RESUMO
In malaria endemic countries, anemia in pregnant women occurs as a result of erythrocyte destruction by Plasmodium infections and other causes including malnutrition. Iron supplementation is recommended as treatment of iron-deficiency anemia. Erythrocyte destruction results in increased release of cytotoxic free heme that is scavenged by haptoglobin (Hp), hemopexin (Hx) and heme oxygenase-1 (HO-1). Paradoxically, iron supplementation in pregnant women has been reported to enhance parasitemia and increase levels of free heme. The relationship between free heme, heme scavengers, and birth outcomes has not been investigated, especially in women who are on iron supplementation. We hypothesized that parasite-infected pregnant women on routine iron supplementation have elevated heme and altered expression of heme scavengers. A cross-sectional study was conducted to determine the association between plasma levels of free heme, HO-1, Hp, Hx, and malaria status in pregnant women who received routine iron supplementation and their birth outcomes. Heme was quantified by colorimetric assay and scavenger protein concentration by ELISA. We demonstrated that iron-supplemented women with asymptomatic parasitemia had increased free heme (mean 75.6 µM; interquartile range [IQR] 38.8-96.5) compared with nonmalaria iron-supplemented women (mean 34.9 µM; IQR 17.4-43.8, P < 0.0001). Women with preterm delivery had lower levels of Hx (mean 656.0 µg/mL; IQR 410.9-861.3) compared with women with full-term delivery (mean: 860.9 µg/mL; IQR 715.2-1055.8, P = 0.0388). Our results indicate that iron supplementation without assessment of circulating levels of free heme and heme scavengers may increase the risk for adverse pregnancy outcomes.
Assuntos
Anemia Ferropriva/tratamento farmacológico , Suplementos Nutricionais/efeitos adversos , Sequestradores de Radicais Livres/uso terapêutico , Ferro/efeitos adversos , Ferro/uso terapêutico , Malária/complicações , Complicações na Gravidez/induzido quimicamente , Adolescente , Adulto , Estudos Transversais , Feminino , Gana , Heme/análise , Humanos , Gravidez , Adulto JovemRESUMO
OBJECTIVE: To determine the natural course of zinc protoporphyrin/heme ratio (ZnPP/H) and its role in the detection of iron deficiency (ID) and iron-deficiency anemia (IDA) in the first 4 months of life in moderately preterm infants. STUDY DESIGN: ZnPP/H was measured at 1 week, 6 weeks and 4 months postnatal age in a prospective cohort of 161 Dutch infants born at a gestational age of 32+0 to 36+6 weeks who did not receive an erythrocyte transfusion or iron supplementation. RESULTS: ZnPP/H levels decreased in the first 6 weeks and increased thereafter. At 4 months postnatal age, ZnPP/H was higher in the 11 (8.5%) infants with IDA (mean (s.d.): 260.8 (16.1)) but not in the 27 (21.3%) infants with ID (mean (s.d.): 177.0 (15.1)) compared with normal infants (mean (s.d.): 157.3 (12.5)). CONCLUSION: In moderately preterm infants, ZnPP/H can be of additional value to detect infants at risk for IDA due to iron-deficient erythropoiesis at 4 months of age.
Assuntos
Anemia Ferropriva/diagnóstico , Heme/análise , Recém-Nascido Prematuro/sangue , Deficiências de Ferro , Protoporfirinas/sangue , Anemia Ferropriva/sangue , Feminino , Ferritinas/sangue , Idade Gestacional , Testes Hematológicos , Humanos , Lactente , Recém-Nascido , Ferro/sangue , Modelos Lineares , Masculino , Países Baixos , Estudos Prospectivos , Curva ROCRESUMO
Rapid and accurate heme quantitation in the research lab has become more desirable as the crucial role that intracellular hemoproteins play in metabolism continues to emerge. Here, the time-honored approaches of pyridine hemochromogen and fluorescence heme assays are compared with direct absorbance-based technologies using the CLARiTY spectrophotometer. All samples tested with these methods were rich in hemoglobin-associated heme, including buffered hemoglobin standards, whole blood from mice, and murine erythroleukemia (MEL) and K562 cells. While the pyridine hemochromogen assay demonstrated the greatest linear range of heme detection, all 3 methods demonstrated similar analytical sensitivities and normalized limits of quantitation of â¼1 µM. Surprisingly, the fluorescence assay was only shown to be distinct in its ability to quantitate extremely small samples. Using the CLARiTY system in combination with pyridine hemochromogen and cell count data, a common hemoglobin extinction coefficient for blood and differentiating MEL and K562 cells of 0.46 µM-1 cm-1 was derived. This value was applied to supplemental experiments designed to measure MEL cell hemoglobinization in response to the addition or removal of factors previously shown to affect heme biosynthesis (e.g., L-glutamine, iron).
Assuntos
Heme/análise , Heme/química , Hemoglobinas/química , Espectrometria de Fluorescência/métodos , Animais , Linhagem Celular Tumoral , Desenho de Equipamento , Índices de Eritrócitos , Feminino , Heme/análogos & derivados , Hemoglobinas/análise , Humanos , Células K562 , Limite de Detecção , Modelos Lineares , Masculino , Camundongos , Reprodutibilidade dos TestesRESUMO
This study considered effects of timing and duration of iron deficiency (ID) on frontal EEG asymmetry in infancy. In healthy term Chinese infants, EEG was recorded at 9 months in three experimental conditions: baseline, peek-a-boo, and stranger approach. Eighty infants provided data for all conditions. Prenatal ID was defined as low cord ferritin or high ZPP/H. Postnatal ID was defined as ≥ two abnormal iron measures at 9 months. Study groups were pre- and postnatal ID, prenatal ID only, postnatal ID only, and not ID. GLM repeated measure analysis showed a main effect for iron group. The pre- and postnatal ID group had negative asymmetry scores, reflecting right frontal EEG asymmetry (mean ± SE: -.18 ± .07) versus prenatal ID only (.00 ± .04), postnatal ID only (.03 ± .04), and not ID (.02 ± .04). Thus, ID at both birth and 9 months was associated with right frontal EEG asymmetry, a neural correlate of behavioral withdrawal and negative emotions.
Assuntos
Ferritinas/sangue , Lobo Frontal/fisiopatologia , Heme/análise , Deficiências de Ferro , Protoporfirinas/análise , Eletroencefalografia , Feminino , Sangue Fetal , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
Heme iron (Fe) release from alginate beads at in vitro simulated gastrointestinal conditions for potential use as oral heme Fe supplement was studied. Five beads at different ratios of sodium alginate (SA)-to-spray-dried bovine blood cells (SDBC) with weight ratios of 1:1.25, 1:2.5, 1:5, 1:10, and 1:15 (w/w) were prepared. Release characteristics of these beads were investigated at in vitro simulated gastrointestinal conditions. Release media pH strongly influenced the controlled Fe release from the beads. The heme Fe-beads in simulated gastric fluid (pH 2) remained in a shrinkage state and Fe release was low: 25.8, 21.1, 11.6, 12.1, and 12.0 % for 1:1.25, 1:2.5, 1:5, 1:10, and 1:15 ratios, respectively. Proportion and amount of Fe released by 1:1.25 and 1:2.5 ratios was higher than the other ratios. The heme Fe-beads swelled and dissociated in simulated intestinal fluid (pH 6), releasing three-fourths of the Fe in 200 min. The morphology studies showed that Fe release followed formation of pores in the alginate matrix, generating erosion of the beads and complete disintegration after 75 and 200 min of gastric and intestinal incubation, respectively. These results indicate that heme Fe-beads may be useful for oral delivery of heme Fe supplement.
Assuntos
Alginatos/química , Suco Gástrico/química , Heme/análise , Heme/química , Ferro/análise , Ferro/química , Microesferas , Animais , Células Sanguíneas , Bovinos , Suco Gástrico/metabolismo , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Técnicas In VitroRESUMO
The study objective was to investigate the addition of rooibos extract (RBE) in blesbok and springbok droëwors, a dried meat sausage with added beef fat, to improve oxidative stability. After a storage period of two weeks, inhibition of lipid oxidation showed to be successful with RBE 1.0% addition. No differences (P>0.05) in heme-iron results within the raw, dried or stored samples were seen. However, a positive correlation between lipid oxidation and heme-iron was noted. The fatty acid profiles suggest that after drying the decrease in polyunsaturated fats could be linked to the increase in lipid oxidation. Flavor and aroma differences between the varying RBE concentrations in the droëwors were detected by the sensory panel. A droëwors formulation using a combination of game meat and beef fat with the addition of RBE at a 1.0% concentration could be a successful addition to the processed meat market.
Assuntos
Aspalathus , Gorduras na Dieta/análise , Ácidos Graxos/análise , Conservação de Alimentos/métodos , Peroxidação de Lipídeos , Produtos da Carne/análise , Extratos Vegetais , Animais , Animais Selvagens , Antílopes , Bovinos , Manipulação de Alimentos , Heme/análise , Humanos , Ferro/análise , Odorantes , Oxirredução , PaladarRESUMO
Date palm is an interesting source of bioactive compounds that could be used as ingredient in meat products; thus a campagne type pork liver pâté was elaborated using fresh date by-products (0, 5, 10 and 15%). Physicochemical properties, pigment and lipid oxidation, residual nitrite level, texture and sensory analysis during 4 days after the elaboration process were evaluated. Date paste mostly incorporated moisture, fibre and phenolic compounds. Physicochemical parameters, myoglobin content and heme iron stability were not severely affected. Addition of 10% of date was enough to avoid lipid oxidation through all storage times. Colour was the most affected parameter; however, in terms of overall acceptability, panellists preferred samples with added date.
Assuntos
Arecaceae/química , Fibras na Dieta , Frutas/química , Fígado , Produtos da Carne/análise , Fenóis , Água , Adulto , Animais , Cor , Comportamento do Consumidor , Dieta , Feminino , Heme/análise , Humanos , Ferro da Dieta/análise , Peroxidação de Lipídeos , Masculino , Pessoa de Meia-Idade , Mioglobina/análise , Nitritos/análise , Preparações de Plantas/química , SuínosRESUMO
OBJECTIVES: To refine the reference range for the zinc protoporphyrin-to-heme ratio (ZnPP/H) of preterm infants, we assessed the impact of maternal risk factors on ZnPP/H and evaluated the impact of changes in iron supplementation on iron status. STUDY DESIGN: The reference range for neonatal ZnPP/H was refined using prospective data from 31 reference infants ≤ 35 weeks' postmenstrual age (PMA) plus retrospective data from 51 infants <30 weeks' PMA, and 59 infants 30-40 weeks' PMA. Cord blood and first week of life values were compared when both were available. The impact of maternal risk factors was assessed by examining prospectively collected ZnPP/H from 48 high-risk infants. The effect of changing iron supplementation guidelines was evaluated by retrospective chart review of serial ZnPP/H from 194 infants. RESULTS: Cord ZnPP/H was lower at 30-35 weeks' gestation than at 24-26 weeks' gestation (P = .01). Cord ZnPP/H values from insulin-dependent diabetic mothers were elevated compared with reference values. Changing the iron supplementation protocol was not associated with improved ZnPP/H measurements. CONCLUSIONS: Cord blood and postnatal reference ranges for ZnPP/H are defined. Iron balance depends on a complex interaction of prenatal and postnatal factors.
Assuntos
Heme/análise , Protoporfirinas/sangue , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Estudos Prospectivos , Fatores de RiscoRESUMO
This study examined the time-dependent effects of a cell permeable SOD mimetic, MnTMPyP, on mitochondrial function in renal ischemia-reperfusion injury (IRI). Male SD rats were subject to either sham operation or bilateral renal ischemia for 45 min followed by reperfusion for 1, 4 or 24 h. A sub-set of animals was treated with either saline vehicle or 5 mg/Kg of MnTMPyP (i.p.). EPR measurements showed that at 1-h reperfusion MnTMPyP prevented a decrease in aconitase activity (p < 0.05) and attenuated the increase in the high spin heme at g = 6 and oxidation of 4Fe4S to 3Fe4S signal at g = 2.015 (p < 0.01). MnTMPyP was effective in preventing loss of mitochondrial complexes and prevented the loss of cytochrome c and Smac/Diablo from mitochondria early in reperfusion. Following 24 h of reperfusion MnTMPyP was effective in attenuating caspase-3 and blocking apoptosis (p < 0.05). In conclusion, MnTMPyP has biphasic effects in renal IRI, inhibiting mitochondrial dysfunction at the early phases of reperfusion and prevention of apoptosis following longer durations of reperfusion.
Assuntos
Antioxidantes/uso terapêutico , Rim/irrigação sanguínea , Metaloporfirinas/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Aconitato Hidratase/análise , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose , Proteínas de Transporte/análise , Caspase 3/análise , Citocromos c/análise , Avaliação Pré-Clínica de Medicamentos , Espectroscopia de Ressonância de Spin Eletrônica , Heme/análise , Marcação In Situ das Extremidades Cortadas , Masculino , Metaloporfirinas/farmacologia , Mitocôndrias/fisiologia , Proteínas Mitocondriais/análise , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Superóxido Dismutase/análise , Fatores de TempoRESUMO
Washed red blood cells (RBCs), supplemented or non-supplemented with sodium azide (to inhibit catalase activity), were exposed to different concentrations of hydrogen peroxide as well as ascorbic acid. Strikingly, catalase within RBCs protected the cells against exogenic hydrogen peroxide even at millimolar concentrations. However, the activity of the erythrocytic catalase failed to protect the RBCs when they were exposed to an oxidative burst of stimulated polymorphonuclear cells (PMNCs) in the presence of several reactive species in addition to peroxide. Oxyhemoglobin, with an excess of hydrogen peroxide, formed oxidized hemoglobin species and caused protein denaturation as well as the rise of heme degradation products which was suspected to falsify zinc protoporphyrin/heme (ZPP/heme) ratio as assessed by hematofluorometry. Our experiments may thus imply that the non-fluorescent hemoglobin background can be modified by reactive oxygen species (ROS) and this can lead to a spurious ZPP/heme ratio. We discuss this phenomenon with respect to ZPP quantification in clinical practice.
Assuntos
Fluorometria , Heme/metabolismo , Estresse Oxidativo , Protoporfirinas/sangue , Eritrócitos/química , Reações Falso-Positivas , Heme/análise , Humanos , Protoporfirinas/metabolismoRESUMO
OBJECTIVE: To investigate associations of dietary iron (total, haem, and non-haem), supplemental iron, and red meat with blood pressure. DESIGN: Cross sectional epidemiological study. SETTING: 17 population samples from Japan, China, the United Kingdom, and the United States participating in the international collaborative study on macro-/micronutrients and blood pressure (INTERMAP). PARTICIPANTS: 4680 adults aged 40-59. MAIN OUTCOME MEASURE: Average of eight blood pressure readings. RESULTS: In multiple linear regression analyses dietary total iron and non-haem iron were consistently inversely associated with blood pressure. With adjustment for potential non-dietary and dietary confounders, dietary total iron intake higher by 4.20 mg/4.2 MJ (2 SD) was associated with -1.39 mm Hg (P<0.01) lower systolic blood pressure. Dietary non-haem iron intake higher by 4.13 mg/4.2 MJ (2 SD) was associated with -1.45 mm Hg (P<0.001) lower systolic blood pressure. Differences were smaller for diastolic blood pressure. In most models haem iron intake from food was positively, non-significantly associated with blood pressure. Iron intake from combined diet and supplements yielded smaller associations than dietary iron alone. Red meat intake was directly associated with blood pressure; 102.6 g/24 h (2 SD) higher intake was associated with 1.25 mm Hg higher systolic blood pressure. Associations between red meat and blood pressure persisted after adjustment for multiple confounders. CONCLUSION: Non-haem iron has a possible role in the prevention and control of adverse blood pressure levels. An unfavourable effect of red meat on blood pressure was observed. These results need confirmation including in prospective studies, clinical trials, and from experimental evidence on possible mechanisms.
Assuntos
Pressão Sanguínea/fisiologia , Hipertensão/etiologia , Ferro da Dieta/efeitos adversos , Produtos da Carne/efeitos adversos , Adulto , Estudos Transversais , Suplementos Nutricionais , Feminino , Heme/análise , Humanos , Ferro da Dieta/administração & dosagem , Modelos Lineares , Masculino , Pessoa de Meia-IdadeRESUMO
La anemia ferropénica es un problema de salud pública a nivel mundial. Los niños pequeños son más vulnerables a esta deficiencia. Determinar los factores de riesgo y protección para la anemia ferropénica en niños menores de 6 años. Estudio descriptivo, transversal. Se evaluaron 100 niños. Edad, género, estratificación social, tipo de lactancia, edad de ablactación, diagnóstico nutricional, características de la dieta (calorías, proteínas y hierro). Hemoglobina (Hb), Hematocrito (HTO), Volumen Corpuscular Medio (VCM), Hemoglobulina Corpuscular Media (HCM), hierro sérico. A las variables se les aplicó un análisis de regresión logística simple. 46 por ciento de los pacientes tenían anemia. Siendo la media para la edad de 19,2 meses, tiempo de lactancia materna exclusiva 5,2 meses, inicio de ablactación de 5,7 meses, hemoglobina de 9,9 g/dl. Se observa que en los niños de menor edad existe un mayor riesgo de presentar anemia. No se demostró una diferencia estadísticamente significativa entre los pacientes anémicos y no anémicos en relación al Gaffar Méndez Castellano y diagnóstico nutricional. Los factores de riesgo para la anemia con valores de Odds Ratio (OR) >1 fueron la edad menor de 24 meses, ausencia de lactancia materna exclusiva en menores de 6 meses, ablactación antes de los 5 meses, dietas hipocalóricas y el hierro sérico < 41 ug/dL. La dieta normoproteica resultó ser factor de protección (OR<1). Se evidenció la importancia de la lactancia materna y de una adecuada alimentación complementaria a partir del 5° mes de la vida como factores de protección para la anemia ferropénica en niños menores de 6 años.
Iron deficiency anemia is considered as a worlwide public health problem. Small children are more vulnerable to this deficiency. To determine the risk and protection factors for iron deficiency anemia in children under 6 years of age. This is a descriptive and cross-sectional study. 100 children were evaluated. Age, gender, social stratification, nursing type, complementary feedings, nutritional diagnosis, characteristic of the diet (calories, proteins and iron). Hemoglobin (Hb), hematocrit (HTO), mean corpuscular volume (VCM), mean corpuscular hemoglobin (HCM), total and fractional proteins, serum iron. 46% of patients wer anemic. Average values were: age 19,2 months, duration of exclusive breastfeeding 5.2 months, beginning of complementary feeding 5,7 months, hemoglobin 9.9 g/dl. Younger children had an increased risk of developin ganemia. There was not a statistically significant difference between anemic and non anemic patients in regard to Graffar and nutritional diagnosis. Risk factors for anemia (Odds Ratio-OR-values >1) were age under 24 months, lack of exclusive breastfeeding in children under 6 months, complementary feedings before 5 months of age, hypocaloric diet and serum iron <41 ug/dL. Normoproteic diets proved to be a protection factor (OR<1). Breastfeeding and appropriate complementary feedings after 5 months of age are protection factors for iron deficiency anemia in children under 6 years of age.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Anemia Ferropriva/imunologia , Anemia Ferropriva/patologia , Anemias Nutricionais/diagnóstico , Deficiências de Ferro/diagnóstico , Heme/análise , Índices de Eritrócitos/fisiologia , Cuidado da Criança , Ingestão de Energia , Composição de AlimentosRESUMO
Nitrite has emerged as an endogenous signaling molecule with potential therapeutic implications for cardiovascular disease. Steady-state levels of nitrite are derived in part from dietary sources; therefore, we investigated the effects of dietary nitrite and nitrate supplementation and deficiency on NO homeostasis and on the severity of myocardial ischemia-reperfusion (MI/R) injury. Mice fed a standard diet with supplementation of nitrite (50 mg/liter) in their drinking water for 7 days exhibited significantly higher plasma levels of nitrite, exhibited significantly higher myocardial levels of nitrite, nitroso, and nitrosyl-heme, and displayed a 48% reduction in infarct size (Inf) after MI/R. Supplemental nitrate (1 g/liter) in the drinking water for 7 days also increased blood and tissue NO products and significantly reduced Inf. A time course of ischemia-reperfusion revealed that nitrite was consumed during the ischemic phase, with an increase in nitroso/nitrosyl products in the heart. Mice fed a diet deficient in nitrite and nitrate for 7 days exhibited significantly diminished plasma and heart levels of nitrite and NO metabolites and a 59% increase in Inf after MI/R. Supplementation of nitrite in the drinking water for 7 days reversed the effects of nitrite deficiency. These data demonstrate the significant influence of dietary nitrite and nitrate intake on the maintenance of steady-state tissue nitrite/nitroso levels and illustrate the consequences of nitrite deficiency on the pathophysiology of MI/R injury. Therefore, nitrite and nitrate may serve as essential nutrients for optimal cardiovascular health and may provide a treatment modality for cardiovascular disease.
Assuntos
Traumatismo por Reperfusão Miocárdica/prevenção & controle , Nitritos/uso terapêutico , Administração Oral , Animais , Suplementos Nutricionais , Avaliação Pré-Clínica de Medicamentos , Heme/análogos & derivados , Heme/análise , Camundongos , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Nitratos/análise , Óxido Nítrico/fisiologia , Nitritos/administração & dosagem , Nitrosação/efeitos dos fármacos , Compostos Nitrosos/análiseRESUMO
AIMS/HYPOTHESIS: Recently, a clear biological link between iron metabolism and diabetes has emerged from epidemiological and experimental studies. We carried out a prospective study of dietary iron intake and incidence of Type 2 diabetes. METHODS: 35,698 postmenopausal women initially aged 55 to 69 years were followed for 11 years. Diet was assessed with a food frequency questionnaire at baseline. RESULTS: Intake of heme iron showed a positive association with incident Type 2 diabetes; the relative risks were 1.0, 1.07, 1.12, 1.14, and 1.28 across quintiles of heme iron (p trend =0.02) after adjustment for non-dietary and dietary risk factors. Heme iron showed a weak positive association among non-drinkers, but the association appeared to be stronger among subjects who consumed more alcohol. For example, in a model restricted to those who drank alcohol at least 15 g/day, adjusted relative risks across quintiles of heme iron were 1.0, 2.26, 3.22, 1.92, and 4.42 (p trend =0.05); and consumers of 30 g/day of more of supplemental iron had an adjusted relative risk equal to 3.03 (95% CI, 1.29-7.12)], compared to those who took no iron supplement. Non-heme iron was inversely associated with incidence of Type 2 diabetes. Amongst non-drinkers adjusted relative risks were 1.0, 0.83, 0.87, 0.72, and 0.67 across quintiles (p trend <0.01). This inverse association was lost among drinkers, in whom there was no association of diabetes incidence with non-heme iron. CONCLUSIONS/INTERPRETATION: Greater dietary heme-iron intake and/or supplemental iron were associated with an increased risk of Type 2 diabetes, especially amongst those who drink alcohol.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Ferro da Dieta/efeitos adversos , Pós-Menopausa , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/etiologia , Suplementos Nutricionais/efeitos adversos , Suplementos Nutricionais/análise , Ingestão de Alimentos , Ingestão de Energia , Feminino , Heme/análise , Humanos , Iowa/epidemiologia , Ferro da Dieta/análise , Carne/efeitos adversos , Carne/análise , Pessoa de Meia-Idade , Análise Multivariada , Seleção de Pacientes , Estudos Prospectivos , Fatores de Risco , Fumar/efeitos adversos , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Human fetuses and neonates ingest erythropoietin (Epo) when they swallow amniotic fluid, colostrum, and human milk. This study was designed to determine whether enterally dosed recombinant Epo (rEpo) stimulates erythropoiesis in preterm neonates. METHODS: Preterm infants (<1500 g birth weight) were randomly assigned to receive feedings supplemented with either rEpo (1000 U/kg per day) or placebo for 14 days (n=36). Reticulocyte counts, serum Epo concentrations, hematocrit, and zinc protoporphyrin to heme ratios were measured at baseline and after 7 and 14 days of study drug administration. Transfusion guidelines were followed. Transfusion requirements, medications, feeding tolerance, and clinical diagnoses were documented. RESULTS: Enteral rEpo was well tolerated. There were no differences in erythropoietic indexes based on treatment group. Serum Epo concentrations were not different in the treatment versus placebo group, nor were transfusion requirements. CONCLUSIONS: Enterally dosed rEpo (1000 U/kg/day) does not significantly influence erythropoiesis or iron utilization when given for a 2-week period, nor does it elevate the serum Epo concentration in preterm or term infants. Oral administration of rEpo is not an effective substitute for parenteral administration.
Assuntos
Nutrição Enteral , Eritropoese/efeitos dos fármacos , Eritropoetina/administração & dosagem , Eritropoetina/farmacologia , Recém-Nascido Prematuro , Administração Oral , Transfusão de Sangue , Inibidores Enzimáticos/sangue , Eritropoetina/sangue , Hematócrito , Heme/análise , Humanos , Lactente , Recém-Nascido , Estudos Prospectivos , Protoporfirinas/sangue , Proteínas Recombinantes , Contagem de Reticulócitos , Fatores de TempoRESUMO
High intake of red meat, but not of white meat, is associated with an increased risk of colon cancer. However, red meat does not promote cancer in rodents. Haemin, added to low-calcium diets, increases colonic proliferation, and haemoglobin, added to high-fat diets, increases the colon tumour incidence in rats, an effect possibly due to peroxyl radicals. We thus speculated that haem might be the promoting agent in meat, and that prevention strategies could use calcium and antioxidants. These hypotheses were tested in rats at the aberrant crypt foci (ACF) stage at 100 days. F344 rats (n = 124) were given an injection of azoxymethane and were then randomized to 11 groups fed with low-calcium (20 micro mol/g) AIN76-based diets, containing 5% safflower oil. Haemin (0.25, 0.5 and 1.5 micro mol/g) or haemoglobin (1.5 and 3 micro mol haem/g) was added to five experimental diets, compared with a control diet without haem. Three other high-haemin diets (1.5 micro mol/g) were supplemented with calcium (250 micro mol/g), antioxidant butylated hydroxyanisole and rutin (0.05% each), and olive oil, which replaced safflower oil. Faecal water was assayed for lipid peroxidation by thiobarbituric acid reactive substances (TBARs) test, and for cytolytic activity. Haemin strikingly increased the ACF size, dose-dependently, from 2.6 to 11.4 crypts/ACF (all P < 0.001). The high-haemin diet also increased the number of ACF per colon (P < 0.001). Promotion was associated with increased faecal water TBARs and cytotoxicity. Calcium, olive oil and antioxidants each inhibited the haemin-induced ACF promotion, and normalized the faecal TBARs and cytotoxicity. The haemoglobin diets increased the number of ACF and faecal TBARs, but not the ACF size or the faecal cytotoxicity. In conclusion, dietary haemin is the most potent known ACF promoter. Haemoglobin is also a potent promoter of colorectal carcinogenesis. The results suggest that myoglobin in red meat could promote colon cancer. Diets high in calcium, or in oxidation-resistant fats, may prevent the possible cancer-promoting effect of red meat.
Assuntos
Colo/efeitos dos fármacos , Colo/patologia , Neoplasias Colorretais/etiologia , Hemina/efeitos adversos , Hemoglobinas/efeitos adversos , Carne/efeitos adversos , Animais , Antioxidantes/farmacologia , Azoximetano/toxicidade , Hidroxianisol Butilado/farmacologia , Cálcio/metabolismo , Dieta , Relação Dose-Resposta a Droga , Fezes/química , Feminino , Heme/análise , Peroxidação de Lipídeos/efeitos dos fármacos , Azeite de Oliva , Óleos de Plantas/farmacologia , Ratos , Ratos Endogâmicos F344 , Rutina/farmacologia , Óleo de Cártamo/farmacologia , Substâncias Reativas com Ácido Tiobarbitúrico , Aumento de PesoRESUMO
OBJECTIVE: Zinc protoporphyrin/heme ratio (ZnPP/H) has been well established as an indicator of functional iron deficiency in subjects 6 months of age to adult. The primary objective of this study was to establish normative values for ZnPP/H in NICU patients and secondarily to explore the utility of this test as an indicator of iron deficiency in neonates. Study design ZnPP/H and complete blood counts were obtained weekly on consecutive NICU patients. Gestational age, growth variables, iron supplementation, erythropoietin treatment, and blood transfusions were documented. Results are reported as mean +/- SD. A value of P <.05 was considered significant. RESULTS: ZnPP/H ratios (n = 639) were evaluated from 143 infants. During the first week of life, ZnPP/H was inversely correlated with gestational age (n = 78, P <.001, r = -0.72). Maternal diabetes, growth retardation, and exposure to chorioamnionitis were independent risk factors for high ZnPP/H. Both iron supplementation and blood transfusion decreased ZnPP/H (P <.001). Erythropoietin treatment was associated with an increase in reticulocyte count and ZnPP/H (P <.001). CONCLUSIONS: ZnPP/H is inversely correlated with gestational age, and the range in all newborn infants is higher than in adults. ZnPP/H is elevated in certain infant subpopulations, which suggests that they may require additional iron supplementation.
Assuntos
Heme/análise , Deficiências de Ferro , Protoporfirinas/sangue , Biomarcadores/sangue , Contagem de Células Sanguíneas , Transfusão de Eritrócitos , Eritropoetina/uso terapêutico , Compostos Ferrosos/uso terapêutico , Idade Gestacional , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Proteínas Recombinantes , Valores de Referência , Fatores de RiscoRESUMO
Inflammatory bowel disease is often associated with iron deficiency anemia and oral iron supplementation may be required. However, iron may increase oxidative stress through the Fenton reaction and thus exacerbate the disease. This study was designed to determine in rats with dextran sulfate sodium (DSS)-induced colitis whether oral iron supplementation increases intestinal inflammation and oxidative stress and whether the addition of an antioxidant, vitamin E, would reduce this detrimental effect. Four groups of rats that consumed 50 g/L DSS in drinking water were studied for 7 d and were fed: a control, nonpurified diet (iron, 270 mg, and dl-alpha-tocopherol acetate, 49 mg/kg); diet + iron (iron, 3000 mg/kg); diet + vitamin E (dl-alpha-tocopherol acetate, 2000 mg/kg) and the diet + both iron and vitamin E, each at the same concentrations as above. Body weight change, rectal bleeding, histological scores, plasma and colonic lipid peroxides (LPO), plasma 8-isoprostane, colonic glutathione peroxidase (GPx) and plasma vitamin E were measured. Iron supplementation increased disease activity as demonstrated by higher histological scores and heavier rectal bleeding. This was associated with an increase in colonic and plasma LPO and plasma 8-isoprostane as well as a decrease in colonic GPx. Vitamin E supplementation decreased colonic inflammation and rectal bleeding but did not affect oxidative stress, suggesting another mechanism for reducing inflammation. In conclusion, oral iron supplementation resulted in an increase in disease activity in this model of colitis. This detrimental effect on disease activity was reduced by vitamin E. Therefore, the addition of vitamin E to oral iron supplementation may be beneficial.
Assuntos
Antioxidantes/metabolismo , Colite/prevenção & controle , Ferro da Dieta/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Vitamina E/metabolismo , Administração Oral , Animais , Colite/induzido quimicamente , Colite/patologia , Sulfato de Dextrana , Suplementos Nutricionais , Modelos Animais de Doenças , Interações Medicamentosas , Fezes/química , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/patologia , Hemorragia Gastrointestinal/prevenção & controle , Glutationa Peroxidase/metabolismo , Heme/análise , Inflamação , Peroxidação de Lipídeos , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Vitamina E/sangueRESUMO
OBJECTIVE: Iron deficiency anemia is known to impair cognitive and psychomotor development. The zinc protoporphyrin/heme (ZPP/H) ratio is a simple, accurate, and sensitive laboratory screening test that detects early iron depletion before the onset of anemia. The objective of this work was to evaluate this test in a primary pediatric practice setting. METHODS: The iron status of a cohort of 361 children was screened during routine examinations at a community pediatric practice. Whole blood hemoglobin concentration, hematocrit ratio, serum transferrin saturation, ferritin concentration, and the ZPP/H ratio were measured. The ZPP/H ratio then was evaluated as a single indicator of iron status by comparing it with other tests for detecting the onset of iron deficiency and for monitoring recovery after iron supplementation. RESULTS: Significant age- and sex-related differences in the ZPP/H ratio were found. In this cohort, serum ferritin concentration and the ZPP/H ratio independently identified the same fraction of iron-deficient patients (3%-4%), and both tests were more specific than was either hemoglobin or hematocrit. A concordance of three iron status parameters changed the prediction of iron deficiency to =1%. Children <3 years of age and adolescent girls had significantly higher ZPP/H results. CONCLUSION: The prevalence of iron deficiency anemia in the typical healthy American pediatric population is low, but iron deficiency without anemia remains relatively common at some stages of development. Increase in the ZPP/H ratio is demonstrated to be a sensitive, specific, and cost-effective test for identifying preanemic iron deficiency in a community pediatric practice. anemia, nutrition, development.
Assuntos
Anemia Ferropriva/diagnóstico , Inibidores Enzimáticos/sangue , Heme Oxigenase (Desciclizante)/antagonistas & inibidores , Heme/análise , Deficiências de Ferro , Protoporfirinas/sangue , Adolescente , Fatores Etários , Anemia Ferropriva/sangue , Criança , Pré-Escolar , Feminino , Ferritinas/sangue , Testes Hematológicos , Heme/antagonistas & inibidores , Humanos , Lactente , Ferro/sangue , Masculino , Análise de Regressão , Sensibilidade e Especificidade , Fatores Sexuais , Transferrina/análiseRESUMO
Novel leads are urgently required for designing antimalarials due to the reduced efficacy of presently available drugs. The malaria parasite has a unique reaction of heme polymerization, which has attracted much attention in the recent past as a target for the design of antimalarial drugs. The process is hampered by non-availability of a proper assay method. Currently available methods are cumbersome and require advanced instrumentation or radioactive substrates. Here, we are describing an assay for hemozoin formation that is simple and reproducible. This assay has routinely been used by us for the identification of potential compounds with antimalarial activity.