A imagem anticlerical no discurso retórico de Afonso Costa: mito ou verdade?

A presente dissertação pretende constituir um estudo sobre a construção da imagem anticlerical de Afonso Costa, ao longo dos tempos, através de uma leitura atenta daquilo que foi dito sobre este autor num universo historiográfico que vai desde a 1ª. República até à atualidade. Assim, ao longo do trabalho, analisaram-se inúmeras fontes (jornais, livros, enciclopédias, dicionários, sítios da Internet), tendo-se feito, passo a passo, uma desmontagem do discurso utilizado pelos diversos autores, tentando encontrar pontos convergentes e divergentes. Por outro lado, confrontou-se o discurso dos vários autores com o de Afonso Costa, tendo-se chegado à conclusão de que a sua imagem anticlerical foi, em grande parte, construída durante a 1ª. República, quer pela corrente de opinião republicana, que assim o idolatrava, quer pela corrente de opinião que se opunha a este estadista. Assim se formava uma imagem anticlerical que se cristalizou durante o Estado Novo. Apenas com a historiografia da democracia, talvez graças ao distanciamento temporal e mental, indutor de objetividade, se faz uma retificação desta imagem que foi criada por uma historiografia baseada em emoções, eivada, pois, de grande subjetividade. /ABSTRACT - The following dissertation attempts to be a study about the construction of the anti-clerical image from Afonso Costa across history, based on a careful reading of historical writing on this author that dates back to the 1st Republic till present day. For this purpose, several sources such as newspapers, books, encyclopaedias, dictionaries and websites were subject of analysis. The approach in speech used by the different authors was deconstructed as a Way to find similar and divergent points of view. Conversely, the speech used by several authors was confronted with Afonso Costa’s own speech. Thus, concluding that his anti-clerical image was in great measure built during the 1st Republic, either by the Republicans who idolized him as well as by those who strongly opposed the Statesmen. An anti-clerical image was therefore created and gained shape during the Estado Novo. Only with the historiography of democracy, and perhaps due to a distance in time and mind, both inducers of subjectivity, this image, which was created by a historiography based in emotion and filled with subjectivity, was rectified

Higher fibrinolytic and inflammatory markers are associated with central venous catheters use in chronic kidney disease patients under haemodialysis

Interruption of blood supply to the heart is a leading cause of death and disability. However, the molecular events that occur during heart ischemia, and how these changes prime consequent cell death upon reperfusion, are poorly understood. Protein SUMOylation is a post-translational modification that has been strongly implicated in the protection of cells against a variety of stressors, including ischemia-reperfusion. In particular, the SUMO2/3-specific protease SENP3 has emerged as an important determinant of cell survival after ischemic infarct. Here, we used the Langendorff perfusion model to examine changes in the levels and localisation of SUMOylated target proteins and SENP3 in whole heart. We observed a 50% loss of SENP3 from the cytosolic fraction of hearts after preconditioning, a 90% loss after ischemia and an 80% loss after ischemia-reperfusion. To examine these effects further, we performed ischemia and ischemia-reperfusion experiments in the cardiomyocyte H9C2 cell line. Similar to whole hearts, ischemia induced a decrease in cytosolic SENP3. Furthermore, shRNA-mediated knockdown of SENP3 led to an increase in the rate of cell death upon reperfusion. Together, our results indicate that cardiac ischemia dramatically alter levels of SENP3 and suggest that this may a mechanism to promote cell survival after ischemia-reperfusion in heart

Cross-talk between inflammation, coagulation/fibrinolysis and vascular access in hemodialysis patients

This work aimed to study the association between fibrinolytic/endothelial cell function and inflammatory markers in chronic kidney disease (CKD) patients undergoing hemodialysis (HD) and recombinant human erythropoietin (rhEPO) therapies, and its relationship with the type of vascular access (VA) used for the HD procedure. As fibrinolytic/endothelial cell function markers we evaluated plasminogen activator inhibitor type-1 (PAI-1), tissue plasminogen activator (tPA) and D-dimers, and as inflammatory markers; C-reactive protein (CRP), soluble interleukin (IL)-2 receptor (s-IL2R), IL-6 and serum albumin levels. The study was performed in 50 CKD patients undergoing regular HD, 11 with a central venous dialysis catheter (CVC) and 39 with an arteriovenous fistula (AVF), and in 25 healthy controls. Compared to controls, CKD patients presented with significantly higher levels of CRP, s-IL2R, IL-6 and D-dimers, and significantly lower levels of PAI-1. The tPA/PAI-1 ratio was significantly higher in CKD patients. We also found statistical significant correlations in CKD patients between D-dimers levels and inflammatory markers: CRP, albumin, s-IL2R and IL-6. When comparing the two groups of CKD patients, we found that those with a CVC presented statistically significant lower levels of hemoglobin concentration and albumin, and higher levels of CRP, IL-6, D-dimers and tPA. Our results showed an association between fibrinolytic/endothelial cell function and increased inflammatory markers in CKD patients. The increased levels of Ddimer, tPA and inflammatory markers in CKD patients using a CVC, led us to propose a relationship between the type of VA chosen for HD, and the risk of thrombogenesis

Resistência à terapêutica com eritropoietina humana recombinante em doentes hemodializados

To better clarify the mechanism of resistance to recombinant human erythropoietin (rhEPO) therapy in haemodialysis patients, we studied systemic changes associated with this resistence in haemodialysis patients under rhEPO therapies, with particular interest on inflammation, leukocyte activation, ironstatus, oxidative stress and erythrocyte damage. We studied 63 chronic kidney disease (CKD) patients under haemodialysis and rhEPO therapies (32 responders and 31 non-responders to rhEPO therapy) and 26 healthy volunteers. In 20 of the CKD patients (10 responders and 10 non-responders to rhEPO therapy), blood samples were also collected immediately after dialysis to study the effect of the haemodialysis procedure. When compared to controls, haemodialysis patients presented lymphopenia, which results, at least in part, from a decrease in total circulating CD3+ T-lymphocytes and affect both the CD4+ and the CD8+ T-cell subsets. These lymphocytes presented markers of enhanced continuous activation state and enhanced ability to produce Th1 related cytokines. Furthermore, haemodialysis patients presented raised markers of an inflammatory process, and of an enhanced neutrophil activation, as showed by the high serum levels of elastase. Concerning to iron status, patients showed increased ferritin and prohepcidin serum levels, and a decrease in transferrin. Furthermore, some changes were observed in erythrocyte membrane protein composition and in band 3 profile, being the decrease in spectrin the most significant change. Higher plasma levels of total antioxidant status (TAS), lipidic peroxidation (TBA) and TBA/TAS ratio were also found. When comparing the two groups of patients, we found that non-responders presented a significant decrease in total lymphocyte and CD4+ T-cell counts, a more accentuated inflammatory process and indicators of enhanced neutrophil activation. No significant differences were found in serum iron status markers between the two groups of patients, except for the soluble transferrin receptor, which was higher among non-responders. Prohepcidin serum levels were significantly lower in non-responders, but were higher than those in the control group. An accentuated decrease in erythrocyte membrane spectrin, alterations in band 3 profile [decrease in band 3 proteolytic fragments (Pfrag) and in Pfrag/band 3 monomer ratio], and a trend to higher values of membrane bound haemoglobin were also found in non-responders patients. In conclusion, although the etiology of resistance to rhEPO therapy is still unknown, our work confirms that inflammation seems to have an important role in its pathophysiology. We also showed that resistance to rhEPO therapy is associated with “functional” iron deficiency, lymphopenia and CD4+ lymphopenia, higher elastase plasma levels, increased interleukin-7 serum levels, and alterations in erythrocyte membrane protein structure and in band 3 profile. Further studies are needed tounderstand the rise in inflammation with the associated need inhigher doses of rhEPO and the reduced iron availability.Com o objectivo de clarificar o mecanismo de resistência à terapêutica com eritropoietina humana recombinante (EPOhr) em doentes hemodializados, estudamos alterações a ela associada, com particular interesse na inflamação, activação leucocitária, ciclo do ferro, stress oxidativo e lesão eritrocitária. Foram estudados 63 doentes renais crónicos (DRC) em hemodiálise e terapêutica com EPOhr (32 respondedores e 31 não respondedores à terapêutica com EPOhr) e 26 indivíduos controlo. Em 20 dos DRC (10 respondedores e 10 não respondedores à terapêutica com EPOhr), foram também colhidas amostras de sangue imediatamente após a hemodiálise para estudar os efeitos deste procedimento. Quando comparados com os controlos, os DRC em hemodiálise apresentaram linfocitopenia, resultante de uma diminuição da contagem dos linfócitos CD3+ e em que ambos os subtipos de linfócitos T CD4+ e CD8+ se encontravam diminuídos. Estes linfócitos apresentavam marcadores celulares de estimulação continuada aumentados e capacidade aumentada de produzir citoquinas associadas com a resposta imune do tipo Th1. Adicionalmente, estes doentes apresentavam marcadores inflamatórios, e aumento na activação dos neutrófilos. No que se refere ao estudo do ciclo do ferro, os DRC apresentavam aumento dos níveis séricos de ferritina e prohepcidina, e uma diminuição na transferrina. Adicionalmente, foram também encontradas alterações na composição proteica da membrana dos eritrócitos e no perfil da banda 3, sendo a diminuição da espectrina a alteração mais significativa. Aumento na capacidade antioxidante total (TAS), na peroxidação lipídica (TBA) e da razão TBA/TAS foram também demonstrados. Quando comparamos os dois grupos de DRC, verificamos que os não respondedores à terapêutica com EPOhr apresentavam diminuição no número total de linfócitos e nos linfócitos T CD4+, e aumento nos marcadores inflamatórios e na activação dos neutrófilos. Não encontramos diferenças significativas nos parâmetros relacionados com o ciclo do ferro, com excepção do receptor solúvel da transferrina, que se encontrava aumentado nos não respondedores. Os níveis séricos de prohepcidina encontravam-se diminuídos nos não respondedores; no entanto, encontravam-se mais elevados que no grupo controlo. Diminuição acentuada no conteúdo em espectrina, alterações no perfil de banda 3 [diminuição fragmentos proteolíticos da banda 3 (Pfrag) e na razão Pfrag/monómero de banda 3], e uma tendência para valores aumentados de hemoglobina ligada à membrana foram também encontrados nos DRC não respondedores à terapêutica com EPOhr. Em conclusão, apesar da etiologia à resistência à terapêutica com EPOhr não estar ainda completamente esclarecidaos nossos resultados confirmam que a inflamação parece ter um papel muito importante. Encontramos também relação entre resistência è terapêutica com EPOhr com défice funcional em ferro, linfocitopenia e linfocitopenia T CD4+, níveis plasmáticos aumentados de elastase, níveis séricos aumentados de interleucina-7, e alterações na estrutura das proteínas de membrana do eritrócito e no perfil de banda 3. Mais estudos serão necessários para se entender a associação entre a inflamação, e resistência à terapêutica com EPOhr e diminuição na disponibilidade em ferro

Effects of statins therapy on LDL subfractions and inflammation in end-stage renal disease patients on dialysis

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The protective role of adiponectin for lipoproteins in end-stage renal disease patients: relationship with diabetes and body mass index

Cardiovascular disease (CVD) events are the main causes of death in end-stage renal disease (ESRD) patients on dialysis. The number and severity of CVD events remain inappropriate and difficult to explain by considering only the classic CVD risk factors. Our aim was to clarify the changes and the relationship of lipoprotein subfractions with other CVD risk factors, namely, body mass index (BMI) and adipokines, inflammation and low-density lipoprotein (LDL) oxidation, and the burden of the most prevalent comorbidities, diabetes mellitus (DM) and hypertension (HT). We studied 194 ESRD patients on dialysis and 22 controls; lipid profile, including lipoprotein subpopulations and oxidized LDL (oxLDL), C-reactive protein (CRP), adiponectin, leptin, and paraoxonase 1 activity were evaluated. Compared to controls, patients presented significantly lower levels of cholesterol, high-density lipoprotein cholesterol (HDLc), LDLc, oxLDL, and intermediate and small HDL and higher triglycerides, CRP, adiponectin, large HDL, very-low-density lipoprotein (VLDL), and intermediate-density lipoprotein- (IDL) B. Adiponectin levels correlated positively with large HDL and negatively with intermediate and small HDL, oxLDL/LDLc, and BMI; patients with DM (n = 17) and with DM+HT (n = 70), as compared to patients without DM or HT (n = 69) or only with HT (n = 38), presented significantly higher oxLDL, oxLDL/LDLc, and leptin and lower adiponectin. Obese patients (n = 45), as compared to normoponderal patients (n = 81), showed lower HDLc, adiponectin, and large HDL and significantly higher leptin, VLDL, and intermediate and small HDL. In ESRD, the higher adiponectin seems to favor atheroprotective HDL modifications and protect LDL particles from oxidative atherogenic changes. However, in diabetic and obese patients, adiponectin presents the lowest values, oxLDL/LDLc present the highest ones, and the HDL profile is the more atherogenic. Our data suggest that the coexistence of DM and adiposity in ESRD patients on dialysis contributes to a higher CVD risk, as showed by their lipid and adipokine profiles.info:eu-repo/semantics/publishedVersio