ABSTRACT
BACKGROUND: Haptoglobin genotypes, and interleukin-6 and -8 participate in the pathophysiology of sickle cell anemia. The expression of cytokines is regulated by genetic mechanisms however the effect of haptoglobin polymorphisms on these cytokines is not fully understood. This study aimed to compare the frequency of haptoglobin genotypes and the interleukin-6 and -8 concentrations in sickle cell anemia patients and controls to investigate the association between haptoglobin genotypes and cytokine levels.METHODS: Sixty sickle cell anemia patients and 74 healthy individuals were analyzed. Haptoglobin genotypes were determined by multiplex polymerase chain reaction, and the interleukin-6 and -8 levels by enzyme linked immunosorbent assay. The association between haptoglobin genotypes and cytokines was investigated by statistical tests.RESULTS:Hp2-1 was the most common genotype in both the cases and controls while Hp1-1 was less frequent among sickle cell anemia patients. Interleukin-6 and -8 levels were higher in patients than controls (p-value <0.0001). There was no significant difference in interleukin-6 and -8 concentrations between the genotypes (p-value >0.05). A similar trend was observed among the controls.CONCLUSION: Although, levels of interleukin-6 and -8 were higher in the sickle cell anemia patients, they appeared not to be related to the haptoglobin genotypes. Further investigations are necessary to identify factors responsible for increased secretion of the interleukin-6 and -8 pro-inflammatory cytokines in patients with sickle cell anemia.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Polymorphism, Genetic , Haptoglobins , Interleukins , Anemia, Sickle CellABSTRACT
O flúor é um elemento natural encontrado em diversas concentrações tanto na água como no solo. É considerado um nutriente benéfico quando presente em níveis ótimos. Apesar de ser utilizado como medicamento em pacientes com osteoporose, sendo capaz de aumentar a densidade óssea, sua eficácia na redução de fraturas ainda apresenta muitas controvérsias, e a exposição a altos níveis e por tempo prolongado, pode levar à fluorose esquelética. Dessa forma o objetivo deste trabalho foi estudar in vitro o efeito do flúor no processo de mineralização por osteoblastos de duas espécies de camundongos com maior e menor densidade óssea, C3H/HeJ (C3) e C57BL/6J (B6) respectivamente. Os osteoblastos isolados da calvária através da digestão enzimática de animais recém nascidos foram expostos a diferentes doses de NaF, e os resultados mostraram que B6 foi mais suscetível ao NaF, apresentando redução da área mineralizada a partir da dose de 10M, enquanto que com C3, a dose significativa foi a partir de 50M, demonstrando que os osteoprogenitores mais diferenciados de C3, são mais resistentes à ação inibitória do flúor. Os testes de unidades formadoras de colônias indicaram um aumento do número de colônias de osteoprogenitores e do número de nódulos mineralizados com a exposição ao NaF. A atividade da metaloproteinase de matriz 2 (MMP-2) também foi aumentada no período de 7 dias em B6 e reduzida nos períodos de 14 e 21 dias em C3, evidenciando que a ação da MMP-2 nestes osteoblastos estão acopladas de forma distinta a diferentes pontos de restrição durante a progressão da diferenciação celular. A dualidade das respostas ao flúor apresentadas pelos modelos experimentais indica que a influência da ação anabólica do flúor, depende do número de alvos em potencial (quantidade de osteoprogenitores presentes na calvária, de células mesenquimais presentes na medula), da atividade intrínseca destes osteoblastos e do estágio de maturação dessas células. Desta forma, a abordagem in vitro...
Fluoride is a natural element found at varying concentrations in drinking water as well as in soil and it is considered a beneficial nutrient at optimal levels. However, although it is well recognized that the fluoride therapy is effective in increasing bone density and it has been used as therapeutic agent to treat osteoporosis, the efficacy in fracture reduction is highly controversial, and exposure to high levels and prolonged time can lead to skeletal fluorosis. The purpose of this study was to investigate the in vitro effects of fluoride exposure during mineralization of two inbread strains, C3H/HeJ (C3) and C57BL/6J (B6), with high and low bone mass respectively. The osteoblasts isolated from newborn mouse calvaria were exposed to several fluoride doses, and the results showed that B6 was more susceptible to NaF, as a reduction in the mineralized area with 10M was already seen; while in C3, the significative dose was with 50 M, indicating that more differentiated osteoprogenitors cells of C3 are more resilient to inhibitory fluoride action. The colony forming unit assays indicate an increase of colony numbers of osteoprogenitors cells and mineralized nodules with NaF treatment. The MMP-2 activity was up-regulated after 7 days of NaF exposure in B6 e down-regulated after 14 and 21 days in C3, showing the distinct coupled action of MMP-2 in different restrictions point during development sequence. The bifasic nature of fluoride responses present by these experimental models indicate that the anabolic action of fluoride is associated to the number of the potential targets (numbers of calvarial osteoprogenitors cells, mesenchymal stem cells), the intrinsic osteoblast activity and the maturation stage of these cells. The cell culture systems can provide molecular and cellular insights, and have the prospective to disclose potential targets and/or better efficacy and safety profile.