Subject(s)
Humans , Fatty Acids/pharmacology , Globins/genetics , Phenylbutyrates/pharmacology , Cells, Cultured , Erythroid Precursor Cells/drug effects , Erythroid Precursor Cells/metabolism , Fatty Acids/chemistry , Fetal Hemoglobin/biosynthesis , Hemoglobinopathies/blood , Hemoglobinopathies/drug therapy , Hemoglobinopathies/genetics , Leukemia, Erythroblastic, Acute , Phenylacetates/pharmacology , Phenylbutyrates/chemistry , Promoter Regions, Genetic/drug effects , Structure-Activity Relationship , Tumor Cells, Cultured , Up-Regulation/drug effectsABSTRACT
BACKGROUND: Hydroxyurea, which induces Fetal hemoglobin (HbF) synthesis, is the only drug widely used in different hemoglobinopathies; however, the response is very variable. We compared the efficacy of hydroxyurea in-vitro in erythroid cultures and in-vivo in the same patients with different hemoglobinopathies to induce HbF production and enhance γ-messenger RNA expression. MATERIALS AND METHODS: A total of 24-patients with different Hemoglobinopathies were given hydroxyurea and their response was studied in-vivo and in-vitro on mononuclear cells collected from them simultaneously. RESULTS: A total of 57.7% of patients (responders) showed no further crisis or transfusion requirements after hydroxyurea therapy with a mean increase in fetal cells (F-cells) of 63.8 ± 59.1% and γ-mRNA expression of 205.5 ± 120.8%. In-vitro results also showed a mean increase in F-cells of 27.2 ± 24.7% and γ-mRNA expression of 119.6% ± 65.4% among the treated cells. Nearly 19.0% of the partial-responders reduced their transfusion requirements by 50% with a mean increase in F-cells of 61.2 ± 25.0% and 28.4 ± 25.3% and γ-mRNA-expression of 21.0% ± 1.4% and 80.0% ± 14.1% in-vivo and in-vitro respectively. The non-responders (15.3%) showed no change in their clinical status and there was no significant increase in F-cells levels and γ-mRNA expression in-vivo or in-vitro. CONCLUSION: Thus, this method may help to predict the in-vivo response to hydroxyurea therapy; however, a much larger study is required.
Subject(s)
Anemia, Sickle Cell/genetics , Adolescent , Adult , Cells, Cultured , Child , Child, Preschool , Erythroid Precursor Cells/metabolism , Female , Fetal Hemoglobin/analysis , Fetal Hemoglobin/biosynthesis , Fetal Hemoglobin/genetics , Hemoglobinopathies , Hydroxyurea/pharmacology , Humans , India , Male , Middle Aged , RNA, Messenger/genetics , beta-Thalassemia/epidemiology , beta-Thalassemia/genetics , Young AdultABSTRACT
To investigate whether hemoglobin (Hb) synthesis is affected by different treatment protocols used for end-stage renal disease, we analyzed the electrophoretic pattern of hemoglobin in 136 adult patients with chronic renal failure. Forty-seven patients were not in a dialysis program (ND), 29 individuals were on continuous ambulatory peritoneal dialysis (CAPD), 33 patients were on hemodialysis(HD), and 27 subjects had received a kidney transplant (KT). We found 3.6 per cent hemoglobin C, 1.4 per cent hemoglobin S and 3.6 per cent beta-thalassemia minor as reported in other studies of Brazilian patients. In addition, we found increased fetal hemoglobin (Hb F) levels in 7.4 per cent of the patients which contrasts with the reported 0.01 per cent prevalence rate of hereditary persistence of Hb F in Brazil. Seven out of ten patients with elevated Hb F belonged to either the CAPD or the KT group. We postulate that stress erythropoiesis is probably the mechanism responsible for the Hb F increase in these patients. However, properly designed clinical studies are still necessary to clarify these questions.
Subject(s)
Adult , Humans , Fetal Hemoglobin/analysis , Fetal Hemoglobin/biosynthesis , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/bloodSubject(s)
Blood Transfusion/adverse effects , Bone Marrow Transplantation , Chelation Therapy , Child , Female , Fetal Diseases/diagnosis , Fetal Hemoglobin/biosynthesis , Genetic Therapy , Homozygote , Humans , Iron , Pregnancy , Prenatal Diagnosis , Splenectomy , Thalassemia/complications , Virus Diseases/etiology , Vitamins/therapeutic useABSTRACT
O presente trabalho se refere a importancia da hiperglicemia na síntese de hemoglobina F. Foram estudados 1027 indivíduos normais e 226 com hiperglicemia (diabéticos descompensados). A hemoglobina F foi dosada pela técnica da Desnaturaçäo alcalina de Betke e cols (1969). Os nossos resultados mostraram que: 1) nos indivíduos com hiperglicemia os níveis de hemoglobina F estäo diminuidos quando comparados com os níveis apresentados pelos indivíduos normais; 2) os níveis diminuídos de hemoglobina F näo estiveram relacionados com determinadas condiçöes que estäo presentes nos diabéticos - faixa etária, tipo de diabete I e II, período da diabete no indivíduo (meses, anos) e evoluçäo clínica da diabete (presença ou ausência de coma). Discute-se sobre a açäo da eritropoietina e da hiperglicemia na eritropoiese: a) acredita-se que a eritropoietina e a hiperglicemia atuam de modo diferente na celula precursora eritróide (BFU-E); b) a eritropoietina estimulando as divisöes celulares tendo como consequencia maior ou menor número de hemácias circulantes; c) a hiperglicemia interferindo na diminuiçäo da produçäo de hemoglobina F. Conclue-se admitindo-se que, o padräo de formaçäo de hemoglobina F no tecido adulto hematopoiético pode ser reversivel na dependência do ambiente metabólico celular, e que, a elucidaçäo destes mecanismos pode ser de particular importância para ajudar no diagnóstico e ou tratamento de variadas disordens hereditárias e adquiridas que envolvem alteraçöes da hemoglobina F