influence of thyroid hormones on hemoglobin A2 and F expression

To evaluate the effect of thyroid hormones on the production of hemoglobin A2 and F [Hb A2 and F]. Sixty three patients were enrolled in this study including new cases of hyperthyroidism, hypothyroidism and thalassemia minor; 28 healthy subjects were used as control group. Assessment of Hb A2, Hb F levels as well as measurement of thyroid hormones were performed for each of them. Hb A2 was significantly higher in hyperthyroid patients than in control group [P=0.002], while Hb F was significantly higher in hypothyroid group in comparison with the control [P=0.012]. Hemoglobin A2 levels are increased in hyperthyroidism and decreased in hypothyroidism, unlike hemoglobin F. This may clarify the effect of thyroid hormones on globin chain synthesis

Efeito da fortificação de farinhas com ferro sobre anemia em pré-escolares, Pelotas, RS / Effect of iron fortification of flour on anemia in preschool children in Pelotas, Brazil

OBJETIVO: A fortificação de farinhas com ferro foi estabelecida por lei no Brasil, em 2004. O objetivo do estudo foi avaliar o impacto da fortificação sobre nível de hemoglobina em crianças menores de seis anos. MÉTODOS: O estudo foi realizado em Pelotas, RS, sendo uma série temporal com três avaliações a cada 12 meses. Em maio de 2004, antes da fortificação das farinhas, foram medidos níveis de hemoglobina em amostra probabilística de 453 crianças. Após 12 e 24 meses, foram estudadas amostras de 923 e 863 crianças, respectivamente. RESULTADOS: Os três grupos estudados foram comparáveis em relação a características demográficas e socioeconômicas. No estudo de linha de base, as médias de hemoglobina foram 11,3±2,8 g/dL. Após a fortificação esses valores foram 11,2±2,8 (12 meses) e 11,3±2,5 g/dL (24 meses), não havendo diferença estatisticamente significativa entre os três momentos estudados (p=0,16). CONCLUSÕES: Nenhum efeito da fortificação foi observado nos níveis de hemoglobina das crianças estudadas, o que pode ser parcialmente explicado pelo consumo insuficiente de farinhas e/ou pela baixa biodisponibilidade do ferro adicionado.

OBJECTIVE: Iron fortification of flour has been sanctioned by the Brazilian government since 2004. The objective of the study was to assess the impact of flour fortification on hemoglobin level in children under six. METHODS: A time-series study was carried out in Pelotas, southern Brazil, consisting of three assessments at a 12-month interval. In May 2004, before flour fortification, hemoglobin measurements were obtained in a probabilistic sample of 453 children. Twelve and 24 months later, samples of 923 and 863 children were studied, respectively. RESULTS: The three groups studied were comparable in terms of demographic and socioeconomic characteristics. At baseline, mean hemoglobin was 11.3±2.8 g/dL. In the post-fortification period, means were 11.2±2.8 (at 12 months) and 11.3±2.5 g/dL (at 24 months), with no statistically significant difference among the three time periods studied (p=0.16). CONCLUSIONS: Fortification had no effect on hemoglobin levels of the children studied. This finding could be partially due to inadequate flour intake and/or low bioavailability of dietary iron.

Ativação da proteína reguladora da homeostase intracelular de ferro (IRP1) pelo pró-oxidante endógeno ácido delta-aminolevulínico / Activation of iron regulatory protein 1 (IRP1) by endogen prooxidant delta-aminolevulinic acid

O ferro é um metal essencial ao organismo, pois está presente em várias proteínas de importância vital, dentre elas a hemoglobina e os citocromos. No entanto, pode também levar à geração de espécies reativas de oxigênio, e por isso necessita de um controle coordenado de sua homeostase a fim de evitar seu acúmulo. Este controle é efetuado pós-transcricionalmente pela proteína IRP1. Esta proteína é sensível aos níveis de ferro, controlando assim a síntese do receptor de transferrina e da ferritina. Quando os níveis de ferro estão baixos, a IRP1 é ativada ligando-se a regiões IRE presentes nos mRNAS destas proteínas, o que leva à inibição da síntese de ferritina e a um estímulo da síntese do receptor de transferrina para que mais ferro seja internalizado...

Possible roles of nitric oxide and peroxynitrite in murine leishmaniasis

Activated macrophages simultaneously synthesize nitric oxide and superoxide anion which can react with each other producing peroxynitrite. Consequently, it has been difficult to assess the precise contribution of each of the formed reactive oxygen- and nitrogenderived species to the microbicidal activities of macrophages, particularly in vivo. To explore this problem, we are examining the formation and potential roles of nitrogen-derived intermediates in Leishmania amazonensis murine infection. Thus far, our results have demonstrated that peroxynitrite is a potent leishmanicidal agent in vitro and that both nitric oxide and peroxynitrite are formed during infection of susceptible BALB/c mouse strain. Nitric oxide was detected as the nitrosyl-hemoglobin complex by electron paramagnetic resonance analysis of blood drawn from mice at different times of infection, and it was shown to increase with the evolution of the disease. These results will be discussed in the context of the dual physiological role of nitric oxide either as a signaling molecule or as a deleterious agent.

Tratamiento con eritropoyetina humana recombinante en período neonatal: indicaciones y controversias / Treatment with recombinant human erythropoietin in the neonate: progress and controversies

La eritropoyetina recombinante (rHuEPO) se utiliza en dos patologías del neonato que se caracterizan por tener niveles inadecuadamente bajos de eritropoyetina circulante: la anemia del prematuro (AP) de muy bajo peso de nacimiento y la anemia hiporregenerativa tardía de la enfermedad hemolítica por incompatibilidad Rh (EHIRh). La experiencia recogida luego de 5 años de utilización en la AP ha demostrado que : a) parece no traer complicaciones; b) para ser efectiva, debe usarse a dosis no inferiores a 500 Ul/kg/semana; c) induce una marcada estimulación de la eritropoyesis, evidenciable por la importante respuesta reticulocitaria observada; d) disminuye significativamente los requerimientos transfuncionales cuando se administra a partir de la 2a. semana de vida; e) no está aún establecida la utilidad de su empleo desde las primeras horas de vida; f) el tratamiento debe durar de 6 a 8 semanas; g) el principal factor limitante de su eficacia terapéutica es la depleción de hierro, por lo que el mismo debe administrarse a dosis de 6 mg/kg/día o superiores mientras dure el tratamiento con rHuEPO. Por lo tanto, su utilización rutinaria parece estar justificada para disminuir la probabilidad de ocurrencia de complicaciones transfuncionales, aunque simultáneamente se deberán realizar los máximos esfuerzos para establecer criterios transfusionales estrictos y disminuir los volúmenes de sangre extraídos para análisis. En niños con EHIRh que han recibido transfusiones intrauterinas se produce una marcada inhibición de la eritropoyesis que demora 2 a 4 meses en recuperarse espontáneamente. El tratamiento con rHuEPO, en los casos comunicados, logró evitar la indicación de transfusiones adicionales. Se encuentran en marcha algunos estudios prospectivos

Ultrastructural aspects of the final stage of hemoglobin biosynthesis

Electron microscopic observations on rabbit embryo, adult rabbit, guinea pig, and human immature erythroid cells showed characteristic hemoglobinized organelles distinguishable from mitochondria by their highly dense matrix, two or three longitudinally arranged double lamellae, and smaller diameters. The presence of hemoglobin (Hb) within these organelles was also demonstrated by electrophoresis of the concentrated supernatant from the isolated, washed and osmotically lysec organelle fraction. The term hemosome has been suggested for these organelles because of their Hb content. We propose that they are the sites of heme integration into the four polypeptide globin chains. The frequency of hemosomes is higher in the peripheral blood erythorid cells of embryos than in the liver erythroid cells, coinciding with the higher Hb synthesis rate in peripheral blood than in the liver. Peripheral blood reticulocytes of rabbits with anemia induced by bleeding presented a lower hemosome frequency than normal reticulocytes. The decrease paralleled the decay of Hb biosynthesis activity. Moreover, Hb biosynthesis induced in HeLa cell and epithelial cell tissue cultures was always associated with the formation of hemosomes. Hemosomegenesis was studied in epithelial tissue culture cells experimentally induced to synthesize Hb, allowing the identification of several stages of hemosome formation in erythroid cells. The morphological data suggest that mitochondria are successively modified to lamellated...

Acción del maleato de perhexilina sobre la curva de disociación de la hemoglobina en pacientes coronarios / Action of the perhexiline maleate on the dissociation curve of the hemoglobin in coronary patients

La desviación hacia la derecha de la curva de disociación de la hemoglobina (CDO) aumenta la liberación de O2 a los tejidos y podría ser un mecanismo útil en la cardiopatía isquémica. Algunos fármacos, como el propranotol, son capaces de producir este efecto. Con objeto de comprobar si el maleato de perhexilina tuviera alguna acción sobre la CDO, se estudiaron once enfermos coronarios tratados con 100-200 mg/día (media, 163). Se analizó la P50 y los niveles de 2,3 DPG antes de comenzar el tratamiento, a las cuatro horas y a los ocho días del inicio del mismo. La P50 pasó de 25,65 + ou - 0,97 mmHg (-x + ou - SD) a 25,93 + ou - 0,99 y a 26,07 + ou - 1,004. Por su parte, el 2,3 DPG aumentó de 14,35 + ou - 1,6 micromoles/g Hb a 14,67 + ou - 1,58 y 14,81 + ou - 1,39. Estas variaciones no fueron estadisticamente significativas. Se concluye que el maleato de perhexilina, con las pautas aqui empleadas, no altera de modo significativo la COD; existe sin embargo cierta tendencia al aumento progresivo y paralelo de P50 y 2,3 DPG que, para hacerse más evidentes, podrían requerir mayores dosis de la droga, más tiempo de tratamiento o un número de pacientes superior

Beta-thalassemia in Brazil

1. Clinical, hematological, genetic and peripheral blood globin synthesis studies were carried out on 17 symptomatic Brazilian thalassemics and ther parents who live in the northeast of Säo Paulo State. The group inclued 8 beta--thalassemia homozygotes, 7 carriers of at least one beta+ gene, one delta beta-/beta--thalassemia double heterozygote and one beta- homozygote also carrying the alfa-chain variant Hb Hasharon (alfa2 47 His beta2). 2. The mean non-alfa/alfa ratio for globin biosynthesis of the patients lacking HbA (beta- homozygotes and delta beta-/beta- double heterozygotes) was 0.26 ñ 0.11 ( mean ñSD), which is not statistically different from the value of 0.32 ñ 0.06 obtained for the carriers of at least one beta+ gene. In contrast, the mean non-alfa/alfa ratio for the thalassemia major patients (0.22 ñ 0.07) was significantly lower than that obtained for the milder cases (0.34 ñ 0.06) although the beta/alfa ratios for the parents of the two groups were similar. 3. The heterogeneity within this group of Brasilian patients having two thalassemic genes, i.e. 60% who are beta- homozygotes and 40% who are carriers of at least one beta+ gene, is consistent with the Italian origin of most of these patients

control of hemoglobin production during hypoxia

The effects of hypoxia on blood were studied in 50 rats subjected to a low pressure in a specially designed room. Based on experimental results and published data, a mathematical model is presented which represents the control system for hemoglobin production in mammals. In the model, it is postulated that the rate of hemoglobin production is controlled by a hormone, erythropoietin, which is released from the kidney in response to reduced renal oxygen supply. Equations are developed which relate erythropoietin release to arterial oxyhemoglobin concentration, and hemoglobin production to plasma erythropoietin concentration with appropriate time delays. The parameters of the model are determined by the least square method. Effects of changes in plasma volume and blood viscosity during hypoxia are included. The results of the model are generally in good agreement with experiment