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- Cardiovascular risk factors in Portuguese obese children and adolescents: impact of small reductions in body mass index imposed by lifestyle modificationsPublication . Nascimento, Henrique; Costa, Elísio; Rocha-Pereira, Petronila; Rego, Carla; Mansilha, Helena Ferreira; Quintanilha, Alexandre; Santos-Silva, Alice; Belo, LuísObjectives: Evaluate cardiovascular risk factors in Portuguese obese children and adolescents and the long-term effects of lifestyle modifications on such risk factors. Design: Transversal cohort study and longitudinal study. Setting: University Hospital S. João and Children's Hospital Maria Pia, Porto. Patients/Participants: 148 obese children and adolescents [81 females (54.7%); mean age of 11.0 years]and 33 controls (sex and age matched) participated in a cross-sectional study. Sixty obese patients agreed to participate in an one year longitudinal study after medical and nutritionist appointments to improve lifestyle modification; a substantial body mass index (BMI) reduction was defined by a decrease in BMI z-score (BMI z-sc) of 0.3 or more over the studied period. Main Outcome measures: Lipid profile (triglycerides, cholesterol, HDLc, LDLc, lipoprotein (a), apolipoproteins A and B) and circulating levels of C-reactive protein (CRP), adiponectin, glucose, and insulin. Results: Compared with the lean children, obese patients demonstrated statistically significantly higher insulin resistance index [Homeostasis model assessment (HOMA)], and triglycerides, LDLc, apolipoprotein (apo) B, insulin and CRP concentrations, whereas their HDLc and apo A levels were significantly lower (cross-sectional study). In the longitudinal study (n=60), a substantial BMI reduction occurred in 17 (28.3%) obese patients which led to a significant reduction in triglycerides, cholesterol, LDLc, apo B, glucose and insulin levels and in HOMA. The ΔBMI values over the studied period correlated inversely and significantly with BMI (P<0.001) and HOMA (P=0.026) values observed at baseline. In multiple linear regression analysis, BMI at baseline remained associated to changes in BMI over the studied period (standardised Beta: -0.271, P=0.05). Conclusion: Our data demonstrates that small reductions in BMI-zc, imposed by lifestyle modifications in obese children and adolescents, improve the cardiovascular risk profile of such patients. Furthermore, patients with higher BMI and/or insulin resistance seem to experience a greater relative reduction in their BMI after lifestyle improvements.
- 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.
- Neutrophil and monocyte activation in chronic kidney disease patients under hemodialysis and its relationship with resistance to recombinant human erythropoietin and to the hemodialysis procedurePublication . Pereira, Rui; Costa, Elísio; Gonçalves, Marta; Miranda, Vasco; Faria, Maria do Sameiro; Quintanilha, Alexandre; Belo, Luís; Lima, Margarida; Santos-Silva, AliceThe aim of the present work was to further clarify leukocyte activation due to hemodialysis (HD) procedures and to investigate its relationship with recombinant human erythropoietin resistance. Therefore, we studied the expression of CXCR1 and CD11b on neutrophils, as well as the monocyte expression of CD11b, HLA-DR, and CD14. We studied 34 chronic kidney disease (CKD) patients under HD and recombinant human erythropoietin treatment (26 responders and 8 nonresponders to recombinant human erythropoietin therapy). All CKD patients' blood samples were collected before and immediately after the HD procedure. Eighteen healthy individuals (blood donors) were also studied as a control group. Hematological data, neutrophil (CD11b and CXCR1), and monocyte (CD11b, HLA-DR, and CD14) cell surface markers were measured in all patients (before and after the HD procedure) and controls. When compared with the controls, CKD patients presented a significant decrease in CXCR1 neutrophil expression, and in CD14 monocyte expression, accompanied by a significant increase in HLA-DR monocyte expression. When comparing the 2 groups of patients, we found that nonresponders showed an additional decrease in CXCR1 neutrophil expression. After the HD procedure, a statistically significant increase in CD14 and CD11b monocyte surface markers and a decrease in CXCR1 neutrophil expression and in HLA-DR monocyte expression was found. These data further strengthen our previous studies, showing that neutrophils and monocytes are activated in CKD patients, particularly in nonresponder patients. Moreover, this activation is due, at least in part, to the HD procedure, although we should not exclude that it can also be due to the enhanced inflammatory process observed in nonresponder patients.