Browsing by Author "Santos-Silva, Alice"
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- Altered erythrocyte membrane band 3 profile in chronic renal failure patients under haemodialysisPublication . Costa, Elísio; Rocha, Susana; Rocha-Pereira, Petronila; Castro, Elisabeth; Reis, Flávio; Teixeira, Frederico; Miranda, Vasco; Sameiro-Faria, Maria; Loureiro, Alfredo; Quintanilha, Alexandre; Belo, Luís; Santos-Silva, AliceOur aim was to study changes in RBC membrane band 3 profile, as a cumulative marker of RBC changes, in chronic renal failure (CRF) patients under haemodialysis and recombinant human erythropoietin (rhEPO) therapy and its linkage with resistance to this therapy. We studied 63 CRF patients, 32 responders and 31 non -responders to rhEPO therapy, and 26 healthy individuals matched for age and gender. We evaluated the band 3 profile and membrane -bound haemoglobin (MBH). Total serum bilirrubin, glutathione peroxidase (GPx) and superoxide dismutase activities, RBC count, haematocrit, haemoglobin concentration, haematimetric indices and reticulocyte were also evaluated. CRF patients presented anaemia, slightly regenerative, as showed by the decreased RBC count, Hb and haematocrit, alongside with an increased reticulocyte count, RPI and RDW values. CRF patients showed a statistically significant decrease in high molecular weight aggregates and proteolytic fragments (Pfrag), and a rise in Band 3 monomer. A rise in GPx and a trend to lower values of MBH were also found in CRF patients. A positive correlation was found between Pfrag and, Hb and haematocrit. When comparing the haematological data between the two groups of CRF patients, we found that non -responders patients were more anaemic, and presented a statistically significant decrease in Pfrag, and a trend for a rise in MBH, suggesting a higher RBC damage. Our data suggest that band 3 profile seems to be a good marker of erythrocyte changes in CRF patients. These changes seem to be associated with a younger RBC population, but also with a rise in RBC damage, which is enhanced in non -responders CRF patients. Band 3 profile could be used as a marker of RBC changes in these patients and in the understanding of the mechanism of resistance to rhEPO therapy.
- Band 3 as a marker of erythrocyte changes in chronic renal failurePublication . Costa, Elísio; Rocha, Susana; Rocha-Pereira, Petronila; Castro, Elisabeth; Miranda, Vasco; Faria, Maria Sameiro; Loureiro, Alfredo; Quintanilha, Alexandre; Belo, Luís; Santos-Silva, Alice
- Banda 3 profile as a marker of oxidative stress in hereditary spherocytosisPublication . Granjo, Elisa; Santos-Silva, Alice; Rebelo, Irene; Nóvoa, Ana; Costa, Elísio; Barbot, José; Ribeiro, Manuela; Quintanilha, Alexandre
- Bilirubin dependent on UGT1A1 polymorphisms, hemoglobin, fasting time and body mass indexPublication . Rodrigues, Carina; Costa, Elísio; Vieira, Emília; Carvalho, João; Santos, Rosário; Rocha-Pereira, Petronila; Santos-Silva, Alice; Bronze-da-Rocha, ElsaIn humans, bilirubin levels are influenced by different factors. This study aims to evaluate the influence of several nongenetic factors (hematologic data, smoking status, alcohol intake, fasting time, physical activity, oral contraceptive therapy and caloric intake) and the genetic contribution of UGT1A1 polymorphisms for the bilirubin levels, in a cohort of young women. Hematologic data, bilirubin and screening of TA duplication in the TATA box region of the UGT1A1 gene were performed in 146 young white women. Body mass index (BMI) and body fat were determined, and a questionnaire about fasting time, smoking habits, oral contraceptive therapy, caloric intake and physical activity was performed. Participants were divided into 3 groups according to the tertiles of bilirubin levels. Subjects from the second and third tertile had significant increases in hemoglobin (Hb) concentration, hematocrit, mean cell Hb and mean cell Hb concentration compared with those in the first tertile. Red blood cell count was significantly increased in subjects in the third tertile. A significant increased frequency was found for the c.-41_-40dupTA allele in homozygosity for both second and third tertiles. Multiple linear regression analysis showed that the c.-41_-40dupTA allele, Hb, BMI and fasting hours were independent variables associated with bilirubin serum levels. Hb concentration, fasting time and BMI were identified as nongenetic causes, together with the genetic UGT1A1 polymorphisms, as the main factors associated with variations in bilirubin levels in a healthy female population.
- Bilirubin levels and redox status in a young healthy populationPublication . Rodrigues, Carina; Rocha, Susana; Nascimento, Henrique; Vieira, Emília; Santos, Rosário; Santos-Silva, Alice; Costa, Elísio; Bronze-da-Rocha, ElsaThe additional TA repeat (c.-41_ -40dupTA) in the promoter of the uridine diphosphate glucuronosyltransferase (UGT1A1) gene is associated with a decrease in gene transcription, a decline in bilirubin conjugation and, therefore, with an increase in circulating unconjugated bilirubin (UCB) [1] . The TA repeat polymorphism is remarkably prevalent in the Caucasian white population and is the main cause of Gilbert’s syndrome [1] . Bilirubin, the key metabolic product of hemoglobin (Hb) catabolism, has antioxidant properties that seem to have a protective effect in oxidative stress conditions, such as in atherosclerosis, coronary heart disease, inflammation, and cancer [2] . Some studies showed that high levels of bilirubin can be toxic to neurons in newborn infants.
- Co-existance of congenital red cell pyruvate kinase and band 3 deficiencyPublication . Branca, Rosa; Costa, Elísio; Rocha, Susana; Coelho, Henrique; Quintanilha, Alexandre; Cabeda, José; Santos-Silva, Alice; Barbot, José
- Coexistence of congenital red cell pyruvate kinase and band 3 deficiencyPublication . Branca, Rosa; Costa, Elísio; Rocha, Susana; Coelho, Henrique; Quintanilha, Alexandre; Cabeda, José; Santos-Silva, Alice; Barbot, JoséThe authors report the case of a 9-year-old Caucasian girl, born in northern Portugal, with chronic nonspherocytic haemolytic anaemia and without family history of anaemia. The aethiological study of this anaemia revealed pyruvate kinase deficiency (PKD), because of two previously described mutations (426Arg fi Trp and 510Arg fi Gln). Since the blood smear revealed features not fully compatible with PKD diagnosis, additional tests were performed for the propositus and her parents, namely red blood cell membrane protein analysis. A decrease in proteins band 3 (15%) and 4.2 (18%) was found in the propositus. Her father presented only a decrease in band 3 (11%). Coexistence of PKD and erythrocyte membrane proteins deficiency in the same patient is very uncommon. Our findings suggest that a careful blood smear observation may lead to the identification of a combined deficiency in erythrocyte membrane proteins and enzymopathies.
- Contribution of red cell mass and UGT1A1 alleles in serum bilirubin levels of the portuguese populationPublication . Rodrigues, Carina; Costa, Elísio; Santos-Silva, Alice; Santos, Rosário; Bronze-da-Rocha, ElsaHepatic glucuronization of insoluble bilirubin is catalyzed by isoenzyme 1A1 of UDP-glucuronosyltransferase (UGT1A1), which is essential for efficient biliary excretion of bilirubin. The main cause of Gilbert syndrome (GS) in all populations studied to date is a TA duplication [(TA)7 allele] in the repetitive TATA-box sequence of the gene promoter, which normally consists of six TA repeats. However, this genetic polymorphism is not sufficient for the clinical phenotype of GS. By this reason, some studies have been performed to provide information about additional factors that could contribute to the pathogenesis of this disease. Recently, it was described that increased red cell mass probably plays a role in the pathogenesis of GS (Buyukasik et al. 2008 Am J Med Sci. 335,115-119). The aim of this work is to investigate the putative role of increased red cell mass and the (TA)7 allele in bilirubin serum levels, in the Portuguese population. This study was performed in 109 volunteer healthy young adults (20.3±1.9 years) without liver and/or hematological disorders, chronic infection, recent inflammation, malignancy, hemorrhage and medication. Blood samples were collected and processed in order to determine bilirubin serum levels, complete blood cells count, and DNA extraction. The TATA-box region was analyzed by PCR amplification followed by subsequent analysis by automated capillary electrophoresis. Among our population, 6 were homozygous for the (TA)7 allele, 55 were heterozygous and 48 were homozygous for the normal allele. One of the subjects was a compound heterozygous for the (TA)5 and (TA)7 alleles. Comparing the blood cells counts and the bilirubin serum levels according to the UGT1A1 genotype, we found statistically differences only in bilirubin levels [(TA)6/(TA)6: 0.49±0.20 mg/dL; (TA)6/(TA)7: 0.70±0.32 mg/dL; (TA)7/(TA)7: 1.10±0.74 mg/dL, p<0.05]. A positive statistically significant correlation (p<0.05) were found between bilirubin serum levels and haematocrit and mean cell volume. Our work showed that higher bilirubin serum levels are correlated with an increase red blood mass. However, no association was found between higher red blood mass and abnormal number of TA repeats in the promoter of UGT1A1 gene. This data suggests that in our population the presence of abnormal number of TA repeats in the UGT1A1 gene is associated with increased bilirubin levels but not with higher red blood mass, as previously described for GS patients.
- Contribution of red cell mass and UGT1A1 alleles in serum bilirubin levels of the portuguese populationPublication . Rodrigues, Carina; Costa, Elísio; Santos-Silva, Alice; Santos, M.R.; Bronze-da-Rocha, ElsaHepatic glucuronization of insoluble bilirubin is catalyzed by isoenzyme 1A1 of UDP-glucuronosyltransferase (UGT1A1), which is essential for efficient biliary excretion of bilirubin. The main cause of Gilbert syndrome (GS) in all populations studied to date is a TA duplication [(TA)7 allele] in the repetitive TATA-box sequence of the gene promoter, which normally consists of six TA repeats. However, this genetic polymorphism is not sufficient for the clinical phenotype of GS. By this reason, some studies have been performed to provide information about additional factors that could contribute to the pathogenesis of this disease. Recently, it was described that increased red cell mass probably plays a role in the pathogenesis of GS. The aim of this work is to investigate the putative role of increased red cell mass and the (TA)7 allele in bilirubin serum levels, in the Portuguese population. This study was performed in 109 volunteer healthy young adults (20.3 ± 1.9 years) without liver and/or hematological disorders, chronic infection, recent inflammation, malignancy, hemorrhage and medication. Blood samples were collected and processed in order to determine bilirubin serum levels, complete blood cells count, and DNA extraction. The TATA-box region was analyzed by PCR amplification followed by subsequent analysis by automated capillary electrophoresis. Among our population, 6 were homozygous for the (TA)7 allele, 55 were heterozygous and 48 were homozygous for the normal allele. One of the subjects was a compound heterozygous for the (TA)5 and (TA)7 alleles. Comparing the blood cells counts and the bilirubin serum levels according to the UGT1A1 genotype, we found statistically differences only in bilirubin levels [(TA)6/(TA)6: 0.49 ± 0.20 mg/dL; (TA)6/(TA)7: 0.70 ± 0.32 mg/dL; (TA)7/(TA)7: 1.10 ± 0.74 mg/dL, p<0.05]. A positive statistically significant correlation (p<0.05) were found between bilirubin serum levels and haematocrit and mean cell volume. Our work showed that higher bilirubin serum levels are correlated with an increase red blood mass. However, no association was found between higher red blood mass and the presence of abnormal number of TA repeats in the promoter of UGT1A1 gene. This data suggests that in our population the presence of abnormal number of TA repeats in the UGT1A1 gene is associated with increased bilirubin levels and that increased haematocrit and mean cell volume could contribute for this phenotype. Further studies comparing a larger group of GS patients, homozygous for the (TA)7) allele, are required to better understand the contribution of the red blood mass in the hiperlirubinemia.
- Contribution of red cell mass and ugt1a1 alleles in serum bilirubin levels of the portuguese populationPublication . Rodrigues, Carina; Costa, Elísio; Santos-Silva, Alice; Bronze-da-Rocha, ElsaHepatic glucuronization of insoluble bilirubin is catalyzed by isoenzyme 1A1 of UDP-glucuronosyltransferase (UGT1A1), which is essential for efficient biliary excretion of bilirubin. The main cause of Gilbert syndrome (GS) in all populations studied to date is a TA duplication [(TA)7 allele] in the repetitive TATA-box sequence of the gene promoter, which normally consists of six TA repeats. However, this genetic polymorphism is not sufficient for the clinical phenotype of GS. By this reason, some studies have been performed to provide information about additional factors that could contribute to the pathogenesis of this disease. Recently, it was described that increased red cell mass probably plays a role in the pathogenesis of GS. The aim of this work is to investigate the putative role of increased red cell mass and the (TA)7 allele in bilirubin serum levels, in the Portuguese population. This study was performed in 109 volunteer healthy young adults (20.3 ± 1.9 years) without liver and/or hematological disorders, chronic infection, recent inflammation, malignancy, hemorrhage and medication. Blood samples were collected and processed in order to determine bilirubin serum levels, complete blood cells count, and DNA extraction. The TATA-box region was analyzed by PCR amplification followed by subsequent analysis by automated capillary electrophoresis. Among our population, 6 were homozygous for the (TA)7 allele, 55 were heterozygous and 48 were homozygous for the normal allele. One of the subjects was a compound heterozygous for the (TA)5 and (TA)7 alleles. Comparing the blood cells counts and the bilirubin serum levels according to the UGT1A1 genotype, we found statistically differences only in bilirubin levels [(TA)6/(TA)6: 0.49 ± 0.20 mg/dL; (TA)6/(TA)7: 0.70 ± 0.32 mg/dL; (TA)7/(TA)7: 1.10 ± 0.74 mg/dL, p<0.05]. A positive statistically significant correlation (p<0.05) were found between bilirubin serum levels and haematocrit and mean cell volume. Our work showed that higher bilirubin serum levels are correlated with an increase red blood mass. However, no association was found between higher red blood mass and the presence of abnormal number of TA repeats in the promoter of UGT1A1 gene. This data suggests that in our population the presence of abnormal number of TA repeats in the UGT1A1 gene is associated with increased bilirubin levels and that increased haematocrit and mean cell volume could contribute for this phenotype. Further studies comparing a larger group of GS patients, homozygous for the (TA)7) allele, are required to better understand the contribution of the red blood mass in the hiperlirubinemia.