RESUMO
Sickle cell disease is an inherited hemoglobinopathy caused by a single amino acid substitution in the ß chain of hemoglobin that causes the hemoglobin to polymerize in the deoxy state. The resulting rigid, sickle-shaped red cells obstruct blood flow causing hemolytic anemia, tissue damage, and premature death. Hemolysis is continual. However, acute exacerbations of sickling called vaso-occlusive crises (VOC) resulting in severe pain occur, often requiring hospitalization. Blood rheology, adhesion of cellular elements of blood to vascular endothelium, inflammation, and activation of coagulation decrease microvascular flow and increase likelihood of VOC. What triggers the transition from steady state to VOC is unknown. This review discusses the interaction of blood rheological factors and the role that autonomic nervous system (ANS) induced vasoconstriction may have in triggering crisis as well as the mechanism of ANS dysfunction in SCD.
Assuntos
Anemia Falciforme/fisiopatologia , Sistema Nervoso Autônomo/fisiopatologia , Hemorreologia , Vasoconstrição/fisiologia , Anemia Falciforme/sangue , Viscosidade Sanguínea , Adesão Celular , Hipóxia Celular , Endotélio Vascular/fisiopatologia , Envelhecimento Eritrocítico , Deformação Eritrocítica , Eritrócitos Anormais/fisiologia , Frequência Cardíaca , Humanos , Hipóxia/fisiopatologia , Isquemia/etiologia , Isquemia/fisiopatologia , Sistema Nervoso Parassimpático/fisiopatologiaRESUMO
We have investigated the normal variations in basal DNA damage detected by Comet assay in leukocytes and micronucleated erythrocytes (MNE) using the Micronucleus test (MN) in peripheral blood cells from 45 female and male mice from different age groups (newborns, 3.5, 12, and 104 weeks) to clarify age and sex-related changes. Comparison of basal DNA damage detected by Comet assay showed significantly increased values in 104 weeks old mice in relation to the other ages (P < or = 0.01), and newborn mice showed higher values in MNE frequency when compared to all the other groups (P < or = 0.01). A positive correlation was observed between Damage Frequency (r =0.382, P = 0.010) and Damage Index (r = 0.640, P < 0.001) and age. Age was also correlated with the ratio of polychromatic erythrocytes/normachromatic erythrocytes (PCE/NCE) (r = -0.473, P = 0.001), and the MNE frequency was positively correlated with the ratio of PCE/NCE (r = 0.454, P = 0.002). These results suggest an age-related slow down of DNA repair efficiency of DNA damage and/or DNA damage accumulation. Furthermore, data on the spontaneous MNE frequency indicate that the reticuloendothelial system matures with age, and there is a close relationship between erythropoiesis and micronucleus induction in erythrocytes. The influence of sex in the parameters analyzed was less clear. In conclusion, age seems to influence in basal DNA damage and should be considered in genotoxicity studies using mice. Finally, comparisons between assays must be made with care when different cells are compared (e.g. leukocytes and erythrocytes), as found with the Comet assay and MN test.
Assuntos
Ensaio Cometa/métodos , Dano ao DNA , Testes para Micronúcleos/métodos , Fatores Etários , Animais , Animais Recém-Nascidos , Reparo do DNA , Eritrócitos Anormais/fisiologia , Feminino , Leucócitos/fisiologia , Masculino , Camundongos , Gravidez , Fatores SexuaisRESUMO
Lactate and H(+) are suggested to promote the sickling process in red blood cells (RBCs) containing hemoglobin S. We demonstrated greater activity of the RBC monocarboxylate cotransporter MCT-1, lower RBC deformability and impaired hematological indices in sickle cell trait (SCT) carriers compared to control subjects, suggesting an involvement of MCT-1 in hemorheological disturbances in SCT carriers.
Assuntos
Deformação Eritrocítica/fisiologia , Eritrócitos Anormais/química , Transportadores de Ácidos Monocarboxílicos/análise , Transportadores de Ácidos Monocarboxílicos/fisiologia , Traço Falciforme/sangue , Adolescente , Adulto , Western Blotting , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Índices de Eritrócitos , Eritrócitos Anormais/fisiologia , Hemoglobinas/análise , Hemorreologia , Humanos , Microcirculação/fisiopatologia , Traço Falciforme/fisiopatologiaRESUMO
BACKGROUND AND OBJECTIVES: Red blood cells (RBCs) from patients with sickle cell disease present reduced deformability. The aim of this study was to analyse the elasticity of stored RBCs from patients with the sickle cell trait (AS). MATERIALS AND METHODS: The cell elasticity was studied, using laser optical tweezers, on storage days 1, 14, 21, 28 and 35. RESULTS: The elasticity of RBC from AS units stored for 1, 14 and 21 days was significantly greater compared with that of control RBC cells stored for the same time-period. More than 30% of the cells from AS units stored for 28 or 35 days were very rigid and escaped from the optical trap. CONCLUSIONS: RBCs became rigid during storage, suggesting that haemoglobin S might compromise the cell elasticity.
Assuntos
Deformação Eritrocítica , Eritrócitos Anormais/fisiologia , Traço Falciforme/sangue , Doadores de Sangue , Preservação de Sangue , Estudos de Casos e Controles , Elasticidade , Humanos , Técnicas In Vitro , Fatores de TempoRESUMO
The measurement of the osmotic fragility of red blood cells of 7 patients with sickle cell anemia and 5 controls was carried out for the unfractionated blood and for cells of the top and bottom layers after centrifugation. The erythrocytes from all patients with sickle cell anemia were more resistant to the osmotic lysis than normal erythrocytes, and the resistance of the bottom layer cells was greater than that of the top layer cells for all cases of sickle cell anemia. In addition, in the cases of sickle cell anemia, the bottom layer contained an elevated percentage (5.0% - 23.7%) of irreversible sickled cells, as compared to 1.3% - 3.6% in the top layer. The decreased osmotic fragility of the erythrocytes in sickle cell anemia probably results from the cell damage which accompanies repeated sickle-unsickle cycles and which reaches its maximum in the irreversibly sickled cells.