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- Cross-talk between inflammation, coagulation/fibrinolysis and vascular access in hemodialysis patientsPublication . Costa, Elísio; Rocha, Susana; Rocha-Pereira, Petronila; Castro, E.; Reis, Flávio; Teixeira, Frederico; Miranda, Vasco; Faria, Maria do Sameiro; Loureiro, Alfredo; Quintanilha, Alexandre; Belo, Luís; Santos-Silva, AliceThis 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.
- Erythrocyte membrane protein destabilization versus clinical outcome in 160 portuguese hereditary spherocytosis patientsPublication . Rocha, Susana; Costa, Elísio; Rocha-Pereira, Petronila; Ferreira, Fátima; Cleto, Esmeralda; Barbot, José; Quintanilha, Alexandre; Belo, Luis; Santos-Silva, AliceHereditary Spherocytosis (HS) is a haemolytic anaemia caused by erythrocyte protein membrane defects - spectrin, ankyrin, band 3 or protein 4.2 - that lead to membrane destabilization. This study aimed to evaluate the prevalence of protein deficiencies and the role of membrane proteins or membrane-linked proteins in membrane disturbance and in HS clinical outcome. A total of 215 Portuguese individuals were studied - 203 from 71 families plus 12 individual unrelated subjects; 160 of them were diagnosed with HS. They were classified as presenting mild, moderate or severe forms of HS according to the degree of haemolytic anaemia. Standardized electrophoretic erythrocyte membrane protein analysis was used to identify and quantify protein deficiencies. Band 3 and ankyrin were found to account for the majority of the erythrocyte protein defects underlying HS. Increasing isolated protein deficiency or increasing imbalance between combined protein deficiencies seemed to underlie HS severity, by increasing membrane destabilization. There was an increased membrane linkage of the cytosolic proteins, glyceraldehyde-3-phosphate dehydrogenase and peroxiredoxin 2, and of denatured haemoglobin, suggesting that this linkage could interfere with membrane structure. Our data suggest that the quantification and the analysis of RBC membrane proteins may be helpful in predicting the clinical outcome of HS.