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1.
Int J Mol Sci ; 23(4)2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35216261

RESUMO

Un-complexed polynuclear ferric oxyhydroxide cannot be administered safely or effectively to patients. When polynuclear iron cores are formed with carbohydrates of various structures, stable complexes with surface carbohydrates driven by multiple interacting sites and forces are formed. These complexes deliver iron in a usable form to the body while avoiding the serious adverse effects of un-complexed forms of iron, such as polynuclear ferric oxyhydroxide. The rate and extent of plasma clearance and tissue biodistribution is variable among the commercially available iron-carbohydrate complexes and is driven principally by the surface characteristics of the complexes which dictate macrophage opsonization. The surface chemistry differences between the iron-carbohydrate complexes results in significant differences in in vivo pharmacokinetic and pharmacodynamic profiles as well as adverse event profiles, demonstrating that the entire iron-carbohydrate complex furnishes the pharmacologic action for these complex products. Currently available physicochemical characterization methods have limitations in biorelevant matrices resulting in challenges in defining critical quality attributes for surface characteristics for this class of complex nanomedicines.


Assuntos
Carboidratos/farmacologia , Carboidratos/farmacocinética , Compostos de Ferro/farmacologia , Compostos de Ferro/farmacocinética , Ferro/farmacologia , Ferro/farmacocinética , Nanopartículas/metabolismo , Administração Intravenosa/métodos , Animais , Compostos Férricos/metabolismo , Humanos
2.
J Nutr ; 151(Suppl 1): 3S-14S, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33582781

RESUMO

This introductory article provides an in-depth technical background for iron fortification, and thus introduces a series of articles in this supplement designed to present the current evidence on the fortification of salt with both iodine and iron, that is, double-fortified salt (DFS). This article reviews our current knowledge of the causes and consequences of iron deficiency and anemia and then, with the aim of assisting the comparison between DFS and other common iron-fortified staple foods, discusses the factors influencing the efficacy of iron-fortified foods. This includes the dietary and physiological factors influencing iron absorption; the choice of an iron compound and the fortification technology that will ensure the necessary iron absorption with no sensory changes; encapsulation of iron fortification compounds to prevent unacceptable sensory changes; the addition of iron absorption enhancers; the estimation of the iron fortification level for each vehicle based on iron requirements and consumption patterns; and the iron status biomarkers that are needed to demonstrate improved iron status in populations regularly consuming the iron-fortified food. The supplement is designed to provide a summary of evidence to date that can help advise policy makers considering DFS as an intervention to address the difficult public health issue of iron deficiency anemia, while at the same time using DFS to target iodine deficiency.


Assuntos
Absorção Fisiológica , Tecnologia de Alimentos , Alimentos Fortificados , Iodo , Ferro da Dieta/administração & dosagem , Ferro da Dieta/farmacocinética , Cloreto de Sódio na Dieta , Anemia Ferropriva/prevenção & controle , Disponibilidade Biológica , Biomarcadores , Humanos , Compostos de Ferro/administração & dosagem , Compostos de Ferro/farmacocinética , Estado Nutricional
3.
Artigo em Inglês | MEDLINE | ID: mdl-29869925

RESUMO

A novel aluminum/olivine composite (AOC) was prepared by wet impregnation followed by calcination and was introduced as an efficient adsorbent for defluoridation. The adsorption of fluoride was modeled with one-, two- and three-parameter isotherm equations by non-linear regression to demonstrate the adsorption equilibrium. The FI was the best-fitted model among the two-parameter isotherms with a R2 value of 0.995. The three-parameter models were found to have better performance with low values of the error functions and high F values. The neural-network-based model was applied for the first time in the isotherm study. The optimized model was framed with eight neurons in hidden layer with a mean square of error of 0.0481 and correlation coefficient greater than 0.999. The neural-based model has the better predictability with a higher F value of 9484 and R2 value of 0.998 compared to regression models, exhibiting the F value and the R2 in the range of 86-3572 and 0.835-0.995, respectively. The material characterization established the formation of the aluminum oxide, silicate, etc. onto the olivine which is conducive of the removal of fluoride by the formation of aluminum fluoride compounds, such as AlF3 in the spent material after defluoridation.


Assuntos
Fluoretos/farmacocinética , Compostos de Ferro/farmacocinética , Compostos de Magnésio/farmacocinética , Redes Neurais de Computação , Silicatos/farmacocinética , Purificação da Água , Absorção Fisico-Química , Alumínio/química , Alumínio/farmacocinética , Óxido de Alumínio/química , Fenômenos Químicos , Fluoretos/química , Compostos de Ferro/química , Cinética , Análise dos Mínimos Quadrados , Compostos de Magnésio/química , Silicatos/química , Temperatura , Purificação da Água/instrumentação , Purificação da Água/métodos
4.
Regul Toxicol Pharmacol ; 97: 17-23, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29857115

RESUMO

Intravenous (IV) iron formulations are complex colloidal suspensions of iron oxide nanoparticles. Small changes in formulation can allow more labile iron to be released after injection causing toxicity. Thus, bioequivalence (BE) evaluation of generic IV iron formulations remains challenging. We evaluated labile iron release in vitro and in vivo using a high performance liquid chromatography chelatable iron assay to develop a relational model to support BE. In vitro labile iron release and in vivo labile iron pharmacokinetics were evaluated for Venofer®, Ferrlecit®, generic sodium ferric gluconate complex, InFeD®, Feraheme® and a pre-clinical formulation GE121333. Labile iron release profiles were studied in vitro in 150 mM saline and a biorelevant matrix (rat serum) at 0.952 mgFe/mL. In vivo plasma labile iron concentration-time profiles (t0-240 min) were studied in rats after a 40 mgFe/kg IV dose. In vitro labile iron release in saline was significantly higher compared to rat serum, especially with InFeD®. An in vitro release constant (iKr) was calculated which correlated well with maximal plasma concentrations in the in vivo rat PK model (R2 = 0.711). These data suggest an in vitro to in vivo correlation model of labile iron release kinetics could be applied to BE. Other generic IV iron formulations need to be studied to validate this model.


Assuntos
Quelantes/química , Desferroxamina/química , Compostos de Ferro/sangue , Nanopartículas/química , Administração Intravenosa , Animais , Compostos de Ferro/administração & dosagem , Compostos de Ferro/farmacocinética , Cinética , Masculino , Nanopartículas/administração & dosagem , Ratos , Ratos Sprague-Dawley
5.
Nanomedicine (Lond) ; 11(7): 783-96, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26979124

RESUMO

BACKGROUND: While carbon-encapsulated iron carbide nanoparticles exhibit strong magnetic properties appealing for biomedical applications, potential side effects of such materials remain comparatively poorly understood. Here, we assess the effects of iron-based nanoparticles in an in vivo long-term study in mice with observation windows between 1 week and 1 year. MATERIALS & METHODS: Functionalized (PEG or IgG) carbon-encapsulated platinum-spiked iron carbide nanoparticles were injected intravenously in mice (single or repeated dose administration). RESULTS: One week after administration, magnetic nanoparticles were predominantly localized in organs of the reticuloendothelial system, particularly the lung and liver. After 1 year, particles were still present in these organs, however, without any evident tissue alterations, such as inflammation, fibrosis, necrosis or carcinogenesis. Importantly, reticuloendothelial system organs presented with normal function. CONCLUSION: This long-term exposure study shows high in vivo compatibility of intravenously applied carbon-encapsulated iron nanoparticles suggesting continuing investigations on such materials for biomedical applications.


Assuntos
Compostos Inorgânicos de Carbono/efeitos adversos , Carbono/efeitos adversos , Materiais Revestidos Biocompatíveis/efeitos adversos , Portadores de Fármacos/efeitos adversos , Compostos de Ferro/efeitos adversos , Nanopartículas/efeitos adversos , Animais , Carbono/administração & dosagem , Carbono/química , Carbono/farmacocinética , Compostos Inorgânicos de Carbono/administração & dosagem , Compostos Inorgânicos de Carbono/química , Compostos Inorgânicos de Carbono/farmacocinética , Materiais Revestidos Biocompatíveis/administração & dosagem , Materiais Revestidos Biocompatíveis/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Feminino , Compostos de Ferro/administração & dosagem , Compostos de Ferro/química , Compostos de Ferro/farmacocinética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/ultraestrutura , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/ultraestrutura , Imãs/efeitos adversos , Imãs/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/administração & dosagem , Nanopartículas/análise , Nanopartículas/química
6.
Contrast Media Mol Imaging ; 7(1): 35-44, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22344878

RESUMO

Islets can be visualized on MRI by labeling with superparamagnetic contrast agent during the transplantation procedure. However, whether the signal intensity reflects the cell number and cellular viability has not been determined. We used a self-synthesized novel superparamagnetic contrast agent -polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles (PVP-SPIO) - to label ß-TC-6 cells (a mouse insulinoma cell line) or primary islets with commercial Feridex as a control. The labeling efficiency of two agents was compared by Prussian blue staining, intracellular iron content determination and MR scanning. Cells were exposed to hypoxia, high-glucose or exogenous H2O2 stimulation before/after PVP-SPIO labeling. Normal and injured cells were also transplanted into renal subcapsule. A clinically used 3.0 T MR scan was performed in vitro and 24 h post-transplantation to investigate the correlation between cellular viability and signal. Our PVP-SPIO displayed superior biocompatibility and magnetic properties. All of the cells could be labeled at 100 µg/ml iron concentration after 24 h incubation. At 100 µg/ml iron concentration, 1 × 105 ß cells labeled with PVP-SPIO could already be visualized in vitro by MRI, less than the detection threshold of Feridex. There existed a linear correlation between the number of labeled cells and R2 value on the T2 -weighted images. The signal intensity and the intracellular iron content declined along with the decreased viability of labeled cells. There was also a significant difference in signal intensity between injured and normal labeled cells after transplantation. From these results, we concluded that PVP-SPIO possessed superior cell labeling efficiency, and ß cells could be labeled without compromising viability and function. The signal intensity on MRI might be a useful predictor to evaluate the number and the viability of PVP-SPIO-labeled cells.


Assuntos
Rastreamento de Células/métodos , Meios de Contraste/análise , Sobrevivência de Enxerto , Compostos de Ferro/análise , Transplante das Ilhotas Pancreáticas , Imageamento por Ressonância Magnética/métodos , Nanopartículas de Magnetita/análise , Óxidos/análise , Povidona/análise , Animais , Hipóxia Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Meios de Contraste/farmacocinética , Dextranos/análise , Dextranos/farmacocinética , Ferrocianetos , Glucose/farmacologia , Peróxido de Hidrogênio/farmacologia , Insulinoma/patologia , Compostos de Ferro/farmacocinética , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Óxidos/farmacocinética , Neoplasias Pancreáticas/patologia , Povidona/análogos & derivados , Povidona/farmacocinética , Coloração e Rotulagem , Ensaio de Cápsula Sub-Renal
7.
Contrast Media Mol Imaging ; 7(1): 51-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22344880

RESUMO

The aim of this work was to investigate the MRI findings on tumor xenografts induced in nude mice by the inoculation of human pancreatic cancer cells labeled with superparamagnetic iron oxide (SPIO), and to monitor the kinetics of SPIO distribution in tumor xenografts. The labeled cancer cells were subcutaneously inoculated into 11 nude mice to induce tumor xenograft. The unlabeled cancer cells served as a control inoculated into nine nude mice. MR imaging was performed with a 1.5 T MR scanner for the tumor xenograft at the first, second and third week after the inoculation. We found that the tumor xenograft was induced in 100% nude mice on MR imaging for both groups in the first week after the inoculation. In the SPIO group, the tumors showed homogeneous hypointensity on T1 - and T2 -weighted and FIESTA images 1 week after inoculation. Two and 3 weeks after inoculation, the center of the tumors was still hypointense on all the above sequences. The tumor periphery was isointense on T1 -weighted, and hyperintense on T2 -weighted and FIESTA images. The tumors in control group were homogeneously hypointense or isointense on T1 -weighted, and hyperintense on T2 -weighted and FIESTA images in the first, second and third week after the inoculation. The size and signal-to-noise ratio of the tumor center in the SPIO group had decreased subsequent to the inoculation in all T1 - and T2 -weighted images and FIESTA. Our results showed the human pancreatic cancer cells labeled with SPIO can induce tumor xenograft in nude mice and MRI can monitor the kinetics of SPIO distribution in tumor xenografts.


Assuntos
Carcinoma Ductal Pancreático/patologia , Rastreamento de Células/métodos , Meios de Contraste , Imageamento Tridimensional/métodos , Compostos de Ferro , Imageamento por Ressonância Magnética/métodos , Óxidos , Neoplasias Pancreáticas/patologia , Animais , Linhagem Celular Tumoral/transplante , Corpo Estriado/patologia , Dextranos/farmacocinética , Humanos , Processamento de Imagem Assistida por Computador , Compostos de Ferro/análise , Compostos de Ferro/farmacocinética , Nanopartículas de Magnetita , Camundongos , Camundongos Nus , Óxidos/análise , Óxidos/farmacocinética , Distribuição Tecidual , Transplante Heterólogo
8.
Ter Arkh ; 84(12): 85-7, 2012.
Artigo em Russo | MEDLINE | ID: mdl-23479997

RESUMO

AIM: To comparatively evaluate the efficiency of preventive treatment with various iron preparations on copper, manganese, and iron metabolic features in adult athletes. SUBJECTS AND METHODS: Forty adult highly qualified sambo wrestlers were examined and divided into 4 groups of 10 persons in each. Group 1 athletes took iron-containing Sorbifer Durules in combination with ascorbic acid; Group 2 received Ferro Gradumet Vitamin C; Group 3 had Hemofer and ascorbic acid; Group 4 took ascorbic acid tablets. The latter group served as a control. Blood samples (15-20 ml) to be tested were taken at the beginning and end of 2-week use of iron preparations. The daily balance of iron, copper, and manganese was estimated following 7-day intake of these preparations. RESULTS: The use of iron-containing preparations in combination with ascorbic acid was ascertained to be accompanied by an increment in the plasma concentration of iron and blood corpuscles, indicating an increased need for this biotic and its deficiency in athletes. When the dose of iron was increased in the iron preparations, there was a substantial rise in the excretion of copper, manganese in particular, through the gastrointestinal tract and kidney and a negative balance of these trace elements in the body. CONCLUSION: Dietary addition of foods containing large amounts of ferrous iron, copper, and manganese is indicated for athletes exposed to higher intensity exercises.


Assuntos
Ácido Ascórbico , Cobre , Compostos de Ferro , Distúrbios do Metabolismo do Ferro/prevenção & controle , Ferro , Manganês , Adulto , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/farmacocinética , Atletas , Cobre/análise , Cobre/metabolismo , Dietoterapia/métodos , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Humanos , Ferro/metabolismo , Compostos de Ferro/administração & dosagem , Compostos de Ferro/farmacocinética , Deficiências de Ferro , Distúrbios do Metabolismo do Ferro/etiologia , Distúrbios do Metabolismo do Ferro/metabolismo , Masculino , Manganês/análise , Manganês/metabolismo , Taxa de Depuração Metabólica/efeitos dos fármacos , Prevenção Primária/métodos , Análise Espectral/métodos , Esportes/fisiologia , Oligoelementos/análise , Oligoelementos/metabolismo , Vitaminas/administração & dosagem , Vitaminas/farmacocinética
9.
Pak J Biol Sci ; 14(20): 945-9, 2011 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-22514896

RESUMO

Rat Everted Gut Sac (EGS) model was employed to study the intestinal uptake of titanium and iron. Incubation of freshly prepared rat EGS in Earle's medium pH = 7.4 containing titanium showed that the absorption of titanium as well as iron was a dose dependent process. Ascorbic acid enhanced the absorption of both metal ions, while NaF (1 mM) as an inhibitor of glycolytic energy supply, decreased their absorption. The Na+-K+ ATPase inhibitor, ouabain (1 mM) reduced intestinal absorption of Titanium. This suggests that titanium uptake is an active transport process as is iron uptake. Iron absorption was reduced approximate by 17% when titanium was presented to incubation medium EGS whereas, the absorption of titanium was decreased by 35% when iron was added to the reaction mixture.


Assuntos
Mucosa Intestinal/metabolismo , Compostos de Ferro/farmacocinética , Titânio/farmacocinética , Animais , Ácido Ascórbico/metabolismo , Transporte Biológico/efeitos dos fármacos , Transporte Biológico Ativo/efeitos dos fármacos , Ácido Cítrico/farmacocinética , Absorção Intestinal , Mucosa Intestinal/efeitos dos fármacos , Masculino , Ouabaína/farmacologia , Ratos , Ratos Wistar , Fluoreto de Sódio/farmacologia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores
10.
Food Nutr Bull ; 31(1 Suppl): S7-21, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20629349

RESUMO

BACKGROUND: Iron fortification of wheat flour is widely used as a strategy to combat iron deficiency. OBJECTIVE: To review recent efficacy studies and update the guidelines for the iron fortification of wheat flour. METHODS: Efficacy studies with a variety of iron-fortified foods were reviewed to determine the minimum daily amounts of additional iron that have been shown to meaningfully improve iron status in children, adolescents, and women of reproductive age. Recommendations were computed by determining the fortification levels needed to provide these additional quantities of iron each day in three different wheat flour consumption patterns. Current wheat flour iron fortification programs in 78 countries were evaluated. RESULTS: When average daily consumption of low-extraction (< or = 0.8% ash) wheat flour is 150 to 300 g, it is recommended to add 20 ppm iron as NaFeEDTA, or 30 ppm as dried ferrous sulfate or ferrous fumarate. If sensory changes or cost limits the use of these compounds, electrolytic iron at 60 ppm is the second choice. Corresponding fortification levels were calculated for wheat flour intakes of < 150 g/day and > 300 g/day. Electrolytic iron is not recommended for flour intakes of < 150 g/day. Encapsulated ferrous sulfate or fumarate can be added at the same concentrations as the non-encapsulated compounds. For high-extraction wheat flour (> 0.8% ash), NaFeEDTA is the only iron compound recommended. Only nine national programs (Argentina, Chile, Egypt, Iran, Jordan, Lebanon, Syria, Turkmenistan, and Uruguay) were judged likely to have a significant positive impact on iron status if coverage is optimized. Most countries use non-recommended, low-bioavailability, atomized, reduced or hydrogen-reduced iron powders. CONCLUSION: Most current iron fortification programs are likely to be ineffective. Legislation needs updating in many countries so that flour is fortified with adequate levels of the recommended iron compounds.


Assuntos
Farinha/análise , Alimentos Fortificados/normas , Ferro/administração & dosagem , Política Nutricional/tendências , Triticum , Adolescente , Adulto , Anemia Ferropriva/prevenção & controle , Criança , Dieta , Estudos de Avaliação como Assunto , Feminino , Guias como Assunto , Humanos , Internacionalidade , Ferro/química , Compostos de Ferro/administração & dosagem , Compostos de Ferro/farmacocinética , Deficiências de Ferro , Masculino , Estado Nutricional , Adulto Jovem
12.
Am J Clin Nutr ; 89(2): 533-8, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19073788

RESUMO

BACKGROUND: Hepcidin is a key regulator of iron homeostasis, but to date no studies have examined the effect of hepcidin on iron absorption in humans. OBJECTIVE: Our objective was to assess relations between both serum hepcidin and serum prohepcidin with nonheme-iron absorption in the presence and absence of food with the use of dual stable-iron-isotope techniques. DESIGN: The study group included 18 healthy nonpregnant women. Women received in random order a supplemental iron source (7.6 mg FeSO4 providing 0.9 mg 58Fe as FeSO4) and 6.8 mg 57Fe ferrous sulfate tracer administered with a nonheme food source [orange-fleshed sweet potato (OFSP): 1.4 mg native Fe]. Iron absorption was determined by analyzing blood samples taken 14 d after dosing with the use of magnetic sector thermal ionization mass spectrometry. Serum hepcidin was assessed by a new competitive serum enzyme-linked immunosorbent assay (ELISA) specific for the refolded, mature 25-amino acid form, and serum prohepcidin was assessed by an ELISA specific for amino acids 28-47 of the hepcidin prohormone. RESULTS: In these women, iron absorption averaged 14.71 +/- 10.7% from the supplemental iron compared with 3.63 +/- 6.5% from the OFSP. Absorption of nonheme iron assessed in the presence (P = 0.038) and absence (P = 0.0296) of food was significantly associated with serum hepcidin but was not significantly related to serum prohepcidin. CONCLUSION: Serum hepcidin, but not prohepcidin, was inversely associated with iron absorption from supplemental and food-based nonheme-iron sources in iron-replete healthy women.


Assuntos
Peptídeos Catiônicos Antimicrobianos/sangue , Suplementos Nutricionais , Absorção Intestinal/efeitos dos fármacos , Ferro da Dieta/farmacocinética , Precursores de Proteínas/sangue , Adolescente , Adulto , Peptídeos Catiônicos Antimicrobianos/farmacologia , Disponibilidade Biológica , Ensaio de Imunoadsorção Enzimática , Feminino , Ferritinas/sangue , Hemoglobinas/análise , Hepcidinas , Humanos , Ipomoea batatas/química , Compostos de Ferro/sangue , Compostos de Ferro/metabolismo , Compostos de Ferro/farmacocinética , Isótopos de Ferro , Ferro da Dieta/sangue , Ferro da Dieta/metabolismo , Espectrometria de Massas , Estado Nutricional , Pré-Menopausa , Precursores de Proteínas/farmacologia , Adulto Jovem
13.
Med Oncol ; 26(1): 105-15, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-18473194

RESUMO

UNLABELLED: Cancer-related anemia is common and multifactorial in origin. Functional iron deficiency (FID) is now recognized as a cause of iron-restricted erythropoiesis and may be one of the major reasons for lack of response to treatment with Erythropoietic Stimulating Agents (ESAs). Numerous studies have shown that intravenous (IV), but not oral, iron therapy effectively provides sufficient iron for optimal erythropoiesis in anemic patients with chronic renal disease receiving ESA therapy. The use of IV iron has also been suggested in the cancer setting. Six recent studies have tested this assumption and are summarized in this review. Four formulations of IV iron are available in Europe, with different pharmacokinetics, iron bioavailability, and risk of acute adverse drug reactions. CONCLUSION: Limited iron stores and FID are common causes of response failure during ESA treatment in cancer patients and should be diagnosed. There is now substantial scientific support for the use of IV iron supplementation to improve response and this has been acknowledged in international and national guidelines. Prospective long-term data on the safety of IV iron in this setting are still awaited. Recommendations concerning the optimal formulation, doses, and schedule of iron supplementation to ESA treatment in cancer-related anemia are provisional awaiting data from prospective, randomized trials.


Assuntos
Anemia Ferropriva , Hematínicos/administração & dosagem , Compostos de Ferro/administração & dosagem , Neoplasias/complicações , Administração Oral , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/etiologia , Esquema de Medicação , Eritropoese/efeitos dos fármacos , Compostos Férricos/administração & dosagem , Compostos Férricos/efeitos adversos , Compostos Férricos/farmacocinética , Óxido de Ferro Sacarado , Compostos Ferrosos/administração & dosagem , Compostos Ferrosos/efeitos adversos , Compostos Ferrosos/farmacocinética , Ácido Glucárico , Hematínicos/efeitos adversos , Hematínicos/farmacocinética , Humanos , Infusões Intravenosas , Compostos de Ferro/efeitos adversos , Compostos de Ferro/farmacocinética , Ferro da Dieta/administração & dosagem , Ferro da Dieta/efeitos adversos , Ferro da Dieta/farmacocinética , Complexo Ferro-Dextran/administração & dosagem , Complexo Ferro-Dextran/efeitos adversos , Complexo Ferro-Dextran/farmacocinética , Maltose/administração & dosagem , Maltose/efeitos adversos , Maltose/análogos & derivados , Maltose/farmacocinética , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Toxicol Appl Pharmacol ; 229(3): 273-80, 2008 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-18384829

RESUMO

The relation between haem biosynthesis and intestinal iron absorption is not well understood, we therefore investigated the effect of compounds that alter haem metabolism on duodenal iron absorption. CD1 mice were treated with either an inhibitor (succinyl acetone (SA)) or stimulator (2-allyl-2-isopropylacetamide (AIA)) of haem biosynthesis. 5-Aminolaevulinic acid (ALA) dehydratase and urinary ALA and porphobilinogen (PBG) levels, were determined. Intestinal iron absorption was assayed with in vivo and in vitro techniques. Liver hepcidin (Hamp1) and duodenal iron transporter mRNA levels were measured using RT-PCR. AIA caused increased hepatic ALA synthase (1.6-fold) and ALA dehydratase (1.4-fold, both p<0.005) activities and increased urinary ALA and PBG excretion (2.1- and 1.4-fold, p<0.005, p<0.05, respectively). In vivo intestinal iron absorption was reduced to 49% of control (p<0.005). Mice treated with SA showed decreased urinary ALA and PBG levels (75 and 55% control, both p<0.005) and reductions in both ALA synthase and ALA dehydratase activities (77 and 56% control, p<0.05, p<0.005, respectively) in the liver. Liver and duodenal haem and cytochrome oxidase levels were not significantly decreased. Iron absorption was enhanced (1.26-fold, p<0.05) and hepatic Hamp1 mRNA was reduced (53% of control, p<0.05). In vitro duodenal iron uptake after mice were injected with SA also demonstrated an increase in Fe(III) reduction and uptake (1.27- and 1.41-fold, p<0.01 respectively). Simultaneous injections of SA and ALA blocked the enhancing effect on iron absorption seen with SA alone. We conclude that alterations in haem biosynthesis can influence iron absorption and in particular, the intermediate ALA seems to be an inhibitor of iron absorption.


Assuntos
Ácido Aminolevulínico/metabolismo , Heme/biossíntese , Absorção Intestinal , Compostos de Ferro/farmacocinética , Alilisopropilacetamida/farmacologia , Ácido Aminolevulínico/urina , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Duodeno/metabolismo , Inibidores Enzimáticos/farmacologia , Hepcidinas , Heptanoatos/farmacologia , Masculino , Camundongos , Porfobilinogênio/metabolismo , Sintase do Porfobilinogênio/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
Int J Vitam Nutr Res ; 77(3): 166-73, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-18214017

RESUMO

The bioavailability (relative bioavailability value; RBV) of iron compounds relative to ferrous sulfate has proven useful in ranking the potential of iron compounds for food fortification. The efficacy of iron-fortified foods however depends on the absolute iron absorption from the fortified food and not on the RBV of the iron compound. Compounds of lower RBV can be used to design efficacious fortified foods by adding them at an appropriately higher level. Efficacy thus depends on the amount of iron added to the food vehicle as well as the daily consumption of the fortified food by the target population, the amount of iron lacking in the diet of the target population in relation to their needs, and the prevalence of widespread infections and other micronutrient deficiencies. The World Health Organization has recently published guidelines for food fortification, which include recommendations for iron fortification compounds and a method of how to define the iron fortification level. The same organization has also published guidelines on the iron status methods to be used to monitor interventions. Recent efficacy studies, which have to a large extent followed these guidelines, have shown good efficacy of iron-fortified salt, fish sauce, wheat flour, and rice in improving the iron status of target populations. However, although we now know how to design an efficacious iron-fortified food, efficacy cannot be ensured in populations with widespread infections and other micronutrient deficiencies. In such situations, other public health measures may be necessary before we can ensure an improvement in iron status.


Assuntos
Alimentos Fortificados , Compostos de Ferro/farmacocinética , Ferro da Dieta/farmacocinética , Animais , Disponibilidade Biológica , Guias como Assunto , Humanos , Absorção Intestinal/efeitos dos fármacos , Compostos de Ferro/administração & dosagem , Compostos de Ferro/metabolismo , Ferro da Dieta/administração & dosagem , Ferro da Dieta/metabolismo , Estado Nutricional , Ratos , Organização Mundial da Saúde
16.
Bioresour Technol ; 98(8): 1622-8, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-16935492

RESUMO

Yeast biomass enriched with iron could represent a new and safer solution for prevention from anaemia development. Such an iron source is less toxic and has better absorbability in organisms. The purpose of our research was the determination of the most suitable iron source in the cultivation medium for the yeast Saccharomyces cerevisiae, regarding good growth and iron accumulation in cells. Iron(III) citrate, iron(III) chloride, iron(III) nitrate and Fe-EDTA complex were used. The uptake of the chosen iron compound, Fe(III) citrate, by the yeasts Candida intermedia and Kluyveromyces marxianus was also investigated. Different growth behaviour of the three yeast strains in the presence of Fe(III) citrate was observed. The highest amounts of accumulated iron in S. cerevisiae, C. intermedia and K. marxianus biomass were about 13, 20 and 34mgFeg(-1)dry wt., respectively. To optimise the accumulation of iron in K. marxianus and to characterise iron enriched yeast biomass, further experiments are needed.


Assuntos
Meios de Cultura/metabolismo , Compostos de Ferro/metabolismo , Leveduras/crescimento & desenvolvimento , Leveduras/metabolismo , Ração Animal , Biomassa , Suplementos Nutricionais , Compostos de Ferro/farmacocinética , Fatores de Tempo
17.
Water Res ; 40(16): 3075-3082, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16901528

RESUMO

Batch tests were conducted to investigate reduction of nitrobenzene in a zerovalent iron system (Fe0) under various conditions. The results indicated that a limited amount of nitrobenzene (ArNO2) could be reduced to aniline by Fe0, but formation of a lepidocrocite (gamma-FeOOH) coating could significantly slow down the reaction. However, augmenting Fe0 with substoichiometric FeCl2 could dramatically accelerate the reaction. Surface-adsorbed Fe(II), not pH nor Cl-, was found to be responsible for rejuvenating the system. O2 and nitrobenzene could be concomitantly reduced by Fe0 in the presence of Fe2+. In the Fe0 system, both nitrobenzene and O2 favored formation of lepidocrocite; in the presence of aq. Fe(II), a stratified corrosion coating could develop, with magnetite (Fe3O4) as the inner layer and lepidocrocite as the outer layer. Fe2+ was not the main reductant for the reactions, but might accelerate the autoreduction of lepidocrocite to magnetite by the underlying Fe0. Our understanding on the role of Fe(II) in conjunction with a stratified, evolving corrosion coating may be useful for establishing an iron aquatic corrosion model.


Assuntos
Compostos de Ferro/química , Nitrobenzenos/química , Nitrobenzenos/farmacocinética , Compostos de Anilina/síntese química , Corrosão , Compostos de Ferro/farmacocinética , Oxirredução , Oxigênio , Soluções , Purificação da Água
18.
Am J Clin Nutr ; 84(1): 150-5, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16825689

RESUMO

BACKGROUND: Although hepcidin is proposed as a regulator of iron absorption, this has not been assessed in humans. OBJECTIVE: Our objective was to assess the relation between serum or urinary prohepcidin and iron absorption in healthy premenopausal women. DESIGN: The subjects were 28 healthy women aged 22-51 y with normal hemoglobin concentrations (120-152 g/L). Absorption of 0.5 mg Fe with 0.2 microCi 59Fe tracer, both as FeSO4, was measured by whole-body scintillation counting 13 d after oral administration. Fasting blood and urine samples were collected the day of and 16 wk after the absorption measurement. Serum and urinary prohepcidin concentrations were measured by an enzyme-linked immunosorbent assay by using an antibody against amino acid residues 28-47 of the proregion. RESULTS: Mean (+/-SD) iron absorption was 36 +/- 19% (range: 4-81%), and serum ferritin (geometric x) was 27 microg/L (range: 4-122 microg/L), as commonly observed in healthy premenopausal women. Serum prohepcidin was 196 microg/L (range: 99-376 microg/L) and, in contrast with urinary prohepcidin, was relatively consistent for the women between 0 and 16 wk. Serum prohepcidin correlated directly with serum ferritin (R2 = 0.28, P < 0.01) but was unrelated to 59Fe absorption, in contrast to serum ferritin (R2 = 0.33, P < 0.01). CONCLUSIONS: Serum prohepcidin concentrations were relatively stable within subjects and correlated with serum ferritin. However, unlike serum ferritin, neither serum nor urinary prohepcidin concentrations were related to iron absorption in healthy women.


Assuntos
Peptídeos Catiônicos Antimicrobianos/sangue , Peptídeos Catiônicos Antimicrobianos/urina , Absorção Intestinal/fisiologia , Ferro da Dieta/farmacocinética , Precursores de Proteínas/sangue , Precursores de Proteínas/urina , Administração Oral , Adulto , Peptídeos Catiônicos Antimicrobianos/fisiologia , Disponibilidade Biológica , Suplementos Nutricionais , Ensaio de Imunoadsorção Enzimática , Feminino , Ferritinas/sangue , Hemoglobinas/análise , Hepcidinas , Humanos , Compostos de Ferro/sangue , Compostos de Ferro/metabolismo , Compostos de Ferro/farmacocinética , Radioisótopos de Ferro , Ferro da Dieta/sangue , Ferro da Dieta/metabolismo , Pessoa de Meia-Idade , Pré-Menopausa , Contagem de Cintilação
19.
Immunopharmacol Immunotoxicol ; 28(1): 175-83, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16684676

RESUMO

The parenteral iron administration effects on the acceleration of lymphomagenesis by radiofrequency exposure were investigated using an animal model that develops spontaneous lymphomas with ageing. Complementary studies of the in vivo uptake of 59Fe-labeled ferric gluconate and ferric-ATP complex showed differences ob absorption and excretion between both iron compounds. In vitro assays of their effects on calcium cellular uptake using a cell model and tissues homogenates showed a molecular structure-dependence. The current results (mortality, clinical and histopathological examinations) demonstrated a synergism between radiofrequency and ferric gluconate, and the increased risk of radiofrequency exposure when it is simultaneous to parenteral iron administration.


Assuntos
Ferro/toxicidade , Linfoma/etiologia , Neoplasias Induzidas por Radiação/patologia , Ondas de Rádio , Trifosfato de Adenosina/farmacologia , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Contagem de Células Sanguíneas , Cálcio/metabolismo , Carcinoma de Ehrlich/patologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Feminino , Compostos Férricos/farmacologia , Ferro/farmacocinética , Compostos de Ferro/farmacocinética , Radioisótopos de Ferro , Contagem de Leucócitos , Peroxidação de Lipídeos/efeitos dos fármacos , Linfoma/induzido quimicamente , Linfoma/mortalidade , Camundongos , Camundongos Endogâmicos , Miocárdio/citologia , Distribuição Tecidual
20.
Arzneimittelforschung ; 55(7): 376-81, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16080276

RESUMO

The bioavailability of the oral iron compound iron(II)-glycine sulfate (ferro sanol duodenal, FSD, 1 x 100 mg Fe/d) was studied in 56 patients with iron deficiency anaemia using a 59Fe-labelling technique and 59Fe-whole-body counting. This technique measures the individual iron loss and allows in patients with substantial blood loss under iron medication a reliable information on the bioavailability of the drug. In all patients, the increased loss of iron (mean 5.8 +/- 4.4 mg/d) was clearly compensated by the iron utilisation (mean: 11.1 +/- 5.6 mg/d) from a daily dosage of 100 mg iron from FSD. A significant increase in the haemoglobin concentration was observed within the monitored treatment period of 6-10 weeks (mean Hb increase from 10.7 +/- 1.7 to 12.1 +/- 1.8 g/dl). FSD has therefore documented a bioavailability of at least 11% from a single daily dose of 100 mg Fe and was effective in the treatment of the anaemia in almost all patients under study.


Assuntos
Anemia Ferropriva/metabolismo , Compostos de Ferro/farmacocinética , Adulto , Anemia Ferropriva/tratamento farmacológico , Disponibilidade Biológica , Feminino , Glicina/análogos & derivados , Glicina/farmacocinética , Glicina/uso terapêutico , Hemoglobinas/metabolismo , Humanos , Absorção Intestinal , Compostos de Ferro/administração & dosagem , Compostos de Ferro/uso terapêutico , Radioisótopos de Ferro , Masculino , Contagem Corporal Total
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