vantagens que apresenta, dentre elas destacam-se: a adesão do paciente, conveniência e praticidade. Em função disto, a maioria dos medicamentos comercializados encontra-se disponível na forma farmacêutica de administração oral, entretanto, o sucesso de um tratamento medicamentoso por esta via requer que a absorção gastrointestinal do fármaco seja suficiente para assegurar a sua disponibilidade no local de ação (VOLPE, 2010). No entanto, a absorção do fármaco no trato gastrointestinal é complexa e pode ser influenciada por vários fatores, os quais têm impacto sobre a dissolução, solubilidade e permeabilidade do fármaco. Com o intuito de aumentar a biodisponibilidade de fármacos, que possuem absorção dificultada pela via oral, a via de administração pela mucosa bucal vem sendo uma alternativa na atualidade farmacêutica. Esta mucosa é um tecido não queratinizado, altamente vascularizado e apresenta poucas enzimas metabolizadoras. Tais características possibilitam boa absorção de fármacos sem que ocorra a metabolização pré-sistêmica, ou efeito de primeira passagem, somando-se ao fato desta apresentar fácil acessibilidade para a administração de fármacos (VRIES, M. E et al., 1991; NIELSEN, H. M &RASSING, M. R, 1999). Nesse sentido, o presente trabalho teve como objetivo avaliar a permeabilidade dos fármacos antirretrovirais (lamivudina e estavudina) por meio de modelo ex vivo em segmentos da mucosa bucal de suínos, com emprego de câmaras de difusão do tipo células de Franz. Para avaliação da permeabilidade bucal dos fármacos antirretrovirais, lamivudina e estavudina, e dos marcadores para transporte transcelular (metoprolol) e paracelular (fluoresceína sódica), empregou-se método ex-vivo, em células de Franz, com segmento de mucosa bucal de suíno ( a 37ºC, meio Ringer- Krebs- HEPES, pH 7,4), e Franz posterior análise das concentrações das substâncias permeadas (fármacos e marcadores) por cromatografia líquida de alta eficiência. Os resultados obtidos, por meio do protocolo desenvolvido, demonstram que o transporte através da via paracelular (marcador fluoresceína) foi mais expressivo que o transporte transcelular (marcador metoprolol), o que provavelmente se deve ao fato dos espaços intercelulares da mucosa bucal serem mais frouxos do que aqueles observados na mucosa intestinal (junções íntimas). Quanto à lamivudina e estavudina, os resultados de permeabilidade indicaram que estes fármacos permearam por mecanismo semelhante ao do metoprolol, isto é, por via transcelular.

When Wells Run Dry: Water and Tourism Along the Western Coast of Nicaragua

This dissertation uses a political ecology approach to examine the relationship between tourism development and groundwater in southwest Nicaragua. Tourism in Nicaragua is a booming industry bolstered by ‘unspoiled’ natural beauty, low crime rates, and government incentives. This growth has led to increased infrastructure, revenue, and employment opportunities for many local communities along the Pacific coast. Not surprisingly, it has also brought concomitant issues of deeper poverty, widening gaps between rich and poor, and competition over natural resources. Adequate provisions of freshwater are necessary to sustain the production and reproduction of tourism; however, it remains uncertain if groundwater supplies can keep pace with demand. The objective of this research is to assess water supply availability amidst tourism development in the Playa Gigante area. It addresses the questions: 1) are local groundwater supplies sufficient to sustain the demand for freshwater imposed by increased tourism development? and 2) is there a power relationship between tourism development and control over local freshwater that would prove inequitable to local populations? Integrating the findings of groundwater monitoring, geological mapping, and ethnographic and survey research from a representative stretch of Pacific coastline, this dissertation shows that diminishing recharge and increased groundwater consumption is creating conflict between stakeholders with various levels of knowledge, power, and access. Although national laws are structured to protect the environment and ensure equitable access to groundwater, the current scramble to secure water has powerful implications on social relations and power structures associated with tourism development. This dissertation concludes that marginalization due to environmental degradation is attributable to the nexus of a political promotion of tourism, poorly enforced state water policies, insufficient water research, and climate change. Greater technical attention to hydrological dynamics and collaboration amongst stakeholders are necessary for equitable access to groundwater, environmental sustainability, and profitability of tourism.

A qualitative exploration of the impact of the economic recession in Spain on working, living and health conditions: reflections based on immigrant workers' experiences

Background: This study aimed to analyse how immigrant workers in Spain experienced changes in their working and employment conditions brought about Spain's economic recession and the impact of these changes on their living conditions and health status. Method: We conducted a grounded theory study. Data were obtained through six focus group discussions with immigrant workers (n = 44) from Colombia, Ecuador and Morocco, and two individual interviews with key informants from Romania living in Spain, selected by theoretical sample. Results: Three categories related to the crisis emerged – previous labour experiences, employment consequences and individual consequences – that show how immigrant workers in Spain (i) understand the change in employment and working conditions conditioned by their experiences in the period prior to the crisis, and (ii) experienced the deterioration in their quality of life and health as consequences of the worsening of employment and working conditions during times of economic recession. Conclusion: The negative impact of the financial crisis on immigrant workers may increase their social vulnerability, potentially leading to the failure of their migratory project and a return to their home countries. Policy makers should take measures to minimize the negative impact of economic crisis on the occupational health of migrant workers in order to strengthen social protection and promote health and well-being.

Essays in dynamic optimal taxation: working experience, unemployment scarring and poverty

This thesis investigates the design of optimal tax systems in dynamic environments. The first essay characterizes the optimal tax system where wages depend on stochastic shocks and work experience. In addition to redistributive and efficiency motives, the taxation of inexperienced workers depends on a second-best requirement that encourages work experience, a social insurance motive and incentive effects. Calibrations using U.S. data yield higher expected optimal marginal income tax rates for experienced workers for most of the inexperienced workers. They confirm that the average marginal income tax rate increases (decreases) with age when shocks and work experience are substitutes (complements). Finally, more variability in experienced workers' earnings prospects leads to increasing tax rates since income taxation acts as a social insurance mechanism. In the second essay, the properties of an optimal tax system are investigated in a dynamic private information economy where labor market frictions create unemployment that destroys workers' human capital. A two-skill type model is considered where wages and employment are endogenous. I find that the optimal tax system distorts the first-period wages of all workers below their efficient levels which leads to more employment. The standard no-distortion-at-the-top result no longer holds due to the combination of private information and the destruction of human capital. I show this result analytically under the Maximin social welfare function and confirm it numerically for a general social welfare function. I also investigate the use of a training program and job creation subsidies. The final essay analyzes the optimal linear tax system when there is a population of individuals whose perceptions of savings are linked to their disposable income and their family background through family cultural transmission. Aside from the standard equity/efficiency trade-off, taxes account for the endogeneity of perceptions through two channels. First, taxing labor decreases income, which decreases the perception of savings through time. Second, taxation on savings corrects for the misperceptions of workers and thus savings and labor decisions. Numerical simulations confirm that behavioral issues push labor income taxes upward to finance saving subsidies. Government transfers to individuals are also decreased to finance those same subsidies.

Biologic therapies and non-melanoma skin cancer rates in three chronic immune-mediated diseases

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

EU citizenship: Citizenship and identity beyond national borders. EU Centre Singapore Background Brief No. 10, October 2013

The 1992 Maastricht Treaty introduced the concept of European Union citizenship. All citizens of the 28 EU member states are also EU citizens through the very fact that their countries are members of the EU. Acquired EU citizenship gives them the right to free movement, settlement and employment across the EU, the right to vote in European elections, and also on paper the right to consular protection from other EU states' embassies when abroad. The concept of citizenship in Europe – and indeed anywhere in the world – has been evolving over the years, and continues to evolve. Against this time scale, the concept of modern citizenship as attached to the nation-state would seem ephemeral. The idea of EU citizenship therefore does not need to be regarded as a revolutionary phenomenon that is bound to mitigate against the natural inclination of European citizens towards national identities, especially in times of economic and financial crises. In fact, the idea of EU citizenship has even been criticised by some scholars as being of little substantive value in addition to whatever rights and freedoms European citizens already have. Nonetheless the ‘constitutional moment’ that the Maastricht Treaty achieved for the idea of EU citizenship has served more than just symbolic value – the EU’s Charter of Fundamental Rights is now legally binding, for instance. The idea of EU citizenship also put pressure on the Union and its leaders to address the perceived democratic deficit that the EU is often accused of. In attempts to cement the political rights of EU citizens, the citizens’ initiative was included in Lisbon Treaty allowing citizens to directly lobby the European Commission for new policy initiatives or changes.

British Balance of Competence Reviews, Part III: More reform than renegotiation or repatriation. EPIN [Working] Paper No. 42/December 2014. [see Abstract for I and II]

This paper, the third in a series for a CEPS project on the ‘The British Question’, is pegged on an ambitious exercise by the British government to review all the competences of the European Union on the basis of evidence submitted by independent stakeholders. The reviews considered in this paper cover the following EU policies: the single market for services, financial markets, the free movement of people, cohesion, energy, agriculture, fisheries, competition, social and employment policies, and fundamental rights. The declared objective of Prime Minister Cameron is to secure a ‘new settlement’ between the UK and the EU. From political speeches in the UK one can identify three different types of possible demand: reform of EU policies, renegotiation of the UK’s specific terms of membership, and repatriation of competences from the EU back to the member states. As most of the reviews are now complete, three points are becoming increasingly clear: i) The reform agenda – past, present or future - concerns virtually every branch of EU policy, including several cases reviewed here that are central to stated UK economic interests. The argument that the EU is ‘unreformable’ is shown to be a myth. ii) The highly sensitive cases of immigration from the EU and social policies may translate into requests for renegotiation of specific conditions for the UK, but further large-scale opt-outs, as in the case of the euro and justice and home affairs, are implausible. iii) While demands for repatriation of EU competences are voiced in general terms in public debate in the UK, no specific proposals emerge from the evidence as regards competences at the level at which they are identified in the treaties, and there is no chance of achieving consensus for such ideas among member states. Michael Emerson and Steven Blockmans, “British Balance of Competence Reviews, Part I: ‘Competences about right, so far’”, CEPS/EPIN Working Paper No. 35, October 2013 (www.ceps.eu/book/british-balance-competence-reviews-part-i-%E2%80%98competences-about-right-so-far%E2%80%99)(http://aei.pitt.edu/45599/); Michael Emerson, Steven Blockmans, Steve Peers and Michael Wriglesworth, “British Balance of Competence Reviews, Part II: Again, a huge contradiction between the evidence and Eurosceptic populism”, CEPS/EPIN Working Paper No. 40, June 2014 (www.ceps.eu/book/british-balance-competence-reviews-part-ii-again-huge-contradiction-between-evidence-and-eurosc)(http://aei.pitt.edu/52452/).

Technology diffusion, services, and endogenous growth in Europe. Is the Lisbon Strategy still alive? Bruges European Economic Research (BEER) Papers 2/May 2005

We explore the role of business services in knowledge accumulation and growth and the determinants of knowledge diffusion including the role of distance. A continuous time model is estimated on several European countries, Japan, and the US. Policy simulations illustrate the benefits for EU growth of the deepening of the single market, the reduction of regulatory barriers, and the accumulation of technology and human capital. Our results support the basic insights of the Lisbon Agenda. Economic growth in Europe is enhanced to the extent that: trade in services increases, technology accumulation and diffusion increase, regulation becomes both less intensive and more uniform across countries, and human capital accumulation increases in all countries.

Regional business cycles and the emergence of sheltered economies in the southern periphery of Europe. Bruges European Economic Research (BEER) Papers 7/November 2006

Recent research has highlighted that in the last few years the evolution of regional disparities in many European states has become pro-cyclical. This represents a change with respect to the predominantly anti-cyclical pattern of the 1960s and 1970s. This paper addresses the question of whether and when this change has taken place in the southern periphery of Europe, before analyzing the factors that may have played a role in such a change. The analysis relies on a regional database that includes the evolution of the GDP per capita of NUTS II regions in five European countries (France, Greece, Italy, Portugal, and Spain) between 1980 and 2000. The results of the analysis support the hypothesis of a change towards a pro-cyclical evolution of regional disparities in the cases of Italy, Portugal, and Spain, but not in those of Greece and France. A relationship between these pro-cyclical patters and the emergence of less dynamic sheltered economies is also detected in peripheral regions. This lack of dynamism is related to the fact that numerous peripheral areas in southern Europe have become increasingly dependent on factors such as transfers or public investment and employment, and therefore are less exposed to changes in market conditions.

EU citizenship, Citizenship and identity beyond national borders. EU Centre Singapore Background Brief No. 10, October 2013

The 1992 Maastricht Treaty introduced the concept of European Union citizenship. All citizens of the 28 EU member states are also EU citizens through the very fact that their countries are members of the EU. Acquired EU citizenship gives them the right to free movement, settlement and employment across the EU, the right to vote in European elections, and also on paper the right to consular protection from other EU states' embassies when abroad. The concept of citizenship in Europe – and indeed anywhere in the world – has been evolving over the years, and continues to evolve. Against this time scale, the concept of modern citizenship as attached to the nation-state would seem ephemeral. The idea of EU citizenship therefore does not need to be regarded as a revolutionary phenomenon that is bound to mitigate against the natural inclination of European citizens towards national identities, especially in times of economic and financial crises. In fact, the idea of EU citizenship has even been criticised by some scholars as being of little substantive value in addition to whatever rights and freedoms European citizens already have. Nonetheless the ‘constitutional moment’ that the Maastricht Treaty achieved for the idea of EU citizenship has served more than just symbolic value – the EU’s Charter of Fundamental Rights is now legally binding, for instance. The idea of EU citizenship also put pressure on the Union and its leaders to address the perceived democratic deficit that the EU is often accused of. In attempts to cement the political rights of EU citizens, the citizens’ initiative was included in Lisbon Treaty allowing citizens to directly lobby the European Commission for new policy initiatives or changes.

Falling Labor Share and Rising Unemployment: Long-Run Consequences of Institutional Shocks? CES Germany & Europe Working Papers, No. 00.2, 1999

The literature on unemployment has mostly focused on labor market issues while the impact of capital foonation is largely neglected Job-creation is often thought to be a matter of encouraging more employment on a given capital stock. In contrast, this paper explicitly deals with the long-run consequences of institutional shocks on capital foonation and employment. It is shown that the usual trade off between employment and wages disappears in the long run. In line with an appropriation model, the estimated values for the long-run elasticities of substitution between capital and labor for Germany and France are substantially greater than one.

Federal States, Industries and Education Level – Effects of TTIP in Germany. Policy Brief #2013/05

A purely microeconomic perspective shows that all major industries and states would benefit from a transatlantic trade and investment partnership (TTIP). The greatest manufacturing and employment effects would be seen in the electronics industry as well as metal processing. Baden-Württemberg, Bavaria and North Rhine-Westphalia would benefit most from this. Furthermore, it becomes apparent that new jobs would be created for all education groups – even for relatively unskilled workers. Their real income could increase even more than that of highly qualified workers.

Role of alternative interventional procedures when endo- and epicardial catheter ablation attempts for ventricular arrhythmias fail.

BACKGROUND Ventricular tachycardia (VT) refractory to antiarrhythmic drugs and standard percutaneous catheter ablation techniques portends a poor prognosis. We characterized the reasons for ablation failure and describe alternative interventional procedures in this high-risk group. METHODS AND RESULTS Sixty-seven patients with VT refractory to 4±2 antiarrhythmic drugs and 2±1 previous endocardial/epicardial catheter ablation attempts underwent transcoronary ethanol ablation, surgical epicardial window (Epi-window), or surgical cryoablation (OR-Cryo; age, 62±11 years; VT storm in 52%). Failure of endo/epicardial ablation attempts was because of VT of intramural origin (35 patients), nonendocardial origin with prohibitive epicardial access because of pericardial adhesions (16), and anatomic barriers to ablation (8). In 8 patients, VT was of nonendocardial origin with a coexisting condition also requiring cardiac surgery. Transcoronary ethanol ablation alone was attempted in 37 patients, OR-Cryo alone in 21 patients, and a combination of transcoronary ethanol ablation and OR-Cryo (5 patients), or transcoronary ethanol ablation and Epi-window (4 patients), in the remainder. Overall, alternative interventional procedures abolished ≥1 inducible VT and terminated storm in 69% and 74% of patients, respectively, although 25% of patients had at least 1 complication. By 6 months post procedures, there was a significant reduction in defibrillator shocks (from a median of 8 per month to 1; P<0.001) and antiarrhythmic drug requirement although 55% of patients had at least 1 VT recurrence, and mortality was 17%. CONCLUSIONS A collaborative strategy of alternative interventional procedures offers the possibility of achieving arrhythmia control in high-risk patients with VT that is otherwise uncontrollable with antiarrhythmic drugs and standard percutaneous catheter ablation techniques.

Compliance program reference : inspections of licensed and unlicensed blood banks (compliance program #7342.001) and inspections of source plasma establishments (compliance program #7342.002).

Mode of access: Internet.

Worklife estimates : effects of race and education.

"February 1986."